RNA regulatory elements and polyadenylation in plants

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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.

Containment penetration design and analysis by finite element methods

International Nuclear Information System (INIS)

Perry, R.F.; Rigamonti, G.; Dainora, J.

1975-01-01

Containment penetration designs which provide complete support to process piping containing high pressure and high temperature fluids and which do not employ cooling coils, require special provisions to sustain loadings associated with normal/abnormal conditions and to limit maximum temperature transmitted to the containment concrete wall. In order to accomodate piping loads and fluid temperatures within code and regulatory limitations, the containment penetration designs require careful analysis of two critical regions: 1) the portion of the penetration sleeve which is exposed to containment ambient conditions and 2) the portion of the penetration which connects the sleeve to process piping (flued head). Analytical models using finite element representation of process piping, penetration flued head, and exposed sleeve were employed to investigate the penetration assembly design. By application of flexible multi-step analyses, different penetration configurations were evaluated to determine the effects of key design parameters. Among the parameters studied were flued head angles with the process piping, sleeve length and wall thickness. Special designs employing fins welded to the sleeve to further lower the temperature at the concrete wall interface were also investigated and fin geometry effects reported. (Auth.)

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.

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.

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).

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

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Sim, B C; Hui, K M

1994-12-01

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

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

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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.

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.

Identification of germline transcriptional regulatory elements in Aedes aegypti

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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.

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.

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.

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

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

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-.

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.

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.

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

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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

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.

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.

Carbon black vs. black carbon and other airborne materials containing elemental carbon: Physical and chemical distinctions

International Nuclear Information System (INIS)

Long, Christopher M.; Nascarella, Marc A.; Valberg, Peter A.

2013-01-01

Airborne particles containing elemental carbon (EC) are currently at the forefront of scientific and regulatory scrutiny, including black carbon, carbon black, and engineered carbon-based nanomaterials, e.g., carbon nanotubes, fullerenes, and graphene. Scientists and regulators sometimes group these EC-containing particles together, for example, interchangeably using the terms carbon black and black carbon despite one being a manufactured product with well-controlled properties and the other being an undesired, incomplete-combustion byproduct with diverse properties. In this critical review, we synthesize information on the contrasting properties of EC-containing particles in order to highlight significant differences that can affect hazard potential. We demonstrate why carbon black should not be considered a model particle representative of either combustion soots or engineered carbon-based nanomaterials. Overall, scientific studies need to distinguish these highly different EC-containing particles with care and precision so as to forestall unwarranted extrapolation of properties, hazard potential, and study conclusions from one material to another. -- Highlights: •Major classes of elemental carbon-containing particles have distinct properties. •Despite similar names, carbon black should not be confused with black carbon. •Carbon black is distinguished by a high EC content and well-controlled properties. •Black carbon particles are characterized by their heterogenous properties. •Carbon black is not a model particle representative of engineered nanomaterials. -- This review demonstrates the significant physical and chemical distinctions between elemental carbon-containing particles e.g., carbon black, black carbon, and engineered nanomaterials

Containment penetration design and analysis by finite element methods

International Nuclear Information System (INIS)

Perry, R.F.; Rigamonti, G.; Dainora, J.

1975-01-01

Containment penetration designs which provide complete support to process piping containing high pressure and high temperature fluids and which do not employ cooling coils, require special provisions to sustain loadings associated with normal/abnormal conditions and to limit maximum temperature transmitted to the containment concrete wall. In order to accommodate piping imposed loads and fluid temperatures within code and regulatory limitations, the containment penetration designs require careful analysis of two critical regions: the portion of the penetration sleeve which is exposed to containment ambient conditions and the portion of the penetration which connects the sleeve to process piping (flued head). The length and thickness of the sleeve must be designed to provide maximum heat dissipation to the atmosphere and minimum heat conduction through the sleeve to meet concrete temperature limitations. The sleeve must have the capability to transmit the postulated piping loads to concrete embedments in the containment shell. The penetration flued head design must be strong enough to transfer high mechanical loads and be flexible enough to accommodate the thermal stresses generated by the high temperature fluid. Analytical models using finite element representations of process piping, penetration flued head, and exposed sleeve were employed to investigate the penetration assembly design. By application of flexible multi-step analyses, different penetration configurations were evaluated to determine the effects of key design parameters. Among the parameters studied were flued head profiles, flued head angles with the process piping, sleeve length and wall thickness. Special designs employing fins welded to the sleeve to lower the temperature at the concrete wall interface were investigated and fin geometry effects reported

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.

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...

Assessment of the sealing system of an ilw transport container in a 9m regulatory impact

International Nuclear Information System (INIS)

Sievwright, R.W.T.; Gray, I.L.S.; Bernasconi, D.J.; McGuinn, P.; Tso, C.F.

1998-01-01

UK Nirex Ltd is developing a range of reusable shielded transport containers (RSTCs) to ensure the safe transport of immobilised intermediate level waste to a future UK deep repository for disposal. The RSTCs use an inset lid for mechanical strength and radiation shielding, but the containment boundary is provided by a separate lid seal member (LSM). The LSM is a semi-flexible steel diaphragm surrounded by a rim which carries a double O-ring seal. The LSM rim is clamped to a flat mating surface on the container body. A finite element model has been developed for an RSTC with a wall thickness of 285 mm, in order to assess its containment performance in 9m regulatory drop tests (IAEA 1996). The challenge was to predict the size of small gaps that might appear between the LSM rim and the RSTC body seal face ; this level of detail would be 1-2 orders of magnitude smaller than the displacements experienced in the impact zone. The model was first validated against a series of one-third scale model drop tests of the RSTC. The validated model was then analysed for 9m regulatory impacts in the six worst impact attitudes. The behavior of the LSM was assessed for each attitude and the seal face (gaps) between the LSM and the body were determined. Although small gaps of about 0.5 mm are predicted, it is likely that containment would be preserved. (authors)

A regulatory view of nuclear containment on UK licensed sites

International Nuclear Information System (INIS)

Bradford, P.M.; McNair, I.J.

1997-01-01

Members of the UK regulatory body, HM Nuclear Installations Inspectorate (NII) have previously presented conference papers and official reports which have dealt separately with either reactor applications or chemical plant applications. The objective of this paper is to draw together a brief overview of the role of containment in protecting against potential radiological and related hazards, and to describe the factors which influence the NII's assessment of containment safety cases. It draws upon the NII's experience of regulating many types of nuclear facility, from those designed in the late 1940s through to the modern plants, such as Sizewell 'B' and THORP. The paper reviews the legislative and regulatory background within which the facilities exist and are operated. Finally, the paper reviews recent, ongoing and planned research in the field of containment, which has been designed to behave under challenge. (author)

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

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.

Tension tests of concrete containment wall elements

International Nuclear Information System (INIS)

Schultz, D.M.; Julien, J.T.; Russel, H.G.

1984-01-01

Tension tests of concrete containment wall elements were conducted as part of a three-phase research program sponsored by the Electric Power Research Institute (EPRI). The objective of the EPRI experimental/analytical program is twofold. The first objective is to provide the utility industry with a test-verified analytical method for making realistic estimates of actual capacities of reinforced and prestressed concrete containments under internal over-pressurization from postulated degraded core accidents. The second objective is to determine qualitative and quantitative leak rate characteristics of typical containment cross-sections with and without penetrations. This paper covers the experimental portion to the EPRI program. The testing program for Phase 1 included eight large-scale specimens representing elements from the wall of a containment. Each specimen was 60-in (1525-mm) square, 24-in (610-mm) thick, and had full-size reinforcing bars. Six specimens were representative of prototypical reinforced concrete containment designs. The remaining two specimens represented prototypical prestressed containment designs. Various reinforcement configurations and loading arrangements resulted in data that permit comparisons of the effects of controlled variables on cracking and subsequent concrete/reinforcement/liner interaction in containment elements. Subtle differences, due to variations in reinforcement patterns and load applications among the eight specimens, are being used to benchmark the codes being developed in the analytical portion of the EPRI program. Phases 2 and 3 of the test program will examine leak rate characteristics and failure mechanisms at penetrations and structural discontinuities. (orig.)

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

Elements for computing and forecasting the leakage rate of the inner containment of nuclear reactor buildings

International Nuclear Information System (INIS)

Asali, M.; Capra, B.; Mazars, J.; Colliat, J.B.

2015-01-01

This study aims at introducing a methodology based on a macro-element discretization to compute and forecast the air leak rate of double-wall reactor buildings during air pressure tests. Assumptions at the basis of a weakly coupled strategy are checked in the case of a typical porous concrete section of an inner containment modeled during a 33 year period including four decennial regulatory pressure tests. However, air leakage due to porosity is only part of in situ measurements. Leakage due to cracking is another part and should be taken into account. A first macro-element is then presented, that superimposes Darcy flow within a porous matrix together with Poiseuille flow within a crack. Those elements are then used in a 3D hydraulic model to compute more accurately the total air leakage rate of considered structures. (authors)

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.

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.

1988-year of high integrity container evaluation, controversy and regulatory action

International Nuclear Information System (INIS)

Jones, D.

1989-01-01

During 1988, the Nuclear Regulatory Commission(NRC) completed review of and prepared technical evaluation reports on several topical reports describing containers designed to meet the 10CFR61 requirements for high integrity containers (HICs). An all metal Ferralium container and a stainless steel/polyethylene lined container were approved by the NRC. However, the NRC did not approve any containers designed from polyethylene material. The NRC staff concluded that polyethylene containers do not meet the structural stability requirements of Part 61, and unless they are combined with some engineered structure or overpack, they are not adequate for disposal of low-level radioactive wastes that require disposal in a structurally stable form. In conflict with these NRC findings, the State of South Carolina Department of Health and Environmental Control (SCDHEC) has given interim approval for continued use of polyethylene containers at the Barnwell disposal site with some restrictions on how the containers are buried depending on the classification of the waste. This paper reviews the applicable federal regulations, presents a chronology of events describing how the controversy over high integrity containers evolved from 1980 to 1989, summarizes the technical issues involved and suggests an approach that waste generators should follow during this situation of regulatory uncertainty

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...

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.

Apparatus for the storage of transport- and storage-containers containing radioactive fuel elements

International Nuclear Information System (INIS)

Vox, A.

1983-01-01

The invention concerns an apparatus for the storage of transport and storage containers containing radioactive fuel elements. For each transport or storage container there is a separate silo-type container of steel, concrete, prestressed concrete or suchlike breakproof and fireproof material, to be placed in the open, that can be opened for removal and placing of the transport or storage container respectively. (orig.) [de

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.

Nuclear fuel element and container

International Nuclear Information System (INIS)

Grubb, W.T.; King, L.H.

1981-01-01

The invention is based on the discovery that a substantial reduction in metal embrittlement or stress corrosion cracking from fuel pellet-cladding interaction can be achieved by the use of a copper layer or liner in proximity to the nuclear fuel, and an intermediate zirconium oxide barrier layer between the copper layer and the zirconium cladding substrate. The intermediate zirconia layer is a good copper diffusion barrier; also, if the zirconium cladding surface is modified prior to oxidation, copper can be deposited by electroless plating. A nuclear fuel element is described which comprises a central core of fuel material and an elongated container using the system outlined above. The method for making the container is again described. It comprises roughening or etching the surface of the zirconium or zirconium alloy container, oxidizing the resulting container, activating the oxidized surface to allow for the metallic coating of such surfaces by electroless deposition and further coating the activated-oxidized surface of the zirconium or zirconium alloy container with copper, iron or nickel or an alloy thereof. (U.K.)

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...

New CSA guideline for the exemption or clearance from regulatory control of materials that contain, or potentially contain, nuclear substances

International Nuclear Information System (INIS)

Rhodes, M.; Kwong, A.

2011-01-01

The Canadian Standards Association (CSA) guideline N292.5, Guideline for the exemption or clearance from regulatory control of materials that contain, or potentially contain, nuclear substances, was recently developed to address a need for guidance on approaches for clearance of materials from facilities licensed by the Canadian Nuclear Safety Commission (CNSC) consistent with Canadian and international recommendations. This guideline is also applicable to determining if an activity associated with materials that contain nuclear substances is exempt from requiring a CNSC licence. The guideline summarizes the regulatory requirements associated with the exemption and clearance of materials and provides a graded approach to designing a survey based on the risk of residual contamination being present. (author)

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

Transcriptional attenuation controls macrolide inducible efflux and resistance in Streptococcus pneumoniae and in other Gram-positive bacteria containing mef/mel(msr(D)) elements.

Science.gov (United States)

Chancey, Scott T; Bai, Xianhe; Kumar, Nikhil; Drabek, Elliott F; Daugherty, Sean C; Colon, Thomas; Ott, Sandra; Sengamalay, Naomi; Sadzewicz, Lisa; Tallon, Luke J; Fraser, Claire M; Tettelin, Hervé; Stephens, David S

2015-01-01

Macrolide resistance, emerging in Streptococcus pneumoniae and other Gram-positive bacteria, is increasingly due to efflux pumps encoded by mef/mel(msr) operons found on discrete mobile genetic elements. The regulation of mef/mel(msr) in these elements is not well understood. We identified the mef(E)/mel transcriptional start, localized the mef(E)/mel promoter, and demonstrated attenuation of transcription as a mechanism of regulation of macrolide-inducible mef-mediated macrolide resistance in S. pneumoniae. The mef(E)/mel transcriptional start site was a guanine 327 bp upstream of mef(E). Consensus pneumococcal promoter -10 (5'-TATACT-3') and -35 (5'-TTGAAC-3') boxes separated by 17 bp were identified 7 bp upstream of the start site. Analysis of the predicted secondary structure of the 327 5' region identified four pairs of inverted repeats R1-R8 predicted to fold into stem-loops, a small leader peptide [MTASMRLR, (Mef(E)L)] required for macrolide induction and a Rho-independent transcription terminator. RNA-seq analyses provided confirmation of transcriptional attenuation. In addition, expression of mef(E)L was also influenced by mef(E)L-dependent mRNA stability. The regulatory region 5' of mef(E) was highly conserved in other mef/mel(msr)-containing elements including Tn1207.1 and the 5612IQ complex in pneumococci and Tn1207.3 in Group A streptococci, indicating a regulatory mechanism common to a wide variety of Gram-positive bacteria containing mef/mel(msr) elements.

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.

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

A regulatory view of containment integrity in the United Kingdom

International Nuclear Information System (INIS)

Bradford, P.M.; Patchett, C.M.

1994-01-01

This paper reviews the approach of HM Nuclear Installations Inspectorate (NII) to containment integrity in the United Kingdom (UK). NII is that part of the regulatory authority, the Health and Safety Executive (HSE), which administers the UK's nuclear site licensing system. A major part of the licensing process lies in the assessment of licensees' submissions for new and existing plant. The purpose of this paper is to: briefly review our revised Safety Assessment Principles, describe our assessment and inspection activities on the primary containment building of the Sizewell B PWR which is progressing to full power operation in 1994 and, to indicate our views on the possible directions for future research into containment design and performance. (author). 5 refs

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.

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...

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

Organic waste process containing at least one radioactive element

International Nuclear Information System (INIS)

Le Roy, F.

1977-01-01

The description is given of an organic waste process containing at least one element from the group comprising strontium, cesium, iodine and ruthenium. It comprises the introduction of the organic waste and gaseous oxygen in a bath of melted salt containing an alkaline carbonate, the bath being maintained at a high temperature between 400 and 1000 0 C and at a pressure of 0.5 to 10 bars, so that the organic waste is burnt and oxidised at least partly, the element selected being retained by the bath of melted salt [fr

Regulatory Concerns on the In-Containment Water Storage System of the Korean Next Generation Reactor

International Nuclear Information System (INIS)

Ahn, Hyung-Joon; Lee, Jae-Hun; Bang, Young-Seok; Kim, Hho-Jung

2002-01-01

The in-containment water storage system (IWSS) is a newly adopted system in the design of the Korean Next Generation Reactor (KNGR). It consists of the in-containment refueling water storage tank, holdup volume tank, and cavity flooding system (CFS). The IWSS has the function of steam condensation and heat sink for the steam release from the pressurizer and provides cooling water to the safety injection system and containment spray system in an accident condition and to the CFS in a severe accident condition. With the progress of the KNGR design, the Korea Institute of Nuclear Safety has been developing Safety and Regulatory Requirements and Guidances for safety review of the KNGR. In this paper, regarding the IWSS of the KNGR, the major contents of the General Safety Criteria, Specific Safety Requirements, Safety Regulatory Guides, and Safety Review Procedures were introduced, and the safety review items that have to be reviewed in-depth from the regulatory viewpoint were also identified

A regulatory view of containment integrity in the United Kingdom

Energy Technology Data Exchange (ETDEWEB)

Bradford, P M; Patchett, C M [Health and Safety Executive, Bootle (United Kingdom). Nuclear Installations Inspectorate

1994-12-31

This paper reviews the approach of HM Nuclear Installations Inspectorate (NII) to containment integrity in the United Kingdom (UK). NII is that part of the regulatory authority, the Health and Safety Executive (HSE), which administers the UK`s nuclear site licensing system. A major part of the licensing process lies in the assessment of licensees` submissions for new and existing plant. The purpose of this paper is to: briefly review our revised Safety Assessment Principles, describe our assessment and inspection activities on the primary containment building of the Sizewell B PWR which is progressing to full power operation in 1994 and, to indicate our views on the possible directions for future research into containment design and performance. (author). 5 refs.

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

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.

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.

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2005-01-05

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

Gains or Losses of Ultratrace Elements in Polyethylene Containers

DEFF Research Database (Denmark)

Heydorn, Kaj; Damsgaard, Else

1982-01-01

The extent of elimination of losses and reduction of blank values in ultratrace elemental analysis can only be ascertained by comprehensive investigations for each element separately. Different, and partially conflicting precautions are found to be needed in the determination of manganese, copper......, selenium, and mercury by neutron-activation analysis when polyethylene irradiation containers are used....

ACGT-containing abscisic acid response element (ABRE) and coupling element 3 (CE3) are functionally equivalent.

Science.gov (United States)

Hobo, T; Asada, M; Kowyama, Y; Hattori, T

1999-09-01

ACGT-containing ABA response elements (ABREs) have been functionally identified in the promoters of various genes. In addition, single copies of ABRE have been found to require a cis-acting, coupling element to achieve ABA induction. A coupling element 3 (CE3) sequence, originally identified as such in the barley HVA1 promoter, is found approximately 30 bp downstream of motif A (ACGT-containing ABRE) in the promoter of the Osem gene. The relationship between these two elements was further defined by linker-scan analyses of a 55 bp fragment of the Osem promoter, which is sufficient for ABA-responsiveness and VP1 activation. The analyses revealed that both motif A and CE3 sequence were required not only for ABA-responsiveness but also for VP1 activation. Since the sequences of motif A and CE3 were found to be similar, motif-exchange experiments were carried out. The experiments demonstrated that motif A and CE3 were interchangeable by each other with respect to both ABA and VP1 regulation. In addition, both sequences were shown to be recognized by a VP1-interacting, ABA-responsive bZIP factor TRAB1. These results indicate that ACGT-containing ABREs and CE3 are functionally equivalent cis-acting elements. Furthermore, TRAB1 was shown to bind two other non-ACGT ABREs. Based on these results, all these ABREs including CE3 are proposed to be categorized into a single class of cis-acting elements.

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

Science.gov (United States)

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

1994-05-01

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

Nonconforming axisymmetric elements for the analysis of containment structures

International Nuclear Information System (INIS)

Choi, C.K.; Kim, S.Y.

1989-01-01

In this study, the behaviors of the conforming isoparametric quadrilateral 4-node and triangular 3-nod axisymmetric solid elements are improved by adding nonconforming displacement modes. The convergence tests and the irregular mesh tests have been established through the analyses of a primary shield wall typed structure. For example study, a containment wall with internal pressure of 60 ksi has been analyzed. It shows that the nonconforming elements behave better than the conforming elements, especially, in the structurally discontinuous regions

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.

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.

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.

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.

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

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

Seismic damage assessment of reinforced concrete containment structures

International Nuclear Information System (INIS)

Cho, HoHyun; Koh, Hyun-Moo; Hyun, Chang-Hun; Kim, Moon-Soo; Shin, Hyun Mock

2003-01-01

This paper presents a procedure for assessing seismic damage of concrete containment structures using the nonlinear time-history numerical analysis. For this purpose, two kinds of damage index are introduced at finite element and structural levels. Nonlinear finite element analysis for the containment structure applies PSC shell elements using a layered approach leading to damage indices at finite element and structural levels, which are then used to assess the seismic damage of the containment structure. As an example of such seismic damage assessment, seismic damages of the containment structure of Wolsong I nuclear power plant in Korea are evaluated against 30 artificial earthquakes generated with a wide range of PGA according to US NRC regulatory guide 1.60. Structural responses and corresponding damage index according to the level of PGA and nonlinearity are investigated. It is also shown that the containment structure behaves elastically for earthquakes corresponding to or lower than DBE. (author)

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.

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

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.

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.

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

Directory of Open Access Journals (Sweden)

Clare Pridans

2014-01-01

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

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.

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.

Analysis of a possible experimental assessment of a prototype fuel element containing burnable poison in the RA-3 reactor

International Nuclear Information System (INIS)

Lerner, Ana Maria; Madariaga, Marcelo

2002-01-01

The Argentine RA-3 research reactor (5 MW) is presently operated with LEU fuel by the National Atomic Energy Commission (CNEA). It belongs to the group of nuclear installations controlled, from the radiological and nuclear safety point of view, by the Nuclear Regulatory Authority (ARN). A new type of fuel elements containing burnable absorbers, with similar enrichment as the standard fuel elements but greater fissile contents, has recently been proposed for a new Argentine reactor design (RRR). In this framework the ARN considers interesting, if technically possible, the performance of an experiment in the RA-3 reactor. The experiment might enable, for such fuel element containing burnable poison, the verification of its neutronic behaviour under irradiation as well as a validation of the calculation line by comparison to measured values. It should be desirable that such experiment could reproduce as much as possible those conditions estimated for the RRR reactor, still under design in Argentina, having Silicide fuel elements with burnable poison, in the shape of cadmium wires in their structure. We here analyse a possible experiment consisting in the loading of a prototype fuel element with burnable poison in a normally loaded RA-3 core configuration. It would essentially be a standard RA-3 fuel element, having cadmium wires in its frame. This experiment would enable the verification of the prototype behaviour under irradiation, its operation limits and conditions, and particularly, the reactivity safety margins established in Argentine Standards, both calculated and measured. The main part of the experiment would imply some 200 full power days of operation at 5 MW, which would be drastically reduced if the reactor power is increased to 10 MW, as foreseen. We also show that under the proposed conditions, the experiment would not represent a significant penalty to the reactor normal operation. (author)

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.

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.

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

ETR fuel element shipping container addendum to PR-T-79-011 (TR-466). Internal technical report

International Nuclear Information System (INIS)

Smith, M.C.

1979-01-01

In July, 1979, EG and G Idaho, Inc. was requested to evaluate the ETR Fuel Element Shipping Container for compliance with existing transport regulations, in order to ship GETR fuel elements from Vallecitos, California to the INEL. Technical report PR-T-79-011 (TR-466), ATR Fuel Element Shipping Container Safety Analysis, was used as a basis for this evaluation. The safety analysis contained in technical report PR-T-79-011 (TR-466) was performed utilizing the ATR, ETR, MTR, and SPERT shipping containers. The report determined the ETR Fuel Element Shipping Container does comply with the existing transport regulations for a Type A quantity, Fissile Class I shipping container. The ETR and GETR fuel elements are essentially identical in physical size, construction, and fissile material content, the analysis documented in this report has determined the shipment of GETR fuel elements in the ETR shipping container to be safe and pose no threat to the public health and safety

Containment performance improvement program

International Nuclear Information System (INIS)

Beckner, W.; Mitchell, J.; Soffer, L.; Chow, E.; Lane, J.; Ridgely, J.

1990-01-01

The Containment Performance Improvement (CPI) program has been one of the main elements in the US Nuclear Regulatory Commission's (NRC's) integrated approach to closure of severe accident issues for US nuclear power plants. During the course of the program, results from various probabilistic risk assessment (PRA) studies and from severe accident research programs for the five US containment types have been examined to identify significant containment challenges and to evaluate potential improvements. The five containment types considered are: the boiling water reactor (BMR) Mark I containment, the BWR Mark II containment, the BWR Mark III containment, the pressurized water reactor (PWR) ice condenser containment, and the PWR dry containments (including both subatmospheric and large subtypes). The focus of the CPI program has been containment performance and accident mitigation, however, insights are also being obtained in the areas of accident prevention and accident management

Alternative splicing of T cell receptor (TCR) alpha chain transcripts containing V alpha 1 or V alpha 14 elements.

Science.gov (United States)

Mahotka, C; Hansen-Hagge, T E; Bartram, C R

1995-10-01

Human acute lymphoblastic leukemia cell lines represent valuable tools to investigate distinct steps of the complex regulatory pathways underlying T cell receptor recombination and expression. A case in point are V delta 2D delta 3 and subsequent V delta 2D delta 3J alpha rearrangements observed in human leukemic pre-B cells as well as in normal lymphopoiesis. The functional expression of these unusual (VD) delta (JC) alpha hybrids is almost exclusively prevented by alternative splicing events. In this report we show that alternative splicing at cryptic splice donor sites within V elements is not a unique feature of hybrid TCR delta/alpha transcripts. Among seven V alpha families analyzed by RT-PCR, alternatively spliced products were observed in TCR alpha recombinations containing V alpha 1 or V alpha 14 elements. In contrast to normal peripheral blood cells and thymocytes, the leukemia cell line JM expressing functional V alpha 1J alpha 3C alpha transcripts lacked evidence of aberrant TCR alpha RNA species.

Bringing a probiotic-containing functional food to the market: microbiological, product, regulatory and labeling issues.

Science.gov (United States)

Sanders, M E; Huis in't Veld, J

1999-01-01

Properly formulated probiotic-containing foods offer consumers a low risk, low cost dietary component that has the potential to promote health in a variety of ways. Several such products are available commercially, although markets in Japan and Europe are more developed than in the USA. Once healthful attributes of a probiotic product have been identified, there remain microbiological, product, regulatory and labeling issues to be addressed prior to marketing. Microbiological and product issues include safety, effective scale-up for manufacturing, definition of probiotic activity, probiotic stability in the product over the course of product manufacture, shelf-life and consumption, definition of effective dose and target population(s), and development of quality assurance approaches. Examples of probiotic-containing foods are given. Regulatory and labeling issues are complicated because they differ for each country, but are likewise critical because they provide the means for communication of the product benefits to the consumer. The regulatory climate worldwide appears to be one of caution about overstating the benefits of such products but at the same time not preventing corporate commitment to marketing.

The nonlinear finite element analysis program NUCAS (NUclear Containment Analysis System) for reinforced concrete containment building

Energy Technology Data Exchange (ETDEWEB)

Lee, Sang Jin; Lee, Hong Pyo; Seo, Jeong Moon [Korea Atomic Energy Research Institute, Taejeon (Korea)

2002-03-01

The maim goal of this research is to develop a nonlinear finite element analysis program NUCAS to accurately predict global and local failure modes of containment building subjected to internal pressure. In this report, we describe the techniques we developed throught this research. An adequate model to the analysis of containment building such as microscopic material model is adopted and it applied into the development Reissner-Mindlin degenerated shell element. To avoid finite element deficiencies, the substitute strains based on the assumed strain method is used in the shell formulation. Arc-length control method is also adopted to fully trace the peak load-displacement path due to crack formation. In addition, a benchmark test suite is developed to investigate the performance of NUCAS and proposed as the future benchmark tests for nonlinear analysis of reinforced concrete. Finally, the input format of NUCAS and the examples of input/output file are described. 39 refs., 65 figs., 8 tabs. (Author)

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...

Impact analysis of a hydrogen isotopes container

International Nuclear Information System (INIS)

Lee, M. S.; Hwang, C. S.; Jeong, H. S.

2003-01-01

The container used for the radioactive materials, containing hydrogen isotopes is evaluated in a view of hypothetical accident. The computational analysis is a cost effective tool to minimize testing and streamline the regulatory procedures, and supports experimental programs to qualify the container for the safe transport of radioactive materials. The numerical analysis of 9m free-drop onto a flat unyielding, horizontal surface has been performed using the explicit finite element computer program ABAQUS. Especially free-drop simulations for 30 .deg. C tilted condition are precisely estimated

Fuel element transport container with a removable cover

International Nuclear Information System (INIS)

Dannehl, G.; Fink, W.; Haenle, G.

1980-01-01

The cover of the fuel element transport container is removably fixed with screws on a flange as mechanical loads have to be expected during the transfer to the disposal plant. A ring-shaped or star-shaped clamping device grips over the cover. It has a clamp claw to lock the cover and permits unscrewing without unlocking the cover. (DG) [de

Probabilistic finite element investigation of prestressing loss in nuclear containment wall segments

International Nuclear Information System (INIS)

Balomenos, Georgios P.; Pandey, Mahesh D.

2017-01-01

Highlights: • Probabilistic finite element framework for assessing concrete strain distribution. • Investigation of prestressing loss based on concrete strain distribution. • Application to 3D nuclear containment wall segments. • Use of ABAQUS with python programing for Monte Carlo simulation. - Abstract: The main function of the concrete containment structures is to prevent radioactive leakage to the environment in case of a loss of coolant accident (LOCA). The Canadian Standard CSA N287.6 (2011) proposes periodic inspections, i.e., pressure testing, in order to assess the strength and design criteria of the containment (proof test) and the leak tightness of the containment boundary (leakage rate test). During these tests, the concrete strains are measured and are expected to have a distribution due to several uncertainties. Therefore, this study aims to propose a probabilistic finite element analysis framework. Then, investigates the relationship between the concrete strains and the prestressing loss, in order to examine the possibility of estimating the average prestressing loss during pressure testing inspections. The results indicate that the concrete strain measurements during the leakage rate test may provide information with respect to the prestressing loss of the bonded system. In addition, the demonstrated framework can be further used for the probabilistic finite element analysis of real scale containments.

Probabilistic finite element investigation of prestressing loss in nuclear containment wall segments

Energy Technology Data Exchange (ETDEWEB)

Balomenos, Georgios P., E-mail: gbalomen@uwaterloo.ca; Pandey, Mahesh D., E-mail: mdpandey@uwaterloo.ca

2017-01-15

Highlights: • Probabilistic finite element framework for assessing concrete strain distribution. • Investigation of prestressing loss based on concrete strain distribution. • Application to 3D nuclear containment wall segments. • Use of ABAQUS with python programing for Monte Carlo simulation. - Abstract: The main function of the concrete containment structures is to prevent radioactive leakage to the environment in case of a loss of coolant accident (LOCA). The Canadian Standard CSA N287.6 (2011) proposes periodic inspections, i.e., pressure testing, in order to assess the strength and design criteria of the containment (proof test) and the leak tightness of the containment boundary (leakage rate test). During these tests, the concrete strains are measured and are expected to have a distribution due to several uncertainties. Therefore, this study aims to propose a probabilistic finite element analysis framework. Then, investigates the relationship between the concrete strains and the prestressing loss, in order to examine the possibility of estimating the average prestressing loss during pressure testing inspections. The results indicate that the concrete strain measurements during the leakage rate test may provide information with respect to the prestressing loss of the bonded system. In addition, the demonstrated framework can be further used for the probabilistic finite element analysis of real scale containments.

Concrete containment tests: Phase 2, Structural elements with liner plates: Interim report

International Nuclear Information System (INIS)

Hanson, N.W.; Roller, J.J.; Schultz, D.M.; Julien, J.T.; Weinmann, T.L.

1987-08-01

The tests described in this report are part of Phase 2 of the Electric Power Research Institute (EPRI) program. The overall objective of the EPRI program is to provide a test-verified analytical method of estimating capacities of concrete reactor containment buildings under internal overpressurization from postulated degraded core accidents. The Phase 2 testing included seven large-scale specimens representing structural elements from reinforced and prestressed concrete reactor containment buildings. Six of the seven test specimens were square wall elements. Of these six specimens, four were used for biaxial tension tests to determine strength, deformation, and leak-rate characteristics of full-scale wall elements representing prestressed concrete containment design. The remaining two square wall elements were used for thermal buckling tests to determine whether buckling of the steel liner plate would occur between anchorages when subjected to a sudden extreme temperature differential. The last of the seven test specimens for Phase 2 represented the region where the wall and the basemat intersect in a prestressed concrete containment building. A multi-directional loading scheme was used to produce high bending moments and shear in the wall/basemat junction region. The objective of this test was to determine if there is potential for liner plate tearing in the junction region. Results presented include observed behavior and extensive measurements of deformations and strains as a function of applied load. The data are being used to confirm analytical models for predicting strength and deformation of containment structures in a separate parallel analytical investigation sponsored by EPRI

Safety analysis report for packaging: the ORNL HFIR unirradiated fuel element shipping container

International Nuclear Information System (INIS)

Evans, J.H.; Boulet, J.A.M.; Eversole, R.E.

1977-11-01

The ORNL HFIR unirradiated fuel element shipping container was designed and fabricated at the Oak Ridge National Laboratory for the transport of HFIR unirradiated fuel elements. The container was evaluated analytically and experimentally to determine its compliance with the applicable regulations governing containers in which radioactive and fissile materials are transported, and the evaluation is the subject of this report. Computational and test procedures were used to determine the structural integrity and thermal behavior of the cask relative to the general standards for normal conditions of transport and the standards for the hypothetical accident conditions. The results of the evaluation demonstrate that the container is in compliance with the applicable regulations

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.

Process and device for cooling of nuclear reactor fuel elements enclosed in a transport container

International Nuclear Information System (INIS)

Stiefel, M.

1986-01-01

In order to remove the post-decay heat of the fuel elements contained in them, transport containers for burnt-up fuel elements can be connected to a water cooling circuit. In order to avoid thermal shocks, a tenside forming foam and air are introduced into the cooling circuit before its entry into the transport container in the direction of flow. The tenside and air continue to be supplied until the temperature inside the transport container has fallen below the temperature at which the foam is destroyed. By adding tenside and air, a two phase mixture is produced, which foams greatly when it enters the transport container and which cools the fuel elements so as to protect them.(orig./HP) [de

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...

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).

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

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

Regulatory requirements for the use of consumer products containing radioactive substances

International Nuclear Information System (INIS)

Mason, G.C.; Paynter, R.A.; Schmitt-Hannig, A.; Sztanyik, L.B.

1996-01-01

In almost 100 years since the discovery of radioactivity, the properties of radioactive materials have been exploited in products such as clocks and watches incorporating luminous paint which are freely available to members of the public. Over time, regulatory authorities have felt it necessary to apply some degree of control to the supply and use of such products in order to protect public health. In many areas of radiation protection, national authorities take note of international recommendations when developing national standards, but the existing detailed guidance of the International Atomic Energy Agency (IAEA) for consumer products is incomplete and out of date. Recently, a thorough revision of the International Basic Safety Standards (BSS) has occurred, which has prompted a review and revision of the related guidance published by the IAEA. A draft Guide on Regulatory Requirements for the Use of Consumer Products Containing Radioactive Substances has now been completed and is currently under review within the IAEA's system for development of documents in its Safety Series of publications. (author)

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.

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.

Nuclear fuel element containing particles of an alloyed Zr, Ti, and Ni getter material

International Nuclear Information System (INIS)

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

1975-01-01

A nuclear fuel element for use in the core of a nuclear reactor is disclosed. The nuclear fuel element has disposed therein an alloy having the essential components of nickel, titanium and zirconium, and the alloy reacts with water, water vapor and reactive gases at reactor ambient temperatures. The alloy is disposed in the plenum of the fuel element in the form of particles in a hollow gas permeable container having a multiplicity of openings of size smaller than the size of the particles. The openings permit gases and liquids entering the plenum to contact the particles of alloy. The container is preferably held in the spring in the plenum of the fuel element. (Official Gazette)

Simplified dynamic buckling assessment of steel containments

International Nuclear Information System (INIS)

Farrar, C.R.; Duffey, T.A.; Renick, D.H.

1993-01-01

A simplified, three-degree-of-freedom analytical procedure for performing a response spectrum buckling analysis of a thin containment shell is developed. Two numerical examples with R/t values which bound many existing steel containments are used to illustrate the procedure. The role of damping on incipient buckling acceleration level is evaluated for a regulatory seismic spectrum using the two numerical examples. The zero-period acceleration level that causes incipient buckling in either of the two containments increases 31% when damping is increased from 1% to 4% of critical. Comparisons with finite element results on incipient buckling levels are favorable

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...

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

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.

Hazardous and other element characterization of new and used domestic plastic food containers using INAA and AAS

International Nuclear Information System (INIS)

Waheed, S.; Rahman, S.; Husnain, S.M.; Siddique, N.

2012-01-01

Instrumental neutron activation analysis (INAA) and flame atomic absorption spectroscopy (FAAS) methodology was developed to characterize the inorganic trace element constituents in new and used domestic plastic food containers. INAA was employed through the variation of irradiation, cooling and counting protocols for the determination of Al, Ba, Br, Co, Cr, Eu, Fe, Hg, K, Mn, Na, Nd, Sb, Sc, Th, Ti, V and Zn while FAAS was used to quantify toxic inorganic elements such as Cd, Pb and Cu. These elements are thought to originate from the polymer manufacturing processes. It was found that there was gradual increase in the concentration of most of these elements from new to used plastic samples. Moreover it was also observed that these inorganic elements are present in higher concentrations in the lower grade containers as compared to the high quality containers. It was also observed that the good quality containers even with the long usage do not degrade to such an extent as the low quality containers. (Orig./A.B.)

Technical and Regulatory Considerations in Using Freight Containers as Industrial Packages

Energy Technology Data Exchange (ETDEWEB)

Hawk, Mark B [ORNL; Opperman, Erich [Washington Savannah River Company; Natali, Ronald [R. B. Natali Consulting, Inc.

2008-01-01

The US Department of Energy (DOE), Office of Environmental Management (EM), is actively pursuing activities to reduce the radiological risk and clean up the environmental legacy of the nation's nuclear weapons programmes. The EM has made significant progress in recent years in the clean-up and closure of sites and is also focusing on longer term activities necessary for the completion of the clean-up programme. The packaging and transportation of contaminated demolition debris and low level waste materials in a safe and cost effective manner are essential in completing this mission. Toward this end, the US Department of Transportation's Final Rule on Hazardous Materials Regulation issued on 26 January 2004, included a new provision authorising the use of freight containers (e.g. 20 and 40 ft ISO containers) as industrial packages type 2 or 3. This paper will discuss the technical and regulatory considerations in using these newly authorised and large packages for the packaging and transportation of low level waste materials.

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.

Discussion of Regulatory Guide 7.10, emphasizing the graded approach for establishing QA programs

International Nuclear Information System (INIS)

Gordon, L.; Lake, W.H.

1983-01-01

To assist applicants in establishing an acceptable QA program to meet the programmatic elements of Appendix E to 10 CFR Part 71, Regulatory Guide 7.10 was developed. Regulatory Guide 7.10 is organized in three self-contained ANNEXES. Guidance applicable to designer/fabricators, to users, and users of radiographic devices are in separate annexes. QA programs for packaging to transport radioactive material are similar in regard to the various operations a licensee may be involved in. However, the appropriate QA/QC effort to verify the program elements may vary significantly. This is referred to as the graded approach. Appendix A in the guide addresses the graded approach

Exemption from Regulatory Control of Goods Containing Small Amounts of Radioactive Material

International Nuclear Information System (INIS)

2012-01-01

Safety Guide on Application of the Concepts of Exclusion, Exemption and Clearance, No. RS-G-1.7 (2004). Nevertheless, the application of the exemption provisions in the BSS require further guidance, particularly with respect to goods containing small amounts of radioactive material. Although attempts have been made to harmonize the approaches among States and some progress has been achieved, further work needs to be done. For example, in some States such goods may be exempted from regulatory control and, in the case of consumer products, freely available to the public, while in other States their use may be subject to authorization with the consequence that they cannot be made freely available to the public. Other States may even refuse to authorize such goods, effectively resulting in their being banned. Such inconsistencies of approach may be a cause of confusion since the reasons for the different approaches will not be clear to manufacturers and suppliers of goods and the public who might use them. It may even result in questioning of the competence of the regulatory body. Further harmonization of the regulatory approaches in Member States in the application of the exemption provision in the BSS is clearly desirable, if not essential. Such goods may be marketed globally, and lack of harmonization can be a cause of confusion among the public and others regarding the risks posed by such goods. Further harmonization would assist regulatory bodies in the efficient and effective use of their limited resources, leaving them more time to devote to those activities and practices that present more significant radiation risks. Furthermore, it would have benefits for international trade.

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.

PARCS - A pre-stressed and reinforced concrete shell element for analysis of containment structures

International Nuclear Information System (INIS)

Buragohain, D.N.; Mukherjee, A.

1993-01-01

Containment structures are designed as pressure vessels against a huge internal pressure build up in the event of a postulated LOCA. In such situations the containment structures experience predominantly in-plane stress in tension. Therefore, pre-stressed concrete has been very frequently used for the construction of containment. For larger plants a dual containment with a pre-stressed concrete inner containment and a reinforced concrete outer containment has been adopted. These structures are required to perform within very stringent safety requirements under extremely severe loading. Naturally, their design has attracted a lot of investigators and a huge volume of literature has been published in previous SMiRT conferences. However, it seems that the structural modeling of the containment has not developed accordingly. It is a common practice to consider the concrete section only in the model and the effects of pre-stress and reinforcements are usually neglected. This is due to the difficulty in including these effects without generating an unduly large model. To include these effects using the existing software, the concrete can be modeled with 3D elements. The reinforcements can be included in the model as bar or cable elements. However, that would require a nodal line along every reinforcement. Therefore, this method would generate a huge model unmanageable even with modern computing facilities. Alternatively, the reinforcements can be assumed to be smeared uniformly within the structure and an average property can be included. This model is acceptable when the reinforcements are very closely spaced. However, for sparsely spaced reinforcements it would result in loss of accuracy, especially in important areas like the vicinity of large openings. In this paper a shell element for the analysis of pre-stressed and reinforced concrete structures has been proposed which alleviates this difficulty. This element can accommodate the reinforcing bars or cables anywhere

Fuel element transport container

International Nuclear Information System (INIS)

Benna, P.; Neuenfeldt, W.

1979-01-01

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

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.

REACTOR FUEL ELEMENTS TESTING CONTAINER

Science.gov (United States)

Whitham, G.K.; Smith, R.R.

1963-01-15

This patent shows a method for detecting leaks in jacketed fuel elements. The element is placed in a sealed tank within a nuclear reactor, and, while the reactor operates, the element is sparged with gas. The gas is then led outside the reactor and monitored for radioactive Xe or Kr. (AEC)

Thermo-elastic stress analysis of containment wall penetrations using improved finite element formulation

International Nuclear Information System (INIS)

Ramani, D.T.; Dimopoulos, A.; Heglin, B.M.

1979-01-01

An increased application of finite element techniques, particularly in evaluating structural integrity of nuclear containment walls around penetration points, has aroused considerable interest. Due to extreme thermal effects in the vicinity of penetrations, the concrete containment wall is subject to unwarranted cracking effects, which must be controlled in accordance with ASME-III Code. This paper essentially deals with a unique finite element method of analysis in which nonlinear heat transfer problem across the penetration assembly in the nuclear containment drywell wall, is formulated. Using this technique, thermal analysis, dealing with an evaluation of temperature distribution around axisymmetric penetration assembly accomodating main steam lines or other vital piping at 600 0 F, is carried out. The method of analysis considers steady-state heat transfer energy balance across the process-pipe, insulation layer, guard-pipe sleeve, two intermediate air layers and an axisymmetric opening in the concrete containment wall, the outer faces of which are maintained at ambient temperature of 120 0 F. (orig.)

Hazardous and other element characterization of new and used domestic plastic food containers using INAA and AAS

International Nuclear Information System (INIS)

Waheed, S.; Rahman, S.; Husnain, S.M.; Siddique, N.

2012-01-01

Instrumental Neutron Activation Analysis (INAA) and Atomic Absorption Spectroscopy methodology was developed to characterize the hazardous and other inorganic trace element constituents in new and used domestic plastic food containers. INAA due to its non destructive, highly sensitive, multielement and low detection limits characteristics was found to be a good technique for the characterization of polymeric products. Through the variation of irradiation, cooling and counting protocols Al, Ba, Br, Co, Cr, Eu, Fe, Hg, K, Mn, Na, Nd, Sb, Sc, Th, Ti, V and Zn were determined, while Atomic Absorption Spectroscopy was used as complementary technique to quantify toxic inorganic elements such as Cd, Pb and Cu. These elements are thought to originate from the polymer manufacturing processes. It was found that there was gradual increase in the concentration of most of these elements from new to used plastic samples. Moreover it was also observed that these inorganic elements are present in higher concentrations in the lower grade containers as compared to the high quality containers. It was also observed that the good quality containers even with the long usage do not degrade to such an extent as the low quality containers. (author)

Direct containment heating models in the CONTAIN code

International Nuclear Information System (INIS)

Washington, K.E.; Williams, D.C.

1995-08-01

The potential exists in a nuclear reactor core melt severe accident for molten core debris to be dispersed under high pressure into the containment building. If this occurs, the set of phenomena that result in the transfer of energy to the containment atmosphere and its surroundings is referred to as direct containment heating (DCH). Because of the potential for DCH to lead to early containment failure, the U.S. Nuclear Regulatory Commission (USNRC) has sponsored an extensive research program consisting of experimental, analytical, and risk integration components. An important element of the analytical research has been the development and assessment of direct containment heating models in the CONTAIN code. This report documents the DCH models in the CONTAIN code. DCH models in CONTAIN for representing debris transport, trapping, chemical reactions, and heat transfer from debris to the containment atmosphere and surroundings are described. The descriptions include the governing equations and input instructions in CONTAIN unique to performing DCH calculations. Modifications made to the combustion models in CONTAIN for representing the combustion of DCH-produced and pre-existing hydrogen under DCH conditions are also described. Input table options for representing the discharge of debris from the RPV and the entrainment phase of the DCH process are also described. A sample calculation is presented to demonstrate the functionality of the models. The results show that reasonable behavior is obtained when the models are used to predict the sixth Zion geometry integral effects test at 1/10th scale

Direct containment heating models in the CONTAIN code

Energy Technology Data Exchange (ETDEWEB)

Washington, K.E.; Williams, D.C.

1995-08-01

The potential exists in a nuclear reactor core melt severe accident for molten core debris to be dispersed under high pressure into the containment building. If this occurs, the set of phenomena that result in the transfer of energy to the containment atmosphere and its surroundings is referred to as direct containment heating (DCH). Because of the potential for DCH to lead to early containment failure, the U.S. Nuclear Regulatory Commission (USNRC) has sponsored an extensive research program consisting of experimental, analytical, and risk integration components. An important element of the analytical research has been the development and assessment of direct containment heating models in the CONTAIN code. This report documents the DCH models in the CONTAIN code. DCH models in CONTAIN for representing debris transport, trapping, chemical reactions, and heat transfer from debris to the containment atmosphere and surroundings are described. The descriptions include the governing equations and input instructions in CONTAIN unique to performing DCH calculations. Modifications made to the combustion models in CONTAIN for representing the combustion of DCH-produced and pre-existing hydrogen under DCH conditions are also described. Input table options for representing the discharge of debris from the RPV and the entrainment phase of the DCH process are also described. A sample calculation is presented to demonstrate the functionality of the models. The results show that reasonable behavior is obtained when the models are used to predict the sixth Zion geometry integral effects test at 1/10th scale.

Regulatory instrument review: Aging management of LWR cables, containment and basemat, reactor coolant pumps, and motor-operated valves

International Nuclear Information System (INIS)

Werry, E.V.; Somasundaram, S.

1995-09-01

The results of Stage 2 of the Regulatory Instrument Review are presented in this volume. Selected regulatory instruments, such as the Code of Federal Regulations (CFR), US Nuclear Regulatory Commission (NRC), Regulatory Guides, and ASME Codes, were investigated to determine the extent to which these regulations apply aging management to selected safety-related components in nuclear power plants. The Regulatory Instrument Review was funded by the NRC under the Nuclear Plant Aging Research (NPAR) program. Stage 2 of the review focused on four safety-related structures and components; namely, cables, containment and basemat, reactor coolant pumps, and motor-operated valves. The review suggests that the primary-emphasis of the regulatory instruments was on the design, construction, start-up, and operation of a nuclear power plant, and that aging issues were primarily addressed after an aging-related problem was recognized. This Stage 2 review confirms the results of the prior review; (see Regulatory Instrument Review: Management of Aging of LWR Major Safety-Related Components NUREG/CR-5490. The observations indicate that the regulations generally address management of age-related degradation indirectly. Specific age-related degradation phenomena frequently are dealt with in bulletins and notices or through generic issues, letters, etc. The major recommendation of this report, therefore, is that the regulatory instruments should more directly and explicitly address the aging phenomenon and the management of the age-related degradation process

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

Directory of Open Access Journals (Sweden)

Arindam Deb

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

Using hexamers to predict cis-regulatory motifs in Drosophila

Directory of Open Access Journals (Sweden)

Kibler Dennis

2005-10-01

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

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.

TECHNICAL AND REGULATORY CONSIDERATIONS IN USING FREIGHT CONTAINERS AS INDUSTRIAL PACKAGES

Energy Technology Data Exchange (ETDEWEB)

Opperman, E; Mark Hawk, M; Ron Natali, R

2007-10-16

The United States (US) Department of Energy (DOE), Office of Environmental Management (EM), is actively pursuing activities to reduce the radiological risk and clean up the environmental legacy of the nation's nuclear weapons programs. EM has made significant progress in recent years in the clean-up and closure of sites and is also focusing on longer-term activities necessary for the completion of the clean-up program. The packaging and transportation of contaminated demolition debris and low-level waste (LLW) materials in a safe and cost-effective manner are essential in completing this mission. Toward this end, the US Department of Transportation's (DOT) Final Rule on Hazardous Materials Regulation Final Rule issued January 26, 2004, included a new provision authorizing the use of Freight Containers (e.g., 20 and 40-foot ISO Containers) as Industrial Packages Type 1, 2, or 3 (IP-1, IP-2, and IP-3). This paper will discuss the technical and regulatory considerations in using these newly authorized and large packages for the packaging and transportation of LLW materials.

Researches on Mathematical Relationship of Five Elements of Containing Notes and Fibonacci Sequence Modulo 5

Directory of Open Access Journals (Sweden)

Zhaoxue Chen

2015-01-01

Full Text Available Considering the five periods and six qi’s theory in TCM almost shares a common basis of stem-branch system with the five elements of containing notes, studying the principle or mathematical structure behind the five elements of containing notes can surely bring a novel view for the five periods and six qi’s researches. By analyzing typical mathematical rules included in He tu, Luo shu, and stem-branch theory in TCM as well as the Fibonacci sequence especially widely existent in the biological world, novel researches are performed on mathematical relationship between the five elements of containing notes and the Fibonacci sequence modulo 5. Enlightened by elementary Yin or Yang number grouping principle of He tu, Luo shu, the 12534 and 31542 key number series of Fibonacci sequence modulo 5 are obtained. And three new arrangements about the five elements of containing notes are then introduced, which have shown close relationship with the two obtained key subsequences of the Fibonacci sequence modulo 5. The novel discovery is quite helpful to recover the scientific secret of the five periods and six qi’s theory in TCM as well as that of whole traditional Chinese culture system, but more data is needed to elucidate the TCM theory further.

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.

Technical findings and regulatory analysis for Generic Safety Issue II.E.4.3, ''Containment Integrity Check''

International Nuclear Information System (INIS)

Serkiz, A.W.

1988-04-01

This report contains the technical findings and regulatory analysis for Generic Safety Issue II.E.4.3, ''Containment Integrity Check.'' An evaluation of the containment isolation history from 1965 to 1983 reveals that (except for a small number of events) containment integrity has been maintained and that the majority of reported events have been events related to exceeding Technical Specification limits (or 0.6 of the allowable leakage level). In addition, more recent risk analyses have shown that allowable leakage rates even if increased by a factor of 10 would not significantly increase risk. Potential methods of continuous monitoring are identified and evaluated. Therefore, these technical findings and risk evaluations support closure of Generic Safety Issue II.E.4.3

[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.

Define rules for the exporter and importer of minerals or ores containing nuclear elements

International Nuclear Information System (INIS)

1969-01-01

The present resolution establishes regulations for the exporter of minerals or ores containing associated nuclear elements, and for the importer of chemical compounds of technical purity grade, containing a quantity of fissile of fertile materials equal to the existent in the exported material

Crystal chemistry, properties and synthesis of microporous silicates containing transition elements

International Nuclear Information System (INIS)

Chukanov, Nikita V; Pekov, Igor V; Rastsvetaeva, Ramiza K

2004-01-01

The review surveys and generalises recent data on synthesis methods, physicochemical properties and crystal chemistry of silicate microporous materials containing transition elements (amphoterosilicates). The frameworks of these materials, unlike those of usual aluminosilicate zeolites, are built from tetrahedrally coordinated atoms along with atoms of various elements (Ti, Nb, Zr, Ta, Sn, W, Fe, Mn, Zn, etc.) with coordination numbers of 6 or 5. Many amphoterosilicates possess ion-exchange properties and can serve as catalysts for redox reactions, sorbents, etc. The structural diversity of synthetic and natural amphoterosilicates provides the basis for the preparation of microporous materials with different properties.

A study on the recovery of TRU elements by a container-aided solid cathode

International Nuclear Information System (INIS)

Kwon, S.W.; Lee, J.H.; Woo, M.S.; Shim, J.B.; Kim, E.H.; Yoo, J.H.; Park, S.W.; Park, H.S.

2005-01-01

Pyroprocessing is a very prominent way for the recovery of the long-lived elements from the spent nuclear fuel. Electrorefining is a key technology of pyroprocessing and generally composed of two recovery steps - deposit of uranium onto a solid cathode and the recovery of TRU (TRansUranic) elements by a liquid cadmium cathode. The liquid cadmium cathode has some problems such as a cadmium volatilization problem, a low separation factor, and a complicates structure. In this study, CASC (Container-Aided Solid Cathode) was proposed as a candidate for replacing a liquid cadmium cathode and the deposition behavior of the cathode was examined during the electrorefining experiments. The CASC is a solid cathode surrounded with a porous ceramic container, where the container is used to capture the dripped deposit from the cathode. In the electrorefining experiment, the uranium used as a surrogate for the TRU elements, was effectively separated from cerium. The anode material and surface area were also investigated during electrolysis experiments for the more efficient electrorefining system. From the results of this study, it is concluded that the container-aided solid cathode can be a potential candidate for replacing a liquid cadmium cathode and the cathode should be developed further for the better electrolysis operation. (author)

Overlapping positive and negative regulatory domains of the human β-interferon gene

International Nuclear Information System (INIS)

Goodbourn, S.; Maniatis, T.

1988-01-01

Virus of poly(I) x poly(C) induction of human β-interferon gene expression requires a 40-base-pair DNA sequence designated the interferon gene regulatory element (IRE). Previous studies have shown that the IRE contains both positive and negative regulatory DNA sequences. To localize these sequences and study their interactions, the authors have examined the effects of a large number of single-base mutations within the IRE on β-interferon gene regulation. They find that the IRE consists of two genetically separable positive regulatory domains and an overlapping negative control sequence. They propose that the β-interferon gene is switched off in uninduced cells by a repressor that blocks the interaction between one of the two positive regulatory sequences and a specific transcription factor. Induction would then lead to inactivation or displacement of the repressor and binding of transcription factors to both positive regulatory domains

Electrochemical synthesis of transition element complexes with carboxyl- and carbonyl-containing ligands

International Nuclear Information System (INIS)

Frolov, V.Yu.; Bolotin, S.N.; Panyushkin, V.T.

2005-01-01

Complexes of d- and f-elements (E = Cu, Ni, Zn, Nd, Tb, Pr, Gd, Er) with carboxyl- and carbonyl-containing ligands were synthesized by the electrochemical method. The products were characterized by elemental analysis, thermal gravimetric analysis and IR spectra. The influence exerted by a number of factors on the process course was studied. The dependence of the electro synthesis parameters on the composition of the forming compounds was established. A new method for anodic synthesis of these compounds was developed [ru

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

Directory of Open Access Journals (Sweden)

Junhua Li

2014-01-01

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

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.

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

Science.gov (United States)

Tarpine, Ryan; Istrail, Sorin

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

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

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Kissinger Jessica C

2007-01-01

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

Acid pressure leaching of a concentrate containing uranium, thorium and rare earth elements

International Nuclear Information System (INIS)

Lan Xinghua; Peng Ruqing.

1987-01-01

The acid pressure leaching of a concentrate containing rinkolite for recovering uranium, thorium and rare earth elements is described. The laboratory and the pilot plant test results are given. Under the optimum leaching conditions, the recovery of uranium, thorium and rare earth elements are 82.9%, 86.0% and 88.3% respectively. These results show that the acid pressure leaching process is a effective process for treating the concentrate

High resolution quantitative element mapping of neuromelanin-containing neurons

Energy Technology Data Exchange (ETDEWEB)

Reinert, Tilo [Nukleare Festkoerperphysik, Universitaet Leipzig, Linnestrasse 5, 04103 Leipzig (Germany)]. E-mail: reinert@physik.uni-leipzig.de; Fiedler, Anja [Nukleare Festkoerperphysik, Universitaet Leipzig, Linnestrasse 5, 04103 Leipzig (Germany); Paul-Flechsig-Institut fuer Hirnforschung, Universitaet Leipzig, Jahnallee 59, 04109 Leipzig (Germany); Morawski, Markus [Paul-Flechsig-Institut fuer Hirnforschung, Universitaet Leipzig, Jahnallee 59, 04109 Leipzig (Germany); Arendt, Thomas [Paul-Flechsig-Institut fuer Hirnforschung, Universitaet Leipzig, Jahnallee 59, 04109 Leipzig (Germany)

2007-07-15

Neuromelanin is a dark coloured intracellular pigment that appears in a specific population of neurons (dopaminergic and noradrenergic) predominantly in the substantia nigra and in the locus coeruleus. In recent years, there is increasing interest in the role of neuromelanin because of a hypothesised link between this pigment and the cell death of neuromelanin-containing neurons in Parkinson's disease (PD). Therefore, the role of neuromelanin in the pathology of PD is an actual focus in neuroscience. We have investigated the elemental contents and distributions of sulphur, calcium, iron, nickel and copper of neuromelanin in dopaminergic neurons for a Parkinson case and a control case (in situ, 6 {mu}m brain sections). There was no difference in the iron concentration between the two cases. However, the calcium concentration was 3-fold higher in the Parkinson case, whereas the copper and nickel concentrations decreased. An ultrastructural investigation of the concentrations of calcium and iron within the neuromelanin suggests that these two elements are not necessarily co-localized.

Finite element analysis of adanced composite structures containing mechanically fastened joints

International Nuclear Information System (INIS)

Baumann, E.

1982-01-01

Although the usual engineering practice is to ignore joint effects in finite element models of overall structures, there are times when the inclusion of fastener effects in a model is necessary for accurate analysis. This paper describes some simple but accurate methods for accommodating this modeling requirement. The approach involves correlation of test results from a few composite mechanically fastened joints with finite element analyses of joints. It is assumed that if the fastener actions in the test articles can be properly predicted by simple finite element techniques, then these same techniques can be applied to large overall structure models. During the course of this test-analysis effort it was determined that it is possible to obtain correct results for overall structure-joint analyses by using simple modeling concepts provided special care is employed. Also, some emphasis is given in this paper to the importance of properly reducing test data in order to obtain meaningful correlations with finite element analysis. Finally, for those interested, the appendix contains brief descriptions of the test results and failure modes explored in the test program. (orig.)

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'.

Nonlinear finite element analysis of nuclear reinforced prestressed concrete containments up to ultimate load capacity

International Nuclear Information System (INIS)

Gupta, A.; Singh, R.K.; Kushwaha, H.S.; Mahajan, S.C.; Kakodkar, A.

1996-01-01

For safety evaluation of nuclear structures a finite element code ULCA (Ultimate Load Capacity Assessment) has been developed. Eight/nine noded isoparametric quadrilateral plate/shell element with reinforcement as a through thickness discrete but integral smeared layer of the element is presented to analyze reinforced and prestressed concrete structures. Various constitutive models such as crushing, cracking in tension, tension stiffening and rebar yielding are studied and effect of these parameters on the reserve strength of structures is brought out through a number of benchmark tests. A global model is used to analyze the prestressed concrete containment wall of a typical 220 MWe Pressurized Heavy Water Reactor (PHWR) up to its ultimate capacity. This demonstrates the adequacy of Indian PHWR containment design to withstand severe accident loads

Process and container system for transferring or transporting fuel elements from a nuclear power station to a store

International Nuclear Information System (INIS)

Vox, A.J.

1984-01-01

A system of containers with three types of containers (an inside container, a transport container and a storage container) is used. One either sets the inside container open on the lid side into the transport container first in the water pond of the nuclear power station, and one then sets the fuel elements into the inside container, or one places the inside container, loaded with fuel elements away from the transport container, into the transport container. Both containers are then closed and are transported to the store as a unit. The storage container open on the lid side is prepared there, the floor of the transport container is opened and this, together with the inside container, is lifted above the storage container or set above the storage container. The inside container is then lowered onto the storage container, the transport container is removed and the lid of the storage container is closed. (orig./HP) [de

MicroRNAs as regulatory elements in psoriasis

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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.

Free-drop analysis of the transport container for hydrogen isotopes

International Nuclear Information System (INIS)

Lee, M. S.; Hong, C. S.; Baek, S. W.; Ahn, D. H.; Kim, K. R.; Lee, S. H.; Lim, S. P.; Jung, H. S.

2002-01-01

The vessel used for the transport of radioactive materials, containing hydrogen isotopes is evaluated for hypothetical accident conditions according to national regulations. The computational analysis is a cost effective tool to minimize testing and streamline the regulatory procedures, and supports experimental programs to qualify the container for the safe transport of radioactive materials. The numerical analysis of 9m free-drop onto a flat unyielding, horizontal surface has been performed using the explicit finite element computer program ABAQUS. Especially free-drop simulations for 30.deg. C tilted condition is precisely estimated

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)

[Spectroscopic Research on Slag Nanocrystal Glass Ceramics Containing Rare Earth Elements].

Science.gov (United States)

Ouyang, Shun-li; Li, Bao-wei; Zhang, Xue-feng; Jia, Xiao-lin; Zhao, Ming; Deng, Lei-bo

2015-08-01

The research group prepared the high-performance slag nanocrystal glass ceramics by utilizing the valuable elements of the wastes in the Chinese Bayan Obo which are characterized by their symbiotic or associated existence. In this paper, inductively coupled plasma emission spectroscopy (ICP), X-ray diffraction (XRD), Raman spectroscopy (Raman) and scanning electron microscopy (SEM) are all used in the depth analysis for the composition and structure of the samples. The experiment results of ICP, XRD and SEM showed that the principal crystalline phase of the slag nanocrystal glass ceramics containing rare earth elements is diopside, its grain size ranges from 45 to 100 nm, the elements showed in the SEM scan are basically in consistent with the component analysis of ICP. Raman analysis indicated that its amorphous phase is a three-dimensional network structure composed by the structural unit of silicon-oxy tetrahedron with different non-bridging oxygen bonds. According to the further analysis, we found that the rare earth microelement has significant effect on the network structure. Compared the nanocrystal slag glass ceramic with the glass ceramics of similar ingredients, we found that generally, the Raman band wavenumber for the former is lower than the later. The composition difference between the glass ceramics and the slag nanocrystal with the similar ingredients mainly lies on the rare earth elements and other trace elements. Therefore, we think that the rare earth elements and other trace elements remains in the slag nanocrystal glass ceramics have a significant effect on the network structure of amorphous phase. The research method of this study provides an approach for the relationship among the composition, structure and performance of the glass ceramics.

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.

12 CFR 562.2 - Regulatory reports.

Science.gov (United States)

2010-01-01

... § 562.2 Regulatory reports. (a) Definition and scope. This section applies to all regulatory reports, as... (TFR) are examples of regulatory reports. Regulatory reports are regulatory documents, not accounting... limited to, the accounting instructions provided in the TFR, guidance contained in OTS regulations...

Radiation sensitive polymers of oxygen-substituted maleimides and elements containing same

International Nuclear Information System (INIS)

Wilson, J.C.

1977-01-01

Radiation sensitive polymers comprising from about 1 to 100 mole % of a polymerized maleimide monomer consisting of a hydrocarbon group having from 2 to 20 carbon atoms, preferably a bridged hydrocarbon group having from 6 to 10 carbon atoms and from 0 to about 99 mole % of at least one additional polymerized ethylenically unsaturated monomer are described. The polymers are soluble in organic solvents, possess desirably high glass transition temperatures and are capable of undergoing a photochemical reaction to yield polymers having isocyanate and oxy-substituted cyclopropane moieties which are capable of crosslinking in the presence of active hydrogen-containing compounds. The polymers are useful in radiation sensitive compositions and elements containing same

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

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James J. Lewis

2016-09-01

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

Determining arsenic in elemental antimony containing selenium and tellurium

International Nuclear Information System (INIS)

Mogileva, M.G.; Kozlova, E.L.

1986-01-01

The authors have developed a method of determining arsenic in metallic antimony containing selenium, tellurium, and mercury, in which they isolated it in elementary form for separation from the antimony and the associated elements (silicon and phosphorus), followed by colorimetric determination of the arsenic from arsenic-molbdenum blue. The reducing agents to reduce the arsenic were sodium hypophosphite and tin(II) chloride, which do not reduce antimony and which do not interfere with the determination. This method of determining arsenic in metallic antimony without preliminary separation of the selenium and tellurium is in no way inferior in accuracy to the method given in All-Union State Standard (GOST) 1367.4-83

Method of removing and recovering elemental sulfur from highly reducing gas streams containing sulfur gases

Science.gov (United States)

Gangwal, Santosh K.; Nikolopoulos, Apostolos A.; Dorchak, Thomas P.; Dorchak, Mary Anne

2005-11-08

A method is provided for removal of sulfur gases and recovery of elemental sulfur from sulfur gas containing supply streams, such as syngas or coal gas, by contacting the supply stream with a catalyst, that is either an activated carbon or an oxide based catalyst, and an oxidant, such as sulfur dioxide, in a reaction medium such as molten sulfur, to convert the sulfur gases in the supply stream to elemental sulfur, and recovering the elemental sulfur by separation from the reaction medium.

Composition containing transuranic elements for use in the homeopathic treatment of aids

International Nuclear Information System (INIS)

Lustig, D.

1996-01-01

A homeopathic remedy consisting of a composition containing one or more transuranic elements, particularly plutonium, for preventing and treating acquired immunodeficiency syndrome (AIDS) in humans, as well as seropositivity for human immunodeficiency virus (HIV). Said composition is characterized in that it uses any chemical or isotopic form of one or more transuranic elements (neptunium, plutonium, americium, curium, berkelium, californium or einsteinium), particularly plutonium, said form being diluted and dynamized according to conventional homeopathic methods, particularly the so-called Hahnemann and Korsakov methods, and provided preferably but not exclusively in the form of lactose and/or saccharose globules or granules impregnated with the active principle of said composition. (author)

Determination of urine metabolites containing radioactivatable elements by molecular neutron activation analysis

International Nuclear Information System (INIS)

Blotcky, A.J.; Rack, E.P.

1986-01-01

As urine is a final stage for the metabolic pathways of essential trace elements or chemical toxins, it is becoming increasingly important to not only report levels of trace elements but to determine the molecular or ionic identity of these trace elements. For a biological system such as urine, a molecular neutron activation analysis (MONAA) approach must involve a deproteinization step, where necessary, to ensure that metabolites such as amino acids, bases, r nucleosides are not protein bound prior to chemical separation. This can involve the simple application of ammonia or acid hydrolysis. All separations for the metabolites containing the radioactivatable element must be performed prior to neutron irradiation and subsequent radioassay for the metabolite. Separation procedures can include high-pressure liquid chromotography (HPLC), ion-exchange chromatography, size exclusion chromatography, solvent extraction, and/or gas chromatography. After separation, the separated metabolite is neutron irradiated and and radioassayed for the radioactivity in the metabolite. A review of previous work involving the determination of hormonal iodine, iodoamino acids, chlorinated pesticides, trimethyl-selenonium, and selenoamino acids in urine is discussed

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

Is container type the biggest predictor of trace element and BPA leaching from drinking water bottles?

Science.gov (United States)

Rowell, Candace; Kuiper, Nora; Preud'Homme, Hugues

2016-07-01

The knowledge-base of bottled water leachate is highly contradictory due to varying methodologies and limited multi-elemental and/or molecular analyses; understanding the range of contaminants and their pathways is required. This study determined the leaching potential and leaching kinetics of trace elements, using consistent comprehensive quantitative and semi-quantitative (79 elements total) analyses, and BPA, using isotopic dilution and MEPS pre-concentration with UHPLC-ESI-QTOF. Statistical methods were used to determine confounders and predictors of leaching and human health risk throughout 12days of UV exposure and after exposure to elevated temperature. Various types of water were used to assess the impact of water quality. Results suggest Sb leaching is primarily dependent upon water quality, not container type. Bottle type is a predictor of elemental leaching for Pb, Ba, Cr, Cu, Mn and Sr; BPA was detected in samples from polycarbonate containers. Health risks from the consumption of bottled water increase after UV exposure. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

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

5 CFR 880.102 - Regulatory structure.

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Regulatory structure. 880.102 Section 880.102 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS... Regulatory structure. (a) This part contains the following subparts: (1) Subpart A contains general...

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.

Trace elements in rock phosphates and P containing mineral and organo-mineral fertilizers sold in Germany

Energy Technology Data Exchange (ETDEWEB)

Kratz, Sylvia, E-mail: sylvia.kratz@jki.bund.de; Schick, Judith; Schnug, Ewald

2016-01-15

68 rock phosphates and 162 P containing (organo-)mineral fertilizers sold in Germany were evaluated with regard to trace element contents. While Al, As, B, Be, Cd, Cr, Mo, Ni, Pb, Sb, Se, Tl, U, and Zn were higher in sedimentary than in igneous rock phosphates, the opposite was true for Co, Cu, Sn, Mn, Ti, Fe, and Sr. Comparing element concentrations to the currently valid legal limit values defined by the German Fertilizer Ordinance, it was found that some PK and many straight P fertilizers (superphosphate, triple superphosphate, partly acidulated rock phosphates) exceeded the limit of 50 mg Cd/kg P{sub 2}O{sub 5}. Mean values for As, Ni, Pb, and Tl remained below legal limits in almost all cases. While no legal limit has been defined for U in Germany yet, the limit of 50 mg U/kg P{sub 2}O{sub 5} for P containing fertilizers proposed by the German Commission for the Protection of Soils was clearly exceeded by mean values for all fertilizer types analyzed. A large share of the samples evaluated in this work contained essential trace elements at high concentrations, with many of them not being declared as such. Furthermore, trace elements supplied with these fertilizers at a fertilization rate leveling P uptake would exceed trace element uptake by crops. This may become most relevant for B and Fe, since many crops are sensitive to an oversupply of B, and Fe loads exceeding plant uptake may immobilize P supplies for the crops by forming Fe phosphate salts. The sample set included two products made from thermochemically treated sewage sludge ash. The products displayed very high concentrations of Fe and Mn and exceeded the legal limit for Ni, emphasizing the necessity to continue research on heavy metal removal from recycled raw materials and the development of environmentally friendly and agriculturally efficient fertilizer products. - Highlights: • Mineral fertilizers (MF) sold in Germany often exceed legal limits for Cd • MF sold in Germany contain high

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.

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

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.

Effectiveness of quenchers to reduce radiolysis of (111)In- or (177)Lu-labelled methionine-containing regulatory peptides. Maintaining radiochemical purity as measured by HPLC.

Science.gov (United States)

de Blois, Erik; Chan, Ho Sze; Konijnenberg, Mark; de Zanger, Rory; Breeman, Wouter A P

2012-01-01

An overview how to measure and to quantify radiolysis by the addition of quenchers and to maintain Radio-Chemical Purity (RCP) of vulnerable methionine-containing regulatory peptides is presented. High RCP was only achieved with a combination of quenchers. However, quantification of RCP is not standardized, and therefore comparison of radiolabelling and RCP of regulatory peptides between different HPLC-systems and between laboratories is cumbersome. Therefore we suggest a set of standardized requirements to quantify RCP by HPLC for radiolabelled DTPA- or DOTA-peptides. Moreover, a dosimetry model was developed to calculate the doses in the reaction vials during radiolabelling and storage of the radiopeptides, and to predict RCP in the presence and absence of quenchers. RCP was measured by HPLC, and a relation between radiation dose and radiolysis of RCP was established. The here described quenchers are tested individually as ƒ(concentration) to investigate efficacy to reduce radiolysis of radiolabelled methionine-containing regulatory peptides.

Detection of Weakly Conserved Ancestral Mammalian RegulatorySequences by Primate Comparisons

Energy Technology Data Exchange (ETDEWEB)

Wang, Qian-fei; Prabhakar, Shyam; Chanan, Sumita; Cheng,Jan-Fang; Rubin, Edward M.; Boffelli, Dario

2006-06-01

Genomic comparisons between human and distant, non-primatemammals are commonly used to identify cis-regulatory elements based onconstrained sequence evolution. However, these methods fail to detectcryptic functional elements, which are too weakly conserved among mammalsto distinguish from nonfunctional DNA. To address this problem, weexplored the potential of deep intra-primate sequence comparisons. Wesequenced the orthologs of 558 kb of human genomic sequence, coveringmultiple loci involved in cholesterol homeostasis, in 6 nonhumanprimates. Our analysis identified 6 noncoding DNA elements displayingsignificant conservation among primates, but undetectable in more distantcomparisons. In vitro and in vivo tests revealed that at least three ofthese 6 elements have regulatory function. Notably, the mouse orthologsof these three functional human sequences had regulatory activity despitetheir lack of significant sequence conservation, indicating that they arecryptic ancestral cis-regulatory elements. These regulatory elementscould still be detected in a smaller set of three primate speciesincluding human, rhesus and marmoset. Since the human and rhesus genomesequences are already available, and the marmoset genome is activelybeing sequenced, the primate-specific conservation analysis describedhere can be applied in the near future on a whole-genome scale, tocomplement the annotation provided by more distant speciescomparisons.

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

Mechanistically Distinct Pathways of Divergent Regulatory DNA Creation Contribute to Evolution of Human-Specific Genomic Regulatory Networks Driving Phenotypic Divergence of Homo sapiens.

Science.gov (United States)

Glinsky, Gennadi V

2016-09-19

Thousands of candidate human-specific regulatory sequences (HSRS) have been identified, supporting the hypothesis that unique to human phenotypes result from human-specific alterations of genomic regulatory networks. Collectively, a compendium of multiple diverse families of HSRS that are functionally and structurally divergent from Great Apes could be defined as the backbone of human-specific genomic regulatory networks. Here, the conservation patterns analysis of 18,364 candidate HSRS was carried out requiring that 100% of bases must remap during the alignments of human, chimpanzee, and bonobo sequences. A total of 5,535 candidate HSRS were identified that are: (i) highly conserved in Great Apes; (ii) evolved by the exaptation of highly conserved ancestral DNA; (iii) defined by either the acceleration of mutation rates on the human lineage or the functional divergence from non-human primates. The exaptation of highly conserved ancestral DNA pathway seems mechanistically distinct from the evolution of regulatory DNA segments driven by the species-specific expansion of transposable elements. Genome-wide proximity placement analysis of HSRS revealed that a small fraction of topologically associating domains (TADs) contain more than half of HSRS from four distinct families. TADs that are enriched for HSRS and termed rapidly evolving in humans TADs (revTADs) comprise 0.8-10.3% of 3,127 TADs in the hESC genome. RevTADs manifest distinct correlation patterns between placements of human accelerated regions, human-specific transcription factor-binding sites, and recombination rates. There is a significant enrichment within revTAD boundaries of hESC-enhancers, primate-specific CTCF-binding sites, human-specific RNAPII-binding sites, hCONDELs, and H3K4me3 peaks with human-specific enrichment at TSS in prefrontal cortex neurons (P sapiens is driven by the evolution of human-specific genomic regulatory networks via at least two mechanistically distinct pathways of creation of

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

Science.gov (United States)

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

2017-09-01

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

Artificial Leaks in Container Closure Integrity Testing: Nonlinear Finite Element Simulation of Aperture Size Originated by a Copper Wire Sandwiched between the Stopper and the Glass Vial.

Science.gov (United States)

Nieto, Alejandra; Roehl, Holger; Brown, Helen; Adler, Michael; Chalus, Pascal; Mahler, Hanns-Christian

2016-01-01

Container closure integrity (CCI) testing is required by different regulatory authorities in order to provide assurance of tightness of the container closure system against possible contamination, for example, by microorganisms. Microbial ingress CCI testing is performed by incubation of the container closure system with microorganisms under specified testing conditions. Physical CCI uses surrogate endpoints, such as coloration by dye solution ingress or gas flow (helium leakage testing). In order to correlate microbial CCI and physical CCI test methods and to evaluate the methods' capability to detect a given leak, artificial leaks are being introduced into the container closure system in a variety of different ways. In our study, artificial leaks were generated using inserted copper wires between the glass vial opening and rubber stopper. However, the insertion of copper wires introduces leaks of unknown size and shape. With nonlinear finite element simulations, the aperture size between the rubber stopper and the glass vial was calculated, depending on wire diameter and capping force. The dependency of the aperture size on the copper wire diameter was quadratic. With the data obtained, we were able to calculate the leak size and model leak shape. Our results suggest that the size as well as the shape of the artificial leaks should be taken into account when evaluating critical leak sizes, as flow rate does not, independently, correlate to hole size. Capping force also affected leak size. An increase in the capping force from 30 to 70 N resulted in a reduction of the aperture (leak size) by approximately 50% for all wire diameters. From 30 to 50 N, the reduction was approximately 33%. Container closure integrity (CCI) testing is required by different regulatory authorities in order to provide assurance of tightness of the container closure system against contamination, for example, by microorganisms. Microbial ingress CCI testing is performed by incubation of the

Numerical Modeling of Local Penetration of Chloride-Containing Medium into Construction Elements Made of Reinforced Concrete

Science.gov (United States)

Ovchinnikov, I. I.; Snezhkina, O. V.; Ovchinnikov, I. G.

2017-11-01

The task of modeling the kinetics of chloride-containing medium penetration into construction elements out of reinforced concrete that have partially damaged anti-corrosion protective coatings is being discussed. As a result, chlorides penetrate the construction element via local surface areas which leads to irregularities between chloride dispersion volumes. The kinetics of chloride penetration is described by the equation of diffusion to solve which the CONDUCT software complex by professor S. Patankar was used. The methodology used to solve the diffusional equation is described. The results of the evaluation of concentration field in the axial section of a cylindrical construction element, which was centrally reinforced, are given. The chloride diffusion was symmetrical to the axis, the medium was applied through the central ring area equal to one third of the side surface area while the rest of the surface was isolated. It was shown that the methodology of evaluation and its algorithm allow one to evaluate the concentration field of chlorides in reinforced concrete structural elements under local or asymmetrical action of the chloride - containing medium. The example given illustrates that after a certain time interval critical the concentration of chlorides develops even in protected areas which are located far from the initial damaged area. This means that the corrosion destruction of reinforced elements develops not only in the immediate damage area, but also further away from it.

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

Algebraic manipulation of the states associated with the U(5)containsO(5)containsO(3) chain of groups: Orthonormalization and matrix elements

International Nuclear Information System (INIS)

Yannouleas, C.; Pacheco, J.M.

1989-01-01

A collection of procedures able to perform algebraic manipulations for the orthonormalization and for the calculation of matrix elements between the states associated with the U(5)containsO(5)containsO(3) chain of groups is presented. These procedures combine both the exact- and the bigfloat-arithmetic modes and thus return arbitrarily accurate results; this is particulary relevant to the Gram-Schmidt orthonormalization, where strong cancellations usually pose serious problems in all floating-point implementations. (orig.)

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

Analyses of a steel containment vessel with an outer contact structure under severe internal overpressurization conditions

International Nuclear Information System (INIS)

Porter, V.L.

1993-01-01

Many Mark-I and Mark-II BWR plants are designed with a steel vessel as the primary containment. Typically, the steel containment vessel (SCV) is enclosed within a reinforced concrete shield building with only a small gap (50--90mm) separating the two structures. This paper describes finite element analyses performed to evaluate the effects of contact and friction between a steel containment vessel and an outer contact structure when the containment vessel is subjected to large internal pressures. These computations were motivated by a joint program on containment integrity involving the Nuclear Power Engineering Corporation (NUPEC) of Japan, the US Nuclear Regulatory Commission (NRC), and Sandia National Laboratories for testing model containments

Waste container and method for containing waste

International Nuclear Information System (INIS)

Ono, Akira; Matsushita, Mitsuhiro; Doi, Makoto; Nakatani, Seiichi.

1990-01-01

In a waste container, water-proof membranes and rare earth element layers are formed on the inner surface of a steel plate concrete container in which steel plates are embedded. Further, rear earth element detectors are disposed each from the inner side of the steel plate concrete container by way of a pressure pipe to the outer side of the container. As a method for actually containing wastes, when a plurality of vessels in which wastes are fixed are collectively enhoused to the waste container, cussioning materials are attached to the inner surface of the container and wastes fixing containers are stacked successively in a plurality of rows in a bag made of elastic materials. Subsequently, fixing materials are filled and tightly sealed in the waste container. When the waste container thus constituted is buried underground, even if it should be deformed to cause intrusion of rain water to the inside of the container, the rare earth elements in the container dissolved in the rain water can be detected by the detectors, the containers are exchanged before the rain water intruding to the inner side is leached to the surrounding ground, to previously prevent the leakage of radioactive nuclides. (K.M.)

76 FR 63969 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

Science.gov (United States)

2011-10-14

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of Amendment No. 1 to Proposed Rule Change To Adopt FINRA Rule 2231 (Customer Account Statements) in the Consolidated... Account Statements) in the Consolidated FINRA Rulebook (``Notice''). The Notice contained incorrect...

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

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.

Investigation on the status of rare earth elements contained in the powder of spent fluorescent lamps

International Nuclear Information System (INIS)

Belardi, G.; Ippolito, N.; Piga, L.; Serracino, M.

2014-01-01

Highlights: • Most of rare earth elements are contained in particles of size finer than 7 μm. • Most of Si, K and Na are contained in the coarser size-fractions. • The phases in the size-fractions of the fluorescent powder have been determined. • Europium is contained in yttrium oxide and in vanadium–yttrium oxides. • The crystallo–chemical composition of all the phases has been determined. - Abstract: The aim of this study is to examine the status of rare earth elements (REE) contained in the chemical compounds that make up the powder of spent fluorescent lamps, with a view of their recovery. The status of REE in the as-received powder, as well as in a few size-class fractions of it, has been established. This way, only those size-class fractions containing high REE concentrations can be considered in a recovery process. The investigation has been carried out using particle-size, chemical, TGA/DTA, XRPD, SEM-EDS and EMPA analyses. The last technique enabled to establish the status of REE within the lattice of the chemical compounds present in the powder. The fineness of the as-received powder and the higher REE concentration in the finest size-classes suggest that physical methods of separation should not be used to separate the REE-containing chemical compounds from each other. Leaching methods seem more suitable with a material of such size

Assessment of stress-strain data suitable for finite-element elastic--plastic analysis of shipping containers

International Nuclear Information System (INIS)

Rack, H.J.; Knorovsky, G.A.

1978-09-01

Stress-strain data which describes the influence of strain rate and temperature on the mechanical response of materials presently being used for light water reactor fuel shipping containers have been assembled. Selection of data has been limited to that which is suitable for use in finite-element elastic--plastic analysis of shipping containers (e.g., they must include complete material history profiles). Based on this information, recommendations have been made for further work which is required to complete the necessary data base

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

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.

Mutational robustness of gene regulatory networks.

Directory of Open Access Journals (Sweden)

Aalt D J van Dijk

Full Text Available Mutational robustness of gene regulatory networks refers to their ability to generate constant biological output upon mutations that change network structure. Such networks contain regulatory interactions (transcription factor-target gene interactions but often also protein-protein interactions between transcription factors. Using computational modeling, we study factors that influence robustness and we infer several network properties governing it. These include the type of mutation, i.e. whether a regulatory interaction or a protein-protein interaction is mutated, and in the case of mutation of a regulatory interaction, the sign of the interaction (activating vs. repressive. In addition, we analyze the effect of combinations of mutations and we compare networks containing monomeric with those containing dimeric transcription factors. Our results are consistent with available data on biological networks, for example based on evolutionary conservation of network features. As a novel and remarkable property, we predict that networks are more robust against mutations in monomer than in dimer transcription factors, a prediction for which analysis of conservation of DNA binding residues in monomeric vs. dimeric transcription factors provides indirect evidence.

Shell finite element of reinforced concrete for internal pressure analysis of nuclear containment building

Energy Technology Data Exchange (ETDEWEB)

Lee, Hong Pyo, E-mail: hplee@kepri.re.k [Nuclear Power Laboratory, Korea Electric Power Research Institute, 103-16 Munji-Dong, Yuseong-Gu, Daejeon 305-380 (Korea, Republic of)

2011-02-15

Research highlights: Finite element program with 9-node degenerated shell element was developed. The developed program was mainly forced to analyze nuclear containment building. Concrete material model is adapted Niwa and Yamada failure criteria. The performance of program developed is verified through various numerical examples. The numerical analysis results similar to the experimental data. - Abstract: This paper describes a 9-node degenerated shell finite element (FE), an analysis program developed for ultimate pressure capacity evaluation and nonlinear analysis of a nuclear containment building. The shell FE developed adopts the Reissner-Mindlin (RM) assumptions to consider the degenerated shell solidification technique and the degree of transverse shear strain occurring in the structure. The material model of the concrete determines the level of the concrete stress and strain by using the equivalent stress-equivalent strain relationship. When a crack occurs in the concrete, the material behavior is expressed through the tension stiffening model that takes adhesive stress into account and through the shear transfer mechanism and compressive strength reduction model of the crack plane. In addition, the failure envelope proposed by Niwa is adopted as the crack occurrence criteria for the compression-tension region, and the failure envelope proposed by Yamada is used for the tension-tension region. The performance of the program developed is verified through various numerical examples. The analysis based on the application of the shell FE developed from the results of verified examples produced results similar to the experiment or other analysis results.

Containment leakage rate testing requirements

International Nuclear Information System (INIS)

Arndt, E.G.

1992-01-01

This report presents the status of several documents under revision or development that provide requirements and guidance for testing nuclear power plant containment systems for leakage rates. These documents include the general revision to 10 CFR Part 50, Appendix J; the regulatory guide affiliated with the revision to Appendix J; the national standard that the regulatory guide endorses, ANSI/ANS-56.8, 'Containment System Leakage Rate Testing Requirements'; and the draft industry Licensing Topical Report, 'Standardized Program for Primary Containment Integrity Testing'. The actual or potential relationships between these documents are also explored

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)

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...

Single nucleotide polymorphism in transcriptional regulatory regions and expression of environmentally responsive genes

International Nuclear Information System (INIS)

Wang, Xuting; Tomso, Daniel J.; Liu Xuemei; Bell, Douglas A.

2005-01-01

Single nucleotide polymorphisms (SNPs) in the human genome are DNA sequence variations that can alter an individual's response to environmental exposure. SNPs in gene coding regions can lead to changes in the biological properties of the encoded protein. In contrast, SNPs in non-coding gene regulatory regions may affect gene expression levels in an allele-specific manner, and these functional polymorphisms represent an important but relatively unexplored class of genetic variation. The main challenge in analyzing these SNPs is a lack of robust computational and experimental methods. Here, we first outline mechanisms by which genetic variation can impact gene regulation, and review recent findings in this area; then, we describe a methodology for bioinformatic discovery and functional analysis of regulatory SNPs in cis-regulatory regions using the assembled human genome sequence and databases on sequence polymorphism and gene expression. Our method integrates SNP and gene databases and uses a set of computer programs that allow us to: (1) select SNPs, from among the >9 million human SNPs in the NCBI dbSNP database, that are similar to cis-regulatory element (RE) consensus sequences; (2) map the selected dbSNP entries to the human genome assembly in order to identify polymorphic REs near gene start sites; (3) prioritize the candidate polymorphic RE containing genes by searching the existing genotype and gene expression data sets. The applicability of this system has been demonstrated through studies on p53 responsive elements and is being extended to additional pathways and environmentally responsive genes

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

Science.gov (United States)

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

2010-11-01

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

75 FR 62893 - Draft Regulatory Guide: Issuance, Availability

Science.gov (United States)

2010-10-13

... the ``Regulatory Guides'' collection of the NRC's Electronic Reading Room at http://www.nrc.gov... NUCLEAR REGULATORY COMMISSION [NRC-2010-0321] Draft Regulatory Guide: Issuance, Availability... Guide, DG-1196, ``Qualification for Cement Grouting for Prestressing Tendons in Containment Structures...

The regulatory effects of low-dose ionizing radiation on Ikaros-autotaxin interaction

Energy Technology Data Exchange (ETDEWEB)

Kang, Hana; Cho, Seong Jun; Kim, Sung Jin; Nam, Seon Young; Yang, Kwang Hee [KHNP Radiation Health Institute, Korea Hydro and Nuclear Power Co, Seoul (Korea, Republic of)

2016-11-15

Ikaros, a transcription factor containing zinc-finger motif, has known as a critical regulator of hematopoiesis in immune system. Ikaros protein modulates the transcription of target genes via binding to the regulatory elements of the genes promoters. However the regulatory function of Ikaros in other organelle except nuclear remains to be determined. This study explored radiation-induced modulatory function of Ikaros in cytoplasm. The results showed that Ikaros protein lost its DNA binding ability after LDIR (low-dose ionizing radiation) exposure. Cell fractionation and Western blot analysis showed that Ikaros protein was translocated into cytoplasm from nuclear by LDIR. This was confirmed by immunofluorescence assay. We identified Autotaxin as a novel protein which potentially interacts with Ikaros through in vitro protein-binding screening. Co-immunoprecipitation assay revealed that Ikaros and Autotaxin are able to bind each other. Autotaxin is a crucial enzyme generating lysophosphatidic acid (LPA), a phospholipid mediator, which has potential regulatory effects on immune cell growth and motility. Our results indicate that LDIR potentially regulates immune system via protein-protein interaction of Ikaros and Autotaxin.

Molecular genetics and epigenetics of CACTA elements

KAUST Repository

Fedoroff, Nina V.

2013-08-21

The CACTA transposons, so named for a highly conserved motif at element ends, comprise one of the most abundant superfamilies of Class 2 (cut-and-paste) plant transposons. CACTA transposons characteristically include subterminal sequences of several hundred nucleotides containing closely spaced direct and inverted repeats of a short, conserved sequence of 14-15 bp. The Supressor-mutator (Spm) transposon, identified and subjected to detailed genetic analysis by Barbara McClintock, remains the paradigmatic element of the CACTA family. The Spm transposon encodes two proteins required for transposition, the transposase (TnpD) and a regulatory protein (TnpA) that binds to the subterminal repeats. Spm expression is subject to both genetic and epigenetic regulation. The Spm-encoded TnpA serves as an activator of the epigenetically inactivated, methylated Spm, stimulating both transient and heritable activation of the transposon. TnpA also serves as a negative regulator of the demethylated active element promoter and is required, in addition to the TnpD, for transposition. © Springer Science+Business Media, New York 2013.

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)

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)

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

Energy Technology Data Exchange (ETDEWEB)

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

2005-06-13

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

Shell finite element of reinforced concrete for internal pressure analysis of nuclear containment building

International Nuclear Information System (INIS)

Lee, Hong Pyo

2011-01-01

Research highlights: → Finite element program with 9-node degenerated shell element was developed. → The developed program was mainly forced to analyze nuclear containment building. → Concrete material model is adapted Niwa and Yamada failure criteria. → The performance of program developed is verified through various numerical examples. → The numerical analysis results similar to the experimental data. - Abstract: This paper describes a 9-node degenerated shell finite element (FE), an analysis program developed for ultimate pressure capacity evaluation and nonlinear analysis of a nuclear containment building. The shell FE developed adopts the Reissner-Mindlin (RM) assumptions to consider the degenerated shell solidification technique and the degree of transverse shear strain occurring in the structure. The material model of the concrete determines the level of the concrete stress and strain by using the equivalent stress-equivalent strain relationship. When a crack occurs in the concrete, the material behavior is expressed through the tension stiffening model that takes adhesive stress into account and through the shear transfer mechanism and compressive strength reduction model of the crack plane. In addition, the failure envelope proposed by Niwa is adopted as the crack occurrence criteria for the compression-tension region, and the failure envelope proposed by Yamada is used for the tension-tension region. The performance of the program developed is verified through various numerical examples. The analysis based on the application of the shell FE developed from the results of verified examples produced results similar to the experiment or other analysis results.

Assessment of the Internal Pressure Fragility of the Hanul NPP Units 3 and 4 Containment Building Using a Nonlinear Finite Element Analysis

Energy Technology Data Exchange (ETDEWEB)

Park, Hyung Kui; Hahm, Dea Gi; Choi, In Kil [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2013-10-15

The sensitivity of the concrete strength is relatively higher compared to that of the steel strength. According to changes in the structure of the material, about 6-10% ultimate internal pressure differences occurred. Thirty sets of an FE model considering the material uncertainty of concrete and steel were composed for the internal pressure fragility assessment. From the internal pressure fragility assessment of the target containment building, the median capacity of liner leakage is estimated to be 116 psi. As can be seen from the Fukushima nuclear power plant accident, the containment building is the final protecting shield to prevent radiation leakage. Thus, a structural soundness evaluation for the containment pressure loads owing to a severe accident is very important. Recently, a probabilistic safety assessment has been commonly used to take into account the possible factors of uncertainty in a structural system. An assessment of the internal pressure fragility of the CANDU type containment buildings considering the correlation of structural material variables, and an assessment of the internal pressure fragility of the CANDU type containment buildings using a nonlinear finite element analysis, were also performed. However, for PWR type containment buildings, a fragility assessment has not been performed yet using a nonlinear finite element model (FEM) analysis. In this study, for the Hanul NPP units 3 and 4 containment building, the internal pressure fragility assessment was established using an FEM analysis. To do this, a three-dimensional finite element model, material property values, and a sensitive analysis were developed. A nonlinear finite element analysis of the Hanul NPP units 3 and 4 containment building was performed for a material sensitivity analysis and internal pressure fragility assessment.

Assessment of the Internal Pressure Fragility of the Hanul NPP Units 3 and 4 Containment Building Using a Nonlinear Finite Element Analysis

International Nuclear Information System (INIS)

Park, Hyung Kui; Hahm, Dea Gi; Choi, In Kil

2013-01-01

The sensitivity of the concrete strength is relatively higher compared to that of the steel strength. According to changes in the structure of the material, about 6-10% ultimate internal pressure differences occurred. Thirty sets of an FE model considering the material uncertainty of concrete and steel were composed for the internal pressure fragility assessment. From the internal pressure fragility assessment of the target containment building, the median capacity of liner leakage is estimated to be 116 psi. As can be seen from the Fukushima nuclear power plant accident, the containment building is the final protecting shield to prevent radiation leakage. Thus, a structural soundness evaluation for the containment pressure loads owing to a severe accident is very important. Recently, a probabilistic safety assessment has been commonly used to take into account the possible factors of uncertainty in a structural system. An assessment of the internal pressure fragility of the CANDU type containment buildings considering the correlation of structural material variables, and an assessment of the internal pressure fragility of the CANDU type containment buildings using a nonlinear finite element analysis, were also performed. However, for PWR type containment buildings, a fragility assessment has not been performed yet using a nonlinear finite element model (FEM) analysis. In this study, for the Hanul NPP units 3 and 4 containment building, the internal pressure fragility assessment was established using an FEM analysis. To do this, a three-dimensional finite element model, material property values, and a sensitive analysis were developed. A nonlinear finite element analysis of the Hanul NPP units 3 and 4 containment building was performed for a material sensitivity analysis and internal pressure fragility assessment

Experimental verification of methods for gamma dose rate calculations in the vicinity of containers with the RA reactor spent fuel elements

International Nuclear Information System (INIS)

Milosevic, M.; Cupac, S.; Pesic, M.

2005-01-01

The methodology for equivalent gamma dose rate determination on the outer surface of existing containers with the spent fuel elements of the RA reactor is briefly summarised, and experimental verification of this methodology in the field of gamma rays near the aluminium channel with spent fuel elements lifted from the stainless steel containers no. 275 in the RA reactor hall is presented. The proposed methodology is founded on: the existing fuel burnup data base; methods and models for the photon source determination in the RA reactor spent fuel elements developed in the Vinca Institute, and validated Monte Carlo codes for the equivalent gamma dose rate calculations. (author) [sr

Nuclear fuel element

International Nuclear Information System (INIS)

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

1976-01-01

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

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)

Performance-based containment leakage testing

International Nuclear Information System (INIS)

Cybulskis, P.

1995-01-01

The U.S. Nuclear Regulatory Commission (NRC) is reviewing regulatory requirements in an effort to revise those that are marginal to safety but impose significant burdens on licensees. Identification of requirements marginal to safety and development and evaluation of alternatives utilize the NRC safety goals and insights from probabilistic risk assessments (PRAs). Since earlier studies found design-basis containment leakage to be a minor contributor to reactor accident risk, containment leakage testing has been selected as a candidate for change in regulations. This paper summarizes the technical analyses supporting the NRC proposal to amend Appendix J of 10 CFR Part 50 as its first effort to decrease unnecessary regulatory burdens on licensees

Disposal/storage container development experience

International Nuclear Information System (INIS)

Morrow, R.W. Jr.; Van Hoesen, S.D.; Fowler, E.; Barreira, D.G.; Emmett, R.W.

1988-01-01

Developmental work is currently underway at the Oak Ridge National Laboratory to design and manufacture a radioactive waste container suitable for both storage and disposal of radioactive wastes. The container is designed to fulfill the Department of Energy and Nuclear Regulatory Commission requirements for on-site storage, as well as the Nuclear Regulatory Commission's requirements for high integrity containers. The project also involves meeting the strict design and manufacturing ANSI/ASME NQA-1 guidelines. Special provisions of the container include a double containment system, with the inner barrier being corrosion resistant, the capability to monitor the internal cavity of the container, and off-gas venting capability. Further, yet related developmental work includes evaluating the cask for other varied uses, such as a processing cask, an ALARA shield, and even the possibility of Department of Transportation approval for an over-the-road transport cask

5 CFR 847.102 - Regulatory structure.

Science.gov (United States)

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Regulatory structure. 847.102 Section 847.102 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS... INSTRUMENTALITIES General Provisions § 847.102 Regulatory structure. (a)(1) Subpart A of this part contains...

RNA-Seq of Bacillus licheniformis: active regulatory RNA features expressed within a productive fermentation

Science.gov (United States)

2013-01-01

Background The production of enzymes by an industrial strain requires a complex adaption of the bacterial metabolism to the conditions within the fermenter. Regulatory events within the process result in a dynamic change of the transcriptional activity of the genome. This complex network of genes is orchestrated by proteins as well as regulatory RNA elements. Here we present an RNA-Seq based study considering selected phases of an industry-oriented fermentation of Bacillus licheniformis. Results A detailed analysis of 20 strand-specific RNA-Seq datasets revealed a multitude of transcriptionally active genomic regions. 3314 RNA features encoded by such active loci have been identified and sorted into ten functional classes. The identified sequences include the expected RNA features like housekeeping sRNAs, metabolic riboswitches and RNA switches well known from studies on Bacillus subtilis as well as a multitude of completely new candidates for regulatory RNAs. An unexpectedly high number of 855 RNA features are encoded antisense to annotated protein and RNA genes, in addition to 461 independently transcribed small RNAs. These antisense transcripts contain molecules with a remarkable size range variation from 38 to 6348 base pairs in length. The genome of the type strain B. licheniformis DSM13 was completely reannotated using data obtained from RNA-Seq analyses and from public databases. Conclusion The hereby generated data-sets represent a solid amount of knowledge on the dynamic transcriptional activities during the investigated fermentation stages. The identified regulatory elements enable research on the understanding and the optimization of crucial metabolic activities during a productive fermentation of Bacillus licheniformis strains. PMID:24079885

RNA-Seq of Bacillus licheniformis: active regulatory RNA features expressed within a productive fermentation.

Science.gov (United States)

Wiegand, Sandra; Dietrich, Sascha; Hertel, Robert; Bongaerts, Johannes; Evers, Stefan; Volland, Sonja; Daniel, Rolf; Liesegang, Heiko

2013-10-01

The production of enzymes by an industrial strain requires a complex adaption of the bacterial metabolism to the conditions within the fermenter. Regulatory events within the process result in a dynamic change of the transcriptional activity of the genome. This complex network of genes is orchestrated by proteins as well as regulatory RNA elements. Here we present an RNA-Seq based study considering selected phases of an industry-oriented fermentation of Bacillus licheniformis. A detailed analysis of 20 strand-specific RNA-Seq datasets revealed a multitude of transcriptionally active genomic regions. 3314 RNA features encoded by such active loci have been identified and sorted into ten functional classes. The identified sequences include the expected RNA features like housekeeping sRNAs, metabolic riboswitches and RNA switches well known from studies on Bacillus subtilis as well as a multitude of completely new candidates for regulatory RNAs. An unexpectedly high number of 855 RNA features are encoded antisense to annotated protein and RNA genes, in addition to 461 independently transcribed small RNAs. These antisense transcripts contain molecules with a remarkable size range variation from 38 to 6348 base pairs in length. The genome of the type strain B. licheniformis DSM13 was completely reannotated using data obtained from RNA-Seq analyses and from public databases. The hereby generated data-sets represent a solid amount of knowledge on the dynamic transcriptional activities during the investigated fermentation stages. The identified regulatory elements enable research on the understanding and the optimization of crucial metabolic activities during a productive fermentation of Bacillus licheniformis strains.

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.

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.

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....

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

Measuring and Modeling the U.S. Regulatory Ecosystem

Science.gov (United States)

Bommarito, Michael J., II; Katz, Daniel Martin

2017-09-01

Over the last 23 years, the U.S. Securities and Exchange Commission has required over 34,000 companies to file over 165,000 annual reports. These reports, the so-called "Form 10-Ks," contain a characterization of a company's financial performance and its risks, including the regulatory environment in which a company operates. In this paper, we analyze over 4.5 million references to U.S. Federal Acts and Agencies contained within these reports to measure the regulatory ecosystem, in which companies are organisms inhabiting a regulatory environment. While individuals across the political, economic, and academic world frequently refer to trends in this regulatory ecosystem, far less attention has been paid to supporting such claims with large-scale, longitudinal data. In this paper, in addition to positing a model of regulatory ecosystems, we document an increase in the regulatory energy per filing, i.e., a warming "temperature." We also find that the diversity of the regulatory ecosystem has been increasing over the past two decades. These findings support the claim that regulatory activity and complexity are increasing, and this framework contributes an important step towards improving academic and policy discussions around legal complexity and regulation.

Repetitive Elements in Mycoplasma hyopneumoniae Transcriptional Regulation.

Directory of Open Access Journals (Sweden)

Amanda Malvessi Cattani

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

Repetitive Elements in Mycoplasma hyopneumoniae Transcriptional Regulation.

Science.gov (United States)

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

2016-01-01

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

The immobilisation of nuclear waste materials containing different alkali elements into single-phase NZP based ceramics

International Nuclear Information System (INIS)

Pet'kov, V.I.; Orlova, A.I.; Trubach, I.G.; Demarin, T.; Kurazhkovskaya, V.S.

2002-01-01

The NZP matrix, which is based on NaZr 2 (PO 4 ) 3 , is a viable candidate for nuclear waste immobilisation. We examined the possibilities of incorporating of alkali elements into the NZP host structure, investigated the conditions of the crystalline solution formation, and determined the regions of the NZP structure compositional stability for a series of complex orthophosphates of titanium or zirconium and alkali elements A m-x A' x M 2-(m-1)/4 (PO 4 ) 3 with m = 1, 3, or 5 and 0 ≤ x ≤ m, where A and A' are mutually different alkali elements and M is Ti or Zr. The phosphates containing Li-Na, Li-K, Li-Rb, Li-Cs, Na-K, Na-Rb, Na-Cs, K-Rb, K-Cs and Rb-Cs pairs were prepared and studied by X-ray powder analysis, IR spectroscopy, simultaneous DTA-TG measurements and electron microprobe analyses. In the systems studied, wide ranges of crystalline phosphate solutions with tailored alkali metal substitutions were formed owing to the large number of sites available for substitution and high degree of flexibility in the NZP structure. It was found that introduction of the less expensive and lighter Ti in the host phase in place of the commonly used Zr permits cheaper ceramics, having in some cases larger alkali element contents, to be obtained. The phases containing alkali metals can be formed, for instance, during phosphate solidification of molten alkali chlorides with radioactive nuclides from the pyroelectrochemical technologies of nuclear fuel recycling

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.

A SINE in the genome of the cephalochordate amphioxus is an Alu element

Science.gov (United States)

Holland, Linda Z.

2006-01-01

Transposable elements of about 300 bp, termed “short interspersed nucleotide elements or SINEs are common in eukaryotes. However, Alu elements, SINEs containing restriction sites for the AluI enzyme, have been known only from primates. Here I report the first SINE found in the genome of the cephalochordate, amphioxus. It is an Alu element of 375 bp that does not share substantial identity with any genomic sequences in vertebrates. It was identified because it was located in the FoxD regulatory region in a cosmid derived from one individual, but absent from the two FoxD alleles of BACs from a second individual. However, searches of sequences of BACs and genomic traces from this second individual gave an estimate of 50-100 copies in the amphioxus genome. The finding of an Alu element in amphioxus raises the question of whether Alu elements in amphioxus and primates arose by convergent evolution or by inheritance from a common ancestor. Genome-wide analyses of transposable elements in amphioxus and other chordates such as tunicates, agnathans and cartilaginous fishes could well provide the answer. PMID:16733535

A regulatory code for neuron-specific odor receptor expression.

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Anandasankar Ray

2008-05-01

Full Text Available Olfactory receptor neurons (ORNs must select-from a large repertoire-which odor receptors to express. In Drosophila, most ORNs express one of 60 Or genes, and most Or genes are expressed in a single ORN class in a process that produces a stereotyped receptor-to-neuron map. The construction of this map poses a problem of receptor gene regulation that is remarkable in its dimension and about which little is known. By using a phylogenetic approach and the genome sequences of 12 Drosophila species, we systematically identified regulatory elements that are evolutionarily conserved and specific for individual Or genes of the maxillary palp. Genetic analysis of these elements supports a model in which each receptor gene contains a zip code, consisting of elements that act positively to promote expression in a subset of ORN classes, and elements that restrict expression to a single ORN class. We identified a transcription factor, Scalloped, that mediates repression. Some elements are used in other chemosensory organs, and some are conserved upstream of axon-guidance genes. Surprisingly, the odor response spectra and organization of maxillary palp ORNs have been extremely well-conserved for tens of millions of years, even though the amino acid sequences of the receptors are not highly conserved. These results, taken together, define the logic by which individual ORNs in the maxillary palp select which odor receptors to express.

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.

Regulatory viewpoint on nuclear fuel quality assurance

International Nuclear Information System (INIS)

Tripp, L.E.

1976-01-01

Considerations of the importance of fuel quality and performance to nuclear safety, ''as low reasonably achievable'' release of radioactive materials in reactor effluents, and past fuel performance problems demonstrate the need for strong regulatory input, review and inspection of nuclear fuel quality assurance programs at all levels. Such a regulatory program is being applied in the United States of America by the US Nuclear Regulatory Commission. Quality assurance requirements are contained within government regulations. Guidance on acceptable methods of implementing portions of the quality assurance program is contained within Regulatory Guides and other NRC documents. Fuel supplier quality assurance program descriptions are reviewed as a part of the reactor licensing process. Inspections of reactor licensee control of their fuel vendors as well as direct inspections of fuel vendor quality assurance programs are conducted on a regularly scheduled basis. (author)

Splinkerette PCR for mapping transposable elements in Drosophila.

Directory of Open Access Journals (Sweden)

Christopher J Potter

2010-04-01

Full Text Available Transposable elements (such as the P-element and piggyBac have been used to introduce thousands of transgenic constructs into the Drosophila genome. These transgenic constructs serve many roles, from assaying gene/cell function, to controlling chromosome arm rearrangement. Knowing the precise genomic insertion site for the transposable element is often desired. This enables identification of genomic enhancer regions trapped by an enhancer trap, identification of the gene mutated by a transposon insertion, or simplifying recombination experiments. The most commonly used transgene mapping method is inverse PCR (iPCR. Although usually effective, limitations with iPCR hinder its ability to isolate flanking genomic DNA in complex genomic loci, such as those that contain natural transposons. Here we report the adaptation of the splinkerette PCR (spPCR method for the isolation of flanking genomic DNA of any P-element or piggyBac. We report a simple and detailed protocol for spPCR. We use spPCR to 1 map a GAL4 enhancer trap located inside a natural transposon, pinpointing a master regulatory region for olfactory neuron expression in the brain; and 2 map all commonly used centromeric FRT insertion sites. The ease, efficiency, and efficacy of spPCR could make it a favored choice for the mapping of transposable element in Drosophila.

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

Structural organization and chromosomal assignment of the mouse embryonic TEA domain-containing factor (ETF) gene.

Science.gov (United States)

Suzuki, K; Yasunami, M; Matsuda, Y; Maeda, T; Kobayashi, H; Terasaki, H; Ohkubo, H

1996-09-01

Embryonic TEA domain-containing factor (ETF) belongs to the family of proteins structurally related to transcriptional enhancer factor-1 (TEF-1) and is implicated in neural development. Isolation and characterization of the cosmid clones encoding the mouse ETF gene (Etdf) revealed that Etdf spans approximately 17.9 kb and consists of 12 exons. The exon-intron structure of Etdf closely resembles that of the Drosophila scalloped gene, indicating that these genes may have evolved from a common ancestor. The multiple transcription initiation sites revealed by S1 protection and primer extension analyses are consistent with the absence of the canonical TATA and CAAT boxes in the 5'-flanking region, which contains many potential regulatory sequences, such as the E-box, N-box, Sp1 element, GATA-1 element, TAATGARAT element, and B2 short interspersed element (SINE) as well as several direct and inverted repeat sequences. The Etdf locus was assigned to the proximal region of mouse chromosome 7 using fluorescence in situ hybridization and linkage mapping analyses. These results provide the molecular basis for studying the regulation, in vivo function, and evolution of Etdf.

Storage container for radioactive fuel elements

International Nuclear Information System (INIS)

1984-01-01

The interim storage cask for spent fuel elements or the glass moulds for high-level radioactive waste are made up of heat-resistant, reinforced concrete with chambers and highgrade steel lining. Cooling systems with natural air circulation are connected with the chambers. (HP) [de

Assessment of risks for employees of France Telecom regarding overvoltage arresters containing radio-elements

International Nuclear Information System (INIS)

Thomassin, A.; Metz, C.; Rannou, A.

2010-01-01

As a great number of overvoltage arresters used by France Telecom to protect its telecommunication network against disturbing voltages (notably lightning) contain radio-elements, this report aims at assessing dose levels and associated risks for employees exposed to radioactive overvoltage arrester when setting them up, exploiting installations containing such arresters, or when removing them. After a presentation of these devices, a modelling of activities and geometries is proposed, as well as computation tools. Different scenarios and exposure situations are considered. As far as risks are concerned, after a recall on cancers and ionizing radiation, and on the exposure of France Telecom employees, the report comments the knowledge on radio-induced cancers; notably breast cancer, skin cancer, and mouth and pharynx cancers

Bioaccumulation of uranium and thorium from the solution containing both elements using various microorganisms

International Nuclear Information System (INIS)

Tsuruta, T.

2006-01-01

The effects of proton, thorium and uranium on the bioaccumulation of thorium and uranium from the solution (pH 3.5) containing uranium and thorium using Streptomyces levoris cells were examined. The amount of thorium accumulated using the cells decreased by the pre-contact between the cells and the solution (pH 3.5) containing no metals, whereas that of uranium was almost unaffected by the treatment. The amount of thorium was almost unaffected by the existence of uranium. On the other hand, the amount of uranium accumulated was strongly affected by the thorium, especially thorium addition after uranium accumulation. The decrease of uranium accumulated by the addition of thorium after the accumulation of uranium was higher than that from the solution containing both elements. Therefore, the contribution of uranium-thorium exchange reaction was higher than that of competition reaction. Accordingly, proton-uranium-thorium exchange reaction was occurred in the accumulation of thorium from the solution containing thorium and uranium. The gram-positive bacteria, such as Micrococcus luteus, Arthrobacter nicotianae, Bacillus subtilis and B. megaterium, has a much higher separation factor as thorium/uranium than that of actinomycetes. These gram-positive bacterial strains can be used for the accumulation of thorium from the solution containing uranium and thorium

Risk acceptance criteria of the Nuclear Regulatory Authority

International Nuclear Information System (INIS)

Felizia, Eduardo R.

2005-01-01

This report describes some of the regulatory and control functions legally conferred upon the Argentine Nuclear Regulatory Authority concerning radiological risks, as well as a critical analysis of the radiological risk acceptance criteria contained in the Argentine regulatory system. A summary of the application of regulatory standards AR 3.1.3. - 'Radiological criteria related to accidents in nuclear power reactors' and AR 4.1.3. - 'Radiological criteria related to accidents in research reactors' to concrete cases is made, while the favourable and unfavourable aspects of the risk acceptance criteria are discussed. The conclusion is that the Argentine regulatory system contains adequate radiological risk acceptance criteria, that the latter are consistent with the radiological protection principles applicable to man and that, for the moment, there is no need to perform any modifications that would broaden the conceptual framework on which such criteria are based. (author) [es

Regulatory supervision of industrial waste containing very low activities of man-made radionuclides at SevRAO facility

International Nuclear Information System (INIS)

Sneve, Malgorzata K.; Kochetkov, Oleg; Monastyrskaya, Svetlana; Barchukov, Valerie; Romanov, Vladimir

2008-01-01

Full text: Large amounts of waste and materials with very low activity level are generated during operation and especially during decommissioning of nuclear facilities. Selection of the optimum economic and ecologically safe management option of such material is complicated by its specific features: very low level radiation exposure to individuals but rather large initial amounts of waste. On the one hand, it is a poor use of limited resources to em place such low activity waste into expensive facilities for radioactive waste storage and disposal if the radiological impact would be very small even for a much less expensive option; on the other hand, there is some apprehension regarding safety both about its disposal to landfills for conventional (non-radioactive) waste disposal, and about its limited or unlimited re-use or re-cycling. To regulate such waste management, a special waste category is introduced - very low level waste (VLLW). This category includes waste containing radionuclides with specific activity levels, which are higher than clearance levels, but do not need high containment and isolation. This paper discusses experience of regulatory development for VLLW control during remediation of radiation hazardous facilities in northwest Russia. The work has promoted identification of some challenges, whose solution has affected the waste management strategy at the sites. One of the main problems resolved was the selection of criteria according to which waste is allocated to the VLLW category. These is turn were partly determined by the radiological criteria chosen for protection of the public during this waste disposal. Elaboration of safe VLLW management strategy depends upon a source of waste generation and of its radiological composition. The VLLW management strategy at an operating enterprise, e.g. a nuclear power plant is rather different from the strategy implemented at the plant under decommissioning, or at storage facilities for the legacy waste

NRC regulatory information conference: Proceedings

International Nuclear Information System (INIS)

1989-09-01

This volume of the report provides the proceedings from the Nuclear Regulatory Commission (NRC) Regulatory Information Conference that was held at the Mayflower Hotel, Washington, DC, on April 18, 19, and 20, 1989. This conference was held by the NRC and chaired by Dr. Thomas E. Mosley, Director, Office of Nuclear Reactor Regulations (NRR) and coordinated by S. Singh Bajwa, Chief, Technical Assistance Management Section, NRR. There were approximately 550 participants from nine countries at the conference. The countries represented were Canada, England, Italy, Japan, Mexico, Spain, Taiwan, Yugoslavia, and the United States. The NRC staff discussed with nuclear industry its regulatory philosophy and approach and the bases on which they have been established. Furthermore, the NRC staff discussed several initiatives that have been implemented recently and their bases as well as NRC's expectations for new initiatives to further improve safety. The figures contained in Appendix A to the volume correspond to the slides that were shown during the presentations. Volume 2 of this report contains the formal papers that were distributed at the beginning of the Regulatory Information Conference and other information about the conference

Structural design of a shipping container of fuel elements, non-irradiated, for research reactors

International Nuclear Information System (INIS)

Morales Uzqueda, Eduardo Mario

2013-01-01

This work is part of a project whose ultimate goal the creation and subsequent discharge of a transport container fuel assemblies for use by the Chilean Commission for Energy Nuclear. In principle it is covered in the design stage, considering the materials and methods used, to further develop a stage of checking voltages in the container to be manufactured. To achieve the first phase of the study is necessary to understand and warn the importance, geometry and content of the fuel elements to be transported, for which there are standards that provide fundamental material for proper classification of both content and container design. Once approved the design of the structure is critical examine both in normal operation and in the case of accidents that are established by international bodies. for appropriate analytical methods that seek to achieve is use a appropriate representation of the behavior of the structure. in addition to strengthen the theory computer simulations of the tests used applied, where the results will be contrasted with the first method of calculation. Results are obtained for the stress field and displacement total delivering the information necessary to approve the container

Feather development genes and associated regulatory innovation predate the origin of Dinosauria.

Science.gov (United States)

Lowe, Craig B; Clarke, Julia A; Baker, Allan J; Haussler, David; Edwards, Scott V

2015-01-01

The evolution of avian feathers has recently been illuminated by fossils and the identification of genes involved in feather patterning and morphogenesis. However, molecular studies have focused mainly on protein-coding genes. Using comparative genomics and more than 600,000 conserved regulatory elements, we show that patterns of genome evolution in the vicinity of feather genes are consistent with a major role for regulatory innovation in the evolution of feathers. Rates of innovation at feather regulatory elements exhibit an extended period of innovation with peaks in the ancestors of amniotes and archosaurs. We estimate that 86% of such regulatory elements and 100% of the nonkeratin feather gene set were present prior to the origin of Dinosauria. On the branch leading to modern birds, we detect a strong signal of regulatory innovation near insulin-like growth factor binding protein (IGFBP) 2 and IGFBP5, which have roles in body size reduction, and may represent a genomic signature for the miniaturization of dinosaurian body size preceding the origin of flight. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

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.

Process for surface treatment of zirconium-containing cladding materials for fuel element or other components for nuclear reactors

International Nuclear Information System (INIS)

Videm, K.G.; Lunde, L.R.; Kooyman, H.H.

1975-01-01

A process for the surface treatment of zirconium-base cladding materials for fuel elements or other components for nuclear reactors is described. The treatment includes pickling the cladding material in a fluoride-containing bath, and then applying a protective coating through oxidation to the pickled cladding material. The fluoride-containing contaminants which remain on the surface of the cladding material during pickling are removed or rendered harmless by anodic oxidation

State/Federal Regulatory Considerations

Science.gov (United States)

This page contains presentations from the Brown to Green: Make the Connection to Renewable Energy workshop held in Santa Fe, New Mexico, during December 10-11, 2008, regarding State/Federal Regulatory Considerations.

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

Analytical predictions for the performance of a reinforced concrete containment model subject to overpressurization

International Nuclear Information System (INIS)

Weatherby, J.R.; Clauss, D.B.

1987-01-01

Under the sponsorship of the US Nuclear Regulatory Commission, Sandia National Laboratories is investigating methods for predicting the structural performance of nuclear reactor containment buildings under hypothesized severe accident conditions. As part of this program, a 1/6th-scale reinforced concrete containment model will be pressurized to failure in early 1987. Data generated by the test will be compared to analytical predictions of the structural response in order to assess the accuracy and reliability of the analytical techniques. As part of the pretest analysis effort, Sandia has conducted a number of analyses of the containment structure using the ABAQUS general purpose finite element code. This paper describes results from a nonlinear axisymmetric shell analysis as well as the material models and failure criteria used in conjunction with the analysis

Final report on fabrication and study of SYNROC containing radioactive waste elements

International Nuclear Information System (INIS)

Reeve, K.D.; Levins, D.M.; Seatonberry, B.W.; Ryan, R.K.; Hart, K.P.; Stevens, G.T.

1987-01-01

Two facilities for the fabrication and testing of Synroc samples containing separate additions of the transuranic actinides americium, plutonium, curium and neptunium, a fission product solution, and two radioisotopes of caesium and strontium were designed, built and operated by the AAEC at the Lucas Heights Research Laboratories. Twenty-one 75 g batches of radioactive Synroc were made and representative samples were characterised by alpha track etching, scanning electron microscopy and aqueous leach testing, mostly at 70 deg C. Where comparisons were possible, radioactive fission products behaved as expected from non-radioactive tests. The leaching behaviour of the actinides was complex but as a group they were the least leachable of all the elements studied

XcisClique: analysis of regulatory bicliques

Directory of Open Access Journals (Sweden)

Grene Ruth

2006-04-01

Full Text Available Abstract Background Modeling of cis-elements or regulatory motifs in promoter (upstream regions of genes is a challenging computational problem. In this work, set of regulatory motifs simultaneously present in the promoters of a set of genes is modeled as a biclique in a suitably defined bipartite graph. A biologically meaningful co-occurrence of multiple cis-elements in a gene promoter is assessed by the combined analysis of genomic and gene expression data. Greater statistical significance is associated with a set of genes that shares a common set of regulatory motifs, while simultaneously exhibiting highly correlated gene expression under given experimental conditions. Methods XcisClique, the system developed in this work, is a comprehensive infrastructure that associates annotated genome and gene expression data, models known cis-elements as regular expressions, identifies maximal bicliques in a bipartite gene-motif graph; and ranks bicliques based on their computed statistical significance. Significance is a function of the probability of occurrence of those motifs in a biclique (a hypergeometric distribution, and on the new sum of absolute values statistic (SAV that uses Spearman correlations of gene expression vectors. SAV is a statistic well-suited for this purpose as described in the discussion. Results XcisClique identifies new motif and gene combinations that might indicate as yet unidentified involvement of sets of genes in biological functions and processes. It currently supports Arabidopsis thaliana and can be adapted to other organisms, assuming the existence of annotated genomic sequences, suitable gene expression data, and identified regulatory motifs. A subset of Xcis Clique functionalities, including the motif visualization component MotifSee, source code, and supplementary material are available at https://bioinformatics.cs.vt.edu/xcisclique/.

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

Identification of a cast iron alloy containing nonstrategic elements

Science.gov (United States)

Cooper, C. V.; Anton, D. L.; Lemkey, F. D.; Nowotny, H.; Bailey, R. S.; Favrow, L. H.; Smeggil, J. G.; Snow, D. B.

1989-01-01

A program was performed to address the mechanical and environmental needs of Stirling engine heater head and regenerator housing components, while reducing the dependence on strategic materials. An alloy was developed which contained no strategic elemental additions per se. The base is iron with additions of manganese, molybdenum, carbon, silicon, niobium, and ferro-chromium. Such an alloy should be producible on a large scale at very low cost. The resulting alloy, designated as NASAUT 4G-Al, contained 15 Mn, 15 Cr, 2 Mo, 1.5 C, 1.0 Si, 1.0 Nb (in weight percent) with a balance of Fe. This alloy was optimized for chemistry, based upon tensile strength, creep-rupture strength, fracture behavior, and fatigue resistance up to 800 C. Alloys were also tested for environmental compatibility. The microstructure and mechanic properties (including hardness) were assessed in the as-cast condition and following several heat treatments, including one designed to simulate a required braze cycle. The alloy was fabricated and characterized in the form of both equiaxed and columnar-grained castings. The columnar grains were produced by directional solidification, and the properties were characterized in both the longitudinal and transverse orientations. The NASAUT 4G-Al alloy was found to be good in cyclic-oxidation resistance and excellent in both hydrogen and hot-corrosion resistance, especially in comparison to the baseline XF-818 alloy. The mechanical properties of yield strength, stress-rupture life, high-cycle-fatigue resistance, and low-cycle-fatigue resistance were good to excellent in comparison to the current alloy for this application, HS-31 (X-40), with precise results depending in a complex manner on grain orientation and temperature. If required, the ductility could be improved by lowering the carbon content.

CONTAIN code analyses of direct containment heating experiments

International Nuclear Information System (INIS)

Williams, D.C.; Griffith, R.O.; Tadios, E.L.; Washington, K.E.

1995-01-01

In some nuclear reactor core-melt accidents, a potential exists for molten core-debris to be dispersed into the containment under high pressure. Resulting energy transfer to the containment atmosphere can pressurize the containment. This process, known as direct containment heating (DCH), has been the subject of extensive experimental and analytical programs sponsored by the U.S. Nuclear Regulatory Commission (NRC). The DCH modeling has been an important focus for the development of the CONTAIN code. Results of a detailed independent peer review of the CONTAIN code were published recently. This paper summarizes work performed in support of the peer review in which the CONTAIN code was applied to analyze DCH experiments. Goals of this work were comparison of calculated and experimental results, CONTAIN DCH model assessment, and development of guidance for code users, including development of a standardized input prescription for DCH analysis

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.

Comparative study of Malaysian and Philippine regulatory infrastructures on radiation and nuclear safety with international standards

International Nuclear Information System (INIS)

Cayabo, Lynette B.

2013-06-01

This study presents the results of the critical reviews, analysis, and comparison of the regulatory infrastructures for radiation and nuclear safety of Malaysis and the Philippines usi ng the IAEA safety requirements, GSR Part 1, G overnment, Legal and Regulatory Framework for Safety'' as the main basis and in part, the GSR Part 3, R adiation Protection and Safety of Radiation Sources: International Basic Safety Standards . The scope of the comparison includes the elements of the relevant legislations, the regulatory system and processes including the core functions of the regulatory body (authorization, review and assessment, inspection and enforcement, development of regulations and guides); and the staffing and training of regulatory body. The respective availabe data of the Malaysian and Philippine regulatory infrastructures and current practices were gathered and analyzed. Recommendations to fill the gaps and strengthen the existing regulatory infrastructure of each country was given using as bases relevant IAEA safety guides. Based on the analysis made, the main findings are: the legislations of both countries do not contain al the elements of teh national policy and strategy for safety as well as those of teh framework for safety in GR Part I. Among the provision that need to be included in the legislations are: emergency planning and response; decommissioning of facilities safe management of radioactive wastes and spent fuel; competence for safety; and technical sevices. Provisions on coordination of different authorities with safety responsibilities within the regulatory framework for safety as well as liaison with advisory bodies and support organizations need to be enhanced. The Philippines needs to establish an independent regulatory body, ie. separate from organizations charged with promotion of nuclear technologies and responsible for facilitiesand activities. Graded approach on the system of notification and authorization by registration and

Proportioning equipment for vibration filling and compacting of grain materials in pipe containers, especially of fuel elements

International Nuclear Information System (INIS)

Pinkas, V.; Filip, Z.; Beranek, J.

1981-01-01

The equipment consists of a base plate to which are attached the fastening collar fo the pipe container and the guide column with the height-adjustable support. The filling pipe is fixed to the support. The proportioning equipment prevents particles of grain material from segregation, thus allowing to achieve homogeneity of the material in the whole volume to be compacted. It also allows determining the height of the column of material in the pipe container without destructive effects on the stacked material. The equipment is designed for the manufacture of shortened fuel elements. (J.B.)

Experimental study of the leakage rate through cracked reinforced concrete wall elements for defining the functional failure criteria of containment buildings

International Nuclear Information System (INIS)

Choun, Young Sun; Cho, Nam So

2004-01-01

Containment buildings in nuclear power plants should maintain their structural safety as well as their functional integrity during an operation period. To maintain the functional integrity, the wall and dome of the containment buildings have to maintain their air tightness under extreme loading conditions such as earthquakes, missile impact, and severe accidents. For evaluating the functional failure of containments, it is important to predict the leak amount through cracked concrete walls. The leakage through concrete cracks has been studied since 1972. Buss examined the flow rate of air through a pre-existing crack in a slab under air pressure. Rizkalla el al. initiated an experimental study for the leakage of prestressed concrete building segments under uniaxial and biaxial loadings to simulate the loading condition of containment buildings under an internal pressure. Recently, Salmon el al. initiated an experimental program for determining the leak rates in typical reinforced concrete shear walls subjected to beyond design basis earthquakes. This study investigates the cracking behavior of reinforced concrete containment wall elements under a uniaxial tension and addresses the outline of the leakage test for unlined containment wall elements

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....

Hydrogen removal from LWR containments by catalytic-coated thermal insulation elements (THINCAT)

International Nuclear Information System (INIS)

Fischer, K.; Broeckerhoff, P.; Ahlers, G.; Gustavsson, V.; Herranz, L.; Polo, J.; Dominguez, T.; Royl, P.

2003-01-01

In the THINCAT project, an alternative concept for hydrogen mitigation in a light water reactor (LWR) containment is being developed. Based on catalytic coated thermal insulation elements of the main coolant loop components, it could be considered either as an alternative to backfitting passive autocatalytic recombiner devices, or as a reinforcement of their preventive effect. The present paper summarises the results achieved at about project mid-term. Potential advantages of catalytic thermal insulation studied in the project are:-reduced risk of unintended ignition,;-no work space obstruction in the containment,;-no need for seismic qualification of additional equipment,;-improved start-up behaviour of recombination reaction. Efforts to develop a suitable catalytic layer resulted in the identification of a coating procedure that ensures high chemical reactivity and mechanical stability. Test samples for use in forthcoming experiments with this coating were produced. Models to predict the catalytic rates were developed, validated and applied in a safety analysis study. Results show that an overall hydrogen concentration reduction can be achieved which is comparable to the reduction obtained using conventional recombiners. Existing experimental information supports the argument of a reduced ignition risk

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

77 FR 69508 - Inservice Inspection of Prestressed Concrete Containment Structures With Grouted Tendons

Science.gov (United States)

2012-11-19

... Containment Structures With Grouted Tendons AGENCY: Nuclear Regulatory Commission. ACTION: Regulatory guide... (RG) 1.90, ``Inservice Inspection of Prestressed Concrete Containment Structures with Grouted Tendons... appropriate surveillance program for prestressed concrete containment structures with grouted tendons...

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.

Interferon-induced transcription of a gene encoding a 15-kDA protein depends on an upstream enhancer element

International Nuclear Information System (INIS)

Reich, N.; Evans, B.; Levy, D.; Fahey, D.; Knight, E. Jr.; Darnell, J.E. Jr.

1987-01-01

A human gene encoding an interferon-induced 15-kDa protein has been isolated from a genomic library. The gene appears to be single-copy and is composed of two exons, the first of which contains the ATG translation initiation codon. In vitro nuclear run-on assays showed that the transcription rate of the gene is stimulated after interferon treatment. To analyze transcriptional regulatory sequences, the authors constructed recombinant plasmids for use in transient transfection assays of HeLa cells. Constructs containing 115 nucleotides 5' to the transcription initiation site were found to be fully inducible by interferon. Assays of deletion mutants identified a critical element for interferon induction located between -115 and -96, just upstream of the CCAAT box. Moreover, a DNA fragment including this region can confer interferon inducibility on a heterologous promoter (thymidine kinase) when cloned in either orientation upstream of the gene or downstream of the gene. These are properties characteristic of an enhancer element that is active only after treatment with interferon. This regulatory sequence may be shared by a group of interferon-induced genes, since a very similar sequence is present within the functional region near the RNA start site of another interferon-induced gene

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

Science.gov (United States)

Fauteux, François; Strömvik, Martina V

2009-01-01

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

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

Directory of Open Access Journals (Sweden)

Fauteux François

2009-10-01

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

Contribution of transposable elements and distal enhancers to evolution of human-specific features of interphase chromatin architecture in embryonic stem cells.

Science.gov (United States)

Glinsky, Gennadi V

2018-03-01

Transposable elements have made major evolutionary impacts on creation of primate-specific and human-specific genomic regulatory loci and species-specific genomic regulatory networks (GRNs). Molecular and genetic definitions of human-specific changes to GRNs contributing to development of unique to human phenotypes remain a highly significant challenge. Genome-wide proximity placement analysis of diverse families of human-specific genomic regulatory loci (HSGRL) identified topologically associating domains (TADs) that are significantly enriched for HSGRL and designated rapidly evolving in human TADs. Here, the analysis of HSGRL, hESC-enriched enhancers, super-enhancers (SEs), and specific sub-TAD structures termed super-enhancer domains (SEDs) has been performed. In the hESC genome, 331 of 504 (66%) of SED-harboring TADs contain HSGRL and 68% of SEDs co-localize with HSGRL, suggesting that emergence of HSGRL may have rewired SED-associated GRNs within specific TADs by inserting novel and/or erasing existing non-coding regulatory sequences. Consequently, markedly distinct features of the principal regulatory structures of interphase chromatin evolved in the hESC genome compared to mouse: the SED quantity is 3-fold higher and the median SED size is significantly larger. Concomitantly, the overall TAD quantity is increased by 42% while the median TAD size is significantly decreased (p = 9.11E-37) in the hESC genome. Present analyses illustrate a putative global role for transposable elements and HSGRL in shaping the human-specific features of the interphase chromatin organization and functions, which are facilitated by accelerated creation of novel transcription factor binding sites and new enhancers driven by targeted placement of HSGRL at defined genomic coordinates. A trend toward the convergence of TAD and SED architectures of interphase chromatin in the hESC genome may reflect changes of 3D-folding patterns of linear chromatin fibers designed to enhance both

Development of finite element models for the study of ageing effects in CANDU 6 concrete containment buildings

Energy Technology Data Exchange (ETDEWEB)

Ding, Y.; Jaffer, S., E-mail: Yuqing.Ding@cnl.ca [Canadian Nuclear Laboratories, Chalk River, Ontario (Canada)

2016-06-15

In nuclear power plants (NPPs), concrete containment buildings (CCBs) provide the final physical barrier against the release of radioactive materials into the environment and protect the nuclear structures housed within the containment building. CCBs have to be maintained to ensure leak tightness and sound structural integrity for the safe operation throughout the life of NPPs. However, the integrity of CCBs may be affected by the ageing of its concrete, post-tensioning cables and reinforcing bars (rebars). Finite element models (FEMs) of CANDU 6 CCBs have been developed using 2 independent finite element programs for the study of the effect of ageing of CCBs. These FEMs have been validated using multiple-source data and have been used for preliminary analyses of the effect of thermal load and ageing degradation on the concrete structure. The modelling assumptions and simplifications, approach, and validation are discussed in this paper. The preliminary analyses for temperature effects and potential applications to the study of ageing degradation in CCBs using the FEMs are briefly introduced. (author)

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.

Asymmetrical distribution of non-conserved regulatory sequences at PHOX2B is reflected at the ENCODE loci and illuminates a possible genome-wide trend

Directory of Open Access Journals (Sweden)

McCallion Andrew S

2009-01-01

Full Text Available Abstract Background Transcriptional regulatory elements are central to development and interspecific phenotypic variation. Current regulatory element prediction tools rely heavily upon conservation for prediction of putative elements. Recent in vitro observations from the ENCODE project combined with in vivo analyses at the zebrafish phox2b locus suggests that a significant fraction of regulatory elements may fall below commonly applied metrics of conservation. We propose to explore these observations in vivo at the human PHOX2B locus, and also evaluate the potential evidence for genome-wide applicability of these observations through a novel analysis of extant data. Results Transposon-based transgenic analysis utilizing a tiling path proximal to human PHOX2B in zebrafish recapitulates the observations at the zebrafish phox2b locus of both conserved and non-conserved regulatory elements. Analysis of human sequences conserved with previously identified zebrafish phox2b regulatory elements demonstrates that the orthologous sequences exhibit overlapping regulatory control. Additionally, analysis of non-conserved sequences scattered over 135 kb 5' to PHOX2B, provides evidence of non-conserved regulatory elements positively biased with close proximity to the gene. Furthermore, we provide a novel analysis of data from the ENCODE project, finding a non-uniform distribution of regulatory elements consistent with our in vivo observations at PHOX2B. These observations remain largely unchanged when one accounts for the sequence repeat content of the assayed intervals, when the intervals are sub-classified by biological role (developmental versus non-developmental, or by gene density (gene desert versus non-gene desert. Conclusion While regulatory elements frequently display evidence of evolutionary conservation, a fraction appears to be undetected by current metrics of conservation. In vivo observations at the PHOX2B locus, supported by our analyses of in

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.

Comments on regulatory reform

Energy Technology Data Exchange (ETDEWEB)

Hendrie, J.M.

1982-01-01

Nuclear regulatory reform is divided into two parts. The first part contains all those matters for which new legislation is required. The second part concerns all those matters that are within the power of the Commission under existing statutes. Recommendations are presented.

Comments on regulatory reform

International Nuclear Information System (INIS)

Hendrie, J.M.

1982-01-01

Nuclear regulatory reform is divided into two parts. The first part contains all those matters for which new legislation is required. The second part concerns all those matters that are within the power of the Commission under existing statutes. Recommendations are presented

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

Science.gov (United States)

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

2016-05-01

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

Growth of tourmaline single crystals containing transition metal elements in hydrothermal solutions

Science.gov (United States)

Setkova, Tatiana; Shapovalov, Yury; Balitsky, Vladimir

2011-03-01

Interest in the growth of tourmaline single crystals is based on the promising piezoelectric and pyroelectric properties of this material compared to quartz crystals currently in use. Moreover, synthetic tourmaline can be used as a substitute for the natural stone in the jewelry industry similar to other synthetic analogues of gemstones. Single crystals of colored Co-, Ni-, Fe-, (Ni,Cr)-, (Ni,Fe)-, and (Co,Ni,Cr)-containing tourmalines with concentration of transition metal elements up to 16 wt% on a seed have been grown from complex boron-containing hydrothermal solutions at a range of temperatures 400-750 °C and pressures 100 MPa. Experiments were conducted under conditions of a thermal gradient in titanium and chromium-nickel autoclaves. Tourmaline growth on a seed crystal occurs only if separate tourmaline-forming components (monocrystalline corundum and quartz bars) are used as charge. All tourmalines specified above grow in analogous (+) direction of the optical axis with a speed of 0.05 mm/day by faces of the trigonal pyramid, except tourmalines containing chromium. They grow in analogous (+0001) direction with a speed 0.05 mm/day, and in antilogous (-0001) direction with a speed of 0.01 mm/day by faces of the trigonal pyramid and in prism direction with a speed of 0.001 mm/day. Along with the large single crystals, a great amount of finest (30-150 μm in size) tourmaline crystals was formed during the runs by spontaneous nucleation both on the surface of the seed crystals and in the charge.

Signal peptide cleavage is essential for surface expression of a regulatory T cell surface protein, leucine rich repeat containing 32 (LRRC32)

OpenAIRE

Chan, Derek V; Somani, Ally-Khan; Young, Andrew B; Massari, Jessica V; Ohtola, Jennifer; Sugiyama, Hideaki; Garaczi, Edina; Babineau, Denise; Cooper, Kevin D; McCormick, Thomas S

2011-01-01

Abstract Background Elevated numbers of regulatory T cells (Tregs) have been implicated in certain cancers. Depletion of Tregs has been shown to increase anti-tumor immunity. Tregs also play a critical role in the suppression of autoimmune responses. The study of Tregs has been hampered by a lack of adequate surface markers. Leucine Rich Repeat Containing 32 (LRRC32), also known as Glycoprotein A Repetitions Predominant (GARP), has been postulated as a novel surface marker of activated Tregs....

Containment long-term operational integrity

International Nuclear Information System (INIS)

Sammataro, R.F.

1990-01-01

Periodic integrated leak rate tests are required to assure that containments continue to meet allowable leakage limits. Although overall performance has been quite good to date, several major containment aging and degradation mechanisms have been identified. Two pilot plant life extension (PLEX) studies serve as models for extending the operational integrity of present containments for light-water cooled nuclear power plants in the United States. One study is for a Boiling-Water Reactor (BWR) and the second is for a Pressurized-Water Reactor (PWR). Research and testing programs for determining the ultimate pressure capacity and failure mechanisms for containments under severe loading conditions and studies for extending the life of current plants beyond the present 40-year licensed lifetime are under way. This paper presents an overview of containment designs in the United States. Also presented are a discussion of the American Society of Mechanical Engineers Boiler and Pressure Vessel Code (ASME Code) and regulatory authority requirements for the design, construction, inservice inspection, leakage testing and repair of steel and concrete containments. Findings for containments from the pilot PLEX studies and continuing containment integrity research and testing programs are discussed. The ASME Code and regulatory requirements together with recommendations from the PLEX studies and containment integrity research and testing provide a basis for continued containment long-term operational integrity. (orig./GL)

Electronic devices containing switchably conductive silicon oxides as a switching element and methods for production and use thereof

Science.gov (United States)

Tour, James M; Yao, Jun; Natelson, Douglas; Zhong, Lin; He, Tao

2013-11-26

In various embodiments, electronic devices containing switchably conductive silicon oxide as a switching element are described herein. The electronic devices are two-terminal devices containing a first electrical contact and a second electrical contact in which at least one of the first electrical contact or the second electrical contact is deposed on a substrate to define a gap region therebetween. A switching layer containing a switchably conductive silicon oxide resides in the the gap region between the first electical contact and the second electrical contact. The electronic devices exhibit hysteretic current versus voltage properties, enabling their use in switching and memory applications. Methods for configuring, operating and constructing the electronic devices are also presented herein.

Device for manipulating a nuclear reactor fuel element in a fuel element pond containing water

International Nuclear Information System (INIS)

Jabsen, F.S.

1977-01-01

Using this device a fuel element can be manipulated inside a water filled storage pond for inspection purposes. A transport arrangement which is normally situated above such a pond is modified for this purpose. A crane bridge runs on rails on the upper edge of the pond. A type of trolley runs transversely to the direction of travel of the bridge between 2 wide flange supports forming the crane support. During movement this trolley moves a submerged combination of periscope and TV camera pendant from it at about half the pond height horizontally along the crane support. 2 vehicles move between these on 4 rollers each, on the under flanges of the crane support at spacings of about one fuel element length. A pendant arm of the same length as the periscope dips vertically into the pond from each vehicle. There is a bar of about fuel element length resting on the lower ends of both arms. The surface of a fuel element lying on this bar can be inspected through the periscope on longitudinal travel of the trolley. The bar with the fuel element can be rotated 90 0 downwards into a vertical position after removal of one or more rotating kingpins and release of a rope hanging on the end away from the kingpin. The rope is actuated by a winch on the crane support. The bar has vertical plates at both ends to hold the fuel element in its vertical position. (HP) [de

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

Directory of Open Access Journals (Sweden)

Diana S José-Edwards

2015-12-01

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

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

Science.gov (United States)

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

2015-12-01

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

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.

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.

Highly accessible AU-rich regions in 3’ untranslated regions are hotspots for binding of regulatory factors

Science.gov (United States)

2017-01-01

Post-transcriptional regulation is regarded as one of the major processes involved in the regulation of gene expression. It is mainly performed by RNA binding proteins and microRNAs, which target RNAs and typically affect their stability. Recent efforts from the scientific community have aimed at understanding post-transcriptional regulation at a global scale by using high-throughput sequencing techniques such as cross-linking and immunoprecipitation (CLIP), which facilitates identification of binding sites of these regulatory factors. However, the diversity in the experimental procedures and bioinformatics analyses has hindered the integration of multiple datasets and thus limited the development of an integrated view of post-transcriptional regulation. In this work, we have performed a comprehensive analysis of 107 CLIP datasets from 49 different RBPs in HEK293 cells to shed light on the complex interactions that govern post-transcriptional regulation. By developing a more stringent CLIP analysis pipeline we have discovered the existence of conserved regulatory AU-rich regions in the 3’UTRs where miRNAs and RBPs that regulate several processes such as polyadenylation or mRNA stability bind. Analogous to promoters, many factors have binding sites overlapping or in close proximity in these hotspots and hence the regulation of the mRNA may depend on their relative concentrations. This hypothesis is supported by RBP knockdown experiments that alter the relative concentration of RBPs in the cell. Upon AGO2 knockdown (KD), transcripts containing “free” target sites show increased expression levels compared to those containing target sites in hotspots, which suggests that target sites within hotspots are less available for miRNAs to bind. Interestingly, these hotspots appear enriched in genes with regulatory functions such as DNA binding and RNA binding. Taken together, our results suggest that hotspots are functional regulatory elements that define an extra layer

Regulatory authority information system RAIS

International Nuclear Information System (INIS)

Ortiz, P.; Mrabit, K.; Miaw, S.

2000-01-01

In this lecture the principles of the regulatory authority information system (RAIS) are presented. RAIS is a tool currently being developed by the IAEA for the Regulatory Authorities. It is a part of a set of supporting actions designed to assist member states in achieving the objectives of the Model project on radiation and waste safety infrastructure. RAIS is a tool that provides the management of the Regulatory Authority with the key information needed for the planning and implementation of activities and to ensure confidence that resources are optimally used. The RAIS contains five modules: Inventory of installations and radiation sources; Authorization process; Inspection and follow-up actions; Information on personal dosimetry; Assessment of effectiveness by means of performance indicators

Dynamic Cluster Analysis: An Unbiased Method for Identifying A+2 Element Containing Compounds in Liquid Chromatographic High-Resolution TOF Mass Spectrometric Data

DEFF Research Database (Denmark)

Andersen, Aaron John Christian; Hansen, Per Juel; Jørgensen, Kevin

2016-01-01

over 2800 u or metabolites which contained other A+2 elements, such as Cu, Ni, Mg, and Zn. It was determined that with an inter-isotopic mass accuracy of 1 ppm, in a fully automated process, using all three parameters, it is possible to specifically filter a chromatogram for S containing metabolites...

Phylum-Level Conservation of Regulatory Information in Nematodes despite Extensive Non-coding Sequence Divergence

Science.gov (United States)

Gordon, Kacy L.; Arthur, Robert K.; Ruvinsky, Ilya

2015-01-01

Gene regulatory information guides development and shapes the course of evolution. To test conservation of gene regulation within the phylum Nematoda, we compared the functions of putative cis-regulatory sequences of four sets of orthologs (unc-47, unc-25, mec-3 and elt-2) from distantly-related nematode species. These species, Caenorhabditis elegans, its congeneric C. briggsae, and three parasitic species Meloidogyne hapla, Brugia malayi, and Trichinella spiralis, represent four of the five major clades in the phylum Nematoda. Despite the great phylogenetic distances sampled and the extensive sequence divergence of nematode genomes, all but one of the regulatory elements we tested are able to drive at least a subset of the expected gene expression patterns. We show that functionally conserved cis-regulatory elements have no more extended sequence similarity to their C. elegans orthologs than would be expected by chance, but they do harbor motifs that are important for proper expression of the C. elegans genes. These motifs are too short to be distinguished from the background level of sequence similarity, and while identical in sequence they are not conserved in orientation or position. Functional tests reveal that some of these motifs contribute to proper expression. Our results suggest that conserved regulatory circuitry can persist despite considerable turnover within cis elements. PMID:26020930

Phylum-Level Conservation of Regulatory Information in Nematodes despite Extensive Non-coding Sequence Divergence.

Directory of Open Access Journals (Sweden)

Kacy L Gordon

2015-05-01

Full Text Available Gene regulatory information guides development and shapes the course of evolution. To test conservation of gene regulation within the phylum Nematoda, we compared the functions of putative cis-regulatory sequences of four sets of orthologs (unc-47, unc-25, mec-3 and elt-2 from distantly-related nematode species. These species, Caenorhabditis elegans, its congeneric C. briggsae, and three parasitic species Meloidogyne hapla, Brugia malayi, and Trichinella spiralis, represent four of the five major clades in the phylum Nematoda. Despite the great phylogenetic distances sampled and the extensive sequence divergence of nematode genomes, all but one of the regulatory elements we tested are able to drive at least a subset of the expected gene expression patterns. We show that functionally conserved cis-regulatory elements have no more extended sequence similarity to their C. elegans orthologs than would be expected by chance, but they do harbor motifs that are important for proper expression of the C. elegans genes. These motifs are too short to be distinguished from the background level of sequence similarity, and while identical in sequence they are not conserved in orientation or position. Functional tests reveal that some of these motifs contribute to proper expression. Our results suggest that conserved regulatory circuitry can persist despite considerable turnover within cis elements.

Analysis of impact of large commercial aircraft on a prestressed containment building

International Nuclear Information System (INIS)

Lee, Kyoungsoo; Han, Sang Eul; Hong, Jung-Wuk

2013-01-01

Highlights: • Aircraft impact analyses are performed using the missile–target interaction method. • A large commercial B747 aircraft is considered with erosion effect. • The rigid wall impact test shows the validity of the developed aircraft model. • The parametric studies on the fictitious containment building are performed. • The plastic failure of the target is governed by the impulse of aircraft at the first momentum peak. - Abstract: In this paper, the results of nonlinear dynamic analyses of a concrete containment building under extreme loads are presented. The impact of a large commercial B747 airliner is investigated as the extreme load, and a rigid wall impact test is performed using commercial nonlinear finite element codes. The impact forces exerted by the aircraft are verified compared with the time-dependent impact force provided by OECD/NEA (2002), which was calculated based on the so-called Riera method. The rigid wall impact analysis shows that the finite element model of a B747 is appropriate for the purpose of the aircraft crash analysis exposed to the external hazard of “Beyond Design-Basis Events” defined by U.S. Nuclear Regulatory Commission. Finally, the applicability of this methodology is further studied and verified by conducting parametric studies on the critical infrastructures of nuclear power plant containment structures

Analysis of impact of large commercial aircraft on a prestressed containment building

Energy Technology Data Exchange (ETDEWEB)

Lee, Kyoungsoo, E-mail: kylee@pvamu.edu [Center for Energy and Environmental Sustainability, Prairie View A and M University, Prairie view, TX, 77446 (United States); Han, Sang Eul, E-mail: hsang@inha.ac.kr [Department of Architectural Engineering, School of Architecture, Inha University, 253 Yonghyundong Nam-gu, Incheon, 402-751 (Korea, Republic of); Hong, Jung-Wuk, E-mail: j.hong@kaist.ac.kr [Department of Civil and Environmental Engineering, KAIST, 373-1 Guseon-dong, Yuseong-gu, Daejeon, 305-701 (Korea, Republic of)

2013-12-15

Highlights: • Aircraft impact analyses are performed using the missile–target interaction method. • A large commercial B747 aircraft is considered with erosion effect. • The rigid wall impact test shows the validity of the developed aircraft model. • The parametric studies on the fictitious containment building are performed. • The plastic failure of the target is governed by the impulse of aircraft at the first momentum peak. - Abstract: In this paper, the results of nonlinear dynamic analyses of a concrete containment building under extreme loads are presented. The impact of a large commercial B747 airliner is investigated as the extreme load, and a rigid wall impact test is performed using commercial nonlinear finite element codes. The impact forces exerted by the aircraft are verified compared with the time-dependent impact force provided by OECD/NEA (2002), which was calculated based on the so-called Riera method. The rigid wall impact analysis shows that the finite element model of a B747 is appropriate for the purpose of the aircraft crash analysis exposed to the external hazard of “Beyond Design-Basis Events” defined by U.S. Nuclear Regulatory Commission. Finally, the applicability of this methodology is further studied and verified by conducting parametric studies on the critical infrastructures of nuclear power plant containment structures.

Continuous improvement of the regulatory framework for the control of medical exposure

International Nuclear Information System (INIS)

Larcher, Ana M.; Ortiz Lopez, Pedro; Arias, Cesar; Marechal, Maria H.; Hernandez Alvarez, Ramon; Ferrer Garcia, Natividad; Castaneda Mucino, Antonia; Faller, Blanca

2008-01-01

One of the key elements to guide the improvement of the regulatory control is the availability of a self-assessment tool for regulatory performance. Although there is general guidance on self-assessment for regulators and users (IAEA), there is a need for more specific advice on how to address challenges and difficulties faced by regulatory bodies, when regulating radiation protection of patients. Examples of these challenges are the need for regulatory initiatives, in cooperation with health and education authorities, professional bodies and equipment suppliers, and to put in place necessary elements that are beyond responsibility of individual user of radiation, to enable them compliance with safety standards. Purpose: Within the programme of the Ibero American Forum of Nuclear and Radiation Safety Regulatory Organizations, a project to develop such a self-assessment tool for the regulatory control of medical exposure has been designed. Method: National experiences in transposing and enforcing the international radiation safety standards, as to how the requirements are included in national regulations are reviewed. Further, difficulties to the implementation of safety requirements are analyzed and a self-assessment approach and possible regulatory solutions a are presented. Results and discussion: In this study the following documents are being produced: 1) transposition of international requirements into national regulations in the six countries of the Forum, 2) difficulties to implement and enforce the requirements, 3) guidance on self-assessment of regulatory framework for medical exposure, 4) suggested contribution to the revision of international radiation safety standards. (author)

MYC cis-Elements in PsMPT Promoter Is Involved in Chilling Response of Paeonia suffruticosa.

Directory of Open Access Journals (Sweden)

Yuxi Zhang

Full Text Available The MPT transports Pi to synthesize ATP. PsMPT, a chilling-induced gene, was previously reported to promote energy metabolism during bud dormancy release in tree peony. In this study, the regulatory elements of PsMPT promoter involved in chilling response were further analyzed. The PsMPT transcript was detected in different tree peony tissues and was highly expressed in the flower organs, including petal, stigma and stamen. An 1174 bp of the PsMPT promoter was isolated by TAIL-PCR, and the PsMPT promoter::GUS transgenic Arabidopsis was generated and analyzed. GUS staining and qPCR showed that the promoter was active in mainly the flower stigma and stamen. Moreover, it was found that the promoter activity was enhanced by chilling, NaCl, GA, ACC and NAA, but inhibited by ABA, mannitol and PEG. In transgenic plants harboring 421 bp of the PsMPT promoter, the GUS gene expression and the activity were significantly increased by chilling treatment. When the fragment from -421 to -408 containing a MYC cis-element was deleted, the chilling response could not be observed. Further mutation analysis confirmed that the MYC element was one of the key motifs responding to chilling in the PsMPT promoter. The present study provides useful information for further investigation of the regulatory mechanism of PsMPT during the endo-dormancy release.

Regulatory control of maintenance activities in Argentine nuclear power plants

International Nuclear Information System (INIS)

Calvo, J.C.; Caruso, G.

2000-01-01

The main maintenance objective is to assure that the safety features of structures, components and systems of nuclear power plants are kept as designed. Therefore, there is a direct relationship between safety and maintenance. Owing to the above mentioned, maintenance activities are considered a relevant regulatory issue for the Argentine Nuclear Regulatory Authority (ARN). This paper describes the regulatory control to maintenance activities of Argentine nuclear power plants. It also addresses essential elements for maintenance control, routine inspections, special inspections during planned outages, audits and license conditions and requirements. (author)

Nitrosylation of Nitric-Oxide-Sensing Regulatory Proteins Containing [4Fe-4S] Clusters Gives Rise to Multiple Iron-Nitrosyl Complexes

Energy Technology Data Exchange (ETDEWEB)

Serrano, Pauline N. [Department of Chemistry, University of California, Davis CA 95616 USA; Wang, Hongxin [Department of Chemistry, University of California, Davis CA 95616 USA; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley CA 94720 USA; Crack, Jason C. [Centre for Molecular and Structural Biochemistry, School of Chemistry, University of East Anglia, Norwich Research Park Norwich NR4 7TJ UK; Prior, Christopher [Centre for Molecular and Structural Biochemistry, School of Chemistry, University of East Anglia, Norwich Research Park Norwich NR4 7TJ UK; Hutchings, Matthew I. [School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ UK; Thomson, Andrew J. [Centre for Molecular and Structural Biochemistry, School of Chemistry, University of East Anglia, Norwich Research Park Norwich NR4 7TJ UK; Kamali, Saeed [University of Tennessee Space Institute, Tullahome TN 37388-9700 USA; Yoda, Yoshitaka [Research and Utilization Division, SPring-8/JASRI, 1-1-1 Kouto, Sayo Hyogo 679-5198 Japan; Zhao, Jiyong [Advanced Photon Source, Argonne National Laboratory, Argonne IL 60439 USA; Hu, Michael Y. [Advanced Photon Source, Argonne National Laboratory, Argonne IL 60439 USA; Alp, Ercan E. [Advanced Photon Source, Argonne National Laboratory, Argonne IL 60439 USA; Oganesyan, Vasily S. [Centre for Molecular and Structural Biochemistry, School of Chemistry, University of East Anglia, Norwich Research Park Norwich NR4 7TJ UK; Le Brun, Nick E. [Centre for Molecular and Structural Biochemistry, School of Chemistry, University of East Anglia, Norwich Research Park Norwich NR4 7TJ UK; Cramer, Stephen P. [Department of Chemistry, University of California, Davis CA 95616 USA; Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley CA 94720 USA

2016-10-25

The reaction of protein-bound iron–sulfur (Fe-S) clusters with nitric oxide (NO) plays key roles in NO-mediated toxicity and signaling. Elucidation of the mechanism of the reaction of NO with DNA regulatory proteins that contain Fe-S clusters has been hampered by a lack of information about the nature of the iron-nitrosyl products formed. Herein, we report nuclear resonance vibrational spectroscopy (NRVS) and density functional theory (DFT) calculations that identify NO reaction products in WhiD and NsrR, regulatory proteins that use a [4Fe-4S] cluster to sense NO. This work reveals that nitrosylation yields multiple products structurally related to Roussin's Red Ester (RRE, [Fe₂(NO)₄(Cys)₂]) and Roussin's Black Salt (RBS, [Fe₄(NO)₇S₃]. In the latter case, the absence of ³²S/³⁴S shifts in the Fe-S region of the NRVS spectra suggest that a new species, Roussin's Black Ester (RBE), may be formed, in which one or more of the sulfide ligands is replaced by Cys thiolates.

Building Nuclear Safety and Security Culture Within Regulatory Body

International Nuclear Information System (INIS)

Huda, K.

2016-01-01

To achieve a higher level of nuclear safety and security, it needs to develop the safety and security culture not only in the facility but also in the regulatory body. The regulatory body, especially needs to develop the safety and security culture within the organization, because it has a function to promote and oversee the culture in the facilities. In this sense, the regulatory body should become a role model. Development of the nuclear safety and security culture should be started by properly understanding its concept and awakening the awareness of individual and organization on the importance of nuclear safety and security. For effectiveness of the culture development in the regulatory body, the following steps are suggested to be taken: setting up of the regulatory requirements, self-assessment, independent assessment review, communication with the licensee, oversight of management system implementation, and integration with regulatory activities. The paper discusses those steps in the framework of development of nuclear safety and security culture in the regulatory body, as well as some important elements in building of the culture in the nuclear facilities. (author)

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.

Nuclear fuel element

International Nuclear Information System (INIS)

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

1975-01-01

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

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...

Analyses of a steel containment vessel with an outer contact structure under severe internal overpressurization conditions

International Nuclear Information System (INIS)

Porter, V.L.

1994-01-01

Many Mark-I and Mark-II BWR plants are designed with a steel vessel as the primary containment. Typically, the steel containment vessel (SCV) is enclosed within a reinforced concrete shield building with only a small gap (74-90 mm) separating the two structures. This paper describes finite element analyses performed to evaluate the effects of contact and friction between a steel containment vessel and an outer contact structure when the containment vessel is subjected to large internal pressures. These computations were motivated by a joint program on containment integrity involving the Nuclear Power Engineering Corporation (NUPEC) of Japan, the US Nuclear Regulatory Commission (NRC), and Sandia National Laboratories for testing model containments. Under severe accident loading conditions, the steel containment vessel in a typical Mark-I or Mark-II plant may deform under internal pressurization such that it contacts the inner surface of a shield building wall. (Thermal expansion from increasing accident temperatures would also close the gap between the SCV and the shield building, but temperature effects are not considered in these analyses.) The amount and location of contact and the pressure at which it occurs all affect how the combined structure behaves. A preliminary finite element model has been developed to analyze a model of a typical steel containment vessel con-ling into contact with an outer structure. Both the steel containment vessel and the outer contact structure were modelled with axisymmetric shell finite elements. Of particular interest are the influence that the contact structure has on deformation and potential failure modes of the containment vessel. Furthermore, the coefficient of friction between the two structures was varied to study its effects on the behavior of the containment vessel and on the uplift loads transmitted to the contact structure. These analyses show that the material properties of an outer contact structure and the amount

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.

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.

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

A role for circadian evening elements in cold-regulated gene expression in Arabidopsis.

Science.gov (United States)

Mikkelsen, Michael D; Thomashow, Michael F

2009-10-01

The plant transcriptome is dramatically altered in response to low temperature. The cis-acting DNA regulatory elements and trans-acting factors that regulate the majority of cold-regulated genes are unknown. Previous bioinformatic analysis has indicated that the promoters of cold-induced genes are enriched in the Evening Element (EE), AAAATATCT, a DNA regulatory element that has a role in circadian-regulated gene expression. Here we tested the role of EE and EE-like (EEL) elements in cold-induced expression of two Arabidopsis genes, CONSTANS-like 1 (COL1; At5g54470) and a gene encoding a 27-kDa protein of unknown function that we designated COLD-REGULATED GENE 27 (COR27; At5g42900). Mutational analysis indicated that the EE/EEL elements were required for cold induction of COL1 and COR27, and that their action was amplified through coupling with ABA response element (ABRE)-like (ABREL) motifs. An artificial promoter consisting solely of four EE motifs interspersed with three ABREL motifs was sufficient to impart cold-induced gene expression. Both COL1 and COR27 were found to be regulated by the circadian clock at warm growth temperatures and cold-induction of COR27 was gated by the clock. These results suggest that cold- and clock-regulated gene expression are integrated through regulatory proteins that bind to EE and EEL elements supported by transcription factors acting at ABREL sequences. Bioinformatic analysis indicated that the coupling of EE and EEL motifs with ABREL motifs is highly enriched in cold-induced genes and thus may constitute a DNA regulatory element pair with a significant role in configuring the low-temperature transcriptome.

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.

Environmental Regulatory Update Table, May/June 1992

Energy Technology Data Exchange (ETDEWEB)

Houlberg, L.M.; Hawkins, G.T.; Lewis, E.B.; Salk, M.S.

1992-07-01

This report contains a bi-monthly update of environmental regulatory activity that is of interest to the Department of Energy. It is provided to DOE operations and contractor staff to assist and support environmental management programs by tracking regulatory developments. Any proposed regulation that raises significant issues for any DOE operation should be reported to the Office of Environmental Guidance (EH-23) as soon as possible so that the Department can make its concerns known to the appropriate regulatory agency. Items of particular interest to EH-23 are indicated by a shading of the RU{number sign}.

Environmental Regulatory Update Table, May/June 1992

Energy Technology Data Exchange (ETDEWEB)

Houlberg, L.M.; Hawkins, G.T.; Lewis, E.B.; Salk, M.S.

1992-07-01

This report contains a bi-monthly update of environmental regulatory activity that is of interest to the Department of Energy. It is provided to DOE operations and contractor staff to assist and support environmental management programs by tracking regulatory developments. Any proposed regulation that raises significant issues for any DOE operation should be reported to the Office of Environmental Guidance (EH-23) as soon as possible so that the Department can make its concerns known to the appropriate regulatory agency. Items of particular interest to EH-23 are indicated by a shading of the RU{number_sign}.

Systematic identification of regulatory variants associated with cancer risk.

Science.gov (United States)

Liu, Song; Liu, Yuwen; Zhang, Qin; Wu, Jiayu; Liang, Junbo; Yu, Shan; Wei, Gong-Hong; White, Kevin P; Wang, Xiaoyue

2017-10-23

Most cancer risk-associated single nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) are noncoding and it is challenging to assess their functional impacts. To systematically identify the SNPs that affect gene expression by modulating activities of distal regulatory elements, we adapt the self-transcribing active regulatory region sequencing (STARR-seq) strategy, a high-throughput technique to functionally quantify enhancer activities. From 10,673 SNPs linked with 996 cancer risk-associated SNPs identified in previous GWAS studies, we identify 575 SNPs in the fragments that positively regulate gene expression, and 758 SNPs in the fragments with negative regulatory activities. Among them, 70 variants are regulatory variants for which the two alleles confer different regulatory activities. We analyze in depth two regulatory variants-breast cancer risk SNP rs11055880 and leukemia risk-associated SNP rs12142375-and demonstrate their endogenous regulatory activities on expression of ATF7IP and PDE4B genes, respectively, using a CRISPR-Cas9 approach. By identifying regulatory variants associated with cancer susceptibility and studying their molecular functions, we hope to help the interpretation of GWAS results and provide improved information for cancer risk assessment.

Finite element modelling of FRC beams containing PVA and Basalt fibres: A comparative study

Science.gov (United States)

Ayub, Tehmina; Khan, Sadaqat Ullah

2017-09-01

The endeavour of current study is to compare the flexural behaviour and three dimensional (3D) finite element analysis (FEA) and the results of FEM are compared with the experimental results of 07 HPFRC beams. Out of seven (07), 01 beam of plain concrete without fibres was cast as a control beam. Three (03) beams containing 1, 2 and 3% volume of PVA fibres were prepared by using HPFRC mixes while, the remaining other three (03) beams were prepared using HPFRC mixes containing 1, 2 and 3% volume of Basalt fibres. In order to ensure flexural failure, three-point bending load was applied at the mid span of all beams. The maximum flexural load and corresponding deflection and strains at the mid span attained prior to the failure were obtained as flexural test results. The FEM results were obtained by simulating all beams in ATENA 3D program and verified through flexural test results. Both of the results of FEM and Experiment showed good agreement with each other.

Signal peptide cleavage is essential for surface expression of a regulatory T cell surface protein, leucine rich repeat containing 32 (LRRC32).

Science.gov (United States)

Chan, Derek V; Somani, Ally-Khan; Young, Andrew B; Massari, Jessica V; Ohtola, Jennifer; Sugiyama, Hideaki; Garaczi, Edina; Babineau, Denise; Cooper, Kevin D; McCormick, Thomas S

2011-05-26

Elevated numbers of regulatory T cells (T(regs)) have been implicated in certain cancers. Depletion of T(regs) has been shown to increase anti-tumor immunity. T(regs) also play a critical role in the suppression of autoimmune responses. The study of T(regs) has been hampered by a lack of adequate surface markers. Leucine Rich Repeat Containing 32 (LRRC32), also known as Glycoprotein A Repetitions Predominant (GARP), has been postulated as a novel surface marker of activated T(regs). However, there is limited information regarding the processing of LRRC32 or the regulatory phenotype and functional activity of T(regs) expressing LRRC32. Using naturally-occurring freshly isolated T(regs), we demonstrate that low levels of LRRC32 are present intracellularly prior to activation and that freshly isolated LRRC32+ T(regs) are distinct from LRRC32- T(regs) with respect to the expression of surface CD62L. Using LRRC32 transfectants of HEK cells, we demonstrate that the N-terminus of LRRC32 is cleaved prior to expression of the protein at the cell surface. Furthermore, we demonstrate using a construct containing a deleted putative signal peptide region that the presence of a signal peptide region is critical to cell surface expression of LRRC32. Finally, mixed lymphocyte assays demonstrate that LRRC32+ T(regs) are more potent suppressors than LRRC32- T(regs). A cleaved signal peptide site in LRRC32 is necessary for surface localization of native LRRC32 following activation of naturally-occurring freshly-isolated regulatory T cells. LRRC32 expression appears to alter the surface expression of activation markers of T cells such as CD62L. LRRC32 surface expression may be useful as a marker that selects for more potent T(reg) populations. In summary, understanding the processing and expression of LRRC32 may provide insight into the mechanism of action of T(regs) and the refinement of immunotherapeutic strategies aimed at targeting these cells.

Signal peptide cleavage is essential for surface expression of a regulatory T cell surface protein, leucine rich repeat containing 32 (LRRC32

Directory of Open Access Journals (Sweden)

Sugiyama Hideaki

2011-05-01

Full Text Available Abstract Background Elevated numbers of regulatory T cells (Tregs have been implicated in certain cancers. Depletion of Tregs has been shown to increase anti-tumor immunity. Tregs also play a critical role in the suppression of autoimmune responses. The study of Tregs has been hampered by a lack of adequate surface markers. Leucine Rich Repeat Containing 32 (LRRC32, also known as Glycoprotein A Repetitions Predominant (GARP, has been postulated as a novel surface marker of activated Tregs. However, there is limited information regarding the processing of LRRC32 or the regulatory phenotype and functional activity of Tregs expressing LRRC32. Results Using naturally-occurring freshly isolated Tregs, we demonstrate that low levels of LRRC32 are present intracellularly prior to activation and that freshly isolated LRRC32+ Tregs are distinct from LRRC32- Tregs with respect to the expression of surface CD62L. Using LRRC32 transfectants of HEK cells, we demonstrate that the N-terminus of LRRC32 is cleaved prior to expression of the protein at the cell surface. Furthermore, we demonstrate using a construct containing a deleted putative signal peptide region that the presence of a signal peptide region is critical to cell surface expression of LRRC32. Finally, mixed lymphocyte assays demonstrate that LRRC32+ Tregs are more potent suppressors than LRRC32- Tregs. Conclusions A cleaved signal peptide site in LRRC32 is necessary for surface localization of native LRRC32 following activation of naturally-occurring freshly-isolated regulatory T cells. LRRC32 expression appears to alter the surface expression of activation markers of T cells such as CD62L. LRRC32 surface expression may be useful as a marker that selects for more potent Treg populations. In summary, understanding the processing and expression of LRRC32 may provide insight into the mechanism of action of Tregs and the refinement of immunotherapeutic strategies aimed at targeting these cells.

Dynamic analysis of reactor containment building using axisymmetric finite element model

International Nuclear Information System (INIS)

Thakkar, S.K.; Dubey, R.N.

1989-01-01

The structural safety of nuclear reactor building during earthquake is of great importance in view of possibility of radiation hazards. The rational evaluation of forces and displacements in various portions of structure and foundation during strong ground motion is most important for safe performance and economic design of the reactor building. The accuracy of results of dynamic analysis is naturally dependent on the type of mathematical model employed. Three types of mathematical models are employed for dynamic analysis of reactor building beam model axisymmetric finite element model and three dimensional model. In this paper emphasis is laid on axisymmetric model. This model of containment building is considered a reinfinement over conventional beam model of the structure. The nuclear reactor building on a rocky foundation is considered herein. The foundation-structure interaction is relatively less in this condition. The objective of the paper is to highlight the significance of modelling of non-axisymmetric portion of building, such as reactor internals by equivalent axisymmetric body, on the structural response of the building

Strengthening Regulatory Competence through Techno-managerial Knowledge Integration: Indian Experience

International Nuclear Information System (INIS)

Kuchibhotla, S.

2016-01-01

Competence development is the process of identifying the competencies required to perform a given job, role or set of tasks successfully at workplace. Strengthening regulatory competence, for the nuclear regulator, is essential to ensure skilled and competent human resources for performing the functions of the Regulatory Body. The strengthening of existing competence level for the Indian nuclear regulator, takes into account the understanding of the elements such as legal basis and regulatory processes governing operations of regulatory body, technological competences for performing regulatory functions, competences pertinent to regulatory practices, and competences related to personal and interpersonal effectiveness within the organization. Competency data from AERB divisions was compiled to identify gaps at various positions with recommendations for making specialized training modules and modifications to basic and refresher training modules. The exercise is aimed at providing continual improvement in skills and knowledge of human resources at AERB in a phased manner. (author)

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...

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

78 FR 14840 - U.S.-EU High Level Regulatory Cooperation Forum-Stakeholder Session

Science.gov (United States)

2013-03-07

... OFFICE OF MANAGEMENT AND BUDGET U.S.-EU High Level Regulatory Cooperation Forum--Stakeholder... the future. Time constraints may prevent some stakeholders from making presentations on April 10th or... stakeholder session agenda will in no way prejudge the specific elements of a future transatlantic regulatory...

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.

Continuous Improvement of the Regulatory Framework for the Control of Medical Exposure

International Nuclear Information System (INIS)

Larcher, A.M.; Ortiz lopez, Pedro; Arias, Cesar; Marechal, Maria H.; Hernandez Alvarez, Ramon; Ferrer Garcia, Natividad; Castaneda Mucino, Antonia; Faller, Blanca

2011-01-01

Background: One of the key elements to guide the improvement of the regulatory control is the availability of a self-assessment tool for regulatory performance. Although there is general guidance on self-assessment for regulators and users (IAEA), there is a need for specific advice on how to address challenges and difficulties faced by regulatory bodies, when regulating radiation protection of patients. Examples of these challenges are the need of regulatory initiatives, in cooperation with health and education authorities, professional bodies and equipment suppliers, and to put in place necessary elements that are beyond responsibility of individual users of radiation, to enable them compliance with safety standards. Purpose: within the programme of the Ibero American Forum of Nuclear and Radiation Safety Regulatory Organizations, a project to develop such a self assessment tool for the regulatory control of medical exposure has been designed. Method: national experiences in transposing and enforcing the international radiation safety standards, as to how the requirements are included in national regulations are reviewed. Further, difficulties to the implementation of safety requirements are included in national regulations are analyzed and a self assessment approach and possible regulatory solutions are presented. Results and discussion: in tis study the following documents are being produced: 1) Transposition of international requirements into national regulations in the six countries of the Forum, 2) difficulties to implement and enforce the requirements, 3) guidance on self assessment of regulatory framework for medical exposure, 4) suggested contribution to the revision of international radiation safety standards. (authors)

Regulatory Oversight for New Projects - Challenges and Improvement in Regulation

International Nuclear Information System (INIS)

Lall, F.

2016-01-01

From inception, there has been rise in number of Nuclear Power Plants (NPP) even though very few accidents / events led to intermittent setbacks. However these accidents / events have posed challenges towards enhancement of safety and scope of regulation in all phases of NPP such as siting, design, construction, commissioning and decommissioning. It is essential to ensure compliance to these enhanced safety requirements during all phases of NPP. New and evolutionary reactors are under threshold for regulatory consideration world over. The variety of technologies and genres by themselves pose challenges to regulatory bodies. These challenges are to be addressed through systematic enhancement of the regulation including updating of regulatory documents. The paper touches upon some key elements to be considered towards such enhancement of regulation during all stages of NPP. These being; ensuring quality assurance, regulatory oversight especially over supply chain and contractors, counterfeit material specifically in case of international dealings, emergency handling in case of multi-unit site, feedback and associated enhancements from international events, construction experience database and feedback for safety enhancement, qualification and acceptance of first of a kind systems, regulatory enforcement specifically in case of imported reactors and maintaining interface between safety and security. Regulation in present context has become dynamic and Regulatory bodies need to continue enhancement of its current regulation taking into account the technological developments, feedback from construction, operation and accidents in the current fleet of plants. The paper touches upon some of these elements and highlights the challenges and improvements in regulation. (author)

A method for selecting cis-acting regulatory sequences that respond to small molecule effectors

Directory of Open Access Journals (Sweden)

Allas Ülar

2010-08-01

Full Text Available Abstract Background Several cis-acting regulatory sequences functioning at the level of mRNA or nascent peptide and specifically influencing transcription or translation have been described. These regulatory elements often respond to specific chemicals. Results We have developed a method that allows us to select cis-acting regulatory sequences that respond to diverse chemicals. The method is based on the β-lactamase gene containing a random sequence inserted into the beginning of the ORF. Several rounds of selection are used to isolate sequences that suppress β-lactamase expression in response to the compound under study. We have isolated sequences that respond to erythromycin, troleandomycin, chloramphenicol, meta-toluate and homoserine lactone. By introducing synonymous and non-synonymous mutations we have shown that at least in the case of erythromycin the sequences act at the peptide level. We have also tested the cross-activities of the constructs and found that in most cases the sequences respond most strongly to the compound on which they were isolated. Conclusions Several selected peptides showed ligand-specific changes in amino acid frequencies, but no consensus motif could be identified. This is consistent with previous observations on natural cis-acting peptides, showing that it is often impossible to demonstrate a consensus. Applying the currently developed method on a larger scale, by selecting and comparing an extended set of sequences, might allow the sequence rules underlying the activity of cis-acting regulatory peptides to be identified.

Enrichment of conserved synaptic activity-responsive element in neuronal genes predicts a coordinated response of MEF2, CREB and SRF.

Directory of Open Access Journals (Sweden)

Fernanda M Rodríguez-Tornos

Full Text Available A unique synaptic activity-responsive element (SARE sequence, composed of the consensus binding sites for SRF, MEF2 and CREB, is necessary for control of transcriptional upregulation of the Arc gene in response to synaptic activity. We hypothesize that this sequence is a broad mechanism that regulates gene expression in response to synaptic activation and during plasticity; and that analysis of SARE-containing genes could identify molecular mechanisms involved in brain disorders. To search for conserved SARE sequences in the mammalian genome, we used the SynoR in silico tool, and found the SARE cluster predominantly in the regulatory regions of genes expressed specifically in the nervous system; most were related to neural development and homeostatic maintenance. Two of these SARE sequences were tested in luciferase assays and proved to promote transcription in response to neuronal activation. Supporting the predictive capacity of our candidate list, up-regulation of several SARE containing genes in response to neuronal activity was validated using external data and also experimentally using primary cortical neurons and quantitative real time RT-PCR. The list of SARE-containing genes includes several linked to mental retardation and cognitive disorders, and is significantly enriched in genes that encode mRNA targeted by FMRP (fragile X mental retardation protein. Our study thus supports the idea that SARE sequences are relevant transcriptional regulatory elements that participate in plasticity. In addition, it offers a comprehensive view of how activity-responsive transcription factors coordinate their actions and increase the selectivity of their targets. Our data suggest that analysis of SARE-containing genes will reveal yet-undescribed pathways of synaptic plasticity and additional candidate genes disrupted in mental disease.

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

Directory of Open Access Journals (Sweden)

Lamprini G Kalampoki

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

Finite Element Analysis of Doorframe Structure of Single Oblique Pole Type in Container Crane

Science.gov (United States)

Cheng, X. F.; Wu, F. Q.; Tang, G.; Hu, X.

2017-07-01

Compared with the composite type, the single oblique pole type has more advantages, such as simple structure, thrift steel and high safe overhead clearance. The finite element model of the single oblique pole type is established in nodes by ANSYS, and more details are considered when the model is simplified, such as the section of Girder and Boom, torque in Girder and Boom occurred by Machinery house and Trolley, density according to the way of simplification etc. The stress and deformation of ten observation points are compared and analyzed, when the trolley is in nine dangerous positions. Based on the result of analysis, six dangerous points are selected to provide reference for the detection and evaluation of container crane.

Postinduction represssion of the β-interferon gene is mediated through two positive regulatory domains

International Nuclear Information System (INIS)

Whittemore, L.A.; Maniatis, T.

1990-01-01

Virus induction of the human β-interferon (β-IFN) gene results in an increase in the rate of β-IFN mRNA synthesis, followed by a rapid postinduction decrease. In this paper, the authors show that two β-IFN promoter elements, positive regulatory domains I and II (PRDI and PRDII), which are required for virus induction of the β-IFN gene are also required for the postinduction turnoff. Although protein synthesis is not necessary for activation, it is necessary for repression of these promoter elements. Examination of nuclear extracts from cells infected with virus reveals the presence of virus-inducible, cycloheximide-sensitive, DNA-binding activities that interact specifically with PRDI or PRDII. They propose that the postinduction repression of β-IFN gene transcription involves virus inducible repressors that either bind directly to the positive regulatory elements of the β-IFN promoter or inactivate the positive regulatory factors bound to PRDI and PRDII

Regulatory and biosafety issues in relation to transgenic animals in food and agriculture, feeds containing genetically modified organisms (GMO) and veterinary biologics

International Nuclear Information System (INIS)

Kochhar, H.P.S.; Gifford, G.A.; Kahn, S.

2005-01-01

biotechnology must be shown to be pure, potent, safe and effective when used according to label recommendations. The Canadian regulatory system relies on the 'precautionary principle' in its approach to regulate the 'product' instead of the 'process'. The regulatory framework captures transgenic animals under the Canadian Environmental Protection Act (CEPA). Food from transgenic animals is assessed for safety by Health Canada under its Novel Foods Regulations of the Food and Drugs Act. Feed containing any genetically modified organism is considered Novel Feed under the Feeds Act and Regulations. The regulation of veterinary biologics, in an effort to prevent and diagnose infectious diseases of animals, relies on effective science-based regulatory controls under the Health of Animals Act and Regulations. The Canadian system of regulation for feeds, veterinary biologics and transgenic animals could be useful to developing countries in the process of establishing an effective framework for new regulations. (author)

Enzymatic Mercury Detoxification: The Regulatory Protein MerR

CERN Multimedia

Ctortecka, B; Walsh, C T; Comess, K M

2002-01-01

Mercury ions and organomercurial reagents are extremely toxic due to their affinity for thiol groups. Many bacteria contain an elaborate detoxification system for a metabolic conversion of toxic Hg$^{2+}$ or organomercurials to less toxic elemental Hg$^0$. The main components of the enzymatic mercury detoxification (see Fig. 1) are the regulatory protein MerR (mercury responsive genetic switch), the organomercurial lyase MerB (cleavage of carbon mercury bonds), and the mercuric ion reductase MerA (reduction of mercuric ions). In these proteins Hg$^{2+}$ is usually coordinated by the thiol groups of cysteines. We utilize the nuclear quadrupole interaction (NQI) of ${\\rm^{199m}}$Hg detected by time differential perturbed angular correlation (TDPAC) to identify the Hg metal site geometries in these proteins in order to elucidate the molecular origin of the ultrasensitivity, selectivity and reaction mechanism of this detoxification system. The short lived TDPAC probe ${\\rm^{199m}}$Hg ($\\tau_{1/2} =$ 43 min) is su...

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

SACE_5599, a putative regulatory protein, is involved in morphological differentiation and erythromycin production in Saccharopolyspora erythraea.

Science.gov (United States)

Kirm, Benjamin; Magdevska, Vasilka; Tome, Miha; Horvat, Marinka; Karničar, Katarina; Petek, Marko; Vidmar, Robert; Baebler, Spela; Jamnik, Polona; Fujs, Štefan; Horvat, Jaka; Fonovič, Marko; Turk, Boris; Gruden, Kristina; Petković, Hrvoje; Kosec, Gregor

2013-12-17

Erythromycin is a medically important antibiotic, biosynthesized by the actinomycete Saccharopolyspora erythraea. Genes encoding erythromycin biosynthesis are organized in a gene cluster, spanning over 60 kbp of DNA. Most often, gene clusters encoding biosynthesis of secondary metabolites contain regulatory genes. In contrast, the erythromycin gene cluster does not contain regulatory genes and regulation of its biosynthesis has therefore remained poorly understood, which has for a long time limited genetic engineering approaches for erythromycin yield improvement. We used a comparative proteomic approach to screen for potential regulatory proteins involved in erythromycin biosynthesis. We have identified a putative regulatory protein SACE_5599 which shows significantly higher levels of expression in an erythromycin high-producing strain, compared to the wild type S. erythraea strain. SACE_5599 is a member of an uncharacterized family of putative regulatory genes, located in several actinomycete biosynthetic gene clusters. Importantly, increased expression of SACE_5599 was observed in the complex fermentation medium and at controlled bioprocess conditions, simulating a high-yield industrial fermentation process in the bioreactor. Inactivation of SACE_5599 in the high-producing strain significantly reduced erythromycin yield, in addition to drastically decreasing sporulation intensity of the SACE_5599-inactivated strains when cultivated on ABSM4 agar medium. In contrast, constitutive overexpression of SACE_5599 in the wild type NRRL23338 strain resulted in an increase of erythromycin yield by 32%. Similar yield increase was also observed when we overexpressed the bldD gene, a previously identified regulator of erythromycin biosynthesis, thereby for the first time revealing its potential for improving erythromycin biosynthesis. SACE_5599 is the second putative regulatory gene to be identified in S. erythraea which has positive influence on erythromycin yield. Like bld

Mobile Source Emissions Regulatory Compliance Data Inventory

Data.gov (United States)

U.S. Environmental Protection Agency — The Mobile Source Emissions Regulatory Compliance Data Inventory data asset contains measured summary compliance information on light-duty, heavy-duty, and non-road...

Shielded container

International Nuclear Information System (INIS)

Fries, B.A.

1978-01-01

A shielded container for transportation of radioactive materials is disclosed in which leakage from the container is minimized due to constructional features including, inter alia, forming the container of a series of telescoping members having sliding fits between adjacent side walls and having at least two of the members including machine sealed lids and at least two of the elements including hand-tightenable caps

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.

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.

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

Techniques of analyzing the impacts of certain electric-utility ratemaking and regulatory-policy concepts. Bibliography

Energy Technology Data Exchange (ETDEWEB)

None

1980-08-01

This bibliography provides documentation for use by state public utility commissions and major nonregulated utilities in evaluating the applicability of a wide range of electric utility rate design and regulatory concepts in light of certain regulatory objectives. Part I, Utility Regulatory Objectives, contains 2084 citations on conservation of energy and capital; efficient use of facilities and resources; and equitable rates to electricity consumers. Part II, Rate Design Concepts, contains 1238 citations on time-of-day rates; seasonally-varying rates; cost-of-service rates; interruptible rates (including the accompanying use of load management techniques); declining block rates; and lifeline rates. Part III, Regulatory Concepts, contains 1282 references on restrictions on master metering; procedures for review of automatic adjustment clauses; prohibitions of rate or regulatory discrimination against solar, wind, or other small energy systems; treatment of advertising expenses; and procedures to protect ratepayers from abrupt termination of service.

Preliminary estimates of the quantities of rare-earth elements contained in selected products and in imports of semimanufactured products to the United States, 2010

Science.gov (United States)

Bleiwas, Donald I.; Gambogi, Joseph

2013-01-01

Rare-earth elements (REEs) are contained in a wide range of products of economic and strategic importance to the Nation. The REEs may or may not represent a significant component of that product by mass, value, or volume; however, in many cases, the embedded REEs are critical for the device’s function. Domestic sources of primary supply and the manufacturing facilities to produce products are inadequate to meet U.S. requirements; therefore, a significant percentage of the supply of REEs and the products that contain them are imported to the United States. In 2011, mines in China produced roughly 97 percent of the world’s supply of REEs, and the country’s production of these elements will likely dominate global supply until at least 2020. Preliminary estimates of the types and amount of rare-earth elements, reported as oxides, in semimanufactured form and the amounts used for electric vehicle batteries, catalytic converters, computers, and other applications were developed to provide a perspective on the Nation’s use of these elements. The amount of rare-earth metals recovered from recycling, remanufacturing, and reuse is negligible when the tonnage of products that contain REEs deposited in landfills and retained in storage is considered. Under favorable market conditions, the recovery of REEs from obsolete products could potentially displace a portion of the supply from primary sources.

Nuclear regulatory review of licensee self-assessment (LSA)

International Nuclear Information System (INIS)

2003-01-01

Licensee self-assessment (LSA) by nuclear power plant operators is described as all the activities that a licensee performs in order to identify opportunities for improvements. An LSA is part of an organisation's holistic management system, which must include other process elements. Particularly important elements are: a process for choosing which identified potential improvements should be implemented and a process of project management for implementing the improvements chosen. Nuclear regulators expect the licensee to run an effective LSA programme, which reflects the licensee's 'priority to safety'. Based on contributions from members of the NEA Committee on Nuclear Regulatory Activities (CNRA), this publication provides an overview of the current regulatory philosophy on and approaches to LSA as performed by licensees. The publication's intended audience is primarily nuclear safety regulators, but government authorities, nuclear power plant operators and the general public may also be interested. (author)

Metal cluster compounds - chemistry and importance; clusters containing isolated main group element atoms, large metal cluster compounds, cluster fluxionality

International Nuclear Information System (INIS)

Walther, B.

1988-01-01

This part of the review on metal cluster compounds deals with clusters containing isolated main group element atoms, with high nuclearity clusters and metal cluster fluxionality. It will be obvious that main group element atoms strongly influence the geometry, stability and reactivity of the clusters. High nuclearity clusters are of interest in there own due to the diversity of the structures adopted, but their intermediate position between molecules and the metallic state makes them a fascinating research object too. These both sites of the metal cluster chemistry as well as the frequently observed ligand and core fluxionality are related to the cluster metal and surface analogy. (author)

Information system fur the management of a regulatory programme

International Nuclear Information System (INIS)

Ortiz, P.; Mrabit, K.; Miaw, S.

1998-01-01

A Regulatory Programme to monitor safety of activities involving radiation sources, implies the existence of a Regulatory Authority empowered by legislation to issue radiation protection regulations and to monitor compliance with those regulations. The core element of the programme is a system of notification and authorization (registration and licensing), inspection and enforcement. The efficiency of this system is largely dependent on the availability of reliable information on the inventory of radiation sources and installations, the administrative status of the facilities (authorization), prompt processing of inspection reports and follow up of regulatory actions, including monitoring deadlines. Essential data relevant to safety, such as personal dosimetry for occupationally exposed individuals, inspection findings and incident reports would provide, in addition, an insight on the overall safety of the country. A simple but comprehensive Regulatory Authority Information System (RAIS) linked to the authorization and inspection process will largely facilitate regulatory decisions and actions. A readily available and reliable information from the various regulatory activities will facilitate planning, optimization of resources, monitoring safety related data, disseminating safety information, making decisions and follow up regulatory actions including monitoring dead lines. The implementation of the system in more than 50 countries will contribute to experience exchange and harmonization of regulatory activities. (author)

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

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.

Pyrometallurgical partitioning of uranium and transuranic elements from rare earth elements by electrorefining and reductive extraction

International Nuclear Information System (INIS)

Uozumi, Koichi; Kinoshita, Kensuke; Inoue, Tadashi; Storvick, T.S.; Krueger, C.L.; Nabelek, C.R.

2001-01-01

High-level liquid waste generated from PUREX reprocessing contains a small amount of transuranic elements, such as Np, Pu, Am, and Cm, with long-lived radioactivities. A pyrometallurgical partitioning process is being developed to recover transuranic elements from such waste. Small amounts of U contained in the high-level liquid waste are also recovered in the process. A key issue for developing the process is effective separation of U and the transuranic elements from the rare-earth elements, because the two elemental groups are chemically analogous. A series of process tests were carried out in the present study to demonstrate that a combination of electrorefining and reductive extraction is useful for separating U and transuranic elements from the rare-earth elements. The results indicate that 99% of U and each transuranic elements is recovered by the combination process as a product, and that the quantity of rare-earth elements contained in the product is smaller than the transuranic elements by weight. The overall mass balance of U and transuranic elements in the system ranged within the experimental errors assigned to sampling and analysis. (author)

Elemental characterization of coal ash and its leachates using sequential extraction techniques

International Nuclear Information System (INIS)

Landsberger, S.; Cerbus, J.F.; Larson, S.

1995-01-01

Over 50 million tons of coal ash are produced annually in North America. Technological improvements in air pollution control have decreased stack emissions but have also increased contaminant concentrations in the ash of coal-fired boiler applications. The leaching of heavy metals and other elements during regulatory tests may cause coal ash to be classified as hazardous waste, complicating land disposal. The hazardous nature of coal ash remains unclear because current toxicity tests fail to effectively characterize the elemental distribution and chemical solubility of trace metals in the landfill environment. Leaching characteristics of ash samples can be investigated with various laboratory extraction procedures in association with multi-elemental analytical techniques (e.g., neutron activation analysis and inductively coupled plasma - atomic emission spectroscopy). Such methods provide more thorough analyses of coal ash leaching dynamics than the regulatory assessments can demonstrate. Regulatory elements including Ag, As, Ba, Cd, Cr, Hg, Pb, and Se were shown to remain in largely insoluble forms while elements such as B and S leached at higher levels. Experimental results may assist operators of coal-fired boiler industries in selecting coal types and disposal options to curtail the leaching of potentially toxic inorganic contaminants. (author) 12 refs.; 4 figs.; 3 tabs

Beyond synergy: The revolutionary elements in horizontal technology

International Nuclear Information System (INIS)

Hatala, R.

1994-01-01

The petroleum industry is undergoing a fundamental restructuring that is changing the shape and texture of the business. Four principles are guiding this restructuring: proactivity, simplicity/focus, flexibility and synergy. These four elements are contained within horizontal technology applications in Canada and are impacting the upstream operating companies and the service and supply sectors. The evolving socio-economic and political environments of these changes within the petroleum industry are examined. The specific resource base potential, financial, regulatory and market forces that support the application of horizontal technology are addressed and their forecast impacts on industry relationships, production and economic trends over the next 5 years are discussed. The blurred distinctions between operating and service sectors will continue such that service entities will participate directly in oil and gas opportunities in consort with operating companies or countries. 4 refs., 3 figs

A system-level model for the microbial regulatory genome.

Science.gov (United States)

Brooks, Aaron N; Reiss, David J; Allard, Antoine; Wu, Wei-Ju; Salvanha, Diego M; Plaisier, Christopher L; Chandrasekaran, Sriram; Pan, Min; Kaur, Amardeep; Baliga, Nitin S

2014-07-15

Microbes can tailor transcriptional responses to diverse environmental challenges despite having streamlined genomes and a limited number of regulators. Here, we present data-driven models that capture the dynamic interplay of the environment and genome-encoded regulatory programs of two types of prokaryotes: Escherichia coli (a bacterium) and Halobacterium salinarum (an archaeon). The models reveal how the genome-wide distributions of cis-acting gene regulatory elements and the conditional influences of transcription factors at each of those elements encode programs for eliciting a wide array of environment-specific responses. We demonstrate how these programs partition transcriptional regulation of genes within regulons and operons to re-organize gene-gene functional associations in each environment. The models capture fitness-relevant co-regulation by different transcriptional control mechanisms acting across the entire genome, to define a generalized, system-level organizing principle for prokaryotic gene regulatory networks that goes well beyond existing paradigms of gene regulation. An online resource (http://egrin2.systemsbiology.net) has been developed to facilitate multiscale exploration of conditional gene regulation in the two prokaryotes. © 2014 The Authors. Published under the terms of the CC BY 4.0 license.

Asbestos-Containing Materials (ACM) and Demolition

Science.gov (United States)

There are specific federal regulatory requirements that require the identification of asbestos-containing materials (ACM) in many of the residential buildings that are being demolished or renovated by a municipality.

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.

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.

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

PROCESSING OF URANIUM-METAL-CONTAINING FUEL ELEMENTS

Science.gov (United States)

Moore, R.H.

1962-10-01

A process is given for recovering uranium from neutronbombarded uranium- aluminum alloys. The alloy is dissolved in an aluminum halide--alkali metal halide mixture in which the halide is a mixture of chloride and bromide, the aluminum halide is present in about stoichiometric quantity as to uranium and fission products and the alkali metal halide in a predominant quantity; the uranium- and electropositive fission-products-containing salt phase is separated from the electronegative-containing metal phase; more aluminum halide is added to the salt phase to obtain equimolarity as to the alkali metal halide; adding an excess of aluminum metal whereby uranium metal is formed and alloyed with the excess aluminum; and separating the uranium-aluminum alloy from the fission- productscontaining salt phase. (AEC)

The pairwise disconnectivity index as a new metric for the topological analysis of regulatory networks

Directory of Open Access Journals (Sweden)

Wingender Edgar

2008-05-01

Full Text Available Abstract Background Currently, there is a gap between purely theoretical studies of the topology of large bioregulatory networks and the practical traditions and interests of experimentalists. While the theoretical approaches emphasize the global characterization of regulatory systems, the practical approaches focus on the role of distinct molecules and genes in regulation. To bridge the gap between these opposite approaches, one needs to combine 'general' with 'particular' properties and translate abstract topological features of large systems into testable functional characteristics of individual components. Here, we propose a new topological parameter – the pairwise disconnectivity index of a network's element – that is capable of such bridging. Results The pairwise disconnectivity index quantifies how crucial an individual element is for sustaining the communication ability between connected pairs of vertices in a network that is displayed as a directed graph. Such an element might be a vertex (i.e., molecules, genes, an edge (i.e., reactions, interactions, as well as a group of vertices and/or edges. The index can be viewed as a measure of topological redundancy of regulatory paths which connect different parts of a given network and as a measure of sensitivity (robustness of this network to the presence (absence of each individual element. Accordingly, we introduce the notion of a path-degree of a vertex in terms of its corresponding incoming, outgoing and mediated paths, respectively. The pairwise disconnectivity index has been applied to the analysis of several regulatory networks from various organisms. The importance of an individual vertex or edge for the coherence of the network is determined by the particular position of the given element in the whole network. Conclusion Our approach enables to evaluate the effect of removing each element (i.e., vertex, edge, or their combinations from a network. The greatest potential value of

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.

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.

Impression creep properties of a semi-solid processed magnesium-aluminum alloy containing calcium and rare earth elements

International Nuclear Information System (INIS)

Nami, B.; Razavi, H.; Miresmaeili, S.M.; Mirdamadi, Sh.; Shabestari, S.G.

2011-01-01

The creep properties of a thixoformed magnesium-aluminum alloy containing calcium and rare earth elements were studied under shear modulus-normalized stresses ranging from 0.0225 to 0.035 at temperatures of 150-212 o C using the impression creep technique. Analysis of the creep mechanism based on a power-law equation indicated that pipe diffusion-controlled dislocation climb is the dominant mechanism during creep. The alloy has a better creep resistance than high-pressure die-cast magnesium-aluminum alloy.

Regulatory Oversight Program, July 1, 1993--March 3, 1997. Volume 2: Appendices

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-12-31

On July, 1993, a Regulatory Oversight (RO) organization was established within the US DOE, Oak Ridge Operations to provide regulatory oversight of the DOE uranium enrichment facilities leased to the United States Enrichment Corporation (USEC). The purpose of the OR program was to ensure continued plant safety, safeguards and security while the plants were transitioned to regulatory oversight by the Nuclear Regulatory Commission (NRC). Volume 2 contains copies of the documents which established the relationship between NRC, DOE, USEC, and DOL (Dept of Labor) required to facilitate regulatory oversight transition.

Regulatory Oversight Program, July 1, 1993 - March 3, 1997. Volume 2: Appendices

International Nuclear Information System (INIS)

1997-01-01

On July, 1993, a Regulatory Oversight (RO) organization was established within the US DOE, Oak Ridge Operations to provide regulatory oversight of the DOE uranium enrichment facilities leased to the United States Enrichment Corporation (USEC). The purpose of the OR program was to ensure continued plant safety, safeguards and security while the plants were transitioned to regulatory oversight by the Nuclear Regulatory Commission (NRC). Volume 2 contains copies of the documents which established the relationship between NRC, DOE, USEC, and DOL (Dept of Labor) required to facilitate regulatory oversight transition

High integrity container evaluation for solid waste disposal burial containers

International Nuclear Information System (INIS)

Josephson, W.S.

1996-01-01

In order to provide radioactive waste disposal practices with the greatest measure of public protection, Solid Waste Disposal (SWD) adopted the Nuclear Regulatory Commission (NRC) requirement to stabilize high specific activity radioactive waste prior to disposal. Under NRC guidelines, stability may be provided by several mechanisms, one of which is by placing the waste in a high integrity container (HIC). During the implementation process, SWD found that commercially-available HICs could not accommodate the varied nature of weapons complex waste, and in response developed a number of disposal containers to function as HICs. This document summarizes the evaluation of various containers that can be used for the disposal of Category 3 waste in the Low Level Burial Grounds. These containers include the VECTRA reinforced concrete HIC, reinforced concrete culvert, and the reinforced concrete vault. This evaluation provides justification for the use of these containers and identifies the conditions for use of each

The path from biomarker discovery to regulatory qualification

CERN Document Server

Goodsaid, Federico

2013-01-01

The Path from Biomarker Discovery to Regulatory Qualification is a unique guide that focuses on biomarker qualification, its history and current regulatory settings in both the US and abroad. This multi-contributed book provides a detailed look at the next step to developing biomarkers for clinical use and covers overall concepts, challenges, strategies and solutions based on the experiences of regulatory authorities and scientists. Members of the regulatory, pharmaceutical and biomarker development communities will benefit the most from using this book-it is a complete and practical guide to biomarker qualification, providing valuable insight to an ever-evolving and important area of regulatory science. For complimentary access to chapter 13, 'Classic' Biomarkers of Liver Injury, by John R. Senior, Associate Director for Science, Food and Drug Administration, Silver Spring, Maryland, USA, please visit the following site:  http://tinyurl.com/ClassicBiomarkers Contains a collection of experiences of different...

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

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

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

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

Some areas of concern in Indian PHWRs from regulatory perspective

Energy Technology Data Exchange (ETDEWEB)

Gupta, V K [Operating Plants Safety Division, Atomic Energy Regulatory Board, Bhabha Atomic Research Centre (BARC), Bombay (India)

1991-04-01

The basic concern from regulatory perspective in the operation of Indian PHWRs is for radiation exposure to the occupational workers and to the members of public during normal operation as well as abnormal conditions. The radiation exposure to the occupational workers is the result of radiation conditions in the plant and the practices followed for operation and maintenance. Both technical and administrative actions are responsible in controlling the radiation exposures. As far as exposure to the members of public is concerned, integrity of heat transport and moderator systems, performance of the ventilation system and integrity of fuel cladding are important elements during normal operation and some of the anticipated operational occurrences. Containment systems play an important role in controlling the impact in public domain during accident conditions. Elaborate emergency preparedness plans ready in advance perfected and optimised through drills and exercises give an assurance that should a mishap occur requiring emergency action in the public domain, adequate and necessary actions to reduce the radiological consequences will be taken. In this context, four areas of interest are: Radiation Exposure of Occupational Workers, Fuel Performance, Containment Systems and Emergency Preparedness in Public Domain. (author)

Some areas of concern in Indian PHWRs from regulatory perspective

International Nuclear Information System (INIS)

Gupta, V.K.

1991-01-01

The basic concern from regulatory perspective in the operation of Indian PHWRs is for radiation exposure to the occupational workers and to the members of public during normal operation as well as abnormal conditions. The radiation exposure to the occupational workers is the result of radiation conditions in the plant and the practices followed for operation and maintenance. Both technical and administrative actions are responsible in controlling the radiation exposures. As far as exposure to the members of public is concerned, integrity of heat transport and moderator systems, performance of the ventilation system and integrity of fuel cladding are important elements during normal operation and some of the anticipated operational occurrences. Containment systems play an important role in controlling the impact in public domain during accident conditions. Elaborate emergency preparedness plans ready in advance perfected and optimised through drills and exercises give an assurance that should a mishap occur requiring emergency action in the public domain, adequate and necessary actions to reduce the radiological consequences will be taken. In this context, four areas of interest are: Radiation Exposure of Occupational Workers, Fuel Performance, Containment Systems and Emergency Preparedness in Public Domain. (author)

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

Ongoing enhancements in the German nuclear regulatory framework with respect to fire safety

Energy Technology Data Exchange (ETDEWEB)

Elsche, Bjoern [e.on Kernkraft, Hannover (Germany); Roewekamp, Marina [Gesellschaft fuer Anlagen- und Reaktorsicherheit (GRS) gGmbH, Koeln (Germany); Neugebauer, Wilfried [AREVA NP, Erlangen (Germany); Gersinska, Rainer [Bundesamt fuer Strahlenschutz (BfS), Salzgitter (Germany). KTA-Geschaeftsstelle

2015-12-15

In the recent past, the regulatory framework for nuclear power plants (NPP) in Germany has been updated and enhanced comprising on the one hand comprehensive high level regulatory documents such as the 'Safety Requirements for Nuclear Power Plants' and, on the other hand, revised state-of-the-art nuclear safety standards and rules being incorporated in a corresponding legal structure. A major enhancement concerns the nuclear fire and explosion protection standards being already available as so-called green print for final comments which are expected to be officially published end of 2015. The update became necessary after approx. ten years for better addressing some lessons learnt form the operating experience, the consideration of post- Fukushima insights, such as more systematically addressing event combinations with fires and taking into account deviations from non-nuclear standards for escape and rescue routes. Moreover, fire protections remains an important issue for nuclear power plants in Germany during the longer term post-commercial safe shutdown period before decommissioning during which the spent fuel elements remain either in the containment or in the spent fuel pool for further years requiring suitable fire protection means being in place.

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.

A regulatory review for products containing glutathione

Directory of Open Access Journals (Sweden)

Nur Hidayah Abd Rahim

2016-01-01

Full Text Available Glutathione is a potent antioxidant as well as has important role for DNA synthesis and repair, protein synthesis, amino acid transport, and enzyme activation. Besides this, Glutathione products are now mainly selling as whitening agent which are mainly marketing through social media (Facebook and different websites. Information is not available whether glutathione product are following the regulatory guidelines of National Pharmaceutical Control Bureau of Malaysia (NPCB for selling, advertisement and promotion. This review was carried out by extracting information about glutathione from scientific database using PubMed, Cochrane Library and Embase. Analysis of the available information, case example of glutathione products showed that a brand of glutathione (Glutacaps HQ did not show the product's registration number from NPCB, and also did not show the name, address, contact number of the advertiser, and even not found the name of the manufacture. Without providing the above mentioned information, the product is selling and promoting through social media (fb which is not allowed by the NPCB guidelines part 4.14. So far, only two clinical trials were conducted on glutathione supplementation for 4 weeks duration. There was no serious or systematic adverse effects reported in clinical trials. As the two clinic trials resulted contradictory outcomes, further studies needed for conformation of the clinic benefits of glutathione. Otherwise, random use of glutathione may be risk for the health of the people. Besides, the marketer mainly promoting glutathione as the skin whitening beauty product instead of using as health supplement, it may cause additional and serious risk to the users as the manufacturer not providing sufficient information about the product, its registration number, manufacturing company, etc.

A novel nonsteroidal antifibrotic oligo decoy containing the TGF-beta element found in the COL1A1 gene which regulates murine schistosomiasis liver fibrosis.

Science.gov (United States)

Boros, D L; Singh, K P; Gerard, H C; Hudson, A P; White, S L; Cutroneo, K R

2005-08-01

Schistosomiasis mansoni disseminated worm eggs in mice and humans induce granulomatous inflammations and cumulative fibrosis causing morbidity and possibly mortality. In this study, intrahepatic and I.V. injections of a double-stranded oligodeoxynucleotide decoy containing the TGF-beta regulatory element found in the distal promoter of the COL1A1 gene into worm-infected mice suppressed TGF-beta1, COL1A1, tissue inhibitor of metalloproteinase-1, and decreased COL3A1 mRNAs to a lesser extent. Sequence comparisons within the mouse genome found homologous sequences within the COL3A1, TGF-beta1, and TIMP-1 5' flanking regions. Cold competition gel mobility shift assays using these homologous sequences with 5' and 3' flanking regions found in the natural COL1A1 gene showed competition. Competitive gel mobility assays in a separate experiment showed no competition using a 5-base mutated or scrambled sequence. Explanted liver granulomas from saline-injected mice incorporated 10.45 +/- 1.7% (3)H-proline into newly synthesized collagen, whereas decoy-treated mice showed no collagen synthesis. Compared with the saline control schistosomiasis mice phosphorothioate double-stranded oligodeoxynucleotide treatment decreased total liver collagen content (i.e. hydroxy-4-proline) by 34%. This novel molecular approach has the potential to be employed as a novel antifibrotic treatment modality. (c) 2005 Wiley-Liss, Inc.

Dry containment of radioactive materials

International Nuclear Information System (INIS)

Williams, C.E.

1980-01-01

A cask for the dry containment of radioactive fuel elements is described. The cask has a cover which contains valved drain and purge passageways. These passageways are sealed by after purge cover seals which are clamped over them and to the outer surface of the cover. The cover seals are tested by providing them with a pair of concentric ring seal elements squeezed between the cover seal and the outer surface of the cover and by forcing a gas under pressure into the annular region between the seal element

Screening of MITF and SOX10 regulatory regions in Waardenburg syndrome type 2.

Directory of Open Access Journals (Sweden)

Viviane Baral

Full Text Available Waardenburg syndrome (WS is a rare auditory-pigmentary disorder that exhibits varying combinations of sensorineural hearing loss and pigmentation defects. Four subtypes are clinically defined based on the presence or absence of additional symptoms. WS type 2 (WS2 can result from mutations within the MITF or SOX10 genes; however, 70% of WS2 cases remain unexplained at the molecular level, suggesting that other genes might be involved and/or that mutations within the known genes escaped previous screenings. The recent identification of a deletion encompassing three of the SOX10 regulatory elements in a patient presenting with another WS subtype, WS4, defined by its association with Hirschsprung disease, led us to search for deletions and point mutations within the MITF and SOX10 regulatory elements in 28 yet unexplained WS2 cases. Two nucleotide variations were identified: one in close proximity to the MITF distal enhancer (MDE and one within the U1 SOX10 enhancer. Functional analyses argued against a pathogenic effect of these variations, suggesting that mutations within regulatory elements of WS genes are not a major cause of this neurocristopathy.

Screening of MITF and SOX10 Regulatory Regions in Waardenburg Syndrome Type 2

Science.gov (United States)

Baral, Viviane; Chaoui, Asma; Watanabe, Yuli; Goossens, Michel; Attie-Bitach, Tania; Marlin, Sandrine; Pingault, Veronique; Bondurand, Nadege

2012-01-01

Waardenburg syndrome (WS) is a rare auditory-pigmentary disorder that exhibits varying combinations of sensorineural hearing loss and pigmentation defects. Four subtypes are clinically defined based on the presence or absence of additional symptoms. WS type 2 (WS2) can result from mutations within the MITF or SOX10 genes; however, 70% of WS2 cases remain unexplained at the molecular level, suggesting that other genes might be involved and/or that mutations within the known genes escaped previous screenings. The recent identification of a deletion encompassing three of the SOX10 regulatory elements in a patient presenting with another WS subtype, WS4, defined by its association with Hirschsprung disease, led us to search for deletions and point mutations within the MITF and SOX10 regulatory elements in 28 yet unexplained WS2 cases. Two nucleotide variations were identified: one in close proximity to the MITF distal enhancer (MDE) and one within the U1 SOX10 enhancer. Functional analyses argued against a pathogenic effect of these variations, suggesting that mutations within regulatory elements of WS genes are not a major cause of this neurocristopathy. PMID:22848661

Screening of MITF and SOX10 regulatory regions in Waardenburg syndrome type 2.

Science.gov (United States)

Baral, Viviane; Chaoui, Asma; Watanabe, Yuli; Goossens, Michel; Attie-Bitach, Tania; Marlin, Sandrine; Pingault, Veronique; Bondurand, Nadege

2012-01-01

Waardenburg syndrome (WS) is a rare auditory-pigmentary disorder that exhibits varying combinations of sensorineural hearing loss and pigmentation defects. Four subtypes are clinically defined based on the presence or absence of additional symptoms. WS type 2 (WS2) can result from mutations within the MITF or SOX10 genes; however, 70% of WS2 cases remain unexplained at the molecular level, suggesting that other genes might be involved and/or that mutations within the known genes escaped previous screenings. The recent identification of a deletion encompassing three of the SOX10 regulatory elements in a patient presenting with another WS subtype, WS4, defined by its association with Hirschsprung disease, led us to search for deletions and point mutations within the MITF and SOX10 regulatory elements in 28 yet unexplained WS2 cases. Two nucleotide variations were identified: one in close proximity to the MITF distal enhancer (MDE) and one within the U1 SOX10 enhancer. Functional analyses argued against a pathogenic effect of these variations, suggesting that mutations within regulatory elements of WS genes are not a major cause of this neurocristopathy.

[Physico-chemical characteristics of endogenous regulatory oligopeptides].

Science.gov (United States)

Zamiatnin, A A

1990-01-01

Analysis of amino acid residue content in endogenous regulatory oligopeptides possessing a preset spectrum of functional activity has been made. It has been shown that compared to proteins the oligopeptides contain a greater number of positively charged and cyclic radicals. All 525 oligopeptides with the preset spectrum of functional activity contained in EROP-Moscow data bank were found to have the same physicochemical characteristics.

Process for introducing radioactive articles into a transport and/or storage container and transporting and/or storing the container and later extraction of the article from the container, and container for transporting and/or storing radioactive articles

International Nuclear Information System (INIS)

Vox, A.J.

1979-01-01

The articles, for example fuel elements, are introduced into the container and the remaining space inside the container is filled with lead, a salt or a mixture of salts of eutectic composition, which freezes at ambient temperature. This makes dry transport possible. To extract the fuel elements, it is sufficient to heat the container, which softens the protective and shielding material. The salt or mixture of salts is suitable for thermal conduction. (DG) [de

Small regulatory RNAs control the multi-cellular adhesive lifestyle of Escherichia coli

DEFF Research Database (Denmark)

Jørgensen, Mikkel Girke; Nielsen, Jesper Sejrup; Boysen, Anders

2012-01-01

Small regulatory RNA molecules have recently been recognized as important regulatory elements of developmental processes in both eukaryotes and bacteria. We here describe a striking example in Escherichia coli that can switch between a single-cell motile lifestyle and a multi-cellular, sessile....... Our demonstration that basal expression of each of the three RNA species is sufficient to downregulate CsgD synthesis and prevent curli formation indicates that all play a prominent role in the curli regulatory network. Our findings provide the first clue as to how the Rcs signalling pathway...... negatively regulates curli synthesis and increase the number of small regulatory RNAs that act directly on the csgD mRNA to five....

The IAEA Regional Training Course on Regulatory Control of Radiation Sources

International Nuclear Information System (INIS)

2000-01-01

Materials of the IAEA Regional Training Course contains 8 presented lectures. Authors deals with regulatory control of radiation sources. The next materials of the IAEA were presented: Organization and implementation of a national regulatory infrastructure governing protection against ionizing radiation and the safety of radiation sources. (IAEA-TECDOC-1067); Safety assessment plants for authorization and inspection of radiation sources (IAEA-TECDOC-1113); Regulatory authority information system RAIS, Version 2.0, Instruction manual

U.S. Nuclear Regulatory Commission natural analogue research program

International Nuclear Information System (INIS)

Kovach, L.A.; Ott, W.R.

1995-01-01

This article describes the natural analogue research program of the U.S. Nuclear Regulatory Commission (US NRC). It contains information on the regulatory context and organizational structure of the high-level radioactive waste research program plan. It also includes information on the conditions and processes constraining selection of natural analogues, describes initiatives of the US NRC, and describes the role of analogues in the licensing process

Infrastructure of the Regulatory Authority and Performance Indexes

International Nuclear Information System (INIS)

Velasquez, Silvia

2001-01-01

This presentation overviews the following issues: elements of a control regulatory program, inspections program, procedures, indexes of users performance, priorities on: registration, criteria for practices of low risk, dose levels in medical exposures, dose constraints and training of personnel. These aspects are considered in the guides prepared within ARCAL XX framework

Regulatory analysis for USI A-1, Water Hammer

International Nuclear Information System (INIS)

Serkiz, A.W.

1984-03-01

This is the staff's regulatory analysis dealing with the resolution of the Unresolved Safety Issue A-1, Water Hammer. This report contains the value-impact analysis for this issue, public comments received, and staff response, or action taken, in response to those comments. The staff's technical findings regarding water hammer in nuclear power plants are contained in NUREG-0927

Proceedings of the Canadian Nuclear Society international conference on containment design

International Nuclear Information System (INIS)

Black, R.K.

1984-01-01

The subject of containment was discussed under the major topic headings of: USA views on containment design operation and regulation, containment structure analysis, containment envelope and energy suppression systems, European views on containment design operation and regulation, containment atmosphere control, Canadian views on containment design operation and regulation, containment analysis, and regulatory requirements, testing, and periodic inspection

MIRA: An R package for DNA methylation-based inference of regulatory activity.

Science.gov (United States)

Lawson, John T; Tomazou, Eleni M; Bock, Christoph; Sheffield, Nathan C

2018-03-01

DNA methylation contains information about the regulatory state of the cell. MIRA aggregates genome-scale DNA methylation data into a DNA methylation profile for independent region sets with shared biological annotation. Using this profile, MIRA infers and scores the collective regulatory activity for each region set. MIRA facilitates regulatory analysis in situations where classical regulatory assays would be difficult and allows public sources of open chromatin and protein binding regions to be leveraged for novel insight into the regulatory state of DNA methylation datasets. R package available on Bioconductor: http://bioconductor.org/packages/release/bioc/html/MIRA.html. nsheffield@virginia.edu.

Regulatory analyses for severe accident issues: an example

International Nuclear Information System (INIS)

Burke, R.P.; Strip, D.R.; Aldrich, D.C.

1984-09-01

This report presents the results of an effort to develop a regulatory analysis methodology and presentation format to provide information for regulatory decision-making related to severe accident issues. Insights and conclusions gained from an example analysis are presented. The example analysis draws upon information generated in several previous and current NRC research programs (the Severe Accident Risk Reduction Program (SARRP), Accident Sequence Evaluation Program (ASEP), Value-Impact Handbook, Economic Risk Analyses, and studies of Vented Containment Systems and Alternative Decay Heat Removal Systems) to perform preliminary value-impact analyses on the installation of either a vented containment system or an alternative decay heat removal system at the Peach Bottom No. 2 plant. The results presented in this report are first-cut estimates, and are presented only for illustrative purposes in the context of this document. This study should serve to focus discussion on issues relating to the type of information, the appropriate level of detail, and the presentation format which would make a regulatory analysis most useful in the decisionmaking process

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.

New families of human regulatory RNA structures identified by comparative analysis of vertebrate genomes.

Science.gov (United States)

Parker, Brian J; Moltke, Ida; Roth, Adam; Washietl, Stefan; Wen, Jiayu; Kellis, Manolis; Breaker, Ronald; Pedersen, Jakob Skou

2011-11-01

Regulatory RNA structures are often members of families with multiple paralogous instances across the genome. Family members share functional and structural properties, which allow them to be studied as a whole, facilitating both bioinformatic and experimental characterization. We have developed a comparative method, EvoFam, for genome-wide identification of families of regulatory RNA structures, based on primary sequence and secondary structure similarity. We apply EvoFam to a 41-way genomic vertebrate alignment. Genome-wide, we identify 220 human, high-confidence families outside protein-coding regions comprising 725 individual structures, including 48 families with known structural RNA elements. Known families identified include both noncoding RNAs, e.g., miRNAs and the recently identified MALAT1/MEN β lincRNA family; and cis-regulatory structures, e.g., iron-responsive elements. We also identify tens of new families supported by strong evolutionary evidence and other statistical evidence, such as GO term enrichments. For some of these, detailed analysis has led to the formulation of specific functional hypotheses. Examples include two hypothesized auto-regulatory feedback mechanisms: one involving six long hairpins in the 3'-UTR of MAT2A, a key metabolic gene that produces the primary human methyl donor S-adenosylmethionine; the other involving a tRNA-like structure in the intron of the tRNA maturation gene POP1. We experimentally validate the predicted MAT2A structures. Finally, we identify potential new regulatory networks, including large families of short hairpins enriched in immunity-related genes, e.g., TNF, FOS, and CTLA4, which include known transcript destabilizing elements. Our findings exemplify the diversity of post-transcriptional regulation and provide a resource for further characterization of new regulatory mechanisms and families of noncoding RNAs.

Hydrogen mitigation systems - a Canadian regulatory perspective

International Nuclear Information System (INIS)

Khosla, J.K.; Rizk, M.

1997-01-01

This is a discussion paper to examine the regulatory requirements that may be necessary for the design, operation and maintenance of the hydrogen mitigation systems. These systems (if deemed necessary to maintain the containment function), may be considered to be a part of the containment systems. Therefore, these requirements are derived mostly from the AECB Regulatory Document R-7, which specifies the requirements for containment systems for CANDU nuclear power plants. Some additional requirements, which are specific to these systems have also been included. These requirements relate to a systematic examination of the hazards of hydrogen, the design basis for the mitigation systems, their functional and design requirements, analytical support to justify their selection, and operating and testing requirements. The requirements for severe accident have not yet been developed. It is, however, anticipated that the design of the hydrogen mitigation system would be such that future requirement can be accommodated. These requirements are intended for application to the new reactors in Canada. For the existing reactors, their application will be subjected to practicability. (author)

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

Molecular analysis of UAS(E), a cis element containing stress response elements responsible for ethanol induction of the KlADH4 gene of Kluyveromyces lactis.

Science.gov (United States)

Mazzoni, C; Santori, F; Saliola, M; Falcone, C

2000-01-01

KlADH4 is a gene of Kluyveromyces lactis encoding a mitochondrial alcohol dehydrogenase activity, which is specifically induced by ethanol and insensitive to glucose repression. In this work, we report the molecular analysis of UAS(E), an element of the KlADH4 promoter which is essential for the induction of KlADH4 in the presence of ethanol. UAS(E) contains five stress response elements (STREs), which have been found in many genes of Saccharomyces cerevisiae involved in the response of cells to conditions of stress. Whereas KlADH4 is not responsive to stress conditions, the STREs present in UAS(E) seem to play a key role in the induction of the gene by ethanol, a situation that has not been observed in the related yeast S. cerevisiae. Gel retardation experiments showed that STREs in the KlADH4 promoter can bind factor(s) under non-inducing conditions. Moreover, we observed that the RAP1 binding site present in UAS(E) binds KlRap1p.

United States Nuclear Regulatory Commission staff practice and procedure digest

International Nuclear Information System (INIS)

1990-03-01

This document contains procedures for review by US Nuclear Regulatory Commission for reviewing and deciding on matters pertaining to nuclear power plant licensing. Also, contained within the document are decisions the Commission has made between July 1972 to September 1989. (F.S.D.)

Prostate cancer risk locus at 8q24 as a regulatory hub by physical interactions with multiple genomic loci across the genome.

Science.gov (United States)

Du, Meijun; Yuan, Tiezheng; Schilter, Kala F; Dittmar, Rachel L; Mackinnon, Alexander; Huang, Xiaoyi; Tschannen, Michael; Worthey, Elizabeth; Jacob, Howard; Xia, Shu; Gao, Jianzhong; Tillmans, Lori; Lu, Yan; Liu, Pengyuan; Thibodeau, Stephen N; Wang, Liang

2015-01-01

Chromosome 8q24 locus contains regulatory variants that modulate genetic risk to various cancers including prostate cancer (PC). However, the biological mechanism underlying this regulation is not well understood. Here, we developed a chromosome conformation capture (3C)-based multi-target sequencing technology and systematically examined three PC risk regions at the 8q24 locus and their potential regulatory targets across human genome in six cell lines. We observed frequent physical contacts of this risk locus with multiple genomic regions, in particular, inter-chromosomal interaction with CD96 at 3q13 and intra-chromosomal interaction with MYC at 8q24. We identified at least five interaction hot spots within the predicted functional regulatory elements at the 8q24 risk locus. We also found intra-chromosomal interaction genes PVT1, FAM84B and GSDMC and inter-chromosomal interaction gene CXorf36 in most of the six cell lines. Other gene regions appeared to be cell line-specific, such as RRP12 in LNCaP, USP14 in DU-145 and SMIN3 in lymphoblastoid cell line. We further found that the 8q24 functional domains more likely interacted with genomic regions containing genes enriched in critical pathways such as Wnt signaling and promoter motifs such as E2F1 and TCF3. This result suggests that the risk locus may function as a regulatory hub by physical interactions with multiple genes important for prostate carcinogenesis. Further understanding genetic effect and biological mechanism of these chromatin interactions will shed light on the newly discovered regulatory role of the risk locus in PC etiology and progression. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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.

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

Regulatory and technical reports compilation for 1980

International Nuclear Information System (INIS)

Oliu, W.E.; McKenzi, L.

1981-04-01

This compilation lists formal regulatory and technical reports and conference proceedings issued in 1980 by the US Nuclear Regulatory Commission. The compilation is divided into four major sections. The first major section consists of a sequential listing of all NRC reports in report-number order. The second major section of this compilation consists of a key-word index to report titles. The third major section contains an alphabetically arranged listing of contractor report numbers cross-referenced to their corresponding NRC report numbers. Finally, the fourth section is an errata supplement

Retroviral vectors encoding ADA regulatory locus control region provide enhanced T-cell-specific transgene expression.

Science.gov (United States)

Trinh, Alice T; Ball, Bret G; Weber, Erin; Gallaher, Timothy K; Gluzman-Poltorak, Zoya; Anderson, French; Basile, Lena A

2009-12-30

Murine retroviral vectors have been used in several hundred gene therapy clinical trials, but have fallen out of favor for a number of reasons. One issue is that gene expression from viral or internal promoters is highly variable and essentially unregulated. Moreover, with retroviral vectors, gene expression is usually silenced over time. Mammalian genes, in contrast, are characterized by highly regulated, precise levels of expression in both a temporal and a cell-specific manner. To ascertain if recapitulation of endogenous adenosine deaminase (ADA) expression can be achieved in a vector construct we created a new series of Moloney murine leukemia virus (MuLV) based retroviral vector that carry human regulatory elements including combinations of the ADA promoter, the ADA locus control region (LCR), ADA introns and human polyadenylation sequences in a self-inactivating vector backbone. A MuLV-based retroviral vector with a self-inactivating (SIN) backbone, the phosphoglycerate kinase promoter (PGK) and the enhanced green fluorescent protein (eGFP), as a reporter gene, was generated. Subsequent vectors were constructed from this basic vector by deletion or addition of certain elements. The added elements that were assessed are the human ADA promoter, human ADA locus control region (LCR), introns 7, 8, and 11 from the human ADA gene, and human growth hormone polyadenylation signal. Retroviral vector particles were produced by transient three-plasmid transfection of 293T cells. Retroviral vectors encoding eGFP were titered by transducing 293A cells, and then the proportion of GFP-positive cells was determined using fluorescence-activated cell sorting (FACS). Non T-cell and T-cell lines were transduced at a multiplicity of infection (MOI) of 0.1 and the yield of eGFP transgene expression was evaluated by FACS analysis using mean fluorescent intensity (MFI) detection. Vectors that contained the ADA LCR were preferentially expressed in T-cell lines. Further improvements

Retroviral vectors encoding ADA regulatory locus control region provide enhanced T-cell-specific transgene expression

Science.gov (United States)

2009-01-01

Background Murine retroviral vectors have been used in several hundred gene therapy clinical trials, but have fallen out of favor for a number of reasons. One issue is that gene expression from viral or internal promoters is highly variable and essentially unregulated. Moreover, with retroviral vectors, gene expression is usually silenced over time. Mammalian genes, in contrast, are characterized by highly regulated, precise levels of expression in both a temporal and a cell-specific manner. To ascertain if recapitulation of endogenous adenosine deaminase (ADA) expression can be achieved in a vector construct we created a new series of Moloney murine leukemia virus (MuLV) based retroviral vector that carry human regulatory elements including combinations of the ADA promoter, the ADA locus control region (LCR), ADA introns and human polyadenylation sequences in a self-inactivating vector backbone. Methods A MuLV-based retroviral vector with a self-inactivating (SIN) backbone, the phosphoglycerate kinase promoter (PGK) and the enhanced green fluorescent protein (eGFP), as a reporter gene, was generated. Subsequent vectors were constructed from this basic vector by deletion or addition of certain elements. The added elements that were assessed are the human ADA promoter, human ADA locus control region (LCR), introns 7, 8, and 11 from the human ADA gene, and human growth hormone polyadenylation signal. Retroviral vector particles were produced by transient three-plasmid transfection of 293T cells. Retroviral vectors encoding eGFP were titered by transducing 293A cells, and then the proportion of GFP-positive cells was determined using fluorescence-activated cell sorting (FACS). Non T-cell and T-cell lines were transduced at a multiplicity of infection (MOI) of 0.1 and the yield of eGFP transgene expression was evaluated by FACS analysis using mean fluorescent intensity (MFI) detection. Results Vectors that contained the ADA LCR were preferentially expressed in T

Small RNA-Controlled Gene Regulatory Networks in Pseudomonas putida

DEFF Research Database (Denmark)

Bojanovic, Klara

evolved numerous mechanisms to controlgene expression in response to specific environmental signals. In addition to two-component systems, small regulatory RNAs (sRNAs) have emerged as major regulators of gene expression. The majority of sRNAs bind to mRNA and regulate their expression. They often have...... multiple targets and are incorporated into large regulatory networks and the RNA chaper one Hfq in many cases facilitates interactions between sRNAs and their targets. Some sRNAs also act by binding to protein targets and sequestering their function. In this PhD thesis we investigated the transcriptional....... Detailed insights into the mechanisms through which P. putida responds to different stress conditions and increased understanding of bacterial adaptation in natural and industrial settings were gained. Additionally, we identified genome-wide transcription start sites, andmany regulatory RNA elements...

Employee Development Capabilities of the Regulatory Authority in the Nuclear Field in Romania

International Nuclear Information System (INIS)

Ghinea, P.

2016-01-01

Full text: The paper provides information about CNCAN (general presentation of CNCAN responsibilities as a regulatory body) and about the general human resources management within our institution regarding the following: legal framework regarding resources; knowledge management; staff employment financial resources continuous focus on improvement of staff performances through dedicated training programmes. The process to develop and maintain the necessary competence and skills of staff of the regulatory body, as an element of knowledge management. Training for CNCAN staff is provided either in-house or through technical cooperation programmes with the IAEA. CNCAN has made arrangements for specific staff training using training courses and programmes provided by international organizations. The specific training is provided predominantly with the economic support from outside of the country. CNCAN has a process to develop and maintain the necessary competence and skills of staff of the regulatory body, as an element of knowledge management. To maintain an appropriate competence level, an annual plan for staff training is in place and each staff member has an individual training plan. Project supports CNCAN in the development of knowledge management and capacity building frameworks to secure long-term availability of regulatory competency. (author

TRUPACT-II container maintenance program plan

International Nuclear Information System (INIS)

1990-11-01

This document details the maintenance/repair and replacement of components, as well as the documentation required and the procedures to be followed to maintain the integrity of the TRUPACT-II container, in accordance with requirements of the TRUPACT-II Container Operations and Maintenance Manual, OM-134, the TRUPACT-II Container Safety Analysis Report (SARP), and the TRUPACT-II Container Certificate of Compliance (Number 9218). The routine shipping and receiving inspections required by the Department of Transportation (DOT), Department of Energy (DOE), Nuclear Regulatory Commission (NRC) and other regulations are not addressed in this document. This document applies to all DOE shipping and receiving sites that use the TRUPACT-II containers

Bromodomain protein 4 discriminates tissue-specific super-enhancers containing disease-specific susceptibility loci in prostate and breast cancer

DEFF Research Database (Denmark)

Zuber, Verena; Bettella, Francesco; Witoelar, Aree

2017-01-01

progression. Although previous approaches have been tried to explain risk associated with SNPs in regulatory DNA elements, so far epigenetic readers such as bromodomain containing protein 4 (BRD4) and super-enhancers have not been used to annotate SNPs. In prostate cancer (PC), androgen receptor (AR) binding......Background: Epigenetic information can be used to identify clinically relevant genomic variants single nucleotide polymorphisms (SNPs) of functional importance in cancer development. Super-enhancers are cell-specific DNA elements, acting to determine tissue or cell identity and driving tumor...... the differential enrichment of SNPs mapping to specific categories of enhancers. We find that BRD4 is the key discriminant of tissue-specific enhancers, showing that it is more powerful than AR binding information to capture PC specific risk loci, and can be used with similar effect in breast cancer (BC...

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.

The development of ISO freight containers as IP-2 packagings

International Nuclear Information System (INIS)

Janicki, M.C.; Vaughan, R.A.

1993-01-01

Design specifications were developed for ISO freight containers to meet the requirements of the transport regulations in the 1985 Edition of IAEA SS6, and to maximize the technical and commercial benefits offered to consignors by this type of container for the transport and handling of bulk LSA/SCO materials. A range of IP-2 ISO freight containers have been designed and built to these specifications and are in use in the UK. This paper discusses the regulatory considerations which had to be reviewed and interpreted in developing freight containers as Industrial Package Type 2 (IP-2) packagings and the development of performance standards to meet the regulatory requirements. Outline details of the packages developed are indicated together with examples of handling equipment developed to facilitate loading and unloading. (J.P.N.)

TRUPACT-II Container Maintenance Program Plan

International Nuclear Information System (INIS)

1991-05-01

This document details the maintenance, repair, and replacement of components, as well as the documentation required and the procedures to be followed to maintain the integrity of the TRUPACT-II container in accordance with OM-134, TRUPACT-II Container Operations and Maintenance Manual; and the TRUPACT-II Container Certificate of Compliance (Number 9218). The routine shipping and receiving inspections required by the Department of Transportation (DOT), Department of Energy (DOE), Nuclear Regulatory Commission (NRC) and other regulations are not addressed in this document. This document applies to all DOE shipping and receiving sites that use the TRUPACT-II containers

Aging of steel containments and liners in nuclear power plants

International Nuclear Information System (INIS)

Naus, D.J.; Oland, C.B.; Ellingwood, B.; Norris, W.E.

1998-02-01

Aging of the containment pressure boundary in light water reactor plants is being addressed to understand the significant factors relating occurrence of corrosion efficacy of inspection and structural capacity reduction of steel containments and liners of concrete containments. and to make recommendations on use of risk models in regulatory decisions. Current regulatory in-service inspection requirements are reviewed and a summary of containment related degradation experience is presented. Current and emerging nondestructive examination techniques and a degradation assessment methodology for characterizing and quantifying the amount of damage present are described. Quantitative tools for condition assessment of aging structures using time dependent structural reliability analysis methods are summarized. Such methods provide a framework for addressing the uncertainties attendant to aging in the decision process. Results of this research provide a means for establishing current and estimating future structural capacity margins of containments, and to address the significance of incidences of reported containment degradation

The application of micro-column solid phase extraction techniques for the determination of rare earth elements in actinide containing matrices

International Nuclear Information System (INIS)

Carney, K.P.; Cummings, D.G.

1995-01-01

The design and characterization of an argon segmented-solid phase extraction system is described. A 200 ul volume micro-column has been constructed for the preconcentration of rare earth elements (REEs) from salt matrices containing uranium. An inductively coupled plasma atomic emission spectrometer has been utilized for simultaneous detection of Sr, Y and the REEs (namely Ce, Eu, La, Nd, Pr, Sm) at levels ranging from 5- to 2000 ppm in LiCl/KCl samples containing U. Preconcentration factors of 100 fold have been demonstrated. The precision, linear dynamic range and column performance of the system will be presented. (author). 5 refs., 5 figs., 3 tabs

Container corporation: The financial, management, and operating implications of a universal beverage container recovery system: Executive summary

Energy Technology Data Exchange (ETDEWEB)

1991-01-01

This report contains an overview of the system. It discusses containers and container materials, elements of the system, and the container recovery cost structure. It includes a financial evaluation and addresses issues of implementation.

77 FR 306 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing of...

Science.gov (United States)

2012-01-04

...). \\2\\ 17 CFR 240.19b-4. Self-Regulatory Organization's Statement of the Terms of Substance of the... contained in Chapter XXIVB. II. Self-Regulatory Organization's Statement of the Purpose of, and Statutory Basis for, the Proposed Rule Change In its filing with the Commission, the self-regulatory organization...

Romanian regulatory framework for uranium mining and milling (present and future)

International Nuclear Information System (INIS)

Rodna, A.L.; Dumitrescu, N.

2002-01-01

In Romania, all operations in the nuclear field, including uranium mining and milling, are regulated by Law no. 111/1996 (republished in 1998), regarding the safe conduct of nuclear activities. These activities can be performed only on the basis of an authorization released by the national regulatory authority, i.e. the National Commission for Nuclear Activities Control. The specific requirements which must be carried out by the owner of an operating licence for a uranium mining and milling operation are stipulated by the Republican Nuclear Safety Norms for Geological Research, Mining and Milling of Nuclear Raw Materials. These regulatory requirements have been in force since 1975. The regulatory norms include provisions that the effective dose limit for workers should not exceed 50 mSv/year and also that liquid effluents released into surface waters must have a content of natural radioactive elements that meets the standards for drinking water. The norms do not contain provisions concerning the conditions under which the mining sites and the uranium processing facilities can be shut down and decommissioned. The norms also do not contain requirements regarding either the rehabilitation of environments affected by abandoned mining and milling activities, nor criteria for the release of the rehabilitated sites for alternative uses. To implement the provisions of Council Directive 96/29 EURATOM in Romania, new Fundamental Radiological Protection Norms have been approved and will soon be published in the 'Monitorul Official' (Official Gazette of Romania). One of the main provisions of these norms is the reduction of the effective dose limit for the workers to 20 mSv/year. Changes in the Republican Nuclear Safety Norms for Geological Research, Mining and Milling of Nuclear Raw Materials, are also planned; these changes will be consistent with the Fundamental Radiological Protection Norms. To cover existing gaps, the new norms for uranium mining and milling will include

Structure and drafting of safeguards regulatory documents

International Nuclear Information System (INIS)

Cole, R.J.; Bennett, C.A.; Edelhertz, H.; Wood, M.T.; Brown, R.J.; Roberts, F.P.

1977-09-01

This study develops hypothesis about the relation between the structure and drafting of safeguards regulatory documents and the ability of document users to understand and implement them in a way that reflects the intent and requirements of the NRC. Four decisions are needed to improve communication: (1) Should improvement of safeguards regulatory documents as communication instruments be an explicit NRC program. (2) What specific methods of communication should be the focus of improvement efforts. (3) What actions to improve communications are feasible and desirable. (4) How should the NRC divide its available effort and resources among desirable actions in order to provide the most effective communication through regulatory documents. This volume contains: introduction, conceptual bases, legal requirements, targets, choice of documents, preparation of documents, readability, and further study of recommended changes in structure and drafting

Regulatory reform in Mexico's natural gas sector

International Nuclear Information System (INIS)

1996-01-01

In recent years Mexico has implemented remarkable structural changes in its economy. However, until recently its large and key energy sector was largely unreformed. This is now changing. In 1995 the Mexican Government introduced legislative changes permitting private sector involvement in natural gas storage, transportation and distribution. Subsequent directives set up a detailed regulatory framework. These developments offer considerable promise, not only for natural gas sector development but also for growth in the closely linked electricity sector. This study analyses the changes which have taken place and the rationale for the regulatory framework which has been established. The study also contains recommendations to assist the Government of Mexico in effectively implementing its natural gas sector reforms and in maximizing the benefits to be realised through the new regulatory framework. (author)

Computer simulations of a generic truck cask in a regulatory fire using the Container Analysis Fire Environment (CAFE) code

International Nuclear Information System (INIS)

Ju, H.; Greiner, M.; Suo-Anttila, A.

2002-01-01

The Container Analysis Fire Environment (CAFE) computer code is designed to predict accurately convection and radiation heat transfer to a thermally massive object engulfed in a large pool fire. It is well suited for design and risk analyses of spent nuclear fuel transport systems. CAFE employs computational fluid dynamics and several fire and radiation models. These models must be benchmarked using experimental results. In this paper, a set of wind velocity conditions are determined which allow CAFE accurately to reproduce recent heat transfer measurements for a thick walled calorimeter in a ST-1 regulatory pool fire. CAFE is then used to predict the response of an intack (thin walled) generic legal weight truck cask. The maximum temperatures reached by internal components are within safe limits. A simple 800 deg. C, grey-radiation fire model gives maximum component temperatures that are somewhat below those predicted by CAFE. (author)

Multiple independent regulatory pathways control UBI4 expression after heat shock in Saccharomyces cerevisiae.

Science.gov (United States)

Simon, J R; Treger, J M; McEntee, K

1999-02-01

Transcription of the polyubiquitin gene UBI4 of Saccharomyces cerevisiae is strongly induced by a variety of environmental stresses, such as heat shock, nutrient depletion and exposure to DNA-damaging agents. This transcriptional response of UBI4 is likely to be the primary mechanism for increasing the pool of ubiquitin for degradation of stress-damaged proteins. Deletion and promoter fusion studies of the 5' regulatory sequences indicated that two different elements, heat shock elements (HSEs) and stress response element (STREs), contributed independently to heat shock regulation of the UBI4 gene. In the absence of HSEs, STRE sequences localized to the intervals -264 to -238 and -215 to -183 were needed for stress control of transcription after heat shock. Site-directed mutagenesis of the STRE (AG4) at -252 to -248 abolished heat shock induction of UBI4 transcription. Northern analysis demonstrated that cells containing either a temperature-sensitive HSF or non-functional Msn2p/Msn4p transcription factors induced high levels of UBI4 transcripts after heat shock. In cells deficient in both heat stress pathways, heat-induced UBI4 transcript levels were considerably lower but not abolished, suggesting a role for another factor(s) in stress control of its expression.

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

76 FR 82017 - Self-Regulatory Organizations; Chicago Board Options Exchange, Incorporated; Notice of Filing of...

Science.gov (United States)

2011-12-29

... 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of Substance of the Proposed Rule... System platform are contained in Chapter XXIVB. II. Self-Regulatory Organization's Statement of the... in sections A, B, and C below, of the most significant parts of such statements. A. Self-Regulatory...

Regulatory Oversight Program, July 1, 1993--March 3, 1997. Volume 3

Energy Technology Data Exchange (ETDEWEB)

NONE

1997-12-31

On July, 1993, a Regulatory Oversight (RO) organization was established within the US DOE, Oak Ridge Operations (ORO) to provide regulatory oversight of the DOE uranium enrichment facilities leased to the United States Enrichment Corporation (USEC). The purpose of the OR program was to ensure continued plant safety, safeguards and security while the plants were transitioned to regulatory oversight by the Nuclear Regulatory Commission (NRC). Volume 3 contains copies of two reports that document the DOE/ORO regulatory oversight inspection and enforcement history for each gaseous diffusion plant site. Each report provides a formal mechanism by which DOE/ORO could communicate the inspection and enforcement history to NRC. The reports encompass the inspection activities that occurred during July 1, 1993 through March 2, 1997.

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

African Journals Online (AJOL)

Arabidopsis plants were transformed with a chimeric construct containing expression cassettes for GFP election marker and CaMV 35S promoter-driven At5g35220 cDNA, via Agro bacterium-mediated method. Two transformants produced pigmentation deficient phenotype. Analysis revealed the decrease of chlorophyll in ...

Finite element analysis of three dimensional crack growth by the use of a boundary element sub model

DEFF Research Database (Denmark)

Lucht, Tore

2009-01-01

A new automated method to model non-planar three dimensional crack growth is proposed which combines the advantages of both the boundary element method and the finite element method. The proposed method links the two methods by a submodelling strategy in which the solution of a global finite...... element model containing an approximation of the crack is interpolated to a much smaller boundary element model containing a fine discretization of the real crack. The method is validated through several numerical comparisons and by comparison to crack growth measured in a test specimen for an engineering...

Containment Sodium Chemistry Models in MELCOR.

Energy Technology Data Exchange (ETDEWEB)

Louie, David [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Humphries, Larry L. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Denman, Matthew R [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

2017-04-01

To meet regulatory needs for sodium fast reactors’ future development, including licensing requirements, Sandia National Laboratories is modernizing MELCOR, a severe accident analysis computer code developed for the U.S. Nuclear Regulatory Commission (NRC). Specifically, Sandia is modernizing MELCOR to include the capability to model sodium reactors. However, Sandia’s modernization effort primarily focuses on the containment response aspects of the sodium reactor accidents. Sandia began modernizing MELCOR in 2013 to allow a sodium coolant, rather than water, for conventional light water reactors. In the past three years, Sandia has been implementing the sodium chemistry containment models in CONTAIN-LMR, a legacy NRC code, into MELCOR. These chemistry models include spray fire, pool fire and atmosphere chemistry models. Only the first two chemistry models have been implemented though it is intended to implement all these models into MELCOR. A new package called “NAC” has been created to manage the sodium chemistry model more efficiently. In 2017 Sandia began validating the implemented models in MELCOR by simulating available experiments. The CONTAIN-LMR sodium models include sodium atmosphere chemistry and sodium-concrete interaction models. This paper presents sodium property models, the implemented models, implementation issues, and a path towards validation against existing experimental data.

Transcriptional Regulatory Network Analysis of MYB Transcription Factor Family Genes in Rice

Directory of Open Access Journals (Sweden)

Shuchi eSmita

2015-12-01

Full Text Available MYB transcription factor (TF is one of the largest TF families and regulates defense responses to various stresses, hormone signaling as well as many metabolic and developmental processes in plants. Understanding these regulatory hierarchies of gene expression networks in response to developmental and environmental cues is a major challenge due to the complex interactions between the genetic elements. Correlation analyses are useful to unravel co-regulated gene pairs governing biological process as well as identification of new candidate hub genes in response to these complex processes. High throughput expression profiling data are highly useful for construction of co-expression networks. In the present study, we utilized transcriptome data for comprehensive regulatory network studies of MYB TFs by top down and guide gene approaches. More than 50% of OsMYBs were strongly correlated under fifty experimental conditions with 51 hub genes via top down approach. Further, clusters were identified using Markov Clustering (MCL. To maximize the clustering performance, parameter evaluation of the MCL inflation score (I was performed in terms of enriched GO categories by measuring F-score. Comparison of co-expressed cluster and clads analyzed from phylogenetic analysis signifies their evolutionarily conserved co-regulatory role. We utilized compendium of known interaction and biological role with Gene Ontology enrichment analysis to hypothesize function of coexpressed OsMYBs. In the other part, the transcriptional regulatory network analysis by guide gene approach revealed 40 putative targets of 26 OsMYB TF hubs with high correlation value utilizing 815 microarray data. The putative targets with MYB-binding cis-elements enrichment in their promoter region, functional co-occurrence as well as nuclear localization supports our finding. Specially, enrichment of MYB binding regions involved in drought-inducibility implying their regulatory role in drought

Innovations in the Delivery of Regulatory Services in Australia

International Nuclear Information System (INIS)

Dillich, J.

2016-01-01

The Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) is the country’s primary authority on radiation protection and nuclear safety. ARPANSA aims to promote safety, security, and emergency preparedness through efficient and effective regulation of nuclear installations, controlled facilities, and radiation sources. Recent initiatives to improve regulation by ‘cutting red tape’ and reducing regulatory burden have been introduced. ARPANSA’s Regulatory Delivery Model emphasises the key elements to good regulation and describes initiatives such as baseline inspection schedule, Performance Objectives and Criteria, and performance deficiencies. These and other initiatives have streamlined inspection efforts, increased risk-based oversight and risk-informed decision making, leading to increased efficiencies for both regulator and licence holder. In addition, ARPANSA has introduced 12 key performance indicators in its self-assessment of regulatory performance against the Australian Government’s Regulator Performance Framework. (author)

BE (fuel element)/ZL (interim storage facility) module. Constituents of the fuel BE data base for BE documentation with respect to the disposal planning and the support of the BE container storage administration

International Nuclear Information System (INIS)

Hoffmann, V.; Deutsch, S.; Busch, V.; Braun, A.

2012-01-01

The securing of spent fuel element disposal from German nuclear power plants is the main task of GNS. This includes the container supply and the disposal analysis and planning. Therefore GNS operates a data base comprising all in Germany implemented fuel elements and all fuel element containers in interim storage facilities. With specific program modules the data base serves an optimized repository planning for all spent fuel elements from German NPPS and the supply of required data for future final disposal. The data base has two functional models: the BE (fuel element) and the ZL (interim storage) module. The contribution presents the data structure of the modules and details of the data base operation.

Development of an air-operated actuator performance monitoring system for regulatory usage

International Nuclear Information System (INIS)

Sung, K. Y.; Kwon, S. J.

2004-01-01

The performance monitoring system of air-operated actuators for regulatory usage has been being developed. Essential elements and operating parameters affecting the actuator performance have been investigated to provide basic information for system development. The monitoring system including an air-operated actuator testing facility and analysis softwares for monitoring and evaluation are also introduced in this paper. As a result of simulated tests, it was known that the system could be a useful tool for the effective monitoring of actuator performance change and fault conditions. This system would be applied to regulatory inspection for utility's data validation and to the training of regulatory staff in future after some modification and expansion

CRISPRing the Human Genome for Functional Regulatory Elements

NARCIS (Netherlands)

R.F.M. Lopes (Rui)

2018-01-01

markdownabstractThe sequence of DNA is a code that contains all the information that is required for life (as we know it). DNA is stored inside the nucleus of cells and its sequence is replicated during cell division to ensure that the genetic information is transmitted to the daughter cells. The

URANIUM OXIDE-CONTAINING FUEL ELEMENT COMPOSITION AND METHOD OF MAKING SAME

Science.gov (United States)

Handwerk, J.H.; Noland, R.A.; Walker, D.E.

1957-09-10

In the past, bodies formed of a mixture of uranium dioxide and aluminum powder have been used in fuel elements; however, these mixtures were found not to be suitable when exposed to temperatures of about 600 deg C, because at such high temperatures the fuel elements were distorted. If uranosic oxide, U/sub 3/O/sub 8/, is substituted for UO/sub 2/, the mechanical properties are not impaired when these materials are used at about 600 deg C and no distortion takes place. The uranosic oxide and aluminum, both in powder form, are first mixed, and after a homogeneous mixture has been obtained, are shaped into fuel elements by extrusion at elevated temperature. Magnesium powder may be used in place of the aluminum.

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

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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.

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)

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

Science.gov (United States)

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