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

African Journals Online (AJOL)

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

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.

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).

Intake of traditional Inuit diet vary in parallel with inflammation as estimated from YKL-40 and hsCRP in Inuit and non-Inuit in Greenland.

Science.gov (United States)

Schæbel, L H; Vestergaard, H; Laurberg, P; Rathcke, C N; Andersen, S

2013-06-01

Chronic low-grade inflammation is involved in the initiation and progression of atherosclerosis and ischemic heart disease. This was rare in pre-western Inuit who lived on a diet that consisted mainly of marine mammals rich in n-3 fatty acids. To assess the association between biomarkers of inflammation and the intake of traditional Inuit diet in addition to Inuit ethnicity. YKL-40 and hsCRP were measured in serum from 535 Inuit and non-Inuit living in the capital city Nuuk in West Greenland or in the main town or a settlement in rural East Greenland. Dietary habits were assessed by an interview-based food frequency questionnaire. The participation rate was 95%. YKL-40 was higher in Inuit than in non-Inuit (p Inuit with a higher intake of traditional Inuit diet (p Inuit from rural compared to urban areas (p Inuit had higher hsCRP compared to non-Inuit (p = 0.003) and hsCRP increased in parallel with intake of traditional Inuit foods (p Inuit (p = 0.004). YKL-40 and hsCRP increased with higher intakes of traditional Inuit diet after adjusting for ethnicity, gender, age, smoking, alcohol intake and BMI. Biomarkers of inflammation vary in parallel with the intake of traditional Inuit diet. A diet based on marine mammals from the Arctic does not reduce inflammatory activity and it may be speculated that markers of inflammation reflect the disease rather than the cause of the disease. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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

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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.

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

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

2010-12-01

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

A hidden service model based on HS-HS anonymous network

Science.gov (United States)

Meng, Yitong; Zhao, Xing; Fei, Jinlong; Zhu, Yuefei

2017-10-01

The Hidden Service provided by Tor anonymous network can effectively protect the anonymity and security of the Hidden server, this article through the analysis of the data packet structure of Tor, three jump transmission mechanism and link establishment protocol and Hidden Service communication process, in view of the Hidden node number too much, link building Service for too long and too redundant link problem. An improved hidden service model HS-HS is proposed that incorporating multiple transmission link and reuse, and at the same time will be important transit point for reuse protection link anonymity, through the ExperimenTor simulation environment test, verify the improved model of HS-HS can be more effective in guarantee anonymity and security, improve the overall efficiency of data transmission, to meet the needs of today's anonymous service.

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.

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

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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.

Cis-regulatory RNA elements that regulate specialized ribosome activity.

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Xue, Shifeng; Barna, Maria

2015-01-01

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

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

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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

Differential proteomic analysis reveals sequential heat stress-responsive regulatory network in radish (Raphanus sativus L.) taproot.

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Wang, Ronghua; Mei, Yi; Xu, Liang; Zhu, Xianwen; Wang, Yan; Guo, Jun; Liu, Liwang

2018-05-01

Differential abundance protein species (DAPS) involved in reducing damage and enhancing thermotolerance in radish were firstly identified. Proteomic analysis and omics association analysis revealed a HS-responsive regulatory network in radish. Heat stress (HS) is a major destructive factor influencing radish production and supply in summer, for radish is a cool season vegetable crop being susceptible to high temperature. In this study, the proteome changes of radish taproots under 40 °C treatment at 0 h (Control), 12 h (Heat12) and 24 h (Heat24) were analyzed using iTRAQ (Isobaric Tag for Relative and Absolute Quantification) approach. In total, 2258 DAPS representing 1542 differentially accumulated uniprotein species which respond to HS were identified. A total of 604, 910 and 744 DAPS was detected in comparison of Control vs. Heat12, Control vs. Heat24, and Heat12 vs. Heat24, respectively. Gene ontology and pathway analysis showed that annexin, ubiquitin-conjugating enzyme, ATP synthase, heat shock protein (HSP) and other stress-related proteins were predominately enriched in signal transduction, stress and defense pathways, photosynthesis and energy metabolic pathways, working cooperatively to reduce stress-induced damage in radish. Based on iTRAQ combined with the transcriptomics analysis, a schematic model of a sequential HS-responsive regulatory network was proposed. The initial sensing of HS occurred at the plasma membrane, and then key components of stress signal transduction triggered heat-responsive genes in the plant protective metabolism to re-establish homeostasis and enhance thermotolerance. These results provide new insights into characteristics of HS-responsive DAPS and facilitate dissecting the molecular mechanisms underlying heat tolerance in radish and other root crops.

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-.

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

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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.

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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.

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

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

2012-09-01

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

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

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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...

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

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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.

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

Superheavy element chemistry. Achievements and perspectives

International Nuclear Information System (INIS)

Schaedel, M.

2007-01-01

Superheavy elements have been synthesized and chemically characterized one-atom-at-a-time up to element 108. Presently, the quest for element 112 is one of the hottest topics in this field. The transactinide elements 104 to 108 are members of group 4 to 8 of the Periodic Table and element 112 belongs into group 12. Chemical properties of some of these elements, like elements 104 and 105, show stunning deviations from simple extrapolations within their respective group while others exhibit great similarities with their lighter homologues elements. First experiments to investigate seaborgium (Sg, element 106) in aqueous solution were performed. Again, in large international collaborations at the GSI, several gas-phase chemistry experiments were performed with hassium (Hs, element 108). Recently, the highly efficient and very clean separation of Hs was applied for nuclear studies of various Hs nuclides investigating their cross section and their nuclear decay properties in the region of the doubly-magic 270 Hs (Z=108, N=162). To overcome certain limitations of the presently used on-line chemical separations the new TransActinide Separation and Chemistry Apparatus (TASCA) - with a gas-filled recoil separator as a front-end tool - was designed and built at the GSI in a collaborative effort. Presently in its commissioning phase, TASCA shall be a key instrument for a big leap into quantitatively and qualitatively new experiments in the region of superheavy elements. (author)

40 CFR 721.10068 - Elemental mercury.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Elemental mercury. 721.10068 Section... Substances § 721.10068 Elemental mercury. (a) Definitions. The definitions in § 721.3 apply to this section... elemental mercury (CAS. No. 7439-97-6) is subject to reporting under this section for the significant new...

PHOTOMETRIC ANALYSIS OF HS Aqr, EG Cep, VW LMi, AND DU Boo

Energy Technology Data Exchange (ETDEWEB)

Djurasevic, G.; Latkovic, O. [Astronomical Observatory, Volgina 7, 11000 Belgrade (Serbia); Bastuerk, Oe.; Y Latin-Small-Letter-Dotless-I lmaz, M. [Astronomy and Space Sciences Research and Application Center, Ankara University, TR-06837 Ahlatl Latin-Small-Letter-Dotless-I bel, Ankara (Turkey); Cal Latin-Small-Letter-Dotless-I skan, S.; Senavc Latin-Small-Letter-Dotless-I , H. V.; K Latin-Small-Letter-Dotless-I l Latin-Small-Letter-Dotless-I coglu, T.; Ekmekci, F. [Department of Astronomy and Space Sciences, Faculty of Science, Ankara University, TR-06100 Tandogan, Ankara (Turkey); Tanr Latin-Small-Letter-Dotless-I verdi, T., E-mail: olivia@aob.rs [Department of Physics, Faculty of Arts and Sciences, Nigde University, 51240 Nigde (Turkey)

2013-03-15

We analyze new multicolor light curves for four close late-type binaries: HS Aqr, EG Cep, VW LMi, and DU Boo, in order to determine the orbital and physical parameters of the systems and estimate the distances. The analysis is done using the modeling code of G. Djurasevic, and is based on up-to-date measurements of spectroscopic elements. All four systems have complex, asymmetric light curves that we model by including bright or dark spots on one or both components. Our findings indicate that HS Aqr and EG Cep are in semi-detached, while VW LMi and DU Boo are in overcontact configurations.

Italian Validation of Homophobia Scale (HS).

Science.gov (United States)

Ciocca, Giacomo; Capuano, Nicolina; Tuziak, Bogdan; Mollaioli, Daniele; Limoncin, Erika; Valsecchi, Diana; Carosa, Eleonora; Gravina, Giovanni L; Gianfrilli, Daniele; Lenzi, Andrea; Jannini, Emmanuele A

2015-09-01

The Homophobia Scale (HS) is a valid tool to assess homophobia. This test is self-reporting, composed of 25 items, which assesses a total score and three factors linked to homophobia: behavior/negative affect, affect/behavioral aggression, and negative cognition. The aim of this study was to validate the HS in the Italian context. An Italian translation of the HS was carried out by two bilingual people, after which an English native translated the test back into the English language. A psychologist and sexologist checked the translated items from a clinical point of view. We recruited 100 subjects aged18-65 for the Italian validation of the HS. The Pearson coefficient and Cronbach's α coefficient were performed to test the test-retest reliability and internal consistency. A sociodemographic questionnaire including the main information as age, geographic distribution, partnership status, education, religious orientation, and sex orientation was administrated together with the translated version of HS. The analysis of the internal consistency showed an overall Cronbach's α coefficient of 0.92. In the four domains, the Cronbach's α coefficient was 0.90 in behavior/negative affect, 0.94 in affect/behavioral aggression, and 0.92 in negative cognition, whereas in the total score was 0.86. The test-retest reliability showed the following results: the HS total score was r = 0.93 (P cognition was r = 0.75 (P validation of the HS revealed the use of this self-report test to have good psychometric properties. This study offers a new tool to assess homophobia. In this regard, the HS can be introduced into the clinical praxis and into programs for the prevention of homophobic behavior.

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...

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

Energy Technology Data Exchange (ETDEWEB)

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

2003-06-01

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

10 CFR 40.11 - Persons using source material under certain Department of Energy and Nuclear Regulatory...

Science.gov (United States)

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Persons using source material under certain Department of Energy and Nuclear Regulatory Commission contracts. 40.11 Section 40.11 Energy NUCLEAR REGULATORY... certain Department of Energy and Nuclear Regulatory Commission contracts. Except to the extent that...

Collective dipole motion in highly excited (272)Hs (Z=108) nuclei

NARCIS (Netherlands)

Tveter, TS; Gaardhoje, JJ; Maj, A; Ramsay, T; Atac, A; Bacelar, J; Bracco, A; Buda, A; Camera, F; Herskind, B; Korten, W; Krolas, W; Menthe, A; Million, B; Nifenecker, H; Pignanelli, M; Pinston, JA; vanderPloeg, H; Schussler, F; Sletten, G

1996-01-01

The heavy nucleus (272)(108)Hs (Z = 108) and its evaporation daughters were produced using the reaction Th-232(Ar-40, gamma xn) with beam energies 10.5 and 15.0 MeV/A. The giant dipole resonance gamma radiation from the hot composite system prior to fission has been isolated using a differential

Modal Identification in an Automotive Multi-Component System Using HS 3D-DIC

Directory of Open Access Journals (Sweden)

Ángel Jesús Molina-Viedma

2018-02-01

Full Text Available The modal characterization of automotive lighting systems becomes difficult using sensors due to the light weight of the elements which compose the component as well as the intricate access to allocate them. In experimental modal analysis, high speed 3D digital image correlation (HS 3D-DIC is attracting the attention since it provides full-field contactless measurements of 3D displacements as main advantage over other techniques. Different methodologies have been published that perform modal identification, i.e., natural frequencies, damping ratios, and mode shapes using the full-field information. In this work, experimental modal analysis has been performed in a multi-component automotive lighting system using HS 3D-DIC. Base motion excitation was applied to simulate operating conditions. A recently validated methodology has been employed for modal identification using transmissibility functions, i.e., the transfer functions from base motion tests. Results make it possible to identify local and global behavior of the different elements of injected polymeric and metallic materials.

Modal Identification in an Automotive Multi-Component System Using HS 3D-DIC.

Science.gov (United States)

Molina-Viedma, Ángel Jesús; López-Alba, Elías; Felipe-Sesé, Luis; Díaz, Francisco A

2018-02-05

The modal characterization of automotive lighting systems becomes difficult using sensors due to the light weight of the elements which compose the component as well as the intricate access to allocate them. In experimental modal analysis, high speed 3D digital image correlation (HS 3D-DIC) is attracting the attention since it provides full-field contactless measurements of 3D displacements as main advantage over other techniques. Different methodologies have been published that perform modal identification, i.e., natural frequencies, damping ratios, and mode shapes using the full-field information. In this work, experimental modal analysis has been performed in a multi-component automotive lighting system using HS 3D-DIC. Base motion excitation was applied to simulate operating conditions. A recently validated methodology has been employed for modal identification using transmissibility functions, i.e., the transfer functions from base motion tests. Results make it possible to identify local and global behavior of the different elements of injected polymeric and metallic materials.

Modal Identification in an Automotive Multi-Component System Using HS 3D-DIC

Science.gov (United States)

López-Alba, Elías; Felipe-Sesé, Luis; Díaz, Francisco A.

2018-01-01

The modal characterization of automotive lighting systems becomes difficult using sensors due to the light weight of the elements which compose the component as well as the intricate access to allocate them. In experimental modal analysis, high speed 3D digital image correlation (HS 3D-DIC) is attracting the attention since it provides full-field contactless measurements of 3D displacements as main advantage over other techniques. Different methodologies have been published that perform modal identification, i.e., natural frequencies, damping ratios, and mode shapes using the full-field information. In this work, experimental modal analysis has been performed in a multi-component automotive lighting system using HS 3D-DIC. Base motion excitation was applied to simulate operating conditions. A recently validated methodology has been employed for modal identification using transmissibility functions, i.e., the transfer functions from base motion tests. Results make it possible to identify local and global behavior of the different elements of injected polymeric and metallic materials. PMID:29401725

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

Science.gov (United States)

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

1988-01-01

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

Italian Validation of Homophobia Scale (HS)

OpenAIRE

Ciocca, Giacomo; Capuano, Nicolina; Tuziak, Bogdan; Mollaioli, Daniele; Limoncin, Erika; Valsecchi, Diana; Carosa, Eleonora; Gravina, Giovanni L.; Gianfrilli, Daniele; Lenzi, Andrea; Jannini, Emmanuele A.

2015-01-01

Introduction: The Homophobia Scale (HS) is a valid tool to assess homophobia. This test is self‐reporting, composed of 25 items, which assesses a total score and three factors linked to homophobia: behavior/negative affect, affect/behavioral aggression, and negative cognition. Aim: The aim of this study was to validate the HS in the Italian context. Methods: An Italian translation of the HS was carried out by two bilingual people, after which an English native translated the test back i...

Italian Validation of Homophobia Scale (HS

Directory of Open Access Journals (Sweden)

Giacomo Ciocca, PsyD, PhD

2015-09-01

Conclusions: The Italian validation of the HS revealed the use of this self‐report test to have good psychometric properties. This study offers a new tool to assess homophobia. In this regard, the HS can be introduced into the clinical praxis and into programs for the prevention of homophobic behavior. Ciocca G, Capuano N, Tuziak B, Mollaioli D, Limoncin E, Valsecchi D, Carosa E, Gravina GL, Gianfrilli D, Lenzi A, and Jannini EA. Italian validation of Homophobia Scale (HS. Sex Med 2015;3:213–218.

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...

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

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

Science.gov (United States)

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

2015-12-01

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

HS5 of the human β-globin Locus Control Region: a developmental stage-specific border in erythroid cells.

NARCIS (Netherlands)

A. Wai (Albert); N. Gillemans (Nynke); S. Raguz-Bolognesi (Selina); S. Pruzina (Sara); G. Zafarana (Gaetano); D.N. Meijer (Dies); F.G. Grosveld (Frank); J.N.J. Philipsen (Sjaak)

2003-01-01

textabstractElements with insulator/border activity have been characterized most extensively in Drosophila melanogaster. In vertebrates, the first example of such an element was provided by a hypersensitive site of the chicken beta-globin locus, cHS4. It has been proposed that the homologous site in

Further Development of HS Field Theory

Science.gov (United States)

Abdurrahman, Abdulmajeed; Faridani, Jacqueline; Gassem, Mahmoud

2006-04-01

We present a systematic treatment of the HS Field theory of the open bosonic string and discuss its relationship to other full string field theories of the open bosonic string such as Witten's theory and the CVS theory. In the development of the HS field theory we encounter infinite dimensional matrices arising from the change of representation between the two theories, i.e., the HS field theory and the full string field theory. We give a general procedure of how to invert these gigantic matrices. The inversion of these matrices involves the computation of many infinite sums. We give the values of these sums and state their generalizations arising from considering higher order vertices (i.e., more than three strings) in string field theory. Moreover, we give a general procedure, on how to evaluate the generalized sums, that can be extended to many generic sums of similar properties. We also discuss the conformal operator connecting the HS field theory to that of the CVS string field theory.

PlantCARE, a plant cis-acting regulatory element database

OpenAIRE

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

1999-01-01

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

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

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...

In silico Analysis of osr40c1 Promoter Sequence Isolated from Indica Variety Pokkali

Directory of Open Access Journals (Sweden)

W.S.I. de Silva

2017-07-01

Full Text Available The promoter region of a drought and abscisic acid (ABA inducible gene, osr40c1, was isolated from a salt-tolerant indica rice variety Pokkali, which is 670 bp upstream of the putative translation start codon. In silico promoter analysis of resulted sequence showed that at least 15 types of putative motifs were distributed within the sequence, including two types of common promoter elements, TATA and CAAT boxes. Additionally, several putative cis-acing regulatory elements which may be involved in regulation of osr40c1 expression under different conditions were found in the 5′-upstream region of osr40c1. These are ABA-responsive element, light-responsive elements (ATCT-motif, Box I, G-box, GT1-motif, Gap-box and Sp1, myeloblastosis oncogene response element (CCAAT-box, auxin responsive element (TGA-element, gibberellin-responsive element (GARE-motif and fungal-elicitor responsive elements (Box E and Box-W1. A putative regulatory element, required for endosperm-specific pattern of gene expression designated as Skn-1 motif, was also detected in the Pokkali osr40c1 promoter region. In conclusion, the bioinformatic analysis of osr40c1 promoter region isolated from indica rice variety Pokkali led to the identification of several important stress-responsive cis-acting regulatory elements, and therefore, the isolated promoter sequence could be employed in rice genetic transformation to mediate expression of abiotic stress induced genes.

SN 2011hs

DEFF Research Database (Denmark)

Bufano, F.; Pignata, G.; Bersten, M.

2014-01-01

Observations spanning a large wavelength range, from X-ray to radio, of the Type IIb supernova 2011hs are presented, covering its evolution during the first year after explosion. The optical light curve presents a narrower shape and a fainter luminosity at peak than previously observed for Type I...

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

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.

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

Serum Pentraxin 3 and hs-CRP Levels in Children with Severe Pulmonary Hypertension

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Cemşit Karakurt

2014-09-01

Full Text Available Background: Pulmonary arterial hypertension secondary to untreated left-to-right shunt defects leads to increased pulmonary blood flow, endothelial dysfunction, increased pulmonary vascular resistance, vascular remodelling, neointimal and plexiform lesions. Some recent studies have shown that inflammation has an important role in the pathophysiology of pulmonary arterial hypertension. Aims: The aim of this study is to evaluate serum pentraxin 3 and high sensitive (hs-C reactive protein (hs-CRP levels in children with severe pulmonary arterial hypertension (PAH secondary to untreated congenital heart defects and evaluate the role of inflammation in pulmonary hypertension. Study Design: Cross sectional study. Methods: After ethics committee approval and receiving consent from parents, there were 31 children were selected for the study with severe PAH, mostly with a left-to-right shunt, who had been assessed by cardiac catheterisation and were taking specific pulmonary vasodilators. The control group consisted of 39 age and gender matched healthy children. After recording data about all the patients including age, gender, weight, haemodynamic studies and vasodilator testing, a physical examination was done for all subjects. Blood was taken from patients and the control group using peripheral veins to analyse serum Pentraxin 3, N-terminal pro-Brain Natriuretic Peptide (NT-ProBNP and hs-CRP levels. Serum Pentraxin-3 levels were measured by enzyme linked immunosorbent assay (ELISA and expressed as ng/mL. Serum hs-CRP levels were measured with an immunonephelometric method and expressed as mg/dL. The serum concentration of NT-proBNP was determined by a chemiluminescent immunumetric assay and expressed as pg/mL. Results: Serum Pentraxin- 3 levels were determined to be 1.28±2.12 (0.12-11.43 in the PAH group (group 1 and 0.40±0.72 (0.07-3.45 in group 2. There was a statistically significant difference between the two groups (p<0.01. Serum hs-CRP levels

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.

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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.

Application value of Serum Hs-CRP, IL-6 and plasma FIB joint detection in COPD

Directory of Open Access Journals (Sweden)

Feng Ji

2016-11-01

.86%; Specificities were 80.46%, 83.91%, 79.31%; Accuracies were 93.10%, 95.40%, 94.83%. Conclusions: COPD illness evolution and severity could be reflected by serum hs-CRP, IL-6 and plasma FIB all in some extent, the joint detection could be a reference on prognostic evaluation.

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

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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.

A tale of three labels: translating the JUPITER trial data into regulatory claims.

Science.gov (United States)

Ridker, Paul M

2011-08-01

Whether a pivotal randomized trial will be interpreted in a similar and consistent manner by different regulatory agencies is uncertain as policy perspectives may play a role in data interpretation and the translation of trial results into clinical practice. Using a contemporary example, to compare and contrast regulatory claims in the United States, Europe, and Canada that derive from a pivotal clinical trial. The recently completed JUPITER trial of rosuvastatin as compared to placebo conducted among 17,802 men and women with LDL-C JUPITER trial provides an opportunity to compare and contrast how regulatory agencies in the United States, Canada, and Europe chose to interpret an identical database. Labeling indications based on earlier statin trials of primary and secondary prevention were also reviewed. JUPITER demonstrated a 44% reduction (p JUPITER trial population by stipulating that those eligible for treatment should be older men and women with hsCRP >2 mg/L, plus one additional risk factor for heart disease. The Canadian label is silent on age and hsCRP (the major trial inclusion criterion), stipulating instead that treatment can be considered for those with 'at least two conventional risk factors for cardiovascular disease,' a group more inclusive than that studied. In contrast, the European Medicines Agency label limits treatment only to 'high risk individuals' ignoring hsCRP and using instead a post hoc definition of 'high risk' that comprised a subgroup of less than 10% of the study population who contributed but 67 events to the study total and did not show statistical significance when compared to placebo. None of the regulatory labels included the trial primary endpoint; instead, each focused on separate and different components of the primary endpoint. Similar discrepancies were found between European and North American regulatory agencies with regard to earlier pivotal trials of statins for primary prevention, but not for secondary prevention. The

[hsCRP protein in children and adolescents with diabetes type 1].

Science.gov (United States)

Głowińska-Olszewska, Barbara; Urban, Mirosława; Peczyńska, Jadwiga; Koput, Alicja

2007-01-01

HsCRP protein is known as a novel marker of low grade inflammatory state, which characterises an atherosclerotic process in its early stages. Contrary to a large amount of data on inflammatory markers in diabetes type 2 and metabolic syndrome in adults, little is known so far about the inflammatory process in diabetes type 1, especially in children. The aim of the study was to estimate the level of hsCRP protein in children and adolescents with diabetes type 1 depending on coexisting additional risk factors for atherosclerosis and microvascular complications. 127 children and adolescents with diabetes duration 6.7+/-3.3 years, aged 14.9+/-3.1, were studied. The control group consisted of 52 healthy children aged 14.9+/-2.8 years, matched acc. to gender. HsCRP level was assessed with use of immunoturbidymetric, latex augmented method (Tina-quant CRP (Latex) HS, Roche). HsCRP in the whole study group was nearly significantly higher compared to control group: 0.17+/-0.2 vs. 0.078+/-0.1 mg/dl, p=0.072. In diabetic hypertensive children (n=38) we found significantly higher levels of hsCRP compared to controls (0.27+/-0.3 vs. 0.07 mg/dl, p=0.008) and compared to diabetic normotensive children (0.13+/-0.22 mg/dl; p=0.024). Diabetic obese patients (n=23) had significantly higer hsCRP compared to controls (0.24+/-0.3 vs. 0.07+/-0.1 mg/dl, p=0.04). In 14 studied diabetic children we found coexisting hypertension and obesity, and we found further increase in hsCRP level - 0.28+/-0.3 mg/dl. In diabetic children with microangiopathy hsCRP level was 0.22+/-0.2 mg/dl, and it was insignificantly higher compared to controls and to diabetic children without complications. Correlation analysis showed interrelations between hsCRP and systolic blood pressure (r=0.2; p=0.04) and HbA1c (r=0.25; p=0.015). In stepwise regression analysis hsCRP was related to systolic blood pressure, HbA1c and the triglycerides level (R=0.37; p=0.003). In children and adolescents with diabetes type 1 we

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.

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.

Q-value effects in the synthesis of superheavy elements

International Nuclear Information System (INIS)

Graeger, Reimar

2010-01-01

Superheavy elements (Z>or similar 104) only exist due to nuclear shell effects, which stabilize them against spontaneous fission (SF). Theoretical calculations predict these shell stabilization effects to reach a maximum at the closures of the next spherical proton and neutron shells, which are anticipated in the region between Z=114 and Z=126 and at N=184. More recent calculations, that also consider deformed nuclear shapes extended this picture and predicted deformed shell closures at Z=108 and at N=162, creating a region of enhanced stability around 270 Hs, confirmed in recent Hs chemistry experiments by measuring the decay of 270 Hs for the first time. Recently, the formation of deformed doubly-magic 270 Hs in the 4n evaporation channel in the fusion reactions 248 Cm( 26 Mg,4n), 244 Pu( 30 Si,4n), 238 U( 36 S,4n), and 226 Ra( 48 Ca,4n) was studied theoretically using a two-parameter Smoluchowski equation. Simple entrance channel arguments make compound nucleus (CN) formation appear favorable for systems with larger mass asymmetry. However, due to a lower reaction Q value, the reactions 238 U( 36 S,4n) 270 Hs and 226 Ra( 48 Ca,4n) 270 Hs are predicted to have higher cross sections compared to the reactions 248 Cm( 26 Mg,4n) 270 Hs and 244 Pu( 30 Si,4n) 270 Hs. The aim of the research done in the framework of this thesis was to study the influence of the reaction (B-Q)-value on the yield of SHE produced in nuclear fusion reactions. Therefore the most promising reactions 36 S+ 238 U and 48 Ca+ 226 Ra have been investigated and compared with the already measured reaction 26 Mg+ 248 Cm. The reaction 36 S+ 238 U was investigated at two beam energies. One correlated decay chain attributed to 270 Hs was found at E * =51 MeV resulting in a cross section of 0.8 -0.7 +2.6 pb. The reaction 48 Ca+ 226 Ra was investigated at three beam energies. Six correlated decay chains attributed to 270 Hs were detected at E * =40 MeV corresponding to a cross section of 8.3 -3.7 +6.7 pb

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

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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

CoCoRaHS: A Community Science Program Providing Valuable Precipitation Data to Guide Decision Making

Science.gov (United States)

Robinson, D. A.; Doesken, N.

2017-12-01

CoCoRaHS is an acronym for the Community Collaborative Rain, Hail and Snow Network. It is long-running, community-based network of volunteers working together to measure and map precipitation (rain, hail and snow). Precipitation is an ideal element for public engagement because it affects everyone, it is so variable in time and space and it impacts so many things. By using a standard precipitation gauge, stressing training and education, utilizing an interactive website, and having observations undergo quality assurance, the CoCoRaHS program provides high-quality data for natural resource, education and research applications. The program currently operates in all states, Canada and the Bahamas. It originated with the Colorado Climate Center at Colorado State University in 1998 due in part to the Fort Collins flood a year prior. Upwards of 12,000 observers submit observations each day. Observations meet federal guidelines and are archived at the U.S. National Centers for Environmental Information. Because of excellent spatial coverage, data quality, practical relevance, and accessibility, CoCoRaHS observations are used by a wide variety of organizations and individuals. The U.S. National Weather Service, hydrologists, emergency managers, city utilities (water supply, storm water), insurance adjusters, the U.S. Department of Agriculture, engineers, mosquito control commissions, ranchers and farmers, outdoor and recreation interests, teachers and students are just some examples of those who use CoCoRaHS data in making well-informed, meaningful decisions. Some examples of community applications and the science utility of CoCoRaHS observations include storm warnings, water supply and demand forecasts, disaster declarations (drought, winter storm, etc.), drought and food production assessments, calibration/validation of remote sensing, infrastructure evaluation and potential redesign (ice and snow loading, bridge, storm and sewer design), recreation planning, and

Intralesional triamcinolone for flares of hidradenitis suppurativa (HS)

DEFF Research Database (Denmark)

Riis, Peter Theut; Boer, Jurr; Prens, Errol P

2016-01-01

(triamcinolone acetonide 10 mg/mL) in the management of acute flares in HS. METHODS: This was a prospective case series evaluating the effect of intralesional corticosteroids for alleviation of acute flares in HS. Physician- and patient-reported outcomes were noted. RESULTS: Significant reductions in physician......-assessed erythema (median score from 2-1, P edema (median score from 2-1, P

HS06 Benchmark for an ARM Server

Science.gov (United States)

Kluth, Stefan

2014-06-01

We benchmarked an ARM cortex-A9 based server system with a four-core CPU running at 1.1 GHz. The system used Ubuntu 12.04 as operating system and the HEPSPEC 2006 (HS06) benchmarking suite was compiled natively with gcc-4.4 on the system. The benchmark was run for various settings of the relevant gcc compiler options. We did not find significant influence from the compiler options on the benchmark result. The final HS06 benchmark result is 10.4.

HS06 benchmark for an ARM server

International Nuclear Information System (INIS)

Kluth, Stefan

2014-01-01

We benchmarked an ARM cortex-A9 based server system with a four-core CPU running at 1.1 GHz. The system used Ubuntu 12.04 as operating system and the HEPSPEC 2006 (HS06) benchmarking suite was compiled natively with gcc-4.4 on the system. The benchmark was run for various settings of the relevant gcc compiler options. We did not find significant influence from the compiler options on the benchmark result. The final HS06 benchmark result is 10.4.

Fe(II)/Cu(II) interaction on goethite stimulated by an iron-reducing bacteria Aeromonas Hydrophila HS01 under anaerobic conditions.

Science.gov (United States)

Tao, Liang; Zhu, Zhen-Ke; Li, Fang-Bai; Wang, Shan-Li

2017-11-01

Copper is a trace element essential for living creatures, but copper content in soil should be controlled, as it is toxic. The physical-chemical-biological features of Cu in soil have a significant correlation with the Fe(II)/Cu(II) interaction in soil. Of significant interest to the current study is the effect of Fe(II)/Cu(II) interaction conducted on goethite under anaerobic conditions stimulated by HS01 (a dissimilatory iron reduction (DIR) microbial). The following four treatments were designed: HS01 with α-FeOOH and Cu(II) (T1), HS01 with α-FeOOH (T2), HS01 with Cu(II) (T3), and α-FeOOH with Cu(II) (T4). HS01 presents a negligible impact on copper species transformation (T3), whereas the presence of α-FeOOH significantly enhanced copper aging contributing to the DIR effect (T1). Moreover, the violent reaction between adsorbed Fe(II) and Cu(II) leads to the decreased concentration of the active Fe(II) species (T1), further inhibiting reactions between Fe(II) and iron (hydr)oxides and decelerating the phase transformation of iron (hydr)oxides (T1). From this study, the effects of the Fe(II)/Cu(II) interaction on goethite under anaerobic conditions by HS01 are presented in three aspects: (1) the accelerating effect of copper aging, (2) the reductive transformation of copper, and (3) the inhibition effect of the phase transformation of iron (hydr)oxides. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

An Evaluation of the Performance Diagnostic Checklist-Human Services (PDC-HS) Across Domains.

Science.gov (United States)

Wilder, David A; Lipschultz, Joshua; Gehrman, Chana

2018-06-01

The Performance Diagnostic Checklist-Human Services (PDC-HS) is an informant-based tool designed to assess the environmental variables that contribute to poor employee performance in human service settings. Although the PDC-HS has been shown to effectively identify variables contributing to problematic performance, interventions based on only two of the four PDC-HS domains have been evaluated to date. In addition, the extent to which PDC-HS-indicated interventions are more effective than nonindicated interventions for two domains remains unclear. In the current study, we administered the PDC-HS to supervisors to assess the variables contributing to infrequent teaching of verbal operants and use of a timer by therapists at a center-based autism treatment program. Each of the four PDC-HS domains was identified as contributing to poor performance for at least one therapist. We then evaluated PDC-HS-indicated interventions for each domain. In addition, to assess the predictive validity of the tool, we evaluated various nonindicated interventions prior to implementing a PDC-HS-indicated intervention for two of the four domains. Results suggest that the PDC-HS-indicated interventions were effective across all four domains and were more effective than the nonindicated interventions for the two domains for which they were evaluated. Results are discussed in terms of the utility of the PDC-HS to identify appropriate interventions to manage therapist performance in human service settings.

Preparation and pharmacokinetic evaluation of curcumin solid dispersion using Solutol® HS15 as a carrier.

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Seo, Sang-Wan; Han, Hyo-Kyung; Chun, Myung-Kwan; Choi, Hoo-Kyun

2012-03-15

Solubility of curcumin at physiological pH was significantly increased by forming solid dispersion (SD) with Solutol® HS15. Since curcumin undergoes hydrolytic degradation, chemical stability study was conducted in pH 1.2, 6.8 and 7.4 buffer media. Solutol® HS15 exhibited superior stabilizing effect to Cremophor® RH40 and Kollidon® 30. The physical state of the dispersed curcumin in the polymer matrix was characterized by differential scanning calorimetry and X-ray diffraction studies. SD preparation transformed curcumin into amorphous form and facilitated micellar incorporation, thereby preventing hydrolysis in aqueous medium. In vitro drug release in pH 6.8 buffer revealed that SD (1:10) improved the dissolution of curcumin with approximately 90% release of the drug within 1h. Pharmacokinetic study of the solid dispersion formulation in rat showed that bioavailability of the drug was significantly improved as compared to pure curcumin. SD containing 1:10 ratio of drug and Solutol® HS15 resulted in approximately 5 fold higher AUC(0-12h). SD formulation was physically stable over the study period of 3 months. Copyright © 2011 Elsevier B.V. All rights reserved.

Human polyomavirus JCV late leader peptide region contains important regulatory elements

International Nuclear Information System (INIS)

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

2006-01-01

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

Regulation of insulin-like growth factor I transcription by cyclic adenosine 3',5'-monophosphate (cAMP) in fetal rat bone cells through an element within exon 1: protein kinase A-dependent control without a consensus AMP response element

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McCarthy, T. L.; Thomas, M. J.; Centrella, M.; Rotwein, P.

1995-01-01

Insulin-like growth factor I (IGF-I) is a locally synthesized anabolic growth factor for bone. IGF-I synthesis by primary fetal rat osteoblasts (Ob) is stimulated by agents that increase the intracellular cAMP concentration, including prostaglandin E2 (PGE2). Previous studies with Ob cultures demonstrated that PGE2 enhanced IGF-I transcription through selective use of IGF-I promoter 1, with little effect on IGF-I messenger RNA half-life. Transient transfection of Ob cultures with an array of promoter 1-luciferase reporter fusion constructs has now allowed localization of a potential cis-acting promoter element(s) responsible for cAMP-stimulated gene expression to the 5'-untranslated region (5'-UTR) of IGF-I exon 1, within a segment lacking a consensus cAMP response element. Our evidence derives from three principal observations: 1) a transfection construct containing only 122 nucleotides (nt) of promoter 1 and 328 nt of the 5'-UTR retained full PGE2-stimulated reporter expression; 2) maximal PGE2-driven reporter expression required the presence of nt 196 to 328 of exon 1 when tested within the context of IGF-I promoter 1; 3) cotransfection of IGF-I promoter-luciferase-reporter constructs with a plasmid encoding the alpha-isoform of the catalytic subunit of murine cAMP-dependent protein kinase (PKA) produced results comparable to those seen with PGE2 treatment, whereas cotransfection with a plasmid encoding a mutant regulatory subunit of PKA that cannot bind cAMP blocked PGE2-induced reporter expression. Deoxyribonuclease I footprinting of the 5'-UTR of exon 1 demonstrated protected sequences at HS3A, HS3B, and HS3D, three of six DNA-protein binding sites previously characterized with rat liver nuclear extracts. Of these three regions, only the HS3D binding site is located within the functionally identified hormonally responsive segment of IGF-I exon 1. These results directly implicate PKA in the control of IGF-I gene transcription by PGE2 and identify a segment of

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...

Relationship of HS CRP and Sacroiliac Joint Inflammation in Undifferentiated Spondyloarthritis.

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Liu, Te-Jung; Chang, Cheng-Chiang; Chen, Liang-Cheng; Chu, Heng-Yi; Hsu, Chun-Sheng; Chang, Shin-Tsu

2018-01-01

Elevation of serum high sensitivity C-reactive protein (hs-CRP) level has been demonstrated as a risk factor for varying diseases, as well as a biomarker for predicting recovery after operation of lumber disc herniation. Our objective was to investigate the relationship between serum hs-CRP and sacroiliac (SI) joint inflammation in patients with undifferentiated spondyloarthritis (uSpA). In this retrospective study, we enrolled patients with uSpA who underwent hs-CRP testing between January 2007 and September 2013. Serum hs-CRP was analyzed at our central laboratory. All enrolled patients underwent skeletal scintigraphic scan with quantitative sacroiliac measurement. A total of 29 patients were enrolled with mean age 32.27 years and female:male ratio of 6:23. Pearson's correlation coefficient showed a significant difference between hs-CRP in serum and SI/S ratio in uSpA, particularly the middle part of the sacroiliac joint, either right side or left side. The significantly high concentration of serum hs-CRP might indicate a systemic inflammatory response to flare-up of the SI joint and might be an indicator of SI inflammation in uSpA.

Relationship of HS CRP and Sacroiliac Joint Inflammation in Undifferentiated Spondyloarthritis

Science.gov (United States)

Liu, Te-Jung; Chang, Cheng-Chiang; Chen, Liang-Cheng; Chu, Heng-Yi; Hsu, Chun-Sheng; Chang, Shin-Tsu

2018-01-01

Abstract Objective Elevation of serum high sensitivity C-reactive protein (hs-CRP) level has been demonstrated as a risk factor for varying diseases, as well as a biomarker for predicting recovery after operation of lumber disc herniation. Our objective was to investigate the relationship between serum hs-CRP and sacroiliac (SI) joint inflammation in patients with undifferentiated spondyloarthritis (uSpA). Methods In this retrospective study, we enrolled patients with uSpA who underwent hs-CRP testing between January 2007 and September 2013. Serum hs-CRP was analyzed at our central laboratory. All enrolled patients underwent skeletal scintigraphic scan with quantitative sacroiliac measurement. Results A total of 29 patients were enrolled with mean age 32.27 years and female:male ratio of 6:23. Pearson’s correlation coefficient showed a significant difference between hs-CRP in serum and SI/S ratio in uSpA, particularly the middle part of the sacroiliac joint, either right side or left side. The significantly high concentration of serum hs-CRP might indicate a systemic inflammatory response to flare-up of the SI joint and might be an indicator of SI inflammation in uSpA. PMID:29785410

Essential oil from Rhaponticum acaule L. roots: Comparative study using HS-SPME/GC/GC–MS and hydrodistillation techniques

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Batoul Benyelles

2014-12-01

Full Text Available The composition of essential oil extracted from Rhaponticum acaule L. roots growing wild in Algeria was studied by hydrodistillation (HD and by Head-Space Solid Phase Micro-Extraction (HS-SPME. Quantitative but not qualitative differences have been found in the chemical composition of both analysed samples depending on the extraction method. However, the oil obtained from R. acaule roots shows that aliphatic alcohols were found to be the major class (69.2%, followed by the terpenes (5.5%, alkenes (5.2% and alkynes (4.0%. In both cases the analysis were carried out using Gas Chromatography (GC and Gas Chromatography–Mass Spectrometry (GC–MS. Our study shows that HS-SPME extraction could be considered as an alternative technique for the isolation of volatiles from plant. 25 components were identified in oil vs. 39 in the HS-SPME. However the oil composition of roots was mainly represented by a variety of aliphatic hydrocarbons (alcohols, aldehydes and ketones and terpenes which are known for their antimicrobial activities.

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

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Wong, S W; Schaffer, P A

1991-05-01

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

CoryneRegNet 4.0 – A reference database for corynebacterial gene regulatory networks

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Baumbach Jan

2007-11-01

Full Text Available Abstract Background Detailed information on DNA-binding transcription factors (the key players in the regulation of gene expression and on transcriptional regulatory interactions of microorganisms deduced from literature-derived knowledge, computer predictions and global DNA microarray hybridization experiments, has opened the way for the genome-wide analysis of transcriptional regulatory networks. The large-scale reconstruction of these networks allows the in silico analysis of cell behavior in response to changing environmental conditions. We previously published CoryneRegNet, an ontology-based data warehouse of corynebacterial transcription factors and regulatory networks. Initially, it was designed to provide methods for the analysis and visualization of the gene regulatory network of Corynebacterium glutamicum. Results Now we introduce CoryneRegNet release 4.0, which integrates data on the gene regulatory networks of 4 corynebacteria, 2 mycobacteria and the model organism Escherichia coli K12. As the previous versions, CoryneRegNet provides a web-based user interface to access the database content, to allow various queries, and to support the reconstruction, analysis and visualization of regulatory networks at different hierarchical levels. In this article, we present the further improved database content of CoryneRegNet along with novel analysis features. The network visualization feature GraphVis now allows the inter-species comparisons of reconstructed gene regulatory networks and the projection of gene expression levels onto that networks. Therefore, we added stimulon data directly into the database, but also provide Web Service access to the DNA microarray analysis platform EMMA. Additionally, CoryneRegNet now provides a SOAP based Web Service server, which can easily be consumed by other bioinformatics software systems. Stimulons (imported from the database, or uploaded by the user can be analyzed in the context of known

Elemental micro-PIXE mapping of hypersensitive lesions in Lagenaria sphaerica (Cucurbitaceae) resistant to Sphaerotheca fuliginea (powdery mildew)

Science.gov (United States)

Weiersbye-Witkowski, I. M.; Przybylowicz, W. J.; Straker, C. J.; Mesjasz-Przybylowicz, J.

1997-07-01

Genotypes of the Southern African cucurbit, Lagenaria sphaerica, that are resistant to powdery-mildew ( Sphaerotheca fuliginea) exhibit foliar hypersensitive (HS) lesions on inoculation with this fungal pathogen. Elemental distributions across radially symmetrical HS lesions, surrounding unlesioned leaf tissue and uninoculated leaf tissue, were obtained using the true elemental imaging system (Dynamic Analysis) of the NAC Van de Graaff nuclear microprobe. Raster scans of 3 MeV protons were complemented by simultaneous PIXE and BS point analyses. The composition of cellulose (C 6H 10O 5) was used as constant matrix composition for scans, and the sample thickness was found from BS spectra. Si and elements heavier than Ca contributed to matrix composition within HS lesions and the locally elevated Ca raised the limits of detection for some trace metals of interest. In comparison to uninoculated tissue, inoculated tissue was characterised by higher overall concentrations of all measured elements except Cu. Fully developed, 6 day-old HS lesions and the surrounding tissue could be divided into five zones, centred on the fungal infection site. Each zone was characterized by distinct local elemental distributions (either depletion, or accumulation to potentially phytotoxic levels).

Normal human serum (HS) prevents oxidant-induced lysis of cultured endothelial cells (ECs)

International Nuclear Information System (INIS)

Callahan, K.S.; Harlan, J.M.

1986-01-01

Most studies demonstrating oxidant lysis of cultured ECs are performed in serum-free media or media containing low concentrations of bovine serum. The authors found that HS protects human and bovine ECs from lysis caused by reagent H 2 O 2 or glucose/glucose oxidase (GO)-generated H 2 O 2 . EC injury was assessed by 51 Cr release, cell detachment, or trypan blue dye exclusion. Protective HS activity was dose-dependent with concentrations greater than or equal to 25% preventing lethal injury. Cytotoxicity at 24 hrs, induced by 20 mU/ml GO, was 90.1 +/- 5.2% without HS vs 1.7 +/- 4.6% with 25% HS present (20 exp). Similar protection was observed with heparinized plasma. Of note, comparable concentrations of bovine serum were devoid of protective activity. Addition of fatty acid-free albumin to the media was also without protective effect. Preliminary characterization showed HS activity was stable to 60 0 C for 30 min, non-dialyzable at 25,000 MW cutoff, and retained in delipidated serum. The HS protection was not merely due to scavenging of exogenous H 2 O 2 as A23187-induced EC lysis was also prevented by HS. Protective activity was not reproduced by purified cerruloplasmin or transferrin. In conclusion, unidentified factor(s) present in HS protect cultured ECs from oxidant-induced lysis. Since endothelium is normally exposed to 100% plasma, the authors suggest that in vitro studies of oxidant-mediated injury be performed in the presence of HS. Factor(s) in HS may play an important role in modulating oxidant-induced vascular injury in vivo

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

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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.

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).

The correlation between hs C-reactive protein and left ventricular mass in obese women

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Idrus Alwi

2006-06-01

Full Text Available Plasma C-reactive protein (CRP concentrations are increased in obese individuals. In this study, we examined the correlation between hsCRP and left ventricular mass (LV mass. Fourty five healthy obese women and fourty five healthy non obese women as the controls group were studied by echocardiography and hsCRP. There was no significant correlation between hsCRP and left ventricular mass in obese women (r = 0.29, p 0.06. There was a significant correlation between hs CRP and body mass index (r = 0.46, p 0,002, and also hsCRP and visceral fat (r= 0.33, p 0.03. (Med J Indones 2006; 15:100-4 Keywords: hs C-reactive protein, LV mass, obese women

Functional annotation of the genome unravels probiotic potential of Bacillus coagulans HS243.

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Kapse, N G; Engineer, A S; Gowdaman, V; Wagh, S; Dhakephalkar, P K

2018-05-30

Spore forming Bacillus species are widely used as probiotics for human dietary supplements and in animal feeds. However, information on genetic basis of their probiotic action is obscure. Therefore, the present investigation was undertaken to elucidate probiotic traits of B. coagulans HS243 through its genome analysis. Genome mining revealed the presence of an arsenal of marker genes attributed to genuine probiotic traits. In silico analysis of HS243 genome revealed the presence of multi subunit ATPases, ADI pathway genes, chologlycine hydrolase, adhesion proteins for surviving and colonizing harsh gastric transit. HS243 genome harbored vitamin and essential amino acid biosynthetic genes, suggesting the use of HS243 as a nutrient supplement. Bacteriocin producing genes highlighted the disease preventing potential of HS243. Thus, this work established that HS243 possessed the genetic repertoire required for surviving harsh gastric transit and conferring health benefits to the host which were further validated by wet lab evidences. Copyright © 2018. Published by Elsevier Inc.

Translation of LINE-1 DNA elements in vitro and in human cells

International Nuclear Information System (INIS)

Leibold, D.M.; Swergold, G.D.; Thayer, R.E.; Singer, M.F.; Fanning, T.G.; Dombroski, B.A.

1990-01-01

The LINE-1(L1) family of interspread DNA sequences found throughout the human genome (L1 Homo sapiens, L1Hs) includes active transposable elements. Current models for the mechanism of transposition involve reverse transcription of an RNA intermediate and utilization of element-encoded proteins. The authors report that an antiserum against the polypeptide encoded by the L1Hs 5' open reading frame (ORF1) detects, in human cells, an endogenous ORF1 protein as well as the ORG1 product of an appropriate transfecting recombinant vector. The endogenous polypeptide is most abundant in teratocarcinoma and choriocarcinoma cells, among those cell lines tested; it appears to be a single species of ∼38 kDa. In contrast, RNAs synthesized in vitro from cDNAs representing full-length, polyadenylylated cytoplasmic L1Hs RNA yield, upon in vitro translation, ORF1 products of slightly different sizes. This is consistent with the fact that the various cDNAs are different and represent transcription of different genomic L1Hs elements. In vitro studies additionally suggest that translation of ORF1 is initiated at the first AUG codon. Finally, in no case was an ORF1-ORF2 fusion protein detected

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.

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.

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

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

2016-04-19

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

Vegetable and Fruit Intakes Are Associated with hs-CRP Levels in Pre-Pubertal Girls

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Pilar Navarro

2017-03-01

Full Text Available The influence of diet on inflammation in children remains unclear. We aimed to analyze the influence of diet on high-sensitivity C-reactive protein (hs-CRP levels in a pre-pubertal population free of other influences that may affect hs-CRP levels. We determined hs-CRP levels in 571 six- to eight-year-old children using an hs-CRP ELISA kit. Information on food and nutrient intake was obtained through a food-frequency questionnaire. Overall dietary quality was assessed using the Healthy Eating Index (HEI. We found that girls in the highest tertile of hs-CRP levels had a higher intake of saturated fatty acid, and lower intakes of fiber and vitamin E and a lower HEI score when compared to those in tertiles 1 and 2. We also observed a significant decrease in fruit and vegetable intakes by hs-CRP tertile. Factor analysis showed that a dietary pattern that was loaded most strongly with vegetable, fruit, fiber and vitamin A and E intakes correlated negatively (−0.132, p < 0.05 with hs-CRP. No such association was found in boys. In conclusion, our data show that girls with a poorer quality diet show higher hs-CRP levels already at a pre-pubertal age.

Impact of Solutol HS 15 on the pharmacokinetic behavior of midazolam upon intravenous administration to male Wistar rats.

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Bittner, Beate; González, Roberto Carlos Bravo; Isel, Hughes; Flament, Christophe

2003-07-01

The pharmacokinetic profile of midazolam (MDZ) and its major metabolites 1'-OH-midazolam (1'OH-MDZ) and 4-OH-midazolam (4OH-MDZ) was investigated in rats. MDZ was administered intravenously at 5 mg/kg either in the absence (NaCl 0.9%, control group) or in the presence of the surfactant Solutol HS 15, a weak inhibitor of cytochrome P450 3A (CYP3A) activity in vitro (Solutol HS 15-treated group). It was found that the pharmacokinetic profiles of MDZ, 1'OH-MDZ and 4OH MDZ did not differ significantly in the two dosing vehicles (P values above 0.2). MDZ exhibited a high plasma clearance (Cl) of 79 and 92 ml/min/kg (corresponding to a blood Cl of 64 and 75 ml/min/kg), a high volume of distribution (V(d)) of 4.0 and 3.6 l/kg, and an area under the plasma concentration-time curve (AUC(t0-tinf)) of 1062 and 932 h.ng/ml in the control group and in the Solutol HS 15-treated group, respectively. The amount of MDZ excreted unchanged into urine was below 0.01% with both dosing vehicles. AUC(t0-tinf) in the control group was 12.3 h.ng/ml for 1'OH-MDZ and 38.8 h.ng/ml 4OH-MDZ. In the Solutol HS 15-treated group, AUC(t0-tinf) was 14 h.ng/ml for 1'OH-MDZ and 35.4 h.ng/ml for 4OH-MDZ. The metabolite concentrations excreted into urine were below the limit of quantification. In the rat, MDZ has a high blood clearance that is limited by liver blood flow. Therefore, weak CYP3A inhibitors like Solutol HS 15 are not likely to affect the hepatic blood clearance of MDZ in vivo.

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...

Investigating the Effect of Inflammation on Atrial Fibrillation Occurrence by Measuring Highly Sensitive C-reactive Protein (hs-CRP

Directory of Open Access Journals (Sweden)

Mahdi Hassanzadeh Delui

2014-05-01

Full Text Available Introduction: Atrial fibrillation (AF is the most prevalent cardiac arrhythmias that cardiologists and internists encounter. The goal of this article is to clarify an overview of the evidence linking inflammation to AF existence, which may highlight the effect of some pharmacological agents that have genuine potential to reduce the clinical burden of AF by modulating inflammatory pathways. Materials and Methods: In a case-control study, 50 patients with atrial fibrillation (AF with different etiologies and 50 patients with sinus rhythm and similar bases were selected. Sampling for highly sensitive c-reactive (hs-CRP was done on the patients presenting with AF to the Ghaem hospital between October 2006 and June 2007. Results: Mean age of the patients was 62 years with maximum of 90 and minimum of 36 and standard deviation of 13.80. The most frequent age group was 71-80years. Fifty-four percent of patients were male and 46% were female. Mean serum hs-CRP levels in AF patients with hypertension (HTN ,Ischemic heart disease(IHD, Valvular heart disease (VHD, HTN+IHD and hyperthyroidism were 8.10, 9.40, 8.68, 10.16 and 5.98 mg/Lit; respectively. There was significant difference between hs-CRP levels in hypertensive patients in the two groups (P=0.010. Similar results were observed in IHD patients, VHD patients and HTN+IHD patients in two groups (P=0.015, P=0.037, P=0.000. Conclusion: In addition to some risk factors like baseline cardiac diseases, aging, thyrotoxicosis, pulmonary embolism, pneumonia and cardiac surgery, there also appears to be consistent links between hs-CRP, a marker of inflammation, and the pathogenesis of AF. Introduction: Atrial fibrillation (AF is the most prevalent cardiac arrhythmias that cardiologists and internists encounter. The goal of this article is to clarify an overview of the evidence linking inflammation to AF existence, which may highlight the effect of some pharmacological agents that have genuine potential to

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

RoHS Compliance - Is the Global Electronics Industry Ready?

OpenAIRE

Head, Marieke; Hróarsson, Hallur

2006-01-01

RoHS is an EU directive that was proposed along with the WEEE Directive in 2002 as a part of a plan to promote extended producer responsibility within the electronics industry. Together, these two directives seek to make electrical and electronic equipment easier to manage both in terms of environmental impacts and recycling. The RoHS Directive seeks to remove lead, cadmium, mercury, hexavalent chromium and two brominated flame retardants from all consumer electrical equipment. This paper dea...

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.

Genome-wide characterization of differentially expressed genes provides insights into regulatory network of heat stress response in radish (Raphanus sativus L.).

Science.gov (United States)

Wang, Ronghua; Mei, Yi; Xu, Liang; Zhu, Xianwen; Wang, Yan; Guo, Jun; Liu, Liwang

2018-03-01

Heat stress (HS) causes detrimental effects on plant morphology, physiology, and biochemistry that lead to drastic reduction in plant biomass production and economic yield worldwide. To date, little is known about HS-responsive genes involved in thermotolerance mechanism in radish. In this study, a total of 6600 differentially expressed genes (DEGs) from the control and Heat24 cDNA libraries of radish were isolated by high-throughput sequencing. With Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, some genes including MAPK, DREB, ERF, AP2, GST, Hsf, and Hsp were predominantly assigned in signal transductions, metabolic pathways, and biosynthesis and abiotic stress-responsive pathways. These pathways played significant roles in reducing stress-induced damages and enhancing heat tolerance in radish. Expression patterns of 24 candidate genes were validated by reverse-transcription quantitative PCR (RT-qPCR). Based mainly on the analysis of DEGs combining with the previous miRNAs analysis, the schematic model of HS-responsive regulatory network was proposed. To counter the effects of HS, a rapid response of the plasma membrane leads to the opening of specific calcium channels and cytoskeletal reorganization, after which HS-responsive genes are activated to repair damaged proteins and ultimately facilitate further enhancement of thermotolerance in radish. These results could provide fundamental insight into the regulatory network underlying heat tolerance in radish and facilitate further genetic manipulation of thermotolerance in root vegetable crops.

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.

Clinical significance of determination of the levels of serum IL-6, TNF-α and hs-CRP in patients with DM2 complicated with coronary heart disease (CHD)

International Nuclear Information System (INIS)

Li Juan; Zhao Qian; Zhang Dajun

2007-01-01

Objective: To investigate the significance of changes of serum IL-6, TNF-α, hs-CRP levels in development of coronary heart disease in patients with type 2 diabetes mellitus. Methods: Serum IL-6, TNF-α (with RIA). hs-CRP (with CLIA) and FPG, TG, cholesterol (with biochemistry) contents were measured in (1) DM2 patients complicated with CHD, n=40 and (2) DlVI2 patients without CHD, n=48. Results: The BMI and FPG, TG levels were significantly higher in patients complicated with heart disease than those in patients without CHD (P<0.05) with the exception of cholesterol. The levels of IL-6, TNF-α and hs-CRP were also significantly higher in patients with heart disease than those in patients without heart disease (P<0.05). Conclusion: The high levels of IL-6, TNF-α and hs-CRP played important role in the development of coronary heart disease. Monitoring those levels might be helpful in assessment of treatment efficacy and outcome prediction. (authors)

Optimization of HS-SPME/GC-MS analysis and its use in the profiling of illicit ecstasy tablets (Part 1).

Science.gov (United States)

Bonadio, Federica; Margot, Pierre; Delémont, Olivier; Esseiva, Pierre

2009-05-30

A headspace solid-phase microextraction procedure (HS-SPME) was developed for the profiling of traces present in 3,4-methylenedioxymethylampethamine (MDMA). Traces were first extracted using HS-SPME and then analyzed by gas chromatography-mass spectroscopy (GC-MS). The HS-SPME conditions were optimized using varying conditions. Optimal results were obtained when 40 mg of crushed MDMA sample was heated at 80 degrees C for 15 min, followed by extraction at 80 degrees C for 15 min with a polydimethylsiloxane/divinylbenzene coated fibre. A total of 31 compounds were identified as traces related to MDMA synthesis, namely precursors, intermediates or by-products. In addition some fatty acids used as tabletting materials and caffeine used as adulterant, were also detected. The use of a restricted set of 10 target compounds was also proposed for developing a screening tool for clustering samples having close profile. 114 seizures were analyzed using an SPME auto-sampler (MultiPurpose Samples MPS2), purchased from Gerstel GMBH & Co. (Germany), and coupled to GC-MS. The data was handled using various pre-treatment methods, followed by the study of similarities between sample pairs based on the Pearson correlation. The results show that HS-SPME, coupled with the suitable statistical method is a powerful tool for distinguishing specimens coming from the same seizure and specimens coming from different seizures. This information can be used by law enforcement personnel to visualize the ecstasy distribution network as well as the clandestine tablet manufacturing.

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.

Developing competitive marketing and sales strategy for HS-Eden

OpenAIRE

Dragusha, Cajup

2016-01-01

Start-ups are faced with variety of challenges and uncertainty therefore comprehensive marketing and sales strategy must be in place to make sure that limited resources are spend wisely in order to minimize uncertainty and pave a path that would lead to successful business. HS Eden is a new-start-up venture created in Lappeenranta University of Technology with an ambition to develop AMB systems for commercial use. The aim of this study was to build a marketing and sales strategy to help HS-Ed...

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

Solutol HS 15, nontoxic polyoxyethylene esters of 12-hydroxystearic acid, reverses multidrug resistance.

Science.gov (United States)

Coon, J S; Knudson, W; Clodfelter, K; Lu, B; Weinstein, R S

1991-02-01

A recently developed non-ionic surfactant called Solutol HS 15 (poly-oxyethylene esters of 12-hydroxystearic acid), with low toxicity in vivo, was shown to reverse completely the multidrug resistance of KB 8-5 and KB 8-5-11 human epidermoid carcinoma cells in vitro but did not potentiate drug toxicity in drug-sensitive KB 3-1 cells. At a concentration of 10% of its own IC50 (mean concentration of drug that causes 50% inhibition of cell growth compared to controls), Solutol HS 15 produced a 35-, 28-, and 42-fold reduction in the resistance of KB 8-5-11 cells to colchicine, vinblastine, and doxorubicin, respectively. Solutol HS 15 was relatively much more potent than the prototypic reversing agent, verapamil, for reversing colchicine resistance, compared to the ability of each agent to reverse colchicine resistance, compared to the ability of each agent to reverse vinblastine resistance. Like verapamil, Solutol HS 15 promoted a 50-fold accumulation of rhodamine 123 in KB 8-5-11 cells, as measured by flow cytometry. Also, Solutol HS 15 and verapamil reduced the efflux of rhodamine 123 from KB 8-5-11 cells previously loaded with rhodamine 123 to a similar low rate. Solutol HS 15 did not affect the transport of alanine or glucose into KB 8-5-11 cells, indicating that its effect upon membrane active transport is not entirely nonspecific. Considering their different structure and different relative potency for reversing colchicine resistance, Solutol HS 15 and verapamil probably reverse multidrug resistance by different mechanisms. Solutol HS 15 merits consideration as a potential therapeutic agent because of its effectiveness for reversing multidrug resistance in vitro and its low toxicity in vivo.

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.

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

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.

Association of HS6ST3 gene polymorphisms with obesity and ...

Indian Academy of Sciences (India)

The heparan sulfate 6-O-sulfotransferase 3 (HS6ST3) gene is involved in heparan sulphate and heparin metabolism, and has been reported to be associated with diabetic retinopathy in type 2 diabetes. We hypothesized that HS6ST3 gene polymorphisms might play an important role in obesity and related phenotypes (such ...

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.

The Antifungal Plant Defensin HsAFP1 Is a Phosphatidic Acid-Interacting Peptide Inducing Membrane Permeabilization

Directory of Open Access Journals (Sweden)

Tanne L. Cools

2017-11-01

Full Text Available HsAFP1, a plant defensin isolated from coral bells (Heuchera sanguinea, is characterized by broad-spectrum antifungal activity. Previous studies indicated that HsAFP1 binds to specific fungal membrane components, which had hitherto not been identified, and induces mitochondrial dysfunction and cell membrane permeabilization. In this study, we show that HsAFP1 reversibly interacts with the membrane phospholipid phosphatidic acid (PA, which is a precursor for the biosynthesis of other phospholipids, and to a lesser extent with various phosphatidyl inositol phosphates (PtdInsP’s. Moreover, via reverse ELISA assays we identified two basic amino acids in HsAFP1, namely histidine at position 32 and arginine at position 52, as well as the phosphate group in PA as important features enabling this interaction. Using a HsAFP1 variant, lacking both amino acids (HsAFP1[H32A][R52A], we showed that, as compared to the native peptide, the ability of this variant to bind to PA and PtdInsP’s is reduced (≥74% and the antifungal activity of the variant is reduced (≥2-fold, highlighting the link between PA/PtdInsP binding and antifungal activity. Using fluorescently labelled HsAFP1 in confocal microscopy and flow cytometry assays, we showed that HsAFP1 accumulates at the cell surface of yeast cells with intact membranes, most notably at the buds and septa. The resulting HsAFP1-induced membrane permeabilization is likely to occur after HsAFP1’s internalization. These data provide novel mechanistic insights in the mode of action of the HsAFP1 plant defensin.

Poly(lactic-co-glycolic) Acid/Solutol HS15-Based Nanoparticles for Docetaxel Delivery.

Science.gov (United States)

Cho, Hyun-Jong; Park, Ju-Hwan; Kim, Dae-Duk; Yoon, In-Soo

2016-02-01

Docetaxel (DCT) is one of anti-mitotic chemotherapeutic agents and has been used for the treatment of gastric cancer as well as head and neck cancer, breast cancer and prostate cancer. Poly(lactic- co-glycolic) acid (PLGA) is one of representative biocompatible and biodegradable polymers, and polyoxyl 15 hydroxystearate (Solutol HS15) is a nonionic solubilizer and emulsifying agent. In this investigation, PLGA/Solutol HS15-based nanoparticles (NPs) for DCT delivery were fabricated by a modified emulsification-solvent evaporation method. PLGA/Solutol HS15/DCT NPs with about 169 nm of mean diameter, narrow size distribution, negative zeta potential, and spherical morphology were prepared. The results of solid-state studies revealed the successful dispersion of DCT in PLGA matrix and its amorphization during the preparation process of NPs. According to the result of in vitro release test, emulsifying property of Solutol HS15 seemed to contribute to the enhanced drug release from NPs at physiological pH. All these findings imply that developed PLGA/Solutol HS15-based NP can be a promising local anticancer drug delivery system for cancer therapy.

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.

Investigating the Effect of Inflammation on Atrial Fibrillation Occurrence by Measuring Highly Sensitive C-reactive Protein (hs-CRP

Directory of Open Access Journals (Sweden)

Mahdi Hassanzadeh Delui

2014-05-01

Full Text Available Introduction: Atrial fibrillation (AF is the most prevalent cardiac arrhythmias that cardiologists and internists encounter. The goal of this article is to clarify an overview of the evidence linking inflammation to AF existence, which may highlight the effect of some pharmacological agents that have genuine potential to reduce the clinical burden of AF by modulating inflammatory pathways. Materials and Methods: In a case-control study, 50 patients with atrial fibrillation (AF with different etiologies and 50 patients with sinus rhythm and similar bases were selected. Sampling for highly sensitive c-reactive (hs-CRP was done on the patients presenting with AF to the Ghaem hospital between October 2006 and June 2007. Results: Mean age of the patients was 62 years with maximum of 90 and minimum of 36 and standard deviation of 13.80. The most frequent age group was 71-80years. Fifty-four percent of patients were male and 46% were female. Mean serum hs-CRP levels in AF patients with hypertension (HTN ,Ischemic heart disease(IHD, Valvular heart disease (VHD, HTN+IHD and hyperthyroidism were 8.10, 9.40, 8.68, 10.16 and 5.98 mg/Lit; respectively. There was significant difference between hs-CRP levels in hypertensive patients in the two groups (P=0.010. Similar results were observed in IHD patients, VHD patients and HTN+IHD patients in two groups (P=0.015, P=0.037, P=0.000. Conclusion: In addition to some risk factors like baseline cardiac diseases, aging, thyrotoxicosis, pulmonary embolism, pneumonia and cardiac surgery, there also appears to be consistent links between hs-CRP, a marker of inflammation, and the pathogenesis of AF.

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

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Arindam Deb

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

Comparison of the atmospheric- and reduced-pressure HS-SPME strategies for analysis of residual solvents in commercial antibiotics using a steel fiber coated with a multiwalled carbon nanotube/polyaniline nanocomposite.

Science.gov (United States)

Ghiasvand, Ali Reza; Nouriasl, Kolsoum; Yazdankhah, Fatemeh

2018-01-01

A low-cost, sensitive and reliable reduced-pressure headspace solid-phase microextraction (HS-SPME) setup was developed and evaluated for direct extraction of residual solvents in commercial antibiotics, followed by determination by gas chromatography with flame ionization detection (GC-FID). A stainless steel narrow wire was made porous and adhesive by platinization by a modified electrophoretic deposition method and coated with a polyaniline/multiwalled carbon nanotube nanocomposite. All experimental variables affecting the extraction efficiency were investigated for both atmospheric-pressure and reduced-pressure conditions. Comparison of the optimal experimental conditions and the results demonstrated that the reduced-pressure strategy leads to a remarkable increase in the extraction efficiency and reduction of the extraction time and temperature (10 min, 25 °Ϲ vs 20 min, 40 °Ϲ). Additionally, the reduced-pressure strategy showed better analytical performances compared with those obtained by the conventional HS-SPME-GC-FID method. Limit of detections, linear dynamic ranges, and relative standard deviations of the reduced-pressure HS-SPME procedure for benzene, toluene, ethylbenzene, and xylene (BTEX) in injectable solid drugs were obtained over the ranges of 20-100 pg g -1 , 0.02-40 μg g -1 , and 2.8-10.2%, respectively. The procedure developed was successful for the analysis of BTEX in commercial containers of penicillin, ampicillin, ceftriaxone, and cefazolin. Graphical abstract Schematic representation of the developed RP-HS-SPME setup.

Changes in Cis-regulatory Elements during Morphological Evolution

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Yu-Lee Paul

2012-10-01

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

Association of Elevated High Sensitivity Cardiac Troponin T(hs-cTnT) Levels with Hemorrhagic Transformation and 3-Month Mortality in Acute Ischemic Stroke Patients with Rheumatic Heart Disease in China.

Science.gov (United States)

Liu, Junfeng; Wang, Deren; Xiong, Yao; Liu, Bian; Hao, Zilong; Tao, Wendan; Liu, Ming

2016-01-01

Elevated levels of high sensitivity cardiac troponin T (hs-cTnT) occur in a substantial proportion of patients with acute ischemic stroke (AIS) and can predict poor outcome and mortality after stroke. Whether elevated hs-cTnT levels can also predict hemorrhagic transformation (HT) or prognosis in AIS patients with rheumatic heart disease (RHD) remains unclear. Data from the Chengdu Stroke Registry on consecutive AIS patients with RHD admitted to West China Hospital within 1 month of stroke onset from October 2011 to February 2014 were examined. Clinico-demographic characteristics, HT, functional outcomes and stroke recurrence were compared between patients with elevated hs-cTnT levels (≥14 ng/L) and patients with normal hs-cTnT levels (mortality and 3-month disability/mortality (all P≤0.029). After controlling for age, sex, hypertension, renal impairment and National Institutes of Health Stroke Scale score on admission, the risk of HT and 3-month mortality was, respectively, 4.0- and 5.5-fold higher in patients with elevated hs-cTnT levels than in patients with normal hs-cTnT levels. Elevated hs-cTnT levels are independently associated with HT and 3-month mortality in AIS patients with RHD. These results with a small cohort should be verified and extended in large studies.

Effect of the administration time of HS6101 on hematopoietic recovery in ICR mice injured by cyclophosphamide

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Shuang XING

2015-06-01

Full Text Available Objective　To explore the effect of the administration time of HS6101 on hematopoietic recovery in ICR mice injured by cyclophosphamide (CTX. Methods　One hundred and three male ICR mice were divided into 4 groups: CTX control, HS6101 prevention, HS6101 treatment, and HS6101 prevention+treatment groups. CTX was intraperitoneally injected into the ICR mice at a dose of 100mg/(kg.d for three consecutive days to establish a chemotherapeutics-injured model. HS6101 at a dose of 27μg/mouse in 0.2ml was subcutaneously injected into the mice 1h before the first administration of CTX in HS6101-prevention group, 1h after the last administration of CTX in HS6101 treatment group, and both at 1h before the first administration and 1h after the last administration of CTX in HS6101 prevention + treatment group. Physiological saline was subcutaneously injected into the mice in CTX control group (0.2ml/mouse. 10μl peripheral blood was collected from the caudal vein for WBC, neutrophil lymphocyte, RBC and platelet counts on day -1, 3, 5, 7, 9, 11, 13, 15, 17 with the MEK-7222K cell analyzer, and the cell count was compared between HS6101 treatment mice and CTX control mice. Another 30 male ICR mice were used for bone marrow colony forming unit (CFU assay and bone marrow histopathological examination, and they were assigned into normal control, CTX control, HS6101 prevention, HS6101treatment and HS6101 prevention + treatment groups (each n=6. On the day 4 and day 9 after CTX injection, mice were sacrificed and bone marrow cells were collected from the left femur for mononuclear cell (MNC isolation. 1×104 MNCs were planted in 1.0ml mouse CFU culture medium M3434 and cultured in incubator with the temperature of 37℃, and 5% CO2 for 7 days. After that, granulocyte macrophage-colony-forming unit (GM-CFU, megakaryocyte colony forming unit (MK-CFU, mixture-colony-forming unit (Mix-CFU, burst-forming unit-erythroid (BFU-E and colony-forming unit-erythroid (CFU

Serum hsCRP: A Novel Marker for Prediction of Cerebrovascular Accidents (Stroke).

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Patgiri, Dibyaratna; Pathak, Mauchumi Saikia; Sharma, Pradeep; Kutum, Tridip; Mattack, Nirmali

2014-12-01

Strokes are caused by disruption of the blood supply to the brain. This may result from either blockage or rupture of a blood vessel. Yearly 15 million people worldwide suffer a stroke. India ranks second worldwide in terms of deaths from stroke. The incidence of stroke increases with age affecting the economically productive middle aged population. Hypertension and male sex are other risk factors for stroke. C-Reactive Protein (CRP) is an acute phase protein whose concentration rises in blood following inflammation. Formerly, assays for CRP detected its rise only after significant inflammation. However, recently developed high sensitivity assays (hsCRP) enable the measurement of CRP in individuals who are apparently healthy. Several studies indicate that hsCRP is elevated in individuals who are at risk of developing Coronary Artery Disease or Cerebrovascular events, the elevation may be found years before the first detection of vascular problems. In the absence of other biochemical markers, the present study aimed to evaluate the predictive and diagnostic role of hsCRP in stroke. The study consisted of 50 patients of acute stroke admitted in Gauhati Medical College and Hospital. The control population consisted of two groups - 50 age and sex matched controls with hypertension (Hypertensive control group) and 50 age and sex matched controls with no obvious disease constituted the Normal control group. hsCRP levels were measured in all the groups and compared statistically. hsCRP is an acute phase reactant whose concentration rises in stroke as well as in those at risk. The rise may be identified even before the appearance of risk factors. Hence, hsCRP may be useful as a predictive and diagnostic marker in stroke.

[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.

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.

Association of Elevated High Sensitivity Cardiac Troponin T(hs-cTnT Levels with Hemorrhagic Transformation and 3-Month Mortality in Acute Ischemic Stroke Patients with Rheumatic Heart Disease in China.

Directory of Open Access Journals (Sweden)

Junfeng Liu

Full Text Available Elevated levels of high sensitivity cardiac troponin T (hs-cTnT occur in a substantial proportion of patients with acute ischemic stroke (AIS and can predict poor outcome and mortality after stroke. Whether elevated hs-cTnT levels can also predict hemorrhagic transformation (HT or prognosis in AIS patients with rheumatic heart disease (RHD remains unclear.Data from the Chengdu Stroke Registry on consecutive AIS patients with RHD admitted to West China Hospital within 1 month of stroke onset from October 2011 to February 2014 were examined. Clinico-demographic characteristics, HT, functional outcomes and stroke recurrence were compared between patients with elevated hs-cTnT levels (≥14 ng/L and patients with normal hs-cTnT levels (<14 ng/L.The final analysis involved 84 patients (31 males; mean age, 61.6±12.2 years, of whom serum hs-cTnT levels were elevated in 58.3%. Renal impairment was independently associated with elevated hs-cTnT levels (OR 4.184, 95%CI 1.17 to 15.01, P = 0.028, and patients with elevated hs-cTnT levels were at significantly higher risk of HT, 3-month mortality and 3-month disability/mortality (all P≤0.029. After controlling for age, sex, hypertension, renal impairment and National Institutes of Health Stroke Scale score on admission, the risk of HT and 3-month mortality was, respectively, 4.0- and 5.5-fold higher in patients with elevated hs-cTnT levels than in patients with normal hs-cTnT levels.Elevated hs-cTnT levels are independently associated with HT and 3-month mortality in AIS patients with RHD. These results with a small cohort should be verified and extended in large studies.

Evaluation of Usefulness of hs-CRP and Ferritin Assays in Patients with Nasal Polyps

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Robert Partyka

2014-01-01

Full Text Available Background. Chronic nature of the nasal polyps, tendency to recurrence, and lack of satisfying treatment need the diagnostic’s parameters which show early inflammatory state as ferritin and hs-CRP. The Aim of Study. Assessment of hs-CRP and ferritin blood levels in nasal polyps patients in evaluation of treatment efficacy. Methods. All 38 patients were divided into 2 groups. Group I included 19 patients with anti-inflammatory therapy 2 weeks after surgery. Group II included 19 patients without anti-inflammatory therapy 2 weeks after surgery. The levels of hs-CRP and ferritin have been assessed before and 2 and 6 weeks after surgical treatment. Results. Research showed statistically significant difference of ferritin’s concentration between examined groups 6 weeks after surgery (P<0.05 and statistically significant difference of hs-CRP concentration 2 and 6 weeks after surgery (P<0.05. Conclusion. (1 The analysis of serum ferritin and hs-CRP concentrations can be useful in early postoperative detection of inflammatory state in patients with nasal polyps and for the effectiveness of therapy. (2 Lack of correlation between mean ferritin and hs-CRP serum levels, at each diagnostic and monitoring stage, shows that they are independent and cannot be determined interchangeably.

Isolation and characterization of an antifungal protein from Bacillus licheniformis HS10.

Science.gov (United States)

Wang, Zhixin; Wang, Yunpeng; Zheng, Li; Yang, Xiaona; Liu, Hongxia; Guo, Jianhua

2014-11-07

Bacillus licheniformis HS10 is a good biocontrol agent against Pseudoperonospora cubensis which caused cucumber downy disease. To identify and characterize the antifungal proteins produced by B.licheniformis HS10, the proteins from HS10 were isolated by using 30-60% ammonium sulfate precipitation, and purified with column chromatography on DEAE Sepharose Fast Flow, RESOURCE Q and Sephadex G-75. And the SDS-PAGE and MALDI-TOF/TOF-MS analysis results demonstrated that the antifungal protein was a monomer with molecular weight of about 55 kDa, identified as carboxypeptidase. Our experiments also showed that the antifungal protein from B. licheniformis HS10 had significantly inhibition on eight different kinds of plant pathogenic fungi, and it was stable with good biological activity at as high as 100°C for 30 min and in pH value ranged from 6 to 10. The biological activity was negatively affected by protease K and 10mM metal cations except Ca(2+). Copyright © 2014 Elsevier Inc. All rights reserved.

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

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Junhua Li

2014-01-01

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

Plasma YKL-40

DEFF Research Database (Denmark)

Jensen, Peter; Wiell, C; Milting, K

2013-01-01

Background  Plasma YKL-40 is an inflammatory biomarker. No useful biomarker exists in patients with psoriasis or psoriatic arthritis. Objective  To measure YKL-40 and high-sensitivity C-reactive protein (hs-CRP) in patients with psoriasis or psoriatic arthritis before and during treatment. Methods......-CRP at inclusion and during 48 weeks of adalimumab treatment. The patients with psoriatic arthritis were divided into responders and non-responders. Results  In patients with psoriasis, the baseline median PASI score was 10.8 and baseline YKL-40 was 45 μg/L. Seventeen per cent had elevated plasma YKL-40 compared...

Chemistry of superheavy elements

International Nuclear Information System (INIS)

Schaedel, M.

2012-01-01

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

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.

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

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

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

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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

Chemical experiments with superheavy elements.

Science.gov (United States)

Türler, Andreas

2010-01-01

Unnoticed by many chemists, the Periodic Table of the Elements has been extended significantly in the last couple of years and the 7th period has very recently been completed with eka-Rn (element 118) currently being the heaviest element whose synthesis has been reported. These 'superheavy' elements (also called transactinides with atomic number > or = 104 (Rf)) have been artificially synthesized in fusion reactions at accelerators in minute quantities of a few single atoms. In addition, all isotopes of the transactinide elements are radioactive and decay with rather short half-lives. Nevertheless, it has been possible in some cases to investigate experimentally chemical properties of transactinide elements and even synthesize simple compounds. The experimental investigation of superheavy elements is especially intriguing, since theoretical calculations predict significant deviations from periodic trends due to the influence of strong relativistic effects. In this contribution first experiments with hassium (Hs, atomic number 108), copernicium (Cn, atomic number 112) and element 114 (eka-Pb) are reviewed.

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'.

DHS HS-STEM Final Report.

Energy Technology Data Exchange (ETDEWEB)

Russell, Anna Christine [Sandia National Laboratories (SNL-CA), Livermore, CA (United States)

2014-09-01

Throughout my HS-STEM internship, I worked on two different projects with a systems analysis group at Sandia National Laboratories in Livermore, California (SNLCA). The first, and primary, project entailed building a conceptual model of health surveillance detection of a bioterror attack. The second project was much smaller in scope and looked at cost tradeoffs between volumetric and surface decontamination after the release of anthrax in a city. Both projects helped me to understand the challenges of planning for a bioterror attack and the importance of preparedness in the public health sector.

High-normal levels of hs-CRP predict the development of non-alcoholic fatty liver in healthy men.

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Jieun Lee

Full Text Available We performed a follow-up study to address whether high sensitivity C-reactive protein (hs-CRP levels within the normal range can predict the development of non-alcoholic fatty liver disease (NAFLD in healthy male subjects. Among15347 male workers between 30 and 59 years old who received annual health check-ups in 2002, a NAFLD-free cohort of 4,138 was followed through December 2009. Alcohol consumption was assessed with a questionnaire. At each visit, abdominal ultrasonography was performed to identify fatty liver disease. The COX proportional hazard model was used to evaluate the relationship between hs-CRP and incident NAFLD. During the follow-up period, 28.8% (1191 of 4138 of participants developed NAFLD. The hazard ratios of NAFLD were increased by hs-CRP categories within the normal range in the non-adjusted model and age-adjusted model. After adjusting for age, exercise, smoking, BMI, systolic BP, triglyceride, and fasting glucose, these incidences were only increased between the lowest and the highest hs-CRP categories. The risk for NAFLD increased as the hs-CRP level increased (p< 0.001. As the hs-CRP level increased within the healthy cohort, the risk of developing NAFLD increased. This trend remained true even if the hs-CRP level remained within the normal range. hs-CRP can be used as a predictor of NAFLD, as well as other obesity-associated diseases. Therefore, individuals with higher hs-CRP levels (even within the normal range may require appropriate follow-up and management to prevent NAFLD development.

On representations of Higher Spin symmetry algebras for mixed-symmetry HS fields on AdS-spaces. Lagrangian formulation

International Nuclear Information System (INIS)

Burdík, C; Reshetnyak, A

2012-01-01

We derive non-linear commutator HS symmetry algebra, which encode unitary irreducible representations of AdS group subject to Young tableaux Y(s 1 ,..., s k ) with κ ≥ 2 rows on d-dimensional anti-de-Sitter space. Auxiliary representations for specially deformed non-linear HS symmetry algebra in terms of generalized Verma module in order to additively convert a subsystem of second-class constraints in the HS symmetry algebra into one with first-class constraints are found explicitly for the case of HS fields for κ = 2 Young tableaux. The oscillator realization over Heisenberg algebra for obtained Verma module is constructed. The results generalize the method of auxiliary representations construction for symplectic sp(2κ) algebra used for mixed-symmetry HS fields on a flat spaces and can be extended on a case of arbitrary HS fields in AdS-space. Gauge-invariant unconstrained reducible Lagrangian formulation for free bosonic HS fields with generalized spin (s 1 , s 2 ) is derived.

Identification of distal regulatory regions in the human alpha IIb gene locus necessary for consistent, high-level megakaryocyte expression.

Science.gov (United States)

Thornton, Michael A; Zhang, Chunyan; Kowalska, Maria A; Poncz, Mortimer

2002-11-15

The alphaIIb/beta3-integrin receptor is present at high levels only in megakaryocytes and platelets. Its presence on platelets is critical for hemostasis. The tissue-specific nature of this receptor's expression is secondary to the restricted expression of alphaIIb, and studies of the alphaIIb proximal promoter have served as a model of a megakaryocyte-specific promoter. We have examined the alphaIIb gene locus for distal regulatory elements. Sequence comparison between the human (h) and murine (m) alphaIIb loci revealed high levels of conservation at intergenic regions both 5' and 3' to the alphaIIb gene. Additionally, deoxyribonuclease (DNase) I sensitivity mapping defined tissue-specific hypersensitive (HS) sites that coincide, in part, with these conserved regions. Transgenic mice containing various lengths of the h(alpha)IIb gene locus, which included or excluded the various conserved/HS regions, demonstrated that the proximal promoter was sufficient for tissue specificity, but that a region 2.5 to 7.1 kb upstream of the h(alpha)IIb gene was necessary for consistent expression. Another region 2.2 to 7.4 kb downstream of the gene enhanced expression 1000-fold and led to levels of h(alpha)IIb mRNA that were about 30% of the native m(alpha)IIb mRNA level. These constructs also resulted in detectable h(alpha)IIb/m(beta)3 on the platelet surface. This work not only confirms the importance of the proximal promoter of the alphaIIb gene for tissue specificity, but also characterizes the distal organization of the alphaIIb gene locus and provides an initial localization of 2 important regulatory regions needed for the expression of the alphaIIb gene at high levels during megakaryopoiesis.

MicroRNAs as regulatory elements in psoriasis

Directory of Open Access Journals (Sweden)

Liu Yuan

2016-01-01

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

TLR5 signaling enhances the proliferation of human allogeneic CD40-activated B cell induced CD4hiCD25+ regulatory T cells.

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Ping-Lung Chan

Full Text Available Although diverse functions of different toll-like receptors (TLR on human natural regulatory T cells have been demonstrated recently, the role of TLR-related signals on human induced regulatory T cells remain elusive. Previously our group developed an ex vivo high-efficient system in generating human alloantigen-specific CD4(hiCD25(+ regulatory T cells from naïve CD4(+CD25(- T cells using allogeneic CD40-activated B cells as stimulators. In this study, we investigated the role of TLR5-related signals on the generation and function of these novel CD4(hiCD25(+ regulatory T cells. It was found that induced CD4(hiCD25(+ regulatory T cells expressed an up-regulated level of TLR5 compared to their precursors. The blockade of TLR5 using anti-TLR5 antibodies during the co-culture decreased CD4(hiCD25(+ regulatory T cells proliferation by induction of S phase arrest. The S phase arrest was associated with reduced ERK1/2 phosphorylation. However, TLR5 blockade did not decrease the CTLA-4, GITR and FOXP3 expressions, and the suppressive function of CD4(hiCD25(+ regulatory T cells. In conclusion, we discovered a novel function of TLR5-related signaling in enhancing the proliferation of CD4(hiCD25(+ regulatory T cells by promoting S phase progress but not involved in the suppressive function of human CD40-activated B cell-induced CD4(hiCD25(+ regulatory T cells, suggesting a novel role of TLR5-related signals in the generation of induced regulatory T cells.

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)

Prediction of HS Soderberg plant PAH emissions from a laboratory evaluation of a pitch

Energy Technology Data Exchange (ETDEWEB)

Castonguay, L.; Mirtchi, A. A.; Proulx, A. L.; Savard, G.; Simard, E.; Steward, N.; Tremblay, C. [Alcan International Ltd., Arvida Research and Development Centre, Jonquiere, PQ (Canada)

1998-12-31

The presence of certain polycyclic aromatic hydrocarbons (PAHs) in coal tar pitch has been identified as a possible limit to the long-term viability of horizontal stud (HS) Soderberg technology, a technology of importance in the aluminum industry. This paper presents the results of a comparative study of pitch PAH content and HS Soderberg cell emissions. Laboratory results are compared with plant emissions for two regular and low PAH pitches with the same softening points. The results indicate the existence of a correlation between pitch PAH content and cell emission, which is valid for regular tar pitches, low tar pitches, as well as for hybrid pitches. These findings make it possible to predict the quantity and distribution of HS Soderberg cell PAH emissions from the analysis of PAHs in the pitch. The results also justify the conclusion that the emission of genotoxic compounds from pitch in the HS Soderberg technology can be decreased by using a pitch with low PAH content. 4 refs., 5 tabs., 5 figs.

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

Science.gov (United States)

Lim, Chun Shen; Brown, Chris M

2016-09-01

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

A3-Coupling catalyzed by robust Au nanoparticles covalently bonded to HS-functionalized cellulose nanocrystalline films

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Jian-Lin Huang

2013-07-01

Full Text Available We decorated HS-functionalized cellulose nanocrystallite (CNC films with monodisperse Au nanoparticles (AuNPs to form a novel nanocomposite catalyst AuNPs@HS-CNC. The uniform, fine AuNPs were made by the reduction of HAuCl4 solution with thiol (HS- group-functionalized CNC films. The AuNPs@HS-CNC nanocomposites were examined by X-ray photoelectron spectroscopy (XPS, TEM, ATR-IR and solid-state NMR. Characterizations suggested that the size of the AuNPs was about 2–3 nm and they were evenly distributed onto the surface of CNC films. Furthermore, the unique nanocomposite Au@HS-CNC catalyst displayed high catalytic efficiency in promoting three-component coupling of an aldehyde, an alkyne, and an amine (A3-coupling either in water or without solvent. Most importantly, the catalyst could be used repetitively more than 11 times without significant deactivation. Our strategy also promotes the use of naturally renewable cellulose to prepare reusable nanocomposite catalysts for organic synthesis.

Fatty acid methyl esters and Solutol HS 15 confer neuroprotection after focal and global cerebral ischemia.

Science.gov (United States)

Lin, Hung Wen; Saul, Isabel; Gresia, Victoria L; Neumann, Jake T; Dave, Kunjan R; Perez-Pinzon, Miguel A

2014-02-01

We previously showed that palmitic acid methyl ester (PAME) and stearic acid methyl ester (SAME) are simultaneously released from the sympathetic ganglion and PAME possesses potent vasodilatory properties which may be important in cerebral ischemia. Since PAME is a potent vasodilator simultaneously released with SAME, our hypothesis was that PAME/SAME confers neuroprotection in rat models of focal/global cerebral ischemia. We also examined the neuroprotective properties of Solutol HS15, a clinically approved excipient because it possesses similar fatty acid compositions as PAME/SAME. Asphyxial cardiac arrest (ACA, 6 min) was performed 30 min after PAME/SAME treatment (0.02 mg/kg, IV). Solutol HS15 (2 ml/kg, IP) was injected chronically for 14 days (once daily). Histopathology of hippocampal CA1 neurons was assessed 7 days after ACA. For focal ischemia experiments, PAME, SAME, or Solutol HS15 was administered following reperfusion after 2 h of middle cerebral artery occlusion (MCAO). 2,3,5-Triphenyltetrazolium staining of the brain was performed 24 h after MCAO and the infarct volume was quantified. Following ACA, the number of surviving hippocampal neurons was enhanced by PAME-treated (68%), SAME-treated (69%), and Solutol-treated HS15 (68%) rats as compared to ACA only-treated groups. Infarct volume was decreased by PAME (83%), SAME (68%), and Solutol HS15 (78%) as compared to saline (vehicle) in MCAO-treated animals. PAME, SAME, and Solutol HS15 provide robust neuroprotection in both paradigms of ischemia. This may prove therapeutically beneficial since Solutol HS15 is already administered as a solublizing agent to patients. With proper timing and dosage, administration of Solutol HS15 and PAME/SAME can be an effective therapy against cerebral ischemia.

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.

Modified application of HS-SPME for quality evaluation of essential oil plant materials.

Science.gov (United States)

Dawidowicz, Andrzej L; Szewczyk, Joanna; Dybowski, Michal P

2016-01-01

The main limitation in the standard application of head space analysis employing solid phase microextraction (HS-SPME) for the evaluation of plants as sources of essential oils (EOs) are different quantitative relations of EO components from those obtained by direct analysis of EO which was got in the steam distillation (SD) process from the same plant (EO/SD). The results presented in the paper for thyme, mint, sage, basil, savory, and marjoram prove that the quantitative relations of EO components established by HS-SPME procedure and direct analysis of EO/SD are similar when the plant material in the HS-SPME process is replaced by its suspension in oil of the same physicochemical character as that of SPME fiber coating. The observed differences in the thyme EO composition estimated by both procedures are insignificant (F(exp)HS-SPME procedure proposed in this paper substantially shortens the evaluation time of plant material quality and thus may improve the efficiency of analytical laboratories. Copyright © 2015 Elsevier B.V. All rights reserved.

Evaluation of the volatile profile of Tuber liyuanum by HS-SPME with GC-MS.

Science.gov (United States)

Liu, Changjiao; Li, Yu

2017-04-01

The volatile components of Tuber liyuanum were determined by HS-SPME with GC-MS for the first time. The effects of different fibre coating, extraction time, extraction temperature and sample amount were studied to get optimal extraction conditions. The optimal conditions were SPME fibre of Carboxen/PDMS, extraction time of 40 min, extraction temperature of 80 °C, sample amount of 2 g. Under these conditions 57 compounds in volatile of T. liyuanum were detected with a resemblance percentage above 80%. Aldehydes and aromatics were the main chemical families identified. The contribution of 3-Octanone(11.67%), phenylethyl alcohol (10.60%), isopentana (9.29%) and methylbutana (8.06%) for the total volatile profile were more significant in T. liyuanum than other compounds.

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.

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

The Role of the Media in South African Construction Health and Safety (H&S

Directory of Open Access Journals (Sweden)

John Smallwood

2012-11-01

Full Text Available A large number of fatalities and injuries occur in the South African construction industry. Traditionally, the print media have dedicated editorial, published news, articles and letters, and have exposed abusive or non-conforming conditions and practices in terms of H&S. Literature also indicates that the print media can influence and has an impact on H&S.Given the level of fatalities and injuries and the potential role of the print media, a postal survey was conducted among editors of construction and related magazines. Findings indicate that: the print media do contribute to and play a role in construction H&S; industry has the capacity and needs to promote H&S on a wider basis; there is a need to improve construction H&S; to a degree, editors are aware of what constitutes unsafe acts and unsafe conditions, and the print media can play an increased role through the review of articles, advertisements, advertorial, editorial and phototgraphs to prevent the depiction of unhealthy and unsafe practices and conditions

PRAS40 is an integral regulatory component of erythropoietin mTOR signaling and cytoprotection.

Directory of Open Access Journals (Sweden)

Zhao Zhong Chong

Full Text Available Emerging strategies that center upon the mammalian target of rapamycin (mTOR signaling for neurodegenerative disorders may bring effective treatment for a number of difficult disease entities. Here we show that erythropoietin (EPO, a novel agent for nervous system disorders, prevents apoptotic SH-SY5Y cell injury in an oxidative stress model of oxygen-glucose deprivation through phosphatidylinositol-3-kinase (PI 3-K/protein kinase B (Akt dependent activation of mTOR signaling and phosphorylation of the downstream pathways of p70 ribosomal S6 kinase (p70S6K, eukaryotic initiation factor 4E-binding protein 1 (4EBP1, and proline rich Akt substrate 40 kDa (PRAS40. PRAS40 is an important regulatory component either alone or in conjunction with EPO signal transduction that can determine cell survival through apoptotic caspase 3 activation. EPO and the PI 3-K/Akt pathways control cell survival and mTOR activity through the inhibitory post-translational phosphorylation of PRAS40 that leads to subcellular binding of PRAS40 to the cytoplasmic docking protein 14-3-3. However, modulation and phosphorylation of PRAS40 is independent of other protective pathways of EPO that involve extracellular signal related kinase (ERK 1/2 and signal transducer and activator of transcription (STAT5. Our studies highlight EPO and PRAS40 signaling in the mTOR pathway as potential therapeutic strategies for development against degenerative disorders that lead to cell demise.

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.

Mechanistic study of solubility enhancement of nifedipine using vitamin E TPGS or solutol HS-15.

Science.gov (United States)

Rajebahadur, Minal; Zia, Hossein; Nues, Anthony; Lee, Chong

2006-01-01

The objective of our study was to find mechanisms responsible for solubility enhancement of nifedipine in solid dispersions of vitamin E TPGS and/or solutol HS-15. Solid dispersions of nifedipine with selected polymers such as vitamin E TPGS, solutol HS-15, PEG(1,000), and lipocol C-10 of varying drug/polymer ratios were prepared by a fusion method. The solubility enhancement was found to be in the order of vitamin E TPGS > solutol HS-15 > lipocol C-10 > PEG(1,000). Lipocol C-10, with a similar hydrophilic-lipophilic value as vitamin E TPGS, showed a comparable retained solubility enhancement during saturation solubility studies but had lower dissolution profile. Overall, vitamin E TPGS showed the best solubility and dissolution performance, while solutol HS-15 and lipocol C-10 demonstrated moderate solubility enhancements. Solid dispersions of vitamin E TPGS as prepared by microfluidization technique initially showed slightly higher solubility compared with samples prepared by fusion method, but eventually it became the same as the study progressed. However, solid dispersion of solutol HS-15 as prepared by microfluidization demonstrated a significant, sustained increased in solubility over its sample when prepared by fusion method. Based on these results, we concluded that enhanced solubility using vitamin E TPGS and solutol HS-15 resulted from a partial conversion of crystalline drug to the amorphous form, increase in wettability of the drug by water soluble polymers, better separation of drug particles, micellar solubilization of drug by high concentrations of surfactant polymers, and interaction between polymer and drug at the molecular level.

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

Modification of the Armijo line search to satisfy the convergence properties of HS method

Directory of Open Access Journals (Sweden)

Mohammed Belloufi

2013-07-01

Full Text Available The Hestenes-Stiefel (HS conjugate gradient algorithm is a useful tool of unconstrainednumerical optimization, which has good numerical performance but no global convergence result under traditional line searches. This paper proposes a line search technique that guarantee the globalconvergence of the Hestenes-Stiefel (HS conjugate gradient method. Numerical tests are presented tovalidate the different approaches.

Human CD40 ligand-expressing type 3 innate lymphoid cells induce IL-10-producing immature transitional regulatory B cells.

Science.gov (United States)

Komlósi, Zsolt I; Kovács, Nóra; van de Veen, Willem; Kirsch, Anna Isabella; Fahrner, Heinz Benedikt; Wawrzyniak, Marcin; Rebane, Ana; Stanic, Barbara; Palomares, Oscar; Rückert, Beate; Menz, Günter; Akdis, Mübeccel; Losonczy, György; Akdis, Cezmi A

2017-09-20

Type 3 innate lymphoid cells (ILC3s) are involved in maintenance of mucosal homeostasis; however, their role in immunoregulation has been unknown. Immature transitional regulatory B (itBreg) cells are innate-like B cells with immunosuppressive properties, and the in vivo mechanisms by which they are induced have not been fully clarified. We aimed to investigate the ILC3-B-cell interaction that probably takes place in human tonsils. ILC3s were isolated from peripheral blood and palatine tonsils, expanded, and cocultured with naive B cells. Tonsillar ILC3s and regulatory B cells were visualized with immunofluorescence histology. ILC3 frequencies were measured in tonsil tissue of allergic and nonallergic patients and in peripheral blood of allergic asthmatic patients and healthy control subjects. A mutually beneficial relationship was revealed between ILC3s and B cells: ILC3s induced IL-15 production in B cells through B cell-activating factor receptor, whereas IL-15, a potent growth factor for ILC3s, induced CD40 ligand (CD40L) expression on circulating and tonsillar ILC3s. IL-15-activated CD40L + ILC3s helped B-cell survival, proliferation, and differentiation of IL-10-secreting, PD-L1-expressing functional itBreg cells in a CD40L- and B cell-activating factor receptor-dependent manner. ILC3s and regulatory B cells were in close connection with each other in palatine tonsils. ILC3 frequency was reduced in tonsil tissue of allergic patients and in peripheral blood of allergic asthmatic patients. Human CD40L + ILC3s provide innate B-cell help and are involved in an innate immunoregulatory mechanism through induction of itBreg cell differentiation, which takes place in palatine tonsils in vivo. This mechanism, which can contribute to maintenance of immune tolerance, becomes insufficient in allergic diseases. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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

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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

Effect of flurbiprofen aretilon on serum hs-CRP, IL-6 levels in patients undergoing esophageal cancer surgery

International Nuclear Information System (INIS)

Li Jiakai

2011-01-01

Objective: To investigate the effect of flurbiprofen axetil on serum high sensitivity C reactive protein (hs-CRP) and interleukin-6 (IL-6) in the patients undergoing esophageal cancer surgery. Methods: Thirty patients were divided into 2 groups with 15 cases each. The patients in groups A were given flurbiprofen axetil and those in group B were not as the controls. Serum hs-CRP (immuno-turbidity method) and IL-6 (RIA) levels were determined before anesthesia induction and after extubation. Results: The levels of serum hs-CRP, IL-6 were significantly higher in group B than those in group A (P<0.05). Conclusion: Flurbiprofen axetil could reduce serum hs-CRP, IL-6 levels in patients undergoing Esophageal cancer surgery. (authors)

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

Mechanism of mucosal permeability enhancement of CriticalSorb® (Solutol® HS15) investigated in vitro in cell cultures.

Science.gov (United States)

Shubber, Saif; Vllasaliu, Driton; Rauch, Cyril; Jordan, Faron; Illum, Lisbeth; Stolnik, Snjezana

2015-02-01

CriticalSorb™, with the principal component Solutol® HS15, is a novel mucosal drug delivery system demonstrated to improve the bioavailability of selected biotherapeutics. The intention of this study is to elucidate mechanism(s) responsible for the enhancement of trans-mucosal absorption of biological drugs by Solutol® HS15. Micelle size and CMC of Solutol® HS15 were determined in biologically relevant media. Polarised airway Calu-3 cell layers were used to measure the permeability of a panel of biological drugs, and to assess changes in TEER, tight junction and F-actin morphology. The rate of cell endocytosis was measured in vitro in the presence of Solutol® HS15 using a membrane probe, FM 2-10. This work initially confirms surfactant-like behaviour of Solutol® HS15 in aqueous media, while subsequent experiments demonstrate that the effect of Solutol® HS15 on epithelial tight junctions is different from a 'classical' tight junction opening agent and illustrate the effect of Solutol® HS15 on the cell membrane (endocytosis rate) and F-actin cytoskeleton. Solutol® HS15 is the principle component of CriticalSorb™ that has shown an enhancement in permeability of medium sized biological drugs across epithelia. This study suggests that its mechanism of action arises primarily from effects on the cell membrane and consequent impacts on the cell cytoskeleton in terms of actin organisation and tight junction opening.

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.

The Value of HbA1c and hs-CRP Combined Detection in Diagnosis of Diabetic Retinopathy%HbA1c、hs-CRP 联合检测诊断糖尿病视网膜病变的价值

Institute of Scientific and Technical Information of China (English)

李孝才; 孙学芬; 吴建霞; 马雪燕

2016-01-01

目的：探讨糖化血红蛋白（HbA1c）和高敏 C 反应蛋白（hs-CRP）联合检测诊断糖尿病视网膜病变的价值。方法：选择正常体检者(A 组）、糖尿病无视网膜病变者(B 组）、糖尿病视网膜病变者(C 组）各72例，采用离子交换液相层析法和胶乳增强免疫比浊法测定 HbA1c 及 hs-CRP。结果：无视网膜病变组和视网膜病变组的 HbA1c 和 hs-CRP（mg/L）含量均比健康对照组高，具有统计学意义（P0.05）；但是 HbA1c +Hs-CRP 诊断糖尿病视网膜病变的特异为90.3%，分别与 HbA1c 和 hs-CRP 存在明显差异（P 0.05); but specific to the HbA1c of hs CRP in the diagnosis of diabetic retinopathy was 90.3%, respectively and hs CRP and HbA1c exist significant difference (P< 0.05). Conclusion:The detection of HBA1c and Hs-CRPis helpful to early detection of diabetic retinopathy, which can be used asmonitoring indicators for progress and treatment effect in type 2 diabetes mellitus patients.

In vitro investigation on the impact of Solutol HS 15 on the uptake of colchicine into rat hepatocytes.

Science.gov (United States)

Bravo González, Roberto Carlos; Boess, Franziska; Durr, Evelyne; Schaub, Nathalie; Bittner, Beate

2004-07-26

In the current investigation, the impact of the surface-active formulation ingredient Solutol HS 15 on the uptake of colchicine into freshly isolated rat hepatocytes was investigated using a centrifugal filtration technique through a silicone oil layer. Colchicine is taken up into the cells by an active transport mechanism. When conducting the experiment at 37 degrees C, it was found that at concentrations below its critical micellar concentration (CMC) of 0.021% (0.0003 and 0.003%, w/v), Solutol HS 15 did not impact the uptake of colchicine. By contrast, at a Solutol HS 15 concentration above its CMC (0.03%, w/v), the amount of colchicine taken up into the cells as well as its uptake velocity were significantly decreased. However, in control experiments performed at 4 degrees C, a temperature at which active transport processes should be significantly slowed down, Solutol HS 15 at 0.03% did not affect colchicine uptake and/or its association with the cells. The described findings might be rationalized by inhibition of colchicine transport either due to direct interaction at the transport site or due to alterations of membrane properties in the presence of Solutol HS 15 at concentrations above its CMC. Moreover, a strong molecular interaction between Solutol HS 15 and colchicine as well as an incorporation of colchicine into micelles formed by Solutol HS 15, this way resulting in a limited contact of colchicine with the cells, cannot be excluded as contributors to the observed effect.

The carriage of potentially pathogenic β-haemolytic streptococci (β-HS in healthy adult inhabitants of Wielkopolska, Poland

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Maciej Bura

2016-09-01

Full Text Available Background . Acute pharyngitis is a common disease in primary health care patients. Beta-hemolytic streptococci (β-HS are a frequent etiological agent, while swab culture from the throat and palatine tonsils is the gold standard for diagnosis. Objectives. The evaluation of the prevalence of potentially pathogenic β-HS carriage in young adult inhabitants of Wielkopolska. Material and methods. The study included 205 healthy young adult (18–44 years old (29.0 ± 6.4 inhabitants (M – 95, F – 110 of Wielkopolska (Poland. Two swabs were taken from the throat: the first one was used to perform a rapid antigenic diagnostic test (RAD T for group A streptococci (GAS and the second to grow a conventional culture. If β-HS grew, isolates were serotyped according to Lancefield. In addition, simple demographic and medical data were collected from the subjects. The study was financed from funds granted within the first edition of the “Give a hand” project (Karol Marcinkowski Poznan University of Medical Sciences. Results . Positive throat cultures were obtained in 15.6% out of 205 persons (n = 32. The distribution of β-HS serogroup results was as follows: group C (GCS – 17 cases (53.1% of cases where β-HS was positive, group F (GFS – 9 cases (28.1%, GAS – 3 people (9.4% and group G (GGS – 3 subjects (9.4%. The growth of the discussed bacteria in cultures was moderate or high in 53% of these cases. RAD T was positive in 5 cases (but only one person had GAS in throat culture. The positive culture result was significantly more frequent in men (62.5% out of 32 cases with β-HS growth, p = 0.0460. Conclusions . 1. The possibility of β-HS carriage must be taken into account when analysing the results of throat swab cultures. 2. GAS carriage is significantly lower than non-GAS carriage. 3. GCS were the most prevalent among non-GAS. 4. Being male may predispose individuals to β-HS carriage.

Mutations in the newly identified RAX regulatory sequence are not a frequent cause of micro/anophthalmia.

Science.gov (United States)

Chassaing, Nicolas; Vigouroux, Adeline; Calvas, Patrick

2009-06-01

Microphthalmia and anophthalmia are at the severe end of the spectrum of abnormalities in ocular development. A few genes (SOX2, OTX2, RAX, and CHX10) have been implicated in isolated micro/anophthalmia, but causative mutations of these genes explain less than a quarter of these developmental defects. A specifically conserved SOX2/OTX2-mediated RAX expression regulatory sequence has recently been identified. We postulated that mutations in this sequence could lead to micro/anophthalmia, and thus we performed molecular screening of this regulatory element in patients suffering from micro/anophthalmia. Fifty-one patients suffering from nonsyndromic microphthalmia (n = 40) or anophthalmia (n = 11) were included in this study after negative molecular screening for SOX2, OTX2, RAX, and CHX10 mutations. Mutation screening of the RAX regulatory sequence was performed by direct sequencing for these patients. No mutations were identified in the highly conserved RAX regulatory sequence in any of the 51 patients. Mutations in the newly identified RAX regulatory sequence do not represent a frequent cause of nonsyndromic micro/anophthalmia.

Clinical diagnostic value of determination of plasma ET, Hcy and serum hs-CRP contents in patients with coronary heart diseases

International Nuclear Information System (INIS)

Chu Jingying; Zhu Xueming

2008-01-01

Objective: To study the clinical diagnostic value of determination of plasma ET, Hcy and serum hs-CRP contents in patients with coronary heart disease (CHD). Methods: Plasma ET, Hcy(with RIA) and serum hs-CRP (with immune turbidimetry) contents were determined in 38 patients with CHD and 35 controls. Results: Plasma ET, Hcy and serum hs-CRP concentration were significantly higher in CHD patients (than those in controls P<0.01). Plasma ET levels were significantly positively correlated with those of plasma Hcy and serum hs-CRP (r=0.6122, 0.5842, P<0.01). Conclusion: Detection of changes of plasma ET, Hcy and serum hs-CRP levels might be of prognostic importance in patients with CHD. (authors)

Protective activity of a novel resveratrol analogue, HS-1793, against DNA damage in 137Cs-irradiated CHO-K1 cells

International Nuclear Information System (INIS)

Jeong, Min Ho; Jo, Young Rae; Yang, Kwang Mo; Jeong, Dong Hyeok; Lee, Chang Geun; Oh, Su Jung; Jeong, Soo Kyung; Jo, Wol Soon; Lee, Ki Won

2014-01-01

Resveratrol has received considerable attention as a polyphenol with anti-oxidant, anti-carcinogenic, and anti-inflammatory effects. Radiation is an important component of therapy for a wide range of malignant conditions. However, it causes damage to normal cells and, hence, can result in adverse side effects. This study was conducted to examine whether HS-1793, a novel resveratrol analogue free from the restriction of metabolic instability and the high dose requirement of resveratrol, induces a protective effect against radiation-induced DNA damage. HS-1793 effectively scavenged free radicals and inhibited radiation-induced plasmid DNA strand breaks in an in vitro assay. HS-1793 significantly decreased reactive oxygen species and cellular DNA damage in 2 Gy-irradiated Chinese hamster ovary (CHO)-K1 cells. In addition, HS-1793 dose-dependently reduced the levels of phosphorylated H2AX in irradiated CHO-K1 cells. These results indicate that HS-1793 has chemical radioprotective activity. Glutathione levels and superoxide dismutase activity in irradiated CHO-K1 cells increased significantly following HS-1793 treatment. The enhanced biological anti-oxidant activity and chemical radioprotective activity of HS-1793 maintained survival of irradiated CHO-K1 cells in a clonogenic assay. Therefore, HS-1793 may be of value as a radioprotector to protect healthy tissue surrounding tumor cells during radiotherapy to obtain better tumor control with a higher dose. (author)

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

Comparative analysis of the aroma chemicals of Melissa officinalis using hydrodistillation and HS-SPME techniques

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Shakeel-u- Rehman

2017-05-01

Full Text Available Headspace solid-phase micro extraction (HS-SPME coupled with gas chromatography–mass spectrometry (GC–MS has been used for the chemical analysis of Melissa officinalis (leaves cultivated in Institute Germplasm. The HS-SPME analysis led to the identification of 22 components constituting 99.1% of the total volatile constituents present in the leaves whereas its hydrodistillate led to the identification of 24 volatile constituents constituting 98.1% of the volatile material. The chemical composition of the SPME and hydrodistilled extract of M. officinalis leaves comprised mainly of oxygenated monoterpenes (78.5% and 57.8% respectively and sesquiterpene hydrocarbons (14.9% and 29.7% respectively. The major components identified in the HS-SPME extract were citronellal (31.1%, citronellol (18.3%, β-caryophyllene (12.0%, (E-citral (11.9%, (Z-citral (9.6%, geraniol (3.6%, (Z-β-ocimene (3.1% and 1-octen-3-ol (2.0% whereas hydrodistilled essential oil was rich in (Z-citral (19.6%, β-caryophyllene (13.2%, (E-citral (11.2%, citronellal (10.2%, germacrene-d (8.3%, δ-3-carene (5.0%, 6-methyl-5-hepten-2-one (3.7% and citronellyl acetate (3.7%. The comparative analysis of volatile constituents of M. officinalis leaf extract using HS-SPME and hydrodistillation techniques shows both qualitative as well as quantitative differences. The current study is the first report involving rapid analysis of volatile components of M. officinalis by HS-SPME.

CriticalSorb: a novel efficient nasal delivery system for human growth hormone based on Solutol HS15.

Science.gov (United States)

Illum, Lisbeth; Jordan, Faron; Lewis, Andrew L

2012-08-20

The absorption enhancing efficiency of CriticalSorb for human growth hormone (MW 22 kDa) was investigated in the conscious rat model. The principle absorption enhancing component of CriticalSorb, Solutol HS15, comprises polyglycol mono- and di-esters of 12-hydroxystearic acid combined with free polyethylene glycol. When administering hGH nasally in rats with increasing concentrations of Solutol HS15, it was found that for a 10%w/v solution formulation a bioavailability of 49% was obtained in the first 2h after administration. Furthermore it was shown that the most effective ratio of Solutol HS15 to hGH was 4:1 on a mg to mg basis. Histopathology studies in rats after 5 days repeated nasal administration showed that Solutol HS15 had no toxic effect on the nasal mucosa. These results have been confirmed in a 6 month repeat nasal toxicity study in rats. It can be concluded that the principle absorption enhancing component of CriticalSorb - Solutol HS15 - is a potent and non- toxic nasal absorption enhancer that warrants further development. Copyright © 2012 Elsevier B.V. All rights reserved.

Genetic diversity and striatal gene networks: focus on the heterogeneous stock-collaborative cross (HS-CC mouse

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Belknap John

2010-10-01

Full Text Available Abstract Background The current study focused on the extent genetic diversity within a species (Mus musculus affects gene co-expression network structure. To examine this issue, we have created a new mouse resource, a heterogeneous stock (HS formed from the same eight inbred strains that have been used to create the collaborative cross (CC. The eight inbred strains capture > 90% of the genetic diversity available within the species. For contrast with the HS-CC, a C57BL/6J (B6 × DBA/2J (D2 F2 intercross and the HS4, derived from crossing the B6, D2, BALB/cJ and LP/J strains, were used. Brain (striatum gene expression data were obtained using the Illumina Mouse WG 6.1 array, and the data sets were interrogated using a weighted gene co-expression network analysis (WGCNA. Results Genes reliably detected as expressed were similar in all three data sets as was the variability of expression. As measured by the WGCNA, the modular structure of the transcriptome networks was also preserved both on the basis of module assignment and from the perspective of the topological overlap maps. Details of the HS-CC gene modules are provided; essentially identical results were obtained for the HS4 and F2 modules. Gene ontology annotation of the modules revealed a significant overrepresentation in some modules for neuronal processes, e.g., central nervous system development. Integration with known protein-protein interactions data indicated significant enrichment among co-expressed genes. We also noted significant overlap with markers of central nervous system cell types (neurons, oligodendrocytes and astrocytes. Using the Allen Brain Atlas, we found evidence of spatial co-localization within the striatum for several modules. Finally, for some modules it was possible to detect an enrichment of transcription binding sites. The binding site for Wt1, which is associated with neurodegeneration, was the most significantly overrepresented. Conclusions Despite the marked

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

Mesenchymal stem cells increase T-regulatory cells and improve healing following trauma and hemorrhagic shock.

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Gore, Amy V; Bible, Letitia E; Song, Kimberly; Livingston, David H; Mohr, Alicia M; Sifri, Ziad C

2015-07-01

Rodent lungs undergo full histologic recovery within 1 week following unilateral lung contusion (LC). However, when LC is followed by hemorrhagic shock (HS), healing is impaired. We hypothesize that the intravenous administration of mesenchymal stem cells (MSCs) in animals undergoing combined LC followed by HS (LCHS) will improve wound healing. Male Sprague-Dawley rats (n = 5-6 per group) were subjected to LCHS with or without the injection of a single intravenous dose of 5 × 10 MSCs following return of shed blood after HS. Rats were sacrificed 7 days following injury. Flow cytometry was used to determine the T-regulatory cell (Treg) population in peripheral blood. Lung histology was graded using a well-established lung injury score (LIS). Components of the LIS include average inflammatory cells per high-power field over 30 fields, interstitial edema, pulmonary edema, and alveolar integrity, with total scores ranging from 0 to 11. Data were analyzed by analysis of variance followed by Tukey's multiple comparison test, expressed as mean (SD). p healing with an LIS unchanged from naive. The addition of HS resulted in a persistently elevated LIS score, whereas the addition of MSCs to LCHS decreased the LIS score back to naive levels. The change in LIS was driven by a significant decrease in edema scores. In rats undergoing LC alone, 10.5% (3.3%) of CD4 cells were Tregs. The addition of HS caused no significant change in Treg population (9.3% [0.7%]), whereas LCHS + MSC significantly increased the population to 18.2% (6.8%) in peripheral blood (p healing following trauma and HS is improved by a single dose of MSCs given immediately after injury. This enhanced healing is associated with an increase in the Treg population and a significant decrease in lung edema score as compared with animals undergoing LCHS. Further study into the role of Tregs in MSC-mediated wound healing is warranted.

The HS6000/20 development system

International Nuclear Information System (INIS)

Schimmel, F.

1989-04-01

In the actual control system of MEA, NIKHEF-K three color displays are in use for graphical representation of the accelerator status information. At the moment the quality of the color displays is bad. The HS6000 development system of the English company Syntel seems to offer a possible solution to replace these displays. In the development system software is developed which finally may run on a target module. The target module, consisting of a processor card with memory and RS232 port and a graphical card, takes care for the control of a color display. The institute has disposed of an experimental set up during two weeks in order to investigate the possibilities and limitations of the development system. The HS6000 development system runs under the OS-9 multi-user and multi-tasking operating system. The operating system takes care for a part of the necessary software to render a computer valuable. The OS-9 operating system disposes of about 60 utility commands. A feature of OS-9 is the application of modular software technique which are based upon memory modules. The interface between the user and the internal functions of the operating system is formed from the shell, the OS-9 command-interpreter code. The software, which has to run on the target module, is written with the help of the Mmacs screen editor, the draw program and the medit editor. The draw program and the medit editor form part of the EGOS ( Enhanced Graphical Output Software) packet. The EGOS packet is a multi-tasking graphical interface for the OS-9 operating system. (author). 1 fig

HS.Register - An Audit-Trail Tool to Respond to the General Data Protection Regulation (GDPR).

Science.gov (United States)

Gonçalves-Ferreira, Duarte; Leite, Mariana; Santos-Pereira, Cátia; Correia, Manuel E; Antunes, Luis; Cruz-Correia, Ricardo

2018-01-01

Introduction The new General Data Protection Regulation (GDPR) compels health care institutions and their software providers to properly document all personal data processing and provide clear evidence that their systems are inline with the GDPR. All applications involved in personal data processing should therefore produce meaningful event logs that can later be used for the effective auditing of complex processes. Aim This paper aims to describe and evaluate HS.Register, a system created to collect and securely manage at scale audit logs and data produced by a large number of systems. Methods HS.Register creates a single audit log by collecting and aggregating all kinds of meaningful event logs and data (e.g. ActiveDirectory, syslog, log4j, web server logs, REST, SOAP and HL7 messages). It also includes specially built dashboards for easy auditing and monitoring of complex processes, crossing different systems in an integrated way, as well as providing tools for helping on the auditing and on the diagnostics of difficult problems, using a simple web application. HS.Register is currently installed at five large Portuguese Hospitals and is composed of the following open-source components: HAproxy, RabbitMQ, Elasticsearch, Logstash and Kibana. Results HS.Register currently collects and analyses an average of 93 million events per week and it is being used to document and audit HL7 communications. Discussion Auditing tools like HS.Register are likely to become mandatory in the near future to allow for traceability and detailed auditing for GDPR compliance.

Tumor vessel normalization by the PI3K inhibitor HS-173 enhances drug delivery.

Science.gov (United States)

Kim, Soo Jung; Jung, Kyung Hee; Son, Mi Kwon; Park, Jung Hee; Yan, Hong Hua; Fang, Zhenghuan; Kang, Yeo Wool; Han, Boreum; Lim, Joo Han; Hong, Soon-Sun

2017-09-10

Tumor vessels are leaky and immature, which causes poor oxygen and nutrient supply to tumor vessels and results in cancer cell metastasis to distant organs. This instability of tumor blood vessels also makes it difficult for anticancer drugs to penetrate and reach tumors. Numerous tumor vessel normalization approaches have been investigated for improving drug delivery into tumors. In this study, we investigated whether phosphoinositide 3-kinase (PI3K) inhibitors are able to improve vascular structure and function over the prolonged period necessary to achieve effective vessel normalization. The PI3K inhibitors, HS-173 and BEZ235 potently suppressed tumor growth and hypoxia, and increased tumor apoptosis in animal models. PI3K inhibitors also induced a regular, flat monolayer of endothelial cells (ECs) in vessels, improving stability of vessel structure, and normalized tumor vessels by increasing vascular maturity, pericyte coverage, basement membrane thickness, and tight-junctions. These effects resulted in a decrease in tumor vessel tortuosity and vessel thinning, and improved vessel function and blood flow. The tumor vessel stabilization effect of the PI3K inhibitor HS-173 also decreased the number of metastatic lung nodules in vivo metastasis model. Furthermore, HS-173 improved the delivery of doxorubicin into the tumor region, enhancing its anticancer effects. Mechanistic studies suggested that PI3K inhibitor HS-173-induced vessel normalization reflected changes in endothelial Notch signaling. Taken together, our findings indicate that vessel normalization by PI3K inhibitors restrained tumor growth and metastasis while improving chemotherapy by enhancing drug delivery into the tumor, suggesting that HS-173 may have a therapeutic value as an enhancer or an anticancer drug. Copyright © 2017 Elsevier B.V. All rights reserved.

HURRICANE AND SEVERE STORM SENTINEL (HS3) FLIGHT REPORTS V1

Data.gov (United States)

National Aeronautics and Space Administration — The Hurricane and Severe Storm Sentinel (HS3) Flight Reports provide information about flights flown by the WB-57 and Global Hawk aircrafts during the Hurricane and...

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.

Changes of serum tumor markers, immunoglobulins, TNF-α and hs-CRP levels in patients with breast cancer and its clinical significance

Institute of Scientific and Technical Information of China (English)

Jian-Gang Dai; Yong-Feng Wu; Mei Li

2017-01-01

Objective: To study the serum tumor markers, immunoglobulin, TNF-α and hs-CRP in breast cancer in different pathological stages of the concentration, and to analyze the clinical significance of early diagnosis of breast cancer. Methods: A total of 130 patients with breast cancer were divided into stage I, II, III and IV according to clinical pathology. In addition, 40 patients with benign breast disease and 35 healthy subjects were selected as benign breast disease group and control group. Serum tumor markers, immunoglobulins, TNF-αand hs-CRP concentrations were measured and compared of all subjects. Results: There were no significant difference in serum tumor markers, immunoglobulin and inflammatory factors between the control group and the benign breast cancer group. The level of serum tumor markers in breast cancer group was significantly higher than that in control group and benign breast cancer group. The levels of serum CA125, CA153 and CEA were gradually increased with the severity enhancing from stage I and IV of breast cancer, and he difference was statistically significant. The level of serum immunoglobulin in breast cancer group was significantly higher than that in control group and benign breast cancer group. The levels of serum IgG and IgM increased gradually severity enhancing from stage I and IV of breast cancer, and the difference was statistically significant. The level of serum TNF-α and hs-CRP in serum of breast cancer group was significantly higher than that of control group and benign breast cancer group. The serum levels of TNF-α and hs-CRP increased gradually with severity enhancing from stage I and IV of breast cancer, and the difference was statistically significant. Conclusion: The level of serum tumor markers in breast cancer patients is increasing. Humoral and inflammatory responses are activated to varying degrees and increase with the aggregation of disease. They may involve regulating the occurrence and metastasis of breast

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

A Novel Shape-Free Plane Quadratic Polygonal Hybrid Stress-Function Element

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Pei-Lei Zhou

2015-01-01

Full Text Available A novel plane quadratic shape-free hybrid stress-function (HS-F polygonal element is developed by employing the principle of minimum complementary energy and the fundamental analytical solutions of the Airy stress function. Without construction of displacement interpolation function, the formulations of the new model are much simpler than those of the displacement-based polygonal elements and can be degenerated into triangular or quadrilateral elements directly. In particular, it is quite insensitive to various mesh distortions and even can keep precision when element shape is concave. Furthermore, the element does not show any spurious zero energy modes. Numerical examples show the excellent performance of the new element, denoted by HSF-AP-19β, in both displacement and stress solutions.

Clinical significance of determination of serum hypersensitive C reactive protein (HS-CRP) levels in patients with acute coronary syndrome (ACS)

International Nuclear Information System (INIS)

Zhai Chunxi; Zhang Fengju; Wang Kejun

2005-01-01

Objective: To study the relationship between changes in serum HS-CRP levels and the status of atherosclerotic plaques in patients with ACS. Methods: Serum HS-CRP levels were measured in 35 patients with ACS at admission, 1 week and 1 month later as well as in 30 controls without recent infection. Results: HS-CRP levels in patients with ACS were significantly higher than those in the controls (P<0.01). The levels were highest at admission and fell gradually. Conclusion: HS-CRP could be a marker reflecting the status of atherosclerotic plaques in patients with ACS. (authors)

Chronic lymphocytic leukemia cells acquire regulatory B-cell properties in response to TLR9 and CD40 activation.

Science.gov (United States)

Ringelstein-Harlev, Shimrit; Avivi, Irit; Fanadka, Mona; Horowitz, Netanel A; Katz, Tami

2018-02-15

Circulating chronic lymphocytic leukemia (CLL) cells share phenotypic features with certain subsets of regulatory B-cells (Bregs). The latter cells have been reported to negatively regulate immune cell responses, mostly by provision of IL-10. The purpose of the current study was to identify and delineate Breg properties of CLL cells. B-cells and T-cells were obtained from the peripheral blood of untreated CLL patients diagnosed according to the 2008 Guidelines of the International Workshop on Chronic Lymphocytic Leukemia. Co-culture assays were used to examine the ability of CLL cells to suppress autologous T-cell immune responses. IL-10 potency of CLL cells was assessed following stimulation with activators of the toll-like receptor 9 (TLR9) or CD40 and was correlated with the inhibitory activity of the cells. TLR9-activated CLL cells were found to increase the frequency of CD4 + CD25 hi FOXp3 + regulatory T-cells (Tregs) and to inhibit autologous CD4 + T-cell proliferation. This signaling cascade proved to control IL-10 generation in CLL cells, which in turn promoted the inhibition of T-cell proliferation by CLL cells. However, CD40 activation of CLL cells, while exhibiting a similar ability to augment Treg frequency, did not either affect IL-10 generation or T-cell proliferation. In conclusion, CLL cells demonstrate a unique clonal quality of adopting Breg properties which promote modulation of T-cell characteristics. TLR9 appears to be a potent activator of regulatory abilities in CLL cells, possibly contributing to preferential immune escape of TLR9-responsive cells.

In silico Analysis of osr40c1 Promoter Sequence Isolated from Indica Variety Pokkali

OpenAIRE

W.S.I. de Silva; M.M.N. Perera; K.L.N.S. Perera; A.M. Wickramasuriya; G.A.U. Jayasekera

2017-01-01

The promoter region of a drought and abscisic acid (ABA) inducible gene, osr40c1, was isolated from a salt-tolerant indica rice variety Pokkali, which is 670 bp upstream of the putative translation start codon. In silico promoter analysis of resulted sequence showed that at least 15 types of putative motifs were distributed within the sequence, including two types of common promoter elements, TATA and CAAT boxes. Additionally, several putative cis-acing regulatory elements which may be involv...

Performance Analysis of an Enhanced PRMA-HS Protocol for LEO Satellite Communication

Institute of Scientific and Technical Information of China (English)

ZHUO Yong-ning; YAN Shao-hu; WU Shi-qi

2005-01-01

The packet reservation multiple access with hindering state (PRMA-HS) is a protocol suitable for LEO satellite mobile communication. Although working well with light system payload (amount of user terminals), the protocol imposes high channel congestion on system with heavy payload, thus degrades the system's quality of service. To controlling the channel congestion, a scheme of enhanced PRMA-HS protocol is proposed, which aims to reduce the collision of voice packets by adopting a mechanism of access control. Through theoretic analysis, the system's mathematic model is presented and the packet drop probability of the scheme is deduced. To testify the performance of the scheme, a simulation is performed and the results support our analysis.

Microanalysis of oligosaccharide HS203 in beagle dog plasma by postcolumn fluorescence derivatization method.

Science.gov (United States)

Sun, Shumeng; Zhao, Xia; Li, Guangsheng; Yu, Guangli; Xing, Xiaoxu; Zeng, Yangyang; Wu, Jian; Wang, Jianing

2012-06-20

A rapid and sensitive postcolumn fluorescence derivatization method was developed for microanalysis of antidiabetic oligosaccharide HS203 in beagle dog plasma. After plasma protein was removed by a simple and fast ultrafiltration method, chromatographic separation was performed on an Asahipak GS-320 HQ column with a mobile phase of 50 mmol/L phosphate buffer (pH 6.7) and acetonitrile (83/17, v/v). The column effluent was monitored by fluorescence detection at 249 nm (excitation) and 435 nm (emission) using guanidine hydrochloride as a postcolumn derivatizing reagent. A satisfactory resolution of the analyte was achieved and the limit of detection was found to be 4 ng (more sensitive than silver staining of HS203 in polyacrylamide gel electrophoresis). The method described above was successfully applied to a pharmacokinetic study of HS203 and to monitor blood glucose level simultaneously in beagle dog. It is also possible to be applied for microanalysis of other oligosaccharides in biological samples. Copyright © 2012 Elsevier Ltd. All rights reserved.

Increased hsCRP is associated with higher risk of aortic valve replacement in patients with aortic stenosis

DEFF Research Database (Denmark)

Blyme, Adam; Nielsen, Olav W.; Asferg, Camilla

2016-01-01

Objective To investigate relations between inflammation and aortic valve stenosis (AS) by measuring high-sensitivity C-reactive protein, at baseline (hsCRP0) and after 1 year (hsCRP1) and exploring associations with aortic valve replacement (AVR). Design We examined 1423 patients from...... the Simvastatin and Ezetimibe in Aortic Stenosis study. Results During first year of treatment, hsCRP was reduced both in patients later receiving AVR (2.3 [0.9–4.9] to 1.8 [0.8–5.4] mg/l, p CRP1...... predicted later AVR (HR = 1.17, p CRP0 (HR = 0.96, p = 0.33), aortic valve area (AVA) and other risk factors. A higher rate of AVR was observed in the group with high hsCRP0 and an increase during the first year (AVRhighCRP0CRP1inc=47.3% versus AVRhighCRP0CRP1dec=27.5%, p

76 FR 64043 - Iowa Regulatory Program

Science.gov (United States)

2011-10-17

...) Requirements for permits for special categories of mining. 27--40.41(207) Permanent regulatory program--small... DEPARTMENT OF THE INTERIOR Office of Surface Mining Reclamation and Enforcement 30 CFR Part 915 [Docket No. IA-016-FOR; Docket ID: OSM-2011-0014] Iowa Regulatory Program AGENCY: Office of Surface Mining...

Impact of Solutol HS 15 on the pharmacokinetic behaviour of colchicine upon intravenous administration to male Wistar rats.

Science.gov (United States)

Bittner, Beate; González, Roberto Carlos Bravo; Walter, Isabelle; Kapps, Martin; Huwyler, Jörg

2003-05-01

In the current investigation, the alkaloid colchicine was administered intravenously to male Wistar rats both as a solution in isotonic sodium chloride (NaCl 0.9%, control group) and in NaCl 0.9%:Solutol HS 15 (95:5) at 1.5 mg/kg. At predetermined time points, plasma and urine were collected from the animals and analysed for colchicine and its demethylated metabolites by LC/MS-MS. In the presence of Solutol HS 15, colchicine clearance (CI) was significantly decreased and its maximum plasma concentration (c(max)) was significantly increased as compared to the control group (CI: 15.6+/-7.0 ml/min/kg vs 34.3+/-2.3 ml/min/kg; c(max) 3055.1+/-587.4 h vs 1260.1+/-223.7 h; pSolutol HS 15 treated group (41.50+/-3.23 vs 1.17+/-0.41% of total dose; pSolutol HS 15 compared with surfactant-free incubations (overall means: 72.25+/-0.50% for FF, 0.80+/-0.02 for lambda, 0.46+/-0.04 for K(e)). In vitro, in rat hepatocytes, the clearance of colchicine was significantly reduced at 0.003% Solutol HS 15 present in the incubation medium (0.86+/-0.15 microl/min/10(-6) cells vs 1.46+/-0.06 microl/min/10(-6) cells). As colchicine exhibits a comparatively high aqueous solubility, an impact of Solutol HS 15 on the solubility of the alkaloid is very unlikely to be a reason for the observed effect. Therefore, our results indicate that the most likely reasons for the changed pharmacokinetic behaviour of colchicine in the presence of Solutol HS 15 are alterations of metabolism and/or transport as well as distribution and elimination processes. Copyright 2003 John Wiley & Sons, Ltd.

Study of High Sensitive C-Reactive Protein (HS-CRP) After Cardiac Rehabilitation Program in Patients Undergoing Isolated CABG.

Science.gov (United States)

Johari Moghadam, Adel; Azizinejad, Saied

2016-12-01

Although cardiac rehabilitation is known as a tool to reduce the overall risk of cardiovascular complications, its specific role in the reduction of hs-CRP as a marker of inflammation and a proven marker of cardiovascular risk needs further investigation. The present study aims at elucidating the effects of a full course of conventional cardiac rehabilitation program for the period of eight weeks, on the levels of hs-CRP in patients who underwent isolated coronary artery bypass surgery. In this case study, 30 consecutive patients who underwent isolated coronary artery bypass surgery (isolated CABGS), and a full 8-week cardiac rehabilitation program in Tehran Heart Center, were investigated. A group of 30 similar patients, who enrolled in the same period of rehabilitation program but did not participate in practice, was considered as a control group. Serum levels of hs-CRP in both groups were measured retrospectively and in similar days before the start of rehabilitation program and at the end of it (or 8 weeks after initial registration for the control group). Levels of hs-CRP in the rehabilitation group and control group were 5.9 7.7 and 6.3 6.9 respectively before start of the program which was not statistically meaningful ( P -Value = 0.833). However, after the program, level of hs-CRP in the two tested groups changed to 2.3 5.1 and 5.7 6.1 respectively which showed a meaningful correlation ( P -Value = 0.023). These results also showed that decrease in hs-CRP level in the rehabilitated group but not in the control group was statistically meaningful (with P -Value of 0.037 and 0.0723 respectively). In patients undergoing coronary bypass surgery, participating in a full course of cardiac rehabilitation for 8 weeks has resulted in a significant reduction in hs-CRP levels as a marker of cardiovascular risk.

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.

Consequences of reductive evolution for gene expression in an obligate endosymbiont.

Science.gov (United States)

Wilcox, Jennifer L; Dunbar, Helen E; Wolfinger, Russell D; Moran, Nancy A

2003-06-01

The smallest cellular genomes are found in obligate symbiotic and pathogenic bacteria living within eukaryotic hosts. In comparison with large genomes of free-living relatives, these reduced genomes are rearranged and have lost most regulatory elements. To test whether reduced bacterial genomes incur reduced regulatory capacities, we used full-genome microarrays to evaluate transcriptional response to environmental stress in Buchnera aphidicola, the obligate endosymbiont of aphids. The 580 genes of the B. aphidicola genome represent a subset of the 4500 genes known from the related organism, Escherichia coli. Although over 20 orthologues of E. coli heat stress (HS) genes are retained by B. aphidicola, only five were differentially expressed after near-lethal heat stress treatments, and only modest shifts were observed. Analyses of upstream regulatory regions revealed loss or degradation of most HS (sigma32) promoters. Genomic rearrangements downstream of an intact HS promoter yielded upregulation of a functionally unrelated and an inactivated gene. Reanalyses of comparable experimental array data for E. coli and Bacillus subtilis revealed that genome-wide differential expression was significantly lower in B. aphidicola. Our demonstration of a diminished stress response validates reports of temperature sensitivity in B. aphidicola and suggests that this reduced bacterial genome exhibits transcriptional inflexibility.

Clinical significance of measurement of serum hs-CRP, TNF-α and M-CSF levels after treatment in patients with periodontitis

International Nuclear Information System (INIS)

Zhang Yunming

2007-01-01

Objective: To explore the significance of changes of serum hs-CRP, TNF-α and M-CSF levels after treatment in patients with periodontitis. Methods: Serum TNF-α, M-CSF (with RIA), hs-CRP (with immuneturbitity method) levels were determined in 38 patients with periodontitis both before and after treatment as well as in 35 controls. Results: Before treatment, the serum hs-CRP, TNF-α and M-CSF levels were significantly higher in the patients than those in controls (P 0.05). Conclusion: Detection of serum hs-CRP, TNF-α and M-CSF levels might reflect the progress of disease in patients with periodontitis. (authors)

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

Mechanism of mucosal permeability enhancement of CriticalSorb® (Solutol® HS15) investigated In Vitro in cell cultures.

OpenAIRE

Shubber, Saif; Vllasaliu, Driton; Rauch, Cyril; Jordan, Faron; Illum, Lisbeth; Stolnik, Snjezana

2015-01-01

Purpose CriticalSorb?, with the principal component Solutol? HS15, is a novel mucosal drug delivery system demonstrated to improve the bioavailability of selected biotherapeutics. The intention of this study is to elucidate mechanism(s) responsible for the enhancement of trans-mucosal absorption of biological drugs by Solutol? HS15. Methods Micelle size and CMC of Solutol? HS15 were determined in biologically relevant media. Polarised airway Calu-3 cell layers were used to measure the permeab...

Analysis of relationship between blood lipid metabolism levels and hs-CRP levels in patients with chronic obstructive pulmonary disease

International Nuclear Information System (INIS)

You Fengjian

2011-01-01

Objective: To study the relationship between blood lipid metabolism levels and hs-CRP levels in the patients with chronic obstructive pulmonary disease. Methods: The levels of plasma blood lipid (with biochemistry) and serum hs-CRP(with high-sensitive immuno turbidimetry) were determined in 96 patients with chronic obstructive pulmonary disease as well as 68 normal controls. Results: The plasma blood lipid levels in 96 patients with chronic obstructive pulmonary disease were significantly lower than those in 68 controls, plasma TC and LDL-C levels were not much difference (P>0.05), plasma HDL-C level was significantly difference (P<0.05), but TG and Lp (a) levels were very prominently difference (P<0.01). And the plasma hs-CRP level was significantly increased also (P<0.01). The close relationship was between blood lipid and hs-CRP levels. Conclusion: The study of relationship between blood lipid levels and hs-CRP levels in patients with COPD was helpful for understand the disease process as well as possible mechanisms. (authors)

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.

Effect of the additives on clouding behavior and thermodynamics of coenzyme Q10-Kolliphor HS15 micelle aqueous solutions

Science.gov (United States)

Hu, Li; Zhang, Jing; Zhu, Chao; Pan, Hong-chun; Liu, Hong

2017-11-01

Herein we investigate the effect of different additives (electrolytes, amino acids, PEG, and sugars) on the cloud points (CP) of coenzyme Q10 (CoQ10) - Kolliphor HS15 (HS15) micelle aqueous solutions. The CP values were decreased with the increase of electrolytes and sugars, following: CPAl3+ reduced the CP. A depression of CP for CoQ10-HS15 micelle solution with PEG was molecular weight of PEG dependent. The significant thermodynamic parameters were also evaluated and discussed.

Clinical Significance of Determination of the Serum Levels of NT-proBNP and hs-CRP in Patients with Acute Coronary Syndrome

International Nuclear Information System (INIS)

Zheng Zhaojun; Zheng Jing; Sun Weili; Yuan Yuan; Tao Jian; Li Weipeng

2010-01-01

To explore the clinical significance the serum levels of N-Terminal proB-Type natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hs-CRP) in patients with acute coronary syndrome,the serum levels of NT-proBNP and hs-CRP in patients and normal controls were determined by ECi Immunity Analyzer and radioimmunoassay respectively. The results showed that the serum levels of NT-proBNP and hs-CRP in patients with acute coronary syndrome were significantly higher than that of controls (P<0.05). The diagnostic specificity for acute coronary syndrome was 100% by combined detection of NT-proBNP and hs-CRP. The results suggest that the combined detection of serum NT-proBNP and hs-CRP levels are very important to evaluate heart function in patients with acute coronary syndrome. (authors)

Correlation of Serum Levels of Vitronectin, Malondialdehyde and Hs-CRP With Disease Severity in Coronary Artery Disease

Directory of Open Access Journals (Sweden)

Alireza Yaghoubi

2015-09-01

Conclusion: The association and correlation between VN, MDA and hs-CRP indicate their involvement in the atherosclerosis process that may lead to progression of CAD. Also, these findings suggested that serum levels of VN, MDA and hs-CRP can help as diagnostic and monitoring markers in CAD patients and as markers of disease severity.

Toenail elemental analysis of Korean young adults by instrumental neutron activation analysis

International Nuclear Information System (INIS)

Lee, O.

2016-01-01

The element contents in toenail clippings of healthy Korean young adults were measured using an instrumental neutron activation analysis. The average contents of elements such as Na, K, Cl, Ca, Fe, Se, and Zn are 449, 474, 1024, 1677, 66, 0.7 and 94 mg/kg in men, whereas those contents in women respectively 332, 476, 836, 1097, 66, 0.8 and 104 mg/kg. The correlation analysis of toenail elements with chronic disease risks showed positive associations between Na and serum HDL-cholesterol, blood pressure, and negative associations between Se and Hs-CRP, between Zn and hemoglobin level. (author)

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...

Clinical application of combined detection of serum hs-CRP, GMP-140 and cTnI in patients with coronary heart diseases

International Nuclear Information System (INIS)

Qin Jibao; Wu Zhaozeng

2010-01-01

Objective: To explore the clinical significance of changes of serum hs-CRP, GMP-140 and cTnI levels in patients with coronary heart diseases. Methods: Serum GMP-140 (with RIA), cTnI (with ELISA) and hs-CRP (with immuno turbidity method) levels were determined in 91 patients with coronary heart diseases (42 SAP, 34UAP, 15AMI) and 35 controls. Results: Serum hs-CRP, GMP-140, cTnI levels in patients with coronary heart diseases were significantly higher than those in controls (P <0.01). Among the patients with of coronary heart diseases, the magnitude of changes of the levels of serum hs-CRP, GMP-140 and cTnI levels in AMI and UAP groups were significantly larger than those in SAP group (P < 0.05). Serum hs-CRP levels were positively correlated with serum GMP-140 and cTnI levels (r = 0.6214, 0.6023, P < 0.01). Conclusion: Serum hs-CRP, GMP140 and cTnI levels were closely related to the diseases process of coronary heart diseases and were of great clinical importance for assessment of the disease and outcome prediction. (authors)

Correlation of Progranulin, Granulin, Adiponectin and Vaspin with Metaflammation (hs-CRP in Indonesian Obese Men

Directory of Open Access Journals (Sweden)

Rosalia E Napitupulu

2013-08-01

Full Text Available BACKGROUND: Obesity is closely related to chronic, low grade systemic inflammation (metaflammation and it leads to further metabolic complications such as hypertension, atherosclerosis, and type 2 diabetes due to the adipocytokine imbalance. This study was carried out to assess the correlation between progranulin, granulin, adiponectin and visceral adipose tissue-derived serine protease inhibitor (Vaspin with metaflammation (high sensitivity C-reactive protein (hs-CRP in centrally obese men. METHODS: This study was observational with a cross sectional design involving 60 men aged 30-60 years, consisted of 43 obese men (waist circumference (WC ≥90 cm and 13 non obese men (WC 105 cm. CONCLUSIONS: We found metaflammation (hs-CRP was significantly correlated with Vaspin, but not with progranulin, granulin and adiponectin, in obese men. We suggest the possibility of a dynamic expression of adipokines related to WC that are subjected to adipocytes hypertrophy-hyperplasia phenomenon. KEYWORDS: progranulin, granulin, adiponectin, Vaspin, hs-CRP, metaflammation, central obesity.

Clinical significance of changes of serum hs-CRP, IL-6 and TNF-α levels after treatment in patients with polycystic ovary syndrome

International Nuclear Information System (INIS)

Yang Wen; Wang Ying

2010-01-01

Objective: To explore the clinical significance of changes of serum hs-CRP, IL-6 and TNF-α levels in patients with polycystic ovary syndrome. Methods: Serum hs-CRP (with immuno turbidity method), IL-6, TNF-α (with RIA) levels were determined in 31 patients with polycystic ovary syndrome both before and after six, month's treatment as well as 35 controls. Results: Before treatment, the serum hs-CRP, IL-6 and TNF-α levels in the 31 patients with polycystic ovary syndrome were significantly higher than those in controls (P 0.05). Serum hs-CRP levels were positive correlate with serum IL-6, TNF-α levels (r=0.6014, 0.5982, P<0.01). Conclusion: Serum hs-CRP, IL-6 and TNF-α levels were correlated to the development of polycystic ovary syndrome (PCOS). (authors)

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)

Optimal Tilt Angle and Orientation of Photovoltaic Modules Using HS Algorithm in Different Climates of China

Directory of Open Access Journals (Sweden)

Mian Guo

2017-10-01

Full Text Available Solar energy technologies play an important role in shaping a sustainable energy future, and generating clean, renewable, and widely distributed energy sources. This paper determines the optimum tilt angle and optimum azimuth angle of photovoltaic (PV panels, employing the harmony search (HS meta-heuristic algorithm. In this study, the ergodic method is first conducted to obtain the optimum tilt angle and the optimum azimuth angle in several cities of China based on the model of Julian dating. Next, the HS algorithm is applied to search for the optimum solution. The purpose of this research is to maximize the extraterrestrial radiation on the collector surface for a specific period. The sun’s position is predicted by the proposed model at different times, and then solar radiation is obtained on various inclined planes with different orientations in each city. The performance of the HS method is compared with that of the ergodic method and other optimization algorithms. The results demonstrate that the tilt angle should be changed once a month, and the best orientation is usually due south in the selected cities. In addition, the HS algorithm is a practical and reliable alternative for estimating the optimum tilt angle and optimum azimuth angle of PV panels.

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.

Two cis-acting elements responsible for posttranscriptional trans-regulation of gene expression of human T-cell leukemia virus type I

International Nuclear Information System (INIS)

Seiki, Motoharu; Inoue, Junichiro; Hidaka, Makoto; Yoshida, Mitsuaki

1988-01-01

The pX sequence of human T-cell leukemia virus type I codes for two nuclear proteins, p40 tax and p27 rex and a cytoplasmic protein, p21 X-III . p40 tax activates transcription from the long terminal repeat (LTR), whereas p27 rex modulates posttranscriptional processing to accumulate gag and env mRNAs that retain intron sequences. In this paper, the authors identify two cis-acting sequence elements needed for regulation by p27 rex : a 5' splice signal and a specific sequence in the 3' LTR. These two sequence elements are sufficient for regulation by p27 rex ; expression of a cellular gene (metallothionein I) became sensitive to rex regulation when the LTR was inserted at the 3' end of this gene. The requirement for these two elements suggests and unusual regulatory mechanism of RNA processing in the nucleus

Elevated levels of Hs-CRP and IL-6 after delivery are associated with depression during the 6 months post partum.

Science.gov (United States)

Liu, Hao; Zhang, Yang; Gao, Yutao; Zhang, Zhenyu

2016-09-30

The objective of this study is to determine whether inflammatory markers (high-sensitivity C-reactive protein (Hs-CRP) and interleukin (IL)-6) early in the postpartum period contribute to the development of postpartum depression (PPD). From 4 May 2014 to 30 June 2014, all eligible women not on medication for depression giving birth at the Beijing Chao-Yang hospital were consecutively recruited and followed up for 6 months. Depression symptoms were measured with the Edinburgh Postnatal Depression Scale (EPDS), and inflammatory biomarkers (Hs-CRP and IL-6) were tested. During the study period, 296 women were enrolled and completed follow-up. In these women, 45 (15.2%) were considered as meeting the criteria for PPD. Serum levels of Hs-CRP and IL-6 in women with PPD were significantly higher than those without PPD (all P<0.0001). Receiver operating characteristics to predict PPD demonstrated areas under the curve of IL-6 of 0.861 (95% confidence interval (CI), 0.801-0.922), which was superior to Hs-CRP (0.837 (95% CI, 0.781-0.894), P<0.01). In multivariate logistic regression analysis, IL-6 and Hs-CRP were independent predictors of PPD. The present study demonstrates a strong relationship between elevated serum Hs-CRP and IL-6 levels at admission and the development of PPD within 6 months. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Exploring Dust Impacts on Tropical Systems from the NASA HS-3 Field Campaign

Science.gov (United States)

Nowottnick, Ed; Colarco, Pete; da Silva, Arlindo; Barahona, Donifan; Hlavka, Dennis

2015-01-01

One of the overall scientific goals of the NASA Hurricane and Severe Storm Sentinel (HS-3) field campaign is to better understand the role of the Saharan Air Layer (SAL) in tropical storm development. During the 2012 HS-3 deployment, the Cloud Physics Lidar (CPL) observed dust within SAL air in close proximity to a developing Nadine (September 11, 2012). Throughout the mission, the NASA GEOS-5 modeling system supported HS-3 by providing 0.25 degrees resolution 5-day global forecasts of aerosols, which were used to support mission planning. The aerosol module was radiatively interactive within the GEOS-5 model, but aerosols were not directly coupled to cloud and precipitation processes. In this study we revisit the aerosol forecasts with an updated version of the GEOS-5 model. For the duration of Hurricane Nadine, we run multiday climate simulations leading up to each respective Global Hawk flight with and without aerosol direct interaction. For each set of simulations, we compare simulated dust mass fluxes to identify differences in SAL entrainment related to the interaction between dust aerosols and the atmosphere. We find that the direct effects of dust induce a low level anticyclonic circulation that temporarily shields Nadine from the intrusion of dry air, leading to a more intense storm.

Osteoprotegerin improves risk detection by traditional cardiovascular risk factors and hsCRP

DEFF Research Database (Denmark)

Mogelvang, Rasmus; Haahr-Pedersen, Sune Ammentorp; Bjerre, Mette

2013-01-01

To evaluate the association of plasma osteoprotegerin (OPG) to hospitalisation for ischaemic heart disease (IHD), ischaemic stroke and all-cause mortality, and the effect of combining plasma OPG and high-sensitivity C-reactive protein (hsCRP)....

Clinical significance of determination of serum hypersensitive C-reactive protein (hs-CRP) and E-selectin levels in patients with coronary heart diseases

International Nuclear Information System (INIS)

Yang Chunxiu

2007-01-01

Objective: To investigate the significance of determination of serum contents of hs-CRP and E-Selectin in patients with coronary heart diseases (CHD). Methods: Serum hs-CRP Contents were determined with immuno-turbidity and E-Selectin contents were determined with ELISA in 58 patients with CHD (35SAP, 20UAP, 13AMI) and 35 controls. Results: Serum levels of hs-CRP and E-Selectin in CHD patients were significantly higher than those in controls (P 0.05). Conclusion: The serum levels of hs-CRP and E-Selectin were correlated to the development of CHD, but not to the coronary artery calibers. (authors)

Effects of Silybum marianum (L.) Gaertn. (silymarin) extract supplementation on antioxidant status and hs-CRP in patients with type 2 diabetes mellitus: a randomized, triple-blind, placebo-controlled clinical trial.

Science.gov (United States)

Ebrahimpour Koujan, Soraiya; Gargari, Bahram Pourghassem; Mobasseri, Majid; Valizadeh, Hadi; Asghari-Jafarabadi, Mohammad

2015-02-15

Diabetes is a serious metabolic disorder and oxidative stress and inflammation contribute to its pathogenesis and complications. Since Silybum marianum (L.) Gaertn. (silymarin) extract is an antioxidant with anti-inflammatory properties, this randomized clinical trial was conducted to evaluate the effects of silymarin supplementation on oxidative stress indices and hs-CRP in type 2 diabetes mellitus patients. For the present paralleled, randomized, triple-blinded, placebo-controlled clinical trial, 40 type 2 diabetes patients aged 25-50 yr old and on stable medication were recruited from the Iranian Diabetes Society and endocrinology clinics in East Azarbayjan (Tabriz, Iran) and randomly assigned into two groups. Patients in the silymarin treatment group received 140 mg, thrice daily of dried extracts of Silybum marianum (n = 20) and those in the placebo group (n = 20) received identical placebos for 45 days. Data pertaining to height, weight, waist circumference and BMI, as well as food consumption, were collected at base line and at the conclusion of the study. Fasting blood samples were obtained and antioxidant indices and hs-CRP were assessed at baseline, as well as at the end of the trial. All 40 patients completed the study and did not report any adverse effects or symptoms with the silymarin supplementation. Silymarin supplementation significantly increased superoxide dismutase (SOD), glutathione peroxidase (GPX) activity and total antioxidant capacity (TAC) compared to patients taking the placebo, by 12.85%, 30.32% and 8.43%, respectively (p concentration significantly decreased by 12.01% (p antioxidant indices (SOD, GPX and TAC) and decrease hs-CRP levels in T2DM patients. Copyright © 2015. Published by Elsevier GmbH.

The Value of PCT, WBC and hs-CRP Tests in the Diagnosis and Prognosis of Children with Pneumonia%小儿肺炎中PCT、WBC、hs-CRP检测对疾病诊断及预后判断价值分析

Institute of Scientific and Technical Information of China (English)

夏兰兰; 李敬

2017-01-01

目的 分析小儿肺炎中PCT、WBC、hs-CRP检测对疾病诊断及预后的判断价值.方法 选取2015年5月至2016年4月在本院住院治疗的肺炎患儿120例作为观察组,健康儿童65例作为对照组.检测治疗前后患儿及健康儿童血清PCT、WBC、hs-CRP的变化.结果 治疗前,细菌感染组WBC数量(15.5±3.4)×109/L、hs-CRP水平(19.8±2.6) mg/L和PCT水平(21.9±2.1)ng/mL均明显高于非细菌感染组(6.8 ±2.3)×109/L、(4.5±2.3)mg/L、(4.7±1.8) ng/mL和健康对照组(8.1 ±1.4)×109/L、(3.5±1.2) mg/L、(1.8±0.5) ng/mL,且差异具有统计学意义(P＜0.05).而非细菌感染组和健康对照组的WBC、hs-CRP和PCT结果差异无统计学意义(P＞0.05);治疗后,细菌感染组WBC数量(7.3±1.4)×109/L、hs-CRP水平(5.1 ± 1.2) mg/L和PCT水平(2.3 ± 1.2) ng/mL均明显低于治疗前,差异具有统计学意义(P＜0.05);WBC、hs-CRP、PCT联合检测的灵敏性95.2％、特异性93.0％、准确度93.3％显著高于WBC、hs-CRP、PCT单独检测,差异具有统计学意义(P＜0.05).结论 在小儿肺炎治疗过程中,动态监测患儿血清的WBC、hs-CRP、PCT的变化,并结合临床,有助于诊疗和判断患儿疾病愈后的情况,具有显著的临床意义,值得推广应用.%Objective To estimate the value of PCT,WBC and hs-CRP tests in the diagnosis and prognosis of children with pneumonia.Methods 120 cases with pneumonia in children were selected from May 2015 to April 2016 in our hospital as the observation group,65 cases of healthy children as the control group.Changes of serum PCT,WBC and hs-CRP tests in children and healthy children before and after treatment were mearued.Results Before treatment,bacterial infection group have WBC count (15.5 ± 3.4) × 109/L,hs-CRP levels (19.8±2.6) mg/L and PCT level (21.9 ±2.1) ng/mL,which were significantly higher than those in non bacterial infection group (6.8 ±2.3) × 109/L,(4.5 ±2.3) mg/L,(4.7 ± 1.8) ng/mL and healthy control group (+ 8.1 �

High-sensitivity c-reactive protein (hs-CRP) value with 90 days mortality in patients with heart failure

Science.gov (United States)

Nursyamsiah; Hasan, R.

2018-03-01

Hospitalization in patients with chronic heart failure is associated with high rates of mortality and morbidity that during treatment and post-treatment. Despite the various therapies available today, mortality and re-hospitalization rates within 60 to 90 days post-hospitalization are still quite high. This period is known as the vulnerable phase. With the prognostic evaluation tools in patients with heart failure are expected to help identify high-risk individuals, then more rigorous monitoring and interventions can be undertaken. To determine whether hs-CRP have an impact on mortality within 90 days in hospitalized patients with heart failure, an observational cohort study was conducted in 39 patients with heart failure who were hospitalized due to worsening chronic heart failure. Patients were followed for up to 90 days after initial evaluation with the primary endpoint is death. Hs-CRP value >4.25 mg/L we found 70% was dead and hs-CRP value <4.25 mg/L only 6.9% was dead whereas the survival within 90 days. p:0.000.In conclusion, there were differences in hs-CRP values between in patients with heart failure who died and survival within 90 days.

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)

Development of a SISAK extraction system for chemical studies of element 108, hassium

International Nuclear Information System (INIS)

Samadani, F.; Alstad, J.; Bjoernstad, T.; Stavsetra, L.; Omtvedt, J.P.

2010-01-01

A liquid-liquid extraction system suitable for studies of chemical properties of Hs (element 108), in the form of HsO 4 , was developed using γ-emitting isotopes of its homologue Os. The system is targeted for the fast on-line extraction system SISAK, which operates in a continuous manner and is suitable for liquid-phase studies of transactinide elements. The distribution of OsO 4 between various dilute NaOH solutions and toluene was studied. Both batch and SISAK on-line experiments were performed to develop an appropriate system. From analysis of the extraction curves equilibrium constants for the formation of the presumed complexes, Na[OsO 4 (OH)] and Na 2 [OsO 4 (OH) 2 ], were obtained: K 1 = (1 ± 0.5) x 10 4 and K 2 = 12 ± 8, respectively. The SISAK system includes a liquid-scintillation detection system for α measurements. Due to quenching effects it is not possible to perform direct measurement of the aqueous phase α's. Therefore, a two-stage extraction method that provides an indirect measurement of the activity in the aqueous phase was developed as part of the proposed system for Hs: Acidification of the raffinate from the first stage result in recovery of OsO 4 , which is highly extractable into toluene. The yield of extraction in the second step, from 0.01 M NaOH solution after acidification with H 2 SO 4 solution, was (90 ± 3)%. (orig.)

HS-173, a Novel PI3K Inhibitor, Attenuates the Activation of Hepatic Stellate Cells in Liver Fibrosis

Science.gov (United States)

Son, Mi Kwon; Ryu, Ye-Lim; Jung, Kyung Hee; Lee, Hyunseung; Lee, Hee Seung; Yan, Hong Hua; Park, Heon Joo; Ryu, Ji-Kan; Suh, Jun–Kyu; Hong, Sungwoo; Hong, Soon-Sun

2013-01-01

Hepatic stellate cells (HSCs) are the primary source of matrix components in liver disease such as fibrosis. Phosphatidylinositol 3-kinase (PI3K) signaling in HSCs has been shown to induce fibrogenesis. In this study, we evaluated the anti-fibrotic activity of a novel imidazopyridine analogue (HS-173) in human HSCs as well as mouse liver fibrosis. HS-173 strongly suppressed the growth and proliferation of HSCs and induced the arrest at the G2/M phase and apoptosis in HSCs. Furthermore, it reduced the expression of extracellular matrix components such as collagen type I, which was confirmed by an in vivo study. We also observed that HS-173 blocked the PI3K/Akt signaling pathway in vitro and in vivo. Taken together, HS-173 suppressed fibrotic responses such as cell proliferation and collagen synthesis by blocking PI3K/Akt signaling. Therefore, we suggest that this compound may be an effective therapeutic agent for ameliorating liver fibrosis through the inhibition of PI3K signaling. PMID:24326778

Correlation of hs-CRP with environmental risk factors of nephropathy in type 2 diabetes

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Jay Prakash Sah

2015-06-01

Full Text Available The objective of the present study was to investigate the association of hs-CRP levels with environmental risk factors of diabetic nephropathy like smoking, drinking alcohol, diet, age of diabetic patient, duration of diabetes, medication of diabetes, and blood pressure medication. A hospital-based quantitative study was conducted at the Department of Clinical Biochemistry of Manipal Teaching Hospital (MTH Pokhara, Nepal, with 89 patients suffering from type 2 diabetes. Blood samples (n=89 from the patients were collected and the serums were separated. On the other hand, data on environmental risk factors of nephropathy were collected by using standard questionnaire. In this study, serum hs-CRP level was not found to be correlated with smoking (p=0.111, alcohol consumption (p=0.722, diet (p=0.496, duration of diabetes (p=0.519, age of diabetic patient (p=0.369, medication of diabetes (p=0.734, and blood pressure medication (p=0.625. Hence, our study concludes that serum hs-CRP value in type 2 diabetic patients is insignificantly correlated with the risk factors especially smoking, drinking alcohol, diet, duration of diabetes, age of diabetic patient, medication of diabetes, and medication of blood pressure.

Lowering the quantification limit of the QubitTM RNA HS assay using RNA spike-in.

Science.gov (United States)

Li, Xin; Ben-Dov, Iddo Z; Mauro, Maurizio; Williams, Zev

2015-05-06

RNA quantification is often a prerequisite for most RNA analyses such as RNA sequencing. However, the relatively low sensitivity and large sample consumption of traditional RNA quantification methods such as UV spectrophotometry and even the much more sensitive fluorescence-based RNA quantification assays, such as the Qubit™ RNA HS Assay, are often inadequate for measuring minute levels of RNA isolated from limited cell and tissue samples and biofluids. Thus, there is a pressing need for a more sensitive method to reliably and robustly detect trace levels of RNA without interference from DNA. To improve the quantification limit of the Qubit™ RNA HS Assay, we spiked-in a known quantity of RNA to achieve the minimum reading required by the assay. Samples containing trace amounts of RNA were then added to the spike-in and measured as a reading increase over RNA spike-in baseline. We determined the accuracy and precision of reading increases between 1 and 20 pg/μL as well as RNA-specificity in this range, and compared to those of RiboGreen(®), another sensitive fluorescence-based RNA quantification assay. We then applied Qubit™ Assay with RNA spike-in to quantify plasma RNA samples. RNA spike-in improved the quantification limit of the Qubit™ RNA HS Assay 5-fold, from 25 pg/μL down to 5 pg/μL while maintaining high specificity to RNA. This enabled quantification of RNA with original concentration as low as 55.6 pg/μL compared to 250 pg/μL for the standard assay and decreased sample consumption from 5 to 1 ng. Plasma RNA samples that were not measurable by the Qubit™ RNA HS Assay were measurable by our modified method. The Qubit™ RNA HS Assay with RNA spike-in is able to quantify RNA with high specificity at 5-fold lower concentration and uses 5-fold less sample quantity than the standard Qubit™ Assay.

HURRICANE AND SEVERE STORM SENTINEL (HS3) HURRICANE IMAGING RADIOMETER (HIRAD) V1

Data.gov (United States)

National Aeronautics and Space Administration — The Hurricane and Severe Storm Sentinel (HS3) Hurricane Imaging Radiometer (HIRAD) was collected by the Hurricane Imaging Radiometer (HIRAD), which was a multi-band...

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

Repetitive Elements in Mycoplasma hyopneumoniae Transcriptional Regulation.

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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.

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.

Association of HS6ST3 gene polymorphisms with obesity and ...

Indian Academy of Sciences (India)

Supplementary data: Association of HS6ST3 gene polymorphisms with obesity and triglycerides: gene × gender interaction. Ke-Sheng Wang, Liang Wang, Xuefeng Liu and Min Zeng. J. Genet. 92, 395–402. Table 1. Associations of 117 SNPs with obesity in the Health ABC and Marshfield samples. Minor. OR Health.

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.

Development of a Direct Headspace Collection Method from Arabidopsis Seedlings Using HS-SPME-GC-TOF-MS Analysis

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Kazuki Saito

2013-04-01

Full Text Available Plants produce various volatile organic compounds (VOCs, which are thought to be a crucial factor in their interactions with harmful insects, plants and animals. Composition of VOCs may differ when plants are grown under different nutrient conditions, i.e., macronutrient-deficient conditions. However, in plants, relationships between macronutrient assimilation and VOC composition remain unclear. In order to identify the kinds of VOCs that can be emitted when plants are grown under various environmental conditions, we established a conventional method for VOC profiling in Arabidopsis thaliana (Arabidopsis involving headspace-solid-phase microextraction-gas chromatography-time-of-flight-mass spectrometry (HS-SPME-GC-TOF-MS. We grew Arabidopsis seedlings in an HS vial to directly perform HS analysis. To maximize the analytical performance of VOCs, we optimized the extraction method and the analytical conditions of HP-SPME-GC-TOF-MS. Using the optimized method, we conducted VOC profiling of Arabidopsis seedlings, which were grown under two different nutrition conditions, nutrition-rich and nutrition-deficient conditions. The VOC profiles clearly showed a distinct pattern with respect to each condition. This study suggests that HS-SPME-GC-TOF-MS analysis has immense potential to detect changes in the levels of VOCs in not only Arabidopsis, but other plants grown under various environmental conditions.

Association of serum hs-CRP and lipids with obesity in school children in a 12-month follow-up study in Japan.

Science.gov (United States)

Nishide, Ritsuko; Ando, Michiko; Funabashi, Hidemitsu; Yoda, Yoshiko; Nakano, Masataka; Shima, Masayuki

2015-03-01

To investigate the association of serum lipids and high-sensitivity C-reactive protein (hs-CRP) with obesity in school children and to explore whether hs-CRP levels could be used to predict the presence or absence of obesity 12 months later. The subjects were school children (6-11 years old) in Japan. Blood sampling and physical measurements were performed in school (2001); low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and hs-CRP levels were measured. Data from children who could be followed 12 months later were analyzed. Subjects weighing 20% or more over his/her standard weight were regarded as obese, and the association of obesity with serum parameters was analyzed. Data from 612 subjects were analyzed (follow-up rate, 75.4%). The mean of each serum parameter was significantly higher (inverse for HDL-C; lower) in obese than that in non-obese children. Logistic regression analysis for obesity at baseline showed that the odds ratio (OR) of hs-CRP was the highest [OR, 2.15; 95% confidence interval (CI), 1.65-2.78 for an interquartile rage (IQR) increase]; the association with triglycerides and LDL-C/HDL-C was significant. At the 12-month follow-up, the OR of high hs-CRP remained the highest of all serum parameters (2.09; 95% CI, 1.63-2.69 for an IQR increase). High levels of triglycerides, LDL-C/HDL-C, and hs-CRP increased the risk of obesity in school children. Hs-CRP is considered to be a better predictor of obesity 12 months later than is LDL-C/HDL-C.

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

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

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Ratti Antonia

2007-12-01

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

DFT study on oxidation of HS(CH2) m SH ( m = 1-8) in oxidative desulfurization

Science.gov (United States)

Song, Y. Z.; Song, J. J.; Zhao, T. T.; Chen, C. Y.; He, M.; Du, J.

2016-06-01

Density functional theory was employed for calculation of HS(CH2) m SH ( m = 1-8) and its derivatives at B3LYP method at 6-31++g ( d, p) level. Using eigenvalues of LUMO and HOMO for HS(CH2) m SH, the standard electrode potentials were estimated by a stepwise multiple regression techniques (MLR), and obtained as E° = 1.500 + 7.167 × 10-3 HOMO-0.229 LUMO with high correlation coefficients of 0.973 and F values of 43.973.

3-O-sulfated heparan sulfate recognized by the antibody HS4C3 contributes [corrected] to the differentiation of mouse embryonic stem cells via fas signaling.

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Kazumi Hirano

Full Text Available Maintenance of self-renewal and pluripotency in mouse embryonic stem cells (mESCs is regulated by the balance between several extrinsic signaling pathways. Recently, we demonstrated that heparan sulfate (HS chains play important roles in the maintenance and differentiation of mESCs by regulating extrinsic signaling. Sulfated HS structures are modified by various sulfotransferases during development. However, the significance of specific HS structures during development remains unclear. Here, we show that 3-O-sulfated HS structures synthesized by HS 3-O-sulfotransferases (3OSTs and recognized by the antibody HS4C3 increase during differentiation of mESCs. Furthermore, expression of Fas on the cell surface of the differentiated cells also increased. Overexpression of the HS4C3-binding epitope in mESCs induced apoptosis and spontaneous differentiation even in the presence of LIF and serum. These data showed that the HS4C3-binding epitope was required for differentiation of mESCs. Up-regulation of the HS4C3-binding epitope resulted in the recruitment of Fas from the cytoplasm to lipid rafts on the cell surface followed by activation of Fas signaling. Indeed, the HS4C3-binding epitope interacted with a region that included the heparin-binding domain (KLRRRVH of Fas. Reduced self-renewal capability in cells overexpressing 3OST resulted from the degradation of Nanog by activated caspase-3, which is downstream of Fas signaling, and was rescued by the inhibition of Fas signaling. We also found that knockdown of 3OST and inhibition of Fas signaling reduced the potential for differentiation into the three germ layers during embryoid body formation. This is the first demonstration that activation of Fas signaling is mediated by an increase in the HS4C3-binding epitope and indicates a novel signaling pathway for differentiation in mESCs.

3-O-sulfated heparan sulfate recognized by the antibody HS4C3 contributes [corrected] to the differentiation of mouse embryonic stem cells via fas signaling.

Science.gov (United States)

Hirano, Kazumi; Sasaki, Norihiko; Ichimiya, Tomomi; Miura, Taichi; Van Kuppevelt, Toin H; Nishihara, Shoko

2012-01-01

Maintenance of self-renewal and pluripotency in mouse embryonic stem cells (mESCs) is regulated by the balance between several extrinsic signaling pathways. Recently, we demonstrated that heparan sulfate (HS) chains play important roles in the maintenance and differentiation of mESCs by regulating extrinsic signaling. Sulfated HS structures are modified by various sulfotransferases during development. However, the significance of specific HS structures during development remains unclear. Here, we show that 3-O-sulfated HS structures synthesized by HS 3-O-sulfotransferases (3OSTs) and recognized by the antibody HS4C3 increase during differentiation of mESCs. Furthermore, expression of Fas on the cell surface of the differentiated cells also increased. Overexpression of the HS4C3-binding epitope in mESCs induced apoptosis and spontaneous differentiation even in the presence of LIF and serum. These data showed that the HS4C3-binding epitope was required for differentiation of mESCs. Up-regulation of the HS4C3-binding epitope resulted in the recruitment of Fas from the cytoplasm to lipid rafts on the cell surface followed by activation of Fas signaling. Indeed, the HS4C3-binding epitope interacted with a region that included the heparin-binding domain (KLRRRVH) of Fas. Reduced self-renewal capability in cells overexpressing 3OST resulted from the degradation of Nanog by activated caspase-3, which is downstream of Fas signaling, and was rescued by the inhibition of Fas signaling. We also found that knockdown of 3OST and inhibition of Fas signaling reduced the potential for differentiation into the three germ layers during embryoid body formation. This is the first demonstration that activation of Fas signaling is mediated by an increase in the HS4C3-binding epitope and indicates a novel signaling pathway for differentiation in mESCs.

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.

Does cooperativity influence the lifetime of the photo-induced HS state?

International Nuclear Information System (INIS)

Letard, Jean-Francois; Costa, Jose Sanchez; Marcen, Silvia; Carbonera, Chiara; Desplanches, Cedric; Kobayashi, Atsushi; Daro, Nathalie; Guionneau, Philippe; Ader, Jean-Pierre

2005-01-01

We have first recalled the T(LIESST) procedure which consists to determine the temperature above which the photo-magnetic effect is erased. In addition we have selected to series of iron(II) spin crossover complexes, the [Fe(PM-L) 2 (NCS) 2 ] and [Fe(bpp) 2 ]X 2 ·nH 2 O families, to analyse the influence of the cooperativity on the stability of the photo-induced HS state. Some of these complexes exhibit gradual thermal spin crossover behaviours while some others undergo an abrupt thermal transition, with and without hysteresis. Interestingly, whatever the cooperativity effect on the thermal spin crossover transition, the lifetime of the metastable state of all these derivates remains governed by the T(LIESST) = T 0 - 0.31 T 1/2 relation. Finally, we have investigated the magnetic and the photomagnetic properties of a [Fe(bpp) 2 ]-Nafion film. Once more the role of the cooperativity on the stability of the photoinduced HS state appears minor. Conversely, the influence of the nature and the geometry of the inner coordination sphere appears preponderant

Detection significance of serum hs-CRP and ALB in premature infants with early infections%血清hs-CRP与ALB检测对早产儿早发感染的临床意义

Institute of Scientific and Technical Information of China (English)

王陈裕; 何海雅; 汤梦倩; 杜姗; 金燕芬; 洪艳; 胡荣全

2017-01-01

OBJECTIVE To explore the clinical diagnostic values of serum high sensitivity C-reactive protein (hs-CRP) and albumin (ALB) in premature infants with early infections .METHODS A total of 156 cases of premature infants hospitalized from Feb .2015 to Mar .2016 in our hospital for treatment were selected as the research ob-jects ,and were divided into infection group (74 cases) and non-infected group (82 cases) according to the infection status of premature infants .Blood samples of premature infants were collected for detection of white blood cell count (WBC) ,platelet count (PLT) and hs-CRP and ALB at 24h after the infants admitted into the neonatal in-tensive care unit .RESULTS There were 74 cases of premature infants had infections in the 156 cases of patients , and the infection rate was 47 .44％ ,which was mainly pneumonia .Totally 90 strains of pathogens were detected in infected premature infants ,including 18 strains of gram-negative bacteria accounting for 20 .00％ ,mainly Esche-richia coli ,and 65 strains of gram-positive bacteria accounting for 72 .22％ ,mainly Staphylococcus aurous and Staphylococcus epidermises .The white blood cell count ,platelet count and albumin of infection group were (13 . 28 ± 4 .20)× 109/L ,(238 .30 ± 41 .02)× 109/L and (26 .54 ± 10 .25)g/L ,which were lower than (17 .10 ± 5 .12) × 109/L ,(261 .05 ± 42 .06) × 109/L and (29 .64 ± 12 .24)g/L in non-infected group ,and hs-CRP and ALB in in-fection group at 24h and 48h were (2 .38 ± 0 .49)mg/L and (22 .03 ± 9 .36)mg/L ,which were significantly higher than (1 .02 ± 0 .21)mg/L and (17 .65 ± 8 .67) mg/L in non-infected group (P<0 .05) .There were 3 ca-ses died in infection group after 48h ,and the mortality rate was 4 .05％ .CONCLUSION Serum hs-CRP and ALB can be used as effective clinical diagnostic indexes of early infection in premature infants ,and hs-CRP and ALB of infants within 24 hours of admission to the NICU can greatly improve the diagnostic sensitivity .%�

Comparison of solutol HS 15, Cremophor EL and novel ethoxylated fatty acid surfactants as multidrug resistance modification agents.

Science.gov (United States)

Buckingham, L E; Balasubramanian, M; Emanuele, R M; Clodfelter, K E; Coon, J S

1995-08-09

Some well-known fatty acid ester surfactants, e.g., Cremophor EL and Solutol HS 15, are modulators of multidrug resistance in vitro and in vivo. Because they are polydisperse, and their active component(s) have not been identified, the therapeutic potential of such surfactants is unclear. To better define the active components of Solutol HS 15 and to make more potent surfactant multidrug resistance modulators, highly purified C-18 fatty acids were esterified with ethylene oxide at 5-200 molar ratios. Unexpectedly, ethylene oxide esters of pure 12-hydroxy stearic acid, the major components of Solutol HS 15, displayed negligible resistance modification activity compared with Solutol HS 15 itself or to stearic and oleic acid esters synthesized under identical conditions. Since oleic acid esters appeared to have good activity, a series of these compounds was prepared to determine the optimal ethylene oxide/fatty acid ratio. The optimal ratio was found to be 20 mole ethylene oxide: I mole fatty acid, with a steep decline in activity for products made with ratios above and below the optimum. The most active oleic acid ester, designated CRL 1337, was 8.4-fold as potent as Solutol HS 15 and over 19-fold as potent as Cremophor EL in promoting rhodamine 123 accumulation in multidrug-resistant KB 8-5-11 cells in vitro. Our results show that the structure of the hydrophobic domain (fatty acid) of surfactants as well as its hydrophile-lipophile balance are critical in determining the potency of surfactants as reversing agents.

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

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.

Clinical significance of measurment of changes of serum IGF-I, hs-CRP levels after treatment in patients with hyperthyroidism and hypothyroidism

International Nuclear Information System (INIS)

Zhu Conggang

2009-01-01

Objective: To explore the clinical significance of changes of serum IGF-I,hs-CRP levels after treatment in patients with hyperthyroidism and hypothyroidism. Methods: Serum IGF-I, hs-CRP(with RIA), and serum hs-CRP with immuno-turbidity methods levels were determined both before and after treatment in 36 cases of hyperthyroidism 30 cases of hypothyroidism as well as 35 controls. Results: Before treatment, the serum IGF-I levels in patients with hyperthyroidism were significantly higher and the levels in patients with hypothyroidism were significantly lower than those in controls (both P<0.01). After treatment for 3 months,the levels were much corrected, but still remained significantly different from those in controls (P<0.05). Before treatment serum hs-CRP levels in both groups of patients were significantly higher than those in controls (P<0.01), but after treatment,the levels were not much different from those in controls. Conclusion: Serum levels of IGF-I and hs-CRP were closely related to the disease process in patients with hyperthyroidism as well as in patients with hypothyroidism, and were much corrected after trentment.(authors)

Development of a SISAK extraction system for chemical studies of element 108, hassium

Energy Technology Data Exchange (ETDEWEB)

Samadani, F.; Alstad, J.; Bjoernstad, T.; Stavsetra, L.; Omtvedt, J.P. [Oslo Univ. (Germany). Dept. of Chemistry

2010-07-01

A liquid-liquid extraction system suitable for studies of chemical properties of Hs (element 108), in the form of HsO{sub 4}, was developed using {gamma}-emitting isotopes of its homologue Os. The system is targeted for the fast on-line extraction system SISAK, which operates in a continuous manner and is suitable for liquid-phase studies of transactinide elements. The distribution of OsO{sub 4} between various dilute NaOH solutions and toluene was studied. Both batch and SISAK on-line experiments were performed to develop an appropriate system. From analysis of the extraction curves equilibrium constants for the formation of the presumed complexes, Na[OsO{sub 4}(OH)] and Na{sub 2}[OsO{sub 4}(OH){sub 2}], were obtained: K{sub 1} = (1 {+-} 0.5) x 10{sup 4} and K{sub 2} = 12 {+-} 8, respectively. The SISAK system includes a liquid-scintillation detection system for {alpha} measurements. Due to quenching effects it is not possible to perform direct measurement of the aqueous phase {alpha}'s. Therefore, a two-stage extraction method that provides an indirect measurement of the activity in the aqueous phase was developed as part of the proposed system for Hs: Acidification of the raffinate from the first stage result in recovery of OsO{sub 4}, which is highly extractable into toluene. The yield of extraction in the second step, from 0.01 M NaOH solution after acidification with H{sub 2}SO{sub 4} solution, was (90 {+-} 3)%. (orig.)

Regulatory aspects of mixed waste

International Nuclear Information System (INIS)

Boyle, R.R.; Orlando, D.A.

1990-01-01

Mixed waste is waste that satisfies the definition of low-level radioactive waste in the Low-Level Radioactive Waste Policy Amendments Act of 1985 (LLRWPAA) and contains hazardous waste that is either: (1) listed as a hazardous waste in 40 CFR 261, Subpart D; or (2) causes the waste to exhibit any of the characteristics identified in 40 CFR 261, Subpart C. Low-level radioactive waste is defined in the LLRWPAA as radioactive material that is not high level waste, spent nuclear fuel, or byproduct material, as defined in Section 11e(2) of the Atomic Energy Act of 1954, and is classified as low-level waste by the U.S. Nuclear Regulatory Commission (NRC). This paper discusses dual regulatory (NRC and Environmental Protection Agency) responsibility, overview of joint NRC/EPA guidance, workshops, national mixed waste survey, and principal mixed waste uncertainties

Exploring the smallest active fragment of HsQSOX1b and finding a highly efficient oxidative engine.

Directory of Open Access Journals (Sweden)

Wenyun Zheng

Full Text Available Human quiescin-sulfhydryl oxidase 1 isoform b (HsQSOX1b is a highly efficient, multiple-domain enzyme that directly inserts disulfide bonds into client protein. However, previous studies have focused mainly on the catalytic activity of the whole protein rather than its domain structure. In this research, we dissected the structure and function of HsQSOX1b and explored its mechanism as a highly efficient sulfhydryl oxidase by analyzing the truncated variants. The results showed that the first HsQSOX1b thioredoxin domain was essential for thiol oxidase activity. The smallest active fragment (SAQ was identified to consist of a helix-rich region (HRR and an essential for respiration and viability/augmenter of liver regeneration (ERV/ALR domain, which remained highly active to oxidize an artificial non-thiol substrate but not small molecular and protein thiols. Our study clearly demonstrated that SAQ is a highly efficient oxidative engine, which shows high efficiency in the de novo disulfide formation and oxygen reduction and that this more efficient oxidative engine is necessary for the highly efficient catalysis of QSOXs compared to Erv1 and Erv2. This study will help address the roles of different HsQSOX1b domains in de novo disulfide formation and encourage the engineering of more efficient QSOX variants for the in vitro folding of disulfide-containing proteins.

Clinical significance of determination of changes of serum hs-CRP, sICAM-1 and TNF-α levels in patients with gestational diabetes mellitus

International Nuclear Information System (INIS)

Yu Qiuyue

2009-01-01

Objective: To study the relationship between changes of serum sensitive C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α) and soluble intercellular adhesion molecule-1 (sICAM-1) levels and development of the disease in patients with gestational diabetes mellitus(GDM). Methods: Serum levels of TNF-α and sICAM-1(with RIA) and hs-CRP(with immunoturbidimetry) were measured in 30 patients with GDM and 30 normal pregnant women as controls. Results: The serum hs-CRP, sICAM-1 and TNF-α contents in the patients with GDM were all significantly higher than those in normal pregnant women (all P<0.01).The serum hs-CRP levels were mutually positivety correlated with TNF-α and sICAM-1 levels (r=0.6097, 0.7213, all P<0.01). Conclusion: Determination of changes of serum hs-CRP, TNF-α and sICAM-1 levels in patients with gestational diabetes mellitus would be helpful for outcome prediction. (authors)

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

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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

The impact of diurnal fasting during Ramadan on the lipid profile, hs-CRP, and serum leptin in stable cardiac patients.

Science.gov (United States)

Khafaji, Hadi Abdul Ridha Hadi; Bener, Abdulbari; Osman, Mohammed; Al Merri, Ajayeb; Al Suwaidi, Jassim

2012-01-01

To study the effect of strict prolonged fasting on lipid profile, serum leptin, and high- sensitivity C-reactive protein (hs-CRP) in patients with different stable cardiac illnesses and look for associated new cardiac events and any correlation between entire variables. A total of 56 patients of different stable cardiac illnesses were followed in our cardiology outpatient for 3 months. Data concerning their ability to fast were collected: New York Heart Association class of congestive cardiac failure, angina class, previous myocardial infarction, previous coronary artery bypass graft, percutaneous coronary intervention, severity of valvular lesion, metallic prosthetic valve, and traditional risk factors (diabetes mellitus, insulin requirement, hypertension, hypercholesterolemia, smoking habit, and obesity). Detailed clinical examination and electrocardiography were performed in all patients in three consecutive visits before, during, and after Ramadan. Echocardiographic and angiographic findings and medication plans were collected from patient records. Lipid profile, serum leptin, and hs-CRP were assessed before, during, and after Ramadan. All patients fasted during Ramadan: 80.4% were male, 67.9% were aged >50 years, 71.4% had no change in their symptoms during fasting while 28.6% felt better. No patient has deteriorated. 91.1% of the patients were compliant with medicine during Ramadan, 73.2% after. 89.3% were compliant with diet during Ramadan with no significant change in body weight in the follow-up period. No cardiac or noncardiac morbidity or mortality was reported. High- density lipoprotein-cholesterol (HDL-C) decreased significantly during compared to before fasting (P = 0.012). Low-density lipoprotein-cholesterol (LDL-C) significantly increased during compared to before fasting (P = 0.022). No statistically significant changes were observed in total cholesterol (TC), triglycerides (TG), serum leptin, or hs-CRP. Significant correlation was observed between

Clinical significance of measurement of changes of serum hs-CRP, IL-6, IL-8 M-CSF levels after treatment in patients with endometriosis

International Nuclear Information System (INIS)

Chen Xiaochao; Zhou Dongxia; Zhang Limin; Liu Hongshu

2008-01-01

Objective: To explore the significance of changes of serum hs-CRP, IL-6, IL-8 and M-CSF levels after treatment in patients with endometriosis. Methods: Serum IL-6, IL-8, M -CSF(with RIA), hs-CRP(with immuneturbidity method)levels were determined in 33 patients with endometriosis both before and after treatment as well as in 35 controls. Results: Before treatment, the serum hs-CRP, IL-6, IL-8 and M-CSF levels were significantly higher in the patients than those in controls (P 0.05). Conclusion: Detection of serum hs-CRP, IL-6, IL-8 and M-CSF levels might reflect the progress of diseases in patients with endometriosis. (authors)

Streptomyces flavogriseus HS1: isolation and characterization of extracellular proteases and their compatibility with laundry detergents.

Science.gov (United States)

Ghorbel, Sofiane; Kammoun, Maher; Soltana, Hala; Nasri, Moncef; Hmidet, Noomen

2014-01-01

The present study describes the isolation of a new protease producing Streptomyces strain HS1 and the biochemical characterization of the secreted proteases. By sequencing of its noted 16S rDNA, HS1 strain was found to have a 100% identity with Streptomyces flavogriseus. The highest protease production was found using FermII media. In these conditions maximum protease production (99 U/mL) was obtained after 96 h incubation at 30°C and 150 rpm. HS1 strain produced at least five proteases as revealed by zymogram technique. The enzyme preparation exhibited activity over a broad range of pH (5-11) and temperature (25-70°C). Optimum activity was observed at a pH of 7.0 and a temperature of 50°C. Proteolytic activity was significantly unaffected by Ca(2+) and Mg(2+). EDTA and PMSF highly decreased the original activity. The crude extracellular proteases showed high stability when used as a detergent additive. These properties offer an interesting potential for enzymatic hydrolysis at the industrial level.

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/.

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.

基于HS-Clustering的风电场机组分组功率预测%Wind Power Forecasting for Clustering Wind Turbines Based on HS-Clustering

Institute of Scientific and Technical Information of China (English)

高小力; 张智博; 田启明; 刘永前

2017-01-01

为了寻求风电场功率预测精度和计算效率二者的平衡,提出了一种基于霍普金斯统计量与聚类算法(HS-Clustering)的风电场机组分组功率预测方法,该方法将霍普金斯统计量与聚类算法的优势有效结合,采用霍普金斯统计量确定场内机组分组个数,通过聚类算法识别不同机组的相似性将风电场分成不同的机组群,然后对每组机群分别建立功率预测模型,从而叠加得到整场输出功率;另外以实测风速、实测功率及二者组合作为机组分组模型输入,分析其对预测精度的影响程度.实例分析表明基于HS-Clustering的分组预测方法可以显著提高预测精度,同时保证较高的计算效率;风速是影响分组效果的主要因素,对于某些分组模型,功率又可以作为风速的重要补充.%In order to balance the forecast accuracy and computational efficiency, a wind power forecasting method for clustering wind turbines is proposed based on effective combination of Hopkins statistics (HS) and clustering methods, in which Hopkins Statistics is used to determine the clustering number of a wind farm, and wind turbines in a wind farm are clustered into several groups according to the identifying of similar characteristics by clustering method.Then power forecasting model of each clustering group is built separately, whose power output is added to obtain whole power output of the wind farm.In addition, the real-time monitoring wind speed, power output and their combination are taken as the inputs for clustered group model, and their influences on the accuracy of clustering forecast model are analyzed.The case analysis shows that the HS-Clustering based forecasting method can effectively forecast the output power of the whole wind farm with better accuracy and higher computational efficiency, wind speed is the main factor affecting clustering results, and wind power can be regarded as an important additional factor as to certain

A Modified Constitutive Model for Tensile Flow Behaviors of BR1500HS Ultra-High-Strength Steel at Medium and Low Temperature Regions

Science.gov (United States)

Zhao, Jun; Quan, Guo-Zheng; Pan, Jia; Wang, Xuan; Wu, Dong-Sen; Xia, Yu-Feng

2018-01-01

Constitutive model of materials is one of the most requisite mathematical model in the finite element analysis, which describes the relationships of flow behaviors with strain, strain rate and temperature. In order to construct such constitutive relationships of ultra-high-strength BR1500HS steel at medium and low temperature regions, the true stress-strain data over a wide temperature range of 293-873 K and strain rate range of 0.01-10 s-1 were collected from a series of isothermal uniaxial tensile tests. The experimental results show that stress-strain relationships are highly non-linear and susceptible to three parameters involving temperature, strain and strain rate. By considering the impacts of strain rate and temperature on strain hardening, a modified constitutive model based on Johnson-Cook model was proposed to characterize flow behaviors in medium and low temperature ranges. The predictability of the improved model was also evaluated by the relative error (W(%)), correlation coefficient (R) and average absolute relative error (AARE). The R-value and AARE-value for modified constitutive model at medium and low temperature regions are 0.9915 & 1.56 % and 0.9570 & 5.39 %, respectively, which indicates that the modified constitutive model can precisely estimate the flow behaviors for BR1500HS steel in the medium and low temperature regions.

P-HS-SFM: a parallel harmony search algorithm for the reproduction of experimental data in the continuous microscopic crowd dynamic models

Science.gov (United States)

Jaber, Khalid Mohammad; Alia, Osama Moh'd.; Shuaib, Mohammed Mahmod

2018-03-01

Finding the optimal parameters that can reproduce experimental data (such as the velocity-density relation and the specific flow rate) is a very important component of the validation and calibration of microscopic crowd dynamic models. Heavy computational demand during parameter search is a known limitation that exists in a previously developed model known as the Harmony Search-Based Social Force Model (HS-SFM). In this paper, a parallel-based mechanism is proposed to reduce the computational time and memory resource utilisation required to find these parameters. More specifically, two MATLAB-based multicore techniques (parfor and create independent jobs) using shared memory are developed by taking advantage of the multithreading capabilities of parallel computing, resulting in a new framework called the Parallel Harmony Search-Based Social Force Model (P-HS-SFM). The experimental results show that the parfor-based P-HS-SFM achieved a better computational time of about 26 h, an efficiency improvement of ? 54% and a speedup factor of 2.196 times in comparison with the HS-SFM sequential processor. The performance of the P-HS-SFM using the create independent jobs approach is also comparable to parfor with a computational time of 26.8 h, an efficiency improvement of about 30% and a speedup of 2.137 times.

Benchmarking (Code2Code) of the 1Hs 3-Bladed Onshore VAWT

DEFF Research Database (Denmark)

Galinos, Christos; Schmidt Paulsen, Uwe

This study is part of the Inflow project. In this report the Nenuphar’s onshore 3-bladed Vertical Axis Wind Turbine (VAWT) prototype (1HS) is modelled in HAWC2 aeroelastic code. In the first part the model properties are summarized. Then the analysis is focused on the rotor performance and various...

HS and E Application Technology branch progress report, July 1982-July 1983

International Nuclear Information System (INIS)

Deitesfeld, C.A.

1984-01-01

This report summarizes the applied research activities of the Health, Safety and Environment (HS and E) Application Technology branch at Rocky Flats Plant from July 1982 to July 1983. In this report, major headings present studies in three fields: general safety, radiation safety and environment, and health and safety engineering and meteorological studies

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....

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

Science.gov (United States)

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

2018-05-31

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

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

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.

Association of HS6ST3 gene polymorphisms with obesity and triglycerides: gene x gender interaction.

Science.gov (United States)

Wang, Ke-Sheng; Wang, Liang; Liu, Xuefeng; Zeng, Min

2013-12-01

The heparan sulfate 6-O-sulfotransferase 3 (HS6ST3) gene is involved in heparan sulphate and heparin metabolism, and has been reported to be associated with diabetic retinopathy in type 2 diabetes.We hypothesized that HS6ST3 gene polymorphisms might play an important role in obesity and related phenotypes (such as triglycerides). We examined genetic associations of 117 single-nucleotide polymorphisms (SNPs) within the HS6ST3 gene with obesity and triglycerides using two Caucasian samples: the Marshfield sample (1442 obesity cases and 2122 controls), and the Health aging and body composition (Health ABC) sample (305 cases and 1336 controls). Logistic regression analysis of obesity as a binary trait and linear regression analysis of triglycerides as a continuous trait, adjusted for age and sex, were performed using PLINK. Single marker analysis showed that six SNPs in the Marshfield sample and one SNP in the Health ABC sample were associated with obesity (P triglycerides in the Marshfield sample (P triglycerides in the Marshfield sample. These findings contribute new insights into the pathogenesis of obesity and triglycerides and demonstrate the importance of gender differences in the aetiology.

Development and validation of the International Hidradenitis Suppurativa Severity Score System (IHS4), a novel dynamic scoring system to assess HS severity

DEFF Research Database (Denmark)

Zouboulis, C C; Tzellos, T; Kyrgidis, A

2017-01-01

BACKGROUND: A validated tool for the dynamic severity assessment of hidradenitis suppurativa/acne inversa (HS) is lacking. OBJECTIVES: To develop and validate a novel dynamic scoring system to assess the severity of HS. METHODS: A Delphi voting procedure was conducted among the members......, as well as examination for correlation (Spearman's rho) and agreement (Cohen's kappa) with existing scores, were engaged to recognize the variables for a new International HS4 (IHS4) that was established by a second Delphi round. RESULTS: Consensus HS4 was based on number of skin lesions, number of skin....... Three candidate scores were presented to the second Delphi round. The resulting IHS4 score is arrived at by the number of nodules (multiplied by 1) plus the number of abscesses (multiplied by 2) plus the number of draining tunnels (multiplied by 4). A total score of 3 or less signifies mild, 4...

Transitioning high sensitivity cardiac troponin I (hs-cTnI) into routine diagnostic use: More than just a sensitivity issue

LENUS (Irish Health Repository)

Lee, Graham R

2016-04-01

High sensitivity cardiac troponin T and I (hs-cTnT and hs-cTnI) assays show analytical, diagnostic and prognostic improvement over contemporary sensitive cTn assays. However, given the importance of troponin in the diagnosis of myocardial infarction, implementing this test requires rigorous analytical and clinical verification across the total testing pathway. This was the aim of this study.

The influence of alkali fatty acids on the properties and the stability of parenteral O/W emulsions modified with solutol HS 15.

Science.gov (United States)

Buszello, K; Harnisch, S; Müller, R H; Müller, B W

2000-03-01

Arachis oil based parenteral O/W emulsions were prepared using soya bean phosphatidylcholine (SPC) and different combinations of co-emulsifiers containing polyethylene glycol fatty acid esters (Solutol HS 15) and alkali fatty acids (sodium laurate, sodium stearate). The parameters measured were droplet size (both by photon correlation spectroscopy and laser diffractometry), pH and zeta potential. All emulsions were subjected to autoclaving. The addition of polyethylene glycol 12-hydroxy stearate (Solutol HS 15) led to a significant decrease of mean oil droplet size. For long-term stability the amount added turned out to be the most important factor. With increased amounts of Solutol HS 15 the packing density of the emulsifier layer and the zeta potential decreased leading to instability. The optimum load of Solutol HS 15 was found to be 15 micromol/ml. Alkali fatty acids markedly improved the physical stability of the emulsions. Improved stability properties conferred to emulsions by alkali fatty acids could be attributed to the zeta potential increase even in the presence of Solutol HS 15. Consequently a mixed emulsifier film was established in which the ionized fatty acids determined the interface charge. In addition to this a strengthening of the molecular interactions occurring between phospholipid and Solutol HS 15 emulsifier in the presence of ionized fatty acids at the O/W interface can be assumed (L. Rydhag, The importance of the phase behaviour of phospholipids for emulsion stability, Fette Seifen Anstrichm. 81 (1979) 168-173). Different co-emulsifier mixtures were shown to have a pronounced impact on the plasma protein adsorption onto emulsion droplets.

Low grade inflammation as measured by levels of YKL-40

DEFF Research Database (Denmark)

Rathcke, Camilla Noelle; Raymond, Ilan; Kistorp, Caroline

2010-01-01

, increasing YKL-40 levels independently predicted overall and CV mortality rate with hazard ratios of 1.58 (95% confidence interval (CI), 1.12-2.23, p=0.009) and 1.57 (95% CI, 1.00-2.46, p=0.049) after adjustment for age, sex, smoking, total cholesterol, hsCRP, NT-proBNP and UACR. In combined Kaplan...

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

Serum YKL-40 predicts long-term mortality in patients with stable coronary disease

DEFF Research Database (Denmark)

Harutyunyan, Marina; Gøtze, Jens P; Winkel, Per

2013-01-01

We investigated whether the inflammatory biomarker YKL-40 could improve the long-term prediction of death made by common risk factors plus high-sensitivity C-reactive protein (hs-CRP) and N-terminal-pro-B natriuretic peptide (NT-proBNP) in patients with stable coronary artery disease (CAD)....

A comparison of osteoprotegerin with adiponectin and high-sensitivity C-reactive protein (hsCRP) as a marker for insulin resistance.

LENUS (Irish Health Repository)

O'Sullivan, Eoin P

2013-01-01

Insulin resistance (IR) is associated with low adiponectin and elevated high sensitivity C-reactive protein (hsCRP). Osteoprotegerin (OPG) has been shown to be elevated in type 2 diabetes, but whether it reflects underlying IR is unclear. We aimed to compare the ability of serum OPG with adiponectin and hsCRP to act as a marker for IR in individuals with normal and abnormal glucose tolerance.

Clinical significance of determination of changes of serum IGF-II, IL-6, IL-8 and hs-CRP levels after treatment in pediatric patients with bronchopneumonia

International Nuclear Information System (INIS)

Wang Guanghui; Chen Chuanbing; Wang Xianwu

2009-01-01

Objective: To explore the clinical significance of changes of serum IGF-II, IL-6, IL-8 and hs-CRP levels after treatment in pediatric patients with bronchopneumonia. Methods: Serum IGF-II, IL-6, IL-8 (with RIA) and hs-CRP (with immunoturbidity method) levels were determined in 36 pediatric patients with bronchopneumonia both before and after treatment as well as in 35 controls. Results: Before treatment, serum IGF-II, IL-6, IL-8 and hs-CRP levels in the patients were significantly higher than those in the controls (P 0.05). Conclusion: Determination of serum IGF-II, IL-6, IL-8 and hs-CRP levels in pediatric patients with bronchopneumonia was important for diagnosis and outcome prediction. (authors)

Determination of Sesquiterpenes in Wines by HS-SPME Coupled with GC-MS

OpenAIRE

Cincotta, Fabrizio; Verzera, Antonella; Tripodi, Gianluca; Condurso, Concetta

2015-01-01

The sesquiterpene compounds present in red wines were characterized and quantified by Headspace Solid-Phase Microextraction in combination with Gas Chromatography–Mass Spectrometry (HS-SPME-GC-MS). Sixteen sesquiterpenes were identified, mainly hydrocarbons but also derived oxygenated compounds. Sesquiterpenes were acyclic, monocyclic, byciclic and tryciclic. Sesquiterpenes were detected in SIM (selected ion monitoring) mode using their characteristics ions. All the sesquiterpenes were identi...

Lipid nanocapsules containing the non-ionic surfactant Solutol HS15 inhibit the transport of calcium through hyperforin-activated channels in neuronal cells.

Science.gov (United States)

Chauvet, Sylvain; Barras, Alexandre; Boukherroub, Rabah; Bouron, Alexandre

2015-12-01

Hyperforin is described as a natural antidepressant inhibiting the reuptake of neurotransmitters and also activating cation channels. However the blood-brain barrier limits the access to the brain of this biomolecule. To circumvent this problem it was envisaged to encapsulate hyperforin into biomimetic lipid nano-carriers like lipid nanocapsules (LNCs). When testing the safety of 25 nm LNCs it appeared that they strongly blocked hyperforin-activated Ca2+ channels of cultured cortical neurons. This inhibition was due to one of their main component: solutol HS15 (polyoxyethylene-660-12-hydroxy stearate), a non-ionic soluble surfactant. Solutol HS15 rapidly depresses in a concentration-dependent manner the entry of Ca2+ through hyperforin-activated channels without influencing store-operated channels. This effect is mimicked by Brij58 but not by PEG600, indicating that the lipid chain of Solutol HS15 is important in determining its effects on the channels. The inhibition of the Ca2+ fluxes depends on the cellular cholesterol content; it is stronger after depleting cholesterol with methyl-β-cyclodextrin and is nearly absent on cells cultured in a cholesterol-rich medium. When chronically applied for 24 h, Solutol HS15 slightly up-regulates the entry of Ca2+ through hyperforin-activated channels. Similar observations were made when testing 25 nm lipid nanocapsules containing the surfactant Solutol HS15. Altogether, this study shows that Solutol HS15 perturbs in a cholesterol-dependent manner the activity of some neuronal channels. This is the first demonstration that LNCs containing this surfactant can influence cellular calcium signaling in the brain, a finding that can have important clinical implications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Clinical significance of determination of changes of serum hs-CRP, TNF-α and E2 levels in female children with simple obesity

International Nuclear Information System (INIS)

Xue Jie; Xu Weiqin; Zhou Hong; Liu Hongshu

2008-01-01

Objective: To explore the clinical significance of changes of serum hs-CRP, TNF-α and E 2 levels in female children with simple obesity. Methods: Serum levels of TNF-α, E 2 (with RIA) and hs-CRP (with immunity turbidity) were detected in 34 female children with simple obesity and 35 controls. Results: In the children with simple obesity, the serum hs-CRP, TNF- α and E 2 levels were significantly higher than those in controls (P 2 levels were mutually positively correlated (r=0.6182, 0.5784, P 2 levels is of help for assessment of severity of obesity as well as outcome prediction in female children. (authors)

On the Correct Application of the 100-40-40 Rule for Combining Responses Due to three Directions of Earthquake Loading

International Nuclear Information System (INIS)

Nie, J.; Morante, R.; Miranda, M.; Braverman, J.

2010-01-01

The 100-40-40 rule is often used with the response spectrum analysis method to determine the maximum seismic responses from structural responses resulting from the three spatial earthquake components. This rule has been referenced in several recent Design Certification applications of nuclear power plants, and appears to be gaining in popularity. However, this rule is described differently in ASCE 4-98 and Regulatory Guide 1.92, consequently causing confusion on correct implementation of this rule in practice. The square root of the sum of the squares method is another acceptable spatial combination method and was used to justify the adequacy of the 100-40-40 rule during the development of the Regulatory Guide 1.92. The 100-40-40 rule, when applied correctly, is almost always conservative compared to the SRSS method, and is only slightly unconservative in rare cases. The purpose of this paper is to describe in detail the proper application of the 100-40-40 rule, as prescribed in ASCE 4-98 and in Regulatory Guide 1.92, and to clarify the confusion caused by the two different formats of this rule.

On the Correct Application of the 100-40-40 Rule for Combining Responses Due to three Directions of Earthquake Loading

Energy Technology Data Exchange (ETDEWEB)

Nie, J.; Morante, R.; Miranda, M., Braverman, J.

2010-07-18

The 100-40-40 rule is often used with the response spectrum analysis method to determine the maximum seismic responses from structural responses resulting from the three spatial earthquake components. This rule has been referenced in several recent Design Certification applications of nuclear power plants, and appears to be gaining in popularity. However, this rule is described differently in ASCE 4-98 and Regulatory Guide 1.92, consequently causing confusion on correct implementation of this rule in practice. The square root of the sum of the squares method is another acceptable spatial combination method and was used to justify the adequacy of the 100-40-40 rule during the development of the Regulatory Guide 1.92. The 100-40-40 rule, when applied correctly, is almost always conservative compared to the SRSS method, and is only slightly unconservative in rare cases. The purpose of this paper is to describe in detail the proper application of the 100-40-40 rule, as prescribed in ASCE 4-98 and in Regulatory Guide 1.92, and to clarify the confusion caused by the two different formats of this rule.

Occupational Accident Declaration Form (HS50)

CERN Multimedia

HR Department

2007-01-01

https://cern.ch/service-procedures/AdminMan/Forms/HS50E.doc •\tIt must be completed within 10 working days of the date on which the accident occurred (§ 29.2.1), unless the person concerned is materially unable to meet this deadline. • The completed formula must be accompanied by a medical certificate giving details of any bodily injuries resulting from the accident (Annex 1, § 5). The medical certificate must be obtained from the doctor who has been consulted for that purpose. Benefits resulting from illnesses and accidents Medical treatment will cease to be reimbursed under the occupational scheme in the event of cure (defined in § 15 as the certified end to the impairment of the patient’s state of health caused by the illness or accident), or consolidation (defined in § 14 as certification that no further improvement in the patient’s state of health can be expected from appropriate medical treatment). The right to such reimbursement shall resume only in the...

Proinsulin, adiponectin and hsCRP in reproductive age women with polycystic ovary syndrome (PCOS)--the effect of metformin treatment.

Science.gov (United States)

Kruszyńska, Aleksandra; Słowińska-Srzednicka, Jadwiga; Jeske, Wojciech; Zgliczyński, Wojciech

2014-01-01

Women with polycystic ovary syndrome (PCOS) often suffer from obesity and insulin resistance. The role of proinsulin, which is known to be an indicator of fertility outcomes in PCOS women, and that of adiponectin, in the pathogenesis of PCOS is not well elucidated. Our objective was to determine proinsulin, adiponectin, hsCRP and other hormonal and metabolic parameters in PCOS women before and after metformin treatment. Two PCOS groups of patients of reproductive age (90 lean and 88 obese or overweight) with two control groups, adjusted for body mass index (BMI), were compared at baseline. 32 PCOS women were studied at baseline, after three and six months of metformin (1,000 mg/day) treatment. Clinical, anthropometric, biochemical and hormonal parameters were assessed. Proinsulin and hsCRP levels were the highest in obese PCOS women and were statistically different than in lean PCOS women (proinsulin: 11.4 v. 6.9 pmol/L; hsCRP 2.46 v. 0.47 mg/L, p treatment only in obese PCOS women. PCOS, when accompanied by obesity, is associated with elevated proinsulin concentrations, which correlates with higher hsCRP and increased FAI. Proinsulin level decreases due to metformin treatment. Our results suggest that obese or overweight PCOS and lean PCOS are characterised by different hormonal and metabolic parameters and have a different response to metformin treatment.

YKL-40, a biomarker of inflammation, is elevated in patients with type 2 diabetes and is related to insulin resistance

DEFF Research Database (Denmark)

Rathcke, C N; Johansen, J S; Vestergaard, H

2006-01-01

YKL-40 participates in inflammatory states and vascular processes, which implies that comparison can be made with other inflammatory markers associated with insulin resistance and type 2 diabetes (T2D). In the present study levels of plasma YKL-40 and serum hsCRP were evaluated in patients with T2D....

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.

77 FR 19033 - Effect of Adding References to HS 6104.32 To Correct the U.S.-Korea FTA Product-Specific Rules of...

Science.gov (United States)

2012-03-29

... INTERNATIONAL TRADE COMMISSION [Investigation No. Korea FTA-103-026] Effect of Adding References to HS 6104.32 To Correct the U.S.- Korea FTA Product-Specific Rules of Origin AGENCY: United States... investigation No. Korea FTA-103-026, Effect of Adding References to HS 6104.32 To Correct the U.S.-Korea FTA...

Clinical significance of determination of changes in serum hs-CRP, IL-6, IL-10, and IL-18 levels after treatment in patients with acute conjunctivitis

International Nuclear Information System (INIS)

Liu Jun

2007-01-01

Objective: To study the clinical significance of changes of serum hs-CRP, IL-6, IL-10 and IL-18 levels in patients with acute conjunctivitis after treatment. Methods: Serum IL-6, IL-10 (with RIA) hs-CRP (with Immuno-turbidity) and IL-18 (with ELISA) levels were measured in 38 patients with acute conjunctivitis both before and after treatment as well as in 35 controls. Results: The serum hs-CRP, IL-6, IL-10 and IL-18 levels in the patients before treatment were significantly higher than those in the controls (P 0.05). Conclusion: Measurement of the changes of serum hs-CRP, IL-6, IL-10 and IL-18 levels after treatment might be inportant for outcome prediction in patients with acute conjunctivitis. (authors)

Comparison and characterization of volatile compounds as markers of oils stability during frying by HS-SPME-GC/MS and Chemometric analysis.

Science.gov (United States)

Ben Hammouda, Ibtissem; Freitas, Flavia; Ammar, Sonda; Da Silva, M D R Gomes; Bouaziz, Mohamed

2017-11-15

The formation and emission of volatile compounds, including the aldehydes and some toxic compounds of oil samples, ROPO pure (100%) and the blended ROPO/RCO (80-20%), were carried out during deep frying at 180°C. The volatile profile of both oil samples was evaluated by an optimized HS-SPME-GC/MS method, before and after 20, 40 and 60 successive sessions of deep-frying. Actually, from 100 detected compounds, aldehydes were found to be the main group formed. In addition, the oil degradation under thermal treatment regarding the volatile compounds were evaluated and compared. Consequently, the blended ROPO/RCO revealed fewer formations of unsaturated aldehydes, including toxic ones, such as acrolein, and showed a greater stability against oxidative thermal degradation compared to ROPO pure. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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.

SugE belongs to the small multidrug resistance (SMR) protein family involved in tributyltin (TBT) biodegradation and bioremediation by alkaliphilic Stenotrophomonas chelatiphaga HS2.

Science.gov (United States)

Hassan, Hamdy A

2018-03-01

Tributyltin (TBT) used in a variety of industrial processes, subsequent discharge into the environment, its fate, toxicity and human exposure are topics of current concern. TBT degradation by alkaliphilic bacteria may be a key factor in the remediation of TBT in high pH contaminated sites. In this study, Stenotrophomonas chelatiphaga HS2 were isolated and identified from TBT contaminated site in Mediterranean Sea. S. chelatiphaga HS2 has vigor capability to transform TBT into dibutyltin and monobutyltin (DBT and MBT) at pH 9 and 7% NaCl (w/v). A gene was amplified and characterized from strain HS2 as SugE protein belongs to SMR protein family, a reverse transcription polymerase chain reaction analysis confirmed that SugE protein involved in the TBT degradation by HS2 strain. TBT bioremediation was investigated in stimulated TBT contaminated sediment samples (pH 9) using S chelatiphaga HS2 in association with E. coli BL21 (DE3)-pET28a(+)-sugE instead of S chelatiphaga HS2 alone reduced significantly the TBT half-life from 12d to 5d, although no TBT degradation appeared using E. coli BL21 (DE3)-pET28a(+)-sugE alone. This finding indicated that SugE gene increased the rate and degraded amount of TBT and is necessary in enhancing TBT bioremediation. Copyright © 2017 Elsevier B.V. All rights reserved.

A novel imidazopyridine derivative, HS-106, induces apoptosis of breast cancer cells and represses angiogenesis by targeting the PI3K/mTOR pathway.

Science.gov (United States)

Li, Guang-Yong; Jung, Kyung Hee; Lee, Hyunseung; Son, Mi Kwon; Seo, JuHyeon; Hong, Sang-Won; Jeong, Yujeong; Hong, Sungwoo; Hong, Soon-Sun

2013-02-01

Abnormal activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway is an essential step for the formation and growth of tumors in humans. HS-106 is an imidazopyridine derivative that inhibits the kinase activity of PI3K by binding to the ATP-binding cleft. We found that this compound suppressed breast cancer cell proliferation and induced apoptosis by specifically inhibiting the activity of target proteins in the PI3K/Akt/mTOR signaling pathway. Cell cycle analysis revealed that treatment with HS-106 resulted in cell cycle arrest at the G(2)/M phase due to up-regulation of p-cdc25 and down-regulation of cyclin B1. Also, HS-106 induced apoptosis by increasing the levels of cleaved caspase-3 and cleaved PARP. In addition, chromatin condensation and apoptotic bodies were detected in HS-106-treated breast cancer cells. Furthermore, HS-106 decreased the expression of hypoxia-inducible factor 1α (HIF-1α), and inhibited tube formation and migration of human umbilical vein endothelial cells (HUVECs) in vitro and blood vessel formation in an in vivo Matrigel plug assay. These results show that HS-106 may be an effective novel therapeutic candidate in clinical trials as a potential treatment for human breast cancers or other advanced malignancies with aberrant PI3K/Akt/mTOR signaling. Crown Copyright © 2012. Published by Elsevier Ireland Ltd. All rights reserved.

The effect of novel surfactants and Solutol HS 15 on paclitaxel aqueous solubility and permeability across a Caco-2 monolayer.

Science.gov (United States)

Alani, Adam W G; Rao, Deepa A; Seidel, Ron; Wang, Jian; Jiao, Jim; Kwon, Glen S

2010-08-01

The effect of novel surfactants on the aqueous solubility and the permeability of paclitaxel across a Caco-2 cell monolayer were examined in this work. The solubility and permeability of paclitaxel was evaluated in the presence of four soft surfactants (SS) KXN441, KXN424, KXN437, and KXN 337 and Solutol HS15. All surfactants increased the aqueous solubility of paclitaxel. Caco-2 cell membrane integrity in the presence of SS and Solutol HS15 was assessed by mannitol permeability and LDH release. All surfactants were tested at 0.5x CMC, 5x CMC and 1.5 mM concentrations. The effect of SSs on paclitaxel permeability was concentration dependent. At all concentrations tested, KXN 441 and Solutol HS 15 showed partially inhibition of drug efflux with no discernable change in mannitol permeability or cytotoxicity as observed with LDH release. At these concentrations, other SSs exhibited some partial efflux inhibition along with compromised membrane integrity and increasing mannitol permeability. In conclusion, all SSs were able to increase the aqueous solubility and permeability of paclitaxel across Caco-2 cells monolayer. However, KXN441 and Solutol HS15 were able to enhance paclitaxel permeability across Caco-2 monolayer without cytotoxicity. (c) 2010 Wiley-Liss, Inc. and the American Pharmacists Association

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.

10 CFR 40.64 - Reports.

Science.gov (United States)

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Reports. 40.64 Section 40.64 Energy NUCLEAR REGULATORY COMMISSION DOMESTIC LICENSING OF SOURCE MATERIAL Records, Reports, and Inspections § 40.64 Reports. (a... in the fabrication of mixed-oxide fuels, shall complete a Nuclear Material Transaction Report in...

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)

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)

A randomized controlled clinical trial investigating the effect of calcium supplement plus low-dose aspirin on hs-CRP, oxidative stress and insulin resistance in pregnant women at risk for pre-eclampsia.

Science.gov (United States)

Asemi, Z; Samimi, M; Heidarzadeh, Z; Khorrammian, H; Tabassi, Z

2012-05-15

Increased levels of pro-inflammatory factors, markers of oxidative stress and insulin resistance during pregnancy have been associated with the development of pre-eclampsia. There is some evidence to suggest that calcium supplement and aspirin can reduce the risk of the disorder. To our knowledge, no reports are available indicating the effects of consumed calcium supplement plus aspirin on high sensitivity C-reactive protein (hs-CRP), oxidative stress parameters and insulin resistance in pregnant women at risk for pre-eclampsia. This study was designed to investigate the effects of consumed calcium supplement plus low-dose aspirin on hs-CRP, oxidative stress parameters and insulin resistance among Iranian pregnant women at risk for pre-eclampsia. This randomized single-blind controlled clinical trial was carried out among 42 pregnant women at risk for pre-eclampsia, primigravida, aged 18-40 year old who were carrying singleton pregnancy at their third trimester. Subjects were randomly assigned to received either the placebo (n = 22) or calcium supplement plus low-dose aspirin (n = 20) for 9 weeks. Calcium supplement plus low-dose aspirin were containing 500 mg carbonate calcium plus 80 mg aspirin. Fasting blood samples were taken at baseline and after 9 weeks intervention to measure serum hs-CRP, oxidative stress parameters including plasma Total Antioxidant Capacity (TAC) and Total Glutathione (GSH), Fasting Plasma Glucose (FPG), serum insulin and HOMA-IR score. Consumption of calcium supplement plus low-dose aspirin resulted in a significant difference serum hs-CRP levels as compared to the placebo (102.87 vs. 3227.75 ng mL(-1), p = 0.01). Also, mean changes for plasma TAC (68.96 vs. -74.46 mmol L(-1), p = 0.04) and total GSH levels (304.33 vs. -39.33 micromol L(-1), p = 0.03) were significantly different between the two groups. No significant differences were found comparing calcium supplement plus low-dose aspirin and placebo in terms of their effects on FPG

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.

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...

Improved selectivity and cytotoxic effects of irinotecan via liposomal delivery: A comparative study on Hs68 and HeLa cells.

Science.gov (United States)

Casadó, Ana; Mora, Margarita; Sagristá, Maria Lluïsa; Rello-Varona, Santi; Acedo, Pilar; Stockert, Juan Carlos; Cañete, Magdalena; Villanueva, Angeles

2017-11-15

Irinotecan (CPT-11) is an effective chemotherapeutic agent widely used to treat different cancers. Otherwise, the liposomal delivery of anti-tumor agents has been shown to be a promising strategy. The aim of this study has been to analyze the effect of liposomal CPT-11 (CPT-11lip) on two human cell lines (Hs68 and HeLa) to establish the suitability of this CPT-11 nanocarrier. We have demonstrated the highest uptake of CPT-11lip in comparison with that of CPT-11sol, in lactate buffer, and that CPT-11lip was internalized in the cells through an endocytic process whereas CPT-11sol does so by passive diffusion. CPT-11lip was not cytotoxic to normal fibroblast Hs68 cells, but induced a massive apoptosis accompanied by cell senescence in HeLa cells. CPT-11lip treatment modified the morphology of HeLa cells, induced different cell cycle alterations and accumulated into lysosomes in both cell lines. In particular, CPT-11lip treatment showed that surviving HeLa cells remained in a state of senescence whereas only a temporal growth arrest was induced in Hs68 cells. Results of RT-PCR indicated that the different responses in Hs68 (survival) and HeLa cells (apoptotic death), seemed to be induced by a p53- and p53- independent mechanism, respectively. An analysis of DNA damage also determined that released CPT-11 from liposomes was able to reach the nucleus and exert a genotoxic effect in both cell lines, which was repaired in Hs68 but not in HeLa cells. All results indicate that phospholipid-cholesterol liposomes possess optimum properties for CPT-11 delivery, being biocompatible and selectively cytotoxic against HeLa tumorigenic cells. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Relationship between degree of risk, cost and level of compliance to occupational health and safety regulations in construction

Directory of Open Access Journals (Sweden)

Abimbola Olukemi Windapo

2013-06-01

Full Text Available This paper investigates the role of statutory health and safety (H&S regulations in managing construction project risks. The study examines whether the decision made by contractors to comply with the regulations, the cost of compliance and savings of H&S regulatory requirements is influenced by the degree or level of risk, which the regulations are trying to prevent. The rationale for the examination stems from previous studies which establish that building designers and contractors perceive the cost of complying with regulations as additional burdens, which they have to conform to, and which are in some cases unnecessary, and also the fact that construction related injuries and fatalities are on the increase. Qualitative and quantitative data obtained from a descriptive survey and H&S site audit by the Master Builder Association of the Western Cape (MBAWC were used as the measurements of risk, level of compliance to regulations, cost of compliance and savings. By correlating the quantitative and qualitative data, there is empirical evidence to support a negative relationship between the degree of risk, level and cost of compliance and cost savings. Based on the study’s findings, this paper concludes that the decision made by contractors to comply with H&S regulatory requirements is influenced by the perceived cost saving on account of compliance and that cost savings are influenced by the probability of accident occurrence which is an element of the degree of risk which the regulation is trying to prevent or control. 

Relationship between degree of risk, cost and level of compliance to occupational health and safety regulations in construction

Directory of Open Access Journals (Sweden)

Abimbola Olukemi Windapo

2013-06-01

Full Text Available This paper investigates the role of statutory health and safety (H&S regulations in managing construction project risks. The study examines whether the decision made by contractors to comply with the regulations, the cost of compliance and savings of H&S regulatory requirements is influenced by the degree or level of risk, which the regulations are trying to prevent. The rationale for the examination stems from previous studies which establish that building designers and contractors perceive the cost of complying with regulations as additional burdens, which they have to conform to, and which are in some cases unnecessary, and also the fact that construction related injuries and fatalities are on the increase. Qualitative and quantitative data obtained from a descriptive survey and H&S site audit by the Master Builder Association of the Western Cape (MBAWC were used as the measurements of risk, level of compliance to regulations, cost of compliance and savings. By correlating the quantitative and qualitative data, there is empirical evidence to support a negative relationship between the degree of risk, level and cost of compliance and cost savings. Based on the study’s findings, this paper concludes that the decision made by contractors to comply with H&S regulatory requirements is influenced by the perceived cost saving on account of compliance and that cost savings are influenced by the probability of accident occurrence which is an element of the degree of risk which the regulation is trying to prevent or control.

Analysis of the optical emission of the young precataclysmic variables HS 1857+5144 and ABELL 65

Science.gov (United States)

Shimansky, V. V.; Pozdnyakova, S. A.; Borisov, N. V.; Bikmaev, I. F.; Vlasyuk, V. V.; Spiridonova, O. I.; Galeev, A. I.; Mel'Nikov, S. S.

2009-10-01

We analyze the physical state and the properties of the close binary systems HS 1857+5144 and Abell 65. We took the spectra of both systems over a wide range of orbital phases with the 6-m telescope of the Special Astrophysical Observatory of the Russian Academy of Sciences (SAO RAS) and obtained their multicolor light curves with the RTT150 and Zeiss-1000 telescopes of the SAO RAS. We demonstrate that both Abell 65 and HS 1857+5144 are young precataclysmic variables (PV) with orbital periods of P orb = 1. d 003729 and P orb = 0. d 26633331, respectively. The observed brightness and spectral variations during the orbital period are due to the radiation of the cold component, which absorbs the short-wave radiation of the hot component and reemits it in the visual part of the spectrum. A joint analysis of the brightness and radial velocity curves allowed us to find the possible and optimum sets of their fundamental parameters. We found the luminosity excesses of the secondary components of HS 1857+5144 and Abell 65 with respect to the corresponding Main Sequence stars to be typical for such objects. The excess luminosities of the secondary components of all young PVs are indicative of their faster relaxation rate towards the quiescent state compared to the rates estimated in earlier studies.

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.

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.

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.

Restriction of the use of hazardous substances (RoHS in the personal computer segment: analysis of the strategic adoption by the manufacturers settled in Brazil

Directory of Open Access Journals (Sweden)

Ademir Brescansin

2015-09-01

Full Text Available The enactment of the RoHS Directive (Restriction of Hazardous Substances in 2003, limiting the use of certain hazardous substances in electronic equipment has forced companies to adjust their products to comply with this legislation. Even in the absence of similar legislation in Brazil, manufacturers of personal computers which are located in this country have been seen to adopt RoHS for products sold in the domestic market and abroad. The purpose of this study is to analyze whether these manufacturers have really adopted RoHS, focusing on their motivations, concerns, and benefits. This is an exploratory study based on literature review and interviews with HP, Dell, Sony, Lenovo, Samsung, LG, Itautec, and Positivo, using summative content analysis. The results showed that initially, global companies adopted RoHS to market products in Europe, and later expanded this practice to all products. Brazilian companies, however, adopted RoHS to participate in the government’s sustainable procurement bidding processes. It is expected that this study can assist manufacturers in developing strategies for reducing or eliminating hazardous substances in their products and processes, as well as help the government to formulate public policies on reducing risks of environmental contamination.

Innovative analysis of HS 6-5-2 drills edges quality

Directory of Open Access Journals (Sweden)

Daicu Raluca

2017-01-01

Full Text Available The paper is analyzing the quality of Ø8 drills edges from HS 6-5-2 steel, using an innovative technique, the measurement of electrical current at cutting. The method is useful to take the right decision about drills acquisition from different suppliers based on the quality/price ratio. Also, it can be made a fast quality comparison of drills that leads to a selection of the acquisition places. The analysis of a drill batch is done using the microscope and the measurement of the electrical current at cutting, showing the better accuracy of the last method.

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)

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.

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...

A comparison study on a sulfonated graphene-polyaniline nanocomposite coated fiber for analysis of nicotine in solid samples through the traditional and vacuum-assisted HS-SPME.

Science.gov (United States)

Ghiasvand, Alireza; Koonani, Samira; Yazdankhah, Fatemeh; Farhadi, Saeid

2018-02-05

A simple, rapid, and reliable headspace solid-phase microextraction (HS-SPME) procedure, reinforced by applying vacuum in the extraction vial, was developed. It was applied for the extraction of nicotine in solid samples prior to determination by gas chromatography-flame ionization detection (GC-FID). First, the surface of a narrow stainless steel wire was made porous and adhesive by platinization to obtain a durable, higher surface area, and resistant fiber. Then, a thin film of sulfonated graphene/polyaniline (Sulf-G/PANI) nanocomposite was synthesized and simultaneously coated on the platinized fiber using the electrophoretic deposition (EPD) method. It was demonstrated that the extraction efficiency remarkably increased by applying the reduced-pressure condition in the extraction vial. To evaluate the conventional HS-SPME and vacuum-assisted HS-SPME (VA-HS-SPME) platforms, all experimental parameters affecting the extraction efficiency including desorption time and temperature, extraction time and temperature and moisture content of sample matrix were optimized. The highest extraction efficiency was obtained at 60°C, 10min (extraction temperature and time) and 280°C, 2min (desorption condition), for VA-HS-SPME strategy, while for conventional HS-SPME the extraction and desorption conditions found to be 100°C, 30min and 280°C, 2min, respectively. The Sulf-G/PANI coated fiber showed high thermal stability, good chemical/mechanical resistance, and long lifetime. For analysis of nicotine in solid samples using VA-HS-SPME-GC-FID, linear dynamic range (LDR) was 0.01-30μgg -1 (R 2 =0.996), the relative standard deviation (RSD%, n=6), for analyses of 1μgg -1 nicotine was calculated 3.4% and limit of detection (LOD) found to be 0.002μgg -1 . The VA-HS-SPME-GC-FID strategy was successfully carried out for quantitation of nicotine in hair and tobacco real samples. Copyright © 2017 Elsevier B.V. All rights reserved.

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

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)

The human homolog of S. cerevisiae CDC27, CDC27 Hs, is encoded by a highly conserved intronless gene present in multiple copies in the human genome

Energy Technology Data Exchange (ETDEWEB)

Devor, E.J.; Dill-Devor, R.M. [Univ. of Iowa College of Medicine, Iowa City (United States)

1994-09-01

We have obtained a number of unique sequences via PCR amplification of human genomic DNA using degenerate primers under low stringency (42{degrees}C). One of these, an 853 bp product, has been identified as a partial genomic sequence of the human homolog of the S. cerevisiae CDC27 gene, CDC27Hs (GenBank No. U00001). This gene, reported by Turgendreich et al. is also designated EST00556 from Adams et al. We have undertaken a more detailed examination of our sequence, MCP34N, and have found that: 1. the genomic sequence is nearly identical to CDC27Hs over its entire 853 bp length; 2. an MCP34N-specific PCR assay of several non-human primate species reveals amplification products in chimpanzee and gorilla genomes having greater than 90% sequence identity with CDC27Hs; and 3. an MCP34N-specific PCR assay of the BIOS hybrid cell line panel gives a discordancy pattern suggesting multiple loci. Based upon these data, we present the following initial characterization: 1. the complete MCP34N sequence identity with CDC27Hs indicates that the latter is encoded by an intronless gene; 2. CDC27Hs is highly conserved among higher primates; and 3. CDC27Hs is present in multiple copies in the human genome. These characteristics, taken together with those initially reported for CDC27Hs, suggest that this is an old gene that carries out an important but, as yet, unknown function in the human brain.

Correlation between Interleukin-6 (IL-6, High Sensitivity C-Reactive Protein (hsCRP, Endothelin-1 (ET-1, Asymmetric Dimethylarginine (ADMA and Insulin Resistance (HOMA-IR in Central Obese Men

Directory of Open Access Journals (Sweden)

Andri Hidayat

2011-04-01

Full Text Available BACKGROUND: Many studies have shown that obesity was closely related to insulin resistance via several pathways such as inflammation, oxidative stress, lipolysis, and endothelial dysfunction. This study was carried out to observe the correlation between inflammation (IL-6 and hsCRP, lipolysis process (ET-1, and endothelial dysfunction (ADMA and insulin resistance (HOMA-IR in centrally obese men. METHODS: This was a cross sectional study on 62 male subjects aged 30–60 years old with waist circumference (WC >90 cm. IL-6, ET-1 and ADMA levels were measured using ELISA method, while hsCRP and insulin were measured using chemiluminescence method. All blood testings were conducted in Prodia Clinical Laboratory. RESULTS: The results showed that WC was significantly correlated with hsCRP (r=0.294, p=0.022, ET-1 (r=0.257, p=0.047 and ADMA (r=0.338, p=0.009. We also found a significant correlation between hsCRP with HOMA-IR (r=0.324, p=0.021, ADMA with HOMA-IR (r=0.280, p=0.045 and IL-6 with hsCRP (r=0.437, p=0.003. CONCLUSIONS: hsCRP and ADMA have significant correlation with HOMA-IR in centrally obese men. HOMA-IR significantly increases in subjects with ADMA above median and either IL-6 or hsCRP above median, as compared to those in the other groups. Inflammation and endothelial dysfunction are important causal pathways of insulin resistance state in centrally obese men. KEYWORDS: obesity, IL-6, hsCRP, ET-1, ADMA, HOMA-IR.

HURRICANE AND SEVERE STORM SENTINEL (HS3) GLOBAL HAWK HIGH ALTITUDE MMIC SOUNDING RADIOMETER (HAMSR) V1

Data.gov (United States)

National Aeronautics and Space Administration — The Hurricane and Severe Storm Sentinel (HS3) Global Hawk High Altitude MMIC Sounding Radiometer (HAMSR) datasets include measurements gathered by the HAMSR...

HIGH-SENSITIVITY C-REACTIVE PROTEIN (hsCRP IN YOUNG ADULTS: RELATION TO AEROBIC CAPACITY, PHYSICAL ACTIVITY AND RISK FACTORS FOR CARDIOVASCULAR DISEASES

Directory of Open Access Journals (Sweden)

K. Mazurek

2011-11-01

Full Text Available Atheromatosis develops as a result of a chronic inflammatory process of the arteries. Inflammatory biomarkers, particularly high-sensitivity C-reactive protein (hsCRP, positively correlate with atheromatosis risk factors and can be used to estimate and predict the risk of cardiovascular events. The purpose of this study was to evaluate the relationship between hsCRP concentration and BMI, body composition, classical risk factors for cardiovascular diseases, energy expenditure for physical activity (WEE and  ·VO2max. 166 volunteers (78 women and 88 men were included in the examinations. Their mean age was 20.2±0.9 years. Health condition was described by the following variables: smoking, WEE,  ·VO2max, body mass index (BMI, waist-to-hip ratio (WHR, fat mass (FM, fat-free mass (FFM, lipid profile, hsCRP, glucose and insulin concentration, and insulin resistance. Between the subgroups created on the basis of hsCRP concentration, in quartiles 1 to 3 and quartile 4, a comparative analysis was carried out. 79.5�0of women and 69.3�0of men had hsCRP values within the references ranges. Moderately high values were found in 14.1�0of women and 22.7�0of men and high in 6.4�0and 7.9�20respectively. Mean values of BMI, FFM, WHR, WEE,  ·VO2max, glucose and triglyceride concentration, and TC/HDL index were significantly lower, while FM and HDL were significantly higher, in women than in men. In the quartile 4 subgroup compared to the quartile 1-3 subgroup, we found significantly lower HDL concentration and a tendency for higher values of BMI (p=0.06 and TC (p=0.07 as well as higher percentages of smoking among men. In young, physically active, healthy persons, serum concentration of hsCRP is not related to physical activity or  ·VO2max.

40 CFR 112.1 - General applicability.

Science.gov (United States)

2010-07-01

... storage tanks deferred under 40 CFR part 280 that supply emergency diesel generators at a nuclear power generation facility licensed by the Nuclear Regulatory Commission and subject to any Nuclear Regulatory... single-family residence; (E) The capacity of pesticide application equipment and related mix containers...

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

The effects of Ti and Sn alloying elements on precipitation strengthened Cu40Zn brass using powder metallurgy and hot extrusion

International Nuclear Information System (INIS)

Li Shufeng; Imai, Hisashi; Atsumi, Haruhiko; Kondoh, Katsuyoshi; Kojima, Akimichi; Kosaka, Yoshiharu; Yamamoto, Koji; Takahashi, Motoi

2012-01-01

Highlights: ► Alloying elements Ti and Sn are proposed as additives in 60/40 brass. ► Super-saturated Ti in powder creates high chemical potential for precipitation. ► Ti is readily segregated in primary particle boundaries in BS40–1.0Ti. ► Sn was proposed as an additive to inhibit segregation of Ti in BS40–1.0Ti. ► The introduction of Sn to BS40–1.0Ti brass effectively impedes Ti segregation. - Abstract: The effects of Ti and Sn alloying elements on the microstructural and mechanical properties of 60/40 brass were studied by powder metallurgy processing. The super-saturated solid solution of Ti creates a high precipitation reaction chemical potential in water-atomized BS40-1.0Ti brass powder. Consequently, BS40–1.0Ti brass was remarkably strengthened by the addition of Ti. However, Ti readily segregated in the primary particle boundaries at elevated temperatures, which detrimentally affected the mechanical properties of BS40–1.0Ti brass. Accordingly, Sn was proposed as an additive to BS40–0.6Sn1.0Ti to inhibit the segregation of Ti. Consequently, the Ti precipitate was retained in the form of CuSn 3 Ti 5 in the interior of grains and grain boundaries rather than in the primary particle boundaries. This result demonstrates that the addition of Sn can effectively hinder Ti segregation in the primary particle boundaries. Sn addition produced significant grain refinement and mechanical strengthening effects in BS40–0.6Sn1.0Ti brass. As a result, outstanding strengthening effects were observed for BS40–0.6Sn1.0Ti sintered at 600 °C, which exhibited a yield strength of 315 MPa, an ultimate tensile strength of 598 MPa, and a Vickers micro-hardness of 216 Hv. These values represent increases of 27.5%, 20.1% and 45.6%, over those of extruded BS40–1.0Ti brass.

The effects of Ti and Sn alloying elements on precipitation strengthened Cu40Zn brass using powder metallurgy and hot extrusion

Energy Technology Data Exchange (ETDEWEB)

Li Shufeng, E-mail: shufenglimail@gmail.com [Joining and Welding Research Institute, Osaka University (Japan); Imai, Hisashi; Atsumi, Haruhiko; Kondoh, Katsuyoshi [Joining and Welding Research Institute, Osaka University (Japan); Kojima, Akimichi; Kosaka, Yoshiharu [San-Etsu metals Co. Ltd., 1892, OHTA, Tonami, Toyama (Japan); Yamamoto, Koji; Takahashi, Motoi [Nippon Atomized Metal Powders Corporation, 87-16, Nishi-Sangao, Noda, Chiba (Japan)

2012-02-15

Highlights: Black-Right-Pointing-Pointer Alloying elements Ti and Sn are proposed as additives in 60/40 brass. Black-Right-Pointing-Pointer Super-saturated Ti in powder creates high chemical potential for precipitation. Black-Right-Pointing-Pointer Ti is readily segregated in primary particle boundaries in BS40-1.0Ti. Black-Right-Pointing-Pointer Sn was proposed as an additive to inhibit segregation of Ti in BS40-1.0Ti. Black-Right-Pointing-Pointer The introduction of Sn to BS40-1.0Ti brass effectively impedes Ti segregation. - Abstract: The effects of Ti and Sn alloying elements on the microstructural and mechanical properties of 60/40 brass were studied by powder metallurgy processing. The super-saturated solid solution of Ti creates a high precipitation reaction chemical potential in water-atomized BS40-1.0Ti brass powder. Consequently, BS40-1.0Ti brass was remarkably strengthened by the addition of Ti. However, Ti readily segregated in the primary particle boundaries at elevated temperatures, which detrimentally affected the mechanical properties of BS40-1.0Ti brass. Accordingly, Sn was proposed as an additive to BS40-0.6Sn1.0Ti to inhibit the segregation of Ti. Consequently, the Ti precipitate was retained in the form of CuSn{sub 3}Ti{sub 5} in the interior of grains and grain boundaries rather than in the primary particle boundaries. This result demonstrates that the addition of Sn can effectively hinder Ti segregation in the primary particle boundaries. Sn addition produced significant grain refinement and mechanical strengthening effects in BS40-0.6Sn1.0Ti brass. As a result, outstanding strengthening effects were observed for BS40-0.6Sn1.0Ti sintered at 600 Degree-Sign C, which exhibited a yield strength of 315 MPa, an ultimate tensile strength of 598 MPa, and a Vickers micro-hardness of 216 Hv. These values represent increases of 27.5%, 20.1% and 45.6%, over those of extruded BS40-1.0Ti brass.

Effects of RoHs and REACH regulations on firm-level production and export, and the role of global value chains : the cases of Malaysia and Vietnam

OpenAIRE

Otsuki, Tsunehiro; Honda, Keiichiro; Michida, Etsuyo; Nabeshima, Kaoru; Ueki, Yasushi

2015-01-01

This paper uses firm-level data to examine the impact of foreign chemical safety regulations such as RoHS and REACH on the production costs and export performance of firms in Malaysia and Vietnam. This paper also investigates the role of global value chains in enhancing the likelihood that a firm complies with RoHS and REACH. We find that in addition to the initial setup costs for compliance, EU RoHS (REACH) implementation imposes on firms additional variable production costs by requiring add...

Association between CD8 T-cell subsets and CD4/CD8 ratio with HS-CRP level in HIV-infected patients on antiretroviral therapy

Science.gov (United States)

Isabela, S.; Nugroho, A.; Harijanto, P. N.

2018-03-01

Due to improved access and adherence to antiretroviral therapy (ART), most HIV-infected persons worldwide are predicted to live longer. Nowadays the cause of death for most HIV-infected persons has changed to serious non-AIDS events (SNAEs) which is due to low-grade viremia. HIV patients with ART who had undergone CD4 cell count above 500/uL and there is an increase in hs-CRP despite an undetectable viral load. Some conditions CD8 cells count do not decrease with CD4 cells repairs. We researched in Prof Kandou General Hospital with a total sample of 35 HIV patients who had received ART with the level of CD4>350/uL. CD8 levels, CD4/CD8 ratio, and hs-CRP were assessed. This research is analytic descriptive with cross-sectional study design and analysis uses Spearman correlation. The mean CD8 during the study was 1291.8 (IQR 319-2610cells/uL), the mean ratio of CD4:CD8 was 0.57 (IQR 0.16-1.24) and median hs-CRP is 2.18 (IQR 0.3-6.6mg/dL). There was a significant positive correlation between CD8 and increased hs-CRP (r=0.369, pCD4/CD8 ratio and hs-CRP (r=-0.370, p<0.05).

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

10 CFR 40.7 - Employee protection.

Science.gov (United States)

2010-01-01

... protected activities. An employee's engagement in protected activities does not automatically render him or... 10 Energy 1 2010-01-01 2010-01-01 false Employee protection. 40.7 Section 40.7 Energy NUCLEAR REGULATORY COMMISSION DOMESTIC LICENSING OF SOURCE MATERIAL General Provisions § 40.7 Employee protection. (a...

18 CFR 35.40 - Ancillary services.

Science.gov (United States)

2010-04-01

... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Ancillary services. 35.40 Section 35.40 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION... Sales of Electric Energy, Capacity and Ancillary Services at Market-Based Rates § 35.40 Ancillary...

"Coding" and "Decoding": hypothesis for the regulatory mechanism involved in heparan sulfate biosynthesis.

Science.gov (United States)

Zhang, Xu; Wang, Fengshan; Sheng, Juzheng

2016-06-16

Heparan sulfate (HS) is widely distributed in mammalian tissues in the form of HS proteoglycans, which play essential roles in various physiological and pathological processes. In contrast to the template-guided processes involved in the synthesis of DNA and proteins, HS biosynthesis is not believed to involve a template. However, it appears that the final structure of HS chains was strictly regulated. Herein, we report research based hypothesis that two major steps, namely "coding" and "decoding" steps, are involved in the biosynthesis of HS, which strictly regulate its chemical structure and biological activity. The "coding" process in this context is based on the distribution of sulfate moieties on the amino groups of the glucosamine residues in the HS chains. The sulfation of these amine groups is catalyzed by N-deacetylase/N-sulfotransferase, which has four isozymes. The composition and distribution of sulfate groups and iduronic acid residues on the glycan chains of HS are determined by several other modification enzymes, which can recognize these coding sequences (i.e., the "decoding" process). The degree and pattern of the sulfation and epimerization in the HS chains determines the extent of their interactions with several different protein factors, which further influences their biological activity. Copyright © 2016 Elsevier Ltd. All rights reserved.

An Atomistic Modeling Study of Alloying Element Impurity Element, and Transmutation Products on the cohesion of A Nickel E5 {001} Twist Grain Boundary

International Nuclear Information System (INIS)

Young, G.A. Jr.; Najafabadi, R.; Strohmayer, W.; Baldrey, D.G.; Hamm, B.; Harris, J.; Sticht, J.; Wimmer, E.

2003-01-01

Atomistic modeling methods were employed to investigate the effects of impurity elements on the metallurgy, irradiation embrittlement, and environmentally assisted cracking of nickel-base alloys exposed to nuclear environments. Calculations were performed via ab initio atomistic modeling methods to ensure the accuracy and reliability of the results. A Griffith-type fracture criterion was used to quantitatively assess the effect of elements or element pairs on the grain boundary cohesive strength. In order of most embrittling to most strengthening, the elements are ranked as: He, Li, S, H, C, Zr, P, Fe, Mn, Nb, Cr, and B. Helium is strongly embrittling (-2.04 eV/atom lowering of the Griffith energy), phosphorus has little effect on the grain boundary (0.1 eV/atom), and boron offers appreciable strengthening (1.03 eV/atom increase in the Griffith energy). Calculations for pairs of elements (H-Li, H-B, H-C, H-P, and H-S) show little interaction on the grain boundary cohesive energy, so that for the conditions studied, linear superposition of elemental effects is a good approximation. These calculations help explain metallurgical effects (e.g. why boron can strengthen grain boundaries), irradiation embrittlement (e.g. how boron transmutation results in grain boundary embrittlement), as well as how grain boundary impurity elements can affect environmentally assisted cracking (i.e. low temperature crack propagation and stress corrosion cracking) of nickel-base alloys

High-sensitivity C-reactive protein (hs-CRP) levels and its relationship with components of polycystic ovary syndrome in Indian adolescent women with polycystic ovary syndrome (PCOS).

Science.gov (United States)

Ganie, Mohd Ashraf; Hassan, Saqib; Nisar, Sobia; Shamas, Nasir; Rashid, Aafia; Ahmed, Ishfaq; Douhat, Syed; Mudassar, Syed; Jan, Vicar M; Rashid, Fouzia

2014-11-01

C-reactive protein (CRP) is a risk marker for type 2 diabetes mellitus and cardiovascular diseases. In polycystic ovary syndrome (PCOS), limited data are available on high-sensitivity C-reactive protein (hs-CRP) levels and its relationship with components of PCOS especially in Indian women. The objective was to determine serum hs-CRP concentration in adolescent women with and without PCOS and to assess possible correlations of serum hs-CRP levels with components of PCOS in Indian women. One hundred and sixty women with PCOS and sixty non-PCOS women having normal menstrual cycles were included. Clinical assessment included anthropometry, Ferriman-Gallwey (FG) score and blood pressure (BP) measurement. Laboratory evaluation included estimation of T4, TSH, LH, FSH, total testosterone, prolactin, cortisol, 17OHP, hs-CRP, lipid profile, and insulin, and glucose after 2-h oral glucose tolerance test. Homeostasis Model Assessment Insulin resistance index (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI) and glucose intolerance was calculated. FG score, LH, FSH, total Testosterone, HOMA-IR and QUICKI were significantly different among women with or without PCOS (p women having PCOS, there was no significant difference between the groups (p > 0.05). A significant and positive correlation was found between hs-CRP and body mass index (BMI) (r = 0.308, p Indian adolescent women suggest that hs-CRP levels may not per se be associated with PCOS, rather can be related to fat mass in this subset of subjects.

Trace elements, potassium, 40K and 137Cs in distinctive parts of fir from Gorski Kotar - Croatia

International Nuclear Information System (INIS)

Barisic, D.; Vertacnik, A.; Lulic, S.; Kauzlaric, Z.; Hus, M.; Seletkovic, Z.; Kezic, N.

1996-01-01

Radionuclides, as well as other cations, which are either constitutive elements/trace elements of soils, or deposited as a fallout through wet/dry deposition processes due to global atmospheric contamination, can migrate upwards by plant uptake. Long-term observations of 137 Cs activities in nectar honeys indicate the uniform lowering of caesium transfer to nectar plants. In the same time, the 137 Cs activities of honey-dew honeys are significantly high and almost constant over long time period after contamination. Due to this, the research of potassium, caesium, as well as some other trace element content in distinctive parts of coniferous trees from Gorski Kotar has been started. The results of total K, Rb, Sr, Co, Cu, Zn and Cr, as well as of 40 K and 137 Cs determination in fir branches and needles from Lividraga (Table 1.) indicate the relatively high cations' mobility in youngest part of fir branches shoots. The majority of observed elements migrates into the youngest shoots, which is especially evident for univalent cations 40 K, total potassium, 137 Cs and rubidium in fir branches. Their concentrations generally are significantly higher in branches than in respective needles. The two-valent cations like strontium or zinc show less significant concentration increase in younger vs. older fir branches' parts (Figure 1.). Strontium concentrations have been increasing in the older needles in contrast to concentrations in fir branches. High 137 Cs activities found in the youngest shoots relatively long time after the soil contamination indicate the fir as a potentially good bioindicator for caesium. high mobility of cations in the youngest parts of fir branches, and theirs piling up in youngest tops of branches and needles suggest the fir to be used as the possible bioindicator of other, especially univalent cations fate. (author)

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)

HS-SPME AS AN EFFICIENT TOOL FOR DISCRIMINATING CHEMOTYPES OF Lippia alba (Mill. N. E. Brown

Directory of Open Access Journals (Sweden)

Aiêrta C. C. da Silva

Full Text Available Lippia alba (Mill. N. E. Brown (Verbenaceae is a medicinal plant for which several biological activities are reported, such as sedative, anxiolytic, anti-ulcer, antifungal, antimicrobial, antioxidant, antispasmodic, anti-nociceptive and anti-inflammatory. It is characterized by the production of essential oils which have been used to classify the plant in different chemotypes. In the Northeast region of Brazil, the presence of three chemotypes are reported: myrcene-citral (chemotype I, limonene-citral (chemotype II and carvone-limonene (chemotype III. In this work, headspace-solid phase microextraction (HS-SPME was used on the analysis of the volatile organic compounds (VOCs of three chemotypes of L. alba from the Northeast region of Brazil, and compared to the essential oils of the plants extracted by hydrodistillation. Volatile compounds from each chemotype were more effectively differentiated when extracted by HS-SPME than by hydrodistillation.

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.

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

Optimum values of average L-shell fluorescence yields for the elements 40 ≤ Z ≤ 95

International Nuclear Information System (INIS)

Mittal, Raj; Singh, N.; Allawadhi, K.L.; Sood, B.S.

1993-01-01

The optimum values of average L-shell fluorescence yields W L , for elements 40 ≤ Z ≤ 95 have been determined using seven sets of experimental and theoretical values of W L reported by various workers. The first and second sets comprise of values of W L evaluated from L X-ray emission cross-sections measured for 22 elements by Mann and for 27 elements by Singh et al respectively. The third set contains most reliable experimental values compiled by Bombynek et al. In the remaining four sets the values of W L calculated from the semi empirical and theoretical values of L-subshell fluorescence yields W 1 and Coster-Kronig transition probabilities (f ij ) and photoionisation and proton induced ionisation cross sections are reported. All the values of W L for a given element reported in different sets are not same and for some elements the values differ from one another by more than 15%. The optimum value of W L for each element amongst the seven values is taken as a mean of group of those values whose standard deviation is almost less than 3% of the mean value. The optimum values are further fitted to the standard cubic form and the coefficients of the fit are a 0 = 0.3542371, a 1 =-0.489949E-02, a 2 0.2052273E-03 and a 3 =-0.8144938E-06. The values thus generated agree with optimum values within nearly 2%. (author). 10 refs., 1 tab

Macrophage inflammatory protein-3α influences growth of K562 leukemia cells in co-culture with anticancer drug-pretreated HS-5 stromal cells

International Nuclear Information System (INIS)

Lee, Y.C.; Chiou, T.-J.; Tzeng, W.-F.; Chu, S.T.

2008-01-01

Stromal cell monolayers have been an important means of studying the regulation of hematopoiesis, because they produce cytokines. Cytosine arabinoside, vincristine, daunorubicin, and doxorubicin are common drugs for hematological cancer therapy, and they may have some effects on bone marrow stroma during chemotherapy. The aim of this study was to elucidate interactions between the bone marrow stromal microenvironment and leukemic cells after drug treatment. We tested the hypothesis that human HS-5 stromal cells, pretreated with anticancer drugs, affected the growth of leukemic K562 cells by changing the cytokines in the culture microenvironment. Thereafter, proliferation of K562 cells increased nearly 2.5-fold compared the co-cultivation with drugs-pretreated HS-5 stromal cells and drugs-untreated HS-5 stromal cells. The results indicated that co-cultivation with HS-5 stromal cells pretreated with drugs caused significant K562 cell proliferation. Cytokines in the microenvironment were detected via the RayBio Human Cytokine Antibody Array Membrane. The levels of the cytokines CKβ, IL-12, IL-13, IGFBP-2, MCP-1, MCP-3, MCP-4, MDC, MIP-1β and MIP-1δ were decreased, with a particularly marked decrease in MIP-3α. In co-culture medium, there was a 20-fold decrease in MIP-3α in daunorubicin-pretreated HS-5 cells and at least a 3-fold decrease in Ara-C-pretreated cells. This indicated a significant effect of anticancer drugs on the stromal cell line. Using phosphorylated Erk and pRb proteins as cell proliferation markers, we found that phosphorylation of these markers in K562 cells was inhibited during co-cultivation with drug-pretreated stromal cells in MIP-3α-supplemented medium and restored by MIP-3α antibody supplement. In conclusion, anticancer drug pretreatment suppresses the negative control exerted by HS-5 cells on leukemic cell proliferation, via modulation of cytokines in the microenvironment, especially at the level of MIP-3α

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.

Accurate double many-body expansion potential energy surface of HS2A2A′) by scaling the external correlation

International Nuclear Information System (INIS)

Zhang Lu-Lu; Song Yu-Zhi; Gao Shou-Bao; Zhang Yuan; Meng Qing-Tian

2016-01-01

A globally accurate single-sheeted double many-body expansion potential energy surface is reported for the first excited state of HS 2 by fitting the accurate ab initio energies, which are calculated at the multireference configuration interaction level with the aug-cc-pV Q Z basis set. By using the double many-body expansion-scaled external correlation method, such calculated ab initio energies are then slightly corrected by scaling their dynamical correlation. A grid of 2767 ab initio energies is used in the least-square fitting procedure with the total root-mean square deviation being 1.406 kcal·mol −1 . The topographical features of the HS 2 (A 2 A′) global potential energy surface are examined in detail. The attributes of the stationary points are presented and compared with the corresponding ab initio results as well as experimental and other theoretical data, showing good agreement. The resulting potential energy surface of HS 2 (A 2 A′) can be used as a building block for constructing the global potential energy surfaces of larger S/H molecular systems and recommended for dynamic studies on the title molecular system. (paper)

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.

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...

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.

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

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

Headspace solid-phase microextraction (HS-SPME) and liquid-liquid extraction (LLE): comparison of the performance in classification of ecstasy tablets. Part 2.

Science.gov (United States)

Bonadio, Federica; Margot, Pierre; Delémont, Olivier; Esseiva, Pierre

2008-11-20

Headspace solid-phase microextraction (HS-SPME) is assessed as an alternative to liquid-liquid extraction (LLE) currently used for 3,4-methylenedioxymethampethamine (MDMA) profiling. Both methods were compared evaluating their performance in discriminating and classifying samples. For this purpose 62 different seizures were analysed using both extraction techniques followed by gas chromatography-mass spectroscopy (GC-MS). A previously validated method provided data for HS-SPME, whereas LLE data were collected applying a harmonized methodology developed and used in the European project CHAMP. After suitable pre-treatment, similarities between sample pairs were studied using the Pearson correlation. Both methods enable to distinguish between samples coming from the same pre-tabletting batches and samples coming from different pre-tabletting batches. This finding emphasizes the use of HS-SPME as an effective alternative to LLE, with additional advantages such as sample preparation and a solvent-free process.

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

Highly sensitive detection of 2,4,6-trichlorophenol based on HS-β-cyclodextrin/gold nanoparticles composites modified indium tin oxide electrode

International Nuclear Information System (INIS)

Zheng, Xiangli; Liu, Shan; Hua, Xiaoxia; Xia, Fangquan; Tian, Dong; Zhou, Changli

2015-01-01

Graphical abstract: Display Omitted -- Highlights: •A novel electrochemical sensing platform by self-assembling of HS-β-cyclodextrin/gold nanoparticles onto indium tin oxide electrode (HS-β-CD/AuNPs/SAM/ITO electrode) surface was constructed. •The proposed electrochemical sensor exhibited high sensitivity for the determination 2,4,6-trichlorophenol which electrochemical activity is very weak. •The newly developed method was successfully applied to quantitatively determine 2,4,6-trichlorophenol in tap water samples. -- ABSTRACT: A new electrochemical sensor for determination of 2,4,6-trichlorophenol (2,4,6-TCP) was fabricated. The characterization of the sensor was studied by scanning electron microscopy, electrochemical impedance spectroscopy and cyclic voltammetry techniques. The electrochemical behavior of 2,4,6-TCP was investigated using cyclic voltammetry and differential pulse voltammetry at the HS-β-cyclodextrin (HS-β-CD)/gold nanoparticles (AuNPs) composite modified indium tin oxide (ITO) electrode. The results showed that the current responses of 2,4,6-TCP greatly enhanced due to the high catalytic activity and enrichment capability of composites. The peak current of 2,4,6-TCP increases linearly with the increase of the 2,4,6-TCP concentration from 3.0 × 10 −9 to 2.8 × 10 −8 M, with the limit of detection of 1.0 × 10 −9 . Further more, the modified electrode was successfully applied to detect the level of 2,4,6-TCP in tap water samples with excellent sensitivity

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

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.

Association between prepulse inhibition of the startle response and latent inhibition of two-way avoidance acquisition: A study with heterogeneous NIH-HS rats.

Science.gov (United States)

Sánchez-González, Ana; Esnal, Aitor; Río-Álamos, Cristóbal; Oliveras, Ignasi; Cañete, Toni; Blázquez, Gloria; Tobeña, Adolf; Fernández-Teruel, Alberto

2016-03-01

This study presents the first evaluation of the associations between responses in two paradigms related to schizophrenia in the genetically heterogeneous NIH-HS rat stock. NIH-HS rats are a stock of genetically heterogeneous animals that have been derived from eight different inbred strains. A rotational breeding schedule has been followed for more than eighty generations, leading to a high level of genetic recombination that makes the NIH-HS rats a unique tool for studying the genetic basis of (biological, behavioral, disease-related) complex traits. Previous work has dealt with the characterization of coping styles, cognitive and anxiety/fear-related profiles of NIH-HS rats. In the present study we have completed their characterization in two behavioral models, prepulse inhibition (PPI) and latent inhibition (LI) of the two-way active avoidance response, that appear to be related to schizophrenia or to schizophrenia-relevant symptoms. We have found that these rats display PPI for each of the four prepulse intensities tested, allowing their stratification in high, medium and low PPI subgroups. When testing these three subgroups for LI of two-way active avoidance acquisition it has been observed that the LowPPI and MediumPPI subgroups present impaired LI, which, along with the fact that the HighPPI group presents significant LI, allows us to hypothesize that responses in these two paradigms are somehow related and that selection of NIH-HS rats for Low vs HighPPI could make a promising animal model for the study of clusters of schizophrenia-relevant symptoms and their underlying neurobiological mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

The mRNA expression of pro- and anti-inflammatory cytokines in T regulatory cells in children with type 1 diabetes.

Directory of Open Access Journals (Sweden)

Maria Górska

2010-06-01

Full Text Available Type 1 diabetes mellitus (T1DM is caused by the autoimmune-mediated destruction of insulin-producing beta cells in the pancreas. T regulatory cells (Tregs represent an active mechanism of suppressing autoreactive T cells that escape central tolerance. The aim of our study was to test the hypothesis that T regulatory cells express pro- and anti-inflammatory cytokines, elements of cytotoxicity and OX40/4-1BB molecules. The examined group consisted of 50 children with T1DM. Fifty two healthy individuals (control group were enrolled into the study. A flow cytometric analysis of T-cell subpopulations was performed using the following markers: anti-CD3, anti-CD4, anti-CD25, anti-CD127, anti-CD134 and anti-CD137. Concurrently with the flow cytometric assessment of Tregs we separated CD4+CD25+CD127dim/- cells for further mRNA analysis. mRNA levels for transcription factor FoxP3, pro- and anti-inflammatory cytokines (interferon gamma, interleukin-2, interleukin-4, interleukin-10, transforming growth factor beta1 and tumor necrosis factor alpha, activatory molecules (OX40, 4-1BB and elements of cytotoxicity (granzyme B, perforin 1 were determined by real-time PCR technique. We found no alterations in the frequency of CD4+CD25highCD127low cells between diabetic and control children. Treg cells expressed mRNA for pro- and anti-inflammatory cytokines. Lower OX40 and higher 4-1BB mRNA but not protein levels in Treg cells in diabetic patients compared to the healthy children were noted. Our observations confirm the presence of mRNA for pro- and anti-inflammatory cytokines in CD4+CD25+CD127dim/- cells in the peripheral blood of children with T1DM. Further studies with the goal of developing new strategies to potentiate Treg function in autoimmune diseases are warranted.

Nuclear Regulatory Commission issuances: August 1994. Volume 40, Number 2

International Nuclear Information System (INIS)

1994-08-01

This report contains the collected issuances of the US Nuclear Regulatory Commission for the month of August, 1994. The report includes issuances of the Commission, the Atomic Safety and Licensing Boards, and the Directors' Decisions. Some of the entities involved include Gulf States Utility company, Sequoyah Fuels Corporation and General Atomics, Georgia Power Company, and Arizona Public Service Company

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.

The efficacy of radiofrequency ablation in the treatment of pediatric arrhythmia and its effects on serum IL-6 and hs-CRP.

Science.gov (United States)

Li, Chunli; Jia, Libo; Wang, Zhenzhou; Niu, Ling; An, Xinjiang

2017-10-01

The aim of this study was to investigate the efficacy of radiofrequency ablation in the treatment of pediatric arrhythmia and to assess the changes in serum interleukin-6 (IL-6) and hs-CRP levels after treatment. Hundred and six children with tachyarrhythmia who were admitted to Xuzhou Children's Hospital from November, 2014 to December, 2015 were recruited for study. The efficacies of radiofrequency in the treatment of different types of arrhythmia were analyzed. Successful ablation was found in 104 cases (98.11%) and recurrence was found in 7 cases (6.73%). Among 62 cases of atrioventricular reentrant tachycardia (AVRT), successful ablation was found in 60 cases (96.77%) and recurrence was found in 3 cases (4.84%). Among 33 cases of atrioventricular nodal reentrant tachycardia (AVNRT), successful ablation was found in 33 cases (100%) and recurrence was found in 2 cases (6.06%). Among 5 cases of ventricular tachycardia (VT), successful ablation was found in 5 cases (100%) and no recurrence was found. Among 4 cases of atrial tachycardia (AT), successful ablation was found in 4 cases (100%) and recurrence was found in 1 case (25%). Among 2 cases of atrial flutter (AFL), successful ablation was found in both (100%) and recurrence was found in 1 case (50%). After operation, the levels of IL-6 and hs-CRP were increased and were continually increased within 6 h after operation. The levels of IL-6 and hs-CRP at 24 h after operation were reduced but still higher than preoperative levels. The duration of radiofrequency and ablation energy were positively correlated with the levels of IL-6 and hs-CRP, while the number of discharges was not significantly correlated with either. In conclusion, radiofrequency ablation is a safe and effective treatment for pediatric arrhythmia. Postoperative monitoring of IL-6 and hs-CRP levels is conducive to understanding postoperative myocardial injury and inflammatory response.

Optimization of Biochemical Screening Methods for Volatile and Unstable Sesquiterpenoids Using HS-SPME-GC-MS

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Trine Bundgaard Andersen

2015-06-01

Full Text Available HS-SPME-GC-MS has been suggested as a fast and robust analytical platform for the product characterization of sesquiterpene synthases. The choice of fiber and injection temperature can have a significant effect on the observed product profile, due to the chemical rearrangements that can occur on the fiber material. Here we present a systematic study on the effects of fiber choice and injection port temperature on the observed sesquiterpenoid profile of four sesquiterpene synthases expressed in Nicotiana benthamiana. We found that the absorbent material PDMS was much less likely to support acid-induced rearrangement of sesquiterpenoids when compared to the adsorbent materials PDMS/DVB, PDMS/CAR, and PDMS/CAR/DVB. Furthermore, utilizing an injection port temperature at 160 °C almost eliminated the inherent thermal instability of germacrene sesquiterpenoids. Thus, for fast screening of sesquiterpene synthases, the results suggest that PDMS fibers and an injection temperature of 160 °C provide a fast and reproducible HS-SPME GC-MS method when using H2 as carrier gas.

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....

Cyclic AMP regulation of the human glycoprotein hormone α-subunit gene is mediated by an 18-base-pair element

International Nuclear Information System (INIS)

Silver, B.J.; Bokar, J.A.; Virgin, J.B.; Vallen, E.A.; Milsted, A.; Nilson, J.H.

1987-01-01

cAMP regulates transcription of the gene encoding the α-subunit of human chorionic gonadotropin (hCG) in the choriocarcinoma cells (BeWo). To define the sequences required for regulation by cAMP, the authors inserted fragments from the 5' flanking region of the α-subunit gene into a test vector containing the simian virus 40 early promoter (devoid of its enhancer) linked to the bacterial chloramphenicol acetyltransferase (CAT) gene. Results from transient expression assays in BeWo cells indicated that a 1500-base-pair (bp) fragment conferred cAMP responsiveness on the CAT gene regardless of position or orientation of the insert relative to the viral promoter. A subfragment extending from position -169 to position -100 had the same effect on cAMP-induced expression. Furthermore, the entire stimulatory effect could be achieved with an 18-bp synthetic oligodeoxynucleotide corresponding to a direct repeat between position -146 and -111. In the absence of cAMP, the α-subunit 5' flanking sequence also enhanced transcription from the simian virus 40 early promoter. They localized this enhancer activity to the same -169/-100 fragment containing the cAMP response element. The 18-bp element alone, however, had no effect on basal expression. Thus, this short DNA sequence serves as a cAMP response element and also functions independently of other promoter-regulatory elements located in the 5' flanking sequence of the α-subunit gene

Metabolism of isoeugenol via isoeugenol-diol by a newly isolated strain of Bacillus subtilis HS8.

Science.gov (United States)

Zhang, Yongmei; Xu, Ping; Han, Shuai; Yan, Haiqin; Ma, Cuiqing

2006-12-01

A bacterium designated as HS8 was newly isolated from soil based on its ability to degrade isoeugenol. The strain was identified as Bacillus subtilis according to its 16S rDNA sequence analysis and biochemical characteristics. The metabolic pathway for the degradation of isoeugenol was examined. Isoeugenol-diol, for the first time, was detected as an intermediate from isoeugenol to vanillin by a bacterial strain. Isoeugenol was converted to vanillin via isoeugenol-diol, and vanillin was then metabolized via vanillic acid to guaiacol by strain HS8. These metabolites, vanillin, vanillic acid, and guaiacol, are all valuable aromatic compounds in flavor production. At the same time, the bipolymerization of isoeugenol was observed, which produced dehydrodiisoeugenol and decreased the vanillin yield. High level of vanillic acid decarboxylase activity was detected in cell-free extract. These findings provided a detailed profile of isoeugenol metabolism by a B. subtilis strain for the first time, which would improve the production of valuable aromatic compounds by biotechnology.

Simultaneous determination of kolliphor HS15 and miglyol 812 in microemulsion formulation by ultra-high performance liquid chromatography coupled with nano quantity analyte detector

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Honggen Zhang

2016-02-01

Full Text Available A novel method for simultaneous determination of kolliphor HS15 and miglyol 812 in microemulsion formulation was developed using ultra-high performance liquid chromatography coupled with a nano quantitation analytical detector (UHPLC–NQAD. All components in kolliphor HS15 and miglyol 812 were well separated on an Acquity BEH C18 column. Mobile phase A was 0.1% trifluoroacetic acid (TFA in water and mobile phase B was acetonitrile. A gradient elution sequence was programed initially with 60% organic solvent, slowly increased to 100% within 8 min. The flow rate was 0.7 mL/min. Good linearity (r>0.95 was obtained in the range of 27.6–1381.1 μg/mL for polyoxyl 15 hydroxystearate in kolliphor HS15, 0.8–202.0 μg/mL for caprylic acid triglyceride and 2.7–221.9 μg/mL for capric acid triglyceride in miglyol 812. The relative standard deviations (RSD ranged from 0.6% to 1.7% for intra-day precision and from 0.4% to 2.7% for inter-day precision. The overall recoveries (accuracy were 99.7%–101.4% for polyoxyl 15 hydroxystearate in kolliphor HS15, 96.7%–99.6% for caprylic acid triglyceride, and 94.1%–103.3% for capric acid triglyceride in miglyol 812. Quantification limits (QL were determined as 27.6 μg/mL for polyoxyl 15 hydroxystearate in kolliphor HS15, 0.8 μg/mL for caprylic acid triglyceride, and 2.7 μg/mL for capric acid triglyceride in miglyol 812. No interferences were observed in the retention time ranges of kolliphor HS15 and miglyol 812. The method was validated in terms of specificity, linearity, precision, accuracy, QL, and robustness. The proposed method has been applied to microemulsion formulation analyses with good recoveries (82.2%–103.4%.

Simultaneous determination of kolliphor HS15 and miglyol 812 in microemulsion formulation by ultra-high performance liquid chromatography coupled with nano quantity analyte detector.

Science.gov (United States)

Zhang, Honggen; Wang, Zhenyu; Liu, Oscar

2016-02-01

A novel method for simultaneous determination of kolliphor HS15 and miglyol 812 in microemulsion formulation was developed using ultra-high performance liquid chromatography coupled with a nano quantitation analytical detector (UHPLC-NQAD). All components in kolliphor HS15 and miglyol 812 were well separated on an Acquity BEH C 18 column. Mobile phase A was 0.1% trifluoroacetic acid (TFA) in water and mobile phase B was acetonitrile. A gradient elution sequence was programed initially with 60% organic solvent, slowly increased to 100% within 8 min. The flow rate was 0.7 mL/min. Good linearity ( r >0.95) was obtained in the range of 27.6-1381.1 μg/mL for polyoxyl 15 hydroxystearate in kolliphor HS15, 0.8-202.0 μg/mL for caprylic acid triglyceride and 2.7-221.9 μg/mL for capric acid triglyceride in miglyol 812. The relative standard deviations (RSD) ranged from 0.6% to 1.7% for intra-day precision and from 0.4% to 2.7% for inter-day precision. The overall recoveries (accuracy) were 99.7%-101.4% for polyoxyl 15 hydroxystearate in kolliphor HS15, 96.7%-99.6% for caprylic acid triglyceride, and 94.1%-103.3% for capric acid triglyceride in miglyol 812. Quantification limits (QL) were determined as 27.6 μg/mL for polyoxyl 15 hydroxystearate in kolliphor HS15, 0.8 μg/mL for caprylic acid triglyceride, and 2.7 μg/mL for capric acid triglyceride in miglyol 812. No interferences were observed in the retention time ranges of kolliphor HS15 and miglyol 812. The method was validated in terms of specificity, linearity, precision, accuracy, QL, and robustness. The proposed method has been applied to microemulsion formulation analyses with good recoveries (82.2%-103.4%).

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

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.

Clinical significance of determination of changes of serum IL-6, hs-CRP and saliva secretory IgA levels after treatment in patients with periodontitis

International Nuclear Information System (INIS)

Wang Tongwu

2009-01-01

Objective: To explore the clinical significance of changes of serum IL-6, hs-CRP and saliva secretory IgA levels after treatment in patients with periodontitis. Methods: Serum IL-6, saliva secretory IgA (with RIA) and serum hs-CRP (with immuno-tarbility method) levels were measured in 42 patients with periodontitis both before and after treatment as well as in 35 controls. Results: Before treatment serum IL-6, hs-CRP and saliva secretory IgA levels in the patients wree significantly higher than those in controls (P 0.05). However, the saliva secreatory IgA levels were still significantly higher than those in controls (P<0.05). Conclusion: There was disturbance of immunomodulation in patients with periodontitis as expressed by the changes of cytokines levels in the course of the diseases. (authors)

18 CFR 40.3 - Availability of Reliability Standards.

Science.gov (United States)

2010-04-01

... Reliability Standards. 40.3 Section 40.3 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT MANDATORY RELIABILITY STANDARDS FOR THE BULK-POWER SYSTEM § 40.3 Availability of Reliability Standards. The Electric Reliability...

Scoring correction for MMPI-2 Hs scale with patients experiencing a traumatic brain injury: a test of measurement invariance.

Science.gov (United States)

Alkemade, Nathan; Bowden, Stephen C; Salzman, Louis

2015-02-01

It has been suggested that MMPI-2 scoring requires removal of some items when assessing patients after a traumatic brain injury (TBI). Gass (1991. MMPI-2 interpretation and closed head injury: A correction factor. Psychological assessment, 3, 27-31) proposed a correction procedure in line with the hypothesis that MMPI-2 endorsement may be affected by symptoms of TBI. This study assessed the validity of the Gass correction procedure. A sample of patients with a TBI (n = 242), and a random subset of the MMPI-2 normative sample (n = 1,786). The correction procedure implies a failure of measurement invariance across populations. This study examined measurement invariance of one of the MMPI-2 scales (Hs) that includes TBI correction items. A four-factor model of the MMPI-2 Hs items was defined. The factor model was found to meet the criteria for partial measurement invariance. Analysis of the change in sensitivity and specificity values implied by partial measurement invariance failed to indicate significant practical impact of partial invariance. Overall, the results support continued use of all Hs items to assess psychological well-being in patients with TBI. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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.

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

PELTIER ELEMENTS

CERN Document Server

Tani, Laurits

2015-01-01

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

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

HURRICANE AND SEVERE STORM SENTINEL (HS3) GLOBAL HAWK ADVANCED VERTICAL ATMOSPHERIC PROFILING SYSTEM (AVAPS) DROPSONDE SYSTEM V2

Data.gov (United States)

National Aeronautics and Space Administration — The Hurricane and Severe Storm Sentinel (HS3) Global Hawk Advanced Vertical Atmospheric Profiling System (AVAPS) Dropsonde System dataset was collected by the...

An efficient approach for electric load forecasting using distributed ART (adaptive resonance theory) and HS-ARTMAP (Hyper-spherical ARTMAP network) neural network

International Nuclear Information System (INIS)

Cai, Yuan; Wang, Jian-zhou; Tang, Yun; Yang, Yu-chen

2011-01-01

This paper presents a neural network based on adaptive resonance theory, named distributed ART (adaptive resonance theory) and HS-ARTMAP (Hyper-spherical ARTMAP network), applied to the electric load forecasting problem. The distributed ART combines the stable fast learning capabilities of winner-take-all ART systems with the noise tolerance and code compression capabilities of multi-layer perceptions. The HS-ARTMAP, a hybrid of an RBF (Radial Basis Function)-network-like module which uses hyper-sphere basis function substitute the Gaussian basis function and an ART-like module, performs incremental learning capabilities in function approximation problem. The HS-ARTMAP only receives the compressed distributed coding processed by distributed ART to deal with the proliferation problem which ARTMAP (adaptive resonance theory map) architecture often encounters and still performs well in electric load forecasting. To demonstrate the performance of the methodology, data from New South Wales and Victoria in Australia are illustrated. Results show that the developed method is much better than the traditional BP and single HS-ARTMAP neural network. -- Research highlights: → The processing of the presented network is based on compressed distributed data. It's an innovation among the adaptive resonance theory architecture. → The presented network decreases the proliferation the Fuzzy ARTMAP architectures usually encounter. → The network on-line forecasts electrical load accurately, stably. → Both one-period and multi-period load forecasting are executed using data of different cities.

Two-photon laser-induced fluorescence studies of HS radicals, DS radicals, and I atoms

Energy Technology Data Exchange (ETDEWEB)

Tiee, J J; Ferris, M J; Loge, G W; Wampler, F B

1983-04-15

A two-photon laser-induced excitation and fluorescence technique has been used to study the A /sup 2/..sigma../sup +/ - X/sup 2/PI transition of HS and DS radicals and various high-lying /sup 4/P/sup 0/, /sup 2/D/sup 0/, and /sup 4/D/sup 0/ states of the I atom. The two-photon excitation cross sections and detection sensitivity are discussed. 13 references, 5 figures.

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

Heme-dependent up-regulation of the α-globin gene expression by transcriptional repressor Bach1 in erythroid cells

International Nuclear Information System (INIS)

Tahara, Tsuyoshi; Sun Jiying; Igarashi, Kazuhiko; Taketani, Shigeru

2004-01-01

The transcriptional factor Bach1 forms a heterodimer with small Maf family, and functions as a repressor of the Maf recognition element (MARE) in vivo. To investigate the involvement of Bach1 in the heme-dependent regulation of the expression of the α-globin gene, human erythroleukemia K562 cells were cultured with succinylacetone (SA), a heme biosynthetic inhibitor, and the level of α-globin mRNA was examined. A decrease of α-globin mRNA was observed in SA-treated cells, which was restored by the addition of hemin. The heme-dependent expression of α-globin occurred at the transcriptional level since the expression of human α-globin gene promoter-reporter gene containing hypersensitive site-40 (HS-40) was decreased when K562 cells were cultured with SA. Hemin treatment restored the decrease of the promoter activity by SA. The regulation of the HS-40 activity by heme was dependent on the NF-E2/AP-1 (NA) site, which is similar to MARE. The NA site-binding activity of Bach1 in K562 increased upon SA-treatment, and the increase was diminished by the addition of hemin. The transient expression of Bach1 and mutated Bach1 lacking CP motifs suppressed the HS-40 activity, and cancellation of the repressor activity by hemin was observed when wild-type Bach1 was expressed. The expression of NF-E2 strengthened the restoration of the Bach1-effect by hemin. Interestingly, nuclear localization of Bach1 increased when cells were treated with SA, while hemin induced the nuclear export of Bach1. These results indicated that heme plays an important role in the induction of α-globin gene expression through disrupting the interaction of Bach1 and the NA site in HS-40 enhancer in erythroid cells

Detection of expression quantitative trait Loci in complex mouse crosses: impact and alleviation of data quality and complex population substructure.

Science.gov (United States)

Iancu, Ovidiu D; Darakjian, Priscila; Kawane, Sunita; Bottomly, Daniel; Hitzemann, Robert; McWeeney, Shannon

2012-01-01

Complex Mus musculus crosses, e.g., heterogeneous stock (HS), provide increased resolution for quantitative trait loci detection. However, increased genetic complexity challenges detection methods, with discordant results due to low data quality or complex genetic architecture. We quantified the impact of theses factors across three mouse crosses and two different detection methods, identifying procedures that greatly improve detection quality. Importantly, HS populations have complex genetic architectures not fully captured by the whole genome kinship matrix, calling for incorporating chromosome specific relatedness information. We analyze three increasingly complex crosses, using gene expression levels as quantitative traits. The three crosses were an F(2) intercross, a HS formed by crossing four inbred strains (HS4), and a HS (HS-CC) derived from the eight lines found in the collaborative cross. Brain (striatum) gene expression and genotype data were obtained using the Illumina platform. We found large disparities between methods, with concordance varying as genetic complexity increased; this problem was more acute for probes with distant regulatory elements (trans). A suite of data filtering steps resulted in substantial increases in reproducibility. Genetic relatedness between samples generated overabundance of detected eQTLs; an adjustment procedure that includes the kinship matrix attenuates this problem. However, we find that relatedness between individuals is not evenly distributed across the genome; information from distinct chromosomes results in relatedness structure different from the whole genome kinship matrix. Shared polymorphisms from distinct chromosomes collectively affect expression levels, confounding eQTL detection. We suggest that considering chromosome specific relatedness can result in improved eQTL detection.

Biocontrol ability of Lysobacter antibioticus HS124 against Phytophthora blight is mediated by the production of 4-hydroxyphenylacetic acid and several lytic enzymes.

Science.gov (United States)

Ko, Hyun-Sun; Jin, Rong-De; Krishnan, Hari B; Lee, Sang-Bog; Kim, Kil-Yong

2009-12-01

Several rhizobacteria play a vital role in plant protection, plant growth promotion and the improvement of soil health. In this study, we have isolated a strain of Lysobacter antibioticus HS124 from rhizosphere and demonstrate its antifungal activity against various pathogens including Phytophthora capsici, a destructive pathogen of pepper plants. L. antibioticus HS124 produced lytic enzymes such as chitinase, beta-1,3-glucanase, lipase, protease, and an antibiotic compound. This antibiotic compound was purified by diaion HP-20, silica gel, sephadex LH-20 column chromatography and high performance liquid chromatography. The purified compound was identified as 4-hydroxyphenylacetic acid by gas chromatography-electron ionization (GC-EI) and gas chromatography-chemical ionization (GC-CI) mass spectrometry. This antibiotic exhibited destructive activity toward P. capsici hyphae. In vivo experiments utilizing green house grown pepper plants demonstrated the protective effect of L. antibioticus HS124 against P. capsici. The growth of pepper plants treated with L. antibioticus culture was enhanced, resulting in greater protection from fungal disease. Optimum growth and protection was found when cultures were grown in presence of Fe(III). Additionally, the activities of pathogenesis-related proteins such as chitinase and beta-1,3-glucanase decreased in roots, but increased in leaves with time after treatment compared to controls. Our results demonstrate L. antibioticus HS124 as a promising candidate for biocontrol of P. capsici in pepper plants.

Pilates versus resistance exercise on the serum levels of hs-CRP, in the abdominal circumference and body mass index (BMI in elderly individuals

Directory of Open Access Journals (Sweden)

Maria Adesilda Silva Pestana

2016-06-01

Full Text Available Recent studies have shown that the elderly exhibit a subclinical state of inflammation associated with increased adipose tissue and several comorbidities. To compare the effects of mat Pilates based exercises and resistance exercise on the serum levels of reactive C protein of high sensitivity (hs-CRP, in the abdominal circumference (AC and the body mass index (BMI in the elderly. It is a randomised clinical trial with a sample of 78 elderly individuals (median age 69 years. The active independent variable investigated was nature of treatment intervention (Pilates mat based exercises vs resistance exercise, and the dependent variables were hs-CRP level, AC and BMI. The statistical analysis used Wilcoxon signed rank and Mann-Whitney tests. The correlation between the continuous variables was assessed using Spearman’s coefficient of correlation. The data were analysed using SPSS software version 17.0, and probability values lower than 5% (p< 0.05 were considered statistically significant. Mat Pilates based exercises exhibited reductions in serum hs-CPR level (Wilcoxon signed rank test; z = -2.466, p = 0.01, BMI (Wilcoxon signed rank test; z = -3.295, p = 0.001 and AC (Wilcoxon signed rank test; z = -3.398, p = 0.01. Mat Pilates based exercises promoted a significant reduction of the serum hs-CRP levels and anthropometric measurements in elderly individuals.

78 FR 54517 - Water Quality Standards Regulatory Clarifications

Science.gov (United States)

2013-09-04

... 131 Water Quality Standards Regulatory Clarifications; Proposed Rule #0;#0;Federal Register / Vol. 78... AGENCY 40 CFR Part 131 [EPA-HQ-OW-2010-0606; FRL-9839-7] RIN 2040-AF 16 Water Quality Standards... Environmental Protection Agency (EPA) is proposing changes to the federal water quality standards (WQS...

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

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.

Quantification of Polyfunctional Thiols in Wine by HS-SPME-GC-MS Following Extractive Alkylation.

Science.gov (United States)

Musumeci, Lauren E; Ryona, Imelda; Pan, Bruce S; Loscos, Natalia; Feng, Hui; Cleary, Michael T; Sacks, Gavin L

2015-07-06

Analyses of key odorous polyfunctional volatile thiols in wines (3-mercaptohexanol (3-MH), 3-mercaptohexylacetate (3-MHA), and 4-mercapto-4-methyl-2-pentanone (4-MMP)) are challenging due to their high reactivity and ultra-trace concentrations, especially when using conventional gas-chromatography electron impact mass spectrometry (GC-EI-MS). We describe a method in which thiols are converted to pentafluorobenzyl (PFB) derivatives by extractive alkylation and the organic layer is evaporated prior to headspace solid phase microextraction (HS-SPME) and GC-EI-MS analysis. Optimal parameters were determined by response surface area modeling. The addition of NaCl solution to the dried SPME vials prior to extraction resulted in up to less than fivefold improvement in detection limits. Using 40 mL wine samples, limits of detection for 4-MMP, 3-MH, and 3-MHA were 0.9 ng/L, 1 ng/L, and 17 ng/L, respectively. Good recovery (90%-109%) and precision (5%-11% RSD) were achieved in wine matrices. The new method was used to survey polyfunctional thiol concentrations in 61 commercial California and New York State wines produced from V. vinifera (Riesling, Gewürztraminer, Cabernet Sauvignon, Sauvignon blanc and non-varietal rosé wines), V. labruscana (Niagara), and Vitis spp. (Cayuga White). Mean 4-MMP concentrations in New York Niagara (17 ng/L) were not significantly different from concentrations in Sauvignon blanc, but were significantly higher than 4-MMP in other varietal wines.

Quantification of Polyfunctional Thiols in Wine by HS-SPME-GC-MS Following Extractive Alkylation

Directory of Open Access Journals (Sweden)

Lauren E. Musumeci

2015-07-01

Full Text Available Analyses of key odorous polyfunctional volatile thiols in wines (3-mercaptohexanol (3-MH, 3-mercaptohexylacetate (3-MHA, and 4-mercapto-4-methyl-2-pentanone (4-MMP are challenging due to their high reactivity and ultra-trace concentrations, especially when using conventional gas-chromatography electron impact mass spectrometry (GC-EI-MS. We describe a method in which thiols are converted to pentafluorobenzyl (PFB derivatives by extractive alkylation and the organic layer is evaporated prior to headspace solid phase microextraction (HS-SPME and GC-EI-MS analysis. Optimal parameters were determined by response surface area modeling. The addition of NaCl solution to the dried SPME vials prior to extraction resulted in up to less than fivefold improvement in detection limits. Using 40 mL wine samples, limits of detection for 4-MMP, 3-MH, and 3-MHA were 0.9 ng/L, 1 ng/L, and 17 ng/L, respectively. Good recovery (90%–109% and precision (5%–11% RSD were achieved in wine matrices. The new method was used to survey polyfunctional thiol concentrations in 61 commercial California and New York State wines produced from V. vinifera (Riesling, Gewürztraminer, Cabernet Sauvignon, Sauvignon blanc and non-varietal rosé wines, V. labruscana (Niagara, and Vitis spp. (Cayuga White. Mean 4-MMP concentrations in New York Niagara (17 ng/L were not significantly different from concentrations in Sauvignon blanc, but were significantly higher than 4-MMP in other varietal wines.

Alfinated coating structure on HS6-5-2 (SW7M high speed steel

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T. Szymczak

2010-10-01

Full Text Available The paper presents the results of immersion alfinated coating structure in AlSi5 silumin on HS6-5-2 (SW7M high speed steel. Alfinating bath temperature was 750 ± 5 ° C, time of sample immersion was τ = 180s. Thickness of obtained coating under specified conditions was g = 150μm. Manufactured coating consists of three layers of different construction phase. The first layer from the substrate „g1`” constructed with a AlFe phase consist of alloy additives constituents of HS6-5-2 (SW7M steel: W, Mo, V, Cr and Si. On it crystallizes the second layer „g1``” of AlFeWMoCr intermetallic phases also containing Si and small amount of V. Last, the outer layer „g2” of the coating is composed with silumin including AlFeWMoCrVSi intermetallic phases. Within all layers of the coating occurs carbides. Penetration of carbides to individual coating layers is mainly due to steel surface partial melting and crystallizing layers „g1`” and „g1``” by alfinating liquid and shifting into her of carbides as well as partial carbides rejection by crystallization front of intermetallic phases occurs in coating.

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

The determination of hexavalent chromium (Cr6+) in electronic and electrical components and products to comply with RoHS regulations

International Nuclear Information System (INIS)

Hua, L.; Chan, Y.C.; Wu, Y.P.; Wu, B.Y.

2009-01-01

Toxicity of hexavalent chromium (Cr 6+ ) was focused on with a publication of EU RoHS directive, a novel method to determine hexavalent chromium is developed. It is a combination of energy dispersion X-ray fluorescence spectrometry (EDXRF), spot test, alkali digestion and UV-vis spectrophotometric analysis. First, by EDXRF screening, the presence or absence of element Cr was established. Spot test was followed to identify the valent state of chromium because Cr 6+ and Cr 3+ normally coexist. After alkali digestion, Cr(VI) was separated without an undersired Cr(VI)-Cr(III) interconversions. With a color reagent (DPC) to chelated with Cr(VI), the solution was finally detected by a UV-vis spectrophotometer at a wavelength of 540 nm which is the basis of analyzing Cr(VI) quantitatively. Some parameters affecting analyses were studied. It was found that when pH in the final solution was 2.0, the extraction time was 60 min, the extraction temperature was 90 deg. C, pH during the extraction process was 7.5-8.5, and a mixed buffer solution (0.5 M K 2 HPO 4 /0.5 M KH 2 PO 4 ) was added up to 1 ml, colorimetric reagent was added to 2 ml, it is optimal for extraction. Under this condition, interferences from Fe 3+ , Pb 2+ , Ag + , etc., were overcome. It was also found that the curves are rectilinear in the range of 0-500 μg l -1 , the correlation coefficient is up to 0.999924, and the recovery rates are more than 85%, the Cr(III)-DPCO complex can be kept stable for 24 h with a relative humidity (RH) range of 60-90%, and a temperature range of 5-40 deg. C. So it can be concluded that the proposed method has a good sensitivity and high precision. It is a more convincing and reliable method due to its relative standard deviation (R.S.D.) <1% after six replicate determinations of Cr(VI) in an Fe-Ni alloy sample

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

Measurement of Activity Coefficients at Infinite Dilution for Alcohols in [BMIM][CH3SO4] using HS-SPME/GC-FID

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A. M. Elias

Full Text Available ABSTRACT The activity coefficient at infinite dilution (&IN1 and distribution ratios at infinite dilution (&IN2 were determined for alkanols (methanol, ethanol, 1-propanol, 1-butanol, 2-butanol, and 2-methyl-2-propanol in the ionic liquid (IL 1-butyl-3-methylimidazolium methyl sulfate ([BMIM][CH3SO4] by HS-SPME (Headspace - Solid Phase Micro Extraction at four temperatures (298.15, 313.15, 333.15, and 353.15K using headspace - solid phase microextraction (SPME-HS. The results showed significant agreement with literature data. In addition, partial molar excess enthalpies at infinite dilution (&IN3, excess Gibbs energies (&IN4, and excess entropies (&IN5 were calculated from the (&IN6 values.

Social Exclusion Index-for Health Surveys (SEI-HS): a prospective nationwide study to extend and validate a multidimensional social exclusion questionnaire.

Science.gov (United States)

van Bergen, Addi P L; Hoff, Stella J M; Schreurs, Hanneke; van Loon, Annelies; van Hemert, Albert M

2017-03-14

Social exclusion (SE) refers to the inability of certain groups or individuals to fully participate in society. SE is associated with socioeconomic inequalities in health, and its measurement in routine public health monitoring is considered key to designing effective health policies. In an earlier retrospective analysis we demonstrated that in all four major Dutch cities, SE could largely be measured with existing local public health monitoring data. The current prospective study is aimed at constructing and validating an extended national measure for SE that optimally employs available items. In 2012, a stratified general population sample of 258,928 Dutch adults completed a version of the Netherlands Public Health Monitor (PHM) questionnaire in which 9 items were added covering aspects of SE that were found to be missing in our previous research. Items were derived from the SCP social exclusion index, a well-constructed 15-item instrument developed by the Netherlands Institute for Social Research (SCP). The dataset was randomly divided into a development sample (N =129,464) and a validation sample (N = 129,464). Canonical correlation analysis was conducted in the development sample. The psychometric properties were studied and compared with those of the original SCP index. All analyses were then replicated in the validation sample. The analysis yielded a four dimensional index, the Social Exclusion Index for Health Surveys (SEI-HS), containing 8 SCP items and 9 PHM items. The four dimensions: "lack of social participation", "material deprivation", "lack of normative integration" and "inadequate access to basic social rights", were each measured with 3 to 6 items. The SEI-HS showed adequate internal consistency for both the general index and for two of four dimension scales. The internal structure and construct validity of the SEI-HS were satisfactory and similar to the original SCP index. Replication of the SEI-HS in the validation sample confirmed its

Optimization of the HS-SPME-GC/MS technique for the analysis of volatile compounds in caprine Coalho cheese using response surface methodology

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Taliana Kênia Alves BEZERRA

2016-03-01

Full Text Available Abstract Caprine Coalho cheese presents great potential for a typical protected designation of origin, considering that this traditional Brazilian cheese presents a slightly salty and acid flavor, combined with a unique texture. This study optimized the HS-SPME-GC-MS methodology for volatile analysis of Coalho cheese, which can be used as a tool to help in the identification of the distinctive aroma profile of this cheese. The conditions of equilibrium time, extraction temperature and time were optimized using the statistical tool factorial experimental design 23, and applying the desirability function. After the evaluation, it was concluded that the optimum extraction conditions comprised equilibrium and extraction time of 20 and 40 minutes, respectively; and ideal extraction temperature of 45 °C. The optimum extraction of volatile compounds in goat Coalho cheese captured 32 volatile compounds: 5 alcohols, 5 esters, 3 ketones, 6 acids, 3 aldehydes, 3 terpenes, and 7 hydrocarbons.

A Headspace Solid Phase Microextraction (HS-SPME method for the chromatographic determination of alkylpyrazines in cocoa samples

Directory of Open Access Journals (Sweden)

Pini Gláucia F.

2004-01-01

Full Text Available A Headspace Solid Phase Microextraction (HS-SPME procedure for isolation and determination of alkylpyrazines in cocoa liquor, using Gas Chromatography with Flame Ionization Detection (GC-FID for the separation and detection of the analytes, is presented here. The HS-SPME operational conditions were optimized using extractions of samples spiked with known amounts of alkylpyrazines typically found on cocoa products. The maximum extraction efficiency was obtained using SPME fibers coated with 65 µm Carbowax/divinylbenzene. Additionally, the best results were achieved with extraction temperature of 60 ºC, 15 min of sample/headspace equilibration time and 45 min extraction time. It was also observed that suspending the samples in saturated aqueous NaCl solution during extractions resulted in a significant increment on the peak areas. This procedure was found to be effective to determine the so-called pyrazinic ratios (quotient between peak areas of alkylpyrazines, which are useful as quality parameters for cocoa liquor.

Simultaneous determination of kolliphor HS15 and miglyol 812 in microemulsion formulation by ultra-high performance liquid chromatography coupled with nano quantity analyte detector

OpenAIRE

Honggen Zhang; Zhenyu Wang; Oscar Liu

2016-01-01

A novel method for simultaneous determination of kolliphor HS15 and miglyol 812 in microemulsion formulation was developed using ultra-high performance liquid chromatography coupled with a nano quantitation analytical detector (UHPLC–NQAD). All components in kolliphor HS15 and miglyol 812 were well separated on an Acquity BEH C18 column. Mobile phase A was 0.1% trifluoroacetic acid (TFA) in water and mobile phase B was acetonitrile. A gradient elution sequence was programed initially with 60%...

Effects of Atorvastatin calcium combined with Aspirin on serum levels of Hcy, NSE, UA, hs-CRP and inflammatory factors of patients with cerebral infarction

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Shu-Qin Zhang

2017-03-01

Full Text Available Objective: To study the effects of Atorvastatin calcium combined with Aspirin on serum levels of homocysteine (Hcy, neuron-specific enolase (NSE, uric acid (UA, high sensitity C-reactive protein (hs-CRP and inflammatory factors of patients with cerebral infarction. Methods: 100 cases of patients with cerebral infarction from March 2014 to May 2016 were treated in the Department of Neurology of our hospital and affiliated to Huazhong University of Science and Technology of traditional Chinese medicine and Western Medicine. The subjects were divided into the control group (n=50 and the treatment group (n=50 randomly. The control group was treated with Aspirin, the treatment group were treated with Atorvastatin calcium combined with Aspirin. The two groups were treated for 28 d. The serum levels of Hcy, NSE, UA, hs- CRP, interleukin-6 (IL-6, interleukin-8 (IL-8 and tumor necrosis factor-α (TNF-α of the two groups before and after treatment were compared. Results: There were no significantly differences of the serum levels of the Hcy, NSE, UA and hs-CRP of the two groups before treatment (P>0.05. After treatment, the serum levels of the Hcy, NSE, UA and hs-CRP of the two groups were significantly lower than before treatment, and that of the treatment group were significantly lower than the control group (P0.05. After treatment, the serum levels of the IL-6, IL-8 and TNF-α of the two groups were significantly lower than before treatment, and that of the treatment group were significantly lower than the control group (P<0.05. Conclusions: Atorvastatin calcium combined with Aspirin can significantly reduce the serum levels of Hcy, NSE, UA, hs-CRP, IL-6, IL-8 and TNF-α of the patients with cerebral infarction.

[Regulatory B cells activated by CpG-ODN combined with anti-CD40 monoclonal antibody inhibit CD4(+)T cell proliferation].

Science.gov (United States)

Wang, Keng; Tao, Lei; Su, Jianbing; Zhang, Yueyang; Zou, Binhua; Wang, Yiyuan; Li, Xiaojuan

2016-09-01

Objective To observe the immunosuppressive function of regulatory B cells (Bregs) in vitro after activated by CpG oligodeoxynucleotide (CpG-ODN) and anti-CD40 mAb. Methods Mice splenic CD5(+)CD1d(high)B cells and CD5(-)CD1d(low)B cells were sorted by flow cytometry. These B cells were first stimulated with CpG-ODN combined with anti-CD40 mAb for 24 hours, and then co-cultured with purified CD4(+)T cells. The interleukin 10 (IL-10) expression in the activated Bregs and other B cell subset, as well as the proliferation and interferon γ (IFN-γ) expression in the CD4(+) T cells activated by anti-CD3 mAb plus anti-CD28 mAb were determined by flow cytometry. Results CD5(+)CD1d(high) B cells activated by CpG-ODN plus anti-CD40 mAb blocked the up-regulated CD4(+)T proliferation and significantly reduced the IFN-γ level. At the same time, activated CD5(-)CD1d(low)B cells showed no inhibitory effect on CD4(+)T cells. Further study revealed that IL-10 expression in the CD5(+)CD1d(high) B cells were much higher than that in the CD5(-)CD1d(low)B cells after stimulated with CpG-ODN combined with anti-CD40 mAb for 24 hours. Conclusion CD5(+)CD1d(high) B cells activated by CpG-ODN combined with anti-CD40 mAb have immune inhibitory effects on CD4(+)T cell activation in vitro , which possibly due to IL-10 secretion.

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)

Impact of stone content on soil moisture measurement with capacitive sensors 10HS (Decagon)

Science.gov (United States)

Deraedt, Deborah; Bernard, Julien; Bietlot, Louise; Clerbois, Laura; Rosière, Clément; Starren, Amandine; Colinet, Gilles; Mercatoris, Benoit; Degré, Aurore

2015-04-01

Lot of soil survey focused on agricultural soils. For practical reasons, those soils have a low stone content. So, most of the soil water content sensors are placed on low stone content soils and the calibration equations are developed for them. Yet some researches take an interest in forest soils that are often much different from the previous ones. The differences lie in their stone content and their slope. Lots of studies have proved the importance of making soil specific calibration of the soil water content sensor. As our lab use regularly the 10HS sensors (Decagon Devices, United States) in forested soil, we decided to evaluate the importance of the stone content in the soil moisture measurement. The soil used for this experimentation comes from Gembloux (50°33'54.9''N, 4°42'11.3''E). It is silt that has been sieved at 2 mm to remove the gravel. The stones used to form the samples come from an experimental site located in the Belgian Ardennes (50°1'52.6''N, 4°53'22.5''E). They are mainly composed of schist with some quartz and sandstone elements. Initially, only five samples were constructed with three replications each. The size and the proportion of stones were the variables. Stones were classified in two groups, the first contains gravels whose size is less than 1,5 cm and a the second contains gravels whose size is comprised between 2 and 3 cm. The proportions of stone selected for the experiment are 0, 20 and 40%. In order to generate validation data, two more samples were constructed with intermediate proportion of stone content (30%). The samples were built in PVC container which dimensions are slightly bigger than the sensor volume of influence (1.1-1.3l). The soil samples were saturated and then dried on a thermal chamber set at about 32°C. During at least 14 days, the samples soil water content was determined by the sensor measurement with the Procheck read-out system (Decagon Devices, United State) and by weighting the samples thrice a day

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

Evaluation of cell count and classification capabilities in body fluids using a fully automated Sysmex XN equipped with high-sensitive Analysis (hsA) mode and DI-60 hematology analyzer system.

Science.gov (United States)

Takemura, Hiroyuki; Ai, Tomohiko; Kimura, Konobu; Nagasaka, Kaori; Takahashi, Toshihiro; Tsuchiya, Koji; Yang, Haeun; Konishi, Aya; Uchihashi, Kinya; Horii, Takashi; Tabe, Yoko; Ohsaka, Akimichi

2018-01-01

The XN series automated hematology analyzer has been equipped with a body fluid (BF) mode to count and differentiate leukocytes in BF samples including cerebrospinal fluid (CSF). However, its diagnostic accuracy is not reliable for CSF samples with low cell concentration at the border between normal and pathologic level. To overcome this limitation, a new flow cytometry-based technology, termed "high sensitive analysis (hsA) mode," has been developed. In addition, the XN series analyzer has been equipped with the automated digital cell imaging analyzer DI-60 to classify cell morphology including normal leukocytes differential and abnormal malignant cells detection. Using various BF samples, we evaluated the performance of the XN-hsA mode and DI-60 compared to manual microscopic examination. The reproducibility of the XN-hsA mode showed good results in samples with low cell densities (coefficient of variation; % CV: 7.8% for 6 cells/μL). The linearity of the XN-hsA mode was established up to 938 cells/μL. The cell number obtained using the XN-hsA mode correlated highly with the corresponding microscopic examination. Good correlation was also observed between the DI-60 analyses and manual microscopic classification for all leukocyte types, except monocytes. In conclusion, the combined use of cell counting with the XN-hsA mode and automated morphological analyses using the DI-60 mode is potentially useful for the automated analysis of BF cells.

Evaluating watershed protection programs in New York City's Cannonsville Reservoir source watershed using SWAT-HS

Science.gov (United States)

Hoang, L.; Mukundan, R.; Moore, K. E.; Owens, E. M.; Steenhuis, T. S.

2017-12-01

New York City (NYC)'s reservoirs supply over one billion gallons of drinking water each day to over nine million consumers in NYC and upstate communities. The City has invested more than $1.5 billion in watershed protection programs to maintain a waiver from filtration for the Catskill and Delaware Systems. In the last 25 years, the NYC Department of Environmental Protection (NYCDEP) has implemented programs in cooperation with upstate communities that include nutrient management, crop rotations, improvement of barnyards and manure storage, implementing tertiary treatment for Phosphorus (P) in wastewater treatment plants, and replacing failed septic systems in an effort to reduce P loads to water supply reservoirs. There have been several modeling studies evaluating the effect of agricultural Best Management Practices (BMPs) on P control in the Cannonsville watershed in the Delaware System. Although these studies showed that BMPs would reduce dissolved P losses, they were limited to farm-scale or watershed-scale estimates of reduction factors without consideration of the dynamic nature of overland flow and P losses from variable source areas. Recently, we developed the process-based SWAT-Hillslope (SWAT-HS) model, a modified version of the Soil and Water Assessment Tool (SWAT) that can realistically predict variable source runoff processes. The objective of this study is to use the SWAT-HS model to evaluate watershed protection programs addressing both point and non-point sources of P. SWAT-HS predicts streamflow very well for the Cannonsville watershed with a daily Nash Sutcliffe Efficiency (NSE) of 0.85 at the watershed outlet and NSE values ranging from 0.56 - 0.82 at five other locations within the watershed. Based on good hydrological prediction, we applied the model to predict P loads using detailed P inputs that change over time due to the implementation of watershed protection programs. Results from P model predictions provide improved projections of P

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

Directory of Open Access Journals (Sweden)

Hui Yu

2013-01-01

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

Evaluation of Hs-CRP levels and interleukin 18 (-137G/C promoter polymorphism in risk prediction of coronary artery disease in first degree relatives.

Directory of Open Access Journals (Sweden)

Rajesh Kumar G

Full Text Available Coronary Artery Disease (CAD is clearly a multifactorial disease that develops from childhood and ultimately leads to death. Several reports revealed having a First Degree Relatives (FDRS with premature CAD is a significant autonomous risk factor for CAD development. C - reactive protein (CRP is a member of the pentraxin family and is the most widely studied proinflammatory biomarker. IL-18 is a pleiotrophic and proinflammatory cytokine which is produced mainly by macrophages and plays an important role in the inflammatory cascade.Hs-CRP levels were estimated by ELISA and Genotyping of IL-18 gene variant located on promoter -137 (G/C by Allele specific PCR in blood samples of 300 CAD patients and 300 controls and 100 FDRS. Promoter Binding sites and Protein interacting partners were identified by Alibaba 2.1 and Genemania online tools respectively. Hs-CRP levels were significantly high in CAD patients followed by FDRS when compared to controls. In IL-18 -137 (G/C polymorphism homozygous GG is significantly associated with occurrence of CAD and Hs-CRP levels were significantly higher in GG genotype subjects when compared to GC and CC. IL-18 was found to be interacting with 100 protein interactants.Our results indicate that Hs-CRP levels and IL-18-137(G/C polymorphism may help to identify risk of future events of CAD in asymptomatic healthy FDRS.