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Sample records for regulatory pathway electronic

  1. DMPD: Regulatory pathways in inflammation. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17967718 Regulatory pathways in inflammation. Mantovani A, Garlanda C, Locati M, Ro....html) (.csml) Show Regulatory pathways in inflammation. PubmedID 17967718 Title Regulatory pathways in infl

  2. Regulatory pathways for vaccines for developing countries.

    Science.gov (United States)

    Milstien, Julie; Belgharbi, Lahouari

    2004-01-01

    Vaccines that are designed for use only in developing countries face regulatory hurdles that may restrict their use. There are two primary reasons for this: most regulatory authorities are set up to address regulation of products for use only within their jurisdictions and regulatory authorities in developing countries traditionally have been considered weak. Some options for regulatory pathways for such products have been identified: licensing in the country of manufacture, file review by the European Medicines Evaluation Agency on behalf of WHO, export to a country with a competent national regulatory authority (NRA) that could handle all regulatory functions for the developing country market, shared manufacturing and licensing in a developing country with competent manufacturing and regulatory capacity, and use of a contracted independent entity for global regulatory approval. These options have been evaluated on the basis of five criteria: assurance of all regulatory functions for the life of the product, appropriateness of epidemiological assessment, applicability to products no longer used in the domestic market of the manufacturing country, reduction of regulatory risk for the manufacturer, and existing rules and regulations for implementation. No one option satisfies all criteria. For all options, national infrastructures (including the underlying regulatory legislative framework, particularly to formulate and implement local evidence-based vaccine policy) must be developed. WHO has led work to develop this capacity with some success. The paper outlines additional areas of action required by the international community to assure development and use of vaccines needed for the developing world. PMID:15042235

  3. Two-Electron Transfer Pathways.

    Science.gov (United States)

    Lin, Jiaxing; Balamurugan, D; Zhang, Peng; Skourtis, Spiros S; Beratan, David N

    2015-06-18

    The frontiers of electron-transfer chemistry demand that we develop theoretical frameworks to describe the delivery of multiple electrons, atoms, and ions in molecular systems. When electrons move over long distances through high barriers, where the probability for thermal population of oxidized or reduced bridge-localized states is very small, the electrons will tunnel from the donor (D) to acceptor (A), facilitated by bridge-mediated superexchange interactions. If the stable donor and acceptor redox states on D and A differ by two electrons, it is possible that the electrons will propagate coherently from D to A. While structure-function relations for single-electron superexchange in molecules are well established, strategies to manipulate the coherent flow of multiple electrons are largely unknown. In contrast to one-electron superexchange, two-electron superexchange involves both one- and two-electron virtual intermediate states, the number of virtual intermediates increases very rapidly with system size, and multiple classes of pathways interfere with one another. In the study described here, we developed simple superexchange models for two-electron transfer. We explored how the bridge structure and energetics influence multielectron superexchange, and we compared two-electron superexchange interactions to single-electron superexchange. Multielectron superexchange introduces interference between singly and doubly oxidized (or reduced) bridge virtual states, so that even simple linear donor-bridge-acceptor systems have pathway topologies that resemble those seen for one-electron superexchange through bridges with multiple parallel pathways. The simple model systems studied here exhibit a richness that is amenable to experimental exploration by manipulating the multiple pathways, pathway crosstalk, and changes in the number of donor and acceptor species. The features that emerge from these studies may assist in developing new strategies to deliver multiple

  4. Quantitative inference of dynamic regulatory pathways via microarray data

    Directory of Open Access Journals (Sweden)

    Chen Bor-Sen

    2005-03-01

    Full Text Available Abstract Background The cellular signaling pathway (network is one of the main topics of organismic investigations. The intracellular interactions between genes in a signaling pathway are considered as the foundation of functional genomics. Thus, what genes and how much they influence each other through transcriptional binding or physical interactions are essential problems. Under the synchronous measures of gene expression via a microarray chip, an amount of dynamic information is embedded and remains to be discovered. Using a systematically dynamic modeling approach, we explore the causal relationship among genes in cellular signaling pathways from the system biology approach. Results In this study, a second-order dynamic model is developed to describe the regulatory mechanism of a target gene from the upstream causality point of view. From the expression profile and dynamic model of a target gene, we can estimate its upstream regulatory function. According to this upstream regulatory function, we would deduce the upstream regulatory genes with their regulatory abilities and activation delays, and then link up a regulatory pathway. Iteratively, these regulatory genes are considered as target genes to trace back their upstream regulatory genes. Then we could construct the regulatory pathway (or network to the genome wide. In short, we can infer the genetic regulatory pathways from gene-expression profiles quantitatively, which can confirm some doubted paths or seek some unknown paths in a regulatory pathway (network. Finally, the proposed approach is validated by randomly reshuffling the time order of microarray data. Conclusion We focus our algorithm on the inference of regulatory abilities of the identified causal genes, and how much delay before they regulate the downstream genes. With this information, a regulatory pathway would be built up using microarray data. In the present study, two signaling pathways, i.e. circadian regulatory

  5. Logical knowledge representation of regulatory relations in biomedical pathways

    DEFF Research Database (Denmark)

    Zambach, Sine; Hansen, Jens Ulrik

    2010-01-01

    Knowledge on regulatory relations, in for example regulatory pathways in biology, is used widely in experiment design by biomedical researchers and in systems biology. The knowledge has typically either been represented through simple graphs or through very expressive differential equation...... simulations of smaller parts of a pathway. In this work we suggest a knowledge representation of the most basic relations in regulatory processes regulates, positively regulates and negatively regulates in logics based on a semantic analysis. We discuss the usage of these relations in biology and in articial...... intelligence for hypothesis development in drug discovery....

  6. Discriminating response groups in metabolic and regulatory pathway networks.

    Science.gov (United States)

    Van Hemert, John L; Dickerson, Julie A

    2012-04-01

    Analysis of omics experiments generates lists of entities (genes, metabolites, etc.) selected based on specific behavior, such as changes in response to stress or other signals. Functional interpretation of these lists often uses category enrichment tests using functional annotations like Gene Ontology terms and pathway membership. This approach does not consider the connected structure of biochemical pathways or the causal directionality of events. The Omics Response Group (ORG) method, described in this work, interprets omics lists in the context of metabolic pathway and regulatory networks using a statistical model for flow within the networks. Statistical results for all response groups are visualized in a novel Pathway Flow plot. The statistical tests are based on the Erlang distribution model under the assumption of independent and identically Exponential-distributed random walk flows through pathways. As a proof of concept, we applied our method to an Escherichia coli transcriptomics dataset where we confirmed common knowledge of the E.coli transcriptional response to Lipid A deprivation. The main response is related to osmotic stress, and we were also able to detect novel responses that are supported by the literature. We also applied our method to an Arabidopsis thaliana expression dataset from an abscisic acid study. In both cases, conventional pathway enrichment tests detected nothing, while our approach discovered biological processes beyond the original studies. We created a prototype for an interactive ORG web tool at http://ecoserver.vrac.iastate.edu/pathwayflow (source code is available from https://subversion.vrac.iastate.edu/Subversion/jlv/public/jlv/pathwayflow). The prototype is described along with additional figures and tables in Supplementary Material. julied@iastate.edu Supplementary data are available at Bioinformatics online.

  7. Integrated systems approach identifies risk regulatory pathways and key regulators in coronary artery disease.

    Science.gov (United States)

    Zhang, Yan; Liu, Dianming; Wang, Lihong; Wang, Shuyuan; Yu, Xuexin; Dai, Enyu; Liu, Xinyi; Luo, Shanshun; Jiang, Wei

    2015-12-01

    Coronary artery disease (CAD) is the most common type of heart disease. However, the molecular mechanisms of CAD remain elusive. Regulatory pathways are known to play crucial roles in many pathogenic processes. Thus, inferring risk regulatory pathways is an important step toward elucidating the mechanisms underlying CAD. With advances in high-throughput data, we developed an integrated systems approach to identify CAD risk regulatory pathways and key regulators. Firstly, a CAD-related core subnetwork was identified from a curated transcription factor (TF) and microRNA (miRNA) regulatory network based on a random walk algorithm. Secondly, candidate risk regulatory pathways were extracted from the subnetwork by applying a breadth-first search (BFS) algorithm. Then, risk regulatory pathways were prioritized based on multiple CAD-associated data sources. Finally, we also proposed a new measure to prioritize upstream regulators. We inferred that phosphatase and tensin homolog (PTEN) may be a key regulator in the dysregulation of risk regulatory pathways. This study takes a closer step than the identification of disease subnetworks or modules. From the risk regulatory pathways, we could understand the flow of regulatory information in the initiation and progression of the disease. Our approach helps to uncover its potential etiology. We developed an integrated systems approach to identify risk regulatory pathways. We proposed a new measure to prioritize the key regulators in CAD. PTEN may be a key regulator in dysregulation of the risk regulatory pathways.

  8. 76 FR 411 - Regulatory Guidance Concerning Electronic Signatures and Documents

    Science.gov (United States)

    2011-01-04

    ... guidance, including memoranda and letters, may no longer be relied upon to the extent they are inconsistent... Concerning Electronic Signatures and Documents AGENCY: Federal Motor Carrier Safety Administration (FMCSA), DOT. ACTION: Notice of regulatory guidance. SUMMARY: FMCSA issues regulatory guidance concerning the...

  9. Neurogenic gene regulatory pathways in the sea urchin embryo.

    Science.gov (United States)

    Wei, Zheng; Angerer, Lynne M; Angerer, Robert C

    2016-01-15

    During embryogenesis the sea urchin early pluteus larva differentiates 40-50 neurons marked by expression of the pan-neural marker synaptotagmin B (SynB) that are distributed along the ciliary band, in the apical plate and pharyngeal endoderm, and 4-6 serotonergic neurons that are confined to the apical plate. Development of all neurons has been shown to depend on the function of Six3. Using a combination of molecular screens and tests of gene function by morpholino-mediated knockdown, we identified SoxC and Brn1/2/4, which function sequentially in the neurogenic regulatory pathway and are also required for the differentiation of all neurons. Misexpression of Brn1/2/4 at low dose caused an increase in the number of serotonin-expressing cells and at higher dose converted most of the embryo to a neurogenic epithelial sphere expressing the Hnf6 ciliary band marker. A third factor, Z167, was shown to work downstream of the Six3 and SoxC core factors and to define a branch specific for the differentiation of serotonergic neurons. These results provide a framework for building a gene regulatory network for neurogenesis in the sea urchin embryo. © 2016. Published by The Company of Biologists Ltd.

  10. Regulatory pathway analysis by high-throughput in situ hybridization.

    Directory of Open Access Journals (Sweden)

    Axel Visel

    2007-10-01

    Full Text Available Automated in situ hybridization enables the construction of comprehensive atlases of gene expression patterns in mammals. Such atlases can become Web-searchable digital expression maps of individual genes and thus offer an entryway to elucidate genetic interactions and signaling pathways. Towards this end, an atlas housing approximately 1,000 spatial gene expression patterns of the midgestation mouse embryo was generated. Patterns were textually annotated using a controlled vocabulary comprising >90 anatomical features. Hierarchical clustering of annotations was carried out using distance scores calculated from the similarity between pairs of patterns across all anatomical structures. This process ordered hundreds of complex expression patterns into a matrix that reflects the embryonic architecture and the relatedness of patterns of expression. Clustering yielded 12 distinct groups of expression patterns. Because of the similarity of expression patterns within a group, members of each group may be components of regulatory cascades. We focused on the group containing Pax6, an evolutionary conserved transcriptional master mediator of development. Seventeen of the 82 genes in this group showed a change of expression in the developing neocortex of Pax6-deficient embryos. Electromobility shift assays were used to test for the presence of Pax6-paired domain binding sites. This led to the identification of 12 genes not previously known as potential targets of Pax6 regulation. These findings suggest that cluster analysis of annotated gene expression patterns obtained by automated in situ hybridization is a novel approach for identifying components of signaling cascades.

  11. Electron transfer pathways in microbial oxygen biocathodes

    Energy Technology Data Exchange (ETDEWEB)

    Freguia, Stefano, E-mail: stefano@kais.kyoto-u.ac.j [Bio-analytical and Physical Chemistry Laboratory, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo-ku, Kyoto 606-8205 (Japan); Tsujimura, Seiya, E-mail: seiya@kais.kyoto-u.ac.j [Bio-analytical and Physical Chemistry Laboratory, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo-ku, Kyoto 606-8205 (Japan); Kano, Kenji, E-mail: kkano@kais.kyoto-u.ac.j [Bio-analytical and Physical Chemistry Laboratory, Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo-ku, Kyoto 606-8205 (Japan)

    2010-01-01

    The ability of some bacteria to enhance the rate of cathodic oxygen reduction to water has been recently discovered, opening the way to an entirely renewable and environmentally friendly concept of biocathode. In this study we reveal that several mechanisms may induce catalytic effects by bacteria. These comprise mechanisms that are putatively beneficial to the bacteria as well as mechanisms which are merely side effects, including quinone autoxidation and direct O{sub 2} reduction by heme compounds. Here we showed that 1 muM of ACNQ is able to generate a significant catalytic wave for oxygen reduction, with onset at approximately 0 V vs. SHE. Similarly, adsorption of hemin on a carbon surface catalyses O{sub 2} reduction to H{sub 2}O{sub 2} with an onset of +0.2 V vs. SHE. To evaluate the catalytic pathways of live cells on cathodic oxygen reduction, two species of electrochemically active bacteria were selected as pure cultures, namely Acinetobacter calcoaceticus and Shewanella putrefaciens. The former appears to exploit a self-excreted redox compound with redox characteristics matching those of pyrroloquinoline quinone (PQQ) for extracellular electron transfer. The latter appears to utilise outer membrane-bound redox compounds. Interaction of quinones and cytochromes with the membrane-bound electron transfer chain is yet to be proven.

  12. Uncovering transcription factor and microRNA risk regulatory pathways associated with osteoarthritis by network analysis.

    Science.gov (United States)

    Song, Zhenhua; Zhang, Chi; He, Lingxiao; Sui, Yanfang; Lin, Xiafei; Pan, Jingjing

    2018-05-01

    Osteoarthritis (OA) is the most common form of joint disease. The development of inflammation have been considered to play a key role during the progression of OA. Regulatory pathways are known to play crucial roles in many pathogenic processes. Thus, deciphering these risk regulatory pathways is critical for elucidating the mechanisms underlying OA. We constructed an OA-specific regulatory network by integrating comprehensive curated transcription and post-transcriptional resource involving transcription factor (TF) and microRNA (miRNA). To deepen our understanding of underlying molecular mechanisms of OA, we developed an integrated systems approach to identify OA-specific risk regulatory pathways. In this study, we identified 89 significantly differentially expressed genes between normal and inflamed areas of OA patients. We found the OA-specific regulatory network was a standard scale-free network with small-world properties. It significant enriched many immune response-related functions including leukocyte differentiation, myeloid differentiation and T cell activation. Finally, 141 risk regulatory pathways were identified based on OA-specific regulatory network, which contains some known regulator of OA. The risk regulatory pathways may provide clues for the etiology of OA and be a potential resource for the discovery of novel OA-associated disease genes. Copyright © 2018 Elsevier Inc. All rights reserved.

  13. DMPD: TLR pathways and IFN-regulatory factors: to each its own. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available Immunol. 2007 Feb;37(2):306-9. (.png) (.svg) (.html) (.csml) Show TLR pathways and IFN-regulatory factors: ...ng) SVG File (.svg) HTML File (.html) CSML File (.csml) Open .csml file with CIOPlayer Open .csml file with

  14. Assessing quality and completeness of human transcriptional regulatory pathways on a genome-wide scale

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    Aifantis Iannis

    2011-02-01

    Full Text Available Abstract Background Pathway databases are becoming increasingly important and almost omnipresent in most types of biological and translational research. However, little is known about the quality and completeness of pathways stored in these databases. The present study conducts a comprehensive assessment of transcriptional regulatory pathways in humans for seven well-studied transcription factors: MYC, NOTCH1, BCL6, TP53, AR, STAT1, and RELA. The employed benchmarking methodology first involves integrating genome-wide binding with functional gene expression data to derive direct targets of transcription factors. Then the lists of experimentally obtained direct targets are compared with relevant lists of transcriptional targets from 10 commonly used pathway databases. Results The results of this study show that for the majority of pathway databases, the overlap between experimentally obtained target genes and targets reported in transcriptional regulatory pathway databases is surprisingly small and often is not statistically significant. The only exception is MetaCore pathway database which yields statistically significant intersection with experimental results in 84% cases. Additionally, we suggest that the lists of experimentally derived direct targets obtained in this study can be used to reveal new biological insight in transcriptional regulation and suggest novel putative therapeutic targets in cancer. Conclusions Our study opens a debate on validity of using many popular pathway databases to obtain transcriptional regulatory targets. We conclude that the choice of pathway databases should be informed by solid scientific evidence and rigorous empirical evaluation. Reviewers This article was reviewed by Prof. Wing Hung Wong, Dr. Thiago Motta Venancio (nominated by Dr. L Aravind, and Prof. Geoff J McLachlan.

  15. Digest: Ant workers might use ancient regulatory pathways to divide labor

    Czech Academy of Sciences Publication Activity Database

    Ernst, Ulrich R.

    2017-01-01

    Roč. 71, č. 1 (2017), s. 193-194 ISSN 0014-3820 Institutional support: RVO:61388963 Keywords : regulatory pathways * social insect * ants Subject RIV: EH - Ecology, Behaviour OBOR OECD: Biology (theoretical, mathematical, thermal, cryobiology, biological rhythm), Evolutionary biology Impact factor: 4.201, year: 2016

  16. Extracellular vesicle communication pathways as regulatory targets of oncogenic transformation.

    Science.gov (United States)

    Choi, Dongsic; Lee, Tae Hoon; Spinelli, Cristiana; Chennakrishnaiah, Shilpa; D'Asti, Esterina; Rak, Janusz

    2017-07-01

    Pathogenesis of human cancers bridges intracellular oncogenic driver events and their impact on intercellular communication. Among multiple mediators of this 'pathological connectivity' the role of extracellular vesicles (EVs) and their subsets (exosomes, ectosomes, oncosomes) is of particular interest for several reasons. The release of EVs from cancer cells represents a unique mechanism of regulated expulsion of bioactive molecules, a process that also mediates cell-to-cell transfer of lipids, proteins, and nucleic acids. Biological effects of these processes have been implicated in several aspects of cancer-related pathology, including tumour growth, invasion, angiogenesis, metastasis, immunity and thrombosis. Notably, the emerging evidence suggests that oncogenic mutations may impact several aspects of EV-mediated cell-cell communication including: (i) EV release rate and protein content; (ii) molecular composition of cancer EVs; (iii) the inclusion of oncogenic and mutant macromolecules in the EV cargo; (iv) EV-mediated release of genomic DNA; (v) deregulation of mechanisms responsible for EV biogenesis (vesiculome) and (vi) mechanisms of EV uptake by cancer cells. Intriguingly, EV-mediated intercellular transfer of mutant and oncogenic molecules between subpopulations of cancer cells, their indolent counterparts and stroma may exert profound biological effects that often resemble (but are not tantamount to) oncogenic transformation, including changes in cell growth, clonogenicity and angiogenic phenotype, or cause cell stress and death. However, several biological barriers likely curtail a permanent horizontal transformation of normal cells through EV-mediated mechanisms. The ongoing analysis and targeting of EV-mediated intercellular communication pathways can be viewed as a new therapeutic paradigm in cancer, while the analysis of oncogenic cargo contained in EVs released from cancer cells into biofluids is being developed for clinical use as a biomarker

  17. Regulatory cross-talks and cascades in rice hormone biosynthesis pathways contribute to stress signaling

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    Arindam Deb

    2016-08-01

    Full Text Available Crosstalk among different hormone signaling pathways play an important role in modulating plant response to both biotic and abiotic stress. Hormone activity is controlled by its bio-availability, which is again influenced by its biosynthesis. Thus independent hormone biosynthesis pathways must be regulated and co-ordinated to mount an integrated response. One of the possibilities is to use cis-regulatory elements to orchestrate expression of hormone biosynthesis genes. Analysis of CREs, associated with differentially expressed hormone biosynthesis related genes in rice leaf under Magnaporthe oryzae attack and drought stress enabled us to obtain insights about cross-talk among hormone biosynthesis pathways at the transcriptional level. We identified some master transcription regulators that co-ordinate different hormone biosynthesis pathways under stress. We found that Abscisic acid and Brassinosteroid regulate Cytokinin conjugation; conversely Brassinosteroid biosynthesis is affected by both Abscisic acid and Cytokinin. Jasmonic acid and Ethylene biosynthesis may be modulated by Abscisic acid through DREB transcription factors. Jasmonic acid or Salicylic acid biosynthesis pathways are co-regulated but they are unlikely to influence each other’s production directly. Thus multiple hormones may modulate hormone biosynthesis pathways through a complex regulatory network, where biosynthesis of one hormone is affected by several other contributing hormones.

  18. The major cellular sterol regulatory pathway is required for Andes virus infection.

    Directory of Open Access Journals (Sweden)

    Josiah Petersen

    2014-02-01

    Full Text Available The Bunyaviridae comprise a large family of RNA viruses with worldwide distribution and includes the pathogenic New World hantavirus, Andes virus (ANDV. Host factors needed for hantavirus entry remain largely enigmatic and therapeutics are unavailable. To identify cellular requirements for ANDV infection, we performed two parallel genetic screens. Analysis of a large library of insertionally mutagenized human haploid cells and a siRNA genomic screen converged on components (SREBP-2, SCAP, S1P and S2P of the sterol regulatory pathway as critically important for infection by ANDV. The significance of this pathway was confirmed using functionally deficient cells, TALEN-mediated gene disruption, RNA interference and pharmacologic inhibition. Disruption of sterol regulatory complex function impaired ANDV internalization without affecting virus binding. Pharmacologic manipulation of cholesterol levels demonstrated that ANDV entry is sensitive to changes in cellular cholesterol and raises the possibility that clinically approved regulators of sterol synthesis may prove useful for combating ANDV infection.

  19. Nitrogen modulation of legume root architecture signaling pathways involves phytohormones and small regulatory molecules.

    Science.gov (United States)

    Mohd-Radzman, Nadiatul A; Djordjevic, Michael A; Imin, Nijat

    2013-10-01

    Nitrogen, particularly nitrate is an important yield determinant for crops. However, current agricultural practice with excessive fertilizer usage has detrimental effects on the environment. Therefore, legumes have been suggested as a sustainable alternative for replenishing soil nitrogen. Legumes can uniquely form nitrogen-fixing nodules through symbiotic interaction with specialized soil bacteria. Legumes possess a highly plastic root system which modulates its architecture according to the nitrogen availability in the soil. Understanding how legumes regulate root development in response to nitrogen availability is an important step to improving root architecture. The nitrogen-mediated root development pathway starts with sensing soil nitrogen level followed by subsequent signal transduction pathways involving phytohormones, microRNAs and regulatory peptides that collectively modulate the growth and shape of the root system. This review focuses on the current understanding of nitrogen-mediated legume root architecture including local and systemic regulations by different N-sources and the modulations by phytohormones and small regulatory molecules.

  20. New regulatory pathways and incentives for sustainable antibiotics: Recent European & US Initiatives

    DEFF Research Database (Denmark)

    Minssen, Timo

    2014-01-01

    ) and the COMBACTE and TRANSLOCATION projects under NewDrugs4BadBugs program, involving the EU Commission and the pharma industry. But also national initiatives, such as the successful Danish ban and regulations on antibiotic use in animal production, as well as educational efforts (the European Antibiotic Awareness......New regulatory pathways and incentives for sustainable antibiotics: Recent European & US Initiatives Posted on March 19, 2014 by Timo Minssen Please find attached a ppt presentation on “New regulatory pathways and incentives for sustainable antibiotics: Recent European & US Initiatives” given...... on March 7, 2014 at the Broad Institute of MIT and Harvard. The presentation was followed by a discussion moderated by US patent attorney Melissa Hunter-Ensor, Partner at Saul Ewing, Boston I started out by emphasizing increasing problems of antimicrobial resistance (AMR) on a global level, providing new...

  1. Regulatory network of secondary metabolism in Brassica rapa: insight into the glucosinolate pathway.

    Directory of Open Access Journals (Sweden)

    Dunia Pino Del Carpio

    Full Text Available Brassica rapa studies towards metabolic variation have largely been focused on the profiling of the diversity of metabolic compounds in specific crop types or regional varieties, but none aimed to identify genes with regulatory function in metabolite composition. Here we followed a genetical genomics approach to identify regulatory genes for six biosynthetic pathways of health-related phytochemicals, i.e carotenoids, tocopherols, folates, glucosinolates, flavonoids and phenylpropanoids. Leaves from six weeks-old plants of a Brassica rapa doubled haploid population, consisting of 92 genotypes, were profiled for their secondary metabolite composition, using both targeted and LC-MS-based untargeted metabolomics approaches. Furthermore, the same population was profiled for transcript variation using a microarray containing EST sequences mainly derived from three Brassica species: B. napus, B. rapa and B. oleracea. The biochemical pathway analysis was based on the network analyses of both metabolite QTLs (mQTLs and transcript QTLs (eQTLs. Co-localization of mQTLs and eQTLs lead to the identification of candidate regulatory genes involved in the biosynthesis of carotenoids, tocopherols and glucosinolates. We subsequently focused on the well-characterized glucosinolate pathway and revealed two hotspots of co-localization of eQTLs with mQTLs in linkage groups A03 and A09. Our results indicate that such a large-scale genetical genomics approach combining transcriptomics and metabolomics data can provide new insights into the genetic regulation of metabolite composition of Brassica vegetables.

  2. Simultaneous genome-wide inference of physical, genetic, regulatory, and functional pathway components.

    Directory of Open Access Journals (Sweden)

    Christopher Y Park

    2010-11-01

    Full Text Available Biomolecular pathways are built from diverse types of pairwise interactions, ranging from physical protein-protein interactions and modifications to indirect regulatory relationships. One goal of systems biology is to bridge three aspects of this complexity: the growing body of high-throughput data assaying these interactions; the specific interactions in which individual genes participate; and the genome-wide patterns of interactions in a system of interest. Here, we describe methodology for simultaneously predicting specific types of biomolecular interactions using high-throughput genomic data. This results in a comprehensive compendium of whole-genome networks for yeast, derived from ∼3,500 experimental conditions and describing 30 interaction types, which range from general (e.g. physical or regulatory to specific (e.g. phosphorylation or transcriptional regulation. We used these networks to investigate molecular pathways in carbon metabolism and cellular transport, proposing a novel connection between glycogen breakdown and glucose utilization supported by recent publications. Additionally, 14 specific predicted interactions in DNA topological change and protein biosynthesis were experimentally validated. We analyzed the systems-level network features within all interactomes, verifying the presence of small-world properties and enrichment for recurring network motifs. This compendium of physical, synthetic, regulatory, and functional interaction networks has been made publicly available through an interactive web interface for investigators to utilize in future research at http://function.princeton.edu/bioweaver/.

  3. Genetic analysis of conidiation regulatory pathways in koji-mold Aspergillus oryzae.

    Science.gov (United States)

    Ogawa, Masahiro; Tokuoka, Masafumi; Jin, Feng Jie; Takahashi, Tadashi; Koyama, Yasuji

    2010-01-01

    Conidia of koji-mold Aspergillus oryzae are often used as starters in the fermented food industry. However, little is known about conidiation regulation in A. oryzae. To improve the productivity of conidia in A. oryzae, it is necessary to understand conidiation regulation in the strain. Therefore, we analyzed the conidiation regulatory system in A. oryzae using 10 kinds of conidiation regulatory gene disruptants. The phenotypes of AorfluG, AorflbA, AorflbB, AorflbC, AorflbD, AorflbE, AorbrlA, AorabaA, AorwetA, and AorfadA mutants are almost identical to those of the corresponding mutants in Aspergillus nidulans. The results indicated that the functions of conidiation regulatory genes are almost conserved between A. oryzae and A. nidulans. However, the severely reduced conidiation phenotype of the AorfluG disruptant in A. oryzae differs from the phenotype of the corresponding mutant in Aspergillus fumigatus in air-exposed culture conditions. These results suggest that A. oryzae, A. nidulans, and A. fumigatus have a G-protein signaling pathway and brlA orthologs in common, and only A. fumigatus has particular brlA activation pathways that are independent of the fluG ortholog. Furthermore, the analyses of AorflbA disruptant and AorfadA dominant-active mutants implicated that AorFadA-mediated G-protein signaling suppresses vegetative growth of A. oryzae.

  4. Electronic SSKIN pathway: reducing device-related pressure ulcers.

    Science.gov (United States)

    Campbell, Natalie

    2016-08-11

    This article describes how an interprofessional project in a London NHS Foundation Trust was undertaken to develop an intranet-based medical device-related pressure ulcer prevention and management pathway for clinical staff working across an adult critical care directorate, where life-threatening events require interventions using medical devices. The aim of this project was to improve working policies and processes to define key prevention strategies and provide clinicians with a clear, standardised approach to risk and skin assessment, equipment use, documentation and reporting clinical data using the Trust's CareVue (electronic medical records), Datix (incident reporting and risk-management tool) and eTRACE (online clinical protocol ordering) systems. The process included the development, trial and local implementation of the pathway using collaborative teamwork and the SSKIN care bundle tool. The experience of identifying issues, overcoming challenges, defining best practice and cascading SSKIN awareness training is shared.

  5. Using consensus bayesian network to model the reactive oxygen species regulatory pathway.

    Directory of Open Access Journals (Sweden)

    Liangdong Hu

    Full Text Available Bayesian network is one of the most successful graph models for representing the reactive oxygen species regulatory pathway. With the increasing number of microarray measurements, it is possible to construct the bayesian network from microarray data directly. Although large numbers of bayesian network learning algorithms have been developed, when applying them to learn bayesian networks from microarray data, the accuracies are low due to that the databases they used to learn bayesian networks contain too few microarray data. In this paper, we propose a consensus bayesian network which is constructed by combining bayesian networks from relevant literatures and bayesian networks learned from microarray data. It would have a higher accuracy than the bayesian networks learned from one database. In the experiment, we validated the bayesian network combination algorithm on several classic machine learning databases and used the consensus bayesian network to model the Escherichia coli's ROS pathway.

  6. The Alternative NF-κB Pathway in Regulatory T Cell Homeostasis and Suppressive Function.

    Science.gov (United States)

    Grinberg-Bleyer, Yenkel; Caron, Rachel; Seeley, John J; De Silva, Nilushi S; Schindler, Christian W; Hayden, Matthew S; Klein, Ulf; Ghosh, Sankar

    2018-04-01

    CD4 + Foxp3 + regulatory T cells (Tregs) are essential regulators of immune responses. Perturbation of Treg homeostasis or function can lead to uncontrolled inflammation and autoimmunity. Therefore, understanding the molecular mechanisms involved in Treg biology remains an active area of investigation. It has been shown previously that the NF-κB family of transcription factors, in particular, the canonical pathway subunits, c-Rel and p65, are crucial for the development, maintenance, and function of Tregs. However, the role of the alternative NF-κB pathway components, p100 and RelB, in Treg biology remains unclear. In this article, we show that conditional deletion of the p100 gene, nfkb2 , in Tregs, resulted in massive inflammation because of impaired suppressive function of nfkb2 -deficient Tregs. Surprisingly, mice lacking RelB in Tregs did not exhibit the same phenotype. Instead, deletion of both relb and nfkb2 rescued the inflammatory phenotype, demonstrating an essential role for p100 as an inhibitor of RelB in Tregs. Our data therefore illustrate a new role for the alternative NF-κB signaling pathway in Tregs that has implications for the understanding of molecular pathways driving tolerance and immunity. Copyright © 2018 by The American Association of Immunologists, Inc.

  7. Nitrogen modulation of legume root architecture signalling pathways involves phytohormones and small regulatory molecules

    Directory of Open Access Journals (Sweden)

    Nadiatul Akmal Mohd-Radzman

    2013-10-01

    Full Text Available Nitrogen, particularly nitrate is an important yield determinant for crops. However, current agricultural practice with excessive fertilizer usage has detrimental effects on the environment. Therefore, legumes have been suggested as a sustainable alternative for replenishing soil nitrogen. Legumes can uniquely form nitrogen-fixing nodules through symbiotic interaction with specialized soil bacteria. Legumes possess a highly plastic root system which modulates its architecture according to the nitrogen availability in the soil. Understanding how legumes regulate root development in response to nitrogen availability is an important step to improving root architecture. The nitrogen-mediated root development pathway starts with sensing soil nitrogen level followed by subsequent signal transduction pathways involving phytohormones, microRNAs and regulatory peptides that collectively modulate the growth and shape of the root system. This review focuses on the current understanding of nitrogen-mediated legume root architecture including local and systemic regulations by different N-sources and the modulations by phytohormones and small regulatory molecules.

  8. [Improving global access to new vaccines: intellectual property, technology transfer, and regulatory pathways].

    Science.gov (United States)

    Crager, Sara Eve

    2015-01-01

    The 2012 World Health Assembly Global Vaccine Action Plan called for global access to new vaccines within 5 years of licensure. Current approaches have proven insufficient to achieve sustainable vaccine pricing within such a timeline. Paralleling the successful strategy of generic competition to bring down drug prices, a clear consensus is emerging that market entry of multiple suppliers is a critical factor in expeditiously bringing down prices of new vaccines. In this context, key target objectives for improving access to new vaccines include overcoming intellectual property obstacles, streamlining regulatory pathways for biosimilar vaccines, and reducing market entry timelines for developing-country vaccine manufacturers by transfer of technology and know-how. I propose an intellectual property, technology, and know-how bank as a new approach to facilitate widespread access to new vaccines in low- and middle-income countries by efficient transfer of patented vaccine technologies to multiple developing-country vaccine manufacturers.

  9. Improving global access to new vaccines: intellectual property, technology transfer, and regulatory pathways.

    Science.gov (United States)

    Crager, Sara Eve

    2014-11-01

    The 2012 World Health Assembly Global Vaccine Action Plan called for global access to new vaccines within 5 years of licensure. Current approaches have proven insufficient to achieve sustainable vaccine pricing within such a timeline. Paralleling the successful strategy of generic competition to bring down drug prices, a clear consensus is emerging that market entry of multiple suppliers is a critical factor in expeditiously bringing down prices of new vaccines. In this context, key target objectives for improving access to new vaccines include overcoming intellectual property obstacles, streamlining regulatory pathways for biosimilar vaccines, and reducing market entry timelines for developing-country vaccine manufacturers by transfer of technology and know-how. I propose an intellectual property, technology, and know-how bank as a new approach to facilitate widespread access to new vaccines in low- and middle-income countries by efficient transfer of patented vaccine technologies to multiple developing-country vaccine manufacturers.

  10. CD38/cADPR Signaling Pathway in Airway Disease: Regulatory Mechanisms

    Directory of Open Access Journals (Sweden)

    Deepak A. Deshpande

    2018-01-01

    Full Text Available Asthma is an inflammatory disease in which proinflammatory cytokines have a role in inducing abnormalities of airway smooth muscle function and in the development of airway hyperresponsiveness. Inflammatory cytokines alter calcium (Ca2+ signaling and contractility of airway smooth muscle, which results in nonspecific airway hyperresponsiveness to agonists. In this context, Ca2+ regulatory mechanisms in airway smooth muscle and changes in these regulatory mechanisms encompass a major component of airway hyperresponsiveness. Although dynamic Ca2+ regulation is complex, phospholipase C/inositol tris-phosphate (PLC/IP3 and CD38-cyclic ADP-ribose (CD38/cADPR are two major pathways mediating agonist-induced Ca2+ regulation in airway smooth muscle. Altered CD38 expression or enhanced cyclic ADP-ribosyl cyclase activity associated with CD38 contributes to human pathologies such as asthma, neoplasia, and neuroimmune diseases. This review is focused on investigations on the role of CD38-cyclic ADP-ribose signaling in airway smooth muscle in the context of transcriptional and posttranscriptional regulation of CD38 expression. The specific roles of transcription factors NF-kB and AP-1 in the transcriptional regulation of CD38 expression and of miRNAs miR-140-3p and miR-708 in the posttranscriptional regulation and the underlying mechanisms of such regulation are discussed.

  11. CD38/cADPR Signaling Pathway in Airway Disease: Regulatory Mechanisms

    Science.gov (United States)

    Deshpande, Deepak A.; Guedes, Alonso G. P.; Graeff, Richard; Dogan, Soner; Subramanian, Subbaya; Walseth, Timothy F.

    2018-01-01

    Asthma is an inflammatory disease in which proinflammatory cytokines have a role in inducing abnormalities of airway smooth muscle function and in the development of airway hyperresponsiveness. Inflammatory cytokines alter calcium (Ca2+) signaling and contractility of airway smooth muscle, which results in nonspecific airway hyperresponsiveness to agonists. In this context, Ca2+ regulatory mechanisms in airway smooth muscle and changes in these regulatory mechanisms encompass a major component of airway hyperresponsiveness. Although dynamic Ca2+ regulation is complex, phospholipase C/inositol tris-phosphate (PLC/IP3) and CD38-cyclic ADP-ribose (CD38/cADPR) are two major pathways mediating agonist-induced Ca2+ regulation in airway smooth muscle. Altered CD38 expression or enhanced cyclic ADP-ribosyl cyclase activity associated with CD38 contributes to human pathologies such as asthma, neoplasia, and neuroimmune diseases. This review is focused on investigations on the role of CD38-cyclic ADP-ribose signaling in airway smooth muscle in the context of transcriptional and posttranscriptional regulation of CD38 expression. The specific roles of transcription factors NF-kB and AP-1 in the transcriptional regulation of CD38 expression and of miRNAs miR-140-3p and miR-708 in the posttranscriptional regulation and the underlying mechanisms of such regulation are discussed. PMID:29576747

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

    Science.gov (United States)

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

    1999-02-01

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

  13. 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

  14. The EbpA-RpoN Regulatory Pathway of the Pathogen Leptospira interrogans Is Essential for Survival in the Environment

    Science.gov (United States)

    Hu, Wei-Lin; Pappas, Christopher J.; Zhang, Jun-Jie; Yang, You-Yun; Yan, Jie

    2016-01-01

    ABSTRACT Leptospira interrogans is the agent of leptospirosis, a reemerging zoonotic disease. It is transmitted to humans through environmental surface waters contaminated by the urine of mammals chronically infected by pathogenic strains able to survive in water for long periods. Little is known about the regulatory pathways underlying environmental sensing and host adaptation of L. interrogans during its enzootic cycle. This study identifies the EbpA-RpoN regulatory pathway in L. interrogans. In this pathway, EbpA, a σ54 activator and putative prokaryotic enhancer-binding protein (EBP), and the alternative sigma factor RpoN (σ54) control expression of at least three genes, encoding AmtB (an ammonium transport protein) and two proteins of unknown function. Electrophoresis mobility shift assay demonstrated that recombinant RpoN and EbpA bind to the promoter region and upstream of these three identified genes, respectively. Genetic disruption of ebpA in L. interrogans serovar Manilae virtually abolished expression of the three genes, including amtB in two independent ebpA mutants. Complementation of the ebpA mutant restored expression of these genes. Intraperitoneal inoculation of gerbils with the ebpA mutant did not affect mortality. However, the ebpA mutant had decreased cell length in vitro and had a significantly lowered cell density at stationary phase when grown with l-alanine as the sole nitrogen source. Furthermore, the ebpA mutant has dramatically reduced long-term survival ability in water. Together, these studies identify a regulatory pathway, the EbpA-RpoN pathway, that plays an important role in the zoonotic cycle of L. interrogans. IMPORTANCE Leptospirosis is a reemerging disease with global importance. However, our understanding of gene regulation of the spirochetal pathogen Leptospira interrogans is still in its infancy, largely due to the lack of robust tools for genetic manipulation of this spirochete. Little is known about how the pathogen

  15. The EbpA-RpoN Regulatory Pathway of the Pathogen Leptospira interrogans Is Essential for Survival in the Environment.

    Science.gov (United States)

    Hu, Wei-Lin; Pappas, Christopher J; Zhang, Jun-Jie; Yang, You-Yun; Yan, Jie; Picardeau, Mathieu; Yang, X Frank

    2017-02-01

    Leptospira interrogans is the agent of leptospirosis, a reemerging zoonotic disease. It is transmitted to humans through environmental surface waters contaminated by the urine of mammals chronically infected by pathogenic strains able to survive in water for long periods. Little is known about the regulatory pathways underlying environmental sensing and host adaptation of L. interrogans during its enzootic cycle. This study identifies the EbpA-RpoN regulatory pathway in L. interrogans In this pathway, EbpA, a σ 54 activator and putative prokaryotic enhancer-binding protein (EBP), and the alternative sigma factor RpoN (σ 54 ) control expression of at least three genes, encoding AmtB (an ammonium transport protein) and two proteins of unknown function. Electrophoresis mobility shift assay demonstrated that recombinant RpoN and EbpA bind to the promoter region and upstream of these three identified genes, respectively. Genetic disruption of ebpA in L. interrogans serovar Manilae virtually abolished expression of the three genes, including amtB in two independent ebpA mutants. Complementation of the ebpA mutant restored expression of these genes. Intraperitoneal inoculation of gerbils with the ebpA mutant did not affect mortality. However, the ebpA mutant had decreased cell length in vitro and had a significantly lowered cell density at stationary phase when grown with l-alanine as the sole nitrogen source. Furthermore, the ebpA mutant has dramatically reduced long-term survival ability in water. Together, these studies identify a regulatory pathway, the EbpA-RpoN pathway, that plays an important role in the zoonotic cycle of L. interrogans IMPORTANCE: Leptospirosis is a reemerging disease with global importance. However, our understanding of gene regulation of the spirochetal pathogen Leptospira interrogans is still in its infancy, largely due to the lack of robust tools for genetic manipulation of this spirochete. Little is known about how the pathogen achieves its

  16. Short-term regulation and alternative pathways of photosynthetic electron transport in Hibiscus rosa-sinensis leaves.

    Science.gov (United States)

    Trubitsin, Boris V; Vershubskii, Alexey V; Priklonskii, Vladimir I; Tikhonov, Alexander N

    2015-11-01

    In this work, using the EPR and PAM-fluorometry methods, we have studied induction events of photosynthetic electron transport in Hibiscus rosa-sinensis leaves. The methods used are complementary, providing efficient tools for in situ monitoring of P700 redox transients and photochemical activity of photosystem II (PSII). The induction of P700(+) in dark-adapted leaves is characterized by the multiphase kinetics with a lag-phase, which duration elongates with the dark-adaptation time. Analyzing effects of the uncoupler monensin and artificial electron carrier methylviologen (MV) on photooxidation of P700 and slow induction of chlorophyll a fluorescence (SIF), we could ascribe different phases of transient kinetics of electron transport processes in dark-adapted leaves to the following regulatory mechanisms: (i) acceleration of electron transfer on the acceptor side of PSI, (ii) pH-dependent modulation of the intersystem electron flow, and (iii) re-distribution of electron fluxes between alternative (linear, cyclic, and pseudocyclic) pathways. Monensin significantly decreases a level of P700(+) and inhibits SIF. MV, which mediates electron flow from PSI to O2 with consequent formation of H2O2, promotes a rapid photooxidation of P700 without any lag-phase peculiar to untreated leaves. MV-mediated water-water cycle (H2O→PSII→PSI→MV→O2→H2O2→H2O) is accompanied by generation of ascorbate free radicals. This suggests that the ascorbate peroxidase system of defense against reactive oxygen species is active in chloroplasts of H. rosa-sinensis leaves. In DCMU-treated chloroplasts with inhibited PSII, the contribution of cyclic electron flow is insignificant as compared to linear electron flow. For analysis of induction events, we have simulated electron transport processes within the framework of our generalized mathematical model of oxygenic photosynthesis, which takes into account pH-dependent mechanisms of electron transport control and re-distribution of

  17. LncRNAs in Secondary Hair Follicle of Cashmere Goat: Identification, Expression, and Their Regulatory Network in Wnt Signaling Pathway.

    Science.gov (United States)

    Bai, Wen L; Zhao, Su J; Wang, Ze Y; Zhu, Yu B; Dang, Yun L; Cong, Yu Y; Xue, Hui L; Wang, Wei; Deng, Liang; Guo, Dan; Wang, Shi Q; Zhu, Yan X; Yin, Rong H

    2018-07-03

    Long noncoding RNAs (lncRNAs) are a novel class of eukaryotic transcripts. They are thought to act as a critical regulator of protein-coding gene expression. Herein, we identified and characterized 13 putative lncRNAs from the expressed sequence tags from secondary hair follicle of Cashmere goat. Furthermore, we investigated their transcriptional pattern in secondary hair follicle of Liaoning Cashmere goat during telogen and anagen phases. Also, we generated intracellular regulatory networks of upregulated lncRNAs at anagen in Wnt signaling pathway based on bioinformatics analysis. The relative expression of six putative lncRNAs (lncRNA-599618, -599556, -599554, -599547, -599531, and -599509) at the anagen phase is significantly higher than that at telogen. Compared with anagen, the relative expression of four putative lncRNAs (lncRNA-599528, -599518, -599511, and -599497) was found to be significantly upregulated at telogen phase. The network generated showed that a rich and complex regulatory relationship of the putative lncRNAs and related miRNAs with their target genes in Wnt signaling pathway. Our results from the present study provided a foundation for further elucidating the functional and regulatory mechanisms of these putative lncRNAs in the development of secondary hair follicle and cashmere fiber growth of Cashmere goat.

  18. Small regulatory RNAs of the RNA interference (RNAi) pathway as a prophylactic treatment against fish pathogenic viruses

    DEFF Research Database (Denmark)

    Schyth, Brian Dall; Hajiabadi, Seyed Amir Hossein Jalali; Kristensen, Lasse Bøgelund Juel

    2011-01-01

    Small RNAs acting in the recently discovered gene regulatory mechanism called RNA interference has a potential as diagnostic signatures of disease and immunological state and when produced synthetically as prophylactic treatment of such diseases. In the RNAi mechanism the cell produces different....... The mechanism can be programmed with several types of small double stranded RNAs - the type of which defines the destiny of the target. One such class of regulatory RNAs called microRNAs are upregulated due to various physiological responses of the cell and they suppress many genes simultaneously believed...... small RNAs which inhibit gene expression through more or less specific interaction with messenger RNAs resulting in repression of translation to protein. In this way cells can turn of genes of specific pathways thereby leading to altered physiological stages of tissues and possibly of whole organisms...

  19. Fragmentation pathways of tungsten hexacarbonyl clusters upon electron ionization

    Energy Technology Data Exchange (ETDEWEB)

    Neustetter, M.; Jabbour Al Maalouf, E.; Denifl, S., E-mail: Stephan.Denifl@uibk.ac.at, E-mail: plimaovieira@fct.unl.pt [Institut für Ionenphysik und Angewandte Physik, Universität Innsbruck, Technikerstrasse 25, A-6020 Innsbruck (Austria); Limão-Vieira, P., E-mail: Stephan.Denifl@uibk.ac.at, E-mail: plimaovieira@fct.unl.pt [Institut für Ionenphysik und Angewandte Physik, Universität Innsbruck, Technikerstrasse 25, A-6020 Innsbruck (Austria); Laboratório de Colisões Atómicas e Moleculares, CEFITEC, Departamento de Física, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, 2829-516 Caparica (Portugal)

    2016-08-07

    Electron ionization of neat tungsten hexacarbonyl (W(CO){sub 6}) clusters has been investigated in a crossed electron-molecular beam experiment coupled with a mass spectrometer system. The molecule is used for nanofabrication processes through electron beam induced deposition and ion beam induced deposition techniques. Positive ion mass spectra of W(CO){sub 6} clusters formed by electron ionization at 70 eV contain the ion series of the type W(CO){sub n}{sup +} (0 ≤ n ≤ 6) and W{sub 2}(CO){sub n}{sup +} (0 ≤ n ≤ 12). In addition, a series of peaks are observed and have been assigned to WC(CO){sub n}{sup +} (0 ≤ n ≤ 3) and W{sub 2}C(CO){sub n}{sup +} (0 ≤ n ≤ 10). A distinct change of relative fragment ion intensity can be observed for clusters compared to the single molecule. The characteristic fragmentation pattern obtained in the mass spectra can be explained by a sequential decay of the ionized organometallic, which is also supported by the study of the clusters when embedded in helium nanodroplets. In addition, appearance energies for the dissociative ionization channels for singly charged ions have been estimated from experimental ion efficiency curves.

  20. Canadian and United States regulatory models compared: doses from atmospheric pathways

    International Nuclear Information System (INIS)

    Peterson, S-R.

    1997-01-01

    CANDU reactors sold offshore are licensed primarily to satisfy Canadian Regulations. For radioactive emissions during normal operation, the Canadian Standards Association's CAN/CSA-N288.1-M87 is used. This standard provides guidelines and methodologies for calculating a rate of radionuclide release that exposes a member of the public to the annual dose limit. To calculate doses from air concentrations, either CSA-N288.1 or the Regulatory Guide 1.109 of the United States Nuclear Regulatory Commission, which has already been used to license light-water reactors in these countries, may be used. When dose predictions from CSA-N288.1 are compared with those from the U.S. Regulatory Guides, the differences in projected doses raise questions about the predictions. This report explains differences between the two models for ingestion, inhalation, external and immersion doses

  1. A Model of an Integrated Immune System Pathway in Homo sapiens and Its Interaction with Superantigen Producing Expression Regulatory Pathway in Staphylococcus aureus: Comparing Behavior of Pathogen Perturbed and Unperturbed Pathway

    Science.gov (United States)

    Tomar, Namrata; De, Rajat K.

    2013-01-01

    Response of an immune system to a pathogen attack depends on the balance between the host immune defense and the virulence of the pathogen. Investigation of molecular interactions between the proteins of a host and a pathogen helps in identifying the pathogenic proteins. It is necessary to understand the dynamics of a normally behaved host system to evaluate the capacity of its immune system upon pathogen attack. In this study, we have compared the behavior of an unperturbed and pathogen perturbed host system. Moreover, we have developed a formalism under Flux Balance Analysis (FBA) for the optimization of conflicting objective functions. We have constructed an integrated pathway system, which includes Staphylococcal Superantigen (SAg) expression regulatory pathway and TCR signaling pathway of Homo sapiens. We have implemented the method on this pathway system and observed the behavior of host signaling molecules upon pathogen attack. The entire study has been divided into six different cases, based on the perturbed/unperturbed conditions. In other words, we have investigated unperturbed and pathogen perturbed human TCR signaling pathway, with different combinations of optimization of concentrations of regulatory and signaling molecules. One of these cases has aimed at finding out whether minimization of the toxin production in a pathogen leads to the change in the concentration levels of the proteins coded by TCR signaling pathway genes in the infected host. Based on the computed results, we have hypothesized that the balance between TCR signaling inhibitory and stimulatory molecules can keep TCR signaling system into resting/stimulating state, depending upon the perturbation. The proposed integrated host-pathogen interaction pathway model has accurately reflected the experimental evidences, which we have used for validation purpose. The significance of this kind of investigation lies in revealing the susceptible interaction points that can take back the

  2. Pathway-based analysis of genome-wide siRNA screens reveals the regulatory landscape of APP processing.

    Directory of Open Access Journals (Sweden)

    Luiz Miguel Camargo

    Full Text Available The progressive aggregation of Amyloid-β (Aβ in the brain is a major trait of Alzheimer's Disease (AD. Aβ is produced as a result of proteolytic processing of the β-amyloid precursor protein (APP. Processing of APP is mediated by multiple enzymes, resulting in the production of distinct peptide products: the non-amyloidogenic peptide sAPPα and the amyloidogenic peptides sAPPβ, Aβ40, and Aβ42. Using a pathway-based approach, we analyzed a large-scale siRNA screen that measured the production of different APP proteolytic products. Our analysis identified many of the biological processes/pathways that are known to regulate APP processing and have been implicated in AD pathogenesis, as well as revealing novel regulatory mechanisms. Furthermore, we also demonstrate that some of these processes differentially regulate APP processing, with some mechanisms favouring production of certain peptide species over others. For example, synaptic transmission having a bias towards regulating Aβ40 production over Aβ42 as well as processes involved in insulin and pancreatic biology having a bias for sAPPβ production over sAPPα. In addition, some of the pathways identified as regulators of APP processing contain genes (CLU, BIN1, CR1, PICALM, TREM2, SORL1, MEF2C, DSG2, EPH1A recently implicated with AD through genome wide association studies (GWAS and associated meta-analysis. In addition, we provide supporting evidence and a deeper mechanistic understanding of the role of diabetes in AD. The identification of these processes/pathways, their differential impact on APP processing, and their relationships to each other, provide a comprehensive systems biology view of the "regulatory landscape" of APP.

  3. Chronic stress and peripheral pain: Evidence for distinct, region-specific changes in visceral and somatosensory pain regulatory pathways.

    Science.gov (United States)

    Zheng, Gen; Hong, Shuangsong; Hayes, John M; Wiley, John W

    2015-11-01

    Chronic stress alters the hypothalamic-pituitary-adrenal (HPA) axis and enhances visceral and somatosensory pain perception. It is unresolved whether chronic stress has distinct effects on visceral and somatosensory pain regulatory pathways. Previous studies reported that stress-induced visceral hyperalgesia is associated with reciprocal alterations of endovanilloid and endocannabinoid pain pathways in DRG neurons innervating the pelvic viscera. In this study, we compared somatosensory and visceral hyperalgesia with respect to differential responses of peripheral pain regulatory pathways in a rat model of chronic, intermittent stress. We found that chronic stress induced reciprocal changes in the endocannabinoid 2-AG (increased) and endocannabinoid degradation enzymes COX-2 and FAAH (decreased), associated with down-regulation of CB1 and up-regulation of TRPV1 receptors in L6-S2 DRG but not L4-L5 DRG neurons. In contrast, sodium channels Nav1.7 and Nav1.8 were up-regulated in L4-L5 but not L6-S2 DRGs in stressed rats, which was reproduced in control DRGs treated with corticosterone in vitro. The reciprocal changes of CB1, TRPV1 and sodium channels were cell-specific and observed in the sub-population of nociceptive neurons. Behavioral assessment showed that visceral hyperalgesia persisted, whereas somatosensory hyperalgesia and enhanced expression of Nav1.7 and Nav1.8 sodium channels in L4-L5 DRGs normalized 3 days after completion of the stress phase. These data indicate that chronic stress induces visceral and somatosensory hyperalgesia that involves differential changes in endovanilloid and endocannabinoid pathways, and sodium channels in DRGs innervating the pelvic viscera and lower extremities. These results suggest that chronic stress-induced visceral and lower extremity somatosensory hyperalgesia can be treated selectively at different levels of the spinal cord. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Regulatory Mechanisms of the Ihh/PTHrP Signaling Pathway in Fibrochondrocytes in Entheses of Pig Achilles Tendon

    Directory of Open Access Journals (Sweden)

    Xuesong Han

    2016-01-01

    Full Text Available This study is aimed at exploring the effect of stress stimulation on the proliferation and differentiation of fibrochondrocytes in entheses mediated via the Indian hedgehog (Ihh/parathyroid hormone-related protein (PTHrP signaling pathway. Differential stress stimulation on fibrochondrocytes in entheses was imposed. Gene expression and protein levels of signaling molecules including collagen type I (Col I, Col II, Col X, Ihh, and PTHrP in the cytoplasm of fibrochondrocytes were detected. Ihh signal blocking group was set up using Ihh signaling pathway-specific blocking agent cyclopamine. PTHrP enhancement group was set up using PTHrP reagent. Ihh/PTHrP double intervention group, as well as control group, was included to study the regulatory mechanisms of the Ihh/PTHrP signaling pathway in fibrochondrocytes. Under low cyclic stress tensile (CTS, PTHrP, Col I, and Col II gene expression and protein synthesis increased. Under high CTS, Ihh and Col X gene expression and protein synthesis increased. Blocking Ihh signaling with cyclopamine resulted in reduced PTHrP gene expression and protein synthesis and increased Col X gene expression and protein synthesis. Ihh and PTHrP coregulate fibrochondrocyte proliferation and differentiation in entheses through negative feedback regulation. Fibrochondrocyte is affected by the CTS. This phenomenon is regulated by stress stimulation through the Ihh/PTHrP signaling pathway.

  5. Regulatory Mechanisms of the Ihh/PTHrP Signaling Pathway in Fibrochondrocytes in Entheses of Pig Achilles Tendon.

    Science.gov (United States)

    Han, Xuesong; Zhuang, Yanfeng; Zhang, Zhihong; Guo, Lin; Wang, Wanming

    2016-01-01

    This study is aimed at exploring the effect of stress stimulation on the proliferation and differentiation of fibrochondrocytes in entheses mediated via the Indian hedgehog (Ihh)/parathyroid hormone-related protein (PTHrP) signaling pathway. Differential stress stimulation on fibrochondrocytes in entheses was imposed. Gene expression and protein levels of signaling molecules including collagen type I (Col I), Col II, Col X, Ihh, and PTHrP in the cytoplasm of fibrochondrocytes were detected. Ihh signal blocking group was set up using Ihh signaling pathway-specific blocking agent cyclopamine. PTHrP enhancement group was set up using PTHrP reagent. Ihh/PTHrP double intervention group, as well as control group, was included to study the regulatory mechanisms of the Ihh/PTHrP signaling pathway in fibrochondrocytes. Under low cyclic stress tensile (CTS), PTHrP, Col I, and Col II gene expression and protein synthesis increased. Under high CTS, Ihh and Col X gene expression and protein synthesis increased. Blocking Ihh signaling with cyclopamine resulted in reduced PTHrP gene expression and protein synthesis and increased Col X gene expression and protein synthesis. Ihh and PTHrP coregulate fibrochondrocyte proliferation and differentiation in entheses through negative feedback regulation. Fibrochondrocyte is affected by the CTS. This phenomenon is regulated by stress stimulation through the Ihh/PTHrP signaling pathway.

  6. Regulatory network of secondary metabolism in Brassica rapa : insight into the glucosinolate pathway

    NARCIS (Netherlands)

    Pino Del Carpio, Dunia; Basnet, Ram Kumar; Arends, Danny; Lin, Ke; De Vos, Ric C H; Muth, Dorota; Kodde, Jan; Boutilier, Kim; Bucher, Johan; Wang, Xiaowu; Jansen, Ritsert; Bonnema, Guusje

    2014-01-01

    Brassica rapa studies towards metabolic variation have largely been focused on the profiling of the diversity of metabolic compounds in specific crop types or regional varieties, but none aimed to identify genes with regulatory function in metabolite composition. Here we followed a genetical

  7. [Effect of baicalin on ATPase and LDH and its regulatory effect on the AC/cAMP/PKA signaling pathway in rats with attention deficit hyperactivity disorder].

    Science.gov (United States)

    Zhou, Rong-Yi; Wang, Jiao-Jiao; You, Yue; Sun, Ji-Chao; Song, Yu-Chen; Yuan, Hai-Xia; Han, Xin-Min

    2017-05-01

    To study the effect of baicalin on synaptosomal adenosine triphosphatase (ATPase) and lactate dehydrogenase (LDH) and its regulatory effect on the adenylate cyclase (AC)/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway in rats with attention deficit hyperactivity disorder (ADHD). A total of 40 SHR rats were randomly divided into five groups: ADHD model, methylphenidate hydrochloride treatment (0.07 mg/mL), and low-dose (3.33 mg/mL), medium-dose (6.67 mg/mL), and high-dose (10 mg/mL) baicalin treatment (n=8 each). Eight WKY rats were selected as normal control group. Percoll density gradient centrifugation was used to prepare brain synaptosomes and an electron microscope was used to observe their structure. Colorimetry was used to measure the activities of ATPase and LDH in synaptosomes. ELISA was used to measure the content of AC, cAMP, and PKA. Compared with the normal control group, the ADHD model group had a significant reduction in the ATPase activity, a significant increase in the LDH activity, and significant reductions in the content of AC, cAMP, and PKA (PATPase activity (PATPase activity (PATPase activity (PATPase and LDH activities in rats with ADHD. The effect of baicalin is dose-dependent, and high-dose baicalin has a significantly greater effect than methylphenidate hydrochloride. Baicalin exerts its therapeutic effect possibly by upregulating the AC/cAMP/PKA signaling pathway.

  8. Modulating Pathways for Electron and Energy Transfer Through Molecules

    DEFF Research Database (Denmark)

    Pirrotta, Alessandro

    Energy transport efficiency and electric conductance are molecular properties that motivates the development of optoelectronic materials, energy storage, and electronic devices. Several experimental techniques allow measurement of these properties and regularly, modeling is employed to find...... correlations between chemical structure and molecular properties. This dissertation discusses the interplay between modeling and experiments toward the assessment of new relations between the molecular structure and properties. In particular, it has been shown how simulations can push the development of new...... experimental techniques, demonstrate the potential of already established techniques, and work in synergy with experiments. It is demonstrated how the use of modeling can expand our understanding of how chemical structure affects molecular properties, which will enable us to design molecules with specific...

  9. Conservation of protein abundance patterns reveals the regulatory architecture of the EGFR-MAPK pathway

    Energy Technology Data Exchange (ETDEWEB)

    Shi, T.; Niepel, M.; McDermott, J. E.; Gao, Y.; Nicora, C. D.; Chrisler, W. B.; Markillie, L. M.; Petyuk, V. A.; Smith, R. D.; Rodland, K. D.; Sorger, P. K.; Qian, W. -J.; Wiley, H. S.

    2016-07-12

    It is not known whether cancer cells generally show quantitative differences in the expression of signaling pathway proteins that could dysregulate signal transduction. To explore this issue, we first defined the primary components of the EGF-MAPK pathway in normal human mammary epithelial cells, identifying 16 core proteins and 10 feedback regulators. We then quantified their absolute abundance across a panel of normal and cancer cell lines. We found that core pathway proteins were expressed at very similar levels across all cell types. In contrast, the EGFR and transcriptionally controlled feedback regulators were expressed at highly variable levels. The absolute abundance of most core pathway proteins was between 50,000- 70,000 copies per cell, but the adaptors SOS1, SOS2, and GAB1 were found at far lower levels (2,000-5,000 per cell). MAPK signaling showed saturation in all cells between 3,000-10,000 occupied EGFR, consistent with the idea that low adaptor levels limit signaling. Our results suggest that the core MAPK pathway is essentially invariant across different cell types, with cell- specific differences in signaling likely due to variable levels of feedback regulators. The low abundance of adaptors relative to the EGFR could be responsible for previous observation of saturable signaling, endocytosis, and high affinity EGFR.

  10. Basic regulatory principles of Escherichia coli's electron transport chain for varying oxygen conditions.

    Science.gov (United States)

    Henkel, Sebastian G; Ter Beek, Alexander; Steinsiek, Sonja; Stagge, Stefan; Bettenbrock, Katja; de Mattos, M Joost Teixeira; Sauter, Thomas; Sawodny, Oliver; Ederer, Michael

    2014-01-01

    For adaptation between anaerobic, micro-aerobic and aerobic conditions Escherichia coli's metabolism and in particular its electron transport chain (ETC) is highly regulated. Although it is known that the global transcriptional regulators FNR and ArcA are involved in oxygen response it is unclear how they interplay in the regulation of ETC enzymes under micro-aerobic chemostat conditions. Also, there are diverse results which and how quinones (oxidised/reduced, ubiquinone/other quinones) are controlling the ArcBA two-component system. In the following a mathematical model of the E. coli ETC linked to basic modules for substrate uptake, fermentation product excretion and biomass formation is introduced. The kinetic modelling focusses on regulatory principles of the ETC for varying oxygen conditions in glucose-limited continuous cultures. The model is based on the balance of electron donation (glucose) and acceptance (oxygen or other acceptors). Also, it is able to account for different chemostat conditions due to changed substrate concentrations and dilution rates. The parameter identification process is divided into an estimation and a validation step based on previously published and new experimental data. The model shows that experimentally observed, qualitatively different behaviour of the ubiquinone redox state and the ArcA activity profile in the micro-aerobic range for different experimental conditions can emerge from a single network structure. The network structure features a strong feed-forward effect from the FNR regulatory system to the ArcBA regulatory system via a common control of the dehydrogenases of the ETC. The model supports the hypothesis that ubiquinone but not ubiquinol plays a key role in determining the activity of ArcBA in a glucose-limited chemostat at micro-aerobic conditions.

  11. Linking mechanistic data to endpoints of regulatory concern using the adverse outcome pathway framework.

    Science.gov (United States)

    In order to increase the uptake and use of high throughput screening data in environmental risk assessment, it is important to establish scientifically credible links between measures of biological pathway perturbation and apical adverse outcomes in humans and wildlife. The adver...

  12. Evolution of branched regulatory genetic pathways: directional selection on pleiotropic loci accelerates developmental system drift.

    Science.gov (United States)

    Johnson, Norman A; Porter, Adam H

    2007-01-01

    Developmental systems are regulated by a web of interacting loci. One common and useful approach in studying the evolution of development is to focus on classes of interacting elements within these systems. Here, we use individual-based simulations to study the evolution of traits controlled by branched developmental pathways involving three loci, where one locus regulates two different traits. We examined the system under a variety of selective regimes. In the case where one branch was under stabilizing selection and the other under directional selection, we observed "developmental system drift": the trait under stabilizing selection showed little phenotypic change even though the loci underlying that trait showed considerable evolutionary divergence. This occurs because the pleiotropic locus responds to directional selection and compensatory mutants are then favored in the pathway under stabilizing selection. Though developmental system drift may be caused by other mechanisms, it seems likely that it is accelerated by the same underlying genetic mechanism as that producing the Dobzhansky-Muller incompatibilities that lead to speciation in both linear and branched pathways. We also discuss predictions of our model for developmental system drift and how different selective regimes affect probabilities of speciation in the branched pathway system.

  13. Alternative photosynthetic electron transport pathways during anaerobiosis in the green alga Chlamydomonas reinhardtii.

    Science.gov (United States)

    Hemschemeier, Anja; Happe, Thomas

    2011-08-01

    Oxygenic photosynthesis uses light as energy source to generate an oxidant powerful enough to oxidize water into oxygen, electrons and protons. Upon linear electron transport, electrons extracted from water are used to reduce NADP(+) to NADPH. The oxygen molecule has been integrated into the cellular metabolism, both as the most efficient electron acceptor during respiratory electron transport and as oxidant and/or "substrate" in a number of biosynthetic pathways. Though photosynthesis of higher plants, algae and cyanobacteria produces oxygen, there are conditions under which this type of photosynthesis operates under hypoxic or anaerobic conditions. In the unicellular green alga Chlamydomonas reinhardtii, this condition is induced by sulfur deficiency, and it results in the production of molecular hydrogen. Research on this biotechnologically relevant phenomenon has contributed largely to new insights into additional pathways of photosynthetic electron transport, which extend the former concept of linear electron flow by far. This review summarizes the recent knowledge about various electron sources and sinks of oxygenic photosynthesis besides water and NADP(+) in the context of their contribution to hydrogen photoproduction by C. reinhardtii. This article is part of a Special Issue entitled: Regulation of Electron Transport in Chloroplasts. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Characterization of regulatory pathways in Xylella fastidiosa: genes and phenotypes controlled by algU.

    Science.gov (United States)

    Shi, Xiang Yang; Dumenyo, C Korsi; Hernandez-Martinez, Rufina; Azad, Hamid; Cooksey, Donald A

    2007-11-01

    Many virulence genes in plant bacterial pathogens are coordinately regulated by "global" regulatory genes. Conducting DNA microarray analysis of bacterial mutants of such genes, compared with the wild type, can help to refine the list of genes that may contribute to virulence in bacterial pathogens. The regulatory gene algU, with roles in stress response and regulation of the biosynthesis of the exopolysaccharide alginate in Pseudomonas aeruginosa and many other bacteria, has been extensively studied. The role of algU in Xylella fastidiosa, the cause of Pierce's disease of grapevines, was analyzed by mutation and whole-genome microarray analysis to define its involvement in aggregation, biofilm formation, and virulence. In this study, an algU::nptII mutant had reduced cell-cell aggregation, attachment, and biofilm formation and lower virulence in grapevines. Microarray analysis showed that 42 genes had significantly lower expression in the algU::nptII mutant than in the wild type. Among these are several genes that could contribute to cell aggregation and biofilm formation, as well as other physiological processes such as virulence, competition, and survival.

  15. Site-specific parameter values for the Nuclear Regulatory Commission's food pathway dose model

    International Nuclear Information System (INIS)

    Hamby, D.M.

    1992-01-01

    Routine operations at the Savannah River Site (SRS) in Western South Carolina result in radionuclide releases to the atmosphere and to the Savannah River. The resulting radiation doses to the off-site maximum individual and the off-site population within 80 km of the SRS are estimated on a yearly basis. These estimates are currently generated using dose models prescribed for the commercial nuclear power industry by the Nuclear Regulatory Commission (NRC). The NRC provides default values for dose-model parameters for facilities without resources to develop site-specific values. A survey of land- and water-use characteristics for the Savannah River area has been conducted to determine site-specific values for water recreation, consumption, and agricultural parameters used in the NRC Regulatory Guide 1.109 (1977) dosimetric models. These site parameters include local characteristics of meat, milk, and vegetable production; recreational and commercial activities on the Savannah River; and meat, milk, vegetable, and seafood consumption rates. This paper describes how parameter data were obtained at the Savannah River Site and the impacts of such data on off-site dose. Dose estimates using site-specific parameter values are compared to estimates using the NRC default values

  16. Application of R to investigate common gene regulatory network pathway among bipolar disorder and associate diseases

    Directory of Open Access Journals (Sweden)

    Nahida Habib

    2016-12-01

    Full Text Available Depression, Major Depression or mental disorder creates severe diseases. Mental illness such as Unipolar Major Depression, Bipolar Disorder, Dysthymia, Schizophrenia, Cardiovascular Diseases (Hypertension, Coronary Heart Disease, Stroke etc., are known as Major Depression. Several studies have revealed the possibilities about the association among Bipolar Disorder, Schizophrenia, Coronary Heart Diseases and Stroke with each other. The current study aimed to investigate the relationships between genetic variants in the above four diseases and to create a common pathway or PPI network. The associated genes of each disease are collected from different gene database with verification using R. After performing some preprocessing, mining and operations using R on collected genes, seven (7 common associated genes are discovered on selected four diseases (SZ, BD, CHD and Stroke. In each of the iteration, the numbers of collected genes are reduced up to 51%, 36%, 10%, 2% and finally less than 1% respectively. Moreover, common pathway on selected diseases has been investigated in this research.

  17. Signalling in the epidermis: the E2F cell cycle regulatory pathway in epidermal morphogenesis, regeneration and transformation.

    Science.gov (United States)

    Ivanova, Iordanka A; D'Souza, Sudhir J A; Dagnino, Lina

    2005-01-01

    The epidermis is the outermost layer in the skin, and it is the first line of defence against the environment. The epidermis also provides a barrier against loss of fluids and electrolytes, which is crucial for life. Essential in the maintenance of this tissue is its ability to continually self-renew and regenerate after injury. These two characteristics are critically dependent on the ability of the principal epidermal cell type, the keratinocyte, to proliferate and to respond to differentiation cues. Indeed, the epidermis is a multilayered tissue composed of keratinocyte stem cells and their differentiated progeny. Central for the control of cell proliferation is the E2F transcription factor regulatory network. This signaling network also includes cyclins, cdk, cdk inhibitors and the retinoblastoma (pRb) family of proteins. The biological importance of the E2F/pRb pathway is emphasized by the fact that a majority of human tumours exhibit alterations that disrupt the ability of pRb proteins to inhibit E2F, leading to permanent activation of the latter. Further, E2F is essential for normal epidermal regeneration after injury. Other member of the E2F signaling pathway are also involved in epidermal development and pathophysiology. Thus, whereas the pRb family of proteins is essential for epidermal morphogenesis, abnormal regulation of cyclins and E2F proteins results in tumorgenesis in this tissue. In this review, we discuss the role of each member of this important growth regulatory network in epidermal formation, homeostasis and carcinogenesis.

  18. Borna disease virus nucleoprotein inhibits type I interferon induction through the interferon regulatory factor 7 pathway

    International Nuclear Information System (INIS)

    Song, Wuqi; Kao, Wenping; Zhai, Aixia; Qian, Jun; Li, Yujun; Zhang, Qingmeng; Zhao, Hong; Hu, Yunlong; Li, Hui; Zhang, Fengmin

    2013-01-01

    Highlights: •IRF7 nuclear localisation was inhibited by BDV persistently infected. •BDV N protein resistant to IFN induction both in BDV infected OL cell and N protein plasmid transfected OL cell. •BDV N protein is related to the inhibition of IRF7 nuclear localisation. -- Abstract: The expression of type I interferon (IFN) is one of the most potent innate defences against viral infection in higher vertebrates. Borna disease virus (BDV) establishes persistent, noncytolytic infections in animals and in cultured cells. Early studies have shown that the BDV phosphoprotein can inhibit the activation of type I IFN through the TBK1–IRF3 pathway. The function of the BDV nucleoprotein in the inhibition of IFN activity is not yet clear. In this study, we demonstrated IRF7 activation and increased IFN-α/β expression in a BDV-persistently infected human oligodendroglia cell line following RNA interference-mediated BDV nucleoprotein silencing. Furthermore, we showed that BDV nucleoprotein prevented the nuclear localisation of IRF7 and inhibited endogenous IFN induction by poly(I:C), coxsackie virus B3 and IFN-β. Our findings provide evidence for a previously undescribed mechanism by which the BDV nucleoprotein inhibits type I IFN expression by interfering with the IRF7 pathway

  19. 17 CFR 249.819 - Form 19b-4, for electronic filing with respect to proposed rule changes by all self-regulatory...

    Science.gov (United States)

    2010-04-01

    ... filing with respect to proposed rule changes by all self-regulatory organizations. 249.819 Section 249..., SECURITIES EXCHANGE ACT OF 1934 Forms for Self-Regulatory Organization Rule Changes and Forms for....819 Form 19b-4, for electronic filing with respect to proposed rule changes by all self-regulatory...

  20. IL-15 Renders Conventional Lymphocytes Resistant to Suppressive Functions of Regulatory T Cells through Activation of the Phosphatidylinositol 3-Kinase Pathway

    NARCIS (Netherlands)

    Ahmed, Melika Ben; Hmida, Nadia Belhadj; Moes, Nicolette; Buyse, Sophie; Abdeladhim, Maha; Louzir, Hechmi; Cerf-Bensussan, Nadine

    2009-01-01

    IL-15 drives chronic inflammation in several human diseases. We have recently shown that IL-15 inhibits the immunosuppressive effects of TGF-beta through blockage of the Smad3-signaling pathway. Data pointing to reciprocal interactions between TGF-beta and CD4(+) regulatory T cells led us to

  1. Endogenous adaptation to low oxygen modulates T-cell regulatory pathways in EAE.

    Science.gov (United States)

    Esen, Nilufer; Katyshev, Vladimir; Serkin, Zakhar; Katysheva, Svetlana; Dore-Duffy, Paula

    2016-01-19

    In the brain, chronic inflammatory activity may lead to compromised delivery of oxygen and glucose suggesting that therapeutic approaches aimed at restoring metabolic balance may be useful. In vivo exposure to chronic mild normobaric hypoxia (10 % oxygen) leads to a number of endogenous adaptations that includes vascular remodeling (angioplasticity). Angioplasticity promotes tissue survival. We have previously shown that induction of adaptive angioplasticity modulates the disease pattern in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE). In the present study, we define mechanisms by which adaptation to low oxygen functionally ameliorates the signs and symptoms of EAE and for the first time show that tissue hypoxia may fundamentally alter neurodegenerative disease. C57BL/6 mice were immunized with MOG, and some of them were kept in the hypoxia chambers (day 0) and exposed to 10 % oxygen for 3 weeks, while the others were kept at normoxic environment. Sham-immunized controls were included in both hypoxic and normoxic groups. Animals were sacrificed at pre-clinical and peak disease periods for tissue collection and analysis. Exposure to mild hypoxia decreased histological evidence of inflammation. Decreased numbers of cluster of differentiation (CD)4+ T cells were found in the hypoxic spinal cords associated with a delayed Th17-specific cytokine response. Hypoxia-induced changes did not alter the sensitization of peripheral T cells to the MOG peptide. Exposure to mild hypoxia induced significant increases in anti-inflammatory IL-10 levels and an increase in the number of spinal cord CD25+FoxP3+ T-regulatory cells. Acclimatization to mild hypoxia incites a number of endogenous adaptations that induces an anti-inflammatory milieu. Further understanding of these mechanisms system may pinpoint possible new therapeutic targets to treat neurodegenerative disease.

  2. A model for genetic and epigenetic regulatory networks identifies rare pathways for transcription factor induced pluripotency

    Science.gov (United States)

    Artyomov, Maxim; Meissner, Alex; Chakraborty, Arup

    2010-03-01

    Most cells in an organism have the same DNA. Yet, different cell types express different proteins and carry out different functions. This is because of epigenetic differences; i.e., DNA in different cell types is packaged distinctly, making it hard to express certain genes while facilitating the expression of others. During development, upon receipt of appropriate cues, pluripotent embryonic stem cells differentiate into diverse cell types that make up the organism (e.g., a human). There has long been an effort to make this process go backward -- i.e., reprogram a differentiated cell (e.g., a skin cell) to pluripotent status. Recently, this has been achieved by transfecting certain transcription factors into differentiated cells. This method does not use embryonic material and promises the development of patient-specific regenerative medicine, but it is inefficient. The mechanisms that make reprogramming rare, or even possible, are poorly understood. We have developed the first computational model of transcription factor-induced reprogramming. Results obtained from the model are consistent with diverse observations, and identify the rare pathways that allow reprogramming to occur. If validated, our model could be further developed to design optimal strategies for reprogramming and shed light on basic questions in biology.

  3. How Adverse Outcome Pathways Can Aid the Development and Use of Computational Prediction Models for Regulatory Toxicology.

    Science.gov (United States)

    Wittwehr, Clemens; Aladjov, Hristo; Ankley, Gerald; Byrne, Hugh J; de Knecht, Joop; Heinzle, Elmar; Klambauer, Günter; Landesmann, Brigitte; Luijten, Mirjam; MacKay, Cameron; Maxwell, Gavin; Meek, M E Bette; Paini, Alicia; Perkins, Edward; Sobanski, Tomasz; Villeneuve, Dan; Waters, Katrina M; Whelan, Maurice

    2017-02-01

    Efforts are underway to transform regulatory toxicology and chemical safety assessment from a largely empirical science based on direct observation of apical toxicity outcomes in whole organism toxicity tests to a predictive one in which outcomes and risk are inferred from accumulated mechanistic understanding. The adverse outcome pathway (AOP) framework provides a systematic approach for organizing knowledge that may support such inference. Likewise, computational models of biological systems at various scales provide another means and platform to integrate current biological understanding to facilitate inference and extrapolation. We argue that the systematic organization of knowledge into AOP frameworks can inform and help direct the design and development of computational prediction models that can further enhance the utility of mechanistic and in silico data for chemical safety assessment. This concept was explored as part of a workshop on AOP-Informed Predictive Modeling Approaches for Regulatory Toxicology held September 24-25, 2015. Examples of AOP-informed model development and its application to the assessment of chemicals for skin sensitization and multiple modes of endocrine disruption are provided. The role of problem formulation, not only as a critical phase of risk assessment, but also as guide for both AOP and complementary model development is described. Finally, a proposal for actively engaging the modeling community in AOP-informed computational model development is made. The contents serve as a vision for how AOPs can be leveraged to facilitate development of computational prediction models needed to support the next generation of chemical safety assessment. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology.

  4. A DegU-P and DegQ-Dependent Regulatory Pathway for the K-state in Bacillus subtilis

    Directory of Open Access Journals (Sweden)

    Mathieu Miras

    2016-11-01

    Full Text Available The K-state in the model bacterium Bacillus subtilis is associated with transformability (competence as well as with growth arrest and tolerance for antibiotics. Entry into the K-state is determined by the stochastic activation of the transcription factor ComK and occurs in about ~15% of the population in domesticated strains. Although the upstream mechanisms that regulate the K-state have been intensively studied and are well understood, it has remained unexplained why undomesticated isolates of B. subtilis are poorly transformable compared to their domesticated counterparts. We show here that this is because fewer cells enter the K-state, suggesting that a regulatory pathway limiting entry to the K-state is missing in domesticated strains. We find that loss of this limitation is largely due to an inactivating point mutation in the promoter of degQ. The resulting low level of DegQ decreases the concentration of phosphorylated DegU, which leads to the de-repression of the srfA operon and ultimately to the stabilization of ComK. As a result, more cells reach the threshold concentration of ComK needed to activate the auto-regulatory loop at the comK promoter. In addition, we demonstrate that the activation of srfA transcription in undomesticated strains is transient, turning off abruptly as cells enter the stationary phase. Thus, the K-state and transformability are more transient and less frequently expressed in the undomesticated strains. This limitation is more extreme than appreciated from studies of domesticated strains. Selection has apparently limited both the frequency and the duration of the bistably expressed K-state in wild strains, likely because of the high cost of growth arrest associated with the K-state. Future modeling of K-state regulation and of the fitness advantages and costs of the K-state must take these features into account.

  5. Pharma Opportunities and Risks Multiply as Regulatory Reform Remakes APAC: Expanded Accelerated Pathways Challenge Developer Value Story, Evidence Collection, and Market Access Strategies.

    Science.gov (United States)

    Grignolo, Alberto; Mingping, Zhang

    2018-01-01

    Sweeping reforms in the largest markets of the Asia-Pacific region are transforming the regulatory and commercial landscape for foreign pharmaceutical companies. Japan, South Korea, and China are leading the charge, establishing mechanisms and infrastructure that both reflect and help drive international regulatory convergence and accelerate delivery of needed, innovative products to patients. In this rapidly evolving regulatory and commercial environment, drug developers can benefit from reforms and proliferating accelerated pathway (AP) frameworks, but only with regulatory and evidence-generation strategies tailored to the region. Otherwise, they will confront significant pricing and reimbursement headwinds. Although APAC economies are at different stages of development, they share a common imperative: to balance pharmaceutical innovation with affordability. Despite the complexity of meeting these sometimes conflicting demands, companies that focus on demonstrating and delivering value for money, and that price new treatments reasonably and sustainably, can succeed both for their shareholders and the region's patient population.

  6. Genetic variation in mitotic regulatory pathway genes is associated with breast tumor grade

    Science.gov (United States)

    Purrington, Kristen S.; Slettedahl, Seth; Bolla, Manjeet K.; Michailidou, Kyriaki; Czene, Kamila; Nevanlinna, Heli; Bojesen, Stig E.; Andrulis, Irene L.; Cox, Angela; Hall, Per; Carpenter, Jane; Yannoukakos, Drakoulis; Haiman, Christopher A.; Fasching, Peter A.; Mannermaa, Arto; Winqvist, Robert; Brenner, Hermann; Lindblom, Annika; Chenevix-Trench, Georgia; Benitez, Javier; Swerdlow, Anthony; Kristensen, Vessela; Guénel, Pascal; Meindl, Alfons; Darabi, Hatef; Eriksson, Mikael; Fagerholm, Rainer; Aittomäki, Kristiina; Blomqvist, Carl; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Wang, Xianshu; Olswold, Curtis; Olson, Janet E.; Mulligan, Anna Marie; Knight, Julia A.; Tchatchou, Sandrine; Reed, Malcolm W.R.; Cross, Simon S.; Liu, Jianjun; Li, Jingmei; Humphreys, Keith; Clarke, Christine; Scott, Rodney; Fostira, Florentia; Fountzilas, George; Konstantopoulou, Irene; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Ekici, Arif B.; Hartmann, Arndt; Beckmann, Matthias W.; Hartikainen, Jaana M.; Kosma, Veli-Matti; Kataja, Vesa; Jukkola-Vuorinen, Arja; Pylkäs, Katri; Kauppila, Saila; Dieffenbach, Aida Karina; Stegmaier, Christa; Arndt, Volker; Margolin, Sara; Balleine, Rosemary; Arias Perez, Jose Ignacio; Pilar Zamora, M.; Menéndez, Primitiva; Ashworth, Alan; Jones, Michael; Orr, Nick; Arveux, Patrick; Kerbrat, Pierre; Truong, Thérèse; Bugert, Peter; Toland, Amanda E.; Ambrosone, Christine B.; Labrèche, France; Goldberg, Mark S.; Dumont, Martine; Ziogas, Argyrios; Lee, Eunjung; Dite, Gillian S.; Apicella, Carmel; Southey, Melissa C.; Long, Jirong; Shrubsole, Martha; Deming-Halverson, Sandra; Ficarazzi, Filomena; Barile, Monica; Peterlongo, Paolo; Durda, Katarzyna; Jaworska-Bieniek, Katarzyna; Tollenaar, Robert A.E.M.; Seynaeve, Caroline; Brüning, Thomas; Ko, Yon-Dschun; Van Deurzen, Carolien H.M.; Martens, John W.M.; Kriege, Mieke; Figueroa, Jonine D.; Chanock, Stephen J.; Lissowska, Jolanta; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Schneeweiss, Andreas; Tapper, William J.; Gerty, Susan M.; Durcan, Lorraine; Mclean, Catriona; Milne, Roger L.; Baglietto, Laura; dos Santos Silva, Isabel; Fletcher, Olivia; Johnson, Nichola; Van'T Veer, Laura J.; Cornelissen, Sten; Försti, Asta; Torres, Diana; Rüdiger, Thomas; Rudolph, Anja; Flesch-Janys, Dieter; Nickels, Stefan; Weltens, Caroline; Floris, Giuseppe; Moisse, Matthieu; Dennis, Joe; Wang, Qin; Dunning, Alison M.; Shah, Mitul; Brown, Judith; Simard, Jacques; Anton-Culver, Hoda; Neuhausen, Susan L.; Hopper, John L.; Bogdanova, Natalia; Dörk, Thilo; Zheng, Wei; Radice, Paolo; Jakubowska, Anna; Lubinski, Jan; Devillee, Peter; Brauch, Hiltrud; Hooning, Maartje; García-Closas, Montserrat; Sawyer, Elinor; Burwinkel, Barbara; Marmee, Frederick; Eccles, Diana M.; Giles, Graham G.; Peto, Julian; Schmidt, Marjanka; Broeks, Annegien; Hamann, Ute; Chang-Claude, Jenny; Lambrechts, Diether; Pharoah, Paul D.P.; Easton, Douglas; Pankratz, V. Shane; Slager, Susan; Vachon, Celine M.; Couch, Fergus J.

    2014-01-01

    Mitotic index is an important component of histologic grade and has an etiologic role in breast tumorigenesis. Several small candidate gene studies have reported associations between variation in mitotic genes and breast cancer risk. We measured associations between 2156 single nucleotide polymorphisms (SNPs) from 194 mitotic genes and breast cancer risk, overall and by histologic grade, in the Breast Cancer Association Consortium (BCAC) iCOGS study (n = 39 067 cases; n = 42 106 controls). SNPs in TACC2 [rs17550038: odds ratio (OR) = 1.24, 95% confidence interval (CI) 1.16–1.33, P = 4.2 × 10−10) and EIF3H (rs799890: OR = 1.07, 95% CI 1.04–1.11, P = 8.7 × 10−6) were significantly associated with risk of low-grade breast cancer. The TACC2 signal was retained (rs17550038: OR = 1.15, 95% CI 1.07–1.23, P = 7.9 × 10−5) after adjustment for breast cancer risk SNPs in the nearby FGFR2 gene, suggesting that TACC2 is a novel, independent genome-wide significant genetic risk locus for low-grade breast cancer. While no SNPs were individually associated with high-grade disease, a pathway-level gene set analysis showed that variation across the 194 mitotic genes was associated with high-grade breast cancer risk (P = 2.1 × 10−3). These observations will provide insight into the contribution of mitotic defects to histological grade and the etiology of breast cancer. PMID:24927736

  7. Managing care pathways combining SNOMED CT, archetypes and an electronic guideline system.

    Science.gov (United States)

    Bernstein, Knut; Andersen, Ulrich

    2008-01-01

    Today electronic clinical guideline systems exist, but they are not well integrated with electronic health records. This paper thus proposes that the patient's "position" in the pathway during the patient journey should be made visible to all involved healthcare parties and the patient. This requires that the generic knowledge, which is represented in the guidelines, is combined with the patient specific information - and then made accessible for all relevant parties. In addition to the decision support provided by the guideline system documentation support can be provided by templates based on archetypes. This paper provides a proposal for how the guideline system and the EHR can be integrated by the use of archetypes and SNOMED CT. SNOMED CT provides the common reference terminology and the semantic links between the systems. The proposal also includes the use of a National Patient Index for storing data about the patient's position in the pathway and for sharing this information by all involved parties.

  8. Process mining routinely collected electronic health records to define real-life clinical pathways during chemotherapy.

    Science.gov (United States)

    Baker, Karl; Dunwoodie, Elaine; Jones, Richard G; Newsham, Alex; Johnson, Owen; Price, Christopher P; Wolstenholme, Jane; Leal, Jose; McGinley, Patrick; Twelves, Chris; Hall, Geoff

    2017-07-01

    There is growing interest in the use of routinely collected electronic health records to enhance service delivery and facilitate clinical research. It should be possible to detect and measure patterns of care and use the data to monitor improvements but there are methodological and data quality challenges. Driven by the desire to model the impact of a patient self-test blood count monitoring service in patients on chemotherapy, we aimed to (i) establish reproducible methods of process-mining electronic health records, (ii) use the outputs derived to define and quantify patient pathways during chemotherapy, and (iii) to gather robust data which is structured to be able to inform a cost-effectiveness decision model of home monitoring of neutropenic status during chemotherapy. Electronic Health Records at a UK oncology centre were included if they had (i) a diagnosis of metastatic breast cancer and received adjuvant epirubicin and cyclosphosphamide chemotherapy or (ii) colorectal cancer and received palliative oxaliplatin and infusional 5-fluorouracil chemotherapy, and (iii) were first diagnosed with cancer between January 2004 and February 2013. Software and a Markov model were developed, producing a schematic of patient pathways during chemotherapy. Significant variance from the assumed care pathway was evident from the data. Of the 535 patients with breast cancer and 420 with colorectal cancer there were 474 and 329 pathway variants respectively. Only 27 (5%) and 26 (6%) completed the planned six cycles of chemotherapy without having unplanned hospital contact. Over the six cycles, 169 (31.6%) patients with breast cancer and 190 (45.2%) patients with colorectal cancer were admitted to hospital. The pathways of patients on chemotherapy are complex. An iterative approach to addressing semantic and data quality issues enabled the effective use of routinely collected patient records to produce accurate models of the real-life experiences of chemotherapy patients and

  9. Electronic cigarettes: patterns of use, health effects, use in smoking cessation and regulatory issues.

    Science.gov (United States)

    Rahman, Muhammad Aziz; Hann, Nicholas; Wilson, Andrew; Worrall-Carter, Linda

    2014-01-01

    Electronic cigarettes (e-cigarettes) are battery-powered devices that vaporize a liquid solution to deliver a dose of inhaled nicotine to the user. There is ongoing debate regarding their regulation. This comprehensive narrative review aimed to discuss key issues including usage patterns, health effects, efficacy in smoking cessation and regulatory concerns with a view to informing future regulation and research agendas. PubMed, Scopus and Web of Science databases were searched using the terms (electronic cigarettes OR e-cigarettes) for articles in English, relevant to humans and published during January 2009-January 2014. The literature search revealed 37 relevant articles. Findings suggest that e-cigarettes are mostly used by middle-aged current smokers, particularly males, to help them for quitting or for recreation. E-cigarettes contain very low levels of multiple toxic substances such as formaldehyde and acrolein, but these levels are many times lower than those found in cigarettes. They were found to have effectiveness in aiding smoking cessation to a limited degree. Debate continues regarding regulating their use for cessation versus heavy restrictions to control recreational use on the basis that it perpetuates nicotine addiction. The cytotoxicity and long term health effects of e-cigarettes are unknown. Nevertheless the e-cigarette market continues to expand, largely driven by middle-aged smokers who claim to be using e-cigarettes in an attempt to reduce or quit smoking. E-cigarettes may have some potential as smoking cessation aids and, in the researchers' view, should therefore be subject to further research and regulation similar to other nicotine replacement therapies.

  10. How Adverse Outcome Pathways Can Aid the Development and Use of Computational Prediction Models for Regulatory Toxicology

    Energy Technology Data Exchange (ETDEWEB)

    Wittwehr, Clemens; Aladjov, Hristo; Ankley, Gerald; Byrne, Hugh J.; de Knecht, Joop; Heinzle, Elmar; Klambauer, Günter; Landesmann, Brigitte; Luijten, Mirjam; MacKay, Cameron; Maxwell, Gavin; Meek, M. E. (Bette); Paini, Alicia; Perkins, Edward; Sobanski, Tomasz; Villeneuve, Dan; Waters, Katrina M.; Whelan, Maurice

    2016-12-19

    Efforts are underway to transform regulatory toxicology and chemical safety assessment from a largely empirical science based on direct observation of apical toxicity outcomes in whole organism toxicity tests to a predictive one in which outcomes and risk are inferred from accumulated mechanistic understanding. The adverse outcome pathway (AOP) framework has emerged as a systematic approach for organizing knowledge that supports such inference. We argue that this systematic organization of knowledge can inform and help direct the design and development of computational prediction models that can further enhance the utility of mechanistic and in silico data for chemical safety assessment. Examples of AOP-informed model development and its application to the assessment of chemicals for skin sensitization and multiple modes of endocrine disruption are provided. The role of problem formulation, not only as a critical phase of risk assessment, but also as guide for both AOP and complementary model development described. Finally, a proposal for actively engaging the modeling community in AOP-informed computational model development is made. The contents serve as a vision for how AOPs can be leveraged to facilitate development of computational prediction models needed to support the next generation of chemical safety assessment.

  11. Expression of E-selectin ligands on circulating tumor cells: cross-regulation with cancer stem cell regulatory pathways?

    International Nuclear Information System (INIS)

    Burdick, Monica M.; Henson, Karissa A.; Delgadillo, Luis F.; Choi, Young Eun; Goetz, Douglas J.; Tees, David F. J.; Benencia, Fabian

    2012-01-01

    Although significant progress has been made in the fight against cancer, successful treatment strategies have yet to be developed to combat those tumors that have metastasized to distant organs. Poor characterization of the molecular mechanisms of cancer spread is a major impediment to designing predictive diagnostics and effective clinical interventions against late stage disease. In hematogenous metastasis, it is widely suspected that circulating tumor cells (CTCs) express specific adhesion molecules that actively initiate contact with the vascular endothelium lining the vessel walls of the target organ. This “tethering” is mediated by ligands expressed by CTCs that bind to E-selectin expressed by endothelial cells. However, it is currently unknown whether expression of functional E-selectin ligands on CTCs is related to cancer stem cell regulatory or maintenance pathways, particularly epithelial-to-mesenchymal transition and the reverse, mesenchymal-to-epithelial transition. In this hypothesis and theory article, we explore the potential roles of these mechanisms on the dynamic regulation of selectin ligands mediating CTC trafficking during metastasis.

  12. DMPD: The interferon regulatory factor family in host defense: mechanism of action. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17502370 The interferon regulatory factor family in host defense: mechanism of acti....html) (.csml) Show The interferon regulatory factor family in host defense: mechanism of action. PubmedID 1...7502370 Title The interferon regulatory factor family in host defense: mechanism

  13. DMPD: Type I interferon [corrected] gene induction by the interferon regulatory factorfamily of transcription factors. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16979567 Type I interferon [corrected] gene induction by the interferon regulatory factorfamily...ng) (.svg) (.html) (.csml) Show Type I interferon [corrected] gene induction by the interferon regulatory factorfamily...orrected] gene induction by the interferon regulatory factorfamily of transcription factors. Authors Honda K

  14. Cellular Assays for Ferredoxins: A Strategy for Understanding Electron Flow through Protein Carriers That Link Metabolic Pathways.

    Science.gov (United States)

    Atkinson, Joshua T; Campbell, Ian; Bennett, George N; Silberg, Jonathan J

    2016-12-27

    The ferredoxin (Fd) protein family is a structurally diverse group of iron-sulfur proteins that function as electron carriers, linking biochemical pathways important for energy transduction, nutrient assimilation, and primary metabolism. While considerable biochemical information about individual Fd protein electron carriers and their reactions has been acquired, we cannot yet anticipate the proportion of electrons shuttled between different Fd-partner proteins within cells using biochemical parameters that govern electron flow, such as holo-Fd concentration, midpoint potential (driving force), molecular interactions (affinity and kinetics), conformational changes (allostery), and off-pathway electron leakage (chemical oxidation). Herein, we describe functional and structural gaps in our Fd knowledge within the context of a sequence similarity network and phylogenetic tree, and we propose a strategy for improving our understanding of Fd sequence-function relationships. We suggest comparing the functions of divergent Fds within cells whose growth, or other measurable output, requires electron transfer between defined electron donor and acceptor proteins. By comparing Fd-mediated electron transfer with biochemical parameters that govern electron flow, we posit that models that anticipate energy flow across Fd interactomes can be built. This approach is expected to transform our ability to anticipate Fd control over electron flow in cellular settings, an obstacle to the construction of synthetic electron transfer pathways and rational optimization of existing energy-conserving pathways.

  15. House dust mite-specific immunotherapy alters the basal expression of T regulatory and FcεRI pathway genes.

    Science.gov (United States)

    Pevec, Branko; Radulovic Pevec, Mira; Stipic Markovic, Asja; Batista, Irena; Rijavec, Matija; Silar, Mira; Kosnik, Mitja; Korosec, Peter

    2012-01-01

    Regulatory T (Treg) cells and IgE-mediated signaling pathways could play important roles in the induction of allergen tolerance during house dust mite-specific subcutaneous immunotherapy (HDM-SCIT). Our aim was to compare the basal expression levels of Treg, T helper 1 (Th1) and Th2 transcription factors and components involved in IgE-mediated signaling in healthy subjects with those in HDM-allergic patients both untreated and successfully treated with HDM-SCIT. Thirty-nine HDM-allergic patients who completed a 3- to 5-year course of mite extract SCIT, 20 mite-allergic controls and 25 healthy controls participated in this study. The efficacy of SCIT was monitored using skin-prick tests (SPTs), total immunoglobulin E (tIgE), specific IgE (sIgE), sIgG(4), nasal challenge and visual analog scale (VAS) scores at several time points. The mRNA levels of forkhead box protein 3 (FOXP3), T-BET, GATA-3, FcεRI, spleen tyrosine kinase (Syk), phosphatidylinositol 3 kinase (PI3K) and SH2 domain-containing inositol phosphatase (SHIP) were quantified by real-time RT-PCR using nonstimulated whole blood samples. Decreased wheal sizes and VAS scores, negative challenges and increased sIgG(4) levels indicated that SCIT was effective in the treated patients. Basal expression levels of FOXP3 and GATA-3 decreased and T-BET levels increased in both treated patients and in healthy controls compared to untreated patients. The IgE-mediated pathway kinases Syk and PI3K exhibited reduced expression, whereas SHIP phosphatase levels were elevated in both treated patients and healthy controls relative to untreated patients. The expression levels of FcεRI were not significantly altered. Immunotherapy using HDM extracts results in a modification of the basal expression levels of several IgE-related signaling factors and induces a highly significant upregulation of Th1-response and downregulation of Th2-response transcription factors. Interestingly, this therapy also appears to reduce the basal

  16. Mechanisms of andrographolide-induced platelet apoptosis in human platelets: regulatory roles of the extrinsic apoptotic pathway.

    Science.gov (United States)

    Lien, Li-Ming; Su, Cheng-Chen; Hsu, Wen-Hsien; Lu, Wan-Jung; Chung, Chi-Li; Yen, Ting-Lin; Chiu, Hou-Chang; Sheu, Joen-Rong; Lin, Kuan-Hung

    2013-11-01

    Andrographolide, a novel nuclear factor-κB (NF-κB) inhibitor, is isolated from the leaves of Andrographis paniculata. Platelet activation is relevant to a variety of coronary heart diseases. Our recent studies revealed that andrographolide possesses potent antiplatelet activity by inhibition of the p38 MAPK/(●) HO-NF-κB-ERK2 cascade. Although platelets are anucleated cells, apoptotic machinery apparatus recently has been found to regulate platelet activation and limit platelet lifespan. Therefore, we further investigated the regulatory effects of andrographolide on platelet apoptotic events. In this study, apoptotic signaling events for caspase-3, -8, and Bid were time (10-60 min)- and dose (25-100 μΜ)-dependently activated by andrographolide in human platelets. Andrographolide could also disrupt mitrochondrial membrane potential. In addition, caspase-8 inhibitor (z-IETD-fmk, 50 μΜ) was found to reverse andrographolide-induced caspase-8 activation, whereas the antagonistic anti-Fas receptor (ZB4, 500 ng/mL) and anti-tumor necrosis factor-R1 (H398, 10 µg/mL) monoclonal antibodies did not. In conclusion, this study for the first time demonstrated that andrographolide might limit platelet lifespan by initiating the caspase-8-dependent extrinsic apoptotic pathway, in spite of no direct evidence that death receptors are involved in this process proved. Overall, the various medicinal properties of andrographolide suggest its potential value in treating patients with thromboembolic disorders. Copyright © 2012 John Wiley & Sons, Ltd.

  17. Mtr Extracellular Electron Transfer Pathways in Fe(III)-reducing or Fe(II)-oxidizing Bacteria: A Genomic Perspective

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Liang; Rosso, Kevin M.; Zachara, John M.; Fredrickson, Jim K.

    2012-12-01

    Originally discovered in the dissimilatory metal-reducing bacterium Shewanella oneidensis MR-1 (MR-1), the Mtr (i.e., metal-reducing) pathway exists in all characterized strains of metal-reducing Shewanella. The protein components identified to date for the Mtr pathway of MR-1 include four multi-heme c-type cytochromes (c-Cyts), CymA, MtrA, MtrC and OmcA, and a porin-like, outer membrane protein MtrB. They are strategically positioned along the width of the MR-1 cell envelope to mediate electron transfer from the quinone/quinol pool in the inner-membrane to the Fe(III)-containing minerals external to the bacterial cells. A survey of microbial genomes revealed homologues of the Mtr pathway in other dissimilatory Fe(III)-reducing bacteria, including Aeromonas hydrophila, Ferrimonas balearica and Rhodoferax ferrireducens, and in the Fe(II)-oxidizing bacteria Dechloromonas aromatica RCB, Gallionella capsiferriformans ES-2 and Sideroxydans lithotrophicus ES-1. The widespread distribution of Mtr pathways in Fe(III)-reducing or Fe(II)-oxidizing bacteria emphasizes the importance of this type of extracellular electron transfer pathway in microbial redox transformation of Fe. Their distribution in these two different functional groups of bacteria also emphasizes the bi-directional nature of electron transfer reactions carried out by the Mtr pathways. The characteristics of the Mtr pathways may be shared by other pathways used by microorganisms for exchanging electrons with their extracellular environments.

  18. An Analysis of the Regulatory Environment Governing Hearsay Electronic Evidence in South Africa: Suggestions for Reform – Part One

    Directory of Open Access Journals (Sweden)

    Lee Swales

    2018-03-01

    Full Text Available The purpose of this two-part article is to examine the regulatory environment governing hearsay electronic evidence in South Africa – with a view to providing clear, practical suggestions for regulatory reform in the context of the South African Law Reform Commission's most recent Discussion Paper on electronic evidence. Technology has become an indispensable part of modern life. In particular, the Internet has facilitated new forms of business enterprise, and shifted basic communication norms. From a legal perspective, technology has presented several novel challenges for courts and legal practitioners to deal with – one of these key challenges relates to electronic evidence and in particular the application of the hearsay rules to the digital environment. The South African Law Reform Commission has identified the application of the hearsay rule as one of the core concerns with regard to electronic evidence, and certain academic analysis has revealed inefficiency in the current legal position which may involve multiple sources of law. Moreover, the Law Society of South Africa has stated that there is some confusion amongst members of the profession in relation to hearsay as it applies to electronic evidence. With the pervasive and burgeoning nature of technology, and with the Internet in mind, it is natural to assume that electronic evidence will be relevant in most forms of legal proceedings in future, and hearsay electronic evidence in particular will play an increasingly important role in years to come. Consequently, part one of this article will consider the key definitional concept in relation to electronic evidence – data messages - and examine whether the definition should be revised. In addition, part one of this article will answer two further critical questions posed by the South African Law Reform Commission in relation to data messages and hearsay evidence, namely: should a data message constitute hearsay? And, how should one

  19. An electronic regulatory document management system for a clinical trial network.

    Science.gov (United States)

    Zhao, Wenle; Durkalski, Valerie; Pauls, Keith; Dillon, Catherine; Kim, Jaemyung; Kolk, Deneil; Silbergleit, Robert; Stevenson, Valerie; Palesch, Yuko

    2010-01-01

    A computerized regulatory document management system has been developed as a module in a comprehensive Clinical Trial Management System (CTMS) designed for an NIH-funded clinical trial network in order to more efficiently manage and track regulatory compliance. Within the network, several institutions and investigators are involved in multiple trials, and each trial has regulatory document requirements. Some of these documents are trial specific while others apply across multiple trials. The latter causes a possible redundancy in document collection and management. To address these and other related challenges, a central regulatory document management system was designed. This manuscript shares the design of the system as well as examples of it use in current studies. Copyright (c) 2009 Elsevier Inc. All rights reserved.

  20. DMPD: The role of the interferon regulatory factor (IRF) family in dendritic celldevelopment and function. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17702640 The role of the interferon regulatory factor (IRF) family in dendritic celldevelopment and function...in dendritic celldevelopment and function. PubmedID 17702640 Title The role of th...e interferon regulatory factor (IRF) family in dendritic celldevelopment and function. Authors Gabriele L, O

  1. Electron microscopy and three-dimensional reconstruction of native thin filaments reveal species-specific differences in regulatory strand densities

    Energy Technology Data Exchange (ETDEWEB)

    Cammarato, Anthony, E-mail: acammara@burnham.org [Department of Physiology and Biophysics, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118 (United States); Craig, Roger [Department of Cell Biology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655 (United States); Lehman, William [Department of Physiology and Biophysics, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118 (United States)

    2010-01-01

    Throughout the animal kingdom striated muscle contraction is regulated by the thin filament troponin-tropomyosin complex. Homologous regulatory components are shared among vertebrate and arthropod muscles; however, unique protein extensions and/or components characterize the latter. The Troponin T (TnT) isoforms of Drosophila indirect flight and tarantula femur muscle for example contain distinct C-terminal extensions and are {approx}20% larger overall than their vertebrate counterpart. Using electron microscopy and three-dimensional helical reconstruction of native Drosophila, tarantula and frog muscle thin filaments we have identified species-specific differences in tropomyosin regulatory strand densities. The strands on the arthropod thin filaments were significantly larger in diameter than those from vertebrates, although not significantly different from each other. These findings reflect differences in the regulatory troponin-tropomyosin complex, which are likely due to the larger TnT molecules aligning and extending along much of the tropomyosin strands' length. Such an arrangement potentially alters the physical properties of the regulatory strands and may help establish contractile characteristics unique to certain arthropod muscles.

  2. Electron microscopy and three-dimensional reconstruction of native thin filaments reveal species-specific differences in regulatory strand densities

    International Nuclear Information System (INIS)

    Cammarato, Anthony; Craig, Roger; Lehman, William

    2010-01-01

    Throughout the animal kingdom striated muscle contraction is regulated by the thin filament troponin-tropomyosin complex. Homologous regulatory components are shared among vertebrate and arthropod muscles; however, unique protein extensions and/or components characterize the latter. The Troponin T (TnT) isoforms of Drosophila indirect flight and tarantula femur muscle for example contain distinct C-terminal extensions and are ∼20% larger overall than their vertebrate counterpart. Using electron microscopy and three-dimensional helical reconstruction of native Drosophila, tarantula and frog muscle thin filaments we have identified species-specific differences in tropomyosin regulatory strand densities. The strands on the arthropod thin filaments were significantly larger in diameter than those from vertebrates, although not significantly different from each other. These findings reflect differences in the regulatory troponin-tropomyosin complex, which are likely due to the larger TnT molecules aligning and extending along much of the tropomyosin strands' length. Such an arrangement potentially alters the physical properties of the regulatory strands and may help establish contractile characteristics unique to certain arthropod muscles.

  3. Electronic transport in single-helical protein molecules: Effects of multiple charge conduction pathways and helical symmetry

    Energy Technology Data Exchange (ETDEWEB)

    Kundu, Sourav, E-mail: sourav.kunduphy@gmail.com; Karmakar, S.N.

    2016-07-15

    We propose a tight-binding model to investigate electronic transport properties of single helical protein molecules incorporating both the helical symmetry and the possibility of multiple charge transfer pathways. Our study reveals that due to existence of both the multiple charge transfer pathways and helical symmetry, the transport properties are quite rigid under influence of environmental fluctuations which indicates that these biomolecules can serve as better alternatives in nanoelectronic devices than its other biological counterparts e.g., single-stranded DNA.

  4. Study on the regulatory mechanism of the lipid metabolism pathways during chicken male germ cell differentiation based on RNA-seq.

    Science.gov (United States)

    Zuo, Qisheng; Li, Dong; Zhang, Lei; Elsayed, Ahmed Kamel; Lian, Chao; Shi, Qingqing; Zhang, Zhentao; Zhu, Rui; Wang, Yinjie; Jin, Kai; Zhang, Yani; Li, Bichun

    2015-01-01

    Here, we explore the regulatory mechanism of lipid metabolic signaling pathways and related genes during differentiation of male germ cells in chickens, with the hope that better understanding of these pathways may improve in vitro induction. Fluorescence-activated cell sorting was used to obtain highly purified cultures of embryonic stem cells (ESCs), primitive germ cells (PGCs), and spermatogonial stem cells (SSCs). The total RNA was then extracted from each type of cell. High-throughput analysis methods (RNA-seq) were used to sequence the transcriptome of these cells. Gene Ontology (GO) analysis and the KEGG database were used to identify lipid metabolism pathways and related genes. Retinoic acid (RA), the end-product of the retinol metabolism pathway, induced in vitro differentiation of ESC into male germ cells. Quantitative real-time PCR (qRT-PCR) was used to detect changes in the expression of the genes involved in the retinol metabolic pathways. From the results of RNA-seq and the database analyses, we concluded that there are 328 genes in 27 lipid metabolic pathways continuously involved in lipid metabolism during the differentiation of ESC into SSC in vivo, including retinol metabolism. Alcohol dehydrogenase 5 (ADH5) and aldehyde dehydrogenase 1 family member A1 (ALDH1A1) are involved in RA synthesis in the cell. ADH5 was specifically expressed in PGC in our experiments and aldehyde dehydrogenase 1 family member A1 (ALDH1A1) persistently increased throughout development. CYP26b1, a member of the cytochrome P450 superfamily, is involved in the degradation of RA. Expression of CYP26b1, in contrast, decreased throughout development. Exogenous RA in the culture medium induced differentiation of ESC to SSC-like cells. The expression patterns of ADH5, ALDH1A1, and CYP26b1 were consistent with RNA-seq results. We conclude that the retinol metabolism pathway plays an important role in the process of chicken male germ cell differentiation.

  5. Diuron treatment reveals the different roles of two cyclic electron transfer pathways in photosystem II in Arabidopsis thaliana.

    Science.gov (United States)

    Jin, Yujian; Chen, Si; Fan, Xiaoji; Song, Hao; Li, Xingxing; Xu, Jiahui; Qian, Haifeng

    2017-04-01

    Three ecotypes of Arabidopsis thaliana, ecotype Columbia (Wild type, Wt) and two mutants (pgr5 and ndf4), were used to evaluate the effects of diuron on photosynthetic activity of A. thaliana. It was found that diuron adversely affected the fresh weight and chlorophyll content of the plants. Chlorophyll fluorescence studies determined that the pgr5 mutant was more sensitive to diuron than Wt and the ndf4 mutant. Gene expression analysis revealed different roles for the two cyclic electron transfer (CET) pathways, NAD(P)H dehydrogenase (NDH) and proton gradient regulation (PGR5) pathways, in the plant after diuron treatment. For example, a gene in the NDH pathway, lhca5, was activated in the low dose (LD) group in the pgr5 mutant, but was down-regulated in the moderate dose (MD) group, along with two other NDH-related genes (ppl2 and ndhH). In the PGR5 pathway, the pgr5 gene was functional under conditions of increased stress (MD group), and was up-regulated to a greater extent in the ndf4 mutant than that in the Wt and pgr5 mutant. Our results suggest that the PGR5 pathway in plants is more important than the NDH pathway during resistance to environmental stress. Deficiencies in the PGR5 pathway could not be counteracted by the NDH pathway, but deficiencies in the NDH pathway could be overcome by stimulating PGR5. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Reaction of H2 with O2 in Excited Electronic States: Reaction Pathways and Rate Constants.

    Science.gov (United States)

    Pelevkin, Alexey V; Loukhovitski, Boris I; Sharipov, Alexander S

    2017-12-21

    Comprehensive quantum chemical analysis with the use of the multireference state-averaged complete active space self-consistent field approach was carried out to study the reactions of H 2 with O 2 in a 1 Δ g , b 1 Σ g + , c 1 Σ u - , and A' 3 Δ u electronically excited states. The energetically favorable reaction pathways and possible intersystem crossings have been revealed. The energy barriers were refined employing the extended multiconfiguration quasi-degenerate second-order perturbation theory. It has been shown that the interaction of O 2 (a 1 Δ g ) and O 2 (A' 3 Δ u ) with H 2 occurs through the H-abstraction process with relatively low activation barriers that resulted in the formation of the HO 2 molecule in A″ and A' electronic states, respectively. Meanwhile, molecular oxygen in singlet sigma states (b 1 Σ g + and c 1 Σ u - ) was proved to be nonreactive with respect to the molecular hydrogen. Appropriate rate constants for revealed reaction and quenching channels have been estimated using variational transition-state theory including corrections for the tunneling effect, possible nonadiabatic transitions, and anharmonicity of vibrations for transition states and reactants. It was demonstrated that the calculated reaction rate constant for the H 2 + O 2 (a 1 Δ g ) process is in reasonable agreement with known experimental data. The Arrhenius approximations for these processes have been proposed for the temperature range T = 300-3000 K.

  7. Identification of co-expression gene networks, regulatory genes and pathways for obesity based on adipose tissue RNA Sequencing in a porcine model

    DEFF Research Database (Denmark)

    Kogelman, Lisette; Cirera Salicio, Susanna; Zhernakova, Daria V.

    2014-01-01

    interactions. Identification of co-expressed and regulatory genes in RNA extracted from relevant tissues representing lean and obese individuals provides an entry point for the identification of genes and pathways of importance to the development of obesity. The pig, an omnivorous animal, is an excellent model...... (modules). Additionally, regulator genes were detected using Lemon-Tree algorithms. Results WGCNA revealed five modules which were strongly correlated with at least one obesity-related phenotype (correlations ranging from -0.54 to 0.72, P ... the association between obesity and other diseases, like osteoporosis (osteoclast differentiation, P = 1.4E-7), and immune-related complications (e.g. Natural killer cell mediated cytotoxity, P = 3.8E-5; B cell receptor signaling pathway, P = 7.2E-5). Lemon-Tree identified three potential regulator genes, using...

  8. How adverse outcome pathways can aid the development and use of computational prediction models for regulatory toxicology

    Science.gov (United States)

    Efforts are underway to transform regulatory toxicology and chemical safety assessment from a largely empirical science based on direct observation of apical toxicity outcomes in whole organism toxicity tests to a predictive one in which outcomes and risk are inferred from accumu...

  9. The TCA Pathway is an Important Player in the Regulatory Network Governing Vibrio alginolyticus Adhesion Under Adversity.

    Science.gov (United States)

    Huang, Lixing; Huang, Li; Yan, Qingpi; Qin, Yingxue; Ma, Ying; Lin, Mao; Xu, Xiaojin; Zheng, Jiang

    2016-01-01

    Adhesion is a critical step in the initial stage of Vibrio alginolyticus infection; therefore, it is important to understand the underlying mechanisms governing the adhesion of V. alginolyticus and determine if environmental factors have any effect. A greater understanding of this process may assist in developing preventive measures for reducing infection. In our previous research, we presented the first RNA-seq data from V. alginolyticus cultured under stress conditions that resulted in reduced adhesion. Based on the RNA-seq data, we found that the Tricarboxylic acid cycle (TCA pathway) might be closely related to adhesion. Environmental interactions with the TCA pathway might alter adhesion. To validate this, bioinformatics analysis, quantitative Real-Time PCR (qPCR), RNAi, and in vitro adhesion assays were performed, while V. alginolyticus was treated with various stresses including temperature, pH, salinity, and starvation. The expression of genes involved in the TCA pathway was confirmed by qPCR, which reinforced the reliability of the sequencing data. Silencing of these genes was capable of reducing the adhesion ability of V. alginolyticus. Adhesion of V. alginolyticus is influenced substantially by environmental factors and the TCA pathway is sensitive to some environmental stresses, especially changes in pH and starvation. Our results indicated that (1) the TCA pathway plays a key role in V. alginolyticus adhesion: (2) the TCA pathway is sensitive to environmental stresses.

  10. The TCA pathway is an important player in the regulatory network governing Vibrio alginolyticus adhesion under adversity

    Directory of Open Access Journals (Sweden)

    Lixing eHuang

    2016-02-01

    Full Text Available Adhesion is a critical step in the initial stage of Vibrio alginolyticus infection; therefore, it is important to understand the underlying mechanisms governing the adhesion of V. alginolyticus and determine if environmental factors have any effect. A greater understanding of this process may assist in developing preventive measures for reducing infection. In our previous research, we presented the first RNA-seq data from V. alginolyticus cultured under stress conditions that resulted in reduced adhesion. Based on the RNA-seq data, we found that the Tricarboxylic acid cycle (TCA pathway might be closely related to adhesion. Environmental interactions with the TCA pathway might alter adhesion. To validate this, bioinformatics analysis, qPCR, RNAi and in vitro adhesion assays were performed, while V. alginolyticus was treated with various stresses including temperature, pH, salinity and starvation. The expression of genes involved in the TCA pathway was confirmed by qPCR, which reinforced the reliability of the sequencing data. Silencing of these genes was capable of reducing the adhesion ability of V. alginolyticus. Adhesion of V. alginolyticus is influenced substantially by environmental factors and the TCA pathway is sensitive to some environmental stresses, especially changes in pH and starvation. Our results indicated that 1 the TCA pathway plays a key role in V. alginolyticus adhesion: 2 the TCA pathway is sensitive to environmental stresses.

  11. Reconstruction of the gene regulatory network involved in the sonic hedgehog pathway with a potential role in early development of the mouse brain.

    Directory of Open Access Journals (Sweden)

    Jinhua Liu

    2014-10-01

    Full Text Available The Sonic hedgehog (Shh signaling pathway is crucial for pattern formation in early central nervous system development. By systematically analyzing high-throughput in situ hybridization data of E11.5 mouse brain, we found that Shh and its receptor Ptch1 define two adjacent mutually exclusive gene expression domains: Shh+Ptch1- and Shh-Ptch1+. These two domains are associated respectively with Foxa2 and Gata3, two transcription factors that play key roles in specifying them. Gata3 ChIP-seq experiments and RNA-seq assays on Gata3-knockdown cells revealed that Gata3 up-regulates the genes that are enriched in the Shh-Ptch1+ domain. Important Gata3 targets include Slit2 and Slit3, which are involved in the process of axon guidance, as well as Slc18a1, Th and Qdpr, which are associated with neurotransmitter synthesis and release. By contrast, Foxa2 both up-regulates the genes expressed in the Shh+Ptch1- domain and down-regulates the genes characteristic of the Shh-Ptch1+ domain. From these and other data, we were able to reconstruct a gene regulatory network governing both domains. Our work provides the first genome-wide characterization of the gene regulatory network involved in the Shh pathway that underlies pattern formation in the early mouse brain.

  12. Coherence, energy and charge transfers in de-excitation pathways of electronic excited state of biomolecules in photosynthesis

    DEFF Research Database (Denmark)

    Bohr, Henrik; Malik, F. Bary

    2013-01-01

    The observed multiple de-excitation pathways of photo-absorbed electronic excited state in the peridinin–chlorophyll complex, involving both energy and charge transfers among its constituents, are analyzed using the bio-Auger (B-A) theory. It is also shown that the usually used F¨orster–Dexter...

  13. Interplay of alternative conjugated pathways and steric interactions on the electronic and optical properties of donor-acceptor conjugated polymers

    KAUST Repository

    Lima, Igo T.; Risko, Chad; Aziz, Saadullah Gary; Da Silva Filho, Demé trio A Da Silva; Bredas, Jean-Luc

    2014-01-01

    Donor-acceptor π-conjugated copolymers are of interest for a wide range of electronic applications, including field-effect transistors and solar cells. Here, we present a density functional theory (DFT) study of the impact of varying the conjugation pathway on the geometric, electronic, and optical properties of donor-acceptor systems. We consider both linear ("in series"), traditional conjugation among the donor-acceptor moieties versus structures where the acceptor units are appended orthogonally to the linear, donor-only conjugated backbone. Long-range-corrected hybrid functionals are used in the investigation with the values of the tuned long-range separation parameters providing an estimate of the extent of conjugation as a function of the oligomer architecture. Considerable differences in the electronic and optical properties are determined as a function of the nature of the conjugation pathway, features that should be taken into account in the design of donor-acceptor copolymers.

  14. Regulatory effect of evodiamine on the malignant biological behaviors and Wnt/β-catenin signaling pathway of colorectal cancer cell lines HT29

    Directory of Open Access Journals (Sweden)

    Yuan-Hui Wang

    2016-04-01

    Full Text Available Objective: To study the regulatory effect of evodiamine on the malignant biological behaviors and Wnt/β-catenin signaling pathway of colorectal cancer cell lines HT29. Methods: Colorectal cancer cell lines HT29 were cultured and divided into blank control group and evodiamine group, and after different treatment, cell viability, proportion of different cell cycle as well as the contents of VEGFA, VEGFB, VEGFC, MMP3, MMP14, Wnt and β-catenin were detected. Results: (1 Cell viability: MTT value of evodiamine group was significantly lower than that of blank control group; (2 Cell cycle: proportion of both S phase and G2/M phase of evodiamine group were lower than those of blank control group, and proportion of G0/ G1 phase was higher than that of blank control group; (3 VEGF and MMP contents: VEGFA, VEGFB, VEGFC, MMP3 and MMP14 contents of evodiamine group were lower than those of blank control group; (4 Wnt/β-catenin signaling pathway: Wnt and β-catenin contents of evodiamine group were lower than those of blank control group. Conclusion: Evodiamine can inhibit the proliferation of colorectal cancer cell lines HT29 and down-regulate the expression of VEGF and MMP, and the effect may be achieved by inhibiting the activation of Wnt/β-catenin signaling pathway.

  15. Regulation of energy partitioning and alternative electron transport pathways during cold acclimation of lodgepole pine is oxygen dependent.

    Science.gov (United States)

    Savitch, Leonid V; Ivanov, Alexander G; Krol, Marianna; Sprott, David P; Oquist, Gunnar; Huner, Norman P A

    2010-09-01

    Second year needles of Lodgepole pine (Pinus contorta L.) were exposed for 6 weeks to either simulated control summer ['summer'; 25 °C/250 photon flux denisty (PFD)], autumn ('autumn'; 15°C/250 PFD) or winter conditions ('winter'; 5 °C/250 PFD). We report that the proportion of linear electron transport utilized in carbon assimilation (ETR(CO2)) was 40% lower in both 'autumn' and 'winter' pine when compared with the 'summer' pine. In contrast, the proportion of excess photosynthetic linear electron transport (ETR(excess)) not used for carbon assimilation within the total ETR(Jf) increased by 30% in both 'autumn' and 'winter' pine. In 'autumn' pine acclimated to 15°C, the increased amounts of 'excess' electrons were directed equally to 21  kPa O2-dependent and 2  kPa O2-dependent alternative electron transport pathways and the fractions of excitation light energy utilized by PSII photochemistry (Φ(PSII)), thermally dissipated through Φ(NPQ) and dissipated by additional quenching mechanism(s) (Φ(f,D)) were similar to those in 'summer' pine. In contrast, in 'winter' needles acclimated to 5 °C, 60% of photosynthetically generated 'excess' electrons were utilized through the 2  kPa O2-dependent electron sink and only 15% by the photorespiratory (21  kPa O2) electron pathway. Needles exposed to 'winter' conditions led to a 3-fold lower Φ(PSII), only a marginal increase in Φ(NPQ) and a 2-fold higher Φ(f,D), which was O2 dependent compared with the 'summer' and 'autumn' pine. Our results demonstrate that the employment of a variety of alternative pathways for utilization of photosynthetically generated electrons by Lodgepole pine depends on the acclimation temperature. Furthermore, dissipation of excess light energy through constitutive non-photochemical quenching mechanisms is O2 dependent.

  16. Basic regulatory principles of Escherichia coli's electron transport chain for varying oxygen conditions

    NARCIS (Netherlands)

    Henkel, S.G.; Ter Beek, A.S.; Steinsiek, S.; Stagge, S.; Bettenbrock, K.; Teixeira De Mattos, M.J.; Sauter, T.; Sawodny, O.; Ederer, M.

    2014-01-01

    For adaptation between anaerobic, micro-aerobic and aerobic conditions Escherichia coli's metabolism and in particular its electron transport chain (ETC) is highly regulated. Although it is known that the global transcriptional regulators FNR and ArcA are involved in oxygen response it is unclear

  17. 78 FR 310 - Draft Revision of Guidance for Industry on Providing Regulatory Submissions in Electronic Format...

    Science.gov (United States)

    2013-01-03

    ... files and advertising and promotional labeling submissions. However, FDA accepts and strongly encourages the submission of master files and advertising and promotional labeling materials electronically, as... Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (the PRA) (44 U.S.C. 3501...

  18. Bottom-up and middle-out approaches to electronic patient information systems: a focus on healthcare pathways

    Directory of Open Access Journals (Sweden)

    Ken Eason

    2013-12-01

    Full Text Available Background A study is reported that examines the use of electronic health record (EHR systems in two UK local health communities.Objective These systems were developed locally and the aim of the study was to explore how well they were supporting the coordination of care along healthcare pathways that cross the organisational boundaries between the agencies delivering health care.Results The paper presents the findings for two healthcare pathways; the Stroke Pathway and a pathway for the care of the frail elderly in their own homes. All the pathways examined involved multiple agencies and many locally tailored EHR systems are in use to aid the coordination of care. However, the ability to share electronic patient information along the pathways was patchy. The development of systems that enabled effective sharing of information was characterised by sociotechnical system development, i.e. associating the technical development with process changes and organisational changes, with local development teams that drew on all the relevant agencies in the local health community and on evolutionary development, as experience grew of the benefits that EHR systems could deliver.Conclusions The study concludes that whilst there may be a role for a national IT strategy, for example, to set standards for systems procurement that facilitate data interchange, most systems development work needs to be done at a ‘middle-out’ level in the local health community, where joint planning between healthcare agencies can occur, and at the local healthcare pathway level where systems can be matched to specific needs for information sharing.

  19. A study of regulatory policies and relevant issues concerning electronic cigarette use in Taiwan.

    Science.gov (United States)

    Jiang, Tzuu Hwa; Cheng, Li Min; Hawkins, Matthew A

    2018-01-01

    Recent technological innovations have increased the amount of tobacco products available to smokers. In particular, electronic cigarettes, sometimes call e-cigarettes, have received substantial attention as their sales have rapidly increased. Electronic cigarettes were invented in China and now have become prevalent worldwide. Electronic cigarettes can be considered fashionable and come in numerous flavors; accordingly, many young adults and students have begun to use e-cigarettes. However, like traditional tobacco products, e-cigarettes have negative influences on human health. After e-cigarettes were introduced into Taiwan, they have not been effectively managed and regulated because of insufficient supporting measures. Related legislation in developed countries can serve as a reference for Taiwan. For this study, the development of e-cigarettes is described and a theoretical analysis was performed from the administration and legal perspectives. In addition to clarifying related problems and offering measures to prevent students from using e-cigarettes, we propose suggestions to help governments improve their strategies to protect students' health. Copyright © 2017 John Wiley & Sons, Ltd.

  20. Regulatory Mechanisms of the Ihh/PTHrP Signaling Pathway in Fibrochondrocytes in Entheses of Pig Achilles Tendon

    OpenAIRE

    Han, Xuesong; Zhuang, Yanfeng; Zhang, Zhihong; Guo, Lin; Wang, Wanming

    2016-01-01

    This study is aimed at exploring the effect of stress stimulation on the proliferation and differentiation of fibrochondrocytes in entheses mediated via the Indian hedgehog (Ihh)/parathyroid hormone-related protein (PTHrP) signaling pathway. Differential stress stimulation on fibrochondrocytes in entheses was imposed. Gene expression and protein levels of signaling molecules including collagen type I (Col I), Col II, Col X, Ihh, and PTHrP in the cytoplasm of fibrochondrocytes were detected. I...

  1. Transcriptome Analysis of Three Sheep Intestinal Regions reveals Key Pathways and Hub Regulatory Genes of Large Intestinal Lipid Metabolism.

    Science.gov (United States)

    Chao, Tianle; Wang, Guizhi; Ji, Zhibin; Liu, Zhaohua; Hou, Lei; Wang, Jin; Wang, Jianmin

    2017-07-13

    The large intestine, also known as the hindgut, is an important part of the animal digestive system. Recent studies on digestive system development in ruminants have focused on the rumen and the small intestine, but the molecular mechanisms underlying sheep large intestine metabolism remain poorly understood. To identify genes related to intestinal metabolism and to reveal molecular regulation mechanisms, we sequenced and compared the transcriptomes of mucosal epithelial tissues among the cecum, proximal colon and duodenum. A total of 4,221 transcripts from 3,254 genes were identified as differentially expressed transcripts. Between the large intestine and duodenum, differentially expressed transcripts were found to be significantly enriched in 6 metabolism-related pathways, among which PPAR signaling was identified as a key pathway. Three genes, CPT1A, LPL and PCK1, were identified as higher expression hub genes in the large intestine. Between the cecum and colon, differentially expressed transcripts were significantly enriched in 5 lipid metabolism related pathways, and CEPT1 and MBOAT1 were identified as hub genes. This study provides important information regarding the molecular mechanisms of intestinal metabolism in sheep and may provide a basis for further study.

  2. A genome-wide analysis of the RNA-guided silencing pathway in coffee reveals insights into its regulatory mechanisms.

    Directory of Open Access Journals (Sweden)

    Christiane Noronha Fernandes-Brum

    Full Text Available microRNAs (miRNAs are derived from self-complementary hairpin structures, while small-interfering RNAs (siRNAs are derived from double-stranded RNA (dsRNA or hairpin precursors. The core mechanism of sRNA production involves DICER-like (DCL in processing the smallRNAs (sRNAs and ARGONAUTE (AGO as effectors of silencing, and siRNA biogenesis also involves action of RNA-Dependent RNA Polymerase (RDR, Pol IV and Pol V in biogenesis. Several other proteins interact with the core proteins to guide sRNA biogenesis, action, and turnover. We aimed to unravel the components and functions of the RNA-guided silencing pathway in a non-model plant species of worldwide economic relevance. The sRNA-guided silencing complex members have been identified in the Coffea canephora genome, and they have been characterized at the structural, functional, and evolutionary levels by computational analyses. Eleven AGO proteins, nine DCL proteins (which include a DCL1-like protein that was not previously annotated, and eight RDR proteins were identified. Another 48 proteins implicated in smallRNA (sRNA pathways were also identified. Furthermore, we identified 235 miRNA precursors and 317 mature miRNAs from 113 MIR families, and we characterized ccp-MIR156, ccp-MIR172, and ccp-MIR390. Target prediction and gene ontology analyses of 2239 putative targets showed that significant pathways in coffee are targeted by miRNAs. We provide evidence of the expansion of the loci related to sRNA pathways, insights into the activities of these proteins by domain and catalytic site analyses, and gene expression analysis. The number of MIR loci and their targeted pathways highlight the importance of miRNAs in coffee. We identified several roles of sRNAs in C. canephora, which offers substantial insight into better understanding the transcriptional and post-transcriptional regulation of this major crop.

  3. Gene Expression Dynamics in Major Endocrine Regulatory Pathways along the Transition from Solitary to Social Life in a Bumblebee, Bombus terrestris

    Directory of Open Access Journals (Sweden)

    Pavel Jedlička

    2016-11-01

    Full Text Available Understanding the social evolution leading to insect eusociality requires, among other, a detailed insight into endocrine regulatory mechanisms that have been co-opted from solitary ancestors to play new roles in the complex life histories of eusocial species. Bumblebees represent well-suited models of a relatively primitive social organization standing on the mid-way to highly advanced eusociality and their queens undergo both, a solitary and a social phase, separated by winter diapause.In the present paper, we characterize the gene expression levels of major endocrine regulatory pathways across tissues, sexes, and life-stages of the buff-tailed bumblebee, Bombus terrestris, with special emphasis on critical stages of the queen’s transition from solitary to social life. We focused on fundamental genes of three pathways: (1 Forkhead box protein O and insulin/insulin-like signaling, (2 Juvenile hormone signaling, and (3 Adipokinetic hormone signaling. Virgin queens were distinguished by higher expression of forkhead box protein O and downregulated insulin-like peptides and juvenile hormone (JH signaling, indicated by low expression of methyl farnesoate epoxidase (MFE and transcription factor Krüppel homolog 1 (Kr-h1. Diapausing queens showed the expected downregulation of JH signaling in terms of low MFE and vitellogenin (Vg expressions, but an unexpectedly high expression of Kr-h1. By contrast, reproducing queens revealed an upregulation of MFE and Vg together with insulin signaling. Surprisingly, the insulin growth factor 1 (IGF-1 turned out to be a queen-specific hormone. Workers exhibited an expression pattern of MFE and Vg similar to that of reproducing queens. Males were characterized by high Kr-h1 expression and low Vg level. The tissue comparison unveiled an unexpected resemblance between the fat body and hypopharyngeal glands across all investigated genes, sexes, and life stages.

  4. Nicotine content of electronic cigarettes, its release in vapour and its consistency across batches: regulatory implications.

    Science.gov (United States)

    Goniewicz, Maciej L; Hajek, Peter; McRobbie, Hayden

    2014-03-01

    Electronic cigarettes (EC) may have a potential for public health benefit as a safer alternative to smoking, but questions have been raised about whether EC should be licensed as a medicine, with accurate labelling of nicotine content. This study determined the nicotine content of the cartridges of the most popular EC brands in the United Kingdom and the nicotine levels they deliver in the vapour, and estimated the safety and consistency of nicotine delivery across batches of the same product as a proxy for quality control for individual brands and within the industry. We studied five UK brands (six products) with high internet popularity. Two samples of each brand were purchased 4 weeks apart, and analysed for nicotine content in the cartridges and nicotine delivery in vapour. The nicotine content of cartridges within the same batch varied by up to 12% relative standard deviation (RSD) and the mean difference between different batches of the same brand ranged from 1% [95% confidence interval (CI) = -5 to 7%] to 20% (95% CI=14-25%) for five brands and 31% (95% CI=21-39%) for the sixth. The puffing schedule used in this study vaporized 10-81% of the nicotine present in the cartridges. The nicotine delivery from 300 puffs ranged from ∼2 mg to ∼15 mg and was not related significantly to the variation of nicotine content in e-liquid (r=0.06, P=0.92). None of the tested products allowed access to e-liquid or produced vapour nicotine concentrations as high as conventional cigarettes. There is very little risk of nicotine toxicity from major electronic cigarette (EC) brands in the United Kingdom. Variation in nicotine concentration in the vapour from a given brand is low. Nicotine concentration in e-liquid is not well related to nicotine in vapour. Other EC brands may be of lower quality and consumer protection regulation needs to be implemented, but in terms of accuracy of labelling of nicotine content and risks of nicotine overdose, regulation over and above

  5. Targeting allergen to FcgammaRI reveals a novel T(H)2 regulatory pathway linked to thymic stromal lymphopoietin receptor.

    Science.gov (United States)

    Hulse, Kathryn E; Reefer, Amanda J; Engelhard, Victor H; Patrie, James T; Ziegler, Steven F; Chapman, Martin D; Woodfolk, Judith A

    2010-01-01

    The molecule H22-Fel d 1, which targets cat allergen to FcgammaRI on dendritic cells (DCs), has the potential to treat cat allergy because of its T-cell modulatory properties. We sought to investigate whether the T-cell response induced by H22-Fel d 1 is altered in the presence of the T(H)2-promoting cytokine thymic stromal lymphopoietin (TSLP). Studies were performed in subjects with cat allergy with and without atopic dermatitis. Monocyte-derived DCs were primed with H22-Fel d 1 in the presence or absence of TSLP, and the resulting T-cell cytokine repertoire was analyzed by flow cytometry. The capacity for H22-Fel d 1 to modulate TSLP receptor expression on DCs was examined by flow cytometry in the presence or absence of inhibitors of Fc receptor signaling molecules. Surprisingly, TSLP alone was a weak inducer of T(H)2 responses irrespective of atopic status; however, DCs coprimed with TSLP and H22-Fel d 1 selectively and synergistically amplified T(H)2 responses in highly atopic subjects. This effect was OX40 ligand independent, pointing to an unconventional TSLP-mediated pathway. Expression of TSLP receptor was upregulated on atopic DCs primed with H22-Fel d 1 through a pathway regulated by FcgammaRI-associated signaling components, including src-related tyrosine kinases and Syk, as well as the downstream molecule phosphoinositide 3-kinase. Inhibition of TSLP receptor upregulation triggered by H22-Fel d 1 blocked TSLP-mediated T(H)2 responses. Discovery of a novel T(H)2 regulatory pathway linking FcgammaRI signaling to TSLP receptor upregulation and consequent TSLP-mediated effects questions the validity of receptor-targeted allergen vaccines. Copyright 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  6. Presence of Tube isoforms in Litopenaeus vannamei suggests various regulatory patterns of signal transduction in invertebrate NF-κB pathway.

    Science.gov (United States)

    Li, Chaozheng; Chen, Yixiao; Weng, Shaoping; Li, Sedong; Zuo, Hongliang; Yu, Xiaoqiang; Li, Haoyang; He, Jianguo; Xu, Xiaopeng

    2014-02-01

    The toll-like receptor (TLR)/NF-κB signaling pathways play critical roles in the innate immune system. The intracellular signal transduction of most TLR pathways in invertebrate cells is triggered by formation of a heterotrimeric complex composed of MyD88, Tube and Pelle. In this study, we identified a Litopenaeus vannamei Pelle (LvPelle) and an isoform of L. vannamei Tube (LvTube) designated as LvTube-1. The interactions among LvPelle, LvTube/LvTube-1 and LvMyD88/LvMyD88-1 were elucidated and their functions during pathogen infections were investigated. Knockdowns of LvPelle and LvTube/LvTube-1 using RNAi strategy led to higher mortalities of shrimps during Vibrio parahemolyticus infection, and could reduce the genome copy number of white spot syndrome virus (WSSV) in the infected muscle tissue but did not affect the mortality caused by WSSV infection. The effects of LvPelle and LvTube/LvTube-1 on promoters containing NF-κB binding motifs were analyzed by dual-luciferase reporter assays and the results demonstrated that LvTube-1 could activate the NF-κB activity to significantly higher level than LvTube did. Moreover, tissue distributions of LvTube and LvTube-1 mRNAs and their expression profiles during pathogen and immune stimulant challenges were different, indicating that they could play different roles in immune responses. This is the first report of Tube isoforms in invertebrates. Together with our previous study on LvMyD88 isoforms, our results suggest that various isoforms of adaptor components may be involved in various regulatory patterns of signal transduction in invertebrate TLR/NF-κB pathway and this could be a strategy adopted by invertebrates to modulate immune responses. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Skeletal muscle hypertrophy and regeneration: interplay between the myogenic regulatory factors (MRFs) and insulin-like growth factors (IGFs) pathways.

    Science.gov (United States)

    Zanou, Nadège; Gailly, Philippe

    2013-11-01

    Adult skeletal muscle can regenerate in response to muscle damage. This ability is conferred by the presence of myogenic stem cells called satellite cells. In response to stimuli such as injury or exercise, these cells become activated and express myogenic regulatory factors (MRFs), i.e., transcription factors of the myogenic lineage including Myf5, MyoD, myogenin, and Mrf4 to proliferate and differentiate into myofibers. The MRF family of proteins controls the transcription of important muscle-specific proteins such as myosin heavy chain and muscle creatine kinase. Different growth factors are secreted during muscle repair among which insulin-like growth factors (IGFs) are the only ones that promote both muscle cell proliferation and differentiation and that play a key role in muscle regeneration and hypertrophy. Different isoforms of IGFs are expressed during muscle repair: IGF-IEa, IGF-IEb, or IGF-IEc (also known as mechano growth factor, MGF) and IGF-II. MGF is expressed first and is observed in satellite cells and in proliferating myoblasts whereas IGF-Ia and IGF-II expression occurs at the state of muscle fiber formation. Interestingly, several studies report the induction of MRFs in response to IGFs stimulation. Inversely, IGFs expression may also be regulated by MRFs. Various mechanisms are proposed to support these interactions. In this review, we describe the general process of muscle hypertrophy and regeneration and decipher the interactions between the two groups of factors involved in the process.

  8. Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants.

    Science.gov (United States)

    Jin, Ying; Andersen, Genevieve; Yorgov, Daniel; Ferrara, Tracey M; Ben, Songtao; Brownson, Kelly M; Holland, Paulene J; Birlea, Stanca A; Siebert, Janet; Hartmann, Anke; Lienert, Anne; van Geel, Nanja; Lambert, Jo; Luiten, Rosalie M; Wolkerstorfer, Albert; Wietze van der Veen, J P; Bennett, Dorothy C; Taïeb, Alain; Ezzedine, Khaled; Kemp, E Helen; Gawkrodger, David J; Weetman, Anthony P; Kõks, Sulev; Prans, Ele; Kingo, Külli; Karelson, Maire; Wallace, Margaret R; McCormack, Wayne T; Overbeck, Andreas; Moretti, Silvia; Colucci, Roberta; Picardo, Mauro; Silverberg, Nanette B; Olsson, Mats; Valle, Yan; Korobko, Igor; Böhm, Markus; Lim, Henry W; Hamzavi, Iltefat; Zhou, Li; Mi, Qing-Sheng; Fain, Pamela R; Santorico, Stephanie A; Spritz, Richard A

    2016-11-01

    Vitiligo is an autoimmune disease in which depigmented skin results from the destruction of melanocytes, with epidemiological association with other autoimmune diseases. In previous linkage and genome-wide association studies (GWAS1 and GWAS2), we identified 27 vitiligo susceptibility loci in patients of European ancestry. We carried out a third GWAS (GWAS3) in European-ancestry subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication. The combined analyses, with 4,680 cases and 39,586 controls, identified 23 new significantly associated loci and 7 suggestive loci. Most encode immune and apoptotic regulators, with some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some of which corresponds to expression quantitative trait loci (eQTLs) at these loci. Together, the identified genes provide a framework for the genetic architecture and pathobiology of vitiligo, highlight relationships with other autoimmune diseases and melanoma, and offer potential targets for treatment.

  9. Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants

    Science.gov (United States)

    Jin, Ying; Andersen, Genevieve; Yorgov, Daniel; Ferrara, Tracey M; Ben, Songtao; Brownson, Kelly M; Holland, Paulene J; Birlea, Stanca A; Siebert, Janet; Hartmann, Anke; Lienert, Anne; van Geel, Nanja; Lambert, Jo; Luiten, Rosalie M; Wolkerstorfer, Albert; van der Veen, JP Wietze; Bennett, Dorothy C; Taïeb, Alain; Ezzedine, Khaled; Kemp, E Helen; Gawkrodger, David J; Weetman, Anthony P; Kõks, Sulev; Prans, Ele; Kingo, Külli; Karelson, Maire; Wallace, Margaret R; McCormack, Wayne T; Overbeck, Andreas; Moretti, Silvia; Colucci, Roberta; Picardo, Mauro; Silverberg, Nanette B; Olsson, Mats; Valle, Yan; Korobko, Igor; Böhm, Markus; Lim, Henry W.; Hamzavi, Iltefat; Zhou, Li; Mi, Qing-Sheng; Fain, Pamela R.; Santorico, Stephanie A; Spritz, Richard A

    2016-01-01

    Vitiligo is an autoimmune disease in which depigmented skin results from destruction of melanocytes1, with epidemiologic association with other autoimmune diseases2. In previous linkage and genome-wide association studies (GWAS1, GWAS2), we identified 27 vitiligo susceptibility loci in patients of European (EUR) ancestry. We carried out a third GWAS (GWAS3) in EUR subjects, with augmented GWAS1 and GWAS2 controls, genome-wide imputation, and meta-analysis of all three GWAS, followed by an independent replication. The combined analyses, with 4,680 cases and 39,586 controls, identified 23 new loci and 7 suggestive loci, most encoding immune and apoptotic regulators, some also associated with other autoimmune diseases, as well as several melanocyte regulators. Bioinformatic analyses indicate a predominance of causal regulatory variation, some corresponding to eQTL at these loci. Together, the identified genes provide a framework for vitiligo genetic architecture and pathobiology, highlight relationships to other autoimmune diseases and melanoma, and offer potential targets for treatment. PMID:27723757

  10. TCDD Induces the Hypoxia-Inducible Factor (HIF-1α Regulatory Pathway in Human Trophoblastic JAR Cells

    Directory of Open Access Journals (Sweden)

    Tien-Ling Liao

    2014-09-01

    Full Text Available The exposure to dioxin can compromise pregnancy outcomes and increase the risk of preterm births. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD has been demonstrated to induce placental hypoxia at the end of pregnancy in a rat model, and hypoxia has been suggested to be the cause of abnormal trophoblast differentiation and placental insufficiency syndromes. In this study, we demonstrate that the non-hypoxic stimulation of human trophoblastic cells by TCDD strongly increased hypoxia inducible factor-1 alpha (HIF-1α stabilization. TCDD exposure induced the generation of reactive oxygen species (ROS and nitric oxide. TCDD-induced HIF-1α stabilization and Akt phosphorylation was inhibited by pretreatment with wortmannin (a phosphatidylinositol 3-kinase (PI3K inhibitor or N-acetylcysteine (a ROS scavenger. The augmented HIF-1α stabilization by TCDD occurred via the ROS-dependent activation of the PI3K/Akt pathway. Additionally, a significant increase in invasion and metallomatrix protease-9 activity was found in TCDD-treated cells. The gene expression of vascular endothelial growth factor and placental growth factor was induced upon TCDD stimulation, whereas the protein levels of peroxisome proliferator-activated receptor γ (PPARγ, PPARγ coactivator-1α, mitochondrial transcription factor, and uncoupling protein 2 were decreased. Our results indicate that an activated HIF-1α pathway, elicited oxidative stress, and induced metabolic stress contribute to TCDD-induced trophoblastic toxicity. These findings may provide molecular insight into the TCDD-induced impairment of trophoblast function and placental development.

  11. Electronic patient information systems and care pathways: the organisational challenges of implementation and integration.

    Science.gov (United States)

    Dent, Mike; Tutt, Dylan

    2014-09-01

    Our interest here is with the 'marriage' of e-patient information systems with care pathways in order to deliver integrated care. We report on the development and implementation of four such pathways within two National Health Service primary care trusts in England: (a) frail elderly care, (b) stroke care, (c) diabetic retinopathy screening and (d) intermediate care. The pathways were selected because each represents a different type of information and data 'couplings', in terms of task interdependency with some pathways/systems reflecting more complex coordinating patterns than others. Our aim here is identify and explain how health professionals and information specialists in two organisational National Health Service primary care trusts organisationally construct and use such systems and, in particular, the implications this has for issues of professional and managerial control and autonomy. The article is informed by an institutionalist analysis. © The Author(s) 2013.

  12. Assessing electronic cigarette effects and regulatory impact: Challenges with user self-reported device power.

    Science.gov (United States)

    Rudy, Alyssa K; Leventhal, Adam M; Goldenson, Nicholas I; Eissenberg, Thomas

    2017-10-01

    Electronic cigarettes (ECIGs) aerosolize liquids for user inhalation that usually contain nicotine. ECIG nicotine emission is determined, in part, by user behavior, liquid nicotine concentration, and electrical power. Whether users are able to report accurately nicotine concentration and device electrical power has not been evaluated. This study's purpose was to examine if ECIG users could provide data relevant to understanding ECIG nicotine emission, particularly liquid nicotine concentration (mg/ml) as well as battery voltage (V) and heater resistance (ohms, Ω) - needed to calculate power (watts, W). Adult ECIG users (N=165) were recruited from Los Angeles, CA for research studies examining the effects of ECIG use. We asked all participants who visited the laboratory to report liquid nicotine concentration, V, and Ω. Liquid nicotine concentration was reported by 89.7% (mean=9.5mg/ml, SD=7.3), and responses were consistent with the distribution of liquids available in commonly marketed products. The majority could not report voltage (51.5%) or resistance (63.6%). Of the 40 participants (24.8%) who reported voltage and resistance, there was a substantial power range (2.2-32,670W) the upper limit of which exceeds that of the highest ECIG reported by any user to our knowledge (i.e., 2512W). If 2512W is taken as the upper limit, only 30 (18.2%) reported valid results (mean 237.3W, SD=370.6; range=2.2-1705.3W). Laboratory, survey, and other researchers interested in understanding ECIG effects to inform users and policymakers may need to use methods other than user self-report to obtain information regarding device power. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Electron Transfer Pathways Facilitating U(VI) Reduction by Fe(II) on Al- vs Fe-Oxides

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, S. D. [Pacific Northwest National Laboratory, Physical Sciences Division, P.O. Box; Becker, U. [The University of Michigan, Department of Earth; Rosso, K. M. [Pacific Northwest National Laboratory, Physical Sciences Division, P.O. Box

    2017-09-06

    This study continues mechanistic development of heterogeneous electron transfer (ET) pathways at mineral surfaces in aquatic environments that enable the reduction U(VI) by surface-associated Fe(II). Using computational molecular simulation within the framework of Marcus Theory, our findings highlight the importance of the configurations and interaction of the electron donor and acceptor species with the substrate, with respect to influencing its electronic structure and thereby the ability of semiconducting minerals to facilitate ET. U(VI) reduction by surface-associated Fe(II) (adsorbed or structurally incorporated into the lattice) on an insulating, corundum (001) surface (α-Al2O3) occurs when proximal inner-sphere (IS) surface complexes are formed, such that ET occurs through a combination of direct exchange (i.e., Fe d- and U f-orbitals overlap through space) and superexchange via intervening surface oxygen atoms. U(VI) reduction by coadsorbed Fe(II) on the isostructural semiconducting hematite (α-Fe2O3) basal surface requires either their direct electronic interaction (e.g., IS complexation) or mediation of this interaction indirectly through the surface via an intrasurface pathway. Conceptually possible longer-range ET by charge-hopping through surface Fe atoms was investigated to determine whether this indirect pathway is competitive with direct ET. The calculations show that energy barriers are large for this conduction-based pathway; interfacial ET into the hematite surface is endothermic (+80.1 kJ/mol) and comprises the rate-limiting step (10–6 s–1). The presence of the IS adsorbates appears to weaken the electronic coupling between underlying Fe ions within the surface, resulting in slower intra-surface ET (10–5 s–1) than expected in the bulk basal plane. Our findings lay out first insights into donor-acceptor communication via a charge-hopping pathway through the surface for heterogeneous reduction of U(VI) by Fe(II) and help provide a basis

  14. The Assessment of Bone Regulatory Pathways, Bone Turnover, and Bone Mineral Density in Vegetarian and Omnivorous Children.

    Science.gov (United States)

    Ambroszkiewicz, Jadwiga; Chełchowska, Magdalena; Szamotulska, Katarzyna; Rowicka, Grażyna; Klemarczyk, Witold; Strucińska, Małgorzata; Gajewska, Joanna

    2018-02-07

    Vegetarian diets contain many beneficial properties as well as carry a risk of inadequate intakes of several nutrients important to bone health. The aim of the study was to evaluate serum levels of bone metabolism markers and to analyze the relationships between biochemical bone markers and anthropometric parameters in children on vegetarian and omnivorous diets. The study included 70 prepubertal children on a lacto-ovo-vegetarian diet and 60 omnivorous children. Body composition, bone mineral content (BMC), and bone mineral density (BMD) were assessed by dual-energy X-ray absorptiometry. Biochemical markers-bone alkaline phosphatase (BALP), C-terminal telopeptide of type I collagen (CTX-I), osteoprotegerin (OPG), nuclear factor κB ligand (RANKL), sclerostin, and Dickkopf-related protein 1 (Dkk-1)-were measured using immunoenzymatic assays. In vegetarians, we observed a significantly higher level of BALP ( p = 0.002) and CTX-I ( p = 0.027), and slightly lower spine BMC ( p = 0.067) and BMD ( p = 0.060) than in omnivores. Concentrations of OPG, RANKL, sclerostin, and Dkk-1 were comparable in both groups of children. We found that CTX-I was positively correlated with BMC, total BMD, and lumbar spine BMD in vegetarians, but not in omnivores. A well-planned vegetarian diet with proper dairy and egg intake does not lead to significantly lower bone mass; however, children following a lacto-ovo-vegetarian diet had a higher rate of bone turnover and subtle changes in bone regulatory markers. CTX-I might be an important marker for the protection of vegetarians from bone abnormalities.

  15. PD1/PD1L pathway, HLA-G and T regulatory cells as new markers of immunosuppression in cancers

    Directory of Open Access Journals (Sweden)

    Paulina Własiuk

    2016-10-01

    Full Text Available The appropriate function of the immune system depends on the effective regulation of the immune response on multiple levels. The key element of an effective immune response to antigenic stimulation is maintaining a homeostasis between activation and inhibitory function of immunocompetent cells and molecules. In pathological conditions such as chronic infections, autoimmune diseases or cancer there are significant alterations, and prevalence of signals of one type over another. Main markers of these dysfunctions are altered expressions of molecules, such as programmed death-1 (PD-1, Human Leukocyte Antigen G (HLA-G, or changed percentages of T regulatory cells (Treg. These indicators of immune system dysfunction may contribute to disease progression, but also could represent good targets for treatment. Interestingly, in recent years there are many new, interesting reports which showed that the role of PD-1, HLA-G or Treg is ambiguous and not always their higher expression or frequency lead to the progression of disease. Recent studies have shown that Treg can suppress bacteria-driven inflammation which promotes carcinogenesis and thus protect the host from cancer development. Moreover, proliferation of hematological tumor cells expressing ILT-2 receptor can be inhibited by HLA-G, in contrast to solid tumors where HLA-G favors tumor escape. In this paper we present characteristics of expressions of PD-1 and its ligands, HLA-G, and frequency of Treg cells in a variety of physiological and pathological conditions associated with chronic infections, autoimmune diseases and cancer. The understanding of the complex interactions between the functional elements of immune system is essential for a detailed characteristics of the mechanisms leading to the development of diseases and identification of more effective targeted therapies.

  16. Phytosterols and Omega 3 Supplementation Exert Novel Regulatory Effects on Metabolic and Inflammatory Pathways: A Proteomic Study

    Directory of Open Access Journals (Sweden)

    Carmen Lambert

    2017-06-01

    reduced (p = 0.013. No changes were observed in the lipid-free plasma proteome with ω3-milk. Our study provides novel results and highlights that the PhyS-milk induces attenuation of the pro-inflammatory pathways, whereas ω3-milk induces improvement in lipid metabolic pathways.

  17. Phosphorylation of Threonine 794 on Tie1 by Rac1/PAK1 Reveals a Novel Angiogenesis Regulatory Pathway.

    Directory of Open Access Journals (Sweden)

    Jessica L Reinardy

    Full Text Available The endothelial receptor tyrosine kinase (RTK Tie1 was discovered over 20 years ago, yet its precise function and mode of action remain enigmatic. To shed light on Tie1's role in endothelial cell biology, we investigated a potential threonine phosphorylation site within the juxtamembrane domain of Tie1. Expression of a non-phosphorylatable mutant of this site (T794A in zebrafish (Danio rerio significantly disrupted vascular development, resulting in fish with stunted and poorly branched intersomitic vessels. Similarly, T794A-expressing human umbilical vein endothelial cells formed significantly shorter tubes with fewer branches in three-dimensional Matrigel cultures. However, mutation of T794 did not alter Tie1 or Tie2 tyrosine phosphorylation or downstream signaling in any detectable way, suggesting that T794 phosphorylation may regulate a Tie1 function independent of its RTK properties. Although T794 is within a consensus Akt phosphorylation site, we were unable to identify a physiological activator of Akt that could induce T794 phosphorylation, suggesting that Akt is not the physiological Tie1-T794 kinase. However, the small GTPase Ras-related C3 botulinum toxin substrate 1 (Rac1, which is required for angiogenesis and capillary morphogenesis, was found to associate with phospho-T794 but not the non-phosphorylatable T794A mutant. Pharmacological activation of Rac1 induced downstream activation of p21-activated kinase (PAK1 and T794 phosphorylation in vitro, and inhibition of PAK1 abrogated T794 phosphorylation. Our results provide the first demonstration of a signaling pathway mediated by Tie1 in endothelial cells, and they suggest that a novel feedback loop involving Rac1/PAK1 mediated phosphorylation of Tie1 on T794 is required for proper angiogenesis.

  18. Exploring the electron transfer pathway in the oxidation of avermectin by CYP107Z13 in Streptomyces ahygroscopicus ZB01.

    Directory of Open Access Journals (Sweden)

    Mei Li

    Full Text Available Streptomyces ahygroscopicus ZB01 can effectively oxidize 4″-OH of avermectin to form 4″-oxo-avermectin. CYP107Z13 is responsible for this site-specific oxidation in ZB01. In the present study, we explored the electron transfer pathway in oxidation of avermectin by CYP107Z13 in ZB01. A putative [3Fe-4S] ferredoxin gene fd68 and two possible NADH-dependent ferredoxin reductase genes fdr18 and fdr28 were cloned from the genomic DNA of ZB01. fd68 gene disruption mutants showed no catalytic activity in oxidation of avermectin to form 4″-oxo-avermectin. To clarify whether FdR18 and FdR28 participate in the electron transfer during avermectin oxidation by CYP107Z13, two whole-cell biocatalytic systems were designed in E. coli BL21 (DE3, with one co-expressing CYP107Z13, Fd68 and FdR18 and the other co-expressing CYP107Z13, Fd68 and FdR28. Both of the two biocatalytic systems were found to be able to mediate the oxidation of avermectin to form 4″-oxo-avermectin. Thus, we propose an electron transfer pathway NADH→FdR18/FdR28→Fd68→CYP107Z13 for oxidation of avermectin to form 4″-oxo-avermectin in ZB01.

  19. Overexpression of the PP2A regulatory subunit Tap46 leads to enhanced plant growth through stimulation of the TOR signalling pathway

    Science.gov (United States)

    Ahn, Chang Sook; Ahn, Hee-Kyung; Pai, Hyun-Sook

    2015-01-01

    Tap46, a regulatory subunit of protein phosphatase 2A (PP2A), plays an essential role in plant growth and development through a functional link with the Target of Rapamycin (TOR) signalling pathway. Here, we have characterized the molecular mechanisms behind a gain-of-function phenotype of Tap46 and its relationship with TOR to gain further insights into Tap46 function in plants. Constitutive overexpression of Tap46 in Arabidopsis resulted in overall growth stimulation with enlarged organs, such as leaves and siliques. Kinematic analysis of leaf growth revealed that increased cell size was mainly responsible for the leaf enlargement. Tap46 overexpression also enhanced seed size and viability under accelerated ageing conditions. Enhanced plant growth was also observed in dexamethasone (DEX)-inducible Tap46 overexpression Arabidopsis lines, accompanied by increased cellular activities of nitrate-assimilating enzymes. DEX-induced Tap46 overexpression and Tap46 RNAi resulted in increased and decreased phosphorylation of S6 kinase (S6K), respectively, which is a sensitive indicator of endogenous TOR activity, and Tap46 interacted with S6K in planta based on bimolecular fluorescence complementation and co-immunoprecipitation. Furthermore, inactivation of TOR by estradiol-inducible RNAi or rapamycin treatment decreased Tap46 protein levels, but increased PP2A catalytic subunit levels. Real-time quantitative PCR analysis revealed that Tap46 overexpression induced transcriptional modulation of genes involved in nitrogen metabolism, ribosome biogenesis, and lignin biosynthesis. These findings suggest that Tap46 modulates plant growth as a positive effector of the TOR signalling pathway and Tap46/PP2Ac protein abundance is regulated by TOR activity. PMID:25399018

  20. Overexpression of the PP2A regulatory subunit Tap46 leads to enhanced plant growth through stimulation of the TOR signalling pathway.

    Science.gov (United States)

    Ahn, Chang Sook; Ahn, Hee-Kyung; Pai, Hyun-Sook

    2015-02-01

    Tap46, a regulatory subunit of protein phosphatase 2A (PP2A), plays an essential role in plant growth and development through a functional link with the Target of Rapamycin (TOR) signalling pathway. Here, we have characterized the molecular mechanisms behind a gain-of-function phenotype of Tap46 and its relationship with TOR to gain further insights into Tap46 function in plants. Constitutive overexpression of Tap46 in Arabidopsis resulted in overall growth stimulation with enlarged organs, such as leaves and siliques. Kinematic analysis of leaf growth revealed that increased cell size was mainly responsible for the leaf enlargement. Tap46 overexpression also enhanced seed size and viability under accelerated ageing conditions. Enhanced plant growth was also observed in dexamethasone (DEX)-inducible Tap46 overexpression Arabidopsis lines, accompanied by increased cellular activities of nitrate-assimilating enzymes. DEX-induced Tap46 overexpression and Tap46 RNAi resulted in increased and decreased phosphorylation of S6 kinase (S6K), respectively, which is a sensitive indicator of endogenous TOR activity, and Tap46 interacted with S6K in planta based on bimolecular fluorescence complementation and co-immunoprecipitation. Furthermore, inactivation of TOR by estradiol-inducible RNAi or rapamycin treatment decreased Tap46 protein levels, but increased PP2A catalytic subunit levels. Real-time quantitative PCR analysis revealed that Tap46 overexpression induced transcriptional modulation of genes involved in nitrogen metabolism, ribosome biogenesis, and lignin biosynthesis. These findings suggest that Tap46 modulates plant growth as a positive effector of the TOR signalling pathway and Tap46/PP2Ac protein abundance is regulated by TOR activity. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  1. Puerarin Suppresses the Self-Renewal of Murine Embryonic Stem Cells by Inhibition of REST-MiR-21 Regulatory Pathway.

    Science.gov (United States)

    Yin, Mengmeng; Yuan, Yin; Cui, Yurong; Hong, Xian; Luo, Hongyan; Hu, Xinwu; Tang, Ming; Hescheler, Jurgen; Xi, Jiaoya

    2015-01-01

    Puerarin shows a wide range of biological activities, including affecting the cardiac differentiation from murine embryonic stem (mES) cells. However, little is known about its effect and mechanism of action on the self-renewal of mES cells. This study aimed to determine the effect of puerarin on the self-renewal and pluripotency of mES cells and its underlying mechanisms. RT-PCR and real-time PCR were used to detect the transcripts of core transcription factors, specific markers for multiple lineages, REST and microRNA-21 (miR-21). Colony-forming assay was performed to estimate the self-renewal capacity of mES cells. Western blotting and wortmannin were employed to explore the role of PI3K/Akt signaling pathway in the inhibitory action of puerarin on REST transcript. Transfected mES cells with antagomir21 were used to confirm the role of miR-21 in the action of puerarin on cell self-renewal. Puerarin significantly decreased the percentage of the self-renewal colonies, and suppressed the transcripts of Oct4, Nanog, Sox2, c-Myc and REST. Besides, PECAM, NCAM and miR-21 were up-regulated both under the self-renewal conditions and at day 4 of differentiation. The PI3K inhibitor wortmannin successfully reversed the mRNA expression changes of REST, Nanog and Sox2. Transfection of antagomir21 efficiently reversed the effects of puerarin on mES cells self-renewal. Inhibition of REST-miR-21 regulatory pathway may be the key mechanism of puerarin-induced suppression of mES cells self-renewal.

  2. The PP2A Regulatory Subunit Tap46, a Component of the TOR Signaling Pathway, Modulates Growth and Metabolism in Plants[W

    Science.gov (United States)

    Ahn, Chang Sook; Han, Jeong-A; Lee, Ho-Seok; Lee, Semi; Pai, Hyun-Sook

    2011-01-01

    Tap42/α4, a regulatory subunit of protein phosphatase 2A, is a downstream effector of the target of rapamycin (TOR) protein kinase, which regulates cell growth in coordination with nutrient and environmental conditions in yeast and mammals. In this study, we characterized the functions and phosphatase regulation of plant Tap46. Depletion of Tap46 resulted in growth arrest and acute plant death with morphological markers of programmed cell death. Tap46 interacted with PP2A and PP2A-like phosphatases PP4 and PP6. Tap46 silencing modulated cellular PP2A activities in a time-dependent fashion similar to TOR silencing. Immunoprecipitated full-length and deletion forms of Arabidopsis thaliana TOR phosphorylated recombinant Tap46 protein in vitro, supporting a functional link between Tap46 and TOR. Tap46 depletion reproduced the signature phenotypes of TOR inactivation, such as dramatic repression of global translation and activation of autophagy and nitrogen mobilization, indicating that Tap46 may act as a positive effector of TOR signaling in controlling those processes. Additionally, Tap46 silencing in tobacco (Nicotiana tabacum) BY-2 cells caused chromatin bridge formation at anaphase, indicating its role in sister chromatid segregation. These findings suggest that Tap46, in conjunction with associated phosphatases, plays an essential role in plant growth and development as a component of the TOR signaling pathway. PMID:21216945

  3. Significant accumulation of persistent organic pollutants and dysregulation in multiple DNA damage repair pathways in the electronic-waste-exposed populations

    Energy Technology Data Exchange (ETDEWEB)

    He, Xiaobo; Jing, Yaqing; Wang, Jianhai; Li, Keqiu [Basic Medical College, Tianjin Medical University, Tianjin 300070 (China); Yang, Qiaoyun [Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin 300070 (China); Zhao, Yuxia [Basic Medical College, Tianjin Medical University, Tianjin 300070 (China); Li, Ran [State Key Joint Laboratory for Environmental Simulation and Pollution Control, College of Environmental Sciences and Engineering and Center for Environment and Health, Peking University, Beijing 100871 (China); Ge, Jie [Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060 (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060 (China); Qiu, Xinghua, E-mail: xhqiu@pku.edu.cn [State Key Joint Laboratory for Environmental Simulation and Pollution Control, College of Environmental Sciences and Engineering and Center for Environment and Health, Peking University, Beijing 100871 (China); Li, Guang, E-mail: lig@tijmu.edu.cn [Basic Medical College, Tianjin Medical University, Tianjin 300070 (China)

    2015-02-15

    Electronic waste (e-waste) has created a worldwide environmental and health problem, by generating a diverse group of hazardous compounds such as persistent organic pollutants (POPs). Our previous studies demonstrated that populations from e-waste exposed region have a significantly higher level of chromosomal aberrancy and incidence of DNA damage. In this study, we further demonstrated that various POPs persisted at a significantly higher concentration in the exposed group than those in the unexposed group. The level of reactive oxygen species and micronucleus rate were also significantly elevated in the exposed group. RNA sequencing analysis revealed 31 genes in DNA damage responses and repair pathways that were differentially expressed between the two groups (Log 2 ratio >1 or <−1). Our data demonstrated that both females and males of the exposed group have activated a series of DNA damage response genes; however many important DNA repair pathways have been dysregulated. Expressions of NEIL1/3 and RPA3, which are critical in initiating base pair and nucleotide excision repairs respectively, have been downregulated in both females and males of the exposed group. In contrast, expression of RNF8, an E3 ligase involved in an error prone non-homologous end joining repair for DNA double strand break, was upregulated in both genders of the exposed group. The other genes appeared to be differentially expressed only when the males or females of the two groups were compared respectively. Importantly, the expression of cell cycle regulatory gene CDC25A that has been implicated in multiple kinds of malignant transformation was significantly upregulated among the exposed males while downregulated among the exposed females. In conclusion, our studies have demonstrated significant correlations between e-waste disposing and POPs accumulation, DNA lesions and dysregulation of multiple DNA damage repair mechanisms in the residents of the e-waste exposed region. - Highlights:

  4. Bridge mediated two-electron transfer reactions: Analysis of stepwise and concerted pathways

    International Nuclear Information System (INIS)

    Petrov, E.G.; May, V.

    2004-01-01

    A theory of nonadiabatic donor (D)-acceptor (A) two-electron transfer (TET) mediated by a single regular bridge (B) is developed. The presence of different intermediate two-electron states connecting the reactant state D -- BA with the product state DBA -- results in complex multiexponential kinetics. The conditions are discussed at which a reduction to two-exponential as well as single-exponential kinetics becomes possible. For the latter case the rate K TET is calculated, which describes the bridge-mediated reaction as an effective two-electron D-A transfer. In the limit of small populations of the intermediate TET states D - B - A, DB -- A, D - BA - , and DB - A - , K TET is obtained as a sum of the rates K TET (step) and K TET (sup) . The first rate describes stepwise TET originated by transitions of a single electron. It starts at D -- BA and reaches DBA -- via the intermediate state D - BA - . These transitions cover contributions from sequential as well as superexchange reactions all including reduced bridge states. In contrast, a specific two-electron superexchange mechanism from D -- BA to DBA -- defines K TET (sup) . An analytic dependence of K TET (step) and K TET (sup) on the number of bridging units is presented and different regimes of D-A TET are studied

  5. Nuclear Envelope Phosphatase 1-Regulatory Subunit 1 (Formerly TMEM188) Is the Metazoan Spo7p Ortholog and Functions in the Lipin Activation Pathway*

    Science.gov (United States)

    Han, Sungwon; Bahmanyar, Shirin; Zhang, Peixiang; Grishin, Nick; Oegema, Karen; Crooke, Roseann; Graham, Mark; Reue, Karen; Dixon, Jack E.; Goodman, Joel M.

    2012-01-01

    Lipin-1 catalyzes the formation of diacylglycerol from phosphatidic acid. Lipin-1 mutations cause lipodystrophy in mice and acute myopathy in humans. It is heavily phosphorylated, and the yeast ortholog Pah1p becomes membrane-associated and active upon dephosphorylation by the Nem1p-Spo7p membrane complex. A mammalian ortholog of Nem1p is the C-terminal domain nuclear envelope phosphatase 1 (CTDNEP1, formerly “dullard”), but its Spo7p-like partner is unknown, and the need for its existence is debated. Here, we identify the metazoan ortholog of Spo7p, TMEM188, renamed nuclear envelope phosphatase 1-regulatory subunit 1 (NEP1-R1). CTDNEP1 and NEP1-R1 together complement a nem1Δspo7Δ strain to block endoplasmic reticulum proliferation and restore triacylglycerol levels and lipid droplet number. The two human orthologs are in a complex in cells, and the amount of CTDNEP1 is increased in the presence of NEP1-R1. In the Caenorhabditis elegans embryo, expression of nematode CTDNEP1 and NEP1-R1, as well as lipin-1, is required for normal nuclear membrane breakdown after zygote formation. The expression pattern of NEP1-R1 and CTDNEP1 in human and mouse tissues closely mirrors that of lipin-1. CTDNEP1 can dephosphorylate lipins-1a, -1b, and -2 in human cells only in the presence of NEP1-R1. The nuclear fraction of lipin-1b is increased when CTDNEP1 and NEP1-R1 are co-expressed. Therefore, NEP1-R1 is functionally conserved from yeast to humans and functions in the lipin activation pathway. PMID:22134922

  6. Regulatory T cells protect mice against coxsackievirus-induced myocarditis through the transforming growth factor beta-coxsackie-adenovirus receptor pathway.

    Science.gov (United States)

    Shi, Yu; Fukuoka, Masahiro; Li, Guohua; Liu, Youan; Chen, Manyin; Konviser, Michael; Chen, Xin; Opavsky, Mary Anne; Liu, Peter P

    2010-06-22

    Coxsackievirus B3 infection is an excellent model of human myocarditis and dilated cardiomyopathy. Cardiac injury is caused either by a direct cytopathic effect of the virus or through immune-mediated mechanisms. Regulatory T cells (Tregs) play an important role in the negative modulation of host immune responses and set the threshold of autoimmune activation. This study was designed to test the protective effects of Tregs and to determine the underlying mechanisms. Carboxyfluorescein diacetate succinimidyl ester-labeled Tregs or naïve CD4(+) T cells were injected intravenously once every 2 weeks 3 times into mice. The mice were then challenged with intraperitoneal coxsackievirus B3 immediately after the last cell transfer. Transfer of Tregs showed higher survival rates than transfer of CD4(+) T cells (P=0.0136) but not compared with the PBS injection group (P=0.0589). Interestingly, Tregs also significantly decreased virus titers and inflammatory scores in the heart. Transforming growth factor-beta and phosphorylated AKT were upregulated in Tregs-transferred mice and coxsackie-adenovirus receptor expression was decreased in the heart compared with control groups. Transforming growth factor-beta decreased coxsackie-adenovirus receptor expression and inhibited coxsackievirus B3 infection in HL-1 cells and neonatal cardiac myocytes. Splenocytes collected from Treg-, CD4(+) T-cell-, and PBS-treated mice proliferated equally when stimulated with heat-inactivated virus, whereas in the Treg group, the proliferation rate was reduced significantly when stimulated with noninfected heart tissue homogenate. Adoptive transfer of Tregs protected mice from coxsackievirus B3-induced myocarditis through the transforming growth factor beta-coxsackie-adenovirus receptor pathway and thus suppresses the immune response to cardiac tissue, maintaining the antiviral immune response.

  7. Regulatory Activities of the President of the Office of Electronic Communications versus competitiveness and fi nancial situation of the enterprises on the example of TP Group

    Directory of Open Access Journals (Sweden)

    Ewa M. Kwiatkowska

    2014-09-01

    Full Text Available Purpose: The aim of this paper is to present the regulatory obligations imposed by the President of the Office of Electronic Communications (hereafter: President of UKE on telecom enterprises with significant market power in the retail and wholesale telecommunications markets. Methodology: The decisions addressed to TP Group entities were analyzed as well as the fi nancial statements presenting the economic volume achieved for the period 2006–2013. Findings: In the analyzed period for entities of the TP Group were applied a range of regulatory obligations, that should result in disabling the use of their monopoly position and transfer their position between telecommunications markets. Regulatory obligations imposed by the President of UKE on TP Group entities did not affect to a significant extent the situation of the group. Fluctuations of analyzed financial f gures seem to be primarily the result of internal management decisions rather than a comprehensive range of sector-specific regulation in telecommunications. These researches indicate the need for a deeper analysis of the perception of the effects of regulatory actions by stakeholders in the telecommunications sector.

  8. Precision controlled atomic resolution scanning transmission electron microscopy using spiral scan pathways

    Science.gov (United States)

    Sang, Xiahan; Lupini, Andrew R.; Ding, Jilai; Kalinin, Sergei V.; Jesse, Stephen; Unocic, Raymond R.

    2017-03-01

    Atomic-resolution imaging in an aberration-corrected scanning transmission electron microscope (STEM) can enable direct correlation between atomic structure and materials functionality. The fast and precise control of the STEM probe is, however, challenging because the true beam location deviates from the assigned location depending on the properties of the deflectors. To reduce these deviations, i.e. image distortions, we use spiral scanning paths, allowing precise control of a sub-Å sized electron probe within an aberration-corrected STEM. Although spiral scanning avoids the sudden changes in the beam location (fly-back distortion) present in conventional raster scans, it is not distortion-free. “Archimedean” spirals, with a constant angular frequency within each scan, are used to determine the characteristic response at different frequencies. We then show that such characteristic functions can be used to correct image distortions present in more complicated constant linear velocity spirals, where the frequency varies within each scan. Through the combined application of constant linear velocity scanning and beam path corrections, spiral scan images are shown to exhibit less scan distortion than conventional raster scan images. The methodology presented here will be useful for in situ STEM imaging at higher temporal resolution and for imaging beam sensitive materials.

  9. Alternative oxidase: a respiratory electron transport chain pathway essential for maintaining photosynthetic performance during drought stress.

    Science.gov (United States)

    Vanlerberghe, Greg C; Martyn, Greg D; Dahal, Keshav

    2016-07-01

    Photosynthesis and respiration are the hubs of energy metabolism in plants. Drought strongly perturbs photosynthesis as a result of both diffusive limitations resulting from stomatal closure, and in some cases biochemical limitations that are associated with a reduced abundance of key photosynthetic components. The effects of drought on respiration, particularly respiration in the light (RL ), are less understood. The plant mitochondrial electron transport chain includes a non-energy conserving terminal oxidase called alternative oxidase (AOX). Several studies have shown that drought increases AOX transcript, protein and maximum capacity. Here we review recent studies comparing wild-type (WT) tobacco to transgenic lines with altered AOX protein amount. Specifically during drought, RL was compromised in AOX knockdown plants and enhanced in AOX overexpression plants, compared with WT. Significantly, these differences in RL were accompanied by dramatic differences in photosynthetic performance. Knockdown of AOX increased the susceptibility of photosynthesis to drought-induced biochemical limitations, while overexpression of AOX delayed the development of such biochemical limitations, compared with WT. Overall, the results indicate that AOX is essential to maintaining RL during drought, and that this non-energy conserving respiration maintains photosynthesis during drought by promoting energy balance in the chloroplast. This review also outlines several areas for future research, including the possibility that enhancement of non-energy conserving respiratory electron sinks may be a useful biotechnological approach to increase plant performance during stress. © 2016 Scandinavian Plant Physiology Society.

  10. New pathways in electronics and optoelectronics driven by new physics of nonconventional materials

    International Nuclear Information System (INIS)

    Kantser, Valeriu

    2015-01-01

    Nonconventional materials (NCM) - 2D materials and topological insulators (TI) - have opened a gateway to search new physical phenomena and states of the condensed matter as well as to pave new platform of modern technology. This stems on their unique attributes - non equivalence of electronic and dielectric states to vacuum ones, topological protection (reduced backscattering), spin momentum locking property, magnetoelectric coupling, generations of new quasiparticles like Majorana fermions. Increasing the surface state contribution in proportion to the bulk is critical to investigate the surface states and for future innovative device applications. The way to achieve this is to configure NCM into nanostructures, which at the same time in combination with others materials significantly enlarge the variety of new states and phenomena. This article reviews the recent progress made in NCM and nano heterostructures investigation. The state of art of different new scenario of engineering topologically interface states in the TI heterostructures are revealed, in particular by using polarization fields and antiferromagnetic ordering. Some of new proposals for innovative electronic and optoelectronic devices are discussed. (author)

  11. Thymic commitment of regulatory T cells is a pathway of TCR-dependent selection that isolates repertoires undergoing positive or negative selection.

    Science.gov (United States)

    Coutinho, A; Caramalho, I; Seixas, E; Demengeot, J

    2005-01-01

    The seminal work of Le Douarin and colleagues (Ohki et al. 1987; Ohki et al. 1988; Salaun et al. 1990; Coutinho et al. 1993) first demonstrated that peripheral tissue-specific tolerance is centrally established in the thymus, by epithelial stromal cells (TEC). Subsequent experiments have shown that TEC-tolerance is dominant and mediated by CD4 regulatory T cells (Treg) that are generated intrathymically by recognition of antigens expressed on TECs (Modigliani et al. 1995; Modigliani et al. 1996a). From these and other observations, in 1996 Modigliani and colleagues derived a general model for the establishment and maintenance of natural tolerance (MM96) (Modigliani et al. 1996b), with two central propositions: (1) T cell receptor (TCR)-dependent sorting of emergent repertoires generates TEC-specific Treg displaying the highest TCR self-affinities below deletion thresholds, thus isolating repertoires undergoing positive and negative selection; (2) Treg are intrathymically committed (and activated) for a unique differentiative pathway with regulatory effector functions. The model explained the embryonic/perinatal time window of natural tolerance acquisition, by developmental programs determining (1) TCR multireactivity, (2) the cellular composition in the thymic stroma (relative abundance of epithelial vs hemopoietic cells), and (3) the dynamics of peripheral lymphocyte pools, built by accumulation of recent thymic emigrants (RTE) that remain recruitable to regulatory functions. We discuss here the MM96 in the light of recent results demonstrating the promiscuous expression of tissue-specific antigens by medullary TECs (Derbinski et al. 2001; Anderson et al. 2002; Gotter et al. 2004) and indicating that Treg represent a unique differentiative pathway (Fontenot et al. 2003; Hori et al. 2003; Khattri et al. 2003), which is adopted by CD4 T cells with high avidity for TEC-antigens (Bensinger et al. 2001; Jordan et al. 2001; Apostolou et al. 2002). In the likelihood that

  12. Defining Data Access Pathways for Atmosphere to Electrons Wind Energy Data

    Science.gov (United States)

    Macduff, M.; Sivaraman, C.

    2016-12-01

    Atmosphere to Electrons (A2e), is a U.S. Department of Energy (DOE) Wind Program research initiative designed to optimize the performance of wind power plants by lowering the levelized cost of energy (LCOE). The Data Archive and Portal (DAP), managed by PNNL and hosted on Amazon Web Services, is a key capability of the A2e initiative. The DAP is used to collect, store, catalog, preserve and disseminate results from the experimental and computational studies representing a diverse user community requiring both open and proprietary data archival solutions(http://a2e.pnnl.gov). To enable consumer access to the data in DAP it is being built on a set of API's that are publically accessible. This includes persistent references for key meta-data objects as well as authenticated access to the data itself. The goal is to make the DAP catalog visible through a variety of data access paths bringing the data and metadata closer to the consumer. By providing persistent metadata records we hope to be able to build services that capture consumer utility and make referencing datasets easier.

  13. Targetting the hemozoin synthesis pathway for antimalarial drug and detected by TEM (Transmission electron microscope)

    Science.gov (United States)

    Abbas, Jamilah; Artanti, Nina; Sundowo, Andini; Dewijanti, Indah Dwiatmi; Hanafi, Muhammad; Lisa, Syafrudin, Din

    2017-11-01

    Malaria is a major public health problem mainly due to the development of resistance by the most lethal causative parasite species, the alarming spread of drug resistance and limited number of effective drug available now. Therefore it is important to discover new antimalarial drug. Malaria is caused by a singlecelled parasite from the genus Plasmodium. Plasmodium falciparum parasite infect red blood cells, ingesting and degradation hemoglobin in the acidic food vacuola trough a sequential metabolic process involving multiple proteases. During these process, hemoglobin is utilized as the predominant source of nutrition. Proteolysis of hemoglobin yields amino acid for protein synthesis as well as toxic heme. Massive degradation of hemoglobin generates large amount of toxic heme. Malaria parasite has evolved a distinct mechanism for detoxification of heme through conversion into insoluble crystalline pigment, known as hemozoin (β hematoin). Hemozoin synthesis is an indispensable process for the parasite and is the target for action of several known antimalarial drug. TEM (Transmission Electron Microscope) technology for hemozoin formation in vitro assay was done in this research. Calophyllum aerophyllum Lauterb as medicinal plants was used as a source of antimalarial drug. Acetone extracts of C. lowii showed growth inhibition against parasite P. falciparum with IC50 = 5.2 µg/mL. Whereas from hexane, acetone and methanol fraction of C. aerophyllum showed growth inhibition with IC50 = 0.054, 0.055 and 0.0054 µg/mL respectively. New drug from Calophyllum might have potential compounds that have unique structures and mechanism of action which required to develop new drug for treatment of sensitive and drug resistant strain of malaria.

  14. Experimental investigation of dissociation pathways of cooled HeH+ following valence electron excitation at 32 nm by intense free-electron-laser radiation

    International Nuclear Information System (INIS)

    Pedersen, H. B.; Lammich, L.; Domesle, C.; Jordon-Thaden, B.; Ullrich, J.; Wolf, A.; Heber, O.; Treusch, R.; Guerassimova, N.

    2010-01-01

    The dissociation pathways of HeH + have been investigated below the first ionization continuum by photoabsorption at 32 nm, using fragment momentum imaging in a crossed-beams experiment at the free-electron laser in Hamburg (FLASH). Investigations were done both for ions with several vibrational levels excited in the ion source and for ions vibrationally cooled in an electrostatic ion trap prior to the irradiation. The product channels He + (1s)+H(nl) and He(1snl)+H + were separated and the He(1snl)+H + channel was particularly studied by coincidence detection of the He and H + fragments on two separate fragment detectors. At 32 nm excitation, the branching ratio between the product channels was found to be σ He + +H /σ He+H + =0.96±0.11 for vibrationally hot and 1.70±0.48 for vibrationally cold ions. The spectra of kinetic energy releases for both channels revealed that photodissociation at 32 nm leads to high Rydberg states (n > or approx. 3-4) of the emerging atomic fragments irrespective of the initial vibrational excitation of HeH + . The fragment angular distributions showed that dissociation into the He+H + channel mostly (∼70%) proceeds through 1 Π states, while for the He + +H channel 1 Σ and 1 Π states are of about equal importance.

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

    Science.gov (United States)

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

    2014-01-01

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

  16. 75 FR 7526 - Withdrawal of Regulatory Guide

    Science.gov (United States)

    2010-02-19

    ...'s Electronic Reading Room at http://www.nrc.gov/reading-rm/doc-collections . Regulatory guides are... NUCLEAR REGULATORY COMMISSION [NRC-2010-0052] Withdrawal of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Withdrawal of Regulatory Guide 1.56, ``Maintenance of Water Purity in Boiling...

  17. Following patient pathways to psycho-oncological treatment: Identification of treatment needs by clinical staff and electronic screening.

    Science.gov (United States)

    Loth, Fanny L; Meraner, Verena; Holzner, Bernhard; Singer, Susanne; Virgolini, Irene; Gamper, Eva M

    2018-04-01

    In this retrospective investigation of patient pathways to psycho-oncological treatment (POT), we compared the number of POT referrals before and after implementation of electronic screening for POT needs and investigated psychosocial predictors for POT wish at a nuclear medicine department. We extracted medical chart information about number of referrals and extent of follow-up contacts. During standard referral (November 2014 to October 2015), POT needs were identified by clinical staff only. In the screening-assisted referral period (November 2015 to October 2016), identification was supported by electronic screening for POT needs. Psychosocial predictors for POT wish were examined using logistic regression. We analysed data from 487 patients during standard referral (mean age 56.4 years; 60.2% female, 88.7% thyroid carcinoma or neuroendocrine tumours) of which 28 patients (5.7%) were referred for POT. Of 502 patients in the screening-assisted referral period (mean age 57.0 years; 55.8% female, 86.6% thyroid carcinoma or neuroendocrine tumours), 69 (13.7%) were referred for POT. Of these, 36 were identified by psycho-oncological (PO) screening and 33 by clinical staff. After PO-screening implementation, referrals increased by a factor of 2.4. The strongest predictor of POT wish was depressive mood (P patients visited the PO outpatient unit additionally to inpatient PO consultations. Our results provide evidence from a real-life setting that PO screening can foster POT referrals, reduce barriers to express the POT wish, and hence help to meet psychosocial needs of this specific patient group. Differences between patients' needs, wish, and POT uptake should be further investigated. © 2018 The Authors. Psycho-Oncology Published by John Wiley & Sons Ltd.

  18. A multienzyme complex channels substrates and electrons through acetyl-CoA and methane biosynthesis pathways in Methanosarcina.

    Directory of Open Access Journals (Sweden)

    Dillon J Lieber

    Full Text Available Multienzyme complexes catalyze important metabolic reactions in many organisms, but little is known about the complexes involved in biological methane production (methanogenesis. A crosslinking-mass spectrometry (XL-MS strategy was employed to identify proteins associated with coenzyme M-coenzyme B heterodisulfide reductase (Hdr, an essential enzyme in all methane-producing archaea (methanogens. In Methanosarcina acetivorans, Hdr forms a multienzyme complex with acetyl-CoA decarbonylase synthase (ACDS, and F420-dependent methylene-H4MPT reductase (Mer. ACDS is essential for production of acetyl-CoA during growth on methanol, or for methanogenesis from acetate, whereas Mer is essential for methanogenesis from all substrates. Existence of a Hdr:ACDS:Mer complex is consistent with growth phenotypes of ACDS and Mer mutant strains in which the complex samples the redox status of electron carriers and directs carbon flux to acetyl-CoA or methanogenesis. We propose the Hdr:ACDS:Mer complex comprises a special class of multienzyme redox complex which functions as a "biological router" that physically links methanogenesis and acetyl-CoA biosynthesis pathways.

  19. Transcriptional regulatory dynamics of the hypothalamic-pituitary-gonadal axis and its peripheral pathways as impacted by the 3-beta HSD inhibitor Trilostane in zebrafish (Danio rerio)

    Science.gov (United States)

    To identify transcription factors (TFs), members of hypothalamic-pituitary- gonadal axis (HPG-axis), TF networks and signaling pathways underlying generalized effects of 3-beta hydroxysteroid dehydrogenase (HSD3B) inhibition, reproductively mature zebrafish (Danio rerio) were exp...

  20. 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...

  1. RNA-Seq transcriptomics and pathway analyses reveal potential regulatory genes and molecular mechanisms in high- and low-residual feed intake in Nordic dairy cattle

    DEFF Research Database (Denmark)

    Salleh, M. S.; Mazzoni, G.; Höglund, J. K.

    2017-01-01

    -throughput RNA sequencing data of liver biopsies from 19 dairy cows were used to identify differentially expressed genes (DEGs) between high- and low-FE groups of cows (based on Residual Feed Intake or RFI). Subsequently, a profile of the pathways connecting the DEGs to FE was generated, and a list of candidate...... genes and biomarkers was derived for their potential inclusion in breeding programmes to improve FE. The bovine RNA-Seq gene expression data from the liver was analysed to identify DEGs and, subsequently, identify the molecular mechanisms, pathways and possible candidate biomarkers of feed efficiency....... On average, 57 million reads (short reads or short mRNA sequences ...

  2. Healthcare information privacy and security regulatory compliance and data security in the age of electronic health records

    CERN Document Server

    Robichau, Bernard Peter

    2014-01-01

    Healthcare is a huge market--20% of yearly GDP in the U.S. It employs tens of thousands of computer programmers and IT administrators Regulations mandate electronic health records by 2015 (for anyone dealing with Medicare/Medicaid), which means new concerns for privacy and security Many medical organizations lagging, putting them at risk for government fines and private lawsuits when a breach in security occurs. Healthcare IT is the growth industry right now, and the need for guidance in regard to privacy and security is huge.

  3. The Crc global regulator inhibits the Pseudomonas putida pWW0 toluene/xylene assimilation pathway by repressing the translation of regulatory and structural genes.

    Science.gov (United States)

    Moreno, Renata; Fonseca, Pilar; Rojo, Fernando

    2010-08-06

    In Pseudomonas putida, the expression of the pWW0 plasmid genes for the toluene/xylene assimilation pathway (the TOL pathway) is subject to complex regulation in response to environmental and physiological signals. This includes strong inhibition via catabolite repression, elicited by the carbon sources that the cells prefer to hydrocarbons. The Crc protein, a global regulator that controls carbon flow in pseudomonads, has an important role in this inhibition. Crc is a translational repressor that regulates the TOL genes, but how it does this has remained unknown. This study reports that Crc binds to sites located at the translation initiation regions of the mRNAs coding for XylR and XylS, two specific transcription activators of the TOL genes. Unexpectedly, eight additional Crc binding sites were found overlapping the translation initiation sites of genes coding for several enzymes of the pathway, all encoded within two polycistronic mRNAs. Evidence is provided supporting the idea that these sites are functional. This implies that Crc can differentially modulate the expression of particular genes within polycistronic mRNAs. It is proposed that Crc controls TOL genes in two ways. First, Crc inhibits the translation of the XylR and XylS regulators, thereby reducing the transcription of all TOL pathway genes. Second, Crc inhibits the translation of specific structural genes of the pathway, acting mainly on proteins involved in the first steps of toluene assimilation. This ensures a rapid inhibitory response that reduces the expression of the toluene/xylene degradation proteins when preferred carbon sources become available.

  4. Modulation of redox regulatory molecules and electron transport chain activity in muscle of air breathing fish Heteropneustes fossilis under air exposure stress.

    Science.gov (United States)

    Paital, Biswaranjan

    2014-01-01

    Responses of redox regulatory system to long-term survival (>18 h) of the catfish Heteropneustes fossilis in air are not yet understood. Lipid and protein oxidation level, oxidant (H2O2) generation, antioxidative status (levels of superoxide dismutase, catalase, glutathione peroxidase and reductase, ascorbic acid and non-protein sulfhydryl) and activities of respiratory complexes (I, II, III and IV) in mitochondria were investigated in muscle of H. fossilis under air exposure condition (0, 3, 6, 12 and 18 h at 25 °C). The increased levels of both H2O2 and tissue oxidation were observed due to the decreased activities of antioxidant enzymes in muscle under water deprivation condition. However, ascorbic acid and non-protein thiol groups were the highest at 18 h air exposure time. A linear increase in complex II activity with air exposure time and an increase up to 12 h followed by a decrease in activity of complex I at 18 h were observed. Negative correlation was observed for complex III and V activity with exposure time. Critical time to modulate the above parameters was found to be 3 h air exposure. Dehydration induced oxidative stress due to modulation of electron transport chain and redox metabolizing enzymes in muscle of H. fossilis was clearly observed. Possible contribution of redox regulatory system in muscle tissue of the fish for long-term survival in air is elucidated. Results of the present study may be useful to understand the redox metabolism in muscle of fishes those are exposed to air in general and air breathing fishes in particular.

  5. 17 CFR 249.822 - Form 19b-7, for electronic filing with respect to proposed rule changes by self-regulatory...

    Science.gov (United States)

    2010-04-01

    ... filing with respect to proposed rule changes by self-regulatory organizations under Section 19(b)(7)(A... proposed rule changes by self-regulatory organizations under Section 19(b)(7)(A) of the Securities Exchange Act of 1934. This form shall be used by self-regulatory organizations, as defined in section 3(a)(25...

  6. 75 FR 22868 - Withdrawal of Regulatory Guide

    Science.gov (United States)

    2010-04-30

    ...'s public Web site under ``Regulatory Guides'' in the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/doc-collections . Regulatory guides are also available for inspection at the NRC's... NUCLEAR REGULATORY COMMISSION [NRC-2010-0167] Withdrawal of Regulatory Guide AGENCY: Nuclear...

  7. The ERK5 and ERK1/2 signaling pathways play opposing regulatory roles during chondrogenesis of adult human bone marrow-derived multipotent progenitor cells.

    Science.gov (United States)

    Bobick, Brent E; Matsche, Alexander I; Chen, Faye H; Tuan, Rocky S

    2010-07-01

    Adult human bone marrow-derived multipotent progenitor cells (MPCs) are able to differentiate into a variety of specialized cell types, including chondrocytes, and are considered a promising candidate cell source for use in cartilage tissue engineering. In this study, we examined the regulation of MPC chondrogenesis by mitogen-activated protein kinases in an attempt to better understand how to generate hyaline cartilage in the laboratory that more closely resembles native tissue. Specifically, we employed the high-density pellet culture model system to assess the roles of ERK5 and ERK1/2 pathway signaling in MPC chondrogenesis. Western blotting revealed that high levels of ERK5 phosphorylation correlate with low levels of MPC chondrogenesis and that as TGF-beta 3-enhanced MPC chondrogenesis proceeds, phospho-ERK5 levels steadily decline. Conversely, levels of phospho-ERK1/2 paralleled the progression of MPC chondrogenesis. siRNA-mediated knockdown of ERK5 pathway components MEK5 and ERK5 resulted in increased MPC pellet mRNA transcript levels of the cartilage-characteristic marker genes SOX9, COL2A1, AGC, L-SOX5, and SOX6, as well as enhanced accumulation of SOX9 protein, collagen type II protein, and Alcian blue-stainable proteoglycan. In contrast, knockdown of ERK1/2 pathway members MEK1 and ERK1 decreased expression of all chondrogenic markers tested. Finally, overexpression of MEK5 and ERK5 also depressed MPC chondrogenesis, as indicated by diminished activity of a co-transfected collagen II promoter-luciferase reporter construct. In conclusion, our results suggest a novel role for the ERK5 pathway as an important negative regulator of adult human MPC chondrogenesis and illustrate that the ERK5 and ERK1/2 kinase cascades play opposing roles regulating MPC cartilage formation. (c) 2010 Wiley-Liss, Inc.

  8. Prognostic implications of molecular and immunohistochemical profiles of the Rb and p53 cell cycle regulatory pathways in primary non-small cell lung carcinoma.

    LENUS (Irish Health Repository)

    Burke, Louise

    2012-02-03

    PURPOSE: Many studies have highlighted the aberrant expression and prognostic significance of individual proteins in either the Rb (particularly cyclin D1, p16INK4A, and pRb) or the p53 (p53 and p21Waf1) pathways in non-small cell lung cancer. We hypothesize that cumulative abnormalities within each and between these pathways would have significant prognostic potential regarding survival. EXPERIMENTAL DESIGN: Our study population consisted of 106 consecutive surgically resected cases of predominantly early-stage non-small cell lung cancer from the National Cancer Institute-Mayo Clinic series, and assessment of proteins involved both immunohistochemical (cyclin D1, p21Waf1, pRb, p16INK4A, and p53) and mutational analysis (p53) in relationship to staging and survival. RESULTS: Cyclin D1 overexpression was noted in 48% of the tumors, p16INK4A negative in 53%, pRb negative in 17%, p53 immunopositive in 50%, p53 mutation frequency in 48%, and p21(Waf1) overexpression in 47%, none with prognostic significance. Cyclin D1 overexpression in pRb-negative tumors revealed a significantly worse prognosis with a mean survival of 2.3 years (P = 0.004). A simultaneous p53 mutation dramatically reduced the mean survival time to 0.9 years (P = 0.007). Cyclin D1 overexpression with either a p53 mutation or a p53 overexpression was also associated with a significantly poorer prognosis (P = 0.0033 and 0.0063, respectively). CONCLUSIONS: Some cumulative abnormalities in the Rb and p53 pathways (e.g., cyclin D1 overexpression and p53 mutations) significantly cooperate to predict a poor prognosis; however, the complexity of the cell cycle protein interaction in any given tumor warrants caution in interpreting survival results when specific protein abnormalities are taken in isolation.

  9. Regulatory activities

    International Nuclear Information System (INIS)

    2001-01-01

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

  10. A cell cycle-dependent regulatory circuit composed of 53BP1-RIF1 and BRCA1-CtIP controls DNA repair pathway choice.

    Science.gov (United States)

    Escribano-Díaz, Cristina; Orthwein, Alexandre; Fradet-Turcotte, Amélie; Xing, Mengtan; Young, Jordan T F; Tkáč, Ján; Cook, Michael A; Rosebrock, Adam P; Munro, Meagan; Canny, Marella D; Xu, Dongyi; Durocher, Daniel

    2013-03-07

    DNA double-strand break (DSB) repair pathway choice is governed by the opposing activities of 53BP1 and BRCA1. 53BP1 stimulates nonhomologous end joining (NHEJ), whereas BRCA1 promotes end resection and homologous recombination (HR). Here we show that 53BP1 is an inhibitor of BRCA1 accumulation at DSB sites, specifically in the G1 phase of the cell cycle. ATM-dependent phosphorylation of 53BP1 physically recruits RIF1 to DSB sites, and we identify RIF1 as the critical effector of 53BP1 during DSB repair. Remarkably, RIF1 accumulation at DSB sites is strongly antagonized by BRCA1 and its interacting partner CtIP. Lastly, we show that depletion of RIF1 is able to restore end resection and RAD51 loading in BRCA1-depleted cells. This work therefore identifies a cell cycle-regulated circuit, underpinned by RIF1 and BRCA1, that governs DSB repair pathway choice to ensure that NHEJ dominates in G1 and HR is favored from S phase onward. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. The new insight on the regulatory role of the vitamin D3 in metabolic pathways characteristic for cancerogenesis and neurodegenerative diseases.

    Science.gov (United States)

    Kubis, Adriana Maria; Piwowar, Agnieszka

    2015-11-01

    Apart from the classical function of regulating intestinal, bone and kidney calcium and phosphorus absorption as well as bone mineralization, there is growing evidence for the neuroprotective function of vitamin D3 through neuronal calcium regulation, the antioxidative pathway, immunomodulation and detoxification. Vitamin D3 and its derivates influence directly or indirectly almost all metabolic processes such as proliferation, differentiation, apoptosis, inflammatory processes and mutagenesis. Such multifactorial effects of vitamin D3 can be a profitable source of new therapeutic solutions for two radically divergent diseases, cancer and neurodegeneration. Interestingly, an unusual association seems to exist between the occurrence of these two pathological states, called "inverse comorbidity". Patients with cognitive dysfunctions or dementia have considerably lower risk of cancer, whereas survivors of cancer have lower prevalence of central nervous system (CNS) disorders. To our knowledge, there are few publications analyzing the role of vitamin D3 in biological pathways existing in carcinogenic and neuropathological disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. A new pathway for transmembrane electron transfer in photosynthetic reaction centers of Rhodobacter sphaeroides not involving the excited special pair.

    NARCIS (Netherlands)

    van Brederode, M.E.; Jones, M.R.; van Mourik, F.; van Stokkum, I.H.M.; van Grondelle, R.

    1997-01-01

    It is generally accepted that electron transfer in bacterial photosynthesis is driven by the first singlet excited state of a special pair of bacteriochlorophylls (P*). We have examined the first steps of electron transfer in a mutant of the Rhodobacter sphaeroides reaction center in which charge

  13. A new pathway for transmembrane electron transfer in photosyntetic reaction centers of Rhodobacter sphaeroides not involving the excited special pair.

    NARCIS (Netherlands)

    van Brederode, M.E.; Jones, M.R.; van Mourik, F.; van Stokkum, I.H.M.; van Grondelle, R.

    1997-01-01

    It is generally accepted that electron transfer in bacterial photosynthesis is driven by the first singlet excited state of a special pair of bacteriochlorophylls (P*). We have examined the first steps of electron transfer in a mutant of the Rhodobacter sphaeroides reaction center in which charge

  14. Knowledge, workflow and electronic document management in the system of the State Nuclear Regulatory Inspectorate of Ukraine. Preparing the platform development and implementation of the Knowledge Portal

    International Nuclear Information System (INIS)

    Bozhko, S.G.; Shevchenko, Yi.A.; Pecheritsya, O.V.; Singayivs'kij, A.M.

    2016-01-01

    The previous paper considered the creation of the system for management of nuclear knowledge, workflow and electronic documents (hereinafter called the Knowledge Portal) in the field of safe nuclear energy use. It presented initial steps needed to make an informed decision on the feasibility of implementing the Knowledge Portal and proposed methodological approaches based on practical experience of the State Nuclear Regulatory Inspectorate of Ukraine and the SSTC NRS. Further pre - project activities of the state body, local authorities, enterprises, institutions and organizations irrespective of ownership (hereinafter called the Institution) involve the development and drawing attention to the package of analytical, technical and feasibility documents. In particular, it is recommended to take into account the results of analyzing world trends in the development of information technology, audit status information and telecommunication systems (hereinafter - ITS) of the Institution, detailed strategy for the development of ITS Institution (hereinafter - the Strategy), the concept of the Knowledge Portal (hereinafter - the Concept) and preliminary technical solution The results of review and approval of the Concept and architecture solution by scientific and technical council of the Institution is the basis for the preparation of Ter ms of Reference (hereinafter - TOR) on the development of the Knowledge Portal, forming schedules for the procurement of hardware and software, works on the development and implementation of portal solutions and information security systems

  15. Remodeling pathway control of mitochondrial respiratory capacity by temperature in mouse heart: electron flow through the Q-junction in permeabilized fibers.

    Science.gov (United States)

    Lemieux, Hélène; Blier, Pierre U; Gnaiger, Erich

    2017-06-06

    Fuel substrate supply and oxidative phosphorylation are key determinants of muscle performance. Numerous studies of mammalian mitochondria are carried out (i) with substrate supply that limits electron flow, and (ii) far below physiological temperature. To analyze potentially implicated biases, we studied mitochondrial respiratory control in permeabilized mouse myocardial fibers using high-resolution respirometry. The capacity of oxidative phosphorylation at 37 °C was nearly two-fold higher when fueled by physiological substrate combinations reconstituting tricarboxylic acid cycle function, compared with electron flow measured separately through NADH to Complex I or succinate to Complex II. The relative contribution of the NADH pathway to physiological respiratory capacity increased with a decrease in temperature from 37 to 25 °C. The apparent excess capacity of cytochrome c oxidase above physiological pathway capacity increased sharply under hypothermia due to limitation by NADH-linked dehydrogenases. This mechanism of mitochondrial respiratory control in the hypothermic mammalian heart is comparable to the pattern in ectotherm species, pointing towards NADH-linked mt-matrix dehydrogenases and the phosphorylation system rather than electron transfer complexes as the primary drivers of thermal sensitivity at low temperature. Delineating the link between stress and remodeling of oxidative phosphorylation is important for understanding metabolic perturbations in disease evolution and cardiac protection.

  16. Removal efficiency and economic cost comparison of hydrated electron-mediated reductive pathways for treatment of bromate

    DEFF Research Database (Denmark)

    Nawaz, Shah; Shah, Noor S.; Khan, Javed Ali

    2017-01-01

    Bromate, a potential carcinogen, is a well known highly persistent and environmentally recalcitrant contaminant. UV-254/sulfite-based advanced reductive pathways (ARPs) were proposed to eliminate bromate successfully from water. Experiments with N2, N2O, 2-chlorophenol, inorganic ions, and differ...

  17. Regulatory effects of the AMPKα-SIRT1 molecular pathway on insulin resistance in PCOS mice: An in vitro and in vivo study.

    Science.gov (United States)

    Tao, Xin; Chen, Lei; Cai, Lisi; Ge, Shuqi; Deng, Xuanying

    2017-12-16

    In order to preliminarily explore the correlation between the AMPKα-SIRT1 pathway and insulin resistance and reproductive function in PCOS mice and find the pathogenesis molecular mechanism and potential therapeutic target of PCOS, we carried out in vitro study of human granulosa KGN cells and in vivo study of PCOS mouse model which was constructed with DHEA, and AICAR and Compound C were applied. We have found that SIRT1 and AMPKα expression in KGN cells gradually decreased as DHEA concentration increased; Mice of the PCOS model were in an obvious status of IR (P PCOS and may serve as a therapeutic target for the development of potential treatments for improving metabolic and reproductive function in PCOS. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2014-11-01

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

  19. Gene mdpC plays a regulatory role in the methyl-tert-butyl ether degradation pathway of Methylibium petroleiphilum strain PM1.

    Science.gov (United States)

    Joshi, Geetika; Schmidt, Radomir; Scow, Kate M; Denison, Michael S; Hristova, Krassimira R

    2015-04-01

    Among the few bacteria known to utilize methyl tert-butyl ether (MTBE) as a sole carbon source, Methylibium petroleiphilum PM1 is a well-characterized organism with a sequenced genome; however, knowledge of the genetic regulation of its MTBE degradation pathway is limited. We investigated the role of a putative transcriptional activator gene, mdpC, in the induction of MTBE-degradation genes mdpA (encoding MTBE monooxygenase) and mdpJ (encoding tert-butyl alcohol hydroxylase) of strain PM1 in a gene-knockout mutant mdpC(-). We also utilized quantitative reverse transcriptase PCR assays targeting genes mdpA, mdpJ and mdpC to determine the effects of the mutation on transcription of these genes. Our results indicate that gene mdpC is involved in the induction of both mdpA and mdpJ in response to MTBE and tert-butyl alcohol (TBA) exposure in PM1. An additional independent mechanism may be involved in the induction of mdpJ in the presence of TBA. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Downregulation of NF-κB and PCNA in the regulatory pathways of apoptosis by cyclooxygenase-2 inhibitors in experimental lung cancer.

    Science.gov (United States)

    Setia, Shruti; Sanyal, Sankar Nath

    2012-10-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are emerging as novel chemopreventive agents against a variety of cancers owing to their capability in blocking the tumor development by cellular proliferation, angiogenesis and by promoting apoptosis. The present study further explored the comparative role of a traditional NSAID, indomethacin and a newly developed coxib, etoricoxib against 9,10-dimethylbenz(a)anthracene (DMBA)-induced lung carcinogenesis in rats. Morphological and histological analysis revealed the occurrence of tumors and lesions along with constricted alveolar spaces in the DMBA treated animals which were largely corrected both by indomethacin and etoricoxib. COX-1 was found to be uniformly expressed in all the groups while COX-2 levels were raised prominently in the DMBA treated animals. Proliferation, as studied by PCNA expression was found to be markedly increased in the DMBA group as compared to the others. Increased NF-κB expression in the DMBA group was found to correct with the co-administration of NSAIDs. Also, fluorescent co-staining of the isolated lung cells revealed a significantly decreased apoptosis and altered mitochondrial membrane potential. In conclusion, these parameters indicate to the chemopreventive action of the two NSAIDs studied in lung cancer and as their mechanism of action suggests, can be achievable both by COX-dependent and COX-independent pathways.

  1. Fragmentation pathways and structural characterization of organophosphorus compounds related to the Chemical Weapons Convention by electron ionization and electrospray ionization tandem mass spectrometry.

    Science.gov (United States)

    Hosseini, Seyed Esmaeil; Saeidian, Hamid; Amozadeh, Ali; Naseri, Mohammad Taghi; Babri, Mehran

    2016-12-30

    For unambiguous identification of Chemical Weapons Convention (CWC)-related chemicals in environmental samples, the availability of mass spectra, interpretation skills and rapid microsynthesis of suspected chemicals are essential requirements. For the first time, the electron ionization single quadrupole and electrospray ionization tandem mass spectra of a series of O-alkyl N-[bis(dimethylamino)methylidene]-P-methylphosphonamidates (Scheme 1, cpd 4) were studied for CWC verification purposes. O-Alkyl N-[bis(dimethylamino)methylidene]-P-methylphosphonamidates were prepared through a microsynthetic method and were analyzed using electron ionization and electrospray ionization mass spectrometry with gas and liquid chromatography, respectively, as MS-inlet systems. General EI and ESI fragmentation pathways were proposed and discussed, and collision-induced dissociation studies of the protonated derivatives of these compounds were performed to confirm proposed fragment ion structures by analyzing mass spectra of deuterated analogs. Mass spectrometric studies revealed some interesting fragmentation pathways during the ionization process, such as McLafferty rearrangement, hydrogen rearrangement and a previously unknown intramolecular electrophilic aromatic substitution reaction. The EI and ESI fragmentation routes of the synthesized compounds 4 were investigated with the aim of detecting and identifying CWC-related chemicals during on-site inspection and/or off-site analysis and toxic chemical destruction monitoring. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  2. Induction of granzyme B expression in T-cell receptor/CD28-stimulated human regulatory T cells is suppressed by inhibitors of the PI3K-mTOR pathway

    Directory of Open Access Journals (Sweden)

    Kelley Todd W

    2009-11-01

    Full Text Available Abstract Background Regulatory T cells (Tregs can employ a cell contact- and granzyme B-dependent mechanism to mediate suppression of bystander T and B cells. Murine studies indicate that granzyme B is involved in the Treg-mediated suppression of anti-tumor immunity in the tumor microenvironment and in the Treg-mediated maintenance of allograft survival. In spite of its central importance, a detailed study of granzyme B expression patterns in human Tregs has not been performed. Results Our data demonstrated that natural Tregs freshly isolated from the peripheral blood of normal adults lacked granzyme B expression. Tregs subjected to prolonged TCR and CD28 triggering, in the presence of IL-2, expressed high levels of granzyme B but CD3 stimulation alone or IL-2 treatment alone failed to induce granzyme B. Treatment of Tregs with the mammalian target of rapamycin (mTOR inhibitor, rapamycin or the PI3 kinase (PI3K inhibitor LY294002 markedly suppressed granzyme B expression. However, neither rapamycin, as previously reported by others, nor LY294002 inhibited Treg proliferation or induced significant cell death in TCR/CD28/IL-2 stimulated cells. The proliferation rate of Tregs was markedly higher than that of CD4+ conventional T cells in the setting of rapamycin treatment. Tregs expanded by CD3/CD28/IL-2 stimulation without rapamycin demonstrated increased in vitro cytotoxic activity compared to Tregs expanded in the presence of rapamycin in both short term (6 hours and long term (48 hours cytotoxicity assays. Conclusion TCR/CD28 mediated activation of the PI3K-mTOR pathway is important for granyzme B expression but not proliferation in regulatory T cells. These findings may indicate that suppressive mechanisms other than granzyme B are utilized by rapamycin-expanded Tregs.

  3. 75 FR 12804 - Withdrawal of Regulatory Guide 8.6

    Science.gov (United States)

    2010-03-17

    ... ``Regulatory Guides'' in the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/doc-collections... NUCLEAR REGULATORY COMMISSION [NRC-2010-0103] Withdrawal of Regulatory Guide 8.6 AGENCY: Nuclear Regulatory Commission. ACTION: Withdrawal of Regulatory Guide 8.6, ``Standard Test Procedure for Geiger-M...

  4. 76 FR 24539 - Final Regulatory Guide: Issuance, Availability

    Science.gov (United States)

    2011-05-02

    ... site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . Electronic copies... NUCLEAR REGULATORY COMMISSION [NRC-2010-0181] Final Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide...

  5. Electronics

    Science.gov (United States)

    2001-01-01

    International Acer Incorporated, Hsin Chu, Taiwan Aerospace Industrial Development Corporation, Taichung, Taiwan American Institute of Taiwan, Taipei, Taiwan...Singapore and Malaysia .5 - 4 - The largest market for semiconductor products is the high technology consumer electronics industry that consumes up...Singapore, and Malaysia . A new semiconductor facility costs around $3 billion to build and takes about two years to become operational

  6. Global regulatory roles of the cAMP/PKA pathway revealed by phenotypic, transcriptomic and phosphoproteomic analyses in a null mutant of the PKA catalytic subunit in Candida albicans.

    Science.gov (United States)

    Cao, Chengjun; Wu, Mei; Bing, Jian; Tao, Li; Ding, Xuefen; Liu, Xiaoyun; Huang, Guanghua

    2017-07-01

    The conserved cAMP-dependent protein kinase (PKA) plays critical roles in the regulation of morphological transitions and virulence in the human fungal pathogen Candida albicans. It has long been thought that the PKA catalytic subunit is essential for cell viability in this fungus. Paradoxically, the single adenylyl cyclase-encoding gene, CYR1, which is required for the production of cAMP in C. albicans, is not essential for cell growth. Here, a double mutant of TPK1 and TPK2 (tpk2/tpk2 tpk1/tpk1, t2t1), which encode two isoforms of the PKA catalytic subunit was successfully generated, suggesting that this subunit is not essential for cell viability. Inactivation of the PKA catalytic subunit blocked filamentation and dramatically attenuated white-to-opaque switching, but promoted sexual mating. Comparative transcriptomic analyses demonstrated that the t2t1 and cyr1/cyr1 mutants exhibited similar global gene expression profiles. Compared with the WT strain, the general transcriptional activity and metabolism were significantly decreased in both the t2t1 and cyr1/cyr1 mutants. Using combined phosphoproteomic and bioinformatic analyses, we identified 181 potential PKA phosphorylation targets, which represent 148 unique proteins involved in a wide spectrum of biological processes. The study sheds new insights into the global regulatory features of the cAMP/PKA pathway in C. albicans. © 2017 John Wiley & Sons Ltd.

  7. Effective Electron Transfer Pathway of the Ternary TiO2/RGO/Ag Nanocomposite with Enhanced Photocatalytic Activity under Visible Light

    Directory of Open Access Journals (Sweden)

    Hongwei Tian

    2017-05-01

    Full Text Available Mesoporous TiO2/reduced graphene oxide/Ag (TiO2/RGO/Ag ternary nanocomposite with an effective electron transfer pathway is obtained by an electrostatic self-assembly method and photo-assisted treatment. Compared with bare mesoporous TiO2 (MT and mesoporous TiO2/RGO (MTG, the ternary mesoporous TiO2/RGO/Ag (MTGA nanocomposite exhibited superior photocatalytic performance for the degradation of methylene blue (MB under visible light, and the degradation rate reached 0.017 min−1, which was 3.4-times higher than that of MTG. What is more, the degradation rate of MTGA nanocomposite after three cycle times is 91.2%, and the composition is unchanged. In addition, we found that the OH•, h+ and especially O2•− contribute to the high photocatalytic activity of MTGA for MB degradation. It is proposed that Ag nanoparticles can form the local surface plasmon resonance (LSPR to absorb the visible light and distract the electrons into MT, and RGO can accept the electrons from MT to accelerate the separation efficiency of photogenerated carriers. The establishment of MTGA ternary nanocomposite makes the three components act synergistically to enhance the photocatalytic performance.

  8. Effect of high electron donor supply on dissimilatory nitrate reduction pathways in a bioreactor for nitrate removal

    DEFF Research Database (Denmark)

    Behrendt, Anna; Tarre, Sheldon; Beliavski, Michael

    2014-01-01

    The possible shift of a bioreactor for NO3- removal from predominantly denitrification (DEN) to dissimilatory nitrate reduction to ammonium (DNRA) by elevated electron donor supply was investigated. By increasing the C/NO3- ratio in one of two initially identical reactors, the production of high...... sulfide concentrations was induced. The response of the dissimilatory NO3- reduction processes to the increased availability of organic carbon and sulfide was monitored in a batch incubation system. The expected shift from a DEN- towards a DNRA-dominated bioreactor was not observed, also not under...

  9. Competitive fragmentation pathways of acetic acid dimer explored by synchrotron VUV photoionization mass spectrometry and electronic structure calculations

    Science.gov (United States)

    Guan, Jiwen; Hu, Yongjun; Zou, Hao; Cao, Lanlan; Liu, Fuyi; Shan, Xiaobin; Sheng, Liusi

    2012-09-01

    In present study, photoionization and dissociation of acetic acid dimers have been studied with the synchrotron vacuum ultraviolet photoionization mass spectrometry and theoretical calculations. Besides the intense signal corresponding to protonated cluster ions (CH3COOH)n.H+, the feature related to the fragment ions (CH3COOH)H+.COO (105 amu) via β-carbon-carbon bond cleavage is observed. By scanning photoionization efficiency spectra, appearance energies of the fragments (CH3COOH).H+ and (CH3COOH)H+.COO are obtained. With the aid of theoretical calculations, seven fragmentation channels of acetic acid dimer cations were discussed, where five cation isomers of acetic acid dimer are involved. While four of them are found to generate the protonated species, only one of them can dissociate into a C-C bond cleavage product (CH3COOH)H+.COO. After surmounting the methyl hydrogen-transfer barrier 10.84 ± 0.05 eV, the opening of dissociative channel to produce ions (CH3COOH)+ becomes the most competitive path. When photon energy increases to 12.4 eV, we also found dimer cations can be fragmented and generate new cations (CH3COOH).CH3CO+. Kinetics, thermodynamics, and entropy factors for these competitive dissociation pathways are discussed. The present report provides a clear picture of the photoionization and dissociation processes of the acetic acid dimer in the range of the photon energy 9-15 eV.

  10. Pre-silencing of genes involved in the electron transport chain (ETC) pathway is associated with responsiveness to abatacept in rheumatoid arthritis.

    Science.gov (United States)

    Derambure, C; Dzangue-Tchoupou, G; Berard, C; Vergne, N; Hiron, M; D'Agostino, M A; Musette, P; Vittecoq, O; Lequerré, T

    2017-05-25

    In the current context of personalized medicine, one of the major challenges in the management of rheumatoid arthritis (RA) is to identify biomarkers that predict drug responsiveness. From the European APPRAISE trial, our main objective was to identify a gene expression profile associated with responsiveness to abatacept (ABA) + methotrexate (MTX) and to understand the involvement of this signature in the pathophysiology of RA. Whole human genome microarrays (4 × 44 K) were performed from a first subset of 36 patients with RA. Data validation by quantitative reverse-transcription (qRT)-PCR was performed from a second independent subset of 32 patients with RA. Gene Ontology and WikiPathways database allowed us to highlight the specific biological mechanisms involved in predicting response to ABA/MTX. From the first subset of 36 patients with RA, a combination including 87 transcripts allowed almost perfect separation between responders and non-responders to ABA/MTX. Next, the second subset of patients 32 with RA allowed validation by qRT-PCR of a minimal signature with only four genes. This latter signature categorized 81% of patients with RA with 75% sensitivity, 85% specificity and 85% negative predictive value. This combination showed a significant enrichment of genes involved in electron transport chain (ETC) pathways. Seven transcripts from ETC pathways (NDUFA6, NDUFA4, UQCRQ, ATP5J, COX7A2, COX7B, COX6A1) were significantly downregulated in responders versus non-responders to ABA/MTX. Moreover, dysregulation of these genes was independent of inflammation and was specific to ABA response. Pre-silencing of ETC genes is associated with future response to ABA/MTX and might be a crucial key to susceptibility to ABA response.

  11. Photoinduced electron transfer pathways in hydrogen-evolving reduced graphene oxide-boosted hybrid nano-bio catalyst.

    Science.gov (United States)

    Wang, Peng; Dimitrijevic, Nada M; Chang, Angela Y; Schaller, Richard D; Liu, Yuzi; Rajh, Tijana; Rozhkova, Elena A

    2014-08-26

    Photocatalytic production of clean hydrogen fuels using water and sunlight has attracted remarkable attention due to the increasing global energy demand. Natural and synthetic dyes can be utilized to sensitize semiconductors for solar energy transformation using visible light. In this study, reduced graphene oxide (rGO) and a membrane protein bacteriorhodopsin (bR) were employed as building modules to harness visible light by a Pt/TiO2 nanocatalyst. Introduction of the rGO boosts the nano-bio catalyst performance that results in hydrogen production rates of approximately 11.24 mmol of H2 (μmol protein)(-1) h(-1). Photoelectrochemical measurements show a 9-fold increase in photocurrent density when TiO2 electrodes were modified with rGO and bR. Electron paramagnetic resonance and transient absorption spectroscopy demonstrate an interfacial charge transfer from the photoexcited rGO to the semiconductor under visible light.

  12. Competitive fragmentation pathways of acetic acid dimer explored by synchrotron VUV photoionization mass spectrometry and electronic structure calculations.

    Science.gov (United States)

    Guan, Jiwen; Hu, Yongjun; Zou, Hao; Cao, Lanlan; Liu, Fuyi; Shan, Xiaobin; Sheng, Liusi

    2012-09-28

    In present study, photoionization and dissociation of acetic acid dimers have been studied with the synchrotron vacuum ultraviolet photoionization mass spectrometry and theoretical calculations. Besides the intense signal corresponding to protonated cluster ions (CH(3)COOH)(n)·H(+), the feature related to the fragment ions (CH(3)COOH)H(+)·COO (105 amu) via β-carbon-carbon bond cleavage is observed. By scanning photoionization efficiency spectra, appearance energies of the fragments (CH(3)COOH)·H(+) and (CH(3)COOH)H(+)·COO are obtained. With the aid of theoretical calculations, seven fragmentation channels of acetic acid dimer cations were discussed, where five cation isomers of acetic acid dimer are involved. While four of them are found to generate the protonated species, only one of them can dissociate into a C-C bond cleavage product (CH(3)COOH)H(+)·COO. After surmounting the methyl hydrogen-transfer barrier 10.84 ± 0.05 eV, the opening of dissociative channel to produce ions (CH(3)COOH)(+) becomes the most competitive path. When photon energy increases to 12.4 eV, we also found dimer cations can be fragmented and generate new cations (CH(3)COOH)·CH(3)CO(+). Kinetics, thermodynamics, and entropy factors for these competitive dissociation pathways are discussed. The present report provides a clear picture of the photoionization and dissociation processes of the acetic acid dimer in the range of the photon energy 9-15 eV.

  13. Promzea: a pipeline for discovery of co-regulatory motifs in maize and other plant species and its application to the anthocyanin and phlobaphene biosynthetic pathways and the Maize Development Atlas.

    Science.gov (United States)

    Liseron-Monfils, Christophe; Lewis, Tim; Ashlock, Daniel; McNicholas, Paul D; Fauteux, François; Strömvik, Martina; Raizada, Manish N

    2013-03-15

    The discovery of genetic networks and cis-acting DNA motifs underlying their regulation is a major objective of transcriptome studies. The recent release of the maize genome (Zea mays L.) has facilitated in silico searches for regulatory motifs. Several algorithms exist to predict cis-acting elements, but none have been adapted for maize. A benchmark data set was used to evaluate the accuracy of three motif discovery programs: BioProspector, Weeder and MEME. Analysis showed that each motif discovery tool had limited accuracy and appeared to retrieve a distinct set of motifs. Therefore, using the benchmark, statistical filters were optimized to reduce the false discovery ratio, and then remaining motifs from all programs were combined to improve motif prediction. These principles were integrated into a user-friendly pipeline for motif discovery in maize called Promzea, available at http://www.promzea.org and on the Discovery Environment of the iPlant Collaborative website. Promzea was subsequently expanded to include rice and Arabidopsis. Within Promzea, a user enters cDNA sequences or gene IDs; corresponding upstream sequences are retrieved from the maize genome. Predicted motifs are filtered, combined and ranked. Promzea searches the chosen plant genome for genes containing each candidate motif, providing the user with the gene list and corresponding gene annotations. Promzea was validated in silico using a benchmark data set: the Promzea pipeline showed a 22% increase in nucleotide sensitivity compared to the best standalone program tool, Weeder, with equivalent nucleotide specificity. Promzea was also validated by its ability to retrieve the experimentally defined binding sites of transcription factors that regulate the maize anthocyanin and phlobaphene biosynthetic pathways. Promzea predicted additional promoter motifs, and genome-wide motif searches by Promzea identified 127 non-anthocyanin/phlobaphene genes that each contained all five predicted promoter

  14. Regulatory Anatomy

    DEFF Research Database (Denmark)

    Hoeyer, Klaus

    2015-01-01

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

  15. Regulatory Governance

    DEFF Research Database (Denmark)

    Kjær, Poul F.; Vetterlein, Antje

    2018-01-01

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

  16. 75 FR 2894 - Withdrawal of Regulatory Guide 1.148

    Science.gov (United States)

    2010-01-19

    ... downloading through the NRC's public Web site under ``Regulatory Guides'' in the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/doc-collections . Regulatory guides are also available for... NUCLEAR REGULATORY COMMISSION [NRC-2010-0013] Withdrawal of Regulatory Guide 1.148 AGENCY: Nuclear...

  17. 75 FR 70044 - Withdrawal of Regulatory Guide 1.39

    Science.gov (United States)

    2010-11-16

    ... downloading through the NRC's public Web site under ``Regulatory Guides'' in the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/doollectionsc-c . Regulatory guides are also available for... NUCLEAR REGULATORY COMMISSION [NRC-2010-0354] Withdrawal of Regulatory Guide 1.39 AGENCY: Nuclear...

  18. 75 FR 5630 - Draft Regulatory Guide: Issuance, Availability

    Science.gov (United States)

    2010-02-03

    ... ``Regulatory Guides'' collection of the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/doc... NUCLEAR REGULATORY COMMISSION [NRC-2010-0031] Draft Regulatory Guide: Issuance, Availability... Guide, DG-4017. FOR FURTHER INFORMATION CONTACT: Gregory Chapman, U.S. Nuclear Regulatory Commission...

  19. Malate-aspartate shuttle and exogenous NADH/cytochrome c electron transport pathway as two independent cytosolic reducing equivalent transfer systems.

    Science.gov (United States)

    Abbrescia, Daniela Isabel; La Piana, Gianluigi; Lofrumento, Nicola Elio

    2012-02-15

    In mammalian cells aerobic oxidation of glucose requires reducing equivalents produced in glycolytic phase to be channelled into the phosphorylating respiratory chain for the reduction of molecular oxygen. Data never presented before show that the oxidation rate of exogenous NADH supported by the malate-aspartate shuttle system (reconstituted in vitro with isolated liver mitochondria) is comparable to the rate obtained on activation of the cytosolic NADH/cytochrome c electron transport pathway. The activities of these two reducing equivalent transport systems are independent of each other and additive. NADH oxidation induced by the malate-aspartate shuttle is inhibited by aminooxyacetate and by rotenone and/or antimycin A, two inhibitors of the respiratory chain, while the NADH/cytochrome c system remains insensitive to all of them. The two systems may simultaneously or mutually operate in the transfer of reducing equivalents from the cytosol to inside the mitochondria. In previous reports we suggested that the NADH/cytochrome c system is expected to be functioning in apoptotic cells characterized by the presence of cytochrome c in the cytosol. As additional new finding the activity of reconstituted shuttle system is linked to the amount of α-ketoglutarate generated inside the mitochondria by glutamate dehydrogenase rather than by aspartate aminotransferase. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Asymmetric ZnO panel-like hierarchical architectures with highly interconnected pathways for free-electron transport and photovoltaic improvements.

    Science.gov (United States)

    Shi, Yantao; Zhu, Chao; Wang, Lin; Li, Wei; Fung, Kwok Kwong; Wang, Ning

    2013-01-02

    Through a rapid and template-free precipitation approach, we synthesized an asymmetric panel-like ZnO hierarchical architecture (PHA) for photoanodes of dye-sensitized solar cells (DSCs). The two sides of the PHA are constructed differently using densely interconnected, mono-crystalline and ultrathin ZnO nanosheets. By mixing these PHAs with ZnO nanoparticles (NPs), we developed an effective and feasible strategy to improve the electrical transport and photovoltaic performance of the composite photoanodes of DSCs. The highly crystallized and interconnected ZnO nanosheets largely minimized the total grain boundaries within the composite photoanodes and thus served as direct pathways for the transport and effective collection of free electrons. Through low-temperature (200 °C) annealing, these novel composite photoanodes achieved high conversion efficiencies of up to 5.59% for ZnO-based quasi-solid DSCs. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. CCR5 signalling, but not DARC or D6 regulatory, chemokine receptors are targeted by herpesvirus U83A chemokine which delays receptor internalisation via diversion to a caveolin-linked pathway

    Directory of Open Access Journals (Sweden)

    Gompels Ursula A

    2009-07-01

    Full Text Available Abstract Background Herpesviruses have evolved chemokines and chemokine receptors, which modulate the recruitment of human leukocytes during the inflammatory response to infection. Early post-infection, human herpesvirus 6A (HHV-6A infected cells express the chemokine receptor U51A and chemokine U83A which have complementary effects in subverting the CC-chemokine family thereby controlling anti-viral leukocyte recruitment. Here we show that, to potentiate this activity, the viral chemokine can also avoid clearance by scavenger chemokine receptors, DARC and D6, which normally regulate an inflammatory response. Conversely, U83A delays internalisation of its signalling target receptor CCR5 with diversion to caveolin rich membrane domains. This mechanism can redirect displaced human chemokines to DARC and D6 for clearance of the anti-viral inflammatory response, leaving the viral chemokine unchecked. Methods Cell models for competitive binding assays were established using radiolabeled human chemokines and cold U83A on CCR5, DARC or D6 expressing cells. Flow cytometry was used to assess specific chemotaxis of CCR5 bearing cells to U83A, and internalisation of CCR5 specific chemokine CCL4 after stimulation with U83A. Internalisation analyses were supported by confocal microscopy of internalisation and co-localisation of CCR5 with caveosome marker caveolin-1, after virus or human chemokine stimulation. Results U83A displaced efficiently human chemokines from CCR5, with a high affinity of 0.01nM, but not from DARC or D6. Signalling via CCR5 resulted in specific chemoattraction of primary human leukocytes bearing CCR5. However, U83A effective binding and signalling to CCR5 resulted in delayed internalisation and recycling up to 2 hours in the absence of continual re-stimulation. This resulted in diversion to a delayed caveolin-linked pathway rather than the rapid clathrin mediated endocytosis previously shown with human chemokines CCL3 or CCL4

  2. CCR5 signalling, but not DARC or D6 regulatory, chemokine receptors are targeted by herpesvirus U83A chemokine which delays receptor internalisation via diversion to a caveolin-linked pathway.

    Science.gov (United States)

    Catusse, Julie; Clark, David J; Gompels, Ursula A

    2009-07-30

    Herpesviruses have evolved chemokines and chemokine receptors, which modulate the recruitment of human leukocytes during the inflammatory response to infection. Early post-infection, human herpesvirus 6A (HHV-6A) infected cells express the chemokine receptor U51A and chemokine U83A which have complementary effects in subverting the CC-chemokine family thereby controlling anti-viral leukocyte recruitment. Here we show that, to potentiate this activity, the viral chemokine can also avoid clearance by scavenger chemokine receptors, DARC and D6, which normally regulate an inflammatory response. Conversely, U83A delays internalisation of its signalling target receptor CCR5 with diversion to caveolin rich membrane domains. This mechanism can redirect displaced human chemokines to DARC and D6 for clearance of the anti-viral inflammatory response, leaving the viral chemokine unchecked. Cell models for competitive binding assays were established using radiolabeled human chemokines and cold U83A on CCR5, DARC or D6 expressing cells. Flow cytometry was used to assess specific chemotaxis of CCR5 bearing cells to U83A, and internalisation of CCR5 specific chemokine CCL4 after stimulation with U83A. Internalisation analyses were supported by confocal microscopy of internalisation and co-localisation of CCR5 with caveosome marker caveolin-1, after virus or human chemokine stimulation. U83A displaced efficiently human chemokines from CCR5, with a high affinity of 0.01nM, but not from DARC or D6. Signalling via CCR5 resulted in specific chemoattraction of primary human leukocytes bearing CCR5. However, U83A effective binding and signalling to CCR5 resulted in delayed internalisation and recycling up to 2 hours in the absence of continual re-stimulation. This resulted in diversion to a delayed caveolin-linked pathway rather than the rapid clathrin mediated endocytosis previously shown with human chemokines CCL3 or CCL4. U83A diverts human chemokines from signalling, but not

  3. Regulatory Physiology

    Science.gov (United States)

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

    1999-01-01

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

  4. Regulatory Benchmarking

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    2017-01-01

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

  5. Regulatory Benchmarking

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    2017-01-01

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

  6. Catabolic and regulatory systems in Shewanella oneidensis MR-1 involved in electricity generation in microbial fuel cells

    Directory of Open Access Journals (Sweden)

    Atsushi eKouzuma

    2015-06-01

    Full Text Available Shewanella oneidensis MR-1 is a facultative anaerobe that respires using a variety of inorganic and organic compounds. MR-1 is also capable of utilizing extracellular solid materials, including anodes in microbial fuel cells (MFCs, as electron acceptors, thereby enabling electricity generation. As MFCs have the potential to generate electricity from biomass waste and wastewater, MR-1 has been extensively studied to identify the molecular systems that are involved in electricity generation in MFCs. These studies have demonstrated the importance of extracellular electron-transfer pathways that electrically connect the quinone pool in the cytoplasmic membrane to extracellular electron acceptors. Electricity generation is also dependent on intracellular catabolic pathways that oxidize electron donors, such as lactate, and regulatory systems that control the expression of genes encoding the components of catabolic and electron-transfer pathways. In addition, recent findings suggest that cell-surface polymers, e.g., exopolysaccharides, and secreted chemicals, which function as electron shuttles, are also involved in electricity generation. Despite these advances in our knowledge on the extracellular electron-transfer processes in MR-1, further efforts are necessary to fully understand the underlying intra- and extra-cellular molecular systems for electricity generation in MFCs. We suggest that investigating how MR-1 coordinates these systems to efficiently transfer electrons to electrodes and conserve electrochemical energy for cell proliferation is important for establishing the biological bases for MFCs.

  7. redD and actII-ORF4, Pathway-Specific Regulatory Genes for Antibiotic Production in Streptomyces coelicolor A3(2), Are Transcribed In Vitro by an RNA Polymerase Holoenzyme Containing σhrdD

    NARCIS (Netherlands)

    Fujii, T.; Gramajo, H.C.; Takano, E.; Bibb, M.J.

    1996-01-01

    redD and actII-ORF4, regulatory genes required for synthesis of the antibiotics undecylprodigiosin and actinorhodin by Streptomyces coelicolor A3(2), were transcribed in vitro by an RNA polymerase holoenzyme containing σhrdD. Disruption of hrdD had no effect on antibiotic production, indicating that

  8. Changes in activities of both photosystems and the regulatory effect of cyclic electron flow in field-grown cotton (Gossypium hirsutum L) under water deficit.

    Science.gov (United States)

    Yi, Xiao-Ping; Zhang, Ya-Li; Yao, He-Sheng; Han, Ji-Mei; Chow, Wah Soon; Fan, Da-Yong; Zhang, Wang-Feng

    2018-01-01

    To clarify the influence of water deficit on the functionality of the photosynthetic apparatus of cotton plants, leaf gas exchange, chlorophyll a fluorescence, and P700 redox state were examined in field-grown cotton Gossypium hirsutum L. cv. Xinluzao 45. In addition, we measured changes in the P515 signal and analyzed the activity of ATP synthase and the trans-thylakoid proton gradient (ΔpH). With increasing water deficit, the net CO 2 assimilation rate (A N ) and stomatal conductance (g s ) significantly decreased, but the maximum quantum efficiency of PSII photochemistry (F v /F m ) did not change. The photochemical activity of photosystem II (PSII) was reflected by the photochemical quenching coefficient (qP), quantum efficiency of photosystem II [Y(II)], and electron transport rate through PSII [ETR(II)], while the activity of photosystem I (PSI) was reflected by the quantum efficiency of photosystem I [Y(I)] and the electron transport rate through PSI [ETR(I)]. Both activities were maintained under mild water deficit, but were slightly decreased under moderate water deficit. Under moderate water deficit, cyclic electron flow (CEF), the fraction of absorbed light dissipated thermally via the ΔpH- and xanthophyll-regulated process [Y(NPQ)], and the fraction of P700 oxidized under a given set of conditions [Y(ND)] increased. Our results suggest that the activities of both photosystems are stable under mild water deficit and decrease only slightly under moderate water deficit. Moderate water deficit stimulates CEF, and the stimulation of CEF is essential for protecting PSI and PSII against photoinhibition. Copyright © 2017 Elsevier GmbH. All rights reserved.

  9. Migration pathways in soils

    International Nuclear Information System (INIS)

    Gronow, J.R.

    1986-01-01

    This study looked at diffusive migration through three types of deformation; the projectile pathways, hydraulic fractures of the sediments and faults, and was divided into three experimental areas: autoradiography, the determination of diffusion coefficients and electron microscopy of model projectile pathways in clay. For the autoradiography, unstressed samples were exposed to two separate isotopes, Pm-147 (a possible model for Am behaviour) and the poorly sorbed iodide-125. The results indicated that there was no enhanced migration through deformed kaolin samples nor through fractured Great Meteor East (GME) sediment, although some was evident through the projectile pathways in GME and possibly through the GME sheared samples. The scanning electron microscopy of projectile pathways in clay showed that emplacement of a projectile appeared to have no effect on the orientation of particles at distances greater than two projectile radii from the centre of a projectile pathway. It showed that the particles were not simply aligned with the direction of motion of the projectile but that, the closer to the surface of a particular pathway, the closer the particles lay to their original orientation. This finding was of interest from two points of view: i) the ease of migration of a pollutant along the pathway, and ii) possible mechanisms of hole closure. It was concluded that, provided that there is no advective migration, the transport of radionuclides through sediments containing these defects would not be significantly more rapid than in undeformed sediments. (author)

  10. 75 FR 28073 - Draft Regulatory Guide: Issuance, Availability

    Science.gov (United States)

    2010-05-19

    ... ``Regulatory Guides'' collection of the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/doc... NUCLEAR REGULATORY COMMISSION [NRC-2010-0181] Draft Regulatory Guide: Issuance, Availability... Guide, DG-3039, ``Standard Format and Content for Emergency Plans for Fuel Cycle and Materials...

  11. 75 FR 45166 - Draft Regulatory Guide: Issuance, Availability

    Science.gov (United States)

    2010-08-02

    ... ``Regulatory Guides'' collection of the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/doc... NUCLEAR REGULATORY COMMISSION [NRC-2010-0265] Draft Regulatory Guide: Issuance, Availability... Guide, DG-3030, ``Nuclear Criticality Safety Standards for Fuels and Material Facilities.'' [[Page 45167...

  12. 75 FR 62893 - Draft Regulatory Guide: Issuance, Availability

    Science.gov (United States)

    2010-10-13

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

  13. 75 FR 58444 - Draft Regulatory Guide: Issuance, Availability

    Science.gov (United States)

    2010-09-24

    ... ``Regulatory Guides'' collection of the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/doc... NUCLEAR REGULATORY COMMISSION [NRC-2010-0305] Draft Regulatory Guide: Issuance, Availability... Guide, DG-1244, ``Availability of Electric Power Sources.'' FOR FURTHER INFORMATION CONTACT: Satish...

  14. 75 FR 29785 - Draft Regulatory Guide: Issuance, Availability

    Science.gov (United States)

    2010-05-27

    ... ``Regulatory Guides'' collection of the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/doc... NUCLEAR REGULATORY COMMISSION [NRC-2010-0187] Draft Regulatory Guide: Issuance, Availability... Guide, DG-1248, ``Nuclear Power Plant Simulation Facilities for Use in Operator Training, License...

  15. Electronic identity

    CERN Document Server

    de Andrade, Norberto Nuno Gomes; Argles, David

    2014-01-01

    With the increasing availability of electronic services, security and a reliable means by which identity is verified is essential.Written by Norberto Andrade the first chapter of this book provides an overview of the main legal and regulatory aspects regarding electronic identity in Europe and assesses the importance of electronic identity for administration (public), business (private) and, above all, citizens. It also highlights the role of eID as a key enabler of the economy.In the second chapter Lisha Chen-Wilson, David Argles, Michele Schiano di Zenise and Gary Wills discuss the user-cent

  16. Dexter energy transfer pathways.

    Science.gov (United States)

    Skourtis, Spiros S; Liu, Chaoren; Antoniou, Panayiotis; Virshup, Aaron M; Beratan, David N

    2016-07-19

    Energy transfer with an associated spin change of the donor and acceptor, Dexter energy transfer, is critically important in solar energy harvesting assemblies, damage protection schemes of photobiology, and organometallic opto-electronic materials. Dexter transfer between chemically linked donors and acceptors is bridge mediated, presenting an enticing analogy with bridge-mediated electron and hole transfer. However, Dexter coupling pathways must convey both an electron and a hole from donor to acceptor, and this adds considerable richness to the mediation process. We dissect the bridge-mediated Dexter coupling mechanisms and formulate a theory for triplet energy transfer coupling pathways. Virtual donor-acceptor charge-transfer exciton intermediates dominate at shorter distances or higher tunneling energy gaps, whereas virtual intermediates with an electron and a hole both on the bridge (virtual bridge excitons) dominate for longer distances or lower energy gaps. The effects of virtual bridge excitons were neglected in earlier treatments. The two-particle pathway framework developed here shows how Dexter energy-transfer rates depend on donor, bridge, and acceptor energetics, as well as on orbital symmetry and quantum interference among pathways.

  17. Imaging ultrafast excited state pathways in transition metal complexes by X-ray transient absorption and scattering using X-ray free electron laser source

    DEFF Research Database (Denmark)

    Chen, Lin X; Shelby, Megan L; Lestrange, Patrick J

    2016-01-01

    This report will describe our recent studies of transition metal complex structural dynamics on the fs and ps time scales using an X-ray free electron laser source, Linac Coherent Light Source (LCLS). Ultrafast XANES spectra at the Ni K-edge of nickel(ii) tetramesitylporphyrin (NiTMP) were measured...... on the low-energy shoulder of the edge, which is aided by the computation of X-ray transitions for postulated excited electronic states. The observed and computed inner shell to valence orbital transition energies demonstrate and quantify the influence of the electronic configuration on specific metal...

  18. As to achieve regulatory action, regulatory approaches

    International Nuclear Information System (INIS)

    Cid, R.; Encinas, D.

    2014-01-01

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

  19. Expression of Wnt/β-Catenin Signaling Pathway and Its Regulatory Role in Type I Collagen with TGF-β1 in Scleral Fibroblasts from an Experimentally Induced Myopia Guinea Pig Model

    Directory of Open Access Journals (Sweden)

    Min Li

    2016-01-01

    Full Text Available Background. To investigate Wnt/β-catenin signaling pathway expression and its regulation of type I collagen by TGF-β1 in scleral fibroblasts from form-deprivation myopia (FDM guinea pig model. Methods. Wnt isoforms were examined using genome microarrays. Scleral fibroblasts from FDM group and self-control (SC group were cultured. Wnt isoforms, β-catenin, TGF-β1, and type I collagen expression levels were examined in the two groups with or without DKK-1 or TGF-β1 neutralizing antibody. Results. For genome microarrays, the expression of Wnt3 in FDM group was significantly greater as confirmed in retinal and scleral tissue. The expression of Wnt3 and β-catenin significantly increased in FDM group and decreased significantly with DKK-1. TGF-β1 expression level decreased significantly in FDM group and increased significantly with DKK-1. Along with morphological misalignment inside and outside cells, the amount of type I collagen decreased in FDM group. Furthermore, type I collagen increased and became regular in DKK-1 intervention group, whereas it decreased and rearranged more disorder in TGF-β1 neutralizing antibody intervention group. Conclusions. The activation of Wnt3/β-catenin signaling pathway was demonstrated in primary scleral fibroblasts in FDM. This pathway further reduced the expression of type I collagen by TGF-β1, which ultimately played a role in scleral remodeling during myopia development.

  20. Accelerators: radiation safety and regulatory compliance

    International Nuclear Information System (INIS)

    Bandyopadhyay, Tapas

    2013-01-01

    Growth of accelerators, both positive ions and electron, is very high in India. This may be because of the wide acceptance of these machines in the industrial purposes, medical uses, material science studies, upcoming ADSS facility and many other reasons. Most of cases for societal uses, accelerators have to be installed in the dense public domain. Accelerators for basic research and development purposes to be installed may in public domain or in isolated site. These accelerators are to be classified into different categories in terms of regulatory compliance. Radiation shield design, HVAC system required to be in place with design so that the dose and effluent discharge in the public domain is within a limit considering different pathways. INDUS I and II at Indore, K-130 and K500 machine at VECC, Pelletron at TIFR, IUAC, BARC, EBC at Mumbai are in operation. Apart from this accelerators, a series of medical accelerators in operation and yet to be operational which are generally producing PET isotopes for the diagnosis purposes. VECC is aiming to operate 30 MeV proton machine with about 500 μA beam current for the production of PET, SPECT isotopes for diagnosis purposes and also therapeutic use in near future. Detail requirement in terms of choice of sites, source term estimation for achieving optimum shield thickness, ventilation system, site layout and planning , radioactive effluent handling both gaseous and liquid, decommission aspects will be discussed. (author)

  1. Response of Chloroplast NAD(PH Dehydrogenase-Mediated Cyclic Electron Flow to a Shortage or Lack in Ferredoxin-Quinone Oxidoreductase-Dependent Pathway in Rice Following Short-Term Heat Stress

    Directory of Open Access Journals (Sweden)

    Jemaa eEssemine

    2016-03-01

    Full Text Available Cyclic electron flow around PSI can protect photosynthetic electron carriers under conditions of stromal over-reduction. The goal of the research reported in this paper was to investigate the responses of both PSI and PSII to a short-term heat stress in two rice lines with different capacities of cyclic electron transfer, i.e. Q4149 with a high capacity (hcef and C4023 with a low capacity (lcef. The absorbance change at 820 nm (ΔA820 was used here to assess the charge separation in the photosystem I (PSI reaction center (P700. The results obtained show that short-term heat stress abolishes the FQR-dependent CEF in rice and accelerates the initial rate of P700+ re-reduction. The P700+ amplitude was slightly increased at a moderate heat-stress (35°C because of a partial restriction of FQR but it was decreased following high heat-stress (42°C. Assessment of PSI and PSII activities shows that PSI is more susceptible to heat stress than photosystem II (PSII. Under high temperature, FQR-dependent CEF was completely removed and NDH-dependent CEF was up-regulated and strengthened to a higher extent in C4023 than in Q4149. Specifically, under normal growth temperature, hcef (Q4149 was characterized by higher FQR- and NDH-dependent CEF rates than lcef (C4023. Following thermal stress, the activation of NDH-pathway was 130% and 10% for C4023 and Q4149, respectively. Thus, the NDH-dependent CEF may constitute the second layer of plant protection and defence against heat stress after the main route, i.e. FQR-dependent CEF, reaches its capacity. We discuss the possibility that under high heat stress, the NDH pathway serves as a safety valve to dissipate excess energy by cyclic photophosphorylation and overcome the stroma over-reduction following inhibition of CO2 assimilation and any shortage or lack in the FQR pathway. The potential role of the NDH-dependent pathway during the evolution of C4 photosynthesis is briefly discussed.

  2. The Proline Regulatory Axis and Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Phang, James Ming; Liu, Wei; Hancock, Chad; Christian, Kyle J., E-mail: phangj@mail.nih.gov [Metabolism and Cancer Susceptibility Section, Basic Research Laboratory, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, MD (United States)

    2012-06-21

    Studies in metabolism and cancer have characterized changes in core pathways involving glucose and glutamine, emphasizing the provision of substrates for building cell mass. But recent findings suggest that pathways previously considered peripheral may play a critical role providing mechanisms for cell regulation. Several of these mechanisms involve the metabolism of non-essential amino acids, for example, the channeling of glycolytic intermediates into the serine pathway for one-carbon transfers. Historically, we proposed that the proline biosynthetic pathway participated in a metabolic interlock with glucose metabolism. The discovery that proline degradation is activated by p53 directed our attention to the initiation of apoptosis by proline oxidase/dehydrogenase. Now, however, we find that the biosynthetic mechanisms and the metabolic interlock may depend on the pathway from glutamine to proline, and it is markedly activated by the oncogene MYC. These findings add a new dimension to the proline regulatory axis in cancer and present attractive potential targets for cancer treatment.

  3. Functional pyruvate formate lyase pathway expressed with two different electron donors in Saccharomyces cerevisiae at aerobic growth

    DEFF Research Database (Denmark)

    Zhang, Yiming; Dai, Zongjie; Krivoruchko, Anastasia

    2015-01-01

    pyruvate decarboxylase and having a reduced glucose uptake rate due to a mutation in the transcriptional regulator Mth1, IMI076 (Pdc-MTH1-ΔT ura3-52). PFL was expressed with two different electron donors, reduced ferredoxin or reduced flavodoxin, respectively, and it was found that the coexpression...

  4. Modularized Smad-regulated TGFβ signaling pathway.

    Science.gov (United States)

    Li, Yongfeng; Wang, Minli; Carra, Claudio; Cucinotta, Francis A

    2012-12-01

    The transforming Growth Factor β (TGFβ) signaling pathway is a prominent regulatory signaling pathway controlling various important cellular processes. TGFβ signaling can be induced by several factors including ionizing radiation. The pathway is regulated in a negative feedback loop through promoting the nuclear import of the regulatory Smads and a subsequent expression of inhibitory Smad7, that forms ubiquitin ligase with Smurf2, targeting active TGFβ receptors for degradation. In this work, we proposed a mathematical model to study the Smad-regulated TGFβ signaling pathway. By modularization, we are able to analyze mathematically each component subsystem and recover the nonlinear dynamics of the entire network system. Meanwhile the excitability, a common feature observed in the biological systems, in the TGFβ signaling pathway is discussed and supported as well by numerical simulation, indicating the robustness of the model. Published by Elsevier Inc.

  5. Professional and Regulatory Search

    Science.gov (United States)

    Professional and Regulatory search are designed for people who use EPA web resources to do their job. You will be searching collections where information that is not relevant to Environmental and Regulatory professionals.

  6. Future nuclear regulatory challenges

    International Nuclear Information System (INIS)

    Royen, J.

    1998-01-01

    In December 1996, the NEA Committee on Nuclear Regulatory Activities concluded that changes resulting from economic deregulation and other recent developments affecting nuclear power programmes have consequences both for licensees and regulatory authorities. A number of potential problems and issues which will present a challenge to nuclear regulatory bodies over the next ten years have been identified in a report just released. (author)

  7. Dealing with chemical reaction pathways and electronic excitations in molecular systems via renormalized and active-space coupled-cluster methods

    Energy Technology Data Exchange (ETDEWEB)

    Piecuch, Piotr; Li, Wei; Lutz, Jesse J. [Department of Chemistry, Michigan State University, East Lansing, MI 48824 (United States); Włoch, Marta [Department of Chemistry, Michigan Technological University, Houghton, Michigan 49931 (United States); Gour, Jeffrey R. [Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA and Department of Chemistry, Stanford University, Stanford, California 94305 (United States)

    2015-01-22

    Coupled-cluster (CC) theory has become the de facto standard for high-accuracy molecular calculations, but the widely used CC and equation-of-motion (EOM) CC approaches, such as CCSD(T) and EOMCCSD, have difficulties with capturing stronger electron correlations that characterize multi-reference molecular problems. This presentation demonstrates that many of these difficulties can be addressed by exploiting the completely renormalized (CR) CC and EOMCC approaches, such as CR-CC(2,3), CR-EOMCCSD(T), and CR-EOMCC(2,3), and their local correlation counterparts applicable to systems with hundreds of atoms, and the active-space CC/EOMCC approaches, such as CCSDt and EOMCCSDt, and their extensions to valence systems via the electron-attached and ionized formalisms.

  8. A wild 'albino' bilberry (Vaccinium myrtillus L. from Slovenia shows three bottlenecks in the anthocyanin pathway and significant differences in the expression of several regulatory genes compared to the common blue berry type.

    Directory of Open Access Journals (Sweden)

    Zala Zorenc

    Full Text Available Relative expressions of structural genes and a number of transcription factors of the anthocyanin pathway relevant in Vaccinium species, and related key enzyme activities were compared with the composition and content of metabolites in skins of ripe fruits of wild albino and blue bilberry (Vaccinium myrtillus found in Slovenia. Compared to the common blue type, the albino variant had a 151-fold lower total anthocyanin and a 7-fold lower total phenolic content in their berry skin, which correlated with lower gene expression of flavonoid 3-O-glycosyltransferase (FGT; 33-fold, flavanone 3-hydroxylase (FHT; 18-fold, anthocyanidin synthase (ANS; 11-fold, chalcone synthase (CHS, 7.6-fold and MYBPA1 transcription factor (22-fold. The expression of chalcone isomerase (CHI, dihydroflavonol 4-reductase (DFR, leucoanthocyanidin reductase (LAR, anthocyanidin reductase (ANR and MYBC2 transcription factor was reduced only by a factor of 1.5-2 in the albino berry skins, while MYBR3 and flavonoid 3',5'-hydroxylase (F3'5'H were increased to a similar extent. Expression of the SQUAMOSA class transcription factor TDR4, in contrast, was independent of the color type and does therefore not seem to be correlated with anthocyanin formation in this variant. At the level of enzymes, significantly lower FHT and DFR activities, but not of phenylalanine ammonia-lyase (PAL and CHS/CHI, were observed in the fruit skins of albino bilberries. A strong increase in relative hydroxycinnamic acid derivative concentrations indicates the presence of an additional bottleneck in the general phenylpropanoid pathway at a so far unknown step between PAL and CHS.

  9. Identification and Characterization of Components of the Mitotic Spindle Checkpoint Pathway in Fission Yeast

    National Research Council Canada - National Science Library

    Kadura, Shelia

    2001-01-01

    .... The fission yeast, Schizosaccharomyces pombe, is a useful system for discovering and characterizing components of this regulatory pathway because genetic approaches can be coupled with excellent cytology...

  10. Regulatory activities; Actividades regulatorias

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-07-01

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

  11. Improving the hydrogen production capacity of Rhodobacter capsulatus by genetically modifying redox balancing pathways

    Energy Technology Data Exchange (ETDEWEB)

    Oeztuerk, Yavuz [TUEBITAK Research Institute for Genetic Engineering and Biotechnology, Gebze Kocaeli (Turkey); Goekce, Abdulmecit [Istanbul Technical Univ. (Turkey). Dept. of Molecular Biology and Genetics; Guergan, Muazzez; Yuecel, Meral [Middle East Technical Univ., Ankara (Turkey). Dept. of Biology

    2010-07-01

    In Rhodobacter capsulatus, balancing the oxidation-reduction potential (redox-balance) is maintained via a number of inter-dependent regulatory mechanisms that enable these organisms to accommodate divergent growth modes. In order to maintain redox homeostasis, this bacterium possesses regulatory mechanisms functioning as electron sinks affecting the oxidation-reduction state of the ubiquinone pool. Under the photoheterotrophic growth conditions with reduced carbon sources, the excess reducing equivalents are primarily consumed via the reduction of CO{sub 2} through the Calvin-Benson-Bassham (CBB) pathway or by the reduction of protons into hydrogen with the use of dinitrogenase enzyme system. In this study, our aim was to develop strategies to funnel the excess reducing equivalents to nitrogenase-dependent hydrogen production by blocking the carbon-fixation pathway. To realize this purpose, CO{sub 2} fixation was blocked by inactivating the Phosphoribulokinase (PRK) of CBB pathway in wild type (MT1131), uptake-hydrogenase (YO3) and cyt cbb{sub 3} oxidase deficient (YO4) strains. The hydrogen production capacity of newly generated strains deficient in the Calvin-Benson-Bassham pathway were analyzed and compared with wild type strains. The results indicated that, the hydrogen production efficiency and capacity of R. capsulatus was further improved by directing the excess reducing equivalents to dinitrogenase-dependent hydrogen production. (orig.)

  12. RMOD: a tool for regulatory motif detection in signaling network.

    Directory of Open Access Journals (Sweden)

    Jinki Kim

    Full Text Available Regulatory motifs are patterns of activation and inhibition that appear repeatedly in various signaling networks and that show specific regulatory properties. However, the network structures of regulatory motifs are highly diverse and complex, rendering their identification difficult. Here, we present a RMOD, a web-based system for the identification of regulatory motifs and their properties in signaling networks. RMOD finds various network structures of regulatory motifs by compressing the signaling network and detecting the compressed forms of regulatory motifs. To apply it into a large-scale signaling network, it adopts a new subgraph search algorithm using a novel data structure called path-tree, which is a tree structure composed of isomorphic graphs of query regulatory motifs. This algorithm was evaluated using various sizes of signaling networks generated from the integration of various human signaling pathways and it showed that the speed and scalability of this algorithm outperforms those of other algorithms. RMOD includes interactive analysis and auxiliary tools that make it possible to manipulate the whole processes from building signaling network and query regulatory motifs to analyzing regulatory motifs with graphical illustration and summarized descriptions. As a result, RMOD provides an integrated view of the regulatory motifs and mechanism underlying their regulatory motif activities within the signaling network. RMOD is freely accessible online at the following URL: http://pks.kaist.ac.kr/rmod.

  13. Transcriptional regulatory programs underlying barley germination and regulatory functions of Gibberellin and abscisic acid

    Science.gov (United States)

    2011-01-01

    Background Seed germination is a complex multi-stage developmental process, and mainly accomplished through concerted activities of many gene products and biological pathways that are often subjected to strict developmental regulation. Gibberellins (GA) and abscisic acid (ABA) are two key phytohormones regulating seed germination and seedling growth. However, transcriptional regulatory networks underlying seed germination and its associated biological pathways are largely unknown. Results The studies examined transcriptomes of barley representing six distinct and well characterized germination stages and revealed that the transcriptional regulatory program underlying barley germination was composed of early, late, and post-germination phases. Each phase was accompanied with transcriptional up-regulation of distinct biological pathways. Cell wall synthesis and regulatory components including transcription factors, signaling and post-translational modification components were specifically and transiently up-regulated in early germination phase while histone families and many metabolic pathways were up-regulated in late germination phase. Photosynthesis and seed reserve mobilization pathways were up-regulated in post-germination phase. However, stress related pathways and seed storage proteins were suppressed through the entire course of germination. A set of genes were transiently up-regulated within three hours of imbibition, and might play roles in initiating biological pathways involved in seed germination. However, highly abundant transcripts in dry barley and Arabidopsis seeds were significantly conserved. Comparison with transcriptomes of barley aleurone in response to GA and ABA identified three sets of germination responsive genes that were regulated coordinately by GA, antagonistically by ABA, and coordinately by GA but antagonistically by ABA. Major CHO metabolism, cell wall degradation and protein degradation pathways were up-regulated by both GA and seed

  14. Transcriptional regulatory programs underlying barley germination and regulatory functions of Gibberellin and abscisic acid

    Directory of Open Access Journals (Sweden)

    Lin Li

    2011-06-01

    Full Text Available Abstract Background Seed germination is a complex multi-stage developmental process, and mainly accomplished through concerted activities of many gene products and biological pathways that are often subjected to strict developmental regulation. Gibberellins (GA and abscisic acid (ABA are two key phytohormones regulating seed germination and seedling growth. However, transcriptional regulatory networks underlying seed germination and its associated biological pathways are largely unknown. Results The studies examined transcriptomes of barley representing six distinct and well characterized germination stages and revealed that the transcriptional regulatory program underlying barley germination was composed of early, late, and post-germination phases. Each phase was accompanied with transcriptional up-regulation of distinct biological pathways. Cell wall synthesis and regulatory components including transcription factors, signaling and post-translational modification components were specifically and transiently up-regulated in early germination phase while histone families and many metabolic pathways were up-regulated in late germination phase. Photosynthesis and seed reserve mobilization pathways were up-regulated in post-germination phase. However, stress related pathways and seed storage proteins were suppressed through the entire course of germination. A set of genes were transiently up-regulated within three hours of imbibition, and might play roles in initiating biological pathways involved in seed germination. However, highly abundant transcripts in dry barley and Arabidopsis seeds were significantly conserved. Comparison with transcriptomes of barley aleurone in response to GA and ABA identified three sets of germination responsive genes that were regulated coordinately by GA, antagonistically by ABA, and coordinately by GA but antagonistically by ABA. Major CHO metabolism, cell wall degradation and protein degradation pathways were up

  15. Minimal metabolic pathway structure is consistent with associated biomolecular interactions

    DEFF Research Database (Denmark)

    Bordbar, Aarash; Nagarajan, Harish; Lewis, Nathan E.

    2014-01-01

    Pathways are a universal paradigm for functionally describing cellular processes. Even though advances in high-throughput data generation have transformed biology, the core of our biological understanding, and hence data interpretation, is still predicated on human-defined pathways. Here, we......, effectively doubling the known regulatory roles for Nac and MntR. This study suggests an underlying and fundamental principle in the evolutionary selection of pathway structures; namely, that pathways may be minimal, independent, and segregated....

  16. Interleukin-2 and STAT5 in regulatory T cell development and function

    OpenAIRE

    Mahmud, Shawn A.; Manlove, Luke S.; Farrar, Michael A.

    2013-01-01

    Interleukin-2 and its downstream target STAT5 have effects on many aspects of immune function. This has been perhaps best documented in regulatory T cells. In this review we summarize the initial findings supporting a role for IL2 and STAT5 in regulatory T cell development and outline more recent studies describing how this critical signaling pathway entrains regulatory T cell differentiation and affects regulatory T cell function.

  17. Modularized TGFbeta-Smad Signaling Pathway

    Science.gov (United States)

    Li, Yongfeng; Wang, M.; Carra, C.; Cucinotta, F. A.

    2011-01-01

    The Transforming Growth Factor beta (TGFbeta) signaling pathway is a prominent regulatory signaling pathway controlling various important cellular processes. It can be induced by several factors, including ionizing radiation. It is regulated by Smads in a negative feedback loop through promoting increases in the regulatory Smads in the cell nucleus, and subsequent expression of inhibitory Smad, Smad7 to form a ubiquitin ligase with Smurf targeting active TGF receptors for degradation. In this work, we proposed a mathematical model to study the radiation-induced Smad-regulated TGF signaling pathway. By modularization, we are able to analyze each module (subsystem) and recover the nonlinear dynamics of the entire network system. Meanwhile the excitability, a common feature observed in the biological systems, along the TGF signaling pathway is discussed by mathematical analysis and numerical simulation.

  18. Robustness and accuracy in sea urchin developmental gene regulatory networks

    Directory of Open Access Journals (Sweden)

    Smadar eBen-Tabou De-Leon

    2016-02-01

    Full Text Available Developmental gene regulatory networks robustly control the timely activation of regulatory and differentiation genes. The structure of these networks underlies their capacity to buffer intrinsic and extrinsic noise and maintain embryonic morphology. Here I illustrate how the use of specific architectures by the sea urchin developmental regulatory networks enables the robust control of cell fate decisions. The Wnt-βcatenin signaling pathway patterns the primary embryonic axis while the BMP signaling pathway patterns the secondary embryonic axis in the sea urchin embryo and across bilateria. Interestingly, in the sea urchin in both cases, the signaling pathway that defines the axis controls directly the expression of a set of downstream regulatory genes. I propose that this direct activation of a set of regulatory genes enables a uniform regulatory response and a clear cut cell fate decision in the endoderm and in the dorsal ectoderm. The specification of the mesodermal pigment cell lineage is activated by Delta signaling that initiates a triple positive feedback loop that locks down the pigment specification state. I propose that the use of compound positive feedback circuitry provides the endodermal cells enough time to turn off mesodermal genes and ensures correct mesoderm vs. endoderm fate decision. Thus, I argue that understanding the control properties of repeatedly used regulatory architectures illuminates their role in embryogenesis and provides possible explanations to their resistance to evolutionary change.

  19. Research and regulatory review

    International Nuclear Information System (INIS)

    Macleod, J.S.; Fryer, D.R.H.

    1979-01-01

    To enable the regulatory review to be effectively undertaken by the regulatory body, there is a need for it to have ready access to information generated by research activities. Certain advantages have been seen to be gained by the regulatory body itself directly allocating and controlling some portion of these activities. The princial reasons for reaching this conclusion are summarised and a brief description of the Inspectorates directly sponsored programme outlined. (author)

  20. A Wnt1 regulated Frizzled-1/β-Catenin signaling pathway as a candidate regulatory circuit controlling mesencephalic dopaminergic neuron-astrocyte crosstalk: Therapeutical relevance for neuron survival and neuroprotection

    Directory of Open Access Journals (Sweden)

    Pluchino Stefano

    2011-07-01

    Full Text Available Abstract Background Dopamine-synthesizing (dopaminergic, DA neurons in the ventral midbrain (VM constitute a pivotal neuronal population controlling motor behaviors, cognitive and affective brain functions, which generation critically relies on the activation of Wingless-type MMTV integration site (Wnt/β-catenin pathway in their progenitors. In Parkinson's disease, DA cell bodies within the substantia nigra pars compacta (SNpc progressively degenerate, with causes and mechanisms poorly understood. Emerging evidence suggests that Wnt signaling via Frizzled (Fzd receptors may play a role in different degenerative states, but little is known about Wnt signaling in the adult midbrain. Using in vitro and in vivo model systems of DA degeneration, along with functional studies in both intact and SN lesioned mice, we herein highlight an intrinsic Wnt1/Fzd-1/β-catenin tone critically contributing to the survival and protection of adult midbrain DA neurons. Results In vitro experiments identifie Fzd-1 receptor expression at a mRNA and protein levels in dopamine transporter (DAT expressing neurons, and demonstrate the ability of exogenous Wnt1 to exert robust neuroprotective effects against Caspase-3 activation, the loss of tyrosine hydroxylase-positive (TH+ neurons and [3H] dopamine uptake induced by different DA-specific insults, including serum and growth factor deprivation, 6-hydroxydopamine and MPTP/MPP+. Co-culture of DA neurons with midbrain astrocytes phenocopies Wnt1 neuroprotective effects, whereas RNA interference-mediated knockdown of Wnt1 in midbrain astrocytes markedly reduces astrocyte-induced TH+ neuroprotection. Likewise, silencing β-catenin mRNA or knocking down Fzd-1 receptor expression in mesencephalic neurons counteract astrocyte-induced TH+ neuroprotection. In vivo experiments document Fzd-1 co-localization with TH+ neurons within the intact SNpc and blockade of Fzd/β-catenin signaling by unilateral infusion of a Fzd

  1. Sorafenib targets the mitochondrial electron transport chain complexes and ATP synthase to activate the PINK1-Parkin pathway and modulate cellular drug response.

    Science.gov (United States)

    Zhang, Conggang; Liu, Zeyu; Bunker, Eric; Ramirez, Adrian; Lee, Schuyler; Peng, Yinghua; Tan, Aik-Choon; Eckhardt, S Gail; Chapnick, Douglas A; Liu, Xuedong

    2017-09-08

    Sorafenib (Nexavar) is a broad-spectrum multikinase inhibitor that proves effective in treating advanced renal-cell carcinoma and liver cancer. Despite its well-characterized mechanism of action on several established cancer-related protein kinases, sorafenib causes variable responses among human tumors, although the cause for this variation is unknown. In an unbiased screening of an oncology drug library, we found that sorafenib activates recruitment of the ubiquitin E3 ligase Parkin to damaged mitochondria. We show that sorafenib inhibits the activity of both complex II/III of the electron transport chain and ATP synthase. Dual inhibition of these complexes, but not inhibition of each individual complex, stabilizes the serine-threonine protein kinase PINK1 on the mitochondrial outer membrane and activates Parkin. Unlike the protonophore carbonyl cyanide m -chlorophenylhydrazone, which activates the mitophagy response, sorafenib treatment triggers PINK1/Parkin-dependent cellular apoptosis, which is attenuated upon Bcl-2 overexpression. In summary, our results reveal a new mechanism of action for sorafenib as a mitocan and suggest that high Parkin activity levels could make tumor cells more sensitive to sorafenib's actions, providing one possible explanation why Parkin may be a tumor suppressor gene. These insights could be useful in developing new rationally designed combination therapies with sorafenib. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. Regulatory Commission of Alaska

    Science.gov (United States)

    Map Help Regulatory Commission of Alaska Login Forgot Password Arrow Image Forgot password? View Cart login Procedures for Requesting Login For Consumers General Information Telephone Electric Natural Gas

  3. New Pathways for Alimentary Mucositis

    Directory of Open Access Journals (Sweden)

    Joanne M. Bowen

    2008-01-01

    Full Text Available Alimentary mucositis is a major dose-limiting toxicity associated with anticancer treatment. It is responsible for reducing patient quality of life and represents a significant economic burden in oncology. The pathobiology of alimentary mucositis is extremely complex, and an increased understanding of mechanisms and pathway interactions is required to rationally design improved therapies. This review describes the latest advances in defining mechanisms of alimentary mucositis pathobiology in the context of pathway activation. It focuses particularly on the recent genome-wide analyses of regimen-related mucosal injury and the identification of specific regulatory pathways implicated in mucositis development. This review also discusses the currently known alimentary mucositis risk factors and the development of novel treatments. Suggestions for future research directions have been raised.

  4. 75 FR 33853 - Draft Regulatory Guide: Issuance, Availability

    Science.gov (United States)

    2010-06-15

    .... Introduction The U.S. Nuclear Regulatory Commission (NRC) is issuing for public comment a draft guide in the... provides text and image files of NRC's public documents. If you do not have access to ADAMS or if there are... ADAMS Accession Number ML100760364. The regulatory analysis is available electronically under ADAMS...

  5. 76 FR 2425 - Draft Regulatory Guide: Reissuance and Availability

    Science.gov (United States)

    2011-01-13

    ... INFORMATION: I. Introduction The U.S. Nuclear Regulatory Commission (NRC) is issuing for public comment a..., the public can gain entry into ADAMS, which provides text and image files of NRC's public [email protected] . The Regulatory Analysis is available electronically under ADAMS Accession Number...

  6. 76 FR 32878 - Draft Regulatory Guide: Issuance, Availability

    Science.gov (United States)

    2011-06-07

    ...: Mekonen [email protected] . SUPPLEMENTARY INFORMATION: I. Introduction The U.S. Nuclear Regulatory..., the public can gain entry into ADAMS, which provides text and image files of the NRC's [email protected] . The Regulatory Analysis is available electronically under ADAMS Accession Number...

  7. 76 FR 5215 - Draft Regulatory Guide: Issuance, Availability

    Science.gov (United States)

    2011-01-28

    ... . SUPPLEMENTARY INFORMATION: I. Introduction The U.S. Nuclear Regulatory Commission (NRC) is issuing for public... . From this page, the public can gain entry into ADAMS, which provides text and image files of NRC's... [email protected] . The Regulatory Analysis is available electronically under ADAMS Accession...

  8. Pathways to man

    International Nuclear Information System (INIS)

    Harley, J.H.

    1980-01-01

    The study of radionuclide pathways leading to man generally has the goal of allowing us to predict human exposure from measurements of the radionuclide concentration in some segment of the environment. This modelling process provides a valuable tool in both the regulatory and health protection fields. However, most of the models in the regulatory field and in the health physics profession were designed to maximize exposure estimates. It is preferable to have scientifically defensible estimates and to add suitable safety factors at the end. Thus we are still faced with the development and validation of suitable models for many of the radionuclides of interest. The most useful models will include means of assessing variability and uncertainty. In this case variability might be considered as the differences in behavior due to age, sex or other factors in animals or man and those differences among plant species or animal species that determine their uptake factors. The uncertainty, on the other hand, would be the estimate of possible error in the experimental measurements. Model parameters would always have some variability even for site-specific cases and broad averages for population groups would have to include a factor expressing the possible variabilty and uncertainity. Thus any exposure calculation would have to be expressed with some range and valid assessments of this range are required

  9. Interfacial reaction pathways and kinetics during annealing of 111-textured Al/TiN bilayers: A synchrotron x-ray diffraction and transmission electron microscopy study

    International Nuclear Information System (INIS)

    Chun, J.-S.; Desjardins, P.; Lavoie, C.; Petrov, I.; Cabral, C. Jr.; Greene, J. E.

    2001-01-01

    Growth of TiN layers in most diffusion-barrier applications is limited to deposition temperatures T s s =450 deg. C on SiO 2 by ultrahigh vacuum reactive magnetron sputter deposition in pure N 2 . Al overlayers, 160 nm thick with inherited 111 preferred orientation, were then deposited at T s =100 deg. C without breaking vacuum. The as-deposited TiN layer is underdense due to the low deposition temperature (T s /T m ≅0.23 in which T m is the melting point) resulting in kinetically limited adatom mobilities leading to atomic shadowing which, in turn, results in a columnar microstructure with both inter- and intracolumnar voids. The Al overlayer is fully dense. Synchrotron x-ray diffraction was used to follow interfacial reaction kinetics during postdeposition annealing of the 111-textured Al/TiN bilayers as a function of time (t a =12-1200 s) and temperature (T a =440-550 deg. C). Changes in bilayer microstructure and microchemistry were investigated using transmission electron microscopy (TEM) and scanning TEM to obtain compositional maps of plan-view and cross-sectional specimens. Interfacial reaction during annealing is initiated at the Al/TiN interface. Al diffuses rapidly into TiN voids during anneals at temperatures ∼ 3 Ti at the interface. Al 3 Ti exhibits a relatively planar growth front extending toward the Al free surface. Analyses of time-dependent x-ray diffraction peak intensities during isothermal annealing as a function of temperature show that Al 3 Ti growth kinetics are, for the entire temperature range investigated, diffusion limited with an activation energy of 1.5±0.2 eV

  10. Liquid pathways generic studies; results, interpretation, and design implications

    International Nuclear Information System (INIS)

    Walker, D.H.; Nutant, J.A.

    1980-01-01

    Offshore Power Systems and the Nuclear Regulatory Commission have evaluated dose consequences resulting from a release of radioactivity to liquid pathways following a postulated core-melt accident. The objective of these studies was to compare the risks from postulated core-melt accidents for the Floating Nuclear Plant with those for a typical land-based nuclear plant. Offshore Power Systems concluded that the differences in liquid pathway risks between plant types are not significant when compared with the air pathways risks. Air pathways risk is similar to or significantly larger than liquid pathways risk depending on the accident scenario. The Nuclear Regulatory Commission judged the liquid pathways risks from the Floating Nuclear Plant to be significantly greater than the liquid pathway risks for the typical land-based plant. Although OPS disagrees with the NRC judgment, design changes dictated by the NRC are being implemented by OPS

  11. Molecular Pathways

    Science.gov (United States)

    Lok, Benjamin H.; Powell, Simon N.

    2012-01-01

    The Rad52 protein was largely ignored in humans and other mammals when the mouse knockout revealed a largely “no-effect” phenotype. However, using synthetic lethal approaches to investigate context dependent function, new studies have shown that Rad52 plays a key survival role in cells lacking the function of the BRCA1-BRCA2 pathway of homologous recombination. Biochemical studies also showed significant differences between yeast and human Rad52, in which yeast Rad52 can promote strand invasion of RPA-coated single-stranded DNA in the presence of Rad51, but human Rad52 cannot. This results in the paradox of how is human Rad52 providing Rad51 function: presumably there is something missing in the biochemical assays that exists in-vivo, but the nature of this missing factor is currently unknown. Recent studies have suggested that Rad52 provides back-up Rad51 function for all members of the BRCA1-BRCA2 pathway, suggesting that Rad52 may be a target for therapy in BRCA pathway deficient cancers. Screening for ways to inhibit Rad52 would potentially provide a complementary strategy for targeting BRCA-deficient cancers in addition to PARP inhibitors. PMID:23071261

  12. NRC Regulatory Agenda

    International Nuclear Information System (INIS)

    1991-10-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considering action, and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  13. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1993-04-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considering action, and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  14. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1990-01-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has proposed or is considering action and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  15. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1991-04-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action or has proposed, or is considering action and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  16. NRC Regulatory Agenda

    International Nuclear Information System (INIS)

    1991-08-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action or has proposed, or is considering action and all petitions for rulemaking which have been received by the commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  17. Trust in regulatory regimes

    NARCIS (Netherlands)

    Six, Frédérique; Verhoest, Koen

    2017-01-01

    Within political and administrative sciences generally, trust as a concept is contested, especially in the field of regulatory governance. This groundbreaking book is the first to systematically explore the role and dynamics of trust within regulatory regimes. Conceptualizing, mapping and analyzing

  18. Nuclear Regulatory legislation

    International Nuclear Information System (INIS)

    1984-06-01

    This compilation of statutes and material pertaining to nuclear regulatory legislation through the 97th Congress, 2nd Session, has been prepared by the Office of the Executive Legal Director, U.S. Nuclear Regulatory Commission, with the assistance of staff, for use as an internal resource document

  19. Improving nuclear regulatory effectiveness

    International Nuclear Information System (INIS)

    2001-01-01

    Ensuring that nuclear installations are operated and maintained in such a way that their impact on public health and safety is as low as reasonably practicable has been and will continue to be the cornerstone of nuclear regulation. In the past, nuclear incidents provided the main impetus for regulatory change. Today, economic factors, deregulation, technological advancements, government oversight and the general requirements for openness and accountability are leading regulatory bodies to review their effectiveness. In addition, seeking to enhance the present level of nuclear safety by continuously improving the effectiveness of regulatory bodies is seen as one of the ways to strengthen public confidence in the regulatory systems. This report covers the basic concepts underlying nuclear regulatory effectiveness, advances being made and future requirements. The intended audience is primarily nuclear safety regulators, but government authorities, nuclear power plant operators and the general public may also be interested. (author)

  20. 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

  1. Preliminary Assessment of the Flow of Used Electronics, In ...

    Science.gov (United States)

    Electronic waste (e-waste) is the largest growing municipal waste stream in the United States. The improper disposal of e-waste has environmental, economic, and social impacts, thus there is a need for sustainable stewardship of electronics. EPA/ORD has been working to improve our understanding of the quantity and flow of electronic devices from initial purchase to final disposition. Understanding the pathways of used electronics from the consumer to their final disposition would provide insight to decision makers about their impacts and support efforts to encourage improvements in policy, technology, and beneficial use. This report is the first stage of study of EPA/ORD's efforts to understand the flows of used electronics and e-waste by reviewing the regulatory programs for the selected states and identifying the key lessons learned and best practices that have emerged since their inception. Additionally, a proof-of-concept e-waste flow model has been developed to provide estimates of the quantity of e-waste generated annually at the national level, as well as for selected states. This report documents a preliminary assessment of available data and development of the model that can be used as a starting point to estimate domestic flows of used electronics from generation, to collection and reuse, to final disposition. The electronics waste flow model can estimate the amount of electronic products entering the EOL management phase based on unit sales dat

  2. Managing Regulatory Body Competence

    International Nuclear Information System (INIS)

    2013-01-01

    In 2001, the IAEA published TECDOC 1254, which examined the way in which the recognized functions of a regulatory body for nuclear facilities results in competence needs. Using the systematic approach to training (SAT), TECDOC 1254 provided a framework for regulatory bodies for managing training and developing and their maintaining their competence. It has been successfully used by many regulators. The IAEA has also introduced a methodology and an assessment tool - Guidelines for Systematic Assessment of Regulatory Competence Needs (SARCoN) - which provides practical guidance on analysing the training and development needs of a regulatory body and, through a gap analysis, guidance on establishing competence needs and how to meet them. In 2009, the IAEA established a steering committee (supported by a bureau) with the mission to advise the IAEA on how it could best assist Member States to develop suitable competence management systems for their regulatory bodies. The committee recommended the development of a safety report on managing staff competence as an integral part of a regulatory body's management system. This Safety Report was developed in response to this request. It supersedes TECDOC 1254, broadens its application to regulatory bodies for all facilities and activities, and builds upon the experience gained through the application of TECDOC 1254 and SARCoN and the feedback received from Member States. This Safety Report applies to the management of adequate competence as needs change, and as such is equally applicable to the needs of States 'embarking' on a nuclear power programme. It also deals with the special case of building up the competence of regulatory bodies as part of the overall process of establishing an 'embarking' State's regulatory system

  3. Establishing exemption and clearance criteria by the regulatory authority

    International Nuclear Information System (INIS)

    Salih, A.E.A.

    2012-04-01

    This Project work discusses the relationship between the concepts of exemption and clearance, and their practical use in the overall scheme of regulatory control of practices. It also discusses how exemptions and clearance is established and the scope of its applications for regulatory control. The concept of general clearance levels for any type of material and any possible pathway of disposal is also introduced in this work. Guidance of the Group of Experts establishing scenarios for general clearance, parameter values, and a nuclide-specific list of calculated clearance levels is also presented. Regulatory authorities are required to develop guidance on exemption and clearance levels to assist licensees and registrants to know which practices and sources within practices are exempted from regulatory control and those to be cleared from further controls. Exemption and clearance levels are tools for assisting the Regulatory Authority to optimize the use of resources. (author)

  4. Cell volume homeostatic mechanisms: effectors and signalling pathways

    DEFF Research Database (Denmark)

    Hoffmann, E K; Pedersen, Stine Helene Falsig

    2011-01-01

    . Later work addressed the mechanisms through which cellular signalling pathways regulate the volume regulatory effectors or flux pathways. These studies were facilitated by the molecular identification of most of the relevant channels and transporters, and more recently also by the increased...

  5. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1990-10-01

    The Regulatory Agenda is a quarterly compilation of all rules on which the NRC has recently completed action or has proposed, or is considering action and of all petitions for rulemaking that the NRC has received that are pending disposition

  6. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1990-04-01

    The Regulatory Agenda is a quarterly compilation of all rules on which the NRC has recently completed action or has proposed, or is considering action and of all petitions for rulemaking that the NRC has received that are pending disposition

  7. Through the regulatory hoop

    International Nuclear Information System (INIS)

    Kirner, N.P.

    1985-01-01

    There are many regulatory hoops through which waste generators, brokers, and disposal site operators must jump to dispose of waste safely. As the proposed exclusionary date of January 1, 1986, approaches, these regulatory hoops have the distinct possibility of multiplying or at least changing shape. The state of Washington, in its role as an Agreement State with the US Nuclear Regulatory Commission, licenses and inspects the commercial operator of the Northwest Compact's low-level radioactive waste disposal site on the Hanford Reservation. Washington has received as much as 53%, or 1.4 million cubic feet per year, of the nation's total volume of waste disposed. To control such a large volume of waste, a regulatory program involving six agencies has developed over the years in Washington

  8. Perceptions of regulatory approaches

    International Nuclear Information System (INIS)

    Halin, Magnus; Leinonen, Ruusaliisa

    2012-01-01

    Ms. Ruusaliisa Leinonen and Mr. Magnus Halin from Fortum gave a joint presentation on industry perceptions of regulatory oversight of LMfS/SC. It was concluded that an open culture of discussion exists between the regulator (STUK) and the licensee, based on the common goal of nuclear safety. An example was provided of on how regulatory interventions helped foster improvements to individual and collective dose rate trends, which had remained static. Regulatory interventions included discussions on the ALARA concept to reinforce the requirement to continuously strive for improvements in safety performance. Safety culture has also been built into regulatory inspections in recent years. Training days have also been organised by the regulatory body to help develop a shared understanding of safety culture between licensee and regulatory personnel. Fortum has also developed their own training for managers and supervisors. Training and ongoing discussion on LMfS/SC safety culture is considered particularly important because both Fortum and the regulatory body are experiencing an influx of new staff due to the demographic profile of their organisations. It was noted that further work is needed to reach a common understanding of safety culture on a practical level (e.g., for a mechanic setting to work), and in relation to the inspection criteria used by the regulator. The challenges associated with companies with a mix of energy types were also discussed. This can make it more difficult to understand responsibilities and decision making processes, including the role of the parent body organisation. It also makes communication more challenging due to increased complexity and a larger number of stakeholders

  9. 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)

  10. 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)

  11. Cleanup standards and pathways analysis methods

    International Nuclear Information System (INIS)

    Devgun, J.S.

    1993-01-01

    Remediation of a radioactively contaminated site requires that certain regulatory criteria be met before the site can be released for unrestricted future use. Since the ultimate objective of remediation is to protect the public health and safety, residual radioactivity levels remaining at a site after cleanup must be below certain preset limits or meet acceptable dose or risk criteria. Release of a decontaminated site requires proof that the radiological data obtained from the site meet the regulatory criteria for such a release. Typically release criteria consist of a composite of acceptance limits that depend on the radionuclides, the media in which they are present, and federal and local regulations. In recent years, the US Department of Energy (DOE) has developed a pathways analysis model to determine site-specific soil activity concentration guidelines for radionuclides that do not have established generic acceptance limits. The DOE pathways analysis computer code (developed by Argonne National Laboratory for the DOE) is called RESRAD (Gilbert et al. 1989). Similar efforts have been initiated by the US Nuclear Regulatory Commission (NRC) to develop and use dose-related criteria based on genetic pathways analyses rather than simplistic numerical limits on residual radioactivity. The focus of this paper is radionuclide contaminated soil. Cleanup standards are reviewed, pathways analysis methods are described, and an example is presented in which RESRAD was used to derive cleanup guidelines

  12. Unusual Synthetic Pathway for an {Fe(NO)2}9 Dinitrosyl Iron Complex (DNIC) and Insight into DNIC Electronic Structure via Nuclear Resonance Vibrational Spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Speelman, Amy L.; Zhang, Bo; Silakov, Alexey; Skodje, Kelsey M.; Alp, E. Ercan; Zhao, Jiyong; Hu, Michael Y.; Kim, Eunsuk; Krebs, Karsten; Lehnert, Nicolai

    2016-06-06

    Dinitrosyl iron complexes (DNICs) are among the most abundant NO-derived cellular species. Monomeric DNICs can exist in the {Fe(NO)2}9 or {Fe(NO)2}10 oxidation state (in the Enemark -Feltham notation). However, experimental studies of analogous DNICs in both oxidation states are rare, which prevents a thorough understanding of the di ff erences in the electronic structures of these species. Here, the {Fe(NO)2}9 DNIC [Fe(dmp)(NO)2](OTf) ( 1 ; dmp = 2,9-dimethyl-1,10- phenanthroline) is synthesized from a ferrous precursor via an unusual pathway, involving disproportionation of an {FeNO}7 complex to yield the {Fe(NO)2}9 DNIC and a ferric species, which is subsequently reduced by NO gas to generate a ferrous complex that re-enters the reaction cycle. In contrast to most {Fe(NO)2}9 DNICs with neutral N-donor ligands, 1 exhibits high solution stability and can be characterized structurally and spectroscopically. Reduction of 1 yields the corresponding {Fe(NO)2}10 DNIC [Fe(dmp)(NO)2](2). The Mo ssbauer isomer shift of 2 is 0.08 mm/s smaller than that of 1 , which indicates that the iron center is slightly more oxidized in the reduced complex. The nuclear resonance vibrational spectra (NRVS) of 1 and 2 are distinct and provide direct experimental insight into di ff erences in bonding in these complexes. In particular, the symmetric out-of-plane Fe -N - O bending mode is shifted to higher energy by 188 cm-1 in 2 in comparison to 1 . Using quantum chemistry centered normal coordinate analysis (QCC-NCA), this is shown to arise from an increase in Fe - NO bond order and a sti ff ening of the Fe(NO)2 unit upon reduction of 1 to 2 . DFT calculations demonstrate that the changes in bonding arise from an iron- centered reduction which leads to a distinct increase in Fe - NO π -back-bonding in

  13. CONSTRUCTION AND ANALYSIS OF IPBR/XYLS HYBRID REGULATORY PROTEINS

    Science.gov (United States)

    IpbR and XylS are related regulatory proteins (having 56% identity). IpbR responds to isopropylbenzene as well as to a variety of hydrophobic chemicals to activate expression of the isopropylbenzene catabolic pathway operon of pRE4 from ipbOP. XylS responds to substituted benzoic...

  14. Transcriptome profiling reveals regulatory mechanisms underlying Corolla Senescence in Petunia

    Science.gov (United States)

    Genetic regulatory mechanisms that govern petal natural senescence in petunia is complicated and unclear. To identify key genes and pathways that regulate the process, we initiated a transcriptome analysis in petunia petals at four developmental time points, including petal opening without anthesis ...

  15. Gene regulatory and signaling networks exhibit distinct topological distributions of motifs

    Science.gov (United States)

    Ferreira, Gustavo Rodrigues; Nakaya, Helder Imoto; Costa, Luciano da Fontoura

    2018-04-01

    The biological processes of cellular decision making and differentiation involve a plethora of signaling pathways and gene regulatory circuits. These networks in turn exhibit a multitude of motifs playing crucial parts in regulating network activity. Here we compare the topological placement of motifs in gene regulatory and signaling networks and observe that it suggests different evolutionary strategies in motif distribution for distinct cellular subnetworks.

  16. Nuclear Regulatory Legislation

    International Nuclear Information System (INIS)

    1989-08-01

    This compilation of statutes and material pertaining to nuclear regulatory legislation through the 100th Congress, 2nd Session, has been prepared by the Office of the General Counsel, US Nuclear Regulatory Commission, with the assistance of staff, for use as an internal resource document. Persons using this document are placed on notice that it may not be used as an authoritative citation in lieu of the primary legislative sources. Furthermore, while every effort has been made to ensure the completeness and accuracy of this material, neither the United States Government, the Nuclear Regulatory Commission, nor any of their employees makes any expressed or implied warranty or assumes liability for the accuracy or completeness of the material presented in this compilation

  17. Regulatory and licensee surveys

    International Nuclear Information System (INIS)

    2009-01-01

    Prior to the workshop two CSNI/WGHOF surveys were distributed. One survey was directed at regulatory bodies and the other was directed at plant licensees. The surveys were: 1 - Regulatory Expectations of Licensees' Arrangements to Ensure Suitable Organisational Structure, Resources and Competencies to Manage Safety (sent to WGHOF regulatory members). The survey requested that the respondents provide a brief overview of the situation related to plant organisations in their country, their regulatory expectations and their formal requirements. The survey addressed three subjects: the demonstration and documentation of organisational structures, resources and competencies, organisational changes, issues for improvement (for both current and new plants). Responses were received from eleven regulatory bodies. 2 - Approaches to Justify Organisational Suitability (sent to selected licensees). The purpose of the survey to was to gain an understanding of how licensees ensure organisational suitability, resources and competencies. This information was used to assist in the development of the issues and subjects that were addressed at the group discussion sessions. Responses were received from over fifteen licensees from nine countries. The survey requested that the licensees provide information on how they ensure effective organisational structures at their plants. The survey grouped the questions into the following four categories: organisational safety functions, resource and competence, decision-making and communication, good examples and improvement needs. The findings from these surveys were used in conjunction with other factors to identify the key issues for the workshop discussion sessions. The responses from these two surveys are discussed briefly in Sections 4 and 5 of this report. More extensive reviews of the regulatory and licensee responses are provided in Appendix 1

  18. 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...

  19. Rationales for regulatory activity

    Energy Technology Data Exchange (ETDEWEB)

    Perhac, R.M. [Univ. of Tennessee, Knoxville, TN (United States)

    1997-02-01

    The author provides an outline which touches on the types of concerns about risk evaluation which are addressed in the process of establishing regulatory guides. Broadly he says regulatory activity serves three broad constituents: (1) Paternalism (private risk); (2) Promotion of social welfare (public risks); (3) Protection of individual rights (public risks). He then discusses some of the major issues encountered in reaching a decision on what is an acceptable level of risk within each of these areas, and how one establishes such a level.

  20. Codes and standards and other guidance cited in regulatory documents

    International Nuclear Information System (INIS)

    Nickolaus, J.R.; Bohlander, K.L.

    1996-08-01

    As part of the U.S. Nuclear Regulatory Commission (NRC) Standard Review Plan Update and Development Program (SRP-UDP), Pacific Northwest National Laboratory developed a listing of industry consensus codes and standards and other government and industry guidance referred to in regulatory documents. The SRP-UDP has been completed and the SRP-Maintenance Program (SRP-MP) is now maintaining this listing. Besides updating previous information, Revision 3 adds approximately 80 citations. This listing identifies the version of the code or standard cited in the regulatory document, the regulatory document, and the current version of the code or standard. It also provides a summary characterization of the nature of the citation. This listing was developed from electronic searches of the Code of Federal Regulations and the NRC's Bulletins, Information Notices, Circulars, Enforcement Manual, Generic Letters, Inspection Manual, Policy Statements, Regulatory Guides, Standard Technical Specifications and the Standard Review Plan (NUREG-0800)

  1. Codes and standards and other guidance cited in regulatory documents

    Energy Technology Data Exchange (ETDEWEB)

    Nickolaus, J.R.; Bohlander, K.L.

    1996-08-01

    As part of the U.S. Nuclear Regulatory Commission (NRC) Standard Review Plan Update and Development Program (SRP-UDP), Pacific Northwest National Laboratory developed a listing of industry consensus codes and standards and other government and industry guidance referred to in regulatory documents. The SRP-UDP has been completed and the SRP-Maintenance Program (SRP-MP) is now maintaining this listing. Besides updating previous information, Revision 3 adds approximately 80 citations. This listing identifies the version of the code or standard cited in the regulatory document, the regulatory document, and the current version of the code or standard. It also provides a summary characterization of the nature of the citation. This listing was developed from electronic searches of the Code of Federal Regulations and the NRC`s Bulletins, Information Notices, Circulars, Enforcement Manual, Generic Letters, Inspection Manual, Policy Statements, Regulatory Guides, Standard Technical Specifications and the Standard Review Plan (NUREG-0800).

  2. Developing regulatory approaches

    International Nuclear Information System (INIS)

    Axelsson, Lars

    2012-01-01

    Lars Axelsson presented SSM progress on oversight of LMfS/SC since the Chester 1 Workshop in 2007. Current SSM approaches for safety culture oversight include targeted safety management and safety culture inspections, compliance inspections which cover aspects of safety management/safety culture and multi-disciplinary team inspections. Examples of themes for targeted inspections include management of ambiguous operational situations or other weak signals, understanding of and attitudes to Human Performance tools, the Safety Department's role and authority and Leadership for safety. All regulatory activities provide inputs for the SSM yearly safety evaluation of each licensee. A form has been developed to capture safety culture observations from inspections and other interactions with licensees. Analysis will be performed to identify patterns and provide information to support planning of specific Safety Culture activities. Training has been developed for regulatory staff to enhance the quality of regulatory interventions on safety culture. This includes a half-day seminar to provide an overview of safety culture, and a workshop which provides more in-depth discussion on cultural issues and how to capture those during regulatory activities. Future plans include guidance for inspectors, and informal seminars on safety culture with licensees

  3. NRC Regulatory Agenda

    International Nuclear Information System (INIS)

    1992-07-01

    This document compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considering action, and all petitions for rule making which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  4. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1993-02-01

    This document is a compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considered action, and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  5. NRC Regulatory Agenda

    International Nuclear Information System (INIS)

    1989-07-01

    This document is a compilation of all rules on which the NRC has proposed or is considering action and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  6. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1992-11-01

    This document provides a compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considering action, and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter

  7. Comments on regulatory reform

    International Nuclear Information System (INIS)

    Hendrie, J.M.

    1982-01-01

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

  8. Comments on regulatory reform

    Energy Technology Data Exchange (ETDEWEB)

    Hendrie, J.M.

    1982-01-01

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

  9. 3 CFR - Regulatory Review

    Science.gov (United States)

    2010-01-01

    ... as a means of promoting regulatory goals. The fundamental principles and structures governing... review. In this time of fundamental transformation, that process—and the principles governing regulation... the Office of Management and Budget (OMB) has reviewed Federal regulations. The purposes of such...

  10. A Regulatory Network Analysis of Orphan Genes in Arabidopsis Thaliana

    Science.gov (United States)

    Singh, Pramesh; Chen, Tianlong; Arendsee, Zebulun; Wurtele, Eve S.; Bassler, Kevin E.

    Orphan genes, which are genes unique to each particular species, have recently drawn significant attention for their potential usefulness for organismal robustness. Their origin and regulatory interaction patterns remain largely undiscovered. Recently, methods that use the context likelihood of relatedness to infer a network followed by modularity maximizing community detection algorithms on the inferred network to find the functional structure of regulatory networks were shown to be effective. We apply improved versions of these methods to gene expression data from Arabidopsis thaliana, identify groups (clusters) of interacting genes with related patterns of expression and analyze the structure within those groups. Focusing on clusters that contain orphan genes, we compare the identified clusters to gene ontology (GO) terms, regulons, and pathway designations and analyze their hierarchical structure. We predict new regulatory interactions and unravel the structure of the regulatory interaction patterns of orphan genes. Work supported by the NSF through Grants DMR-1507371 and IOS-1546858.

  11. Pathway Distiller - multisource biological pathway consolidation.

    Science.gov (United States)

    Doderer, Mark S; Anguiano, Zachry; Suresh, Uthra; Dashnamoorthy, Ravi; Bishop, Alexander J R; Chen, Yidong

    2012-01-01

    One method to understand and evaluate an experiment that produces a large set of genes, such as a gene expression microarray analysis, is to identify overrepresentation or enrichment for biological pathways. Because pathways are able to functionally describe the set of genes, much effort has been made to collect curated biological pathways into publicly accessible databases. When combining disparate databases, highly related or redundant pathways exist, making their consolidation into pathway concepts essential. This will facilitate unbiased, comprehensive yet streamlined analysis of experiments that result in large gene sets. After gene set enrichment finds representative pathways for large gene sets, pathways are consolidated into representative pathway concepts. Three complementary, but different methods of pathway consolidation are explored. Enrichment Consolidation combines the set of the pathways enriched for the signature gene list through iterative combining of enriched pathways with other pathways with similar signature gene sets; Weighted Consolidation utilizes a Protein-Protein Interaction network based gene-weighting approach that finds clusters of both enriched and non-enriched pathways limited to the experiments' resultant gene list; and finally the de novo Consolidation method uses several measurements of pathway similarity, that finds static pathway clusters independent of any given experiment. We demonstrate that the three consolidation methods provide unified yet different functional insights of a resultant gene set derived from a genome-wide profiling experiment. Results from the methods are presented, demonstrating their applications in biological studies and comparing with a pathway web-based framework that also combines several pathway databases. Additionally a web-based consolidation framework that encompasses all three methods discussed in this paper, Pathway Distiller (http://cbbiweb.uthscsa.edu/PathwayDistiller), is established to allow

  12. Allorecognition pathways in transplant rejection and tolerance.

    Science.gov (United States)

    Ali, Jason M; Bolton, Eleanor M; Bradley, J Andrew; Pettigrew, Gavin J

    2013-10-27

    With the advent of cellular therapies, it has become clear that the success of future therapies in prolonging allograft survival will require an intimate understanding of the allorecognition pathways and effector mechanisms that are responsible for chronic rejection and late graft loss.Here, we consider current understanding of T-cell allorecognition pathways and discuss the most likely mechanisms by which these pathways collaborate with other effector mechanisms to cause allograft rejection. We also consider how this knowledge may inform development of future strategies to prevent allograft rejection.Although both direct and indirect pathway CD4 T cells appear active immediately after transplantation, it has emerged that indirect pathway CD4 T cells are likely to be the dominant alloreactive T-cell population late after transplantation. Their ability to provide help for generating long-lived alloantibody is likely one of the main mechanisms responsible for the progression of allograft vasculopathy and chronic rejection.Recent work has suggested that regulatory T cells may be an effective cellular therapy in transplantation. Given the above, adoptive therapy with CD4 regulatory T cells with indirect allospecificity is a rational first choice in attempting to attenuate the development and progression of chronic rejection; those with additional properties that enable inhibition of germinal center alloantibody responses hold particular appeal.

  13. Regulatory T cells in skin.

    Science.gov (United States)

    Ali, Niwa; Rosenblum, Michael D

    2017-11-01

    Foxp3 + CD4 + regulatory T (Treg) cells are a subset of immune cells that function to regulate tissue inflammation. Skin is one of the largest organs and is home to a large proportion of the body's Treg cells. However, relative to other tissues (such as the spleen and gastrointestinal tract) the function of Treg cells in skin is less well defined. Here, we review our understanding of how Treg cells migrate to skin and the cellular and molecular pathways required for their maintenance in this tissue. In addition, we outline what is known about the specialized functions of Treg cells in skin. Namely, the orchestration of stem cell-mediated hair follicle regeneration, augmentation of wound healing, and promoting adaptive immune tolerance to skin commensal microbes. A comprehensive understanding of the biology of skin Treg cells may lead to novel therapeutic approaches that preferentially target these cells to treat cutaneous autoimmunity, skin cancers and disorders of skin regeneration. © 2017 John Wiley & Sons Ltd.

  14. Structural pathway of regulated substrate transfer and threading through an Hsp100 disaggregase.

    Science.gov (United States)

    Deville, Célia; Carroni, Marta; Franke, Kamila B; Topf, Maya; Bukau, Bernd; Mogk, Axel; Saibil, Helen R

    2017-08-01

    Refolding aggregated proteins is essential in combating cellular proteotoxic stress. Together with Hsp70, Hsp100 chaperones, including Escherichia coli ClpB, form a powerful disaggregation machine that threads aggregated polypeptides through the central pore of tandem adenosine triphosphatase (ATPase) rings. To visualize protein disaggregation, we determined cryo-electron microscopy structures of inactive and substrate-bound ClpB in the presence of adenosine 5'- O -(3-thiotriphosphate), revealing closed AAA+ rings with a pronounced seam. In the substrate-free state, a marked gradient of resolution, likely corresponding to mobility, spans across the AAA+ rings with a dynamic hotspot at the seam. On the seam side, the coiled-coil regulatory domains are locked in a horizontal, inactive orientation. On the opposite side, the regulatory domains are accessible for Hsp70 binding, substrate targeting, and activation. In the presence of the model substrate casein, the polypeptide threads through the entire pore channel and increased nucleotide occupancy correlates with higher ATPase activity. Substrate-induced domain displacements indicate a pathway of regulated substrate transfer from Hsp70 to the ClpB pore, inside which a spiral of loops contacts the substrate. The seam pore loops undergo marked displacements, along with ordering of the regulatory domains. These asymmetric movements suggest a mechanism for ATPase activation and substrate threading during disaggregation.

  15. Electronics and electronic systems

    CERN Document Server

    Olsen, George H

    1987-01-01

    Electronics and Electronic Systems explores the significant developments in the field of electronics and electronic devices. This book is organized into three parts encompassing 11 chapters that discuss the fundamental circuit theory and the principles of analog and digital electronics. This book deals first with the passive components of electronic systems, such as resistors, capacitors, and inductors. These topics are followed by a discussion on the analysis of electronic circuits, which involves three ways, namely, the actual circuit, graphical techniques, and rule of thumb. The remaining p

  16. Nuclear Regulatory Commission information digest

    International Nuclear Information System (INIS)

    1990-03-01

    The Nuclear Regulatory Commission information digest provides summary information regarding the US Nuclear Regulatory Commission, its regulatory responsibilities, and areas licensed by the commission. This is an annual publication for the general use of the NRC Staff and is available to the public. The digest is divided into two parts: the first presents an overview of the US Nuclear Regulatory Commission and the second provides data on NRC commercial nuclear reactor licensees and commercial nuclear power reactors worldwide

  17. Bottom-up GGM algorithm for constructing multiple layered hierarchical gene regulatory networks

    Science.gov (United States)

    Multilayered hierarchical gene regulatory networks (ML-hGRNs) are very important for understanding genetics regulation of biological pathways. However, there are currently no computational algorithms available for directly building ML-hGRNs that regulate biological pathways. A bottom-up graphic Gaus...

  18. Characteristics of regulatory regimes

    Directory of Open Access Journals (Sweden)

    Noralv Veggeland

    2013-03-01

    Full Text Available The overarching theme of this paper is institutional analysis of basic characteristics of regulatory regimes. The concepts of path dependence and administrative traditions are used throughout. Self-reinforcing or positive feedback processes in political systems represent a basic framework. The empirical point of departure is the EU public procurement directive linked to OECD data concerning use of outsourcing among member states. The question is asked: What has caused the Nordic countries, traditionally not belonging to the Anglo-Saxon market-centred administrative tradition, to be placed so high on the ranking as users of the Market-Type Mechanism (MTM of outsourcing in the public sector vs. in-house provision of services? A thesis is that the reason may be complex, but might be found in an innovative Scandinavian regulatory approach rooted in the Nordic model.

  19. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1993-07-01

    The NRC Regulatory Agenda is a compilation of all rules on which the NRC has recently completed action, or has proposed action, or is considering action, and all petitions for rulemaking which have been received by the Commission and are pending disposition by the Commission. The Regulatory Agenda is updated and issued each quarter. The rules on which final action has been taken since March 31, 1993 are: Repeal of NRC standards of conduct; Fitness-for-duty requirements for licensees who possess, use, or transport Category I material; Training and qualification of nuclear power plant personnel; Monitoring the effectiveness of maintenance at nuclear power plants; Licensing requirements for land disposal of radioactive wastes; and Licensees' announcements of safeguards inspections

  20. A flexible regulatory framework

    International Nuclear Information System (INIS)

    Silvennoinen, T.

    2000-01-01

    Regulatory reform of the Finnish electricity market meant opening up potentially competitive parts of the electricity sector to competition and eliminating all unnecessary forms of regulation covering generation, wholesale supply, retail supply, and foreign trade in electricity. New types of control and regulatory mechanisms and institutions were set up for those parts of the electricity industry that were excluded from competition, such as network operations. Network activities now have to be licensed, whereas no licence is needed for generation or supply. A new sector-specific regulatory authority was established in 1995 to coincide with the implementation of the Electricity Market Act, known as the Electricity Market Authority. This is responsible for regulating network activities and retail supply to captive customers. The core function of the authority, which employs some 14 people, is to promote the smooth operation of the Finnish electricity market and to oversee the implementation of the Electricity Market Act and its provisions. Its most important duties are linked to overseeing the process by which network companies price their electricity. As price regulation no longer exists, all the companies in the electricity sector set their tariffs independently, even network companies. The job of controlling the pricing of network services is handed by the Electricity Market Authority, following the principles of competition control. Pricing control takes place ex post - after a pricing system has been adopted by a company and concentrates on individual cases and companies. There is no ex ante system of setting or approving prices and tariffs by the regulator. The tariffs and pricing of network services can be evaluated, however, by both the Electricity Market Authority and the Finnish Competition Authority, which have overlapping powers as regards the pricing of network activities. The Finnish regulatory framework can be described as a system of light

  1. 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

  2. Regulatory aspects of radiopharmaceuticals

    International Nuclear Information System (INIS)

    Kristensen, K.

    1985-01-01

    Regulatory systems in the field of radiopharmaceuticals have two main purposes: efficacy and safety. Efficacy expresses the quality of the diagnostic and therapeutic process for the patient. Safety involves the patient, the staff, and the environment. The world situation regarding regulations for radiopharmaceuticals is reviewed on the basis of a survey in WHO Member States. The main content of such regulations is discussed. The special properties of radiopharmaceuticals compared with ordinary drugs may call for modified regulations. Several countries are preparing such regulations. Close co-operation and good understanding among scientists working in hospital research, industry and regulatory bodies will be of great importance for the fast and safe introduction of new radiopharmaceuticals for the benefit of the patient. Before introducing new legislation in this field, a radiopharmaceutical expert should analyse the situation in the country and the relationship to the existing regulations. It is expected that the most important factor in promoting the fast introduction of new, safe and effective radiopharmaceuticals will be the training of people working within the regulatory bodies. It is foreseen that the IAEA and WHO will have an important role to play by providing expert advice and training in this area. (author)

  3. pathways in myogenesis

    Directory of Open Access Journals (Sweden)

    Marta Milewska

    2014-05-01

    Full Text Available The commitment of myogenic cells in skeletal muscle differentiation requires earlier irreversible interruption of the cell cycle. At the molecular level, several key regulators of the cell cycle have been identified: cyclin-dependent kinases and their cyclins stimulate the cell cycle progress and its arrest is determined by the activity of cdk inhibitors (Cip/Kip and INK protein families and pocket protein family: Rb, p107 and p130. The biological activity of cyclin/cdk complexes allows the successive phases of the cell cycle to occur. Myoblast specialization, differentiation and fusion require the activity of myogenic regulatory factors, which include MyoD, myogenin, Myf5 and MRF4. MyoD and Myf5 play a role in muscle cell specialization, myogenin controls the differentiation process, whereas MRF4 is involved in myotube maturation. The deregulation of the cell cycle leads to uncontrolled proliferation, which antagonizes the functions of myogenic factors and it explains the lack of differentiation-specific gene expression in dividing cells. Conversely, the myogenic factor MyoD seems to cooperate with cell cycle inhibitors leading to inhibition of cell cycle progress and commitment to the differentiation process. The hypophosphorylated form of Rb and cdk inhibitors play an important role in permanent arrest of the cell cycle in differentiated myotubes. Furthermore, cyclin/cdk complexes not only regulate cell division by phosphorylation of several substrates, but may also control other cellular processes such as signal transduction, differentiation and apoptosis. Beyond regulating the cell cycle, Cip/Kip proteins play an important role in cell death, transcription regulation, cell fate determination, cell migration and cytoskeletal dynamics. The article summarizes current knowledge concerning the interactions of intracellular signaling pathways controlling crucial stages of fetal and regenerative myogenesis.

  4. Advancing the Adverse Outcome Pathway Framework - an ...

    Science.gov (United States)

    The ability of scientists to conduct whole organism toxicity tests to understand chemical safety has been significantly outpaced by the rapid synthesis of new chemicals. Therefore, to increase efficiencies in chemical risk assessment, scientists are turning to mechanistic-based studies, making greater use of in vitro and in silico methods, to screen for potential environmental and human health hazards. A framework that has gained traction for capturing available knowledge describing the linkage between mechanistic data and apical toxicity endpoints, required for regulatory assessments, is the adverse outcome pathway (AOP). A number of international activities have focused on AOP development and plausible applications to regulatory decision-making. These interactions have prompted dialog between research scientists and regulatory communities to consider how best to use the AOP framework in risk assessment. While expert-facilitated discussions have been instrumental in moving the science of AOPs forward, it was recognized that a survey of the broader scientific community would aid in identifying shortcomings and guiding future initiatives for the AOP framework. To that end, a ?‘Horizon Scanning’ exercise was conducted to solicit questions from the global scientific and regulatory communities concerning the challenges or limitations that must be addressed to realize the full potential of the AOP framework in research and regulatory decision making. The m

  5. Setting the stage to advance the adverse outcome pathway (AOP) framework through horizon scanning

    Science.gov (United States)

    Recognizing the international interest surrounding the adverse outcome pathway framework, which captures existing information describing causal linkages between a molecular initiating event through levels of biological organization to an adverse outcome of regulatory significance...

  6. Rising utilization of inpatient pediatric asthma pathways.

    Science.gov (United States)

    Kaiser, Sunitha V; Rodean, Jonathan; Bekmezian, Arpi; Hall, Matt; Shah, Samir S; Mahant, Sanjay; Parikh, Kavita; Morse, Rustin; Puls, Henry; Cabana, Michael D

    2018-02-01

    Clinical pathways are detailed care plans that operationalize evidence-based guidelines into an accessible format for health providers. Their goal is to link evidence to practice to optimize patient outcomes and delivery efficiency. It is unknown to what extent inpatient pediatric asthma pathways are being utilized nationally. (1) Describe inpatient pediatric asthma pathway design and implementation across a large hospital network. (2) Compare characteristics of hospitals with and without pathways. We conducted a descriptive, cross-sectional, survey study of hospitals in the Pediatric Research in Inpatient Settings Network (75% children's hospitals, 25% community hospitals). Our survey determined if each hospital used a pathway and pathway characteristics (e.g. pathway elements, implementation methods). Hospitals with and without pathways were compared using Chi-square tests (categorical variables) and Student's t-tests (continuous variables). Surveys were distributed to 3-5 potential participants from each hospital and 302 (74%) participants responded, representing 86% (106/123) of surveyed hospitals. From 2005-2015, the proportion of hospitals utilizing inpatient asthma pathways increased from 27% to 86%. We found variation in pathway elements, implementation strategies, electronic medical record integration, and compliance monitoring across hospitals. Hospitals with pathways had larger inpatient pediatric programs [mean 12.1 versus 6.1 full-time equivalents, p = 0.04] and were more commonly free-standing children's hospitals (52% versus 23%, p = 0.05). From 2005-2015, there was a dramatic rise in implementation of inpatient pediatric asthma pathways. We found variation in many aspects of pathway design and implementation. Future studies should determine optimal implementation strategies to better support hospital-level efforts in improving pediatric asthma care and outcomes.

  7. The SUMO Pathway in Mitosis.

    Science.gov (United States)

    Mukhopadhyay, Debaditya; Dasso, Mary

    2017-01-01

    Mitosis is the stage of the cell cycle during which replicated chromosomes must be precisely divided to allow the formation of two daughter cells possessing equal genetic material. Much of the careful spatial and temporal organization of mitosis is maintained through post-translational modifications, such as phosphorylation and ubiquitination, of key cellular proteins. Here, we will review evidence that sumoylation, conjugation to the SUMO family of small ubiquitin-like modifiers, also serves essential regulatory roles during mitosis. We will discuss the basic biology of sumoylation, how the SUMO pathway has been implicated in particular mitotic functions, including chromosome condensation, centromere/kinetochore organization and cytokinesis, and what cellular proteins may be the targets underlying these phenomena.

  8. Schedules for Regulatory Regimes

    International Nuclear Information System (INIS)

    Austvik, Ole Gunnar

    2003-01-01

    The idea of regulating transporters' terms of operations is that if the market itself does not produce optimal outcomes, then it can be mimicked to do so through regulatory and other public instruments. The first-best solution could be a subsidized (publicly owned) enterprise that sets tariffs according to marginal costs. This has been the tradition in many European countries in the aftermath of WW2. Due to lack of innovative pressure on and x-inefficiency in these companies, this solution is today viewed as inferior to the system of regulating independent (privately owned) firms. When the European gas market becomes liberalized, part of the process in many countries is to (partially) privatise the transport utilities. Privatised or not, in a liberalized market, the transport utilities should face an independent authority that overviews their operations not only in technical, but also in economic terms. Under regulation, a ''visible hand'' is introduced to correct the imperfect market's ''invisible hand''. By regulating the framework and conditions for how firms may operate, public authorities seek to achieve what is considered optimal for the society. The incentives and disincentives given for pricing and production should create mechanisms leading to an efficient allocation of resources and ''acceptable'' distribution of income. As part of intervening into firms' behavior, regulation may be introduced to direct the firm to behave in certain ways. The framework and regulatory mechanisms for the market must then be constructed in a way that companies voluntarily produce an amount at a price that gives maximal profits and simultaneously satisfies social goals. The regulations should lead to consistency between the company's desire to maximize profits and the society's desire for maximizing welfare, as in a perfectly competitive market. This is the core of regulatory economics

  9. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2009-01-01

    In this last part is reviewed international regulatory activities and bilateral agreements including two parts: concerning European atomic energy community with European commission proposal for a council directive setting up a community framework for nuclear safety, update of the nuclear illustrative programme in the context of the second strategic energy review, european commission recommendation on criteria for the export of radioactive waste and spent fuel to third countries and a communication on nuclear non-proliferation and the second part in relation with international atomic energy agency with a joint convention on the safety of spent fuel management and on safety of radioactive waste management (third review meeting). (N.C.)

  10. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2002-01-01

    Different international regulatory activities are presented: recommendation on the protection of the public against exposure to radon in drinking water supplies, amendment to the legislation implementing the regulation on imports of agricultural products originating in third countries following the Chernobyl accident, resolution on the commission green paper towards a European strategy for the security of energy supply, declaration of mandatory nature of the international code for the safe carriage of packaged irradiated nuclear fuel, plutonium and high level radioactive wastes on board ships, adoption of action plan against nuclear terrorism. (N.C.)

  11. The core to regulatory reform

    International Nuclear Information System (INIS)

    Partridge, J.W. Jr.

    1993-01-01

    Federal Energy Regulatory Commission (FERC) Orders 436, 500, and 636, the Clean Air Act Amendments of 1990, Public Utility Holding Company Act reform, and the 1992 Energy Policy Act all can have significant effects on an LDC's operations. Such changes in an LDC's environments must be balanced by changes within the utility, its marketplace, and its state regulatory environment. The question is where to start. For Columbia Gas Distribution Cos., based in Columbus, OH, the new operating foundation begins with each employee. Internal strength is critical in designing initiatives that meet the needs of the marketplace and are well-received by regulators. Employees must understand not only the regulatory environment in which the LDC operates, but also how their work contributes to a positive regulatory relationship. To achieve this, Columbia initiated the COntinuing Regulatory Education program, or CORE, in 1991. CORE is a regulatory-focused, information-initiative program coordinated by Columbia's Regulatory Policy, Planning, and Government Affairs Department. The CORE programs can take many forms, such as emerging issue discussions, dialogues with regulators and key parties, updates on regulatory fillings, regulatory policy meetings, and formal training classes. The speakers and discussion facilitators can range from human resource department trainers to senior officers, from regulatory department staff members to external experts, or from state commissioners to executives from other LDCs. The goals of CORE initiatives are to: Support a professional level of regulatory expertise through employee participation in well-developed regulatory programs presented by credible experts. Encourage a constructive state regulatory environment founded on communication and cooperation. CORE achieves these goals via five program levels: introductory basics, advanced learning, professional expertise, crossfunctional dialogues, and external idea exchanges

  12. Politically Induced Regulatory Risk and Independent Regulatory Agencies

    OpenAIRE

    Strausz, Roland

    2015-01-01

    Uncertainty in election outcomes generates politically induced regulatory risk. Political parties' risk attitudes towards such risk depend on a fluctuation effect that hurts both parties and an output--expansion effect that benefits at least one party. Notwithstanding the parties' risk attitudes, political parties have incentives to negotiate away all regulatory risk by pre-electoral bargaining. Efficient pre-electoral bargaining outcomes fully eliminate politically induced regulatory risk. P...

  13. Regulatory networks, legal federalism, and multi-level regulatory systems

    OpenAIRE

    Kerber, Wolfgang; Wendel, Julia

    2016-01-01

    Transnational regulatory networks play important roles in multi-level regulatory regimes, as e.g, the European Union. In this paper we analyze the role of regulatory networks from the perspective of the economic theory of legal federalism. Often sophisticated intermediate institutional solutions between pure centralisation and pure decentralisation can help to solve complex tradeoff problems between the benefits and problems of centralised and decentralised solutions. Drawing upon the insight...

  14. Quantitative trait loci and metabolic pathways

    Science.gov (United States)

    McMullen, M. D.; Byrne, P. F.; Snook, M. E.; Wiseman, B. R.; Lee, E. A.; Widstrom, N. W.; Coe, E. H.

    1998-01-01

    The interpretation of quantitative trait locus (QTL) studies is limited by the lack of information on metabolic pathways leading to most economic traits. Inferences about the roles of the underlying genes with a pathway or the nature of their interaction with other loci are generally not possible. An exception is resistance to the corn earworm Helicoverpa zea (Boddie) in maize (Zea mays L.) because of maysin, a C-glycosyl flavone synthesized in silks via a branch of the well characterized flavonoid pathway. Our results using flavone synthesis as a model QTL system indicate: (i) the importance of regulatory loci as QTLs, (ii) the importance of interconnecting biochemical pathways on product levels, (iii) evidence for “channeling” of intermediates, allowing independent synthesis of related compounds, (iv) the utility of QTL analysis in clarifying the role of specific genes in a biochemical pathway, and (v) identification of a previously unknown locus on chromosome 9S affecting flavone level. A greater understanding of the genetic basis of maysin synthesis and associated corn earworm resistance should lead to improved breeding strategies. More broadly, the insights gained in relating a defined genetic and biochemical pathway affecting a quantitative trait should enhance interpretation of the biological basis of variation for other quantitative traits. PMID:9482823

  15. 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

  16. Visions of regulatory renewal

    International Nuclear Information System (INIS)

    Edgeworth, A.

    1998-01-01

    The economic contribution of the CEPA (Canadian Energy Pipeline Association) member companies to Canada's trade balance was discussed. CEPA member companies transport 95 per cent of the crude oil and natural gas produced in Canada to domestic and export markets. This represents a total of 5.6 Tcf of gas annually. Half of Canada's natural gas and oil production is exported to U.S. markets. All of these exports are transported by pipeline. CEPA member companies operate 90,000 km of pipeline from British Columbia to Quebec. Expansions are needed as a result of a significant increase in demand for natural gas and crude oil since 1990. Several issues exist for regulatory renewal. They include the need to create a level playing field, the overseeing of tolls and contract renewal terms, changing risk/reward trade-offs, the right to confidentiality of information and price discovery mechanism. The drivers for regulatory reform at Westcoast Energy are the need for pricing flexibility, customers desire for toll certainty, decontracting and opposition to rolled-in expansions for gathering and processing. An overview of Westcoast Energy's negotiated toll settlement, its implications, and the components of Westcoast Energy's 'light handed regulation' (LHR) was presented

  17. The regulatory dynamic

    International Nuclear Information System (INIS)

    Dybwad, C.

    2001-01-01

    An outline of the activities and efforts expanded by the National Energy Board to adjust to the changing natural gas market was provided in this presentation. The author began by defining the role of the National Energy Board in energy markets. It must ensure the adoption of rules and procedures that result in a more competitive and efficient market. Light-handed regulatory techniques are the norm, and the National Energy Board is now committed to facilitating the availability and flow of information so that all parties know where opportunities exist, the terms offered to buy or sell goods and services, their quality and costs. It will specialize in providing new participants with information on the workings of the market, who the players are, the regulatory processes in place, and how, when and where the market can be accessed. The manner in which the Board deals with information was reviewed, providing examples along the way to clarify some points. Some of the documents produced by the National Energy Board are being reviewed with the intent of making them easier to read and understand. Audio streaming over the Internet is another avenue being pursued to ensure individuals can listen in real time to hearings without having to be present in the room. The National Energy Board is also exploring alternative dispute resolution techniques. Consultation with energy market participants represents another facet of these efforts to be more accessible and responsive

  18. Glucose- and nitrogen sensing and regulatory mechanisms in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Rødkaer, Steven V; Færgeman, Nils J.

    2014-01-01

    Pro- and eukaryotic cells are constantly challenged by varying concentrations of nutrients in their environment. Perceiving and adapting to such changes are therefore crucial for cellular viability. Thus, numerous specialized cellular receptors continuously sense and react to the availability...... of nutrients such as glucose and nitrogen. When stimulated, these receptors initiate various cellular signaling pathways, which in concert constitute a complex regulatory network. To ensure a highly specific response, these pathways and networks cross-communicate with each other and are regulated at several...

  19. Regulatory inspection of BARC facilities

    International Nuclear Information System (INIS)

    Rajdeep; Jayarajan, K.

    2017-01-01

    Nuclear and radiation facilities are sited, constructed, commissioned, operated and decommissioned, in conformity with the current safety standards and codes. Regulatory bodies follow different means to ensure compliance of the standards for the safety of the personnel, the public and the environment. Regulatory Inspection (RI) is one of the important measures employed by regulatory bodies to obtain the safety status of a facility or project and to verify the fulfilment of the conditions stipulated in the consent

  20. Trichomes: different regulatory networks lead to convergent structures.

    Science.gov (United States)

    Serna, Laura; Martin, Cathie

    2006-06-01

    Sometimes, proteins, biological structures or even organisms have similar functions and appearances but have evolved through widely divergent pathways. There is experimental evidence to suggest that different developmental pathways have converged to produce similar outgrowths of the aerial plant epidermis, referred to as trichomes. The emerging picture suggests that trichomes in Arabidopsis thaliana and, perhaps, in cotton develop through a transcriptional regulatory network that differs from those regulating trichome formation in Antirrhinum and Solanaceous species. Several lines of evidence suggest that the duplication of a gene controlling anthocyanin production and subsequent divergence might be the major force driving trichome formation in Arabidopsis, whereas the multicellular trichomes of Antirrhinum and Solanaceous species appear to have a different regulatory origin.

  1. The FDA “Deeming Rule” and Tobacco Regulatory Research

    OpenAIRE

    Backinger, Cathy L.; Meissner, Helen I.; Ashley, David L.

    2016-01-01

    In May 2016, the Food and Drug Administration extended its tobacco regulatory authorities to other products meeting the definition of a tobacco product (Deeming Rule). This authority now includes, but is not limited to, electronic nicotine delivery systems (ENDS), such as electronic cigarettes, as well as all cigars, pipes, and hookahs (waterpipes). The FDA’s Center for Tobacco Products has been able to fund research projects addressing these newly deemed tobacco products through a variety of...

  2. Survival pathways under stress

    Indian Academy of Sciences (India)

    First page Back Continue Last page Graphics. Survival pathways under stress. Bacteria survive by changing gene expression. pattern. Three important pathways will be discussed: Stringent response. Quorum sensing. Proteins performing function to control oxidative damage.

  3. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2012-01-01

    This section gathers the following national legislative and regulatory activities sorted by country: Bulgaria: General legislation; Czech Republic: General legislation; France: General legislation, Regulatory infrastructure and activity; Germany: General legislation; India: Liability and compensation, Organisation and structure; Ireland: Radiation protection, General legislation; Korea (Republic of): Organisation and structure; Lithuania: Regulatory infrastructure and activity, Radioactive waste management, Radiation protection, international cooperation, Nuclear safety; Poland: General legislation; Romania: Environmental protection; Russian Federation: Radioactive waste management; Slovenia: Nuclear safety; Spain: Liability and compensation, Nuclear security; Sweden: Nuclear safety; Turkey: Radiation protection, Regulatory infrastructure and activity, Nuclear safety, Liability and compensation; United States: General legislation

  4. Self-sustained oscillations of complex genomic regulatory networks

    International Nuclear Information System (INIS)

    Ye Weiming; Huang Xiaodong; Huang Xuhui; Li Pengfei; Xia Qinzhi; Hu Gang

    2010-01-01

    Recently, self-sustained oscillations in complex networks consisting of non-oscillatory nodes have attracted great interest in diverse natural and social fields. Oscillatory genomic regulatory networks are one of the most typical examples of this kind. Given an oscillatory genomic network, it is important to reveal the central structure generating the oscillation. However, if the network consists of large numbers of genes and interactions, the oscillation generator is deeply hidden in the complicated interactions. We apply the dominant phase-advanced driving path method proposed in Qian et al. (2010) to reduce complex genomic regulatory networks to one-dimensional and unidirectionally linked network graphs where negative regulatory loops are explored to play as the central generators of the oscillations, and oscillation propagation pathways in the complex networks are clearly shown by tree branches radiating from the loops. Based on the above understanding we can control oscillations of genomic networks with high efficiency.

  5. Development of an international BRC [Below Regulatory Concern] limit

    International Nuclear Information System (INIS)

    Kennedy, W.E. Jr.

    1987-07-01

    The International Atomic Energy Agency (IAEA) has recently investigated the exemption from regulatory control of radiation sources containing limited quantities of radioactive materials. Early efforts were entitled de minimis and were aimed at establishing a philosophical basis and radiation dose limits. The main objectives of more recent work on exemption are to illustrate a method for developing practical radiological criteria, to establish generic criteria, and to determine the practicability of the preliminary exemption principles. The method used to develop the criteria relies on models to evaluate the potential radiation exposure pathways and scenarios for individuals and population groups potentially present following the unrestricted release of materials. This paper describes the assessment methods, presents the generic results expressed in terms of the limiting concentrations of selected radionuclides in municipal waste, and provides a comparison with recent regulatory efforts in the United States for considering selected wastes being Below Regulatory Concern (BRC). 17 refs., 4 tabs

  6. Regulatory audit to the Argentine teletherapy units

    International Nuclear Information System (INIS)

    Kay, J.M.

    1995-01-01

    As a consequence of an erroneous calibration of the ionization chamber dosimeter of a new licensed 6 Mev electron lineal accelerator that caused accidental overexposures in the first patients under treatment, the Regulatory Board decided to perform an audit to every teletherapy unit (accelerator and telegammatherapy units) in Argentina. The audit was carried out at the en of 1994 in 27 accelerators and 107 telegammatherapy units. The objectives of the audit were the control of the mechanical and optical aspects of the each accelerator and telegammatherapy unit and the control of the calibration of their radiation beams. The last action was undertaken to detect as soon as possible, any eventual accidental overexposure or underexposure of patients under treatment. The audit was conducted by the author and performed for a team of 22 inspectors who worked in groups of 2 to 3 people and completed the inspection of the teletherapy units of the whole country in 3 months. As a result of the audit, the Regulatory Board had in a short period a clear panorama of the performance of each teletherapy unit of the country and also confirmed that no accidental situation had happened. The audit revealed the necessity of imposing urgent regulatory requirements not related to the calibration of the radiation beam in 5% of the cases, as well as non-urgent requirements of different importance in approximately other 60% of the cases. (author)

  7. Pathways Intern Report

    Science.gov (United States)

    Huggett, Daniel James

    2017-01-01

    The National Aeronautics and Space Administration (NASA) provides a formal training program for prospective employees titled, Pathways Intern Employment. The Pathways program targets graduate and undergraduate students who strive to become an active contributor to NASA's goal of space exploration. The report herein provides an account of Daniel Huggett's Pathways experience for the Spring and Summer 2017 semesters.

  8. Neurophysiology and itch pathways.

    Science.gov (United States)

    Schmelz, Martin

    2015-01-01

    As we all can easily differentiate the sensations of itch and pain, the most straightforward neurophysiologic concept would consist of two specific pathways that independently encode itch and pain. Indeed, a neuronal pathway for histamine-induced itch in the peripheral and central nervous system has been described in animals and humans, and recently several non-histaminergic pathways for itch have been discovered in rodents that support a dichotomous concept differentiated into a pain and an itch pathway, with both pathways being composed of different "flavors." Numerous markers and mediators have been found that are linked to itch processing pathways. Thus, the delineation of neuronal pathways for itch from pain pathways seemingly proves that all sensory aspects of itch are based on an itch-specific neuronal pathway. However, such a concept is incomplete as itch can also be induced by the activation of the pain pathway in particular when the stimulus is applied in a highly localized spatial pattern. These opposite views reflect the old dispute between specificity and pattern theories of itch. Rather than only being of theoretic interest, this conceptual problem has key implication for the strategy to treat chronic itch as key therapeutic targets would be either itch-specific pathways or unspecific nociceptive pathways.

  9. Effects of Sunphenon and Polyphenon 60 on proteolytic pathways ...

    Indian Academy of Sciences (India)

    2016-08-26

    Aug 26, 2016 ... The effect of Sunphenon and Polyphenon 60 in oxidative stress response, myogenic regulatory factors, inflammatory cytokines, apoptotic and proteolytic pathways on H2O2-induced myotube atrophy was addressed. Cellular responses of H2O2-induced C2C12cells were examined, including mRNA ...

  10. Adverse outcome pathways: opportunities, limitations and open questions

    NARCIS (Netherlands)

    Leist, M.; Ghallab, A.; Graepel, R.; Marchan, R.; Hassan, R.; Bennekou, S.H.; Limonciel, A.; Vinken, M.; Schildknecht, S.; Waldmann, T.; Danen, E.; Ravenzwaay, B. van; Kamp, H.; Gardner, I.; Godoy, P.; Bois, F.Y.; Braeuning, A.; Reif, R.; Oesch, F.; Drasdo, D.; Höhme, S.; Schwarz, M.; Hartung, T.; Braunbeck, T.; Beltman, J.; Vrieling, H.; Sanz, F.; Forsby, A.; Gadaleta, D.; Fisher, C.; Kelm, J.; Fluri, D.; Ecker, G.; Zdrazil, B.; Terron, A.; Jennings, P.; Burg, B. van der; Dooley, S.; Meijer, A.H.; Willighagen, E.; Martens, M.; Evelo, C.; Mombelli, E.; Taboureau, O.; Mantovani, A.; Hardy, B.; Koch, B.; Escher, S.; van Thriel, C.; Cadenas, C.; Kroese, D.; Water, B. van de; Hengstler, J.G.

    2017-01-01

    Adverse outcome pathways (AOPs) are a recent toxicological construct that connects, in a formalized, transparent and quality-controlled way, mechanistic information to apical endpoints for regulatory purposes. AOP links a molecular initiating event (MIE) to the adverse outcome (AO) via key events

  11. Regulatory actions post - Fukushima

    International Nuclear Information System (INIS)

    Ciurea Ercau, C.

    2013-01-01

    The paper presents the results of the safety reviews performed in Romania after the Fukushima accident and the resulting actions for improving the safety. The actions taken by the National Commission for Nuclear Activities Control (CNCAN) to improve the regulatory framework include the development of new regulations and the enhancement of inspection practices, taking account of the lessons learned from the Fukushima accident. A regulation on the response to transients, accidents and emergency situations at nuclear power plants has been developed, which includes requirements on transient and accident scenarios that have to be covered by the Emergency Operating Procedures (EOPs), accident scenarios to be covered by the Severe Accident Management Guidelines (SAMGs), emergency situations to be covered by the on-site emergency response plan and emergency response procedures. (authors)

  12. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2010-01-01

    Concerning International regulatory activities, we find for the european atomic energy community an entry into force of the lisbon treaty (2009), it amends the treaty on European union and replaces the treaty establishing the European Community by the new treaty on the functioning of the European Union; more, an amendment to council regulation on the conditions governing imports of agricultural products originating in third countries following the accident at the Chernobyl nuclear power station (2009). About International atomic energy agency is reported an open-ended meeting of technical and legal experts for sharing of information on states implementation of the code of conduct on the safety and security of radioactive sources and its supplementary guidance on the import and export of radioactive sources (2010). (N.C.)

  13. Regulatory mark; Marco regulatorio

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-10-15

    This chapter is based on a work performed in distinct phases. The first phase consisted in of the analysis regulatory legislation existent in Brazil for the sugar-alcohol sector since the beginning of the X X century. This analysis allowed the identification of non existent points and legal devices related to the studied aspects, and that were considered as problematic for the sector expansion. In the second phase, related treaties and international agreements was studied and possible obstacles for the brazilian bio ethanol exportation for the international market. Initiatives were examined at European Union, United States of America, Caribbean and countries of the sub-Saharan Africa. In this phase, policies were identified related to the incentives and adoption of use of bio fuels added to the gasoline in countries or group of countries considered as key for the consolidation of bio ethanol as a world commodity.

  14. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2003-01-01

    Among international regulatory activities we find resolutions adopted by the IAEA general conference (2003), through European Union we find proposals for directives on nuclear safety and radioactive waste management, new regulation on the application of EURATOM safeguards, control of high activity sealed radioactive sources, recommendation on the protection and information of the public with regard to the continued contamination of certain wild food products following the Chernobyl accident, proposals for decisions authorizing the Member states to sign and ratify the Protocol to amend the Paris convention, p)proposals for a directive on environment liability with regard to the prevention and remedying of environmental damage, proposal of a regulation on the law applicable to non-contractual obligation. (N.C.)

  15. Nuclear Regulatory Commission Issuances

    International Nuclear Information System (INIS)

    1992-01-01

    This is the thirty-sixth volume of issuances (1-396) of the Nuclear Regulatory Commission and its Atomic Safety and Licensing Boards, Administrative Law Judges, and Office Directors. It covers the period from July 1, 1992-December 31, 1992. Atomic Safety and Licensing Boards are authorized by Section 191 of the Atomic Energy Act of 1954. These Boards, comprised of three members conduct adjudicatory hearings on applications to construct and operate nuclear power plants and related facilities and issue initial decisions which, subject to internal review and appellate procedures, become the final Commission action with respect to those applications. Boards are drawn from the Atomic Safety and Licensing Board Panel, comprised of lawyers, nuclear physicists and engineers, environmentalists, chemists, and economists. The Atomic Energy Commission first established Licensing Boards in 1962 and the Panel in 1967

  16. Regulatory focus in groupt contexts

    NARCIS (Netherlands)

    Faddegon, Krispijn Johannes

    2009-01-01

    The thesis examines the influence of group processes on the regulatory focus of individual group members. It is demonstrated that the group situation can affect group members' regulatory focus both in a top-down fashion (via the identitiy of the group) and in a bottom-up fashion (emerging from the

  17. Disclosure as a regulatory tool

    DEFF Research Database (Denmark)

    Sørensen, Karsten Engsig

    2006-01-01

    The chapter analyses how disclure can be used as a regulatory tool and analyses how it has been applied so far in the area of financial market law and consumer law.......The chapter analyses how disclure can be used as a regulatory tool and analyses how it has been applied so far in the area of financial market law and consumer law....

  18. 12 CFR 562.2 - Regulatory reports.

    Science.gov (United States)

    2010-01-01

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

  19. Conserved Transcriptional Regulatory Programs Underlying Rice and Barley Germination

    Science.gov (United States)

    Lin, Li; Tian, Shulan; Kaeppler, Shawn; Liu, Zongrang; An, Yong-Qiang (Charles)

    2014-01-01

    Germination is a biological process important to plant development and agricultural production. Barley and rice diverged 50 million years ago, but share a similar germination process. To gain insight into the conservation of their underlying gene regulatory programs, we compared transcriptomes of barley and rice at start, middle and end points of germination, and revealed that germination regulated barley and rice genes (BRs) diverged significantly in expression patterns and/or protein sequences. However, BRs with higher protein sequence similarity tended to have more conserved expression patterns. We identified and characterized 316 sets of conserved barley and rice genes (cBRs) with high similarity in both protein sequences and expression patterns, and provided a comprehensive depiction of the transcriptional regulatory program conserved in barley and rice germination at gene, pathway and systems levels. The cBRs encoded proteins involved in a variety of biological pathways and had a wide range of expression patterns. The cBRs encoding key regulatory components in signaling pathways often had diverse expression patterns. Early germination up-regulation of cell wall metabolic pathway and peroxidases, and late germination up-regulation of chromatin structure and remodeling pathways were conserved in both barley and rice. Protein sequence and expression pattern of a gene change quickly if it is not subjected to a functional constraint. Preserving germination-regulated expression patterns and protein sequences of those cBRs for 50 million years strongly suggests that the cBRs are functionally significant and equivalent in germination, and contribute to the ancient characteristics of germination preserved in barley and rice. The functional significance and equivalence of the cBR genes predicted here can serve as a foundation to further characterize their biological functions and facilitate bridging rice and barley germination research with greater confidence. PMID

  20. Virginia Power's regulatory reduction program

    International Nuclear Information System (INIS)

    Miller, G.D.

    1996-01-01

    Virginia Power has two nuclear plants, North Anna and Surry Power Stations, which have two units each for a total of four nuclear units. In 1992, the Nuclear Regulatory Commission solicited comments from the nuclear industry to obtain their ideas for reducing the regulatory burden on nuclear facilities. Pursuant to the new regulatory climate, Virginia Power developed an internal program to evaluate and assess the regulatory and self-imposed requirements to which they were committed, and to pursue regulatory relief or internal changes where possible and appropriate. The criteria were that public safety must be maintained, and savings must be significant. Up to the date of the conference, over US$22 million of one-time saving had been effected, and US$2.75 million in annual savings

  1. Anti-regulatory T cells

    DEFF Research Database (Denmark)

    Andersen, Mads Hald

    2017-01-01

    responses to tumours or inhibiting autoimmunity development. However, recent studies report the discovery of self-reactive pro-inflammatory T cells—termed anti-regulatory T cells (anti-Tregs)—that target immune-suppressive cells. Thus, regulatory cells can now be defined as both cells that suppress immune...... reactions as well as effector cells that counteract the effects of suppressor cells and support immune reactions. Self-reactive anti-Tregs have been described that specifically recognize human leukocyte antigen-restricted epitopes derived from proteins that are normally expressed by regulatory immune cells......Our initial understanding of immune-regulatory cells was based on the discovery of suppressor cells that assure peripheral T-cell tolerance and promote immune homeostasis. Research has particularly focused on the importance of regulatory T cells (Tregs) for immune modulation, e.g. directing host...

  2. Alternative Cell Death Pathways and Cell Metabolism

    Directory of Open Access Journals (Sweden)

    Simone Fulda

    2013-01-01

    Full Text Available While necroptosis has for long been viewed as an accidental mode of cell death triggered by physical or chemical damage, it has become clear over the last years that necroptosis can also represent a programmed form of cell death in mammalian cells. Key discoveries in the field of cell death research, including the identification of critical components of the necroptotic machinery, led to a revised concept of cell death signaling programs. Several regulatory check and balances are in place in order to ensure that necroptosis is tightly controlled according to environmental cues and cellular needs. This network of regulatory mechanisms includes metabolic pathways, especially those linked to mitochondrial signaling events. A better understanding of these signal transduction mechanisms will likely contribute to open new avenues to exploit our knowledge on the regulation of necroptosis signaling for therapeutic application in the treatment of human diseases.

  3. 75 FR 11166 - Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission...

    Science.gov (United States)

    2010-03-10

    ... the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission; Notice of Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission March 2, 2010. The Federal Energy Regulatory Commission (FERC) and the Nuclear Regulatory Commission (NRC) will hold...

  4. Ontario regulatory update

    International Nuclear Information System (INIS)

    Thompson, P.

    1998-01-01

    This paper provides a summary of recent events which when combined add up to a gradual but unmistakable movement of the energy sector in Ontario towards a fully competitive market. Some of the events precipitating this movement towards competition include the passing of the Energy Competition Act of 1998 (Bill 35), electricity deregulation, regulatory reform of the natural gas sector, and changes to the consumer protection legislation. The role of the Ontario Energy Board was also updated to bring it in line with the demands of the competitive marketplace. Among the new roles that the Board will assume are to facilitate competition, to maintain fair and reasonable rates, and to facilitate rational expansion. Another objective is to provide opportunities for including energy efficiency in government policies. Implications of the changes in the OEB's mandate for market participants were also discussed, including (1) regulated gas sales and delivery mechanisms, (2) transactional services, (3) contract restructuring, (4) consumer protection, (5) supervision of competitive market participants, and (6) market surveillance

  5. Regulatory risk coherence

    International Nuclear Information System (INIS)

    Remick, F.J.

    1992-01-01

    As one of the most progressive users of risk assessment in decision making, the US Nuclear Regulatory Commission (NRC) is in a position to play an important role in influencing the development of standard government wide policies for the application of risk assessment in decision making. The NRC, with the support of the nuclear industry, should use the opportunity provided by its experience with risk assessment to actively encourage the adoption of standard national and international health-based safety goals and at the same time accelerate its own efforts to implement the safety goals it has already developed for itself. There are signs of increased recognition of the need for consistency and coherence in the application of risk assessment in government decision making. The NRC and the nuclear industry have recently taken a great step toward establishing a consistant and coherent risk assessment-based culture in the US nuclear industry. As a result of Generic Letter 88-20, which asks each commercial nuclear power plant licensee to perform an individual plant examination by September 1992, for the first time a risk assessment characterizing initiating events in each plant will exist

  6. 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

  7. Electronic technology

    International Nuclear Information System (INIS)

    Kim, Jin Su

    2010-07-01

    This book is composed of five chapters, which introduces electronic technology about understanding of electronic, electronic component, radio, electronic application, communication technology, semiconductor on its basic, free electron and hole, intrinsic semiconductor and semiconductor element, Diode such as PN junction diode, characteristic of junction diode, rectifier circuit and smoothing circuit, transistor on structure of transistor, characteristic of transistor and common emitter circuit, electronic application about electronic equipment, communication technology and education, robot technology and high electronic technology.

  8. The Danish Regulatory Reform of Telecommunications

    DEFF Research Database (Denmark)

    Skouby, Knud Erik

    1998-01-01

    An overview of the liberalisation process and regulatory reform of telecommunications in Denmark......An overview of the liberalisation process and regulatory reform of telecommunications in Denmark...

  9. The Electron

    Energy Technology Data Exchange (ETDEWEB)

    Thomson, George

    1972-01-01

    Electrons are elementary particles of atoms that revolve around and outside the nucleus and have a negative charge. This booklet discusses how electrons relate to electricity, some applications of electrons, electrons as waves, electrons in atoms and solids, the electron microscope, among other things.

  10. Dissecting microregulation of a master regulatory network

    Directory of Open Access Journals (Sweden)

    Kaimal Vivek

    2008-02-01

    Full Text Available Abstract Background The master regulator p53 tumor-suppressor protein through coordination of several downstream target genes and upstream transcription factors controls many pathways important for tumor suppression. While it has been reported that some of the p53's functions are microRNA-mediated, it is not known as to how many other microRNAs might contribute to the p53-mediated tumorigenesis. Results Here, we use bioinformatics-based integrative approach to identify and prioritize putative p53-regulated miRNAs, and unravel the miRNA-based microregulation of the p53 master regulatory network. Specifically, we identify putative microRNA regulators of a transcription factors that are upstream or downstream to p53 and b p53 interactants. The putative p53-miRs and their targets are prioritized using current knowledge of cancer biology and literature-reported cancer-miRNAs. Conclusion Our predicted p53-miRNA-gene networks strongly suggest that coordinated transcriptional and p53-miR mediated networks could be integral to tumorigenesis and the underlying processes and pathways.

  11. Strengthening Regulatory Competence in a Changing Nuclear Regulatory Environment

    International Nuclear Information System (INIS)

    Illizastigui, P.F.

    2016-01-01

    The paper addresses the approach followed by the Cuban National Center for Nuclear Safety for the management of current and new competences of its regulatory staff with the aim of allowing those staff to effectively fulfill their core regulatory functions. The approach is realized through an Integrated System for Competence Building, which is based on the IAEA recommendations, shown to be effective in ensuring the necessary competence in the relevant areas. In the author’s opinion, competence of the regulatory staff in the area of human and organizational factors is of paramount importance and needs to be further strengthened in order to be able to assess safety performance at the facilities and detect early signs of deteriorating safety performance. The former is defined by the author as the core regulatory function “Analysis” which covers the entire spectrum of assessment tasks carried out by the regulatory staff to: a) detect declining safety performance, b) diagnose latent weaknesses (root causes) and c) make effective safety culture interventions. The author suggests that competence associated with the fulfillment of the analysis function is distinctly identified and dealt with separately in the current system of managing regulatory competence. (author)

  12. Hard electronics; Hard electronics

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-03-01

    Hard material technologies were surveyed to establish the hard electronic technology which offers superior characteristics under hard operational or environmental conditions as compared with conventional Si devices. The following technologies were separately surveyed: (1) The device and integration technologies of wide gap hard semiconductors such as SiC, diamond and nitride, (2) The technology of hard semiconductor devices for vacuum micro- electronics technology, and (3) The technology of hard new material devices for oxides. The formation technology of oxide thin films made remarkable progress after discovery of oxide superconductor materials, resulting in development of an atomic layer growth method and mist deposition method. This leading research is expected to solve such issues difficult to be easily realized by current Si technology as high-power, high-frequency and low-loss devices in power electronics, high temperature-proof and radiation-proof devices in ultimate electronics, and high-speed and dense- integrated devices in information electronics. 432 refs., 136 figs., 15 tabs.

  13. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2004-01-01

    The 48. session of the IAEA general conference was held in Vienna from 20 to 24 september 2004 with the participation of delegates from 125 members states and representatives of various international organisations. A number of resolutions were adopted by the conference in the following fields: nuclear safety, radiation, transport and waste safety. The general conference also adopted a resolution on measures to protect against nuclear terrorism. The Director General decided in 2003 to appoint a group of experts to explore and advise on issues related to nuclear liability. This group called the International Expert Group on Nuclear Liability (I.N.L.E.X.) consists of 20 experts members from nuclear power and non nuclear power countries and from shipping and non shipping states. It serves three major functions: to create a forum of expertise to explore and advise on issues related to nuclear liability; to enhance global adherence by nuclear and non nuclear states to an effective nuclear liability regime, inter alia, on the basis of the convention on supplementary compensation for nuclear damage and the annex thereto, the Vienna convention on civil liability for nuclear damage, the Paris convention on third party liability in the field of nuclear energy, the joint protocol relating to the application of the vienna convention and the paris convention and the amendments thereto; and to assist in the development and strengthening of the national nuclear liability legal frameworks in IAEA members states to protect the public and the environment and to enhance nuclear safety. The second part of international regulatory concerns a directive on public access to environmental information made by the European Parliament. (N.C.)

  14. 78 FR 1634 - Regulatory Agenda

    Science.gov (United States)

    2013-01-08

    ... amendments include updates to organizational information, use of the term ``disability'' in lieu of the term.../00/13 Regulatory Flexibility Analysis Required: No. Agency Contact: Robert W. Cosgrove, External...

  15. 78 FR 44329 - Regulatory Agenda

    Science.gov (United States)

    2013-07-23

    ... amendments include updates to organizational information, use of the term ``disability'' in lieu of the term.../00/13 Regulatory Flexibility Analysis Required: No. Agency Contact: Robert W. Cosgrove, External...

  16. 78 FR 44279 - Regulatory Agenda

    Science.gov (United States)

    2013-07-23

    ... Vol. 78 Tuesday, No. 141 July 23, 2013 Part XI Department of Justice Semiannual Regulatory Agenda #0;#0;Federal Register / Vol. 78 , No. 141 / Tuesday, July 23, 2013 / Unified Agenda#0;#0; [[Page 44280

  17. Recent regulatory issues in Finland

    International Nuclear Information System (INIS)

    Laaksonen, J.; Tiipana, P.

    2001-01-01

    This paper presents general regulatory issues from Finland since the last WWER Regulators Forum meeting in Odessa 11-13 October 2000. More specific issues concerning Loviisa NPP are described in the Annex of this paper. (author)

  18. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2016-01-01

    This section treats of the following National legislative and regulatory activities: 1 - France: General legislation, regulations and instruments; Nuclear trade (including non-proliferation); International co-operation; 2 - India: Licensing and regulatory infrastructure; Liability and compensation; 3 - Ireland: Nuclear safety and radiological protection (including nuclear emergency planning); Transport of radioactive material; Nuclear trade (including non-proliferation); 4 - Lithuania: Licensing and regulatory infrastructure; Nuclear safety and radiological protection (including nuclear emergency planning); Radioactive waste management; 5 - Luxembourg: Nuclear safety and radiological protection (including nuclear emergency planning); 6 - Slovak Republic: International co-operation; General legislation, regulations and instruments; 7 - Spain: Radioactive materials (including physical protection); Radioactive waste management; 8 - United States: Licensing and regulatory infrastructure

  19. Quality assurance within regulatory bodies

    International Nuclear Information System (INIS)

    1999-06-01

    The IAEA directed extensive efforts during the years 1991 to 1995 to the integral revision of all NUSS quality assurance publications, which were approved and issued as Safety Series No.50-C/SG-Q, Quality Assurance for Safety in Nuclear Power Plants and other Nuclear Installations (1996). When these quality assurance publications were developed, their prime focus was on requirements against which work performed by the licensees could be measured and assessed by the regulatory bodies. In this way, they only helped to facilitate the functions of regulators. No requirements or recommendations were provided on how the regulators should ensure the effective implementation of their own activities. The present publication is a first attempt to collect, integrate and offer available experience to directly support performance of regulatory activities. It presents a comprehensive compilation on the application of quality assurance principles and methods by regulatory bodies to their activities. The aim is consistent good performance of regulatory activities through a systematic approach

  20. State/Federal Regulatory Considerations

    Science.gov (United States)

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

  1. Regulatory competition in partnership law.

    OpenAIRE

    Siems, Mathias

    2009-01-01

    Regulatory competition in company law has been extensively debated in the last few decades, but it has rarely been discussed whether there could also be regulatory competition in partnership law. This article fills this gap. It addresses the partnership law of the US, the UK, Germany, and France, and presents empirical data on the different types of partnerships and companies established in these jurisdictions. The main focus is on the use of a limited liability partnership (LLP) outside its ...

  2. Nuclear regulatory developments in Canada

    International Nuclear Information System (INIS)

    Binder, M.

    2012-01-01

    This paper from CNSC discusses nuclear regulatory developments in Canada. It starts with the Fukushima accident and the effect on the nuclear sector. It summarises what CNSC has done, what it has learned and their plans going forward. It has made recommendations to IAEA for international enhancements to regulatory procedures. It outline the activities of Canada's nuclear power plants, Canada's uranium projects, deep geological repository and waste management as well as nuclear research in Canada.

  3. Regulatory facility guide for Ohio

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, S.S.; Bock, R.E.; Francis, M.W.; Gove, R.M.; Johnson, P.E.; Kovac, F.M.; Mynatt, J.O. [Oak Ridge National Lab., TN (United States); Rymer, A.C. [Transportation Consulting Services, Knoxville, TN (United States)

    1994-02-28

    The Regulatory Facility Guide (RFG) has been developed for the DOE and contractor facilities located in the state of Ohio. It provides detailed compilations of international, federal, and state transportation-related regulations applicable to shipments originating at destined to Ohio facilities. This RFG was developed as an additional resource tool for use both by traffic managers who must ensure that transportation operations are in full compliance with all applicable regulatory requirements and by oversight personnel who must verify compliance activities.

  4. Electron radiography

    Science.gov (United States)

    Merrill, Frank E.; Morris, Christopher

    2005-05-17

    A system capable of performing radiography using a beam of electrons. Diffuser means receive a beam of electrons and diffuse the electrons before they enter first matching quadrupoles where the diffused electrons are focused prior to the diffused electrons entering an object. First imaging quadrupoles receive the focused diffused electrons after the focused diffused electrons have been scattered by the object for focusing the scattered electrons. Collimator means receive the scattered electrons and remove scattered electrons that have scattered to large angles. Second imaging quadrupoles receive the collimated scattered electrons and refocus the collimated scattered electrons and map the focused collimated scattered electrons to transverse locations on an image plane representative of the electrons' positions in the object.

  5. Pathways from Poverty.

    Science.gov (United States)

    Baldwin, Barbara, Ed.

    1995-01-01

    Articles in this theme issue are based on presentations at the Pathways from Poverty Workshop held in Albuquerque, New Mexico, on May 18-25, 1995. The event aimed to foster development of a network to address rural poverty issues in the Western Rural Development Center (WRDC) region. Articles report on outcomes from the Pathways from Poverty…

  6. Crystallization Pathways in Biomineralization

    Science.gov (United States)

    Weiner, Steve; Addadi, Lia

    2011-08-01

    A crystallization pathway describes the movement of ions from their source to the final product. Cells are intimately involved in biological crystallization pathways. In many pathways the cells utilize a unique strategy: They temporarily concentrate ions in intracellular membrane-bound vesicles in the form of a highly disordered solid phase. This phase is then transported to the final mineralization site, where it is destabilized and crystallizes. We present four case studies, each of which demonstrates specific aspects of biological crystallization pathways: seawater uptake by foraminifera, calcite spicule formation by sea urchin larvae, goethite formation in the teeth of limpets, and guanine crystal formation in fish skin and spider cuticles. Three representative crystallization pathways are described, and aspects of the different stages of crystallization are discussed. An in-depth understanding of these complex processes can lead to new ideas for synthetic crystallization processes of interest to materials science.

  7. Guidelines for using electronic and social media: the regulatory perspective.

    Science.gov (United States)

    Spector, Nancy; Kappel, Dawn M

    2012-09-30

    Social media can be a very effective way of communicating in nursing, but guidelines for appropriate use by healthcare providers are essential. This article briefly introduces the phenomenon of social media and introduces three actual scenarios where nurses unintentionally violated appropriate use of social media in healthcare. The scenarios are discussed related to social media, career, concerns, and nursing regulation. Incorporating these and other examples with data from board of nursing cases, the nature of complaints against nurses is explored as well as common myths and misunderstandings about using social media platforms. Guidelines for appropriate use by nurses and available resources to inform policy are highlighted. Next steps in social media in nursing should include development of organizational level policies and educational programs on the use of social media.

  8. HPV: Molecular pathways and targets.

    Science.gov (United States)

    Gupta, Shilpi; Kumar, Prabhat; Das, Bhudev C

    2018-04-05

    Infection of high-risk human papillomaviruses (HPVs) is a prerequisite for the development of cervical carcinoma. HPV infections are also implicated in the development of other types of carcinomas. Chronic or persistent infection of HPV is essential but HPV alone is inadequate, additional endogenous or exogenous cues are needed along with HPV to induce cervical carcinogenesis. The strategies that high-risk HPVs have developed in differentiating epithelial cells to reach a DNA-synthesis competent state leading to tumorigenic transformation are basically due to overexpression of the E6 and E7 oncoproteins and the activation of diverse cellular regulatory or signaling pathways that are targeted by them. Moreover, the Wnt/β-catenin/Notch and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathways are deregulated in various cancers, and have also been implicated in HPV-induced cancers. These are basically related to the "cancer hallmarks," and include sustaining proliferative signals, the evasion of growth suppression and immune destruction, replicative immortality, inflammation, invasion, metastasis and angiogenesis, as well as genome instability, resisting cell death, and deregulation of cellular energetics. These information could eventually aid in identifying or developing new diagnostic, prognostic biomarkers, and may contribute to design more effective targeted therapeutics and treatment strategies. Although surgery, chemotherapy and radiotherapy can cure more than 90% of women with early stage cervical cancer, the recurrent and metastatic disease remains a major cause of cancer mortality. Numerous efforts have been made to design new drugs and develop gene therapies to treat cervical cancer. In recent years, research on treatment strategies has proposed several options, including the role of HPV E5, E6, and E7 oncogenes, which are retained and overexpressed in most of the cervical cancers and whose respective oncoproteins are critical to the induction

  9. Review of the chronic exposure pathways models in MACCS [MELCOR Accident Consequence Code System] and several other well-known probabilistic risk assessment models

    International Nuclear Information System (INIS)

    Tveten, U.

    1990-06-01

    The purpose of this report is to document the results of the work performed by the author in connection with the following task, performed for US Nuclear Regulatory Commission, (USNRC) Office of Nuclear Regulatory Research, Division of Systems Research: MACCS Chronic Exposure Pathway Models: Review the chronic exposure pathway models implemented in the MELCOR Accident Consequence Code System (MACCS) and compare those models to the chronic exposure pathway models implemented in similar codes developed in countries that are members of the OECD. The chronic exposures concerned are via: the terrestrial food pathways, the water pathways, the long-term groundshine pathway, and the inhalation of resuspended radionuclides pathway. The USNRC has indicated during discussions of the task that the major effort should be spent on the terrestrial food pathways. There is one chapter for each of the categories of chronic exposure pathways listed above

  10. 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.

  11. Radioactive waste below regulatory concern

    International Nuclear Information System (INIS)

    Neuder, S.M.

    1987-01-01

    The U.S. Nuclear Regulatory Commission (NRC) published two notices in the Federal Register concerning radioactive waste below regulatory concern. The first, a Commission Policy Statement and Implementation Plan published August 29, 1986, concerns petition to exempt specific radioactive waste streams from the regulations. The second, an Advanced Notice of Proposed Rulemaking published Decemger 2, 1986, addresses the concept of generic rulemaking by the NRC on radioactive wastes that are below regulatory concern. Radioactive waste determined to be below regulatory concern would not be subject to regulatory control and would not need to go to a licensed low-level radioactive waste disposal site. The Policy Statement and Implementation Plan describe (1) the information a petitioner should file in support of a petition to exempt a specific waste stream, (2) the decision criteria the Commission intends to use for judging the petition, and (3) the internal administrative procedures to use be followed in order to permit the Commission to act upon the petition in an expedited manner

  12. The Regulatory Independence of FANR

    International Nuclear Information System (INIS)

    ALNuaimi, Fatema; Choi, Kwang Shik

    2012-01-01

    Regulatory independence is meant to provide a conservative system of policy making in order to comply with the problems that are forecasted upon the basis of assumptions. The Federal Authorization of Nuclear Regulation (FANR) is a regulatory commission that was formed to be regulatory body that governs the generation of nuclear power in United Arab Emirates. It was established under the UAE nuclear law (9/2009) as an independent regulatory body that was tasked with the regulation of all nuclear activities in the United Arab Emirates. As an independent body, FANR was tasked with ensuring that the regulation of the nuclear sector is done in effective and transparent manner to ensure its accountability to the people. Being independent, the regulatory body develops national nuclear regulations based on laid down safety standards by the International Atomic Energy Agency, ensuring that they are based on scientific and proven technologies The role of FANR is to ensure that the all corporations that undertake nuclear activities follow the laid down procedures and objectives and ensure safety measures are taken keenly to ensure the safety of the workers and the general public while at the same time ensuring the environment is free from nuclear radiations

  13. 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

  14. The Regulatory Independence of FANR

    Energy Technology Data Exchange (ETDEWEB)

    ALNuaimi, Fatema; Choi, Kwang Shik [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of)

    2012-05-15

    Regulatory independence is meant to provide a conservative system of policy making in order to comply with the problems that are forecasted upon the basis of assumptions. The Federal Authorization of Nuclear Regulation (FANR) is a regulatory commission that was formed to be regulatory body that governs the generation of nuclear power in United Arab Emirates. It was established under the UAE nuclear law (9/2009) as an independent regulatory body that was tasked with the regulation of all nuclear activities in the United Arab Emirates. As an independent body, FANR was tasked with ensuring that the regulation of the nuclear sector is done in effective and transparent manner to ensure its accountability to the people. Being independent, the regulatory body develops national nuclear regulations based on laid down safety standards by the International Atomic Energy Agency, ensuring that they are based on scientific and proven technologies The role of FANR is to ensure that the all corporations that undertake nuclear activities follow the laid down procedures and objectives and ensure safety measures are taken keenly to ensure the safety of the workers and the general public while at the same time ensuring the environment is free from nuclear radiations

  15. Electrons, Electronic Publishing, and Electronic Display.

    Science.gov (United States)

    Brownrigg, Edwin B.; Lynch, Clifford A.

    1985-01-01

    Provides a perspective on electronic publishing by distinguishing between "Newtonian" publishing and "quantum-mechanical" publishing. Highlights include media and publishing, works delivered through electronic media, electronic publishing and the printed word, management of intellectual property, and recent copyright-law issues…

  16. Quadrupolar transfer pathways

    Science.gov (United States)

    Antonijevic, Sasa; Bodenhausen, Geoffrey

    2006-06-01

    A set of graphical conventions called quadrupolar transfer pathways is proposed to describe a wide range of experiments designed for the study of quadrupolar nuclei with spin quantum numbers I = 1, 3/2, 2, 5/2, etc. These pathways, which inter alea allow one to appreciate the distinction between quadrupolar and Zeeman echoes, represent a generalization of the well-known coherence transfer pathways. Quadrupolar transfer pathways not merely distinguish coherences with different orders -2 I ⩽ p ⩽ +2 I, but allow one to follow the fate of coherences associated with single transitions that have the same coherence orderp=mIr-mIs but can be distinguished by a satellite orderq=(mIr)2-(mIs)2.

  17. HDR-Pathways

    Data.gov (United States)

    Department of Veterans Affairs — Pathways is a SOAP/REST web service interface accessed via HTTPS that provides administrative data (Appointments, Exam Requests and Exams information) from VistA in...

  18. Updating the Wnt pathways

    Science.gov (United States)

    Yu, Jia; Virshup, David M.

    2014-01-01

    In the three decades since the discovery of the Wnt1 proto-oncogene in virus-induced mouse mammary tumours, our understanding of the signalling pathways that are regulated by the Wnt proteins has progressively expanded. Wnts are involved in an complex signalling network that governs multiple biological processes and cross-talk with multiple additional signalling cascades, including the Notch, FGF (fibroblast growth factor), SHH (Sonic hedgehog), EGF (epidermal growth factor) and Hippo pathways. The Wnt signalling pathway also illustrates the link between abnormal regulation of the developmental processes and disease manifestation. Here we provide an overview of Wnt-regulated signalling cascades and highlight recent advances. We focus on new findings regarding the dedicated Wnt production and secretion pathway with potential therapeutic targets that might be beneficial for patients with Wnt-related diseases. PMID:25208913

  19. Multi-tissue omics analyses reveal molecular regulatory networks for puberty in composite beef cattle

    Science.gov (United States)

    Puberty is a complex physiological event by which animals mature into an adult capable of sexual reproduction. In order to enhance our understanding of the genes and regulatory pathways and networks involved in puberty, we characterized the transcriptome of five reproductive tissues (i.e., hypothal...

  20. REGULATORY FUNDAMENTALS FOR IMPLEMENTATION OF INFORMATION TECHNOLOGY PROJECTS IN INDUSTRY

    Directory of Open Access Journals (Sweden)

    L. V. Gubich

    2016-01-01

    Full Text Available The article provides an overview of the existing regulatory basis for the development of IIST. The features of IT projects management and a brief description of methodological recommendations on implementation of IT projects of the State scientific and technical Program «Electronic enterprise resource planning (CALS-ERP-technology» for 2011–2015 are considered.

  1. Regulatory authority information system RAIS

    International Nuclear Information System (INIS)

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

    2000-01-01

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

  2. Transparency of nuclear regulatory activities

    International Nuclear Information System (INIS)

    2007-01-01

    One of the main missions of nuclear regulators is to protect the public, and this cannot be completely achieved without public confidence. The more a regulatory process is transparent, the more such confidence will grow. Despite important cultural differences across countries, a number of common features characterise media and public expectations regarding any activity with an associated risk. A common understanding of transparency and main stakeholders' expectations in the field of nuclear safety were identified during this workshop, together with a number of conditions and practices aimed at improving the transparency of nuclear regulatory activities. These conditions and practices are described herein, and will be of particular interest to all those working in the nuclear regulatory field. Their implementation may, however, differ from one country to another depending on national context. (authors)

  3. Thick filament mechano-sensing is a calcium-independent regulatory mechanism in skeletal muscle.

    Science.gov (United States)

    Fusi, L; Brunello, E; Yan, Z; Irving, M

    2016-10-31

    Recent X-ray diffraction studies on actively contracting fibres from skeletal muscle showed that the number of myosin motors available to interact with actin-containing thin filaments is controlled by the stress in the myosin-containing thick filaments. Those results suggested that thick filament mechano-sensing might constitute a novel regulatory mechanism in striated muscles that acts independently of the well-known thin filament-mediated calcium signalling pathway. Here we test that hypothesis using probes attached to the myosin regulatory light chain in demembranated muscle fibres. We show that both the extent and kinetics of thick filament activation depend on thick filament stress but are independent of intracellular calcium concentration in the physiological range. These results establish direct control of myosin motors by thick filament mechano-sensing as a general regulatory mechanism in skeletal muscle that is independent of the canonical calcium signalling pathway.

  4. Regulatory authority infrastructure for Namibia

    International Nuclear Information System (INIS)

    Shangula, K.

    2001-01-01

    The Republic of Namibia is participating in the International Atomic Energy Agency's Model Project for the Improvement of National Regulatory Authority Infrastructures in Member States. The paper illustrates our experience in solving problems and difficulties confronted in establishing an effective regulatory authority operating within the existing national infrastructure that should be supported by the Government. An effective regulatory authority is seen as part of the wider administrative scope of our Government through ministerial mandates given by the State from time to time, guaranteeing its independence when implementing legal provisions under statutes. Sections of the report illustrate our experience in the following areas: 1. National radiation protection policy 2. Structure of our national regulatory authority 3. Laws and regulations 4. Provisions for notification, authorization and registration 5. In-depth security measures for radiation sources and radioactive material 6. Systems for the inspection of radiation sources, radioactive materials, enforcement of legal provisions 7. Extent of the applications of radiation sources and radioactive materials in the country. The paper provides information regarding existing Government policy on radiation protection; structure and legal aspects of the national regulatory, including statutes and regulations; the extent of application and uses of radiation sources and security of radioactive materials; human resources: strengths and constraints; management practices and financing of regulatory authority; and plans for emergency recovery of orphan sources. National plans for management of disused sources, recovery of orphan sources, abnormal emergencies, communication of information to affected persons on exposure effects, and the safety training of persons using these applications are discussed. the paper provides a summary and some suggestions of the way forward for Namibia. (author)

  5. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2014-01-01

    This section treats of the following activities sorted by country: 1 - Belarus: International cooperation, Organisation and structure, Licensing and regulatory infrastructure, Nuclear safety and radiological protection; 2 - France: Nuclear safety and radiological protection, Radioactive waste management, Environmental protection, Liability and compensation, International co-operation; 3 - Hungary: General legislation, Radioactive waste management, Nuclear security; 4 - Ireland: Nuclear safety and radiological protection (including emergency planning); 5 - Lithuania: Licensing and regulatory infrastructure; 6 - Moldova: Nuclear safety and radiological protection; 7 - Portugal: Radioactive waste management, Nuclear safety and radiological protection; 8 - Slovak Republic: Radioactive waste management, Liability and compensation; 9 - Spain: Radioactive waste management; 10 - Ukraine: Radioactive waste management; 11 - United Kingdom: Organisation and structure

  6. Glycoconjugate Vaccines: The Regulatory Framework.

    Science.gov (United States)

    Jones, Christopher

    2015-01-01

    Most vaccines, including the currently available glycoconjugate vaccines, are administered to healthy infants, to prevent future disease. The safety of a prospective vaccine is a key prerequisite for approval. Undesired side effects would not only have the potential to damage the individual infant but also lead to a loss of confidence in the respective vaccine-or vaccines in general-on a population level. Thus, regulatory requirements, particularly with regard to safety, are extremely rigorous. This chapter highlights regulatory aspects on carbohydrate-based vaccines with an emphasis on analytical approaches to ensure the consistent quality of successive manufacturing lots.

  7. Regulatory frameworks for decentralised energy

    International Nuclear Information System (INIS)

    Woodman, Bridget; Baker, Philip

    2008-01-01

    This paper considers aspects of the current regulatory frameworks for markets and infrastructure which can inhibit the deployment of decentralised energy. The government has stated that decentralised energy can make a positive contribution to reducing the UK's carbon emissions, but recognises that at the moment the technologies face market and regulatory barriers. If it is to become a viable alternative to centralised generation, energy market design and the regulation of energy infrastructure will have to evolve to ensure that decentralised options are no longer locked out. (author)

  8. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2014-01-01

    This section of the Bulletin presents a summary of the recent national legislative and regulatory activities sorted by country and topic: - Algeria: Nuclear security. - France: Radioactive waste management; Nuclear safety and radiological protection; General legislation; International co-operation. - Germany: International trade. - Indonesia: Nuclear security, General legislation. - Ireland: Nuclear safety and radiological protection; General legislation. - Lithuania: Nuclear security; Nuclear safety and radiological protection. - Slovak Republic: International co-operation; Liability and compensation; Environmental protection. - Switzerland: Radioactive waste management. - United Arab Emirates: Liability and compensation. - United States: Radioactive waste management; Licensing and regulatory infrastructure

  9. 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)

  10. The Herbaspirillum seropedicae SmR1 Fnr orthologs controls the cytochrome composition of the electron transport chain.

    Science.gov (United States)

    Batista, Marcelo B; Sfeir, Michelle Z T; Faoro, Helisson; Wassem, Roseli; Steffens, Maria B R; Pedrosa, Fábio O; Souza, Emanuel M; Dixon, Ray; Monteiro, Rose A

    2013-01-01

    The transcriptional regulatory protein Fnr, acts as an intracellular redox sensor regulating a wide range of genes in response to changes in oxygen levels. Genome sequencing of Herbaspirillum seropedicae SmR1 revealed the presence of three fnr-like genes. In this study we have constructed single, double and triple fnr deletion mutant strains of H. seropedicae. Transcriptional profiling in combination with expression data from reporter fusions, together with spectroscopic analysis, demonstrates that the Fnr1 and Fnr3 proteins not only regulate expression of the cbb3-type respiratory oxidase, but also control the cytochrome content and other component complexes required for the cytochrome c-based electron transport pathway. Accordingly, in the absence of the three Fnr paralogs, growth is restricted at low oxygen tensions and nitrogenase activity is impaired. Our results suggest that the H. seropedicae Fnr proteins are major players in regulating the composition of the electron transport chain in response to prevailing oxygen concentrations.

  11. H2S and polysulfide metabolism: Conventional and unconventional pathways.

    Science.gov (United States)

    Olson, Kenneth R

    2018-03-01

    It is now well established that hydrogen sulfide (H 2 S) is an effector of a wide variety of physiological processes. It is also clear that many of the effects of H 2 S are mediated through reactions with cysteine sulfur on regulatory proteins and most of these are not mediated directly by H 2 S but require prior oxidation of H 2 S and the formation of per- and polysulfides (H 2 S n , n = 2-8). Attendant with understanding the regulatory functions of H 2 S and H 2 S n is an appreciation of the mechanisms that control, i.e., both increase and decrease, their production and catabolism. Although a number of standard "conventional" pathways have been described and well characterized, novel "unconventional" pathways are continuously being identified. This review summarizes our current knowledge of both the conventional and unconventional. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. 76 FR 20759 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-04-13

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate..., 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange.... For more information about the rulebook consolidation process, see Information Notice, March 12, 2008...

  13. 76 FR 40412 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-07-08

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate..., Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission... a more limited application by their terms. For more information about the rulebook consolidation...

  14. 75 FR 60157 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2010-09-29

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate..., 2010, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange... information about the rulebook consolidation process, see Information Notice, March 12, 2008 (Rulebook...

  15. 75 FR 71164 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2010-11-22

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate..., 2010, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange.... For more information about the rulebook consolidation process, see Information Notice, March 12, 2008...

  16. 76 FR 12380 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2011-03-07

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of Amendment No. 1..., the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange... information about the rulebook consolidation process, see Information Notice, March 12, 2008 (Rulebook...

  17. 76 FR 66344 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2011-10-26

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change... 31, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a National Association of... consolidation process, see Information Notice, March 12, 2008 (Rulebook Consolidation Process). For convenience...

  18. 75 FR 17456 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2010-04-06

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change..., Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission... terms. For more information about the rulebook consolidation process, see Information Notice, March 12...

  19. Regulatory Control of Radiation Sources. Safety Guide

    International Nuclear Information System (INIS)

    2009-01-01

    This Safety Guide is intended to assist States in implementing the requirements established in Safety Standards Series No. GS-R-1, Legal and Governmental Infrastructure for Nuclear, Radiation, Radioactive Waste and Transport Safety, for a national regulatory infrastructure to regulate any practice involving radiation sources in medicine, industry, research, agriculture and education. The Safety Guide provides advice on the legislative basis for establishing regulatory bodies, including the effective independence of the regulatory body. It also provides guidance on implementing the functions and activities of regulatory bodies: the development of regulations and guides on radiation safety; implementation of a system for notification and authorization; carrying out regulatory inspections; taking necessary enforcement actions; and investigating accidents and circumstances potentially giving rise to accidents. The various aspects relating to the regulatory control of consumer products are explained, including justification, optimization of exposure, safety assessment and authorization. Guidance is also provided on the organization and staffing of regulatory bodies. Contents: 1. Introduction; 2. Legal framework for a regulatory infrastructure; 3. Principal functions and activities of the regulatory body; 4. Regulatory control of the supply of consumer products; 5. Functions of the regulatory body shared with other governmental agencies; 6. Organization and staffing of the regulatory body; 7. Documentation of the functions and activities of the regulatory body; 8. Support services; 9. Quality management for the regulatory system.

  20. Control of Metastatic Progression by microRNA Regulatory Networks

    Science.gov (United States)

    Pencheva, Nora; Tavazoie, Sohail F.

    2015-01-01

    Aberrant microRNA (miRNA) expression is a defining feature of human malignancy. Specific miRNAs have been identified as promoters or suppressors of metastatic progression. These miRNAs control metastasis through divergent or convergent regulation of metastatic gene pathways. Some miRNA regulatory networks govern cell-autonomous cancer phenotypes, while others modulate the cell-extrinsic composition of the metastatic microenvironment. The use of small RNAs as probes into the molecular and cellular underpinnings of metastasis holds promise for the identification of candidate genes for potential therapeutic intervention. PMID:23728460

  1. Electron detector

    International Nuclear Information System (INIS)

    Hashimoto, H.; Mogami, A.

    1975-01-01

    A device for measuring electron densities at a given energy level in an electron beam or the like having strong background noise, for example, in the detection of Auger electric energy spectrums is described. An electron analyzer passes electrons at the given energy level and at the same time electrons of at least one adjacent energy level. Detecting means associated therewith produce signals indicative of the densities of the electrons at each energy level and combine these signals to produce a signal indicative of the density of the electrons of the given energy level absent background noise

  2. 75 FR 39299 - Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Notice of Filing and Immediate Effectiveness...

    Science.gov (United States)

    2010-07-08

    ... French as the Bourse de Montr[eacute]al Inc. II. Self-Regulatory Organization's Statement of the Purpose... submitted by any of the following methods: Electronic Comments Use the Commission's Internet comment form...

  3. Development of an Ingestion Pathway Model for AXAIRQ

    Energy Technology Data Exchange (ETDEWEB)

    Simpkins, A.A.

    1999-01-13

    AXAIRQ is a dose mode code used for prospective accident assessment at the Savannah River Site and is primarily used to show regulatory compliance. For completeness of pathway analysis, an ingestion model, AXINGST, has been developed for use with, and incorporation in, AXAIRQ. Currently available ingestion models were referenced as a basis for AXINGST. AXINGST calculates a conservative ingestion dose following an atmospheric release of radionuclides and includes site specific variables where applicable.

  4. Ingestion Pathway Transfer Factors for Plutonium and Americium

    International Nuclear Information System (INIS)

    Blanchard, A.

    1999-01-01

    Overall transfer factors for major ingestion pathways are derived for plutonium and americium. These transfer factors relate the radionuclide concentration in a given foodstuff to deposition on the soil. Equations describing basic relationships consistent with Regulatory Guide 1.109 are followed. Updated values and coefficients from IAEA Technical Reports Series No. 364 are used when a available. Preference is given to using factors specific to the Savannah River Site

  5. Penalized differential pathway analysis of integrative oncogenomics studies.

    Science.gov (United States)

    van Wieringen, Wessel N; van de Wiel, Mark A

    2014-04-01

    Through integration of genomic data from multiple sources, we may obtain a more accurate and complete picture of the molecular mechanisms underlying tumorigenesis. We discuss the integration of DNA copy number and mRNA gene expression data from an observational integrative genomics study involving cancer patients. The two molecular levels involved are linked through the central dogma of molecular biology. DNA copy number aberrations abound in the cancer cell. Here we investigate how these aberrations affect gene expression levels within a pathway using observational integrative genomics data of cancer patients. In particular, we aim to identify differential edges between regulatory networks of two groups involving these molecular levels. Motivated by the rate equations, the regulatory mechanism between DNA copy number aberrations and gene expression levels within a pathway is modeled by a simultaneous-equations model, for the one- and two-group case. The latter facilitates the identification of differential interactions between the two groups. Model parameters are estimated by penalized least squares using the lasso (L1) penalty to obtain a sparse pathway topology. Simulations show that the inclusion of DNA copy number data benefits the discovery of gene-gene interactions. In addition, the simulations reveal that cis-effects tend to be over-estimated in a univariate (single gene) analysis. In the application to real data from integrative oncogenomic studies we show that inclusion of prior information on the regulatory network architecture benefits the reproducibility of all edges. Furthermore, analyses of the TP53 and TGFb signaling pathways between ER+ and ER- samples from an integrative genomics breast cancer study identify reproducible differential regulatory patterns that corroborate with existing literature.

  6. Codes and standards and other guidance cited in regulatory documents. Revision 1

    Energy Technology Data Exchange (ETDEWEB)

    Ankrum, A.; Nickolaus, J.; Vinther, R.; Maguire-Moffitt, N.; Hammer, J.; Sherfey, L.; Warner, R. [Pacific Northwest Lab., Richland, WA (United States)

    1994-08-01

    As part of the US Nuclear Regulatory Commission (NRC) Standard Review Plan Update and Development Program, Pacific Northwest Laboratory developed a listing of industry consensus codes and standards and other government and industry guidance referred to in regulatory documents. In addition to updating previous information, Revision 1 adds citations from the NRC Inspection Manual and the Improved Standard Technical Specifications. This listing identifies the version of the code or standard cited in the regulatory document, the regulatory document, and the current version of the code or standard. It also provides a summary characterization of the nature of the citation. This listing was developed from electronic searches of the Code of Federal Regulations and the NRC`s Bulletins, Information Notices, Circulars, Generic Letters, Policy Statements, Regulatory Guides, and the Standard Review Plan (NUREG-0800).

  7. Codes and standards and other guidance cited in regulatory documents. Revision 1

    International Nuclear Information System (INIS)

    Ankrum, A.; Nickolaus, J.; Vinther, R.; Maguire-Moffitt, N.; Hammer, J.; Sherfey, L.; Warner, R.

    1994-08-01

    As part of the US Nuclear Regulatory Commission (NRC) Standard Review Plan Update and Development Program, Pacific Northwest Laboratory developed a listing of industry consensus codes and standards and other government and industry guidance referred to in regulatory documents. In addition to updating previous information, Revision 1 adds citations from the NRC Inspection Manual and the Improved Standard Technical Specifications. This listing identifies the version of the code or standard cited in the regulatory document, the regulatory document, and the current version of the code or standard. It also provides a summary characterization of the nature of the citation. This listing was developed from electronic searches of the Code of Federal Regulations and the NRC's Bulletins, Information Notices, Circulars, Generic Letters, Policy Statements, Regulatory Guides, and the Standard Review Plan (NUREG-0800)

  8. Radiation practices and regulatory control

    International Nuclear Information System (INIS)

    1997-01-01

    The general principles to be observed in the regulatory control of ionizing radiation use and practices are specified in the guide. It also takes into account of additions and alterations needed for for compliance with the European Union (EU) directives that have not been mentioned in other STUK/ST-guides. (6 refs.)

  9. Management systems for regulatory authorities

    International Nuclear Information System (INIS)

    Mpandanyama, Rujeko Lynette

    2015-02-01

    For a regulatory body to fulfil its statutory obligations, there is need to develop and implement a regulatory management system that has the necessary arrangements for achieving and maintaining high quality performance in regulating the safety of nuclear and radiation facilities under its authority. Hence, the regulatory management system needs to fully integrate the human resources, processes and physical resources of the organization. This study sought to provide an understanding of the concept, principles, policies and fundamentals of management systems as they relate to regulatory systems in the field of radiation protection and to make appropriate recommendations to ensure that an effective management system exists for the control of ionizing radiation and radiation sources and addresses all relevant stakeholders in Zimbabwe. A comparative analysis was done on the current management status and the ideal management system, which led to the identification of the gaps existing. The main key that was found to be of significance was lack of linkages between processes and management tools within the institution. (au)

  10. Private Equity and Regulatory Capital

    NARCIS (Netherlands)

    Bongaerts, D.; Charlier, E.

    2008-01-01

    Regulatory Capital requirements for European banks have been put forward in the Basel II Capital Framework and subsequently in the Capital Requirements Directive (CRD) of the EU. We provide a detailed discussion of the capital requirements for private equity investments under the simple risk weight

  11. Radiation practices and regulatory control

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-06-01

    The general principles to be observed in the regulatory control of ionizing radiation use and practices are specified in the guide. It also takes into account of additions and alterations needed for for compliance with the European Union (EU) directives that have not been mentioned in other STUK/ST-guides. (6 refs.).

  12. Regulatory perspectives of concept assessment

    International Nuclear Information System (INIS)

    Flavelle, Peter A.

    1987-09-01

    The Atomic Energy Control Board is the head agency for the regulatory review of the Assessment of the Canadian Concept for Nuclear Fuel Waste Disposal being done by Atomic Energy of Canada Limited and Ontario Hydro. This paper describes the regulatory perspective of how the Concept Assessment could demonstrate the feasibility of a disposal conforming to regulatory requirements. The long-term aspects of Concept Assessment encourage the use of various predictive techniques for different time scales. Each technique will have a different potential for establishing confidence in the predictions. The predicted performance of a facility during operation should have a very high confidence, as it can be based on standard engineering calculations and the predictions can be validated later by monitoring during operation. The predictions of the transient period following closure of the facility should achieve a medium level of confidence, since they can be based on extrapolations of predictions of operational performance, using models that can be calibrated with monitoring data and with averaged input data derived from natural analog studies. Predictions based on fundamental processes will have a medium level of confidence when made to intermediate times after closure. Long-term predictions using generic or typical input data or Monte Carlo calculations of simplified models will have the least confidence and yet they can still contribute to the confidence that the disposal concept will conform to regulatory requirements

  13. NRC regulatory information conference: Proceedings

    International Nuclear Information System (INIS)

    1989-09-01

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

  14. 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....

  15. Regulatory networks in pollen development under cold stress

    Directory of Open Access Journals (Sweden)

    Kamal Dev Sharma

    2016-03-01

    Full Text Available Cold stress modifies anthers’ metabolic pathways to induce pollen sterility. Cold-tolerant plants, unlike the susceptible ones, produce high proportion of viable pollen. Anthers in susceptible plants, when exposed to cold stress, increase abscisic acid (ABA metabolism and reduce ABA catabolism. Increased ABA negatively regulates expression of tapetum cell wall bound invertase and monosaccharide transport genes resulting in distorted carbohydrate pool in anther. Cold-stress also reduces endogenous levels of the bioactive gibberellins (GAs, GA4 and GA7, in susceptible anthers by repression of the GA biosynthesis genes. Here we discuss recent findings on mechanisms of cold susceptibility in anthers which determine pollen sterility. We also discuss differences in regulatory pathways between cold-stressed anthers of susceptible and tolerant plants that decide pollen sterility or viability.

  16. Probabilistic pathway construction.

    Science.gov (United States)

    Yousofshahi, Mona; Lee, Kyongbum; Hassoun, Soha

    2011-07-01

    Expression of novel synthesis pathways in host organisms amenable to genetic manipulations has emerged as an attractive metabolic engineering strategy to overproduce natural products, biofuels, biopolymers and other commercially useful metabolites. We present a pathway construction algorithm for identifying viable synthesis pathways compatible with balanced cell growth. Rather than exhaustive exploration, we investigate probabilistic selection of reactions to construct the pathways. Three different selection schemes are investigated for the selection of reactions: high metabolite connectivity, low connectivity and uniformly random. For all case studies, which involved a diverse set of target metabolites, the uniformly random selection scheme resulted in the highest average maximum yield. When compared to an exhaustive search enumerating all possible reaction routes, our probabilistic algorithm returned nearly identical distributions of yields, while requiring far less computing time (minutes vs. years). The pathways identified by our algorithm have previously been confirmed in the literature as viable, high-yield synthesis routes. Prospectively, our algorithm could facilitate the design of novel, non-native synthesis routes by efficiently exploring the diversity of biochemical transformations in nature. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Development of digital library system on regulatory documents for nuclear power plants

    International Nuclear Information System (INIS)

    Lee, K. H.; Kim, K. J.; Yoon, Y. H.; Kim, M. W.; Lee, J. I.

    2001-01-01

    The main objective of this study is to establish nuclear regulatory document retrieval system based on internet. With the advancement of internet and information processing technology, information management patterns are going through a new paradigm. Getting along the current of the time, it is general tendency to transfer paper-type documents into electronic-type documents through document scanning and indexing. This system consists of nuclear regulatory documents, nuclear safety documents, digital library, and information system with index and full text

  18. minepath.org: a free interactive pathway analysis web server.

    Science.gov (United States)

    Koumakis, Lefteris; Roussos, Panos; Potamias, George

    2017-07-03

    ( www.minepath.org ) is a web-based platform that elaborates on, and radically extends the identification of differentially expressed sub-paths in molecular pathways. Besides the network topology, the underlying MinePath algorithmic processes exploit exact gene-gene molecular relationships (e.g. activation, inhibition) and are able to identify differentially expressed pathway parts. Each pathway is decomposed into all its constituent sub-paths, which in turn are matched with corresponding gene expression profiles. The highly ranked, and phenotype inclined sub-paths are kept. Apart from the pathway analysis algorithm, the fundamental innovation of the MinePath web-server concerns its advanced visualization and interactive capabilities. To our knowledge, this is the first pathway analysis server that introduces and offers visualization of the underlying and active pathway regulatory mechanisms instead of genes. Other features include live interaction, immediate visualization of functional sub-paths per phenotype and dynamic linked annotations for the engaged genes and molecular relations. The user can download not only the results but also the corresponding web viewer framework of the performed analysis. This feature provides the flexibility to immediately publish results without publishing source/expression data, and get all the functionality of a web based pathway analysis viewer. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  19. Intricacies of hedgehog signaling pathways: A perspective in tumorigenesis

    International Nuclear Information System (INIS)

    Kar, Swayamsiddha; Deb, Moonmoon; Sengupta, Dipta; Shilpi, Arunima; Bhutia, Sujit Kumar; Patra, Samir Kumar

    2012-01-01

    The hedgehog (HH) signaling pathway is a crucial negotiator of developmental proceedings in the embryo governing a diverse array of processes including cell proliferation, differentiation, and tissue patterning. The overall activity of the pathway is significantly curtailed after embryogenesis as well as in adults, yet it retains many of its functional capacities. However, aberration in HH signaling mediates the initiation, proliferation and continued sustenance of malignancy in different tissues to varying degrees through different mechanisms. In this review, we provide an overview of the role of constitutively active aberrant HH signaling pathway in different types of human cancer and the underlying molecular and genetic mechanisms that drive tumorigenesis in that particular tissue. An insight into the various modes of anomalous HH signaling in different organs will provide a comprehensive knowledge of the pathway in these tissues and open a window for individually tailored, tissue-specific therapeutic interventions. The synergistic cross talking of HH pathway with many other regulatory molecules and developmentally inclined signaling pathways may offer many avenues for pharmacological advances. Understanding the molecular basis of abnormal HH signaling in cancer will provide an opportunity to inhibit the deregulated pathway in many aggressive and therapeutically challenging cancers where promising options are not available.

  20. Intricacies of hedgehog signaling pathways: A perspective in tumorigenesis

    Energy Technology Data Exchange (ETDEWEB)

    Kar, Swayamsiddha; Deb, Moonmoon; Sengupta, Dipta; Shilpi, Arunima; Bhutia, Sujit Kumar [Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha 769008 (India); Patra, Samir Kumar, E-mail: samirp@nitrkl.ac.in [Epigenetics and Cancer Research Laboratory, Biochemistry and Molecular Biology Group, Department of Life Science, National Institute of Technology, Rourkela, Odisha 769008 (India)

    2012-10-01

    The hedgehog (HH) signaling pathway is a crucial negotiator of developmental proceedings in the embryo governing a diverse array of processes including cell proliferation, differentiation, and tissue patterning. The overall activity of the pathway is significantly curtailed after embryogenesis as well as in adults, yet it retains many of its functional capacities. However, aberration in HH signaling mediates the initiation, proliferation and continued sustenance of malignancy in different tissues to varying degrees through different mechanisms. In this review, we provide an overview of the role of constitutively active aberrant HH signaling pathway in different types of human cancer and the underlying molecular and genetic mechanisms that drive tumorigenesis in that particular tissue. An insight into the various modes of anomalous HH signaling in different organs will provide a comprehensive knowledge of the pathway in these tissues and open a window for individually tailored, tissue-specific therapeutic interventions. The synergistic cross talking of HH pathway with many other regulatory molecules and developmentally inclined signaling pathways may offer many avenues for pharmacological advances. Understanding the molecular basis of abnormal HH signaling in cancer will provide an opportunity to inhibit the deregulated pathway in many aggressive and therapeutically challenging cancers where promising options are not available.

  1. Yeast glucose pathways converge on the transcriptional regulation of trehalose biosynthesis

    Directory of Open Access Journals (Sweden)

    Apweiler Eva

    2012-06-01

    Full Text Available Abstract Background Cellular glucose availability is crucial for the functioning of most biological processes. Our understanding of the glucose regulatory system has been greatly advanced by studying the model organism Saccharomyces cerevisiae, but many aspects of this system remain elusive. To understand the organisation of the glucose regulatory system, we analysed 91 deletion mutants of the different glucose signalling and metabolic pathways in Saccharomyces cerevisiae using DNA microarrays. Results In general, the mutations do not induce pathway-specific transcriptional responses. Instead, one main transcriptional response is discerned, which varies in direction to mimic either a high or a low glucose response. Detailed analysis uncovers established and new relationships within and between individual pathways and their members. In contrast to signalling components, metabolic components of the glucose regulatory system are transcriptionally more frequently affected. A new network approach is applied that exposes the hierarchical organisation of the glucose regulatory system. Conclusions The tight interconnection between the different pathways of the glucose regulatory system is reflected by the main transcriptional response observed. Tps2 and Tsl1, two enzymes involved in the biosynthesis of the storage carbohydrate trehalose, are predicted to be the most downstream transcriptional components. Epistasis analysis of tps2Δ double mutants supports this prediction. Although based on transcriptional changes only, these results suggest that all changes in perceived glucose levels ultimately lead to a shift in trehalose biosynthesis.

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

    Science.gov (United States)

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

    2015-04-23

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

  3. Electron/electron acoustic instability

    International Nuclear Information System (INIS)

    Gary, S.P.

    1987-01-01

    The electron acoustic wave becomes a normal mode of an unmagnetized collisionless plasma in the presence of two electron components with similar densities, but strongly disparate temperatures. The characteristic frequency of this mode is the plasma frequency of the cooler electron component. If these two electron components have a relative drift speed several times the thermal speed of the cooler component, the electron/electron acoustic instability may arise. This paper describes the parametric dependences of the threshold drift speed and maximum growth rate of this instability, and compares these with the same properties of the electron/ion acoustic instability. Under the condition of zero current, the electron/ion acoustic instability typically has the lower threshold drift speed, so that observation of the electron/electron acoustic instability is a strong indication of the presence of an electrical current in the plasma

  4. Regulatory effects of fisetin on microglial activation.

    Science.gov (United States)

    Chuang, Jing-Yuan; Chang, Pei-Chun; Shen, Yi-Chun; Lin, Chingju; Tsai, Cheng-Fang; Chen, Jia-Hong; Yeh, Wei-Lan; Wu, Ling-Hsuan; Lin, Hsiao-Yun; Liu, Yu-Shu; Lu, Dah-Yuu

    2014-06-26

    Increasing evidence suggests that inflammatory processes in the central nervous system that are mediated by microglial activation play a key role in neurodegeneration. Fisetin, a plant flavonol commonly found in fruits and vegetables, is frequently added to nutritional supplements due to its antioxidant properties. In the present study, treatment with fisetin inhibited microglial cell migration and ROS (reactive oxygen species) production. Treatment with fisetin also effectively inhibited LPS plus IFN-γ-induced nitric oxide (NO) production, and inducible nitric oxide synthase (iNOS) expression in microglial cells. Furthermore, fisetin also reduced expressions of iNOS and NO by stimulation of peptidoglycan, the major component of the Gram-positive bacterium cell wall. Fisetin also inhibited the enhancement of LPS/IFN-γ- or peptidoglycan-induced inflammatory mediator IL (interlukin)-1 β expression. Besides the antioxidative and anti-inflammatory effects of fisetin, our study also elucidates the manner in fisetin-induced an endogenous anti-oxidative enzyme HO (heme oxygenase)-1 expression. Moreover, the regulatory molecular mechanism of fisetin-induced HO-1 expression operates through the PI-3 kinase/AKT and p38 signaling pathways in microglia. Notably, fisetin also significantly attenuated inflammation-related microglial activation and coordination deficit in mice in vivo. These findings suggest that fisetin may be a candidate agent for the development of therapies for inflammation-related neurodegenerative diseases.

  5. Biosimilars: a regulatory perspective from America.

    Science.gov (United States)

    Kay, Jonathan

    2011-05-12

    Biosimilars are protein products that are sufficiently similar to a biopharmaceutical already approved by a regulatory agency. Several biotechnology companies and generic drug manufacturers in Asia and Europe are developing biosimilars of tumor necrosis factor inhibitors and rituximab. A biosimilar etanercept is already being marketed in Colombia and China. In the US, several natural source products and recombinant proteins have been approved as generic drugs under Section 505(b)(2) of the Food, Drug, and Cosmetic Act. However, because the complexity of large biopharmaceuticals makes it difficult to demonstrate that a biosimilar is structurally identical to an already approved biopharmaceutical, this Act does not apply to biosimilars of large biopharmaceuticals. Section 7002 of the Patient Protection and Affordable Care Act of 2010, which is referred to as the Biologics Price Competition and Innovation Act of 2009, amends Section 351 of the Public Health Service Act to create an abbreviated pathway that permits a biosimilar to be evaluated by comparing it with only a single reference biological product. This paper reviews the processes for approval of biosimilars in the US and the European Union and highlights recent changes in federal regulations governing the approval of biosimilars in the US.

  6. Regulatory Effects of Fisetin on Microglial Activation

    Directory of Open Access Journals (Sweden)

    Jing-Yuan Chuang

    2014-06-01

    Full Text Available Increasing evidence suggests that inflammatory processes in the central nervous system that are mediated by microglial activation play a key role in neurodegeneration. Fisetin, a plant flavonol commonly found in fruits and vegetables, is frequently added to nutritional supplements due to its antioxidant properties. In the present study, treatment with fisetin inhibited microglial cell migration and ROS (reactive oxygen species production. Treatment with fisetin also effectively inhibited LPS plus IFN-γ-induced nitric oxide (NO production, and inducible nitric oxide synthase (iNOS expression in microglial cells. Furthermore, fisetin also reduced expressions of iNOS and NO by stimulation of peptidoglycan, the major component of the Gram-positive bacterium cell wall. Fisetin also inhibited the enhancement of LPS/IFN-γ- or peptidoglycan-induced inflammatory mediator IL (interlukin-1 β expression. Besides the antioxidative and anti-inflammatory effects of fisetin, our study also elucidates the manner in fisetin-induced an endogenous anti-oxidative enzyme HO (heme oxygenase-1 expression. Moreover, the regulatory molecular mechanism of fisetin-induced HO-1 expression operates through the PI-3 kinase/AKT and p38 signaling pathways in microglia. Notably, fisetin also significantly attenuated inflammation-related microglial activation and coordination deficit in mice in vivo. These findings suggest that fisetin may be a candidate agent for the development of therapies for inflammation-related neurodegenerative diseases.

  7. Pathway-based analyses.

    Science.gov (United States)

    Kent, Jack W

    2016-02-03

    New technologies for acquisition of genomic data, while offering unprecedented opportunities for genetic discovery, also impose severe burdens of interpretation and penalties for multiple testing. The Pathway-based Analyses Group of the Genetic Analysis Workshop 19 (GAW19) sought reduction of multiple-testing burden through various approaches to aggregation of highdimensional data in pathways informed by prior biological knowledge. Experimental methods testedincluded the use of "synthetic pathways" (random sets of genes) to estimate power and false-positive error rate of methods applied to simulated data; data reduction via independent components analysis, single-nucleotide polymorphism (SNP)-SNP interaction, and use of gene sets to estimate genetic similarity; and general assessment of the efficacy of prior biological knowledge to reduce the dimensionality of complex genomic data. The work of this group explored several promising approaches to managing high-dimensional data, with the caveat that these methods are necessarily constrained by the quality of external bioinformatic annotation.

  8. Induction of cytoprotective pathways is central to the extension of lifespan conferred by multiple longevity pathways.

    Directory of Open Access Journals (Sweden)

    David E Shore

    Full Text Available Many genetic and physiological treatments that extend lifespan also confer resistance to a variety of stressors, suggesting that cytoprotective mechanisms underpin the regulation of longevity. It has not been established, however, whether the induction of cytoprotective pathways is essential for lifespan extension or merely correlated. Using a panel of GFP-fused stress response genes, we identified the suites of cytoprotective pathways upregulated by 160 gene inactivations known to increase Caenorhabditis elegans longevity, including the mitochondrial UPR (hsp-6, hsp-60, the ER UPR (hsp-4, ROS response (sod-3, gst-4, and xenobiotic detoxification (gst-4. We then screened for other gene inactivations that disrupt the induction of these responses by xenobiotic or genetic triggers, identifying 29 gene inactivations required for cytoprotective gene expression. If cytoprotective responses contribute directly to lifespan extension, inactivation of these genes would be expected to compromise the extension of lifespan conferred by decreased insulin/IGF-1 signaling, caloric restriction, or the inhibition of mitochondrial function. We find that inactivation of 25 of 29 cytoprotection-regulatory genes shortens the extension of longevity normally induced by decreased insulin/IGF-1 signaling, disruption of mitochondrial function, or caloric restriction, without disrupting normal longevity nearly as dramatically. These data demonstrate that induction of cytoprotective pathways is central to longevity extension and identify a large set of new genetic components of the pathways that detect cellular damage and couple that detection to downstream cytoprotective effectors.

  9. Pathways to youth homelessness.

    Science.gov (United States)

    Martijn, Claudine; Sharpe, Louise

    2006-01-01

    Research documents high levels of psychopathology among homeless youth. Most research, however, has not distinguished between disorders that are present prior to homelessness and those that develop following homelessness. Hence whether psychological disorders are the cause or consequence of homelessness has not been established. The aim of this study is to investigate causal pathways to homelessness amongst currently homeless youth in Australia. The study uses a quasi-qualitative methodology to generate hypotheses for larger-scale research. High rates of psychological disorders were confirmed in the sample 35 homeless youth aged 14-25. The rates of psychological disorders at the point of homelessness were greater than in normative samples, but the rates of clinical disorder increased further once homeless. Further in-depth analyses were conducted to identify the temporal sequence for each individual with a view to establishing a set of causal pathways to homelessness and trajectories following homelessness that characterised the people in the sample. Five pathways to homelessness and five trajectories following homelessness were identified that accounted for the entire sample. Each pathway constituted a series of interactions between different factors similar to that described by Craig and Hodson (1998. Psychological Medicine, 28, 1379-1388) as "complex subsidiary pathways". The major findings were that (1) trauma is a common experience amongst homeless youth prior to homelessness and figured in the causal pathways to homelessness for over half of the sample; (2) once homeless, for the majority of youth there is an increase in the number of psychological diagnoses including drug and alcohol diagnoses; and (3) crime did not precede homelessness for all but one youth; however, following homelessness, involvement in criminal activity was common and became a distinguishing factor amongst youth. The implications of these findings for future research and service

  10. The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of pathway/genome databases

    Science.gov (United States)

    Caspi, Ron; Altman, Tomer; Dale, Joseph M.; Dreher, Kate; Fulcher, Carol A.; Gilham, Fred; Kaipa, Pallavi; Karthikeyan, Athikkattuvalasu S.; Kothari, Anamika; Krummenacker, Markus; Latendresse, Mario; Mueller, Lukas A.; Paley, Suzanne; Popescu, Liviu; Pujar, Anuradha; Shearer, Alexander G.; Zhang, Peifen; Karp, Peter D.

    2010-01-01

    The MetaCyc database (MetaCyc.org) is a comprehensive and freely accessible resource for metabolic pathways and enzymes from all domains of life. The pathways in MetaCyc are experimentally determined, small-molecule metabolic pathways and are curated from the primary scientific literature. With more than 1400 pathways, MetaCyc is the largest collection of metabolic pathways currently available. Pathways reactions are linked to one or more well-characterized enzymes, and both pathways and enzymes are annotated with reviews, evidence codes, and literature citations. BioCyc (BioCyc.org) is a collection of more than 500 organism-specific Pathway/Genome Databases (PGDBs). Each BioCyc PGDB contains the full genome and predicted metabolic network of one organism. The network, which is predicted by the Pathway Tools software using MetaCyc as a reference, consists of metabolites, enzymes, reactions and metabolic pathways. BioCyc PGDBs also contain additional features, such as predicted operons, transport systems, and pathway hole-fillers. The BioCyc Web site offers several tools for the analysis of the PGDBs, including Omics Viewers that enable visualization of omics datasets on two different genome-scale diagrams and tools for comparative analysis. The BioCyc PGDBs generated by SRI are offered for adoption by any party interested in curation of metabolic, regulatory, and genome-related information about an organism. PMID:19850718

  11. Electronic Connection Between the Quinone and Cytochrome c Redox Pools and Its Role in Regulation of Mitochondrial Electron Transport and Redox Signaling

    Science.gov (United States)

    Sarewicz, Marcin; Osyczka, Artur

    2015-01-01

    Mitochondrial respiration, an important bioenergetic process, relies on operation of four membranous enzymatic complexes linked functionally by mobile, freely diffusible elements: quinone molecules in the membrane and water-soluble cytochromes c in the intermembrane space. One of the mitochondrial complexes, complex III (cytochrome bc1 or ubiquinol:cytochrome c oxidoreductase), provides an electronic connection between these two diffusible redox pools linking in a fully reversible manner two-electron quinone oxidation/reduction with one-electron cytochrome c reduction/oxidation. Several features of this homodimeric enzyme implicate that in addition to its well-defined function of contributing to generation of proton-motive force, cytochrome bc1 may be a physiologically important point of regulation of electron flow acting as a sensor of the redox state of mitochondria that actively responds to changes in bioenergetic conditions. These features include the following: the opposing redox reactions at quinone catalytic sites located on the opposite sides of the membrane, the inter-monomer electronic connection that functionally links four quinone binding sites of a dimer into an H-shaped electron transfer system, as well as the potential to generate superoxide and release it to the intermembrane space where it can be engaged in redox signaling pathways. Here we highlight recent advances in understanding how cytochrome bc1 may accomplish this regulatory physiological function, what is known and remains unknown about catalytic and side reactions within the quinone binding sites and electron transfers through the cofactor chains connecting those sites with the substrate redox pools. We also discuss the developed molecular mechanisms in the context of physiology of mitochondria. PMID:25540143

  12. 77 FR 52791 - Regulatory Capital Rules: Regulatory Capital, Implementation of Basel III, Minimum Regulatory...

    Science.gov (United States)

    2012-08-30

    ... the Basel Committee on Banking Supervision (BCBS) in ``Basel III: A Global Regulatory Framework for... seeking comment on the two related NPRs published elsewhere in today's Federal Register. The two related... them on Regulations.gov without change, including any business or personal information that you provide...

  13. Association of Regulatory Boards of Optometry

    Science.gov (United States)

    ... website of the Association of Regulatory Boards of Optometry (ARBO). ARBO's web site is designed to provide resources to regulatory boards of optometry throughout the world. State/Provincial/Territorial Boards of ...

  14. Small Business Administration Semiannual Regulatory Agenda

    Science.gov (United States)

    2010-12-20

    ... small business concerns owned and controlled by women, and to women wishing to start a small business... Business Administration Semiannual Regulatory Agenda] Part XVII Small Business Administration Semiannual Regulatory Agenda [[Page 79864

  15. The Political Economy of Regulatory Risk

    OpenAIRE

    Strausz, Roland

    2009-01-01

    I investigate the argument that, in a two–party system with different regulatory objectives, political uncertainty generates regulatory risk. I show that this risk has a fluctuation effect that hurts both parties and an output–expansion effect that benefits one party. Consequently, at least one party dislikes regulatory risk. Moreover, both political parties gain from eliminating regulatory risk when political divergence is small or the winning probability of the regulatory–risk–averse party ...

  16. Nuclear Regulatory Commission 1989 Information Digest

    International Nuclear Information System (INIS)

    1989-03-01

    The Nuclear Regulatory Commission 1989 Information Digest provides summary information regarding the US Nuclear Regulatory Commission, its regulatory responsibilities, and areas licensed by the Commission. This is the first of an annual publication for the general use of the NRC staff and is available to the public. The Digest is divided into two parts: the first presents an overview of the US Nuclear Regulatory Commission and the second provides data on NRC commercial nuclear reactor licensees and commercial nuclear power reactors worldwide

  17. Internalisation of membrane progesterone receptor-α after treatment with progesterone: Potential involvement of a clathrin-dependent pathway.

    Science.gov (United States)

    Foster, Helen; Reynolds, Alan; Stenbeck, Gudrun; Dong, Jing; Thomas, Peter; Karteris, Emmanouil

    2010-01-01

    Internalisation and recycling of seven trans-membrane domain receptors is a critical regulatory event for their signalling. The mechanism(s) by which membrane progesterone receptor-α (mPRα) number is regulated on the cell surface is unclear. In this study, we investigated the cellular distribution of mPRα and mechanisms of mPRα trafficking using a cell line derived from a primary culture of human myometrial cells (M11) as an experimental model. RT-PCR and immunofluorescent analysis demonstrated expression of mPRα in M11 cells with mPRα primarily distributed on the cell surface under basal conditions. For the first time, plasma membrane localisation of mPRα was confirmed using immuno-gold transmission electron microscopy. Stimulation of M11 cells with progesterone (P4, 100 nM) resulted in internalisation of mPRα from the plasma membrane to the cytoplasm (10 min) and subsequent partial translocation back to the cell surface (20 min). We investigated potential endocytotic pathways involved in trafficking of mPRα after its internalisation. Partial co-localisation of clathrin with mPRα was obvious after 10 min of P4 treatment. Of note, chlorpromazine (inhibitor of clathrin-mediated pathway) inhibited the endocytosis of mPRα, whereas treatment with nystatin (inhibitor of caveolae-mediated pathway) did not affect internalisation. Collectively, these data suggest that mPRα is expressed on the cell surface of M11 cells and undergoes endocytosis after P4 stimulation primarily via a clathrin-mediated pathway.

  18. Regulation of Telecommunications: The Choice Between Market and Regulatory Failures

    Directory of Open Access Journals (Sweden)

    Dmitrii Trubnikov

    2017-04-01

    Full Text Available Purpose – The paper examines the main regulatory frameworks of the telecommunications industry through the concept of market failure and analyses how and why the policy often leads to undesirable outcomes that might be considered as regulatory failure. Methodology/approach/design – The research uses the EU regulatory framework for electronic communications as a base for the analysis of the main policy objectives through the prism of the market failure theory with an eye to the interests of the main market players in the telecommunications markets. Findings – About any aspect of regulation allows to find ways to create opportunities for some groups of the industry and stifle activity of others. Despite the theory of market failure provides reasonable justifications for regulation of telecommunications markets, it is possible to argue that many of these problems are mainly the consequence of the policy and could be better solved by market mechanisms. Originality/value – The results of the research allow to look at the problems of telecommunications development and issues of the high level of concentration of the telecommunications markets as regulatory formed problems rather than consequences of the inherited industry’s characteristics.

  19. Electronic emission and electron guns

    International Nuclear Information System (INIS)

    Roy, Amitava

    2010-01-01

    This paper reviews the process of electron emission from metal surface. Although electrons move freely in conductors like metals, they normally do not leave the metal without some manipulation. In fact, heating and bombardment are the two primary ways in which electrons are emitted through the use of a heating element behind the cathode (termed thermionic emission) or as a result of bombardment with a beam of electrons, ions, or metastable atoms (termed secondary emission). Another important emission mechanism called Explosive Electron Emission (EEE) is also often used in various High Voltage Pulse Power Systems to generate very high current (few hundreds of kA) pulsed electron beams. The electron gun is the device in that it shoots off a continuous (or pulsed) stream of electrons. A brief idea about the evolution of the electron gun components and their basis of functioning are also discussed. (author)

  20. Regulatory point of view of SAT application

    International Nuclear Information System (INIS)

    Juhasz, L.

    2002-01-01

    I present the regulatory system for monitoring operator training and check competency of operator personnel in Hungary and the effects of SAT to the regulatory framework/practice related to recruitment, training and authorisation of operating personnel. Also I introduce an application to manage the initial and refreshing training to regulatory bodies. (author)

  1. 40 CFR 92.6 - Regulatory structure.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Regulatory structure. 92.6 Section 92... Regulations for Locomotives and Locomotive Engines § 92.6 Regulatory structure. This section provides an overview of the regulatory structure of this part. (a) The regulations of this part 92 are intended to...

  2. 40 CFR 94.6 - Regulatory structure.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Regulatory structure. 94.6 Section 94... for Compression-Ignition Marine Engines § 94.6 Regulatory structure. This section provides an overview of the regulatory structure of this part. (a) The regulations of this Part 94 are intended to control...

  3. Sticker electronics

    KAUST Repository

    Hussain, Muhammad Mustafa; Torres Sevilla, Galo Andres; Diaz Cordero, Marlon Steven

    2017-01-01

    Electronic stickers may be manufactured on flexible substrates (110, 120, 130) as layers and packaged together. The package may then have an adhesive applied to one side to provide capability for sticking the electronic devices to surfaces

  4. ELECTRONIC SIGNATURES

    African Journals Online (AJOL)

    10332324

    "[to] promote the understanding and, acceptance of and growth in the number of electronic transactions .... Chapter III of the ECT Act is based on the UNCITRAL Model Law on Electronic. Commerce ... Communications Technology Law 146. 22.

  5. Policies built upon pathways

    NARCIS (Netherlands)

    Musterd, S.; Kovács, Z.; Musterd, S.; Kovács, Z.

    2013-01-01

    After the general introductions, the first substantive part of this volume (Part II) provides concise research-based discussions of policies developed in recognition of the important role played by the pathways along which city-regions have travelled. Our research has shown that it is highly

  6. Synthetic Metabolic Pathways

    DEFF Research Database (Denmark)

    topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Synthetic Metabolic Pathways: Methods and Protocols aims to ensure successful results in the further study...

  7. Electronic components

    CERN Document Server

    Colwell, Morris A

    1976-01-01

    Electronic Components provides a basic grounding in the practical aspects of using and selecting electronics components. The book describes the basic requirements needed to start practical work on electronic equipment, resistors and potentiometers, capacitance, and inductors and transformers. The text discusses semiconductor devices such as diodes, thyristors and triacs, transistors and heat sinks, logic and linear integrated circuits (I.C.s) and electromechanical devices. Common abbreviations applied to components are provided. Constructors and electronics engineers will find the book useful

  8. Understand electronics

    CERN Document Server

    Bishop, Owen

    2013-01-01

    Understand Electronics provides a readable introduction to the exciting world of electronics for the student or enthusiast with little previous knowledge. The subject is treated with the minimum of mathematics and the book is extensively illustrated.This is an essential guide for the newcomer to electronics, and replaces the author's best-selling Beginner's Guide to Electronics.The step-by-step approach makes this book ideal for introductory courses such as the Intermediate GNVQ.

  9. Electronic Commerce

    OpenAIRE

    Slavko Đerić

    2016-01-01

    Electronic commerce can be defined in different ways. Any definition helps to understand and explain that concept as better as possible.. Electronic commerce is a set of procedures and technologies that automate the tasks of financial transactions using electronic means. Also, according to some authors, electronic commerce is defined as a new concept, which is being developed and which includes process of buying and selling or exchanging products, services or information via computer networks...

  10. 75 FR 21686 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2010-04-26

    ... to pay arbitration awards to remain in the securities industry presents regulatory risks and is...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of Proposed Rule... Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``SEC'' or...

  11. 76 FR 21932 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

    Science.gov (United States)

    2011-04-19

    ... statement therein, as follows: I. Introduction On February 4, 2011, the Financial Industry Regulatory...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting Approval of a... Financial Industry Regulatory Authority, Inc. (``FINRA'') to amend Rule 13806 of the Code of Arbitration...

  12. 75 FR 63878 - Self-Regulatory Organizations; Self-Regulatory Organizations; Notice of Filing and Immediate...

    Science.gov (United States)

    2010-10-18

    ...-Regulatory Organizations; Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of...(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of Substance... Public Reference Room. II. Self-Regulatory Organization's Statement of the Purpose of, and Statutory...

  13. Regulatory aspects of NPP safety

    International Nuclear Information System (INIS)

    Kastchiev, G.

    1999-01-01

    Extensive review of the NPP Safety is presented including tasks of Ministry of Health, Ministry of Internal Affairs, Ministry of Environment and Waters, Ministry of Defense in the field of national system for monitoring the nuclear power. In the frame of national nuclear safety legislation Bulgaria is in the process of approximation of the national legislation to that of EC. Detailed analysis of the status of regulatory body, its functions, organisation structure, responsibilities and future tasks is included. Basis for establishing the system of regulatory inspections and safety enforcement as well as intensification of inspections is described. Assessment of safety modifications is concerned with complex program for reconstruction of Units 1-4 of Kozloduy NPP, as well as for modernisation of Units 5 and 6. Qualification and licensing of the NPP personnel, Year 2000 problem, priorities and the need of international assistance are mentioned

  14. 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

  15. Compliance. Regulatory policy P-211

    International Nuclear Information System (INIS)

    2001-05-01

    This regulatory policy describes the basic principles and directives for establishing and conducting the Canadian Nuclear Safety Commission (CNSC) Compliance Program. The program is aimed at securing compliance by regulated persons with regulatory requirements made under the Nuclear Safety and Control Act ('the Act'). The policy applies to persons who are regulated by the CNSC through the Act, regulations and licences, as well as by decisions and orders made under the Act. The policy applies to officers and employees of the CNSC, and its authorized representatives or agents, who are involved in developing and carrying out compliance activities. Compliance, in the context of this policy, means conformity by regulated persons with the legally binding requirements of the Act, and the CNSC regulations, licences, decisions, and orders made under the Act. Compliance activities are CNSC measures of promotion, verification and enforcement aimed at securing compliance by regulated person with the applicable legally binding requirements. (author)

  16. Electronic Publishing.

    Science.gov (United States)

    Lancaster, F. W.

    1989-01-01

    Describes various stages involved in the applications of electronic media to the publishing industry. Highlights include computer typesetting, or photocomposition; machine-readable databases; the distribution of publications in electronic form; computer conferencing and electronic mail; collaborative authorship; hypertext; hypermedia publications;…

  17. Regulatory aspects of emergency planning

    International Nuclear Information System (INIS)

    Jamgochian, M.T.

    1986-01-01

    The paper discusses the advances that have been made in the USA in the field of emergency planning over the past several years and considers regulatory changes that may be on the horizon. The paper examines the importance of severe accident source terms and their relationship to emergency preparedness, recent research results of work on source terms, and the experience gained from evaluation of licensee performance during annual emergency preparedness exercises. (author)

  18. Regulatory Office for Network Industries

    International Nuclear Information System (INIS)

    2005-01-01

    The main goal of the economic regulation of network industries is to ensure a balance between the interests of consumers and investors and to encourage providing high-quality goods and services. The task of the regulatory authority is to protect the interests of consumers against monopolistic behaviour of regulated enterprises. At the same time, the regulatory office has to protect the interests of investors by giving them an opportunity to achieve an adequate return on their investments. And last, but not least, the regulatory office has to provide regulated enterprises with appropriate incentives to make them function in an efficient and effective manner and to guarantee the security of delivery of energies and related services. All this creates an efficient regulatory framework that is capable of attracting the required amount and type of investments. This also means providing third party access to the grids, the opening of energy markets, the un-bundling of accounts according to production, distribution, transmission and other activities and the establishment of a transparent and stable legislative environment for regulated companies, investors and consumers. Otherwise, in the long run consumers may suffer from a serious deterioration of service quality, although in the short run they are protected against increased prices. Under the Act No. 276/2001 Coll. on Regulation of Network Industries and on amendment of some acts the Office for Regulation of Network Industries has been commissioned to implement the main objectives of regulation of network industries. By network industries the Act No. 276/2001 Coll. on Regulation means the following areas: (a) Production, purchase, transit and distribution of electricity; (b) Production, purchase, transit and distribution of gas; (c) Production, purchase and distribution of heat; (d) Water management activities relating to the operation of the public water supply system or the public sewerage system; (e) Water management

  19. The conduct of regulatory activities

    International Nuclear Information System (INIS)

    Wright, H.A.

    1975-01-01

    The main emphasis is placed on the legal responsibility of the utility in UK to build and operate its plant to avoid any nuclear hazard. The regulatory practices have endeavoured to inculcate a proper emphasis towards safety by the people who comprise the management of the utility, and to avoid any erosion of their legal responsibility as the best and possibly only practical means to achieve adequate safety standards. (orig./HP) [de

  20. Regulatory control, legislation and framework

    International Nuclear Information System (INIS)

    Parthasarathy, K.S.

    1998-01-01

    The legislation and regulations, a regulatory authority to authorise and inspect the regulated activities and to enforce the legislation and regulations, sufficient financial and man-power resources are the essential parts of a national infrastructure to implement the Basic Safety Standards. The legal framework consists of legislation (Act passed by Parliament) and the regulations (framed by the government and endorsed by the Parliament). This paper is primarily deals with the the legal framework set up in India for atomic energy activities

  1. Regulatory change and monetary policy

    OpenAIRE

    Bank for International Settlements

    2015-01-01

    Report submitted by a Working Group established by the Committee on the Global Financial System and the Markets Committee. The Group was chaired by Ulrich Bindseil (European Central Bank) and William R Nelson (Federal Reserve Board). Financial regulation is evolving, as policymakers seek to strengthen the financial system in order to make it more robust and resilient. Changes in the regulatory environment are likely to have an impact on financial system structure and on the behaviour of finan...

  2. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2009-01-01

    This part gathers the national legislative and regulatory activities. The subjects tackled are as follow: radiological protection (Belgium), transport of radioactive materials (Belgium, France), general legislation (Brazil, Ireland, Republic of Moldova, Serbia, Turkey), third part liability (Japan), radioactive waste management (Korea, Romania, Slovenia, Usa), regime of radioactive materials (Romania), organisation and structure (Switzerland), regime of nuclear installations (Usa), regulations on nuclear trade (Usa). (N.C)

  3. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2015-01-01

    This section treats of the following National legislative and regulatory activities: 1 - Canada: Liability and compensation; 2 - France: Liability and compensation; Nuclear safety and radiological protection; 3 - Greece: Organisation and structure; 4 - Hungary: General legislation; 5 - India: Liability and compensation; 6 - Japan: Liability and compensation; 7 - Korea: Liability and compensation; 8 - Lithuania: General legislation; Transport of radioactive material; 9 - Slovak Republic: International co-operation; Liability and compensation; 10 - Slovenia: General legislation; 11 - Switzerland: Liability and compensation; 12 - United States: Radioactive waste management

  4. Principles of good regulatory research

    International Nuclear Information System (INIS)

    Rogers, K.

    1991-01-01

    The Commissioner of the US Regulatory Commission addresses several important research-related subjects. The paper describes the Agency philosophy with respect to independence, openness, efficiency, clarity, and reliability; research philosophy with respect to the need for research, the need for quality, and the need for efficiency; research areas with respect to plant aging, human factors, severe accident analysis, advanced reactors, and radioactive waste management; and systems approach to reactor operations, training, licensing, and maintenance

  5. Life cycle analysis of transportation fuel pathways

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2012-02-24

    The purpose of this work is to improve the understanding of the concept of life cycle analysis (LCA) of transportation fuels and some of its pertinent issues among non-technical people, senior managers, and policy makers. This work should provide some guidance to nations considering LCA-based policies and to people who are affected by existing policies or those being developed. While the concept of employing LCA to evaluate fuel options is simple and straightforward, the act of putting the concept into practice is complex and fraught with issues. Policy makers need to understand the limitations inherent in carrying out LCA work for transportation fuel systems. For many systems, even those that have been employed for a 100 years, there is a lack of sound data on the performance of those systems. Comparisons between systems should ideally be made using the same tool, so that differences caused by system boundaries, allocation processes, and temporal issues can be minimized (although probably not eliminated). Comparing the results for fuel pathway 1 from tool A to those of fuel system 2 from tool B introduces significant uncertainty into the results. There is also the question of the scale of system changes. LCA will give more reliable estimates when it is used to examine small changes in transportation fuel pathways than when used to estimate large scale changes that replace current pathways with completely new pathways. Some LCA tools have been developed recently primarily for regulatory purposes. These tools may deviate from ISO principles in order to facilitate simplicity and ease of use. In a regulatory environment, simplicity and ease of use are worthy objectives and in most cases there is nothing inherently wrong with this approach, particularly for assessing relative performance. However, the results of these tools should not be confused with, or compared to, the results that are obtained from a more complex and rigorous ISO compliant LCA. It should be

  6. Regulatory Myeloid Cells in Transplantation

    Science.gov (United States)

    Rosborough, Brian R.; Raïch-Regué, Dàlia; Turnquist, Heth R.; Thomson, Angus W.

    2013-01-01

    Regulatory myeloid cells (RMC) are emerging as novel targets for immunosuppressive (IS) agents and hold considerable promise as cellular therapeutic agents. Herein, we discuss the ability of regulatory macrophages (Mreg), regulatory dendritic cells (DCreg) and myeloid-derived suppressor cells (MDSC) to regulate alloimmunity, their potential as cellular therapeutic agents and the IS agents that target their function. We consider protocols for the generation of RMC and the selection of donor- or recipient-derived cells for adoptive cell therapy. Additionally, the issues of cell trafficking and antigen (Ag) specificity following RMC transfer are discussed. Improved understanding of the immunobiology of these cells has increased the possibility of moving RMC into the clinic to reduce the burden of current IS agents and promote Ag-specific tolerance. In the second half of this review, we discuss the influence of established and experimental IS agents on myeloid cell populations. IS agents believed historically to act primarily on T cell activation and proliferation are emerging as important regulators of RMC function. Better insights into the influence of IS agents on RMC will enhance our ability to develop cell therapy protocols to promote the function of these cells. Moreover, novel IS agents may be designed to target RMC in situ to promote Ag-specific immune regulation in transplantation and usher in a new era of immune modulation exploiting cells of myeloid origin. PMID:24092382

  7. MinePath: Mining for Phenotype Differential Sub-paths in Molecular Pathways

    Science.gov (United States)

    Koumakis, Lefteris; Kartsaki, Evgenia; Chatzimina, Maria; Zervakis, Michalis; Vassou, Despoina; Marias, Kostas; Moustakis, Vassilis; Potamias, George

    2016-01-01

    Pathway analysis methodologies couple traditional gene expression analysis with knowledge encoded in established molecular pathway networks, offering a promising approach towards the biological interpretation of phenotype differentiating genes. Early pathway analysis methodologies, named as gene set analysis (GSA), view pathways just as plain lists of genes without taking into account either the underlying pathway network topology or the involved gene regulatory relations. These approaches, even if they achieve computational efficiency and simplicity, consider pathways that involve the same genes as equivalent in terms of their gene enrichment characteristics. Most recent pathway analysis approaches take into account the underlying gene regulatory relations by examining their consistency with gene expression profiles and computing a score for each profile. Even with this approach, assessing and scoring single-relations limits the ability to reveal key gene regulation mechanisms hidden in longer pathway sub-paths. We introduce MinePath, a pathway analysis methodology that addresses and overcomes the aforementioned problems. MinePath facilitates the decomposition of pathways into their constituent sub-paths. Decomposition leads to the transformation of single-relations to complex regulation sub-paths. Regulation sub-paths are then matched with gene expression sample profiles in order to evaluate their functional status and to assess phenotype differential power. Assessment of differential power supports the identification of the most discriminant profiles. In addition, MinePath assess the significance of the pathways as a whole, ranking them by their p-values. Comparison results with state-of-the-art pathway analysis systems are indicative for the soundness and reliability of the MinePath approach. In contrast with many pathway analysis tools, MinePath is a web-based system (www.minepath.org) offering dynamic and rich pathway visualization functionality, with the

  8. Regulatory difficulties in a developing country

    International Nuclear Information System (INIS)

    Jacobs, W.R. Jr.

    1978-01-01

    The regulatory agency assigned the task of regulating the initial entry into the field of nuclear power generation by a developing country has a very difficult job. Based on the authors' experience during the start-up and initial operation of Ko-Ri Unit I, the first power reactor in the Republic of Korea, observations on regulatory difficulties and recommendations for improved regulatory effectiveness are offered. The problem areas can be loosely grouped into three general categories: (1) Lack of adequate technical knowledge which is the basis for all effective regulation; (2) Difficulties with understanding and utilization of the required regulatory documentation; (3) Failure to establish the proper regulatory environment. Examples are cited from actual experience during the Ko-Ri Unit I start-up to demonstrate the impact that regulatory activities can have on a plant construction and testing programme. The problems encountered are not unique to developing countries but also exist in the United States of America. Recommendations are offered which should be beneficial to either newly formed regulatory agencies or agencies wishing to improve their abilities and effectiveness. These include: (1) Additional training of regulatory inspectors in plant operations; (2) Additional experience gained by participation in regulatory activities in other countries; (3) Increased attention given to regulatory documents, especially plant technical specifications; (4) Establishment of formal lines of communication between the utility and the regulatory agency; (5) Clear definition of regulatory responsibilities to avoid areas of overlapping jurisdiction; (6) Active participation by the regulatory staff very early in the project. It is hoped that these and other recommendations offered will greatly improve regulatory effectiveness and at the same time demonstrate that when the decision is made to 'go nuclear', a strong commitment must be made to develop and support a technically

  9. Regulatory Non-Coding RNAs in Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Alessandro Rosa

    2013-07-01

    Full Text Available The most part of our genome encodes for RNA transcripts are never translated into proteins. These include families of RNA molecules with a regulatory function, which can be arbitrarily subdivided in short (less than 200 nucleotides and long non-coding RNAs (ncRNAs. MicroRNAs, which act post-transcriptionally to repress the function of target mRNAs, belong to the first group. Included in the second group are multi-exonic and polyadenylated long ncRNAs (lncRNAs, localized either in the nucleus, where they can associate with chromatin remodeling complexes to regulate transcription, or in the cytoplasm, acting as post-transcriptional regulators. Pluripotent stem cells, such as embryonic stem cells (ESCs or induced pluripotent stem cells (iPSCs, represent useful systems for modeling normal development and human diseases, as well as promising tools for regenerative medicine. To fully explore their potential, however, a deep understanding of the molecular basis of stemness is crucial. In recent years, increasing evidence of the importance of regulation by ncRNAs in pluripotent cells is accumulating. In this review, we will discuss recent findings pointing to multiple roles played by regulatory ncRNAs in ESC and iPSCs, where they act in concert with signaling pathways, transcriptional regulatory circuitries and epigenetic factors to modulate the balance between pluripotency and differentiation.

  10. Heart morphogenesis gene regulatory networks revealed by temporal expression analysis.

    Science.gov (United States)

    Hill, Jonathon T; Demarest, Bradley; Gorsi, Bushra; Smith, Megan; Yost, H Joseph

    2017-10-01

    During embryogenesis the heart forms as a linear tube that then undergoes multiple simultaneous morphogenetic events to obtain its mature shape. To understand the gene regulatory networks (GRNs) driving this phase of heart development, during which many congenital heart disease malformations likely arise, we conducted an RNA-seq timecourse in zebrafish from 30 hpf to 72 hpf and identified 5861 genes with altered expression. We clustered the genes by temporal expression pattern, identified transcription factor binding motifs enriched in each cluster, and generated a model GRN for the major gene batteries in heart morphogenesis. This approach predicted hundreds of regulatory interactions and found batteries enriched in specific cell and tissue types, indicating that the approach can be used to narrow the search for novel genetic markers and regulatory interactions. Subsequent analyses confirmed the GRN using two mutants, Tbx5 and nkx2-5 , and identified sets of duplicated zebrafish genes that do not show temporal subfunctionalization. This dataset provides an essential resource for future studies on the genetic/epigenetic pathways implicated in congenital heart defects and the mechanisms of cardiac transcriptional regulation. © 2017. Published by The Company of Biologists Ltd.

  11. Regulatory Oversight of Cell and Gene Therapy Products in Canada.

    Science.gov (United States)

    Ridgway, Anthony; Agbanyo, Francisca; Wang, Jian; Rosu-Myles, Michael

    2015-01-01

    Health Canada regulates gene therapy products and many cell therapy products as biological drugs under the Canadian Food and Drugs Act and its attendant regulations. Cellular products that meet certain criteria, including minimal manipulation and homologous use, may be subjected to a standards-based approach under the Safety of Human Cells, Tissues and Organs for Transplantation Regulations. The manufacture and clinical testing of cell and gene therapy products (CGTPs) presents many challenges beyond those for protein biologics. Cells cannot be subjected to pathogen removal or inactivation procedures and must frequently be administered shortly after final formulation. Viral vector design and manufacturing control are critically important to overall product quality and linked to safety and efficacy in patients through concerns such as replication competence, vector integration, and vector shedding. In addition, for many CGTPs, the value of nonclinical studies is largely limited to providing proof of concept, and the first meaningful data relating to appropriate dosing, safety parameters, and validity of surrogate or true determinants of efficacy must come from carefully designed clinical trials in patients. Addressing these numerous challenges requires application of various risk mitigation strategies and meeting regulatory expectations specifically adapted to the product types. Regulatory cooperation and harmonisation at an international level are essential for progress in the development and commercialisation of these products. However, particularly in the area of cell therapy, new regulatory paradigms may be needed to harness the benefits of clinical progress in situations where the resources and motivation to pursue a typical drug product approval pathway may be lacking.

  12. Sticker electronics

    KAUST Repository

    Hussain, Muhammad Mustafa

    2017-09-08

    Electronic stickers may be manufactured on flexible substrates (110, 120, 130) as layers and packaged together. The package may then have an adhesive applied to one side to provide capability for sticking the electronic devices to surfaces. The stickers can be wrappable, placed on surfaces, glued on walls or mirrors or wood or stone, and have electronics (112, 122, 132) which may or may not be ultrathin. Packaging for the electronic sticker can use polymer on cellulose manufacturing and/or three dimensional (3-D) printing. The electronic stickers may provide lighting capability, sensing capability, and/or recharging capabilities.

  13. Basic electronics

    CERN Document Server

    Holbrook, Harold D

    1971-01-01

    Basic Electronics is an elementary text designed for basic instruction in electricity and electronics. It gives emphasis on electronic emission and the vacuum tube and shows transistor circuits in parallel with electron tube circuits. This book also demonstrates how the transistor merely replaces the tube, with proper change of circuit constants as required. Many problems are presented at the end of each chapter. This book is comprised of 17 chapters and opens with an overview of electron theory, followed by a discussion on resistance, inductance, and capacitance, along with their effects on t

  14. Novel Evasion Mechanisms of the Classical Complement Pathway.

    Science.gov (United States)

    Garcia, Brandon L; Zwarthoff, Seline A; Rooijakkers, Suzan H M; Geisbrecht, Brian V

    2016-09-15

    Complement is a network of soluble and cell surface-associated proteins that gives rise to a self-amplifying, yet tightly regulated system with fundamental roles in immune surveillance and clearance. Complement becomes activated on the surface of nonself cells by one of three initiating mechanisms known as the classical, lectin, and alternative pathways. Evasion of complement function is a hallmark of invasive pathogens and hematophagous organisms. Although many complement-inhibition strategies hinge on hijacking activities of endogenous complement regulatory proteins, an increasing number of uniquely evolved evasion molecules have been discovered over the past decade. In this review, we focus on several recent investigations that revealed mechanistically distinct inhibitors of the classical pathway. Because the classical pathway is an important and specific mediator of various autoimmune and inflammatory disorders, in-depth knowledge of novel evasion mechanisms could direct future development of therapeutic anti-inflammatory molecules. Copyright © 2016 by The American Association of Immunologists, Inc.

  15. The Fog signaling pathway: Insights into signaling in morphogenesis

    Science.gov (United States)

    Manning, Alyssa J.; Rogers, Stephen L.

    2014-01-01

    Epithelia form the building blocks of many tissue and organ types. Epithelial cells often form a contiguous 2-dimensional sheet that is held together by strong adhesions. The mechanical properties conferred by these adhesions allow the cells to undergo dramatic three-dimensional morphogenetic movements while maintaining cell–cell contacts during embryogenesis and post-embryonic development. The Drosophila Folded gastrulation pathway triggers epithelial cell shape changes that drive gastrulation and tissue folding and is one of the most extensively studied examples of epithelial morphogenesis. This pathway has yielded key insights into the signaling mechanisms and cellular machinery involved in epithelial remodeling. In this review, we discuss principles of morphogenesis and signaling that have been discovered through genetic and cell biological examination of this pathway. We also consider various regulatory mechanisms and the system's relevance to mammalian development. We propose future directions that will continue to broaden our knowledge of morphogenesis across taxa. PMID:25127992

  16. Building pathway graphs from BioPAX data in R.

    Science.gov (United States)

    Benis, Nirupama; Schokker, Dirkjan; Kramer, Frank; Smits, Mari A; Suarez-Diez, Maria

    2016-01-01

    Biological pathways are increasingly available in the BioPAX format which uses an RDF model for data storage. One can retrieve the information in this data model in the scripting language R using the package rBiopaxParser , which converts the BioPAX format to one readable in R. It also has a function to build a regulatory network from the pathway information. Here we describe an extension of this function. The new function allows the user to build graphs of entire pathways, including regulated as well as non-regulated elements, and therefore provides a maximum of information. This function is available as part of the rBiopaxParser distribution from Bioconductor.

  17. Risk-based Regulatory Evaluation Program methodology

    International Nuclear Information System (INIS)

    DuCharme, A.R.; Sanders, G.A.; Carlson, D.D.; Asselin, S.V.

    1987-01-01

    The objectives of this DOE-supported Regulatory Evaluation Progrwam are to analyze and evaluate the safety importance and economic significance of existing regulatory guidance in order to assist in the improvement of the regulatory process for current generation and future design reactors. A risk-based cost-benefit methodology was developed to evaluate the safety benefit and cost of specific regulations or Standard Review Plan sections. Risk-based methods can be used in lieu of or in combination with deterministic methods in developing regulatory requirements and reaching regulatory decisions

  18. Electronic licensing filing system development and implementation experience

    International Nuclear Information System (INIS)

    Walderhaug, J.

    1993-01-01

    The Electronic Licensing Filing System (ELFS) is a microcomputer-based integrated document search and retrieval system for the Nuclear Regulatory Affairs Division of Southern California Edison (SCE). ELFS allows the user access to the current licensing basis of a subject by providing an easily searchable electronic information data base consisting of regulatory correspondence, design-bases documentation, licensing documents [updated final safety and analysis report (UFSAR) and technical specifications], and regulatory guidance or directives [10CFR, generic letters, bulletins, notices, circulars, regulatory guides, policy statements, and selected US Nuclear Regulatory Commission (NRC) regulations]. It is used in the preparation of correspondence and submittals to the NRC, 50.59 safety evaluations, design-bases reconstitution, and commitment tracking and management

  19. Electronic Commerce and Electronic Business

    Indian Academy of Sciences (India)

    R. Narasimhan (Krishtel eMaging) 1461 1996 Oct 15 13:05:22

    This special issue is motivated by the recent upsurge of research activity in the areas of electronic commerce and electronic business both in India and all over the world. The current ... Monte Carlo methods for pricing financial options are then.

  20. Electronic Government and Electronic Participation

    NARCIS (Netherlands)

    Tambouris, E; Scholl, H.J.; Janssen, M.F.W.H.A.; Wimmer, M.A.; Tarabanis, K; Gascó, M; Klievink, A.J.; Lindgren, I; Milano, M; Panagiotopoulos, P; Pardo, T.A.; Parycek, P; Sæbø, Ø

    2016-01-01

    Electronic government and electronic participation continue to transform the public sector and society worldwide and are constantly being transformed themselves by emerging information and communication technologies.This book presents papers from the 14th International Federation for Information

  1. Electronic Government and Electronic Participation

    NARCIS (Netherlands)

    Tambouris, E.; Scholl, H.J.; Janssen, M.F.W.H.A.; Wimmer, M.A.; Tarabanis, K.; Gascó, M.; Klievink, A.J.; Lindgren, I.; Milano, M.; Panagiotopoulos, P.; Pardo, T.A.; Parycek, P.; Sæbø, O.

    2015-01-01

    Electronic government and electronic participation continue to transform the public sector and society worldwide and are constantly being transformed themselves by emerging information and communication technologies. This book presents papers from the 14th International Federation for Information

  2. PathwayAccess: CellDesigner plugins for pathway databases.

    Science.gov (United States)

    Van Hemert, John L; Dickerson, Julie A

    2010-09-15

    CellDesigner provides a user-friendly interface for graphical biochemical pathway description. Many pathway databases are not directly exportable to CellDesigner models. PathwayAccess is an extensible suite of CellDesigner plugins, which connect CellDesigner directly to pathway databases using respective Java application programming interfaces. The process is streamlined for creating new PathwayAccess plugins for specific pathway databases. Three PathwayAccess plugins, MetNetAccess, BioCycAccess and ReactomeAccess, directly connect CellDesigner to the pathway databases MetNetDB, BioCyc and Reactome. PathwayAccess plugins enable CellDesigner users to expose pathway data to analytical CellDesigner functions, curate their pathway databases and visually integrate pathway data from different databases using standard Systems Biology Markup Language and Systems Biology Graphical Notation. Implemented in Java, PathwayAccess plugins run with CellDesigner version 4.0.1 and were tested on Ubuntu Linux, Windows XP and 7, and MacOSX. Source code, binaries, documentation and video walkthroughs are freely available at http://vrac.iastate.edu/~jlv.

  3. Electron Tree

    DEFF Research Database (Denmark)

    Appelt, Ane L; Rønde, Heidi S

    2013-01-01

    The photo shows a close-up of a Lichtenberg figure – popularly called an “electron tree” – produced in a cylinder of polymethyl methacrylate (PMMA). Electron trees are created by irradiating a suitable insulating material, in this case PMMA, with an intense high energy electron beam. Upon discharge......, during dielectric breakdown in the material, the electrons generate branching chains of fractures on leaving the PMMA, producing the tree pattern seen. To be able to create electron trees with a clinical linear accelerator, one needs to access the primary electron beam used for photon treatments. We...... appropriated a linac that was being decommissioned in our department and dismantled the head to circumvent the target and ion chambers. This is one of 24 electron trees produced before we had to stop the fun and allow the rest of the accelerator to be disassembled....

  4. `Twisted' electrons

    Science.gov (United States)

    Larocque, Hugo; Kaminer, Ido; Grillo, Vincenzo; Leuchs, Gerd; Padgett, Miles J.; Boyd, Robert W.; Segev, Mordechai; Karimi, Ebrahim

    2018-04-01

    Electrons have played a significant role in the development of many fields of physics during the last century. The interest surrounding them mostly involved their wave-like features prescribed by the quantum theory. In particular, these features correctly predict the behaviour of electrons in various physical systems including atoms, molecules, solid-state materials, and even in free space. Ten years ago, new breakthroughs were made, arising from the new ability to bestow orbital angular momentum (OAM) to the wave function of electrons. This quantity, in conjunction with the electron's charge, results in an additional magnetic property. Owing to these features, OAM-carrying, or twisted, electrons can effectively interact with magnetic fields in unprecedented ways and have motivated materials scientists to find new methods for generating twisted electrons and measuring their OAM content. Here, we provide an overview of such techniques along with an introduction to the exciting dynamics of twisted electrons.

  5. Organization of nuclear regulatory activities

    International Nuclear Information System (INIS)

    Blidaru, Valentin

    2008-01-01

    The paper presents the structure, missions and organizational aspects of the CNCAN, the National Commission for the control of nuclear activities in Romania. The paper addresses the following main issues: 1.General aspects; 2.Organizational structure of the NRA in Romania; 3.General description of the Division for Nuclear Safety Assessments; 4.Specific activities; 5.Regulatory approaches and practices. Under the title of 'General aspects' the following three basic statements are highlighted: 1.CNCAN is a governmental organization responsible for the development of the regulatory framework, the control of its implementation and the licensing of nuclear facilities; 2.CNCAN is the national authority competent in exercising the regulatory activity, authorization and control in the nuclear field provided by the law No. 111/ 1996 republished in 1998; 3.The Commission exercises its functions independently of the ministries and other authorities of the public control administration being subordinated to the Romanian Government. The organizational structure is as follows: - President, the Managerial Council and the Advisory Council coordinating the four General Divisions that are responsible for: - Nuclear Safety with Division of Nuclear Safety Assessment and Division of Nuclear Objectives Surveillance; - Radiological Safety with Division of Radiological Safety Assessment and Division of Operational Radiation Protection; - Surveillance of Environmental Radioactivity with Division of Assessment and Analysis and Division of National Network; - Development and Resource with the Division of Economy and Division of Human Resources. In addition under direct coordination of the President operate the Division of Radiation Protection, Transport and Radioactive Waste and the Division of International Cooperation and Communication. Specific activities are listed describing among others the issues of: - Safety of nuclear installation; - Evaluation relating to licensing of nuclear

  6. The Rose (Rosa hybrida) NAC Transcription Factor 3 Gene, RhNAC3, Involved in ABA Signaling Pathway Both in Rose and Arabidopsis

    OpenAIRE

    Jiang, Guimei; Jiang, Xinqiang; Lü, Peitao; Liu, Jitao; Gao, Junping; Zhang, Changqing

    2014-01-01

    Plant transcription factors involved in stress responses are generally classified by their involvement in either the abscisic acid (ABA)-dependent or the ABA-independent regulatory pathways. A stress-associated NAC gene from rose (Rosa hybrida), RhNAC3, was previously found to increase dehydration tolerance in both rose and Arabidopsis. However, the regulatory mechanism involved in RhNAC3 action is still not fully understood. In this study, we isolated and analyzed the upstream regulatory seq...

  7. Electron irradiation of zeolites

    International Nuclear Information System (INIS)

    Wang, S.X.; Wang, L.M.; Ewing, R.C.

    1999-01-01

    Three different zeolites (analcime, natrolite, and zeolite-Y) were irradiated with 200 keV and 400 keV electrons. All zeolites amorphized under a relatively low electron fluence. The transformation from the crystalline-to-amorphous state was continuous and homogeneous. The electron fluences for amorphization of the three zeolites at room temperature were: 7.0 x 10 19 e - /cm 2 (analcime), 1.8 x 10 20 e - /cm 2 (natrolite), and 3.4 x 10 20 e - /cm 2 (zeolite-Y). The different susceptibilities to amorphization are attributed to the different channel sizes in the structures which are the pathways for the release of water molecules and Na + . Natrolite formed bubbles under electron irradiation, even before complete amorphization. Analcime formed bubbles after amorphization. Zeolite-Y did not form bubbles under irradiation. The differences in bubble formation are attributed to the different channel sizes of the three zeolites. The amorphization dose was also measured at different temperatures. An inverse temperature dependence of amorphization dose was observed for all three zeolites: electron dose for amorphization decreased with increasing temperature. This unique temperature effect is attributed to the fact that zeolites are thermally unstable. A semi-empirical model was derived to describe the temperature effect of amorphization in these zeolites

  8. 75 FR 21781 - Regulatory Agenda

    Science.gov (United States)

    2010-04-26

    ...-AB58 Specifications, and Certification Criteria for Electronic Health Record Technology (Rulemaking... Electronic Submission of Data From Studies Evaluating Human Drugs and Biologics....... 0910-AC52 137 Over-the... 147 Cigars Subject to the Family Smoking Prevention and Tobacco Control Act 0910-AG38 Food and Drug...

  9. A global regulatory science agenda for vaccines.

    Science.gov (United States)

    Elmgren, Lindsay; Li, Xuguang; Wilson, Carolyn; Ball, Robert; Wang, Junzhi; Cichutek, Klaus; Pfleiderer, Michael; Kato, Atsushi; Cavaleri, Marco; Southern, James; Jivapaisarnpong, Teeranart; Minor, Philip; Griffiths, Elwyn; Sohn, Yeowon; Wood, David

    2013-04-18

    The Decade of Vaccines Collaboration and development of the Global Vaccine Action Plan provides a catalyst and unique opportunity for regulators worldwide to develop and propose a global regulatory science agenda for vaccines. Regulatory oversight is critical to allow access to vaccines that are safe, effective, and of assured quality. Methods used by regulators need to constantly evolve so that scientific and technological advances are applied to address challenges such as new products and technologies, and also to provide an increased understanding of benefits and risks of existing products. Regulatory science builds on high-quality basic research, and encompasses at least two broad categories. First, there is laboratory-based regulatory science. Illustrative examples include development of correlates of immunity; or correlates of safety; or of improved product characterization and potency assays. Included in such science would be tools to standardize assays used for regulatory purposes. Second, there is science to develop regulatory processes. Illustrative examples include adaptive clinical trial designs; or tools to analyze the benefit-risk decision-making process of regulators; or novel pharmacovigilance methodologies. Included in such science would be initiatives to standardize regulatory processes (e.g., definitions of terms for adverse events [AEs] following immunization). The aim of a global regulatory science agenda is to transform current national efforts, mainly by well-resourced regulatory agencies, into a coordinated action plan to support global immunization goals. This article provides examples of how regulatory science has, in the past, contributed to improved access to vaccines, and identifies gaps that could be addressed through a global regulatory science agenda. The article also identifies challenges to implementing a regulatory science agenda and proposes strategies and actions to fill these gaps. A global regulatory science agenda will enable

  10. Pathway analysis of IMC

    DEFF Research Database (Denmark)

    Skrypnyuk, Nataliya; Nielson, Flemming; Pilegaard, Henrik

    2009-01-01

    We present the ongoing work on the pathway analysis of a stochastic calculus. Firstly we present a particular stochastic calculus that we have chosen for our modeling - the Interactive Markov Chains calculus, IMC for short. After that we specify a few restrictions that we have introduced into the...... into the syntax of IMC in order to make our analysis feasible. Finally we describe the analysis itself together with several theoretical results that we have proved for it.......We present the ongoing work on the pathway analysis of a stochastic calculus. Firstly we present a particular stochastic calculus that we have chosen for our modeling - the Interactive Markov Chains calculus, IMC for short. After that we specify a few restrictions that we have introduced...

  11. Aquatic pathway 2

    International Nuclear Information System (INIS)

    1977-01-01

    This third part of the investigation discusses the preliminary results of sub-investigations concerning problems of the release of radioactive substances into the environment via the water pathway. On the basis of papers on the emission into the draining ditch and the exchange processes there, investigations of a possible incorporation via different exposure pathways are reported. Special regard is paid to drinking water supply aquatic foodstuffs, the river sediment, the utilisation of the agricultural surfaces and the draining ditch including its pre-pollution. The dynamics of contamination processes is reported on with regard to the problem of accidents. The colloquium will give an outline of the progress made so far and admit participants' suggestions for further work on the sub-investigations. The following colloquia will report further findings, in particular effects on aquatic ecosystems. (orig.) [de

  12. The medical dictionary for regulatory activities (MedDRA).

    Science.gov (United States)

    Brown, E G; Wood, L; Wood, S

    1999-02-01

    The International Conference on Harmonisation has agreed upon the structure and content of the Medical Dictionary for Regulatory Activities (MedDRA) version 2.0 which should become available in the early part of 1999. This medical terminology is intended for use in the pre- and postmarketing phases of the medicines regulatory process, covering diagnoses, symptoms and signs, adverse drug reactions and therapeutic indications, the names and qualitative results of investigations, surgical and medical procedures, and medical/social history. It can be used for recording adverse events and medical history in clinical trials, in the analysis and tabulations of data from these trials and in the expedited submission of safety data to government regulatory authorities, as well as in constructing standard product information and documentation for applications for marketing authorisation. After licensing of a medicine, it may be used in pharmacovigilance and is expected to be the preferred terminology for international electronic regulatory communication. MedDRA is a hierarchical terminology with 5 levels and is multiaxial: terms may exist in more than 1 vertical axis, providing specificity of terms for data entry and flexibility in data retrieval. Terms in MedDRA were derived from several sources including the WHO's adverse reaction terminology (WHO-ART), Coding Symbols for a Thesaurus of Adverse Reaction Terms (COSTART), International Classification of Diseases (ICD) 9 and ICD9-CM. It will be maintained, further developed and distributed by a Maintenance Support Services Organisation (MSSO). It is anticipated that using MedDRA will improve the quality of data captured on databases, support effective analysis by providing clinically relevant groupings of terms and facilitate electronic communication of data, although as a new tool, users will need to invest time in gaining expertise in its use.

  13. Pathways to diversification

    OpenAIRE

    Al Hashemi, Hamed

    2016-01-01

    A fundamental research question in regional economic development, is why some regions are able to diversify into new products and industries, while others continue to face challenges in diversification? This doctorate research explores the different pathways to diversification. It follows the three-stage modular structure of DBA for Cranfield School of Management. This thesis consists of a systematic literature review, a single qualitative case study on UAE, and a research synthesis of publis...

  14. 75 FR 79049 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2010-12-17

    ... site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . The regulatory... NUCLEAR REGULATORY COMMISSION [NRC-2008-0427] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 3.12...

  15. 75 FR 45173 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2010-08-02

    ... ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . In addition, regulatory guides are... NUCLEAR REGULATORY COMMISSION [NRC-2008-0638] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.151...

  16. 76 FR 18262 - Notice of issuance of Regulatory Guide

    Science.gov (United States)

    2011-04-01

    ... site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . The regulatory... NUCLEAR REGULATORY COMMISSION [NRC-2009-0277] Notice of issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.44...

  17. 76 FR 14107 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2011-03-15

    ... site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . The regulatory... NUCLEAR REGULATORY COMMISSION [NRC-2009-0276] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.43...

  18. 76 FR 14108 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2011-03-15

    ... site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . The regulatory... NUCLEAR REGULATORY COMMISSION [NRC-2009-0275] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.50...

  19. The Glymphatic Pathway.

    Science.gov (United States)

    Benveniste, Helene; Lee, Hedok; Volkow, Nora D

    2017-01-01

    The overall premise of this review is that cerebrospinal fluid (CSF) is transported within a dedicated peri-vascular network facilitating metabolic waste clearance from the central nervous system while we sleep. The anatomical profile of the network is complex and has been defined as a peri-arterial CSF influx pathway and peri-venous clearance routes, which are functionally coupled by interstitial bulk flow supported by astrocytic aquaporin 4 water channels. The role of the newly discovered system in the brain is equivalent to the lymphatic system present in other body organs and has been termed the "glymphatic pathway" or "(g)lymphatics" because of its dependence on glial cells. We will discuss and review the general anatomy and physiology of CSF from the perspective of the glymphatic pathway, a discovery which has greatly improved our understanding of key factors that control removal of metabolic waste products from the central nervous system in health and disease and identifies an additional purpose for sleep. A brief historical and factual description of CSF production and transport will precede the ensuing discussion of the glymphatic system along with a discussion of its clinical implications.

  20. Exploring the miRNA regulatory network using evolutionary correlations.

    Directory of Open Access Journals (Sweden)

    Benedikt Obermayer

    2014-10-01

    Full Text Available Post-transcriptional regulation by miRNAs is a widespread and highly conserved phenomenon in metazoans, with several hundreds to thousands of conserved binding sites for each miRNA, and up to two thirds of all genes under miRNA regulation. At the same time, the effect of miRNA regulation on mRNA and protein levels is usually quite modest and associated phenotypes are often weak or subtle. This has given rise to the notion that the highly interconnected miRNA regulatory network exerts its function less through any individual link and more via collective effects that lead to a functional interdependence of network links. We present a Bayesian framework to quantify conservation of miRNA target sites using vertebrate whole-genome alignments. The increased statistical power of our phylogenetic model allows detection of evolutionary correlation in the conservation patterns of site pairs. Such correlations could result from collective functions in the regulatory network. For instance, co-conservation of target site pairs supports a selective benefit of combinatorial regulation by multiple miRNAs. We find that some miRNA families are under pronounced co-targeting constraints, indicating a high connectivity in the regulatory network, while others appear to function in a more isolated way. By analyzing coordinated targeting of different curated gene sets, we observe distinct evolutionary signatures for protein complexes and signaling pathways that could reflect differences in control strategies. Our method is easily scalable to analyze upcoming larger data sets, and readily adaptable to detect high-level selective constraints between other genomic loci. We thus provide a proof-of-principle method to understand regulatory networks from an evolutionary perspective.

  1. Regulation of Gene Expression in Shewanella oneidensis MR-1 during Electron Acceptor Limitation and Bacterial Nanowire Formation

    Science.gov (United States)

    Barchinger, Sarah E.; Pirbadian, Sahand; Baker, Carol S.; Leung, Kar Man; Burroughs, Nigel J.; El-Naggar, Mohamed Y.

    2016-01-01

    ABSTRACT In limiting oxygen as an electron acceptor, the dissimilatory metal-reducing bacterium Shewanella oneidensis MR-1 rapidly forms nanowires, extensions of its outer membrane containing the cytochromes MtrC and OmcA needed for extracellular electron transfer. RNA sequencing (RNA-Seq) analysis was employed to determine differential gene expression over time from triplicate chemostat cultures that were limited for oxygen. We identified 465 genes with decreased expression and 677 genes with increased expression. The coordinated increased expression of heme biosynthesis, cytochrome maturation, and transport pathways indicates that S. oneidensis MR-1 increases cytochrome production, including the transcription of genes encoding MtrA, MtrC, and OmcA, and transports these decaheme cytochromes across the cytoplasmic membrane during electron acceptor limitation and nanowire formation. In contrast, the expression of the mtrA and mtrC homologs mtrF and mtrD either remains unaffected or decreases under these conditions. The ompW gene, encoding a small outer membrane porin, has 40-fold higher expression during oxygen limitation, and it is proposed that OmpW plays a role in cation transport to maintain electrical neutrality during electron transfer. The genes encoding the anaerobic respiration regulator cyclic AMP receptor protein (CRP) and the extracytoplasmic function sigma factor RpoE are among the transcription factor genes with increased expression. RpoE might function by signaling the initial response to oxygen limitation. Our results show that RpoE activates transcription from promoters upstream of mtrC and omcA. The transcriptome and mutant analyses of S. oneidensis MR-1 nanowire production are consistent with independent regulatory mechanisms for extending the outer membrane into tubular structures and for ensuring the electron transfer function of the nanowires. IMPORTANCE Shewanella oneidensis MR-1 has the capacity to transfer electrons to its external surface

  2. An overview of bioinformatics methods for modeling biological pathways in yeast.

    Science.gov (United States)

    Hou, Jie; Acharya, Lipi; Zhu, Dongxiao; Cheng, Jianlin

    2016-03-01

    The advent of high-throughput genomics techniques, along with the completion of genome sequencing projects, identification of protein-protein interactions and reconstruction of genome-scale pathways, has accelerated the development of systems biology research in the yeast organism Saccharomyces cerevisiae In particular, discovery of biological pathways in yeast has become an important forefront in systems biology, which aims to understand the interactions among molecules within a cell leading to certain cellular processes in response to a specific environment. While the existing theoretical and experimental approaches enable the investigation of well-known pathways involved in metabolism, gene regulation and signal transduction, bioinformatics methods offer new insights into computational modeling of biological pathways. A wide range of computational approaches has been proposed in the past for reconstructing biological pathways from high-throughput datasets. Here we review selected bioinformatics approaches for modeling biological pathways inS. cerevisiae, including metabolic pathways, gene-regulatory pathways and signaling pathways. We start with reviewing the research on biological pathways followed by discussing key biological databases. In addition, several representative computational approaches for modeling biological pathways in yeast are discussed. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  3. Electronic Commerce

    Directory of Open Access Journals (Sweden)

    Slavko Đerić

    2016-12-01

    Full Text Available Electronic commerce can be defined in different ways. Any definition helps to understand and explain that concept as better as possible.. Electronic commerce is a set of procedures and technologies that automate the tasks of financial transactions using electronic means. Also, according to some authors, electronic commerce is defined as a new concept, which is being developed and which includes process of buying and selling or exchanging products, services or information via computer networks, including the Internet. Electronic commerce is not limited just to buying and selling, but it also includes all pre-sales and after-sales ongoing activities along the supply chain. Introducing electronic commerce, using the Internet and Web services in business, realizes the way to a completely new type of economy - internet economy.

  4. Wetlands: The changing regulatory landscape

    International Nuclear Information System (INIS)

    Glick, R.M.

    1993-01-01

    Protection of wetlands became a national issue in 1988 when President George Bush pledged no net loss of wetlands in the US under his open-quotes environmental presidency.close quotes As wetlands became a national issue, the job of protecting them became an obligation for many groups, including hydro-power developers. Now, when a site selected for development includes an area that may be classified as a wetland, the developer quickly discovers the importance of recognizing and protecting these natural habitats. Federal legislation severely limits development of wetland, and most states increase the restrictions with their own wetlands regulations. The difficulty of defining wetlands complicates federal and state enforcement. Land that appears to be dry may in fact be classified as a wetland. So, even if a site appears dry, potential hydro developers must confirm whether or not any jurisdictional wetlands are present. Regulated lands include much more than marshes and swamps. Further complicating the definition of wetlands, a recent court decision found that even artificially created wetlands, such as man-made ponds, may be subject to regulation. Hydro developers must be aware of current regulatory requirements before they consider development of any site that may contain wetlands. To be certain that a site is open-quotes buildableclose quotes from the standpoint of wetlands regulation, a developer must verify (with the help of state agencies) that the property does not contain any jurisdictional wetlands. If it does, the regulatory process before development becomes much more complicated. For the short term, uncertainty abounds and extreme caution is in order. Because the regulatory process has become so complex and an agreeable definition of wetlands so elusive, the trend among the Corps and collaborating agencies is to constrict nationwide permits in favor of narrowing the jurisdictional definition of wetlands

  5. Regulatory aspects of NPP safety

    International Nuclear Information System (INIS)

    Stuller, J.; Brandejs, P.; Miasnikov, A.; Svab, M.

    1999-01-01

    In beginning, a history of legislative process regulating industrial utilisation of nuclear energy is given, including detailed list of decrees issued by the first regulatory body supervising Czech nuclear installations - Czechoslovak Atomic Energy Commission (CSKAE). Current status of nuclear regulations and radiation protection, especially in connection with Atomic Act (Act No 18/1997 Coll.), is described. The Atomic Act transfers into the Czech legal system a number of obligations following from the Vienna Convention on Civil Liability for Nuclear Damage and Joint Protocol relating to the Application of the Vienna and Paris Convention, to which the Czech Republic had acceded. Actual duties and competence of current nuclear regulatory body - State Office for Nuclear Safety (SUJB) - are given in detail. Execution of the State supervision of peaceful utilisation of nuclear energy and ionising radiation is laid out in several articles of the Act, which comprises: control activities of the SUJB, remedial measures, penalties. Material and human resources are sufficient for fulfilment of the basic functions for which SUJB is authorised by the law. For 1998, the SUJB allotted staff of 149, approximately 2/3 of that number are nuclear safety and radiation protection inspectors. The SUJB budget for 1998 is approximately 180 million Czech crowns (roughly 6 million US dollars). Inspection activity of SUJB is carried out in three different ways: routine inspections, planned specialised inspections, inspections as a response to a certain situation (ad-hoc inspections). Approach to the licensing of major plant upgrades and backfittings are mainly illustrated on the Temelin NPP licensing. Regulatory position and practices concerning review activities are presented. (author)

  6. Defining Tobacco Regulatory Science Competencies.

    Science.gov (United States)

    Wipfli, Heather L; Berman, Micah; Hanson, Kacey; Kelder, Steven; Solis, Amy; Villanti, Andrea C; Ribeiro, Carla M P; Meissner, Helen I; Anderson, Roger

    2017-02-01

    In 2013, the National Institutes of Health and the Food and Drug Administration funded a network of 14 Tobacco Centers of Regulatory Science (TCORS) with a mission that included research and training. A cross-TCORS Panel was established to define tobacco regulatory science (TRS) competencies to help harmonize and guide their emerging educational programs. The purpose of this paper is to describe the Panel's work to develop core TRS domains and competencies. The Panel developed the list of domains and competencies using a semistructured Delphi method divided into four phases occurring between November 2013 and August 2015. The final proposed list included a total of 51 competencies across six core domains and 28 competencies across five specialized domains. There is a need for continued discussion to establish the utility of the proposed set of competencies for emerging TRS curricula and to identify the best strategies for incorporating these competencies into TRS training programs. Given the field's broad multidisciplinary nature, further experience is needed to refine the core domains that should be covered in TRS training programs versus knowledge obtained in more specialized programs. Regulatory science to inform the regulation of tobacco products is an emerging field. The paper provides an initial list of core and specialized domains and competencies to be used in developing curricula for new and emerging training programs aimed at preparing a new cohort of scientists to conduct critical TRS research. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Probabilistic safety assessment - regulatory perspective

    International Nuclear Information System (INIS)

    Solanki, R.B.; Paul, U.K.; Hajra, P.; Agarwal, S.K.

    2002-01-01

    Full text: Nuclear power plants (NPPs) have been designed, constructed and operated mainly based on deterministic safety analysis philosophy. In this approach, a substantial amount of safety margin is incorporated in the design and operational requirements. Additional margin is incorporated by applying the highest quality engineering codes, standards and practices, and the concept of defence-in-depth in design and operating procedures, by including conservative assumptions and acceptance criteria in plant response analysis of postulated initiating events (PIEs). However, as the probabilistic approach has been improved and refined over the years, it is possible for the designer, operator and regulator to get a more detailed and realistic picture of the safety importance of plant design features, operating procedures and operational practices by using probabilistic safety assessment (PSA) along with the deterministic methodology. At present, many countries including USA, UK and France are using PSA insights in their decision making along with deterministic basis. India has also made substantial progress in the development of methods for carrying out PSA. However, consensus on the use of PSA in regulatory decision-making has not been achieved yet. This paper emphasises on the requirements (e.g.,level of details, key modelling assumptions, data, modelling aspects, success criteria, sensitivity and uncertainty analysis) for improving the quality and consistency in performance and use of PSA that can facilitate meaningful use of the PSA insights in the regulatory decision-making in India. This paper also provides relevant information on international scenario and various application areas of PSA along with progress made in India. The PSA perspective presented in this paper may help in achieving consensus on the use of PSA for regulatory / utility decision-making in design and operation of NPPs

  8. Advanced Electronics

    Science.gov (United States)

    2017-07-21

    AFRL-RV-PS- AFRL-RV-PS- TR-2017-0114 TR-2017-0114 ADVANCED ELECTRONICS Ashwani Sharma 21 Jul 2017 Interim Report APPROVED FOR PUBLIC RELEASE...NUMBER Advanced Electronics 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 62601F 6. AUTHOR(S) 5d. PROJECT NUMBER 4846 Ashwani Sharma 5e. TASK NUMBER...Approved for public release; distribution is unlimited. (RDMX-17-14919 dtd 20 Mar 2018) 13. SUPPLEMENTARY NOTES 14. ABSTRACT The Space Electronics

  9. Electron spectroscopy

    International Nuclear Information System (INIS)

    Hegde, M.S.

    1979-01-01

    An introduction to the various techniques in electron spectroscopy is presented. These techniques include: (1) UV Photoelectron spectroscopy, (2) X-ray Photoelectron spectroscopy, (3) Auger electron spectroscopy, (4) Electron energy loss spectroscopy, (5) Penning ionization spectroscopy and (6) Ion neutralization spectroscopy. The radiations used in each technique, the basis of the technique and the special information obtained in structure determination in atoms and molecules by each technique are summarised. (A.K.)

  10. Quantifying electron fluxes in methanogenic microbial communities

    NARCIS (Netherlands)

    Junicke, H.

    2015-01-01

    Anaerobic digestion is a widely applied process in which close interactions between different microbial groups result in the formation of renewable energy in the form of biogas. Nevertheless, the regulatory mechanisms of the electron transfer between acetogenic bacteria and methanogenic archaea in

  11. Regulatory guidance for license renewal

    International Nuclear Information System (INIS)

    Thoma, John A.

    1991-01-01

    The proposed 10 CFR Part 54 rule proceduralizes the process for license renewal by identifying both the administrative and technical requirements for a renewal application. To amplify and support this regulation, written guidance has been provided in the form of a draft Regulatory Guide (DG 1009) and a draft Standard Review Plan for License Renewal (NUREG 1299). This guidance is scheduled to be finalized in 1992. Similar guidance will be provided for the proposed revisions to 10 CFR Part 51 concerning the environmental aspects of license renewal. (author)

  12. Advances in Canadian regulatory practice

    International Nuclear Information System (INIS)

    Waddington, J.G.

    1993-03-01

    The new General Amendments to the Regulations, new recommendations on dose limits, developments in techniques and safety thinking, and aging of plant are all contributing to the need for a significant number of new regulatory document on a wide range of topics. this paper highlights a number of initiatives taken in response to these pressures, giving a brief background to the initiative and, where possible, outlining some of the ideas in the document licensing guides on new dose limits, dosimetry, safety analysis, reliability, fault tree analysis, reporting requirements, human factors, software, the ALARA principle, backfitting and the licensing process. (Author) 29 refs., fig., 4 tabs

  13. A flood-based information flow analysis and network minimization method for gene regulatory networks.

    Science.gov (United States)

    Pavlogiannis, Andreas; Mozhayskiy, Vadim; Tagkopoulos, Ilias

    2013-04-24

    Biological networks tend to have high interconnectivity, complex topologies and multiple types of interactions. This renders difficult the identification of sub-networks that are involved in condition- specific responses. In addition, we generally lack scalable methods that can reveal the information flow in gene regulatory and biochemical pathways. Doing so will help us to identify key participants and paths under specific environmental and cellular context. This paper introduces the theory of network flooding, which aims to address the problem of network minimization and regulatory information flow in gene regulatory networks. Given a regulatory biological network, a set of source (input) nodes and optionally a set of sink (output) nodes, our task is to find (a) the minimal sub-network that encodes the regulatory program involving all input and output nodes and (b) the information flow from the source to the sink nodes of the network. Here, we describe a novel, scalable, network traversal algorithm and we assess its potential to achieve significant network size reduction in both synthetic and E. coli networks. Scalability and sensitivity analysis show that the proposed method scales well with the size of the network, and is robust to noise and missing data. The method of network flooding proves to be a useful, practical approach towards information flow analysis in gene regulatory networks. Further extension of the proposed theory has the potential to lead in a unifying framework for the simultaneous network minimization and information flow analysis across various "omics" levels.

  14. Inference of Transcription Regulatory Network in Low Phytic Acid Soybean Seeds

    Directory of Open Access Journals (Sweden)

    Neelam Redekar

    2017-11-01

    Full Text Available A dominant loss of function mutation in myo-inositol phosphate synthase (MIPS gene and recessive loss of function mutations in two multidrug resistant protein type-ABC transporter genes not only reduce the seed phytic acid levels in soybean, but also affect the pathways associated with seed development, ultimately resulting in low emergence. To understand the regulatory mechanisms and identify key genes that intervene in the seed development process in low phytic acid crops, we performed computational inference of gene regulatory networks in low and normal phytic acid soybeans using a time course transcriptomic data and multiple network inference algorithms. We identified a set of putative candidate transcription factors and their regulatory interactions with genes that have functions in myo-inositol biosynthesis, auxin-ABA signaling, and seed dormancy. We evaluated the performance of our unsupervised network inference method by comparing the predicted regulatory network with published regulatory interactions in Arabidopsis. Some contrasting regulatory interactions were observed in low phytic acid mutants compared to non-mutant lines. These findings provide important hypotheses on expression regulation of myo-inositol metabolism and phytohormone signaling in developing low phytic acid soybeans. The computational pipeline used for unsupervised network learning in this study is provided as open source software and is freely available at https://lilabatvt.github.io/LPANetwork/.

  15. Polymer electronics

    CERN Document Server

    Hsin-Fei, Meng

    2013-01-01

    Polymer semiconductor is the only semiconductor that can be processed in solution. Electronics made by these flexible materials have many advantages such as large-area solution process, low cost, and high performance. Researchers and companies are increasingly dedicating time and money in polymer electronics. This book focuses on the fundamental materials and device physics of polymer electronics. It describes polymer light-emitting diodes, polymer field-effect transistors, organic vertical transistors, polymer solar cells, and many applications based on polymer electronics. The book also disc

  16. Electronics Industry

    National Research Council Canada - National Science Library

    Bell, Robert; Carroll-Garrison, Martina; Donovan, Daniel; Fisher, John; Guemmer, Paul; Harms, Robert; Kelly, Timothy; Love, Mattie; McReynolds, James; Ward, Ralph

    2006-01-01

    .... Government action to preserve strategic access to semiconductor producers is clearly needed to ensure DoD electronic systems can be built without compromising sensitive technology, though every...

  17. Microfluidic electronics.

    Science.gov (United States)

    Cheng, Shi; Wu, Zhigang

    2012-08-21

    Microfluidics, a field that has been well-established for several decades, has seen extensive applications in the areas of biology, chemistry, and medicine. However, it might be very hard to imagine how such soft microfluidic devices would be used in other areas, such as electronics, in which stiff, solid metals, insulators, and semiconductors have previously dominated. Very recently, things have radically changed. Taking advantage of native properties of microfluidics, advances in microfluidics-based electronics have shown great potential in numerous new appealing applications, e.g. bio-inspired devices, body-worn healthcare and medical sensing systems, and ergonomic units, in which conventional rigid, bulky electronics are facing insurmountable obstacles to fulfil the demand on comfortable user experience. Not only would the birth of microfluidic electronics contribute to both the microfluidics and electronics fields, but it may also shape the future of our daily life. Nevertheless, microfluidic electronics are still at a very early stage, and significant efforts in research and development are needed to advance this emerging field. The intention of this article is to review recent research outcomes in the field of microfluidic electronics, and address current technical challenges and issues. The outlook of future development in microfluidic electronic devices and systems, as well as new fabrication techniques, is also discussed. Moreover, the authors would like to inspire both the microfluidics and electronics communities to further exploit this newly-established field.

  18. Electron holography

    CERN Document Server

    Tonomura, Akira

    1993-01-01

    Holography was devised for breaking through the resolution limit of electron microscopes The advent of a "coherent" field emission electron beam has enabled the use of Electron Holography in various areas of magnetic domain structures observation, fluxon observation in superconductors, and fundamental experiments in physics which have been inaccessible using other techniques After examining the fundamentals of electron holography and its applications to the afore mentioned fields, a detailed discussion of the Aharonov-Bohm effect and the related experiments is presented Many photographs and illustrations are included to elucidate the text

  19. Regulatory barriers blocking standardization of interoperability.

    Science.gov (United States)

    Zhong, Daidi; Kirwan, Michael J; Duan, Xiaolian

    2013-07-12

    Developing and implementing a set of personal health device interoperability standards is key to cultivating a healthy global industry ecosystem. The standardization organizations, including the Institute of Electrical and Electronics Engineers 11073 Personal Health Device Workgroup (IEEE 11073-PHD WG) and Continua Health Alliance, are striving for this purpose. However, factors like the medial device regulation, health policy, and market reality have placed non-technical barriers over the adoption of technical standards throughout the industry. These barriers have significantly impaired the motivations of consumer device vendors who desire to enter the personal health market and the overall success of personal health industry ecosystem. In this paper, we present the affect that these barriers have placed on the health ecosystem. This requires immediate action from policy makers and other stakeholders. The current regulatory policy needs to be updated to reflect the reality and demand of consumer health industry. Our hope is that this paper will draw wide consensus amongst its readers, policy makers, and other stakeholders.

  20. Pathways to plausibility

    DEFF Research Database (Denmark)

    Wahlberg, Ayo

    2008-01-01

    Herbal medicine has long been contrasted to modern medicine in terms of a holistic approach to healing, vitalistic theories of health and illness and an emphasis on the body’s innate self-healing capacities. At the same time, since the early 20th century, the cultivation, preparation and mass...... production of herbal medicines have become increasingly industrialised, scientificised and commercialised. What is more, phytochemical efforts to identify and isolate particular ‘active ingredients’ from whole-plant extracts have intensified, often in response to increasing regulatory scrutiny of the safety...... and quality of herbal medicinal products. In this paper, I examine whether describing these developments in terms of a biomedical ‘colonisation’ of herbal medicine, as has been common, allows us to sufficiently account for the mundane collaborative efforts of herbalists, botanists, phytochemists...