WorldWideScience

Sample records for lyrica regulatory post

  1. Listening to Lyrica: contested illnesses and pharmaceutical determinism.

    Science.gov (United States)

    Barker, Kristin K

    2011-09-01

    Fibromyalgia syndrome is a debilitating pain disorder of unknown origins and a paradigmatic contested illness. As with other contested illnesses, the reality of fibromyalgia is disputed by many physicians. Thus, millions of individuals who are diagnosed with fibromyalgia must cope with chronic symptoms as well as medical and public skepticism. In this context, the U.S. Federal Drug Administration's approval of Lyrica, the first prescription medication specifically for the management of fibromyalgia, is of considerable interest. In this paper I examine the cultural logic whereby the existence (and marketing) of an officially approved prescription medication for a condition lends support to the biomedical existence of the condition itself. I label this logic pharmaceutical determinism and argue that it represents an important new phase in the proliferation of contested illness diagnoses. Using the case of Lyrica, I describe the role that pharmaceutical companies and pharmaceuticals themselves play in promoting and legitimating contested diagnoses and validating those who are so diagnosed. Through a narrative analysis of the Lyrica direct-to-consumer advertising campaign and the responses of fibromyalgia sufferers to the introduction and marketing of Lyrica, I demonstrate the symbiotic relationship between the interests of the pharmaceutical industry, contested illness legitimization, and medicalization. I also provide a gender analysis of this relationship, foregrounding how contested illnesses continue to be shaped by their feminization in a cultural context that equates women with irrationality. Finally, I address the consequences and limitations of relying on the pharmaceutical industry for illness validation.

  2. A DFT investigation of structure, spectroscopic properties and tautomerism of the anticonvulsant drug Lyrica

    Science.gov (United States)

    Sadeghzade, Zohre; Beyramabadi, S. Ali; Morsali, Ali

    2015-03-01

    The Lyrica (Pregabalin) is a novel anticonvulsant and neuropathic pain drug, which could exist as four possible conformers. Herein, employing density functional theory (DFT), and handling the solvent effects with the PCM model, the structural parameters, energetic behavior, natural bond orbital analysis (NBO), as well as tautomerism mechanization of the Lyrica are investigated. The L1 (-OH form) is the most stable conformer of the Lyrica, which can be tautomerized to the L5 (-NH form) tautomer. The tautomerism reaction includes an intramolecular-proton transfer, which affects considerably the structural parameters and atomic charges of the L1. The DFT-computed NMR chemical shifts and IR vibrational frequencies are good in agreement with the experimental values, confirming suitability of the optimized geometry for the Lyrica.

  3. Post-marketing drug withdrawals: Pharmacovigilance success, regulatory problems.

    Science.gov (United States)

    Aronson, Jeffrey K

    2017-03-30

    Modern pharmacovigilance began in the 1960s, since when the subject has grown markedly, interest having particularly increased since 2010. One index of its success is the increasing speed with which serious adverse drug reactions are discovered after marketing of a medicinal product. However, the speed with which products have subsequently been withdrawn as a result of the discovery of serious adverse reactions has not consistently changed. This highlights problems that regulators and manufacturers face when serious reactions are discovered, with difficulties in deciding which of several consequent actions to take: to add specific warnings (cautions) or contraindications to the product label; to issue a Direct Healthcare Professional Communication; to allow informed patients to decide whether they will take the drug; or, in the most serious cases, to withdraw the product or revoke the licence. Conflicts of interest may inhibit decision-making. Recommendations that arise from these observations are that: health professionals and patients should be more vigorously encouraged to report suspected adverse drug reactions; regulatory authorities and drug manufacturers should take quicker confirmatory action when serious suspected adverse drug reactions are reported, even anecdotally, with formal studies to test for causality conducted sooner rather than later, applying lower than usual thresholds for suspicion; temporary suspensions or restrictions could be considered during such assessments; universal guidelines are needed for determining when a drug should be withdrawn if serious adverse drug reactions are suspected; there should be more rigorous monitoring and verification of deaths and reporting of reasons for drop-outs during clinical trials, with more transparency in reporting adverse events and ready access to premarketing clinical study reports; post-marketing drug monitoring systems and medicines regulation in low-to-middle income economies, especially in Africa

  4. Localizing potentially active post-transcriptional regulations in the Ewing's sarcoma gene regulatory network

    Directory of Open Access Journals (Sweden)

    Delyon Bernard

    2010-11-01

    Full Text Available Abstract Background A wide range of techniques is now available for analyzing regulatory networks. Nonetheless, most of these techniques fail to interpret large-scale transcriptional data at the post-translational level. Results We address the question of using large-scale transcriptomic observation of a system perturbation to analyze a regulatory network which contained several types of interactions - transcriptional and post-translational. Our method consisted of post-processing the outputs of an open-source tool named BioQuali - an automatic constraint-based analysis mimicking biologist's local reasoning on a large scale. The post-processing relied on differences in the behavior of the transcriptional and post-translational levels in the network. As a case study, we analyzed a network representation of the genes and proteins controlled by an oncogene in the context of Ewing's sarcoma. The analysis allowed us to pinpoint active interactions specific to this cancer. We also identified the parts of the network which were incomplete and should be submitted for further investigation. Conclusions The proposed approach is effective for the qualitative analysis of cancer networks. It allows the integrative use of experimental data of various types in order to identify the specific information that should be considered a priority in the initial - and possibly very large - experimental dataset. Iteratively, new dataset can be introduced into the analysis to improve the network representation and make it more specific.

  5. Post-crisis regulatory reforms and bank performance: lessons from Asia

    OpenAIRE

    Casu, B.; Deng, B.; Ferrari, Alessandra

    2016-01-01

    Based on a large dataset from eight Asian economies, we test the impact of post-crisis regulatory reforms on the performance of depository institutions in countries at different levels of financial development. We allow for technological heterogeneity and estimate a set of country-level stochastic cost frontiers followed by a deterministic bootstrapped meta-frontier to evaluate cost efficiency and cost technology. Our results support the view that liberalization policies have a positive impac...

  6. Elucidating MicroRNA Regulatory Networks Using Transcriptional, Post-transcriptional, and Histone Modification Measurements

    Directory of Open Access Journals (Sweden)

    Sara J.C. Gosline

    2016-01-01

    Full Text Available MicroRNAs (miRNAs regulate diverse biological processes by repressing mRNAs, but their modest effects on direct targets, together with their participation in larger regulatory networks, make it challenging to delineate miRNA-mediated effects. Here, we describe an approach to characterizing miRNA-regulatory networks by systematically profiling transcriptional, post-transcriptional and epigenetic activity in a pair of isogenic murine fibroblast cell lines with and without Dicer expression. By RNA sequencing (RNA-seq and CLIP (crosslinking followed by immunoprecipitation sequencing (CLIP-seq, we found that most of the changes induced by global miRNA loss occur at the level of transcription. We then introduced a network modeling approach that integrated these data with epigenetic data to identify specific miRNA-regulated transcription factors that explain the impact of miRNA perturbation on gene expression. In total, we demonstrate that combining multiple genome-wide datasets spanning diverse regulatory modes enables accurate delineation of the downstream miRNA-regulated transcriptional network and establishes a model for studying similar networks in other systems.

  7. Elucidating MicroRNA Regulatory Networks Using Transcriptional, Post-transcriptional, and Histone Modification Measurements.

    Science.gov (United States)

    Gosline, Sara J C; Gurtan, Allan M; JnBaptiste, Courtney K; Bosson, Andrew; Milani, Pamela; Dalin, Simona; Matthews, Bryan J; Yap, Yoon S; Sharp, Phillip A; Fraenkel, Ernest

    2016-01-12

    MicroRNAs (miRNAs) regulate diverse biological processes by repressing mRNAs, but their modest effects on direct targets, together with their participation in larger regulatory networks, make it challenging to delineate miRNA-mediated effects. Here, we describe an approach to characterizing miRNA-regulatory networks by systematically profiling transcriptional, post-transcriptional and epigenetic activity in a pair of isogenic murine fibroblast cell lines with and without Dicer expression. By RNA sequencing (RNA-seq) and CLIP (crosslinking followed by immunoprecipitation) sequencing (CLIP-seq), we found that most of the changes induced by global miRNA loss occur at the level of transcription. We then introduced a network modeling approach that integrated these data with epigenetic data to identify specific miRNA-regulated transcription factors that explain the impact of miRNA perturbation on gene expression. In total, we demonstrate that combining multiple genome-wide datasets spanning diverse regulatory modes enables accurate delineation of the downstream miRNA-regulated transcriptional network and establishes a model for studying similar networks in other systems.

  8. Elongation factor P mediates a novel post-transcriptional regulatory pathway critical for bacterial virulence

    DEFF Research Database (Denmark)

    Zou, S Betty; Roy, Hervé; Ibba, Michael;

    2012-01-01

    Bacterial pathogens detect and integrate multiple environmental signals to coordinate appropriate changes in gene expression including the selective expression of virulence factors, changes to metabolism and the activation of stress response systems. Mutations that abolish the ability of the path......Bacterial pathogens detect and integrate multiple environmental signals to coordinate appropriate changes in gene expression including the selective expression of virulence factors, changes to metabolism and the activation of stress response systems. Mutations that abolish the ability...... of the pathogen to respond to external cues are typically attenuating. Here we discuss our recent discovery of a novel post-transcriptional regulatory pathway critical for Salmonella virulence and stress resistance. The enzymes PoxA and YjeK coordinately attach a unique beta-amino acid onto a highly conserved...... our laboratory and others now suggests that EF-P, previously thought to be essential, instead plays an ancillary role in translation by regulating the synthesis of a relatively limited subset of proteins. Other observations suggest that the eukaryotic homolog of EF-P, eIF5A, may illicit similar...

  9. Evaluation of self-regulatory online learning in a blended course for post-registration nursing students in Taiwan.

    Science.gov (United States)

    Chen, Shu-Wen; Stocker, Joel; Wang, Ruey-Hsia; Chung, Yueh-Chin; Chen, Mei-Fang

    2009-10-01

    Online learning has become a common means of enhancing face-to-face classroom learning and is at the center of most collaborative, multimedia educational environments. There is some evidence that students' self-regulatory (SR) learning can be facilitated in a web-based learning environment, but studies of the effectiveness of self-directed online courses for post-registration nursing students have been few, and the results have been inconclusive. This study qualitatively examined the ways in which adding an online, asynchronous learning component to a nursing course might facilitate post-registration nursing students' self-regulatory learning. Learners' asynchronous communication on an online bulletin board comprised the qualitative dataset. Content related to their e-learning activities and experiences was extracted and generalized in order to examine the possible effects of this online interaction on SR learning. The themes that emerged indicated that students practiced SR learning skills through their online peer interaction. We propose several strategies for facilitating a self-regulatory learning environment based on these results from a course for post-registration nursing students in Taiwan.

  10. Regulatory inhibition of biological tissue mineralization by calcium phosphate through post-nucleation shielding by fetuin-A

    Science.gov (United States)

    Chang, Joshua C.; Miura, Robert M.

    2016-04-01

    In vertebrates, insufficient availability of calcium and inorganic phosphate ions in extracellular fluids leads to loss of bone density and neuronal hyper-excitability. To counteract this problem, calcium ions are usually present at high concentrations throughout bodily fluids—at concentrations exceeding the saturation point. This condition leads to the opposite situation where unwanted mineral sedimentation may occur. Remarkably, ectopic or out-of-place sedimentation into soft tissues is rare, in spite of the thermodynamic driving factors. This fortunate fact is due to the presence of auto-regulatory proteins that are found in abundance in bodily fluids. Yet, many important inflammatory disorders such as atherosclerosis and osteoarthritis are associated with this undesired calcification. Hence, it is important to gain an understanding of the regulatory process and the conditions under which it can go awry. In this manuscript, we extend mean-field continuum classical nucleation theory of the growth of clusters to encompass surface shielding. We use this formulation to study the regulation of sedimentation of calcium phosphate salts in biological tissues through the mechanism of post-nuclear shielding of nascent mineral particles by binding proteins. We develop a mathematical description of this phenomenon using a countable system of hyperbolic partial differential equations. A critical concentration of regulatory protein is identified as a function of the physical parameters that describe the system.

  11. The Caenorhabditis elegans vulva: a post-embryonic gene regulatory network controlling organogenesis.

    Science.gov (United States)

    Ririe, Ted O; Fernandes, Jolene S; Sternberg, Paul W

    2008-12-23

    The Caenorhabditis elegans vulva is an elegant model for dissecting a gene regulatory network (GRN) that directs postembryonic organogenesis. The mature vulva comprises seven cell types (vulA, vulB1, vulB2, vulC, vulD, vulE, and vulF), each with its own unique pattern of spatial and temporal gene expression. The mechanisms that specify these cell types in a precise spatial pattern are not well understood. Using reverse genetic screens, we identified novel components of the vulval GRN, including nhr-113 in vulA. Several transcription factors (lin-11, lin-29, cog-1, egl-38, and nhr-67) interact with each other and act in concert to regulate target gene expression in the diverse vulval cell types. For example, egl-38 (Pax2/5/8) stabilizes the vulF fate by positively regulating vulF characteristics and by inhibiting characteristics associated with the neighboring vulE cells. nhr-67 and egl-38 regulate cog-1, helping restrict its expression to vulE. Computational approaches have been successfully used to identify functional cis-regulatory motifs in the zmp-1 (zinc metalloproteinase) promoter. These results provide an overview of the regulatory network architecture for each vulval cell type.

  12. Post-Transcriptional Regulation by the Csr Global Regulatory System in Escherichia coli

    OpenAIRE

    Suzuki, Kazushi; 鈴木, 一史

    2007-01-01

    In many species of bacteria, the Csr (carbon storage regulator) global regulatory system coordinates the expression of various genes. In Escherichia coli, the central component of this system, CsrA, is a RNA-binding protein. The CsrA is a homodimer and binds to leader segments of target mRNAs, affecting their translation and stability. CsrA activity is regulated by two small non-coding RNAs, CsrB and CsrC. These RNAs contain multiple CsrA-binding sequences and act by sequestering CsrA. In thi...

  13. The post-transcriptional regulatory system CSR controls the balance of metabolic pools in upper glycolysis of Escherichia coli.

    Science.gov (United States)

    Morin, Manon; Ropers, Delphine; Letisse, Fabien; Laguerre, Sandrine; Portais, Jean-Charles; Cocaign-Bousquet, Muriel; Enjalbert, Brice

    2016-05-01

    Metabolic control in Escherichia coli is a complex process involving multilevel regulatory systems but the involvement of post-transcriptional regulation is uncertain. The post-transcriptional factor CsrA is stated as being the only regulator essential for the use of glycolytic substrates. A dozen enzymes in the central carbon metabolism (CCM) have been reported as potentially controlled by CsrA, but its impact on the CCM functioning has not been demonstrated. Here, a multiscale analysis was performed in a wild-type strain and its isogenic mutant attenuated for CsrA (including growth parameters, gene expression levels, metabolite pools, abundance of enzymes and fluxes). Data integration and regulation analysis showed a coordinated control of the expression of glycolytic enzymes. This also revealed the imbalance of metabolite pools in the csrA mutant upper glycolysis, before the phosphofructokinase PfkA step. This imbalance is associated with a glucose-phosphate stress. Restoring PfkA activity in the csrA mutant strain suppressed this stress and increased the mutant growth rate on glucose. Thus, the carbon storage regulator system is essential for the effective functioning of the upper glycolysis mainly through its control of PfkA. This work demonstrates the pivotal role of post-transcriptional regulation to shape the carbon metabolism.

  14. Complementary Post Transcriptional Regulatory Information is Detected by PUNCH-P and Ribosome Profiling

    Science.gov (United States)

    Zur, Hadas; Aviner, Ranen; Tuller, Tamir

    2016-01-01

    Two novel approaches were recently suggested for genome-wide identification of protein aspects synthesized at a given time. Ribo-Seq is based on sequencing all the ribosome protected mRNA fragments in a cell, while PUNCH-P is based on mass-spectrometric analysis of only newly synthesized proteins. Here we describe the first Ribo-Seq/PUNCH-P comparison via the analysis of mammalian cells during the cell-cycle for detecting relevant differentially expressed genes between G1 and M phase. Our analyses suggest that the two approaches significantly overlap with each other. However, we demonstrate that there are biologically meaningful proteins/genes that can be detected to be post-transcriptionally regulated during the mammalian cell cycle only by each of the approaches, or their consolidation. Such gene sets are enriched with proteins known to be related to intra-cellular signalling pathways such as central cell cycle processes, central gene expression regulation processes, processes related to chromosome segregation, DNA damage, and replication, that are post-transcriptionally regulated during the mammalian cell cycle. Moreover, we show that combining the approaches better predicts steady state changes in protein abundance. The results reported here support the conjecture that for gaining a full post-transcriptional regulation picture one should integrate the two approaches. PMID:26898226

  15. Contribution of industry funded post-marketing studies to drug safety: survey of notifications submitted to regulatory agencies

    Science.gov (United States)

    Prugger, Christof; Doshi, Peter; Ostrowski, Kerstin; Witte, Thomas; Hüsgen, Dieter; Keil, Ulrich

    2017-01-01

    Objectives To investigate the practice of post-marketing studies in Germany during a three year period and to evaluate whether these trials meet the aims specified in the German Medicinal Products Act. Design Survey of notifications submitted to German regulatory agencies before post-marketing studies were carried out, 2008-10. Setting Notifications obtained through freedom of information requests to the three authorities responsible for registering post-marketing studies in Germany. Main outcome measures Descriptive statistics of post-marketing studies, including the products under study, intended number of patients, intended number of participating physicians, proposed remunerations, study plan and protocol, and availability of associated scientific publications and reports on adverse drug reactions. Results Information was obtained from 558 studies, with a median of 600 (mean 2331, range 2-75 000) patients and 63 (270, 0-7000) participating physicians per study. The median remuneration to physicians per patient was €200 (€441, €0-€7280) (£170, £0-£6200; $215, $0-$7820), with a total remuneration cost of more than €217m for 558 studies registered over the three year period. The median remuneration per participating physician per study was €2000 (mean €19 424), ranging from €0 to €2 080 000. There was a broad range of drugs and non-drug products, of which only a third represented recently approved drugs. In many notifications, data, information, and results were, by contract, strictly confidential and the sole property of the respective sponsor. No single adverse drug reaction report could be identified from any of the 558 post-marketing studies. Less than 1% of studies could be verified as published in scientific journals. Conclusions Post-marketing studies are not improving drug safety surveillance. Sample sizes are generally too small to allow the detection of rare adverse drug reactions, and many participating physicians are

  16. Contribution of industry funded post-marketing studies to drug safety: survey of notifications submitted to regulatory agencies.

    Science.gov (United States)

    Spelsberg, Angela; Prugger, Christof; Doshi, Peter; Ostrowski, Kerstin; Witte, Thomas; Hüsgen, Dieter; Keil, Ulrich

    2017-02-07

     To investigate the practice of post-marketing studies in Germany during a three year period and to evaluate whether these trials meet the aims specified in the German Medicinal Products Act.  Survey of notifications submitted to German regulatory agencies before post-marketing studies were carried out, 2008-10.  Notifications obtained through freedom of information requests to the three authorities responsible for registering post-marketing studies in Germany.  Descriptive statistics of post-marketing studies, including the products under study, intended number of patients, intended number of participating physicians, proposed remunerations, study plan and protocol, and availability of associated scientific publications and reports on adverse drug reactions.  Information was obtained from 558 studies, with a median of 600 (mean 2331, range 2-75 000) patients and 63 (270, 0-7000) participating physicians per study. The median remuneration to physicians per patient was €200 (€441, €0-€7280) (£170, £0-£6200; $215, $0-$7820), with a total remuneration cost of more than €217m for 558 studies registered over the three year period. The median remuneration per participating physician per study was €2000 (mean €19 424), ranging from €0 to €2 080 000. There was a broad range of drugs and non-drug products, of which only a third represented recently approved drugs. In many notifications, data, information, and results were, by contract, strictly confidential and the sole property of the respective sponsor. No single adverse drug reaction report could be identified from any of the 558 post-marketing studies. Less than 1% of studies could be verified as published in scientific journals.  Post-marketing studies are not improving drug safety surveillance. Sample sizes are generally too small to allow the detection of rare adverse drug reactions, and many participating physicians are strictly obliged to maintain confidentiality towards the

  17. Post-translational hydroxylation by 2OG/Fe(II-dependent oxygenases as a novel regulatory mechanism in bacteria

    Directory of Open Access Journals (Sweden)

    Laura M van Staalduinen

    2015-01-01

    Full Text Available Protein hydroxylation has been well-studied in eukaryotic systems. The structural importance of hydroxylation of specific proline and lysine residues during collagen biosynthesis is well established while, recently, key roles for post-translational hydroxylation in signalling and degradation pathways have been discovered. The function of hydroxylation in signalling is highlighted by its role in the hypoxic response of eukaryotic cells, where oxygen dependent hydroxylation of the hypoxia inducible transcription factor both targets it for degradation and blocks its activation. In contrast, the role of protein hydroxylation has been largely understudied in prokaryotes. Recently, an evolutionarily conserved class of ribosomal oxygenases (ROX that catalyze the hydroxylation of specific residues in the ribosome has been identified in bacteria. ROX activity has been linked to cell growth, and has been found to have a direct impact on bulk protein translation. This discovery of ribosomal protein hydroxylation in bacteria could lead to new therapeutic targets for regulating bacterial growth, as well as, shed light on new prokaryotic hydroxylation signalling pathways. In this review, recent structural and functional studies will be highlighted and discussed, underscoring the regulatory potential of post-translational hydroxylation in bacteria.

  18. Post-Translational Modifications of Kaposi’s Sarcoma-Associated Herpesvirus (KSHV Regulatory Proteins-SUMO and KSHV

    Directory of Open Access Journals (Sweden)

    Mel eCampbell

    2012-02-01

    Full Text Available Reactivation from a latent state is an important feature of infection and disease caused by many herpesviruses. KSHV latency can be envisioned as an outcome that is balanced between factors that promote viral gene expression and lytic replication against those that facilitate gene silencing and establish or maintain latency. A large body of work has focused on the activities of the key viral regulatory proteins involved in KSHV latent or lytic states. Moreover, recent studies have also begun to document the importance of epigenetic landscape evolution of the KSHV viral genome during latency and reactivation. However, one area of KSHV molecular virology that remains largely unanswered is the precise role of post-translational modifications on the activities of viral factors that function during latency and reactivation. In this review, we will summarize the post-translational modifications associated with three viral factors whose activities contribute to the viral state. The viral proteins discussed are the two major KSHV encoded transcription factors, K-Rta and K-bZIP (KSHV basic leucine zipper and the viral latency-associated nuclear antigen (LANA. A special emphasis will be placed on the role of the sumoylation pathway in the modulation of the KSHV lifecycle. Newly uncovered SUMO-dependent properties of LANA and K-Rta will also be presented, namely LANA histone-targeting SUMO E3 ligase activity and K-Rta SUMO-targeted ubiquitin ligase function.

  19. Emissions to the Atmosphere from Amine-Based Post Combustion CO2 Capture Plant – Regulatory Aspects

    Directory of Open Access Journals (Sweden)

    Azzi Merched

    2014-09-01

    Full Text Available Amine-based Post Combustion Capture (PCC of CO2 is a readily available technology that can be deployed to reduce CO2 emissions from coal fired power plants. However, PCC plants will likely release small quantities of amine and amine degradation products to the atmosphere along with the treated flue gas. The possible environmental effects of these emissions have been examined through different studies carried out around the world. Based on flue gas from a 400 MW ultra-supercritical coal fired power plant Aspen-Plus PCC process simulations were used to predict the potential atmospheric emissions from the plant. Different research initiatives carried out in this area have produced new knowledge that has significantly reduced the risk perception for the release of amine and amine degradation products to the atmosphere. In addition to the reduction of the CO2 emissions, the PCC technology will also help in reducing SOx and NO2 emissions. However, some other pollutants such as NH3 and aerosols will increase if appropriate control technologies are not adopted. To study the atmospheric photo-oxidation of amines, attempts are being made to develop chemical reaction schemes that can be used for air quality assessment. However, more research is still required in this area to estimate the reactivity of amino solvents in the presence of other pollutants such as NOx and other volatile organic compounds in the background air. Current air quality guidelines may need to be updated to include limits for the additional pollutants such as NH3, nitrosamines and nitramines once more information related to their emissions is available. This paper focuses on describing the predicted concentrations of major pollutants that are expected to be released from a coal fired power plant obtained by ASPEN-Plus PCC process simulations in terms of current air quality regulations and other regulatory aspects.

  20. Utility of registries for post-marketing evaluation of medicines. A survey of Swedish health care quality registries from a regulatory perspective.

    Science.gov (United States)

    Feltelius, Nils; Gedeborg, Rolf; Holm, Lennart; Zethelius, Björn

    2017-06-01

    The aim of this study was to describe content and procedures in some selected Swedish health care quality registries (QRs) of relevance to regulatory decision-making. A workshop was organized with participation of seven Swedish QRs which subsequently answered a questionnaire regarding registry content on drug treatments and outcomes. Patient populations, coverage, data handling and quality control, as well as legal and ethical aspects are presented. Scientific publications from the QRs are used as a complementary measure of quality and scientific relevance. The registries under study collect clinical data of high relevance to regulatory and health technology agencies. Five out of seven registries provide information on the drug of interest. When applying external quality criteria, we found a high degree of fulfillment, although information on medication was not sufficient to answer all questions of regulatory interest. A notable strength is the option for linkage to the Prescribed Drug Registry and to information on education and socioeconomic status. Data on drugs used during hospitalization were also collected to some extent. Outcome measures collected resemble those used in relevant clinical trials. All registries collected patient-reported outcome measures. The number of publications from the registries was substantial, with studies of appropriate design, including randomized registry trials. Quality registries may provide a valuable source of post-marketing data on drug effectiveness, safety, and cost-effectiveness. Closer collaboration between registries and regulators to improve quality and usefulness of registry data could benefit both regulatory utility and value for health care providers.

  1. Distinct regulatory mechanisms of the human ferritin gene by hypoxia and hypoxia mimetic cobalt chloride at the transcriptional and post-transcriptional levels.

    Science.gov (United States)

    Huang, Bo-Wen; Miyazawa, Masaki; Tsuji, Yoshiaki

    2014-12-01

    Cobalt chloride has been used as a hypoxia mimetic because it stabilizes hypoxia inducible factor-1α (HIF1-α) and activates gene transcription through a hypoxia responsive element (HRE). However, differences between hypoxia and hypoxia mimetic cobalt chloride in gene regulation remain elusive. Expression of ferritin, the major iron storage protein, is regulated at the transcriptional and posttranscriptional levels through DNA and RNA regulatory elements. Here we demonstrate that hypoxia and cobalt chloride regulate ferritin heavy chain (ferritin H) expression by two distinct mechanisms. Both hypoxia and cobalt chloride increased HIF1-α but a putative HRE in the human ferritin H gene was not activated. Instead, cobalt chloride but not hypoxia activated ferritin H transcription through an antioxidant responsive element (ARE), to which Nrf2 was recruited. Intriguingly, cobalt chloride downregulated ferritin H protein expression while it upregulated other ARE-regulated antioxidant genes in K562 cells. Further characterization demonstrated that cobalt chloride increased interaction between iron regulatory proteins (IRP1 and IRP2) and iron responsive element (IRE) in the 5'UTR of ferritin H mRNA, resulting in translational block of the accumulated ferritin H mRNA. In contrast, hypoxia had marginal effect on ferritin H transcription but increased its translation through decreased IRP1-IRE interaction. These results suggest that hypoxia and hypoxia mimetic cobalt chloride employ distinct regulatory mechanisms through the interplay between DNA and mRNA elements at the transcriptional and post-transcriptional levels.

  2. Contrasting evolutionary dynamics of the developmental regulator PAX9, among bats, with evidence for a novel post-transcriptional regulatory mechanism.

    Directory of Open Access Journals (Sweden)

    Caleb D Phillips

    Full Text Available Morphological evolution can be the result of natural selection favoring modification of developmental signaling pathways. However, little is known about the genetic basis of such phenotypic diversity. Understanding these mechanisms is difficult for numerous reasons, yet studies in model organisms often provide clues about the major developmental pathways involved. The paired-domain gene, PAX9, is known to be a key regulator of development, particularly of the face and teeth. In this study, using a comparative genetics approach, we investigate PAX9 molecular evolution among mammals, focusing on craniofacially diversified (Phyllostomidae and conserved (Vespertilionidae bat families, and extend our comparison to other orders of mammal. Open-reading frame analysis disclosed signatures of selection, in which a small percentage of residues vary, and lineages acquire different combinations of variation through recurrent substitution and lineage specific changes. A few instances of convergence for specific residues were observed between morphologically convergent bat lineages. Bioinformatic analysis for unknown PAX9 regulatory motifs indicated a novel post-transcriptional regulatory mechanism involving a Musashi protein. This regulation was assessed through fluorescent reporter assays and gene knockdowns. Results are compatible with the hypothesis that the number of Musashi binding-elements in PAX9 mRNA proportionally regulates protein translation rate. Although a connection between morphology and binding element frequency was not apparent, results indicate this regulation would vary among craniofacially divergent bat species, but be static among conserved species. Under this model, Musashi's regulatory control of alternative human PAX9 isoforms would also vary. The presence of Musashi-binding elements within PAX9 of all mammals examined, chicken, zebrafish, and the fly homolog of PAX9, indicates this regulatory mechanism is ancient, originating basal

  3. Coordination of improvement of higher education personnel: regulatory officer field of post-graduate studies in Brazil

    Directory of Open Access Journals (Sweden)

    Rogerio Junior Boratim

    2014-12-01

    Full Text Available This paper aims to present a sociological reflection on the role of the Coordination of Improvement of Higher Education Personnel (CAPES as the regulator that institutionalized the field of postgraduate studies in Brazil with public universities. The methodological and theoretical assumptions underpin the theory of the scientific field of Pierre Bourdieu and seek to demonstrate that the CAPES as a political entity linked to the federal government brokered and legitimized the involvement of the holders of teacher-researchers greater symbolic capital (scientific recognition among peers-competitors , giving them the prerogative to set rules for the evaluation and funding of post-graduate studies. Nevertheless, these legitimate borrowers (dominant in the field of post-graduate consolidated merit system amalgamated by one academic productivism, establishing universities within a performance culture that brings the trailer individualism, utilitarianism and the casualization of labor and relations in the university field.

  4. Integrative Analysis Using Proteome and Transcriptome Data From Yeast to Unravel Regulatory Patterns at Post-Transcriptional Level

    DEFF Research Database (Denmark)

    Olivares Hernandez, Roberto; Usaite, Renata; Nielsen, Jens

    2010-01-01

    Exist several studies on the correlation between proteome and transcriptome and these studies have shown that generally there is only a weak positive correlation between the,e two omes, which means that post-transcriptional events play an important role in determining the protein levels in the cell......RNA is related to the gene function We could further identify that for genes belonging to amino acid biosynthetic pathways there is no translational regulation, meaning that there is generally a good correlation between mRNA and protein levels We also found that there is generally translational control for large...

  5. A systematic computational analysis of the rRNA–3′ UTR sequence complementarity suggests a regulatory mechanism influencing post-termination events in metazoan translation

    Science.gov (United States)

    Pánek, Josef; Kolář, Michal; Herrmannová, Anna; Valášek, Leoš Shivaya

    2016-01-01

    Nucleic acid sequence complementarity underlies many fundamental biological processes. Although first noticed a long time ago, sequence complementarity between mRNAs and ribosomal RNAs still lacks a meaningful biological interpretation. Here we used statistical analysis of large-scale sequence data sets and high-throughput computing to explore complementarity between 18S and 28S rRNAs and mRNA 3′ UTR sequences. By the analysis of 27,646 full-length 3′ UTR sequences from 14 species covering both protozoans and metazoans, we show that the computed 18S rRNA complementarity creates an evolutionarily conserved localization pattern centered around the ribosomal mRNA entry channel, suggesting its biological relevance and functionality. Based on this specific pattern and earlier data showing that post-termination 80S ribosomes are not stably anchored at the stop codon and can migrate in both directions to codons that are cognate to the P-site deacylated tRNA, we propose that the 18S rRNA–mRNA complementarity selectively stabilizes post-termination ribosomal complexes to facilitate ribosome recycling. We thus demonstrate that the complementarity between 18S rRNA and 3′ UTRs has a non-random nature and very likely carries information with a regulatory potential for translational control. PMID:27190231

  6. Regulation of the CDP-choline pathway by sterol regulatory element binding proteins involves transcriptional and post-transcriptional mechanisms.

    Science.gov (United States)

    Ridgway, Neale D; Lagace, Thomas A

    2003-06-15

    The synthesis of phosphatidylcholine (PtdCho) by the CDP-choline pathway is under the control of the rate-limiting enzyme CTP:phosphocholine cytidylyltransferase (CCT). Sterol regulatory element binding proteins (SREBPs) have been proposed to regulate CCT at the transcriptional level, or via the synthesis of lipid activators or substrates of the CDP-choline pathway. To assess the contributions of these two mechanisms, we examined CCTalpha expression and PtdCho synthesis by the CDP-choline pathway in cholesterol and fatty acid auxotrophic CHO M19 cells inducibly expressing constitutively active nuclear forms of SREBP1a or SREBP2. Induction of either SREBP resulted in increased expression of mRNAs for sterol-regulated genes, elevated fatty acid and cholesterol synthesis (>10-50-fold) and increased PtdCho synthesis (2-fold). CCTalpha mRNA was increased 2-fold by enforced expression of SREBP1a or SREBP2. The resultant increase in CCTalpha protein and activity (2-fold) was restricted primarily to the soluble fraction of cells, and increased CCTalpha activity in vivo was not detected. Inhibition of the synthesis of fatty acids or their CoA esters by cerulenin or triacsin C respectively following SREBP induction effectively blocked the accompanying elevation in PtdCho synthesis. Thus PtdCho synthesis was driven by increased synthesis of fatty acids or a product thereof. These data show that transcriptional activation of CCTalpha is modest relative to that of other SREBP-regulated genes, and that stimulation of PtdCho synthesis by SREBPs in CHO cells is due primarily to increased fatty acid synthesis.

  7. Dissecting the expression relationships between RNA-binding proteins and their cognate targets in eukaryotic post-transcriptional regulatory networks

    Science.gov (United States)

    Nishtala, Sneha; Neelamraju, Yaseswini; Janga, Sarath Chandra

    2016-05-01

    RNA-binding proteins (RBPs) are pivotal in orchestrating several steps in the metabolism of RNA in eukaryotes thereby controlling an extensive network of RBP-RNA interactions. Here, we employed CLIP (cross-linking immunoprecipitation)-seq datasets for 60 human RBPs and RIP-ChIP (RNP immunoprecipitation-microarray) data for 69 yeast RBPs to construct a network of genome-wide RBP- target RNA interactions for each RBP. We show in humans that majority (~78%) of the RBPs are strongly associated with their target transcripts at transcript level while ~95% of the studied RBPs were also found to be strongly associated with expression levels of target transcripts when protein expression levels of RBPs were employed. At transcript level, RBP - RNA interaction data for the yeast genome, exhibited a strong association for 63% of the RBPs, confirming the association to be conserved across large phylogenetic distances. Analysis to uncover the features contributing to these associations revealed the number of target transcripts and length of the selected protein-coding transcript of an RBP at the transcript level while intensity of the CLIP signal, number of RNA-Binding domains, location of the binding site on the transcript, to be significant at the protein level. Our analysis will contribute to improved modelling and prediction of post-transcriptional networks.

  8. Preliminary identification and analysis of point mutations corre-lated with response to interferon-α in hepatitis B virus post-transcriptional regulatory elements

    Institute of Scientific and Technical Information of China (English)

    XING Tong-jing; LUO Kang-xian; HOU Jin-lin

    2005-01-01

    Background It is still unclear whether viral genetic variability influences response to interferon(IFN)-α treatment. Recent reports suggest that IFN-α effects may be associated with hepatitis B virus(HBV) post-transcriptional regulation. This study was designed to explore the heterogeneity of HBV post-transcriptional regulatory elements (HPRE) and the relationship between the diversity of HPRE and the response to IFN-α treatment. Methods The HPRE sequences from 31 Chinese patients infected with HBV were determined by directly sequencing of polymerase chain reaction (PCR) product, and comparing them to those from Caucasian patients. Subsequently, eukaryotic expression vectors containing HPRE at various points were constructed and transfected into HepG2 cells, which were then exposed to recombinant human cytokines. Results The T to C point mutation at nt 1504 and the C to T (G) at nt 1508 in HPRE were found in 21 and 19 patients with chronic hepatitis B, respectively; the C to T point mutation at nt 1509 was found in 17 patients. These point mutations did not exist in the HPRE of the Caucasian patients. The activity of the CAT gene obviously increased in the case of T to C point mutation at nt 1504, but did not change in the case of the C to T (G) mutations at nt 1508 and 1509. The activity of the CAT gene at these point mutations of HPRE could be inhibited by IFN-α/γ and tumor necrosis factor (TNF)-α except for the point mutations at nt 1508 of HPRE which may escape the suppression role of IFN-α on HPRE. Conclusions There are point mutations between the HPRE of Chinese and Caucasian HBV patients, which might be correlated with response to IFN-α. The variation of HPRE might affect the function of HPRE and influence the regulative function of IFN-α other than that of IFN-γ or TNF-α on HPRE.

  9. SSR markers in transcripts of genes linked to post-transcriptional and transcriptional regulatory functions during vegetative and reproductive development of Elaeis guineensis.

    Science.gov (United States)

    Tranbarger, Timothy John; Kluabmongkol, Wanwisa; Sangsrakru, Duangjai; Morcillo, Fabienne; Tregear, James W; Tragoonrung, Somvong; Billotte, Norbert

    2012-01-03

    The oil palm (Elaeis guineensis Jacq.) is a perennial monocotyledonous tropical crop species that is now the world's number one source of edible vegetable oil, and the richest dietary source of provitamin A. While new elite genotypes from traditional breeding programs provide steady yield increases, the long selection cycle (10-12 years) and the large areas required to cultivate oil palm make genetic improvement slow and labor intensive. Molecular breeding programs have the potential to make significant impacts on the rate of genetic improvement but the limited molecular resources, in particular the lack of molecular markers for agronomic traits of interest, restrict the application of molecular breeding schemes for oil palm. In the current study, 6,103 non-redundant ESTs derived from cDNA libraries of developing vegetative and reproductive tissues were annotated and searched for simple sequence repeats (SSRs). Primer pairs from sequences flanking 289 EST-SSRs were tested to detect polymorphisms in elite breeding parents and their crosses. 230 of these amplified PCR products, 88 of which were polymorphic within the breeding material tested. A detailed analysis and annotation of the EST-SSRs revealed the locations of the polymorphisms within the transcripts, and that the main functional category was related to transcription and post-transcriptional regulation. Indeed, SSR polymorphisms were found in sequences encoding AP2-like, bZIP, zinc finger, MADS-box, and NAC-like transcription factors in addition to other transcriptional regulatory proteins and several RNA interacting proteins. The identification of new EST-SSRs that detect polymorphisms in elite breeding material provides tools for molecular breeding strategies. The identification of SSRs within transcripts, in particular those that encode proteins involved in transcriptional and post-transcriptional regulation, will allow insight into the functional roles of these proteins by studying the phenotypic traits

  10. Regulatory agencies and regulatory risk

    OpenAIRE

    Knieps, Günter; Weiß, Hans-Jörg

    2007-01-01

    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...

  11. PDA PAC iAM 2017 Survey on Post Approval Change Is the regulatory environment hindering much needed innovation in the Pharma Industry?

    Science.gov (United States)

    Seymour, Melissa

    2017-08-17

    As part of the effort to identify, assess and address current barriers to PACs, the PDA administered a global, blinded, cross-functional survey to document industry experience with PACs in the current global regulatory environment, and to better understand the regulatory complexity and burden on the industry. The survey interrogated on specific points related to annual volume of PACs, reasons, time commitments/cycle time, impact of regional differences on change implementation, current use of tools (e.g. PACMPs), impact on supply chain complexity (e.g. inventory, variants to manage, non-compliance to filings, drug shortages), manufacturing innovation, and resources needed. Copyright © 2017, Parenteral Drug Association.

  12. Regulatory review and confidence building in post-closure safety assessments and safety cases for near surface disposal facilities, IAEA ASAM coordinated research project

    Energy Technology Data Exchange (ETDEWEB)

    Belfadhel, M.B. [Canadian Nuclear Safety Commission, Waste and Geosciences Div., Ottawa, Ontario (Canada)]. E-mail: Benbelfadhelm@cnsc-ccsn.gc.ca; Bennett, D.G. [Galson Science Limited, Oakham (United Kingdom); Gonzales, A. [Iberdrola Ingeniera y Consultoria, Madrid (Spain); Metcalf, P. [International Atomic Energy Agency, Vienna (Austria); Nys, V. [Association Vincotte Nucleaire, Brussels (Belgium); Simeonov, G. [Nuclear Regulatory Agency, Sofia (Bulgaria); Zeleznik, N. [ARAO-Agency of Radwaste Management, Ljubljana (Slovenia)

    2006-07-01

    The IAEA successfully concluded a Coordinated Research Program (CRP) called ISAM, which focused on the development of an Improved Safety Assessment Methodology for near-surface radioactive waste disposal facilities (1997-2002). In November 2002, and as an extension of ISAM, the IAEA launched a new CRP called ASAM, designed to test the Application of the Safety Assessment Methodology by considering a range of near surface disposal facilities. The ASAM work programme is being implemented by three application working groups and two cross-cutting working groups. The application working groups are testing the applicability of the ISAM methodology by assessing an existing disposal facility in Hungary, a copper mine in South Africa, and a hypothetical facility containing heterogenous wastes, such as disused sealed sources. The first cross-cutting working group is addressing a number of technical issues that are common to all near-surface disposal facilities, while the second group, the Regulatory Review Working Group (RRWG) is developing guidance on how to gain confidence in safety assessments and safety cases, and on how to conduct regulatory reviews of safety assessments. This paper provides a brief overview of the work being conducted by the Regulatory Review Working Group. (author)

  13. Effects of over-expression of the regulatory enzymes DraT and DraG on the ammonium-dependent post-translational regulation of nitrogenase reductase in Azospirillum brasilense.

    Science.gov (United States)

    Huergo, Luciano F; Souza, Emanuel M; Steffens, Maria B R; Yates, M Geoffrey; Pedrosa, Fábio O; Chubatsu, Leda S

    2005-03-01

    Nitrogen fixation in Azospirillum brasilense is regulated at transcriptional and post-translational levels. Post-translational control occurs through the reversible ADP-ribosylation of dinitrogenase reductase (Fe Protein), mediated by the dinitrogenase reductase ADP-ribosyltransferase (DraT) and dinitrogenase reductase glycohydrolase (DraG). Although the DraT and DraG activities are regulated in vivo, the molecules responsible for such regulation remain unknown. We have constructed broad-host-range plasmids capable of over-expressing, upon IPTG induction, the regulatory enzymes DraT and DraG as six-histidine-N-terminal fused proteins (His). Both DraT-His and DraG-His are functional in vivo. We have analyzed the effects of DraT-His and DraG-His over-expression on the post-translational modification of Fe Protein. The DraT-His over-expression led to Fe Protein modification in the absence of ammonium addition, while cells over-expressing DraG-His showed only partial ADP-ribosylation of Fe Protein by adding ammonium. These results suggest that both DraT-His and DraG-His lose their regulation upon over-expression, possible by titrating out negative regulators.

  14. Advanced flowcytometric analysis of regulatory T cells: CD127 downregulation early post stem cell transplantation and altered Treg/CD3(+)CD4(+)-ratio in severe GvHD or relapse.

    Science.gov (United States)

    Bremm, Melanie; Huenecke, Sabine; Lehrnbecher, Thomas; Ponstingl, Eva; Mueller, Regine; Heinze, Annekathrin; Bug, Gesine; Quaiser, Andrea; Kapinsky, Michael; Brehm, Claudia; Bader, Peter; Schneider, Gisbert; Klingebiel, Thomas; Koehl, Ulrike

    2011-10-28

    Regulatory T cells (Tregs) are of crucial importance to suppress graft versus host disease (GvHD) post allogeneic stem cell transplantation (SCT), but are also known to impair antitumor immunity. However, Treg longitudinal studies are rare and in this respect advanced flowcytometric approaches for Treg characterization are necessary. To investigate the relation of both the percentage and the absolute numbers of Tregs on GvHD or relapse we measured CD4(+)CD25(+/hi)CD127(lo/-) Tregs in 239 peripheral blood (PB) samples of 16 patients during the first two years post-SCT. A 10-color flowcytometric panel was established to evaluate Treg subpopulations and has been tested in ten healthy individuals. In patients we demonstrated a decrease in CD127 expression on T cells early post-SCT which increases during the first year. Moreover, Tregs reached higher absolute numbers in patients with GvHD≤grade I compared to those with GvHD grades II-IV. In contrast, the percentage of Tregs was significantly higher in patients with GvHD grades II-IV or disease relapse compared to those without GvHD. These patients fit into the range of healthy individuals where a median value of 7.5% and 6.4% of T helper cells were characterized as CD4(+)CD25(+/hi)CD127(lo/-) and CD4(+)CD25(+/hi) Tregs, respectively. Furthermore, Tregs could be further subdivided into 40% naïve, 51% central memory and 9% effector memory Tregs. Our results showed for the first time a downregulation of CD127 expression on T cells including Tregs in patients early post-SCT. Additionally, new insights into the recovery of Tregs regarding GvHD and relapse were provided. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Post-translational serine/threonine phosphorylation and lysine acetylation: a novel regulatory aspect of the global nitrogen response regulator GlnR in S. coelicolor M145.

    Directory of Open Access Journals (Sweden)

    Rafat Amin

    2016-08-01

    Full Text Available Soil-dwelling Streptomyces bacteria such as S. coelicolor have to constantly adapt to the nitrogen (N availability in their habitat. Thus, strict transcriptional and post-translational control of the N-assimilation is fundamental for survival of this species. GlnR is a global response regulator that controls transcription of the genes related to the N-assimilation in S. coelicolor and other members of the Actinomycetales. GlnR represents an atypical orphan response regulator that is not activated by the phosphorylation of the conserved aspartate residue (Asp 50. We have applied transcriptional analysis, LC-MS/MS analysis and electrophoretic mobility shift assays (EMSAs to understand the regulation of GlnR in S. coelicolor M145. The expression of glnR and GlnR-target genes was revisited under four different N-defined conditions and a complex N-rich condition. Although, the expression of selected GlnR-target genes was strongly responsive to changing N-concentrations, the glnR expression itself was independent of the N-availability. Using LC-MS/MSanalysis we demonstrated that GlnR was post-translationally modified. The post-translational modifications of GlnR comprise phosphorylation of the serine/threonine residues and acetylation of lysine residues. In the complex N-rich medium GlnR was phosphorylated on six serine/ threonine residues and acetylated on one lysine residue. Under defined N-excess conditions only two phosphorylated residues were detected whereas under defined N-limiting conditions no phosphorylation was observed. GlnR phosphorylation is thus clearly correlated with N-rich conditions. Furthermore, GlnR was acetylated on four lysine residues independently of the N-concentration in the defined media and on only one lysine residue in the complex N-rich medium. Using EMSAs we demonstrated that phosphorylation inhibited the binding of GlnR to its targets genes, whereas acetylation had little influence on the formation of GlnR-DNA complex

  16. 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....

  17. 10 CFR 160.6 - Posting.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Posting. 160.6 Section 160.6 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) TRESPASSING ON COMMISSION PROPERTY § 160.6 Posting. Notices stating the pertinent prohibitions of §§ 160.3 and 160.4 and penalties of § 160.5 will be conspicuously posted at all entrances...

  18. 10 CFR 73.75 - Posting.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Posting. 73.75 Section 73.75 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) PHYSICAL PROTECTION OF PLANTS AND MATERIALS Records and Reports § 73.75 Posting. (a... criminal penalties, and associated posting requirements, under section 229 of the Atomic Energy Act...

  19. Regulatory network operations in the Pathway Tools software

    Directory of Open Access Journals (Sweden)

    Paley Suzanne M

    2012-09-01

    Full Text Available Abstract Background Biologists are elucidating complex collections of genetic regulatory data for multiple organisms. Software is needed for such regulatory network data. Results The Pathway Tools software supports storage and manipulation of regulatory information through a variety of strategies. The Pathway Tools regulation ontology captures transcriptional and translational regulation, substrate-level regulation of enzyme activity, post-translational modifications, and regulatory pathways. Regulatory visualizations include a novel diagram that summarizes all regulatory influences on a gene; a transcription-unit diagram, and an interactive visualization of a full transcriptional regulatory network that can be painted with gene expression data to probe correlations between gene expression and regulatory mechanisms. We introduce a novel type of enrichment analysis that asks whether a gene-expression dataset is over-represented for known regulators. We present algorithms for ranking the degree of regulatory influence of genes, and for computing the net positive and negative regulatory influences on a gene. Conclusions Pathway Tools provides a comprehensive environment for manipulating molecular regulatory interactions that integrates regulatory data with an organism’s genome and metabolic network. Curated collections of regulatory data authored using Pathway Tools are available for Escherichia coli, Bacillus subtilis, and Shewanella oneidensis.

  20. Recommendations on legislative and regulatory framework and regulatory body of nuclear security in China

    Institute of Scientific and Technical Information of China (English)

    PU Jilong; LI Xiaoyan

    2007-01-01

    This paper describes the definition of nuclear security that has been changing from the cold war age to the post-911 period, and clarifies the close relationship and yet a clear distinction between nuclear security, nuclear safety and nuclear safeguard. Based on analyses of the current state of nuclear security activities in China as well as the requirements and the law infrastructure, a legislative and regulatory framework of nuclear security and the mandate of a regulatory body in China are recommended.

  1. Federal Trade Commission Semiannual Regulatory Agenda

    Science.gov (United States)

    2010-12-20

    ... Management and Budget in accordance with the provisions of Executive Order No. 12866 ``Regulatory Planning... the RFA are: (1) the Automotive Fuel Ratings, Certification, and Posting Rule, 16 CFR 306; (2) the Pay... codified at 16 CFR 321, 322; (7) Retail Food Store Advertising and Marketing Practices, 16 CFR 424; (8) the...

  2. 10 CFR 34.53 - Posting.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Posting. 34.53 Section 34.53 Energy NUCLEAR REGULATORY COMMISSION LICENSES FOR INDUSTRIAL RADIOGRAPHY AND RADIATION SAFETY REQUIREMENTS FOR INDUSTRIAL RADIOGRAPHIC OPERATIONS Radiation Safety Requirements § 34.53 Posting. All areas in which industrial radiography is...

  3. 77 FR 58592 - Modified Norway Post Agreement

    Science.gov (United States)

    2012-09-21

    ... Modified Norway Post Agreement AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recently-filed Postal Service request to include a modified Norway Post Agreement... existing bilateral agreement for inbound competitive services with Posten Norge AS (Modified Norway...

  4. Regulatory affairs for biomaterials and medical devices

    CERN Document Server

    Amato, Stephen F; Amato, B

    2015-01-01

    All biomaterials and medical devices are subject to a long list of regulatory practises and policies which must be adhered to in order to receive clearance. This book provides readers with information on the systems in place in the USA and the rest of the world. Chapters focus on a series of procedures and policies including topics such as commercialization, clinical development, general good practise manufacturing and post market surveillance.Addresses global regulations and regulatory issues surrounding biomaterials and medical devicesEspecially useful for smaller co

  5. Isolation of highly suppressive CD25+FoxP3+ T regulatory cells from G-CSF-mobilized donors with retention of cytotoxic anti-viral CTLs: application for multi-functional immunotherapy post stem cell transplantation.

    Science.gov (United States)

    Samuel, Edward R; Beloki, Lorea; Newton, Katy; Mackinnon, Stephen; Lowdell, Mark W

    2014-01-01

    Previous studies have demonstrated the effective control of cytomegalovirus (CMV) infections post haematopoietic stem cell transplant through the adoptive transfer of donor derived CMV-specific T cells (CMV-T). Strategies for manufacturing CMV immunotherapies has involved a second leukapheresis or blood draw from the donor, which in the unrelated donor setting is not always possible. We have investigated the feasibility of using an aliquot of the original G-CSF-mobilized graft as a starting material for manufacture of CMV-T and examined the activation marker CD25 as a targeted approach for identification and isolation following CMVpp65 peptide stimulation. CD25+ cells isolated from G-CSF-mobilized apheresis revealed a significant increase in the proportion of FoxP3 expression when compared with conventional non-mobilized CD25+ cells and showed a superior suppressive capacity in a T cell proliferation assay, demonstrating the emergence of a population of Tregs not present in non-mobilized apheresis collections. The expansion of CD25+ CMV-T in short-term culture resulted in a mixed population of CD4+ and CD8+ T cells with CMV-specificity that secreted cytotoxic effector molecules and lysed CMVpp65 peptide-loaded phytohaemagglutinin-stimulated blasts. Furthermore CD25 expanded cells retained their suppressive capacity but did not maintain FoxP3 expression or secrete IL-10. In summary our data indicates that CD25 enrichment post CMV stimulation in G-CSF-mobilized PBMCs results in the simultaneous generation of both a functional population of anti-viral T cells and Tregs thus illustrating a potential single therapeutic strategy for the treatment of both GvHD and CMV reactivation following allogeneic haematopoietic stem cell transplantation. The use of G-CSF-mobilized cells as a starting material for cell therapy manufacture represents a feasible approach to alleviating the many problems incurred with successive donations and procurement of cells from unrelated donors

  6. La Poste

    CERN Multimedia

    2004-01-01

    http://www.cern.ch/cern50/ The French Post Office has issued ten commemorative envelopes bearing original images depicting CERN and its history. This special fiftieth anniversary collector's edition will be available on the French Post Office (« La Poste ») stand at the Open Day on 16 October, in the CMS experiment hall at Cessy. Information for collectors: a pictorial postmark and date stamp have been specially designed and produced for the occasion with the assistance of CERN's graphics team. Sending a philatelic souvenir is a great way to commemorate the Open Day, so La Poste will be setting up a large post-box for that very purpose next to its stand. A perfect way to send images of CERN all around the world...

  7. Regulatory guidance document

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    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.

  8. Regulatory principles governing Salmonella and Yersinia virulence

    Science.gov (United States)

    Erhardt, Marc; Dersch, Petra

    2015-01-01

    Enteric pathogens such as Salmonella and Yersinia evolved numerous strategies to survive and proliferate in different environmental reservoirs and mammalian hosts. Deciphering common and pathogen-specific principles for how these bacteria adjust and coordinate spatiotemporal expression of virulence determinants, stress adaptation, and metabolic functions is fundamental to understand microbial pathogenesis. In order to manage sudden environmental changes, attacks by the host immune systems and microbial competition, the pathogens employ a plethora of transcriptional and post-transcriptional control elements, including transcription factors, sensory and regulatory RNAs, RNAses, and proteases, to fine-tune and control complex gene regulatory networks. Many of the contributing global regulators and the molecular mechanisms of regulation are frequently conserved between Yersinia and Salmonella. However, the interplay, arrangement, and composition of the control elements vary between these closely related enteric pathogens, which generate phenotypic differences leading to distinct pathogenic properties. In this overview we present common and different regulatory networks used by Salmonella and Yersinia to coordinate the expression of crucial motility, cell adhesion and invasion determinants, immune defense strategies, and metabolic adaptation processes. We highlight evolutionary changes of the gene regulatory circuits that result in different properties of the regulatory elements and how this influences the overall outcome of the infection process. PMID:26441883

  9. Regulatory T cell memory

    Science.gov (United States)

    Rosenblum, Michael D.; Way, Sing Sing; Abbas, Abul K.

    2016-01-01

    Memory for antigen is a defining feature of adaptive immunity. Antigen-specific lymphocyte populations show an increase in number and function after antigen encounter and more rapidly re-expand upon subsequent antigen exposure. Studies of immune memory have primarily focused on effector B cells and T cells with microbial specificity, using prime challenge models of infection. However, recent work has also identified persistently expanded populations of antigen-specific regulatory T cells that protect against aberrant immune responses. In this Review, we consider the parallels between memory effector T cells and memory regulatory T cells, along with the functional implications of regulatory memory in autoimmunity, antimicrobial host defence and maternal fetal tolerance. In addition, we discuss emerging evidence for regulatory T cell memory in humans and key unanswered questions in this rapidly evolving field. PMID:26688349

  10. NRC regulatory initiatives

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, T.C. [Nuclear Regulatory Commission (United States)

    1989-11-01

    The US Nuclear Regulatory Commission (NRC) is addressing several low-level waste disposal issues that will be important to waste generators and to States and Compacts developing new disposal capacity. These issues include Greater-Than-Class C (GTCC) waste, mixed waste, below regulatory concern (BRC) waste, and the low-level waste data base. This paper discusses these issues and their current status.

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

    DEFF Research Database (Denmark)

    Valen, Eivind; Sandelin, Albin; Winther, Ole;

    2009-01-01

    A major goal in post-genome biology is the complete mapping of the gene regulatory networks for every organism. Identification of regulatory elements is a prerequisite for realizing this ambitious goal. A common problem is finding regulatory patterns in promoters of a group of co-expressed genes...... present a new computational method for identifying transcription factor binding sites in promoters using a discriminatory approach with a large negative set encompassing a significant sample of the promoters from the relevant genome. The sequences are described by a probabilistic model and the most...

  12. Monitoring post

    DEFF Research Database (Denmark)

    Hansen, Pelle Guldborg; Jespersen, Andreas Maaløe

    2013-01-01

    This blog reports on the rumour that White House considers establishing a nudge unit similar to the UK Behavioural Insights Team. Given The Nudging Networks purpose and the work of the iNudgeYou-team this post is updated continuously to follow the US debate as it unfolds. Which issues are raised......? How is the debate different from the one in the UK? And how does our work relate to the issues raised? The post has already been referenced in several US media, including US News....

  13. 美国对冲基金监管与欧美监管转型--以后金融危机时代为背景%US Hedge Fund Regulation and Euramerican Regulatory Transition---On the Background of Post Financial Crisis Era

    Institute of Scientific and Technical Information of China (English)

    丛彦国

    2015-01-01

    对冲基金在美国已经有半个多世纪的历史,但是目前对于对冲基金并没有统一的界定。美国对冲基金的组织形式包括有限合伙企业和有限责任公司,结构上包括单一基金结构、目标基金加联接基金结构和平行基金结构。美国对冲基金的监管又包括投资顾问的监管和基金具体行为的监管。美国对冲基金监管规则的完善是以后金融危机时代为背景的,与此相伴的是欧美对冲基金监管的转型,表现为欧盟《另类投资基金管理人指令》、欧盟《金融工具市场指令》、《欧洲市场基础设施监管规则》、美国《多德-弗兰克法案》、美国《海外账户税收合规法案》等的出台,以及监管的强化、国际化等新趋势。%Hedge fund has a history of more than half a century in the United States. However, it has never been formally universally defined. US hedge fund organizational forms include limited partnership and limited liability company, and its structures include single fund, master-feeder funds and parallel funds. US hedge fund regulations include investment advisers and fund activities' regulations. The improvement of US hedge fund regulation rules is on the background of Post Financial Crisis Era with the transition of Euramerican regulatory, and it is behaving as enactments of EU Alternative Investment Fund Managers Directive, Markets in Financial Instruments Directive, European Market Infrastructure Regulation, US Dodd-Frank Act and Foreign Account Tax Compliance Act, etc. At the same time, there are many new trends of the regulatory, such as reinforcement, internationalization, etc.

  14. 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.

  15. Europe's regulatory role in post-crisis global finance

    NARCIS (Netherlands)

    Mügge, D.

    2014-01-01

    Before the crisis, the European Union (EU) had emerged as a major force in global financial governance (GFG). The contributions to this collection examine the different dimensions of the EU's role in GFG and how they have been affected by the recent crisis. Taking a bird's eye view, this introductio

  16. SUCROSE SYNTHASE: ELUCIDATION OF COMPLEX POST-TRANSLATIONAL REGULATORY MECHANISMS

    Energy Technology Data Exchange (ETDEWEB)

    Steven C. Huber

    2009-05-12

    Studies have focused on the enzyme sucrose synthase, which plays an important role in the metabolism of sucrose in seeds and tubers. There are three isoforms of SUS in maize, referred to as SUS1, SUS-SH1, and SUS2. SUS is generally considered to be tetrameric protein but recent evidence suggests that SUS can also occur as a dimeric protein. The formation of tetrameric SUS is regulated by sucrose concentration in vitro and this could also be an important factor in the cellular localization of the protein. We found that high sucrose concentrations, which promote tetramer formation, also inhibit the binding of SUS1 to actin filaments in vitro. Previously, high sucrose concentrations were shown to promote SUS association with the plasma membrane. The specific regions of the SUS molecule involved in oligomerization are not known, but we identified a region of the SUS1 moelcule by bioinformatic analysis that was predicted to form a coiled coil. We demonstrated that this sequence could, in fact, self-associate as predicted for a coiled coil, but truncation analysis with the full-length recombinant protein suggested that it was not responsible for formation of dimers or tetramers. However, the coiled coil may function in binding of other proteins to SUS1. Overall, sugar availability may differentially influence the binding of SUS to cellular structures, and these effects may be mediated by changes in the oligomeric nature of the enzyme.

  17. 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...

  18. Ex Ante or Ex Post? Risk, Hedging and Prudence in the Restructured Power Business

    Energy Technology Data Exchange (ETDEWEB)

    Makholm, Jeff D.; Meehan, Eugene T.; Sullivan, Julia E.

    2006-04-15

    Inconsistent regulatory decisions continue to frustrate the establishment of a new ex ante regulatory equilibrium that will serve to prevent unfair and inefficient ex post prudence disallowances. Extreme volatility in gas and power markets will continue to tax the uneasy regulatory status quo until a new equilibrium can be established. (author)

  19. REGULATORY T CELLS AND VASECTOMY

    Science.gov (United States)

    Rival, Claudia; Wheeler, Karen; Jeffrey, Sarah; Qiao, Hui; Luu, Brian; Tewalt, Eric F; Engelhard, Victor H; Tardif, Stephen; Hardy, Daniel; del Rio, Roxana; Teuscher, Cory; Tung, Kenneth

    2013-01-01

    CD4+CD25+ regulatory T cells (Tregs) strongly influence the early and late autoimmune responses to meiotic germ cell antigens (MGCA) and the gonadal immunopathology in vasectomized mice. This is supported by the published and recently acquired information presented here. Within 24 hours of unilateral vasectomy (uni-vx) the ipsilateral epididymis undergoes epithelial cell apoptosis followed by necrosis, severe inflammation, and granuloma formation. Unexpectedly, vasectomy alone induced MGCA-specific tolerance. In contrast, uni-vx plus simultaneous Treg depletion resulted in MGCA-specific autoimmune response and bilateral autoimmune orchitis. Both tolerance and autoimmunity were strictly linked to the early epididymal injury. We now discovered that testicular autoimmunity in uni-vx mice did not occur when Treg depletion was delayed by one week. Remarkably, this delayed Treg depletion also prevented tolerance induction. Therefore, tolerance depends on a rapid de novo Treg response to MGCA exposed after vasectomy. Moreover, tolerance was blunted in mice genetically deficient in PD-1 ligand, suggesting the involvement of induced Treg. We conclude that pre-existing natural Treg prevents post-vasectomy autoimmunity, whereas vasectomy-induced Treg maintains post-vasectomy tolerance. We further discovered that vasectomized mice were still resistant to autoimmune orchitis induction for at least 12–16 months; thus, tolerance is long-lasting. Although significant sperm autoantibodies of low titers became detectable in uni-vx mice at seven months, the antibody titers fluctuated over time, suggesting a dynamic “balance” between the autoimmune and tolerance states. Finally, we observed severe epididymal fibrosis and hypo-spermatogenesis at 12 months after uni-vx: findings of highly critical clinical significance. PMID:24080233

  20. Nuclear Regulatory Commission information digest

    Energy Technology Data Exchange (ETDEWEB)

    None,

    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.

  1. SUSPICIOUS POST

    CERN Multimedia

    Relations with the Host States Service

    2001-01-01

    If you receive a suspicious letter or package in the post, please do not open it and contact the Fire Brigade Tel. 74444. They will contact the CERN Medical Service. This is especially important in today's current situation with regard to the Anthrax scare. For further information, the Permanent Mission of Switzerland to the International Organisations in Geneva recommends the following web sites:   http://www.admin.ch/ch/f/cf/brennpunkt/03.html http://www.who.int/emc-documents/zoonoses/whoemczdi986c.html

  2. Hastening the regulatory process

    Energy Technology Data Exchange (ETDEWEB)

    Stringham, G. [Canadian Association of Petroleum Producers, Calgary, AB (Canada)

    2001-07-01

    The state of the Canadian oil industry was discussed during this power point presentation with particular emphasis on its production, exports, drilling, industry revenues and capital investment levels. The proposed projects in each of northern Alberta's oil sands deposits, the Athabasca, Peace River and Cold Lake were were announced, along with the inventory of major Alberta projects and the projection of oil sands capital investment. Since 1998, $9 billion has been invested and a further $33 billion has been announced for new or expanded oil sands projects. The year 2000 estimates for Canadian crude oil and natural gas production are 2.3 million barrels per day and 6.3 trillion cubic feet per year respectively. This represented a record year for production of both crude oil and natural gas. In 2000, more than 15,500 wells were drilled in Canada. A graph depicting Canadian crude oil supply forecasted a steady increase in supply from year 2000 to 2010. The Canadian Association of Petroleum Producers (CAPP) completed a review of the Alberta Energy and Utilities Board regulatory and enforcement processes. Both industry and government efforts are focusing on eliminating regulatory overlap and duplication. Some of the main areas of interest for exploration, drilling, production and pipeline facilities include the examination of regulatory processes for environmentally sensitive areas, rural municipalities with planning bylaws, aboriginal lands and additional fees. 8 figs.

  3. 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...

  4. Clinical research: regulatory issues.

    Science.gov (United States)

    Wermeling, D P

    1999-02-01

    The regulatory issues faced by institutions performing clinical research are described. Many institutions do not have on staff an expert who understands the regulatory issues involved in managing investigational new drug research and who knows the institution's obligations under the federal rules. Because pharmacists understand the FDA regulations that apply to the management of drugs in clinical research, institutions are asking pharmacists to expand their role and manage clinical research offices. Many authorities govern various aspects of investigational drug research. FDA has published regulations for good clinical practice (GCP), and the International Conference on Harmonisation is developing an international standard for the proper management of clinical trials. The guidelines published by the Joint Commission on Accreditation of Healthcare Organizations aim to protect patients who are in the institution to receive health care and also participate in clinical trials. The Social Security Administration Acts specifically state that only items and services that are reasonable and necessary for the diagnosis and treatment of injury or disease can be billed to the government; research-related billings are excluded from coverage. Proper management of drug research is crucial to the success of a research program that is integrated with patient care.

  5. Toxicogenomics in regulatory ecotoxicology

    Science.gov (United States)

    Ankley, Gerald T.; Daston, George P.; Degitz, Sigmund J.; Denslow, Nancy D.; Hoke, Robert A.; Kennedy, Sean W.; Miracle, Ann L.; Perkins, Edward J.; Snape, Jason; Tillitt, Donald E.; Tyler, Charles R.; Versteeg, Donald

    2006-01-01

    Recently, we have witnessed an explosion of different genomic approaches that, through a combination of advanced biological, instrumental, and bioinformatic techniques, can yield a previously unparalleled amount of data concerning the molecular and biochemical status of organisms. Fueled partially by large, well-publicized efforts such as the Human Genome Project, genomic research has become a rapidly growing topical area in multiple biological disciplines. Since 1999, when the term “toxicogenomics” was coined to describe the application of genomics to toxicology (1), a rapid increase in publications on the topic has occurred (Figure 1). The potential utility of toxicogenomics in toxicological research and regulatory activities has been the subject of scientific discussions and, as with any new technology, has evoked a wide range of opinion (2–6). VIEWPOINT © 2006 american chemical Society july 1, 2006 / EnvironmEntal SciEncE & tEchnology n 4055 The purpose of this feature article is to consider the roles of toxicogenomics in the field of regulatory ecotoxicology, explore current limitations in the science and practice of genomics, and propose possible avenues to approach and resolve some of the major challenges. A significant amount of input to our analysis came from a workshop sponsored by the Society of Environmental Toxicology and Chemistry (SETAC) in Pellston, Mich., in September 2005. A complete list of names and affiliations of the experts participating in that workshop is provided online in Table 1 of the Supporting Information for this paper.

  6. Effect of Salmonella infection on cecal tonsil regulatory T cell properties in chickens

    Science.gov (United States)

    Two experiments were conducted to study Regulatory T cell (Treg) properties post-Salmonella infection in broiler birds. Four-day-old broiler chicks were orally infected with 5x106 CFU/ml Salmonella enteritidis or sterile PBS (control). Samples were collected at 4, 7, 10, and 14 d post-infection. ...

  7. Decoding the role of regulatory element polymorphisms in complex disease.

    Science.gov (United States)

    Vockley, Christopher M; Barrera, Alejandro; Reddy, Timothy E

    2017-04-01

    Genetic variation in gene regulatory elements contributes to diverse human diseases, ranging from rare and severe developmental defects to common and complex diseases such as obesity and diabetes. Early examples of regulatory mechanisms of human diseases involve large chromosomal rearrangements that change the regulatory connections within the genome. Single nucleotide variants in regulatory elements can also contribute to disease, potentially via demonstrated associations with changes in transcription factor binding, enhancer activity, post-translational histone modifications, long-range enhancer-promoter interactions, or RNA polymerase recruitment. Establishing causality between non-coding genetic variants, gene regulation, and disease has recently become more feasible with advances in genome-editing and epigenome-editing technologies. As establishing causal regulatory mechanisms of diseases becomes routine, functional annotation of target genes is likely to emerge as a major bottleneck for translation into patient benefits. In this review, we discuss the history and recent advances in understanding the regulatory mechanisms of human disease, and new challenges likely to be encountered once establishing those mechanisms becomes rote. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. 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

  9. 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.

  10. Regulatory considerations for biosimilars

    Directory of Open Access Journals (Sweden)

    Ranjani Nellore

    2010-01-01

    Full Text Available Currently there is considerable interest in the legislative debate around generic biological drugs or "biosimilars" in the EU and US due to the large, lucrative market that it offers to the industry. While some countries have issued a few regulatory guidelines as well as product specific requirements, there is no general consensus as to a single, simple mechanism similar to the bioequivalence determination that leads to approval of generic small molecules all over the world. The inherent complex nature of the molecules, along with complicated manufacturing and analytical techniques to characterize them make it difficult to rely on a single human pharmacokinetic study for assurance of safety and efficacy. In general, the concept of comparability has been used for evaluation of the currently approved "similar" biological where a step by step assessment on the quality, preclinical and clinical aspects is made. In India, the focus is primarily on the availability and affordability of life-saving drugs. In this context every product needs to be evaluated on its own merit irrespective of the innovator brand. The formation of the National Biotechnology Regulatory Authority may provide a step in the right direction for regulation of these complex molecules. However, in order to have an efficient machinery for initial approval and ongoing oversight with a country-specific focus, cooperation with international authorities for granting approvals and continuous risk-benefit review is essential. Several steps are still needed for India to be perceived as a country that leads the world in providing quality biological products.

  11. 75 FR 54210 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

    Science.gov (United States)

    2010-09-03

    ...-2010-032] Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of... Transactions August 30, 2010. On June 17, 2010, the Financial Industry Regulatory Authority, Inc....

  12. 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 g

  13. Reconsidering Styles of Regulatory Enforcement

    DEFF Research Database (Denmark)

    May, Peter J.; Winter, Søren

    2000-01-01

    This study addresses enforcement styles of regulatory inspectors, based on an examination of the municipal enforcement of agro-environmental policies in Denmark. Our findings make three contributions to the regulatory literature. One contribution is to add empirical support for theorizing about i...

  14. Reconsidering Styles of Regulatory Enforcement

    DEFF Research Database (Denmark)

    J. May, Peter; Winter, Søren

    2007-01-01

    This study addresses enforcement styles of regulatory inspectors based on an examination of the municipal enforcement of agro-environmental policies in Denmark. Our findings make three contributions to the regulatory literature. One contribution is to add empirical support for theorizing about in...

  15. Regulatory Foci and Organizational Commitment

    Science.gov (United States)

    Markovits, Yannis; Ullrich, Johannes; van Dick, Rolf; Davis, Ann J.

    2008-01-01

    We use regulatory focus theory to derive specific predictions regarding the differential relationships between regulatory focus and commitment. We estimated a structural equation model using a sample of 520 private and public sector employees and found in line with our hypotheses that (a) promotion focus related more strongly to affective…

  16. Disclosure as a regulatory tool

    DEFF Research Database (Denmark)

    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....

  17. Anti-regulatory T cells

    DEFF Research Database (Denmark)

    Andersen, Mads Hald

    2017-01-01

    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...... 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...

  18. Regulatory coordination of clustered microRNAs based on microRNA-transcription factor regulatory network

    Directory of Open Access Journals (Sweden)

    Wang Jin

    2011-12-01

    Full Text Available Abstract Background MicroRNA (miRNA is a class of small RNAs of ~22nt which play essential roles in many crucial biological processes and numerous human diseases at post-transcriptional level of gene expression. It has been revealed that miRNA genes tend to be clustered, and the miRNAs organized into one cluster are usually transcribed coordinately. This implies a coordinated regulation mode exerted by clustered miRNAs. However, how the clustered miRNAs coordinate their regulations on large scale gene expression is still unclear. Results We constructed the miRNA-transcription factor regulatory network that contains the interactions between transcription factors (TFs, miRNAs and non-TF protein-coding genes, and made a genome-wide study on the regulatory coordination of clustered miRNAs. We found that there are two types of miRNA clusters, i.e. homo-clusters that contain miRNAs of the same family and hetero-clusters that contain miRNAs of various families. In general, the homo-clustered as well as the hetero-clustered miRNAs both exhibit coordinated regulation since the miRNAs belonging to one cluster tend to be involved in the same network module, which performs a relatively isolated biological function. However, the homo-clustered miRNAs show a direct regulatory coordination that is realized by one-step regulation (i.e. the direct regulation of the coordinated targets, whereas the hetero-clustered miRNAs show an indirect regulatory coordination that is realized by a regulation comprising at least three steps (e.g. the regulation on the coordinated targets by a miRNA through a sequential action of two TFs. The direct and indirect regulation target different categories of genes, the former predominantly regulating genes involved in emergent responses, the latter targeting genes that imply long-term effects. Conclusion The genomic clustering of miRNAs is closely related to the coordinated regulation in the gene regulatory network. The pattern of

  19. Regulatory Streamlining and Improvement

    Energy Technology Data Exchange (ETDEWEB)

    Mark A. Carl

    2006-07-11

    The Interstate Oil and Gas Compact Commission (IOGCC) engaged in numerous projects outlined under the scope of work discussed in the United States Department of Energy (DOE) grant number DE-FC26-04NT15456 awarded to the IOGCC. Numerous projects were completed that were extremely valuable to state oil and gas agencies as a result of work performed utilizing resources provided by the grant. There are numerous areas in which state agencies still need assistance. This additional assistance will need to be addressed under future scopes of work submitted annually to DOE's Project Officer for this grant. This report discusses the progress of the projects outlined under the grant scope of work for the 2005-2006 areas of interest, which are as follows: Area of Interest No. 1--Regulatory Streamlining and Improvement: This area of interest continues to support IOGCC's regulatory streamlining efforts that include the identification and elimination of unnecessary duplications of efforts between and among state and federal programs dealing with exploration and production on public lands. Area of Interest No. 2--Technology: This area of interest seeks to improve efficiency in states through the identification of technologies that can reduce costs. Area of Interest No. 3--Training and Education: This area of interest is vital to upgrading the skills of regulators and industry alike. Within the National Energy Policy, there are many appropriate training and education opportunities. Education was strongly endorsed by the President's National Energy Policy Development group. Acting through the governors offices, states are very effective conduits for the dissemination of energy education information. While the IOGCC favors the development of a comprehensive, long-term energy education plan, states are also supportive of immediate action on important concerns, such as energy prices, availability and conservation. Area of Interest No. 4--Resource Assessment and

  20. 75 FR 30453 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2010-06-01

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving..., Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a National Association of Securities Dealers... National Association of Securities Dealers, Inc., the Financial Industry Regulatory Authority, Inc., or...

  1. 75 FR 40000 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2010-07-13

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change Relating to the Restated Certificate of Incorporation of Financial Industry Regulatory Authority, Inc. July 2, 2010. On May 21, 2010, Financial Industry Regulatory Authority, Inc....

  2. Regulating regulatory T cells.

    Science.gov (United States)

    Le, N T; Chao, N

    2007-01-01

    Regulatory T cells (Tregs) are a specialized subpopulation of T cells that act to suppress activation of other immune cells and thereby maintain immune system homeostasis, self-tolerance as well as control excessive response to foreign antigens. The mere concept of Tregs was the subject of significant controversy among immunologists for many years owing to the paucity of reliable markers for defining these cells and the ambiguity of the nature and molecular basis of suppressive phenomena. However, recent advances in the molecular characterization of this cell population have firmly established their existence and their vital role in the vertebrate immune system. Of interest, accumulating evidence from both humans and experimental animal models has implicated the involvement of Tregs in the development of graft-versus-host disease (GVHD). The demonstration that Tregs could separate GVHD from graft-versus-tumor (GVT) activity suggests that their immunosuppressive potential could be manipulated to reduce GVHD without detrimental consequence on GVT effect. Although a variety of T lymphocytes with suppressive capabilities have been reported, the two best-characterized subsets are the naturally arising, intrathymic-generated Tregs (natural Tregs) and the peripherally generated, inducible Tregs (inducible Tregs). This review summarizes our current knowledge of the generation, function and regulation of these two populations of Tregs during an immune response. Their role in the development of GVHD and their therapeutic potential for the prevention and treatment of GVHD will also be described.

  3. Internationalization of regulatory requirements.

    Science.gov (United States)

    Juillet, Y

    2003-02-01

    The aim of harmonisation of medicines regulatory requirements is to allow the patient quicker access to new drugs and to avoid animal and human duplications. Harmonisation in the European Union (EU) is now completed, and has led to the submission of one dossier in one language study leading to European marketing authorizations, thanks in particular to efficacy guidelines published at the European level. With the benefit of the European experience since 1989, more than 40 guidelines have been harmonised amongst the EU, Japan and the USA through the International Conference on Harmonisation (ICH). ICH is a unique process gathering regulators and industry experts from the three regions. Its activity is built on expertise and trust. The Common Technical Document (CTD), an agreed common format for application in the three regions, is a logical follow-up to the ICH first phase harmonising the content of the dossier. The CTD final implementation in July 2003 will have considerable influence on the review process and on the exchange of information in the three regions.

  4. Proteome-wide analysis of lysine acetylation suggests its broad regulatory scope in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Henriksen, Peter; Wagner, Sebastian Alexander; Weinert, Brian Tate;

    2012-01-01

    Post-translational modification of proteins by lysine acetylation plays important regulatory roles in living cells. The budding yeast Saccharomyces cerevisiae is a widely used unicellular eukaryotic model organism in biomedical research. S. cerevisiae contains several evolutionary conserved lysin...

  5. Vaccines in Argentina: a regulatory view.

    Science.gov (United States)

    Pérez, A C; Diez, R A

    2003-07-28

    In Argentina, vaccines for immuno-preventable diseases are regulated by the national regulatory agency, the Administración Nacional de Medicamentos, Alimentos y Tecnología Médica (the National Administration of Drugs, Food and Medical Devices, or ANMAT) created in 1992 to ensure efficacy and safety of drugs, food and medical devices available in the country, according to Law 16,463 and Decree 150/92. ANMAT has licensed 84 out of 157 vaccines registered in Argentina. Since 1994, ANMAT evaluated, approved and inspected 20 clinical trials with vaccines (1.8% of the 1062 trials approved by the agency since that time). The National System of Pharmaco-vigilance has received 318 communications of eventual adverse post-vaccination events (0.3% of the total). In addition, ANMAT provides support to the National Immunisation Programme. The current procedure is to follow international guidelines in the field, to be prepared for new, rapidly changing scenarios.

  6. Healthcare regulatory concepts in Brazil.

    Science.gov (United States)

    Oliveira, Robson Rocha de; Elias, Paulo Eduardo Mangeon

    2012-06-01

    The healthcare regulatory concepts used in Brazilian scientific publications on healthcare management were reviewed. A typo-logical classification for regulatory concepts was developed from the most current ideas in five disciplines: life sciences, law, economics, sociology and political science. Four ideas stood out: control, balance, adaptation and direction, with greatest emphasis on the technical nature of regulation. The political nature of regulation was secondary. It was considered that dis-cussion of healthcare regulatory concepts was connected with comprehension of the role that the state plays in this sector. De-finition of the forms of state intervention is the key convergence point between the different ways of conceptualizing healthcare regulation.

  7. 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...

  8. Regulatory Snapshots: integrative mining of regulatory modules from expression time series and regulatory networks.

    Directory of Open Access Journals (Sweden)

    Joana P Gonçalves

    Full Text Available Explaining regulatory mechanisms is crucial to understand complex cellular responses leading to system perturbations. Some strategies reverse engineer regulatory interactions from experimental data, while others identify functional regulatory units (modules under the assumption that biological systems yield a modular organization. Most modular studies focus on network structure and static properties, ignoring that gene regulation is largely driven by stimulus-response behavior. Expression time series are key to gain insight into dynamics, but have been insufficiently explored by current methods, which often (1 apply generic algorithms unsuited for expression analysis over time, due to inability to maintain the chronology of events or incorporate time dependency; (2 ignore local patterns, abundant in most interesting cases of transcriptional activity; (3 neglect physical binding or lack automatic association of regulators, focusing mainly on expression patterns; or (4 limit the discovery to a predefined number of modules. We propose Regulatory Snapshots, an integrative mining approach to identify regulatory modules over time by combining transcriptional control with response, while overcoming the above challenges. Temporal biclustering is first used to reveal transcriptional modules composed of genes showing coherent expression profiles over time. Personalized ranking is then applied to prioritize prominent regulators targeting the modules at each time point using a network of documented regulatory associations and the expression data. Custom graphics are finally depicted to expose the regulatory activity in a module at consecutive time points (snapshots. Regulatory Snapshots successfully unraveled modules underlying yeast response to heat shock and human epithelial-to-mesenchymal transition, based on regulations documented in the YEASTRACT and JASPAR databases, respectively, and available expression data. Regulatory players involved in

  9. Taking Stock of Regulatory Variation.

    Science.gov (United States)

    Maurano, Matthew T; Stamatoyannopoulos, John A

    2015-07-29

    Three recent studies measure individual variation in regulatory DNA accessibility. What do they tell us about the prospects of assessing variation in single cells and across populations? Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Current Regulations and Regulatory Actions

    Science.gov (United States)

    This site will provide basic information on clean air permitting under the title V operating permits program, provide access to state and regional permitting programs, and maintain access to proposed and final regulatory requirements.

  11. 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.

  12. Electronic Commerce Removing Regulatory Impediments

    Science.gov (United States)

    1992-05-01

    AD-A252 691 ELECTRONIC COMMERCE Removing Regulatory Impediments ~DuiG A% ELECTE I JUL1 8 1992 0 C D Daniel J. Drake John A. Ciucci ... - ""N ST AT KE...Management Institute 6400 Goldsboro Road Bethesda, Maryland 20817-5886 92 LMI Executive Summary ELECTRONIC COMMERCE : REMOVING REGULATORY IMPEDIMENTS... Electronic Commerce techniques, such as electronic mail and electronic data interchange (EDI), enable Government agencies to conduct business without the

  13. PROACTIVE REGULATORY INTERVENTION IN EU COMMUNICATIONS SECTOR AND ITS FORESEEABLE FUTURE

    Directory of Open Access Journals (Sweden)

    Mantas Barčys

    2013-06-01

    Full Text Available Purpose – to review and provide insights on the issues concerning ex ante regulatory approach in EU telecommunications (hereinafter – electronic communications industry, identify and emphasise benefits, main challenges and further regulatory prospective. Design/methodology/approach – based on current regulatory framework and analysis of academic literature, author discusses problematic issues related to the needs and further perspectives of proactive regulatory regime in EU electronic communications sector. Findings – the author reviews special qualities for different regulatory regimes (ex ante, ex post and examines them in the context of sharp developments of the industry and EU regulatory policy. Research limitations/implications –the analysis aims to convey the main understanding on the regulatory specifics of the communications industry, the main features, distinguishing communications industry from the others and foreseeable regulatory perspectives Practical implications – the core aspect of the paper is to evaluate current regulatory approach of the EU electronic communications sector and assess potential regulatory approaches in the context of making self-sustaining pro-competitive market structure, technological development. Originality/Value – the paper highlights some significant changes between two regulatory approaches in the light of specific features in EU electronic communications. Author provides his insights on the status and perspectives on application for both regulatory methods. Apparently, these issues have so far been subjected too little academic analysis. As shown in this paper, regulatory policy can have the essential impact on the activities taken by other players. The decision to give an even bigger role to competition rules, do not mean to eliminate sector specifics itself. With this in mind, EU legislators are not able to eliminate proactive regulatory control, thus reducing ex ante rules progressively

  14. Post engineered nanomaterials lifespan: nanowastes classification, legislative development/implementation challenges, and proactive approaches

    CSIR Research Space (South Africa)

    Musee, N

    2012-05-01

    Full Text Available -1 NANOLCA Symposium, "Safety issues and regulatory challenges of nanomaterials", San Sebastian, Spain, 3-4 May 2012 Post engineered nanomaterials lifespan: nanowastes classification, legislative development/implementation challenges, and proactive...

  15. Establishing a regulatory value chain model: An innovative approach to strengthening medicines regulatory systems in resource-constrained settings.

    Science.gov (United States)

    Chahal, Harinder Singh; Kashfipour, Farrah; Susko, Matt; Feachem, Neelam Sekhri; Boyle, Colin

    2016-05-01

    Medicines Regulatory Authorities (MRAs) are an essential part of national health systems and are charged with protecting and promoting public health through regulation of medicines. However, MRAs in resource-constrained settings often struggle to provide effective oversight of market entry and use of health commodities. This paper proposes a regulatory value chain model (RVCM) that policymakers and regulators can use as a conceptual framework to guide investments aimed at strengthening regulatory systems. The RVCM incorporates nine core functions of MRAs into five modules: (i) clear guidelines and requirements; (ii) control of clinical trials; (iii) market authorization of medical products; (iv) pre-market quality control; and (v) post-market activities. Application of the RVCM allows national stakeholders to identify and prioritize investments according to where they can add the most value to the regulatory process. Depending on the economy, capacity, and needs of a country, some functions can be elevated to a regional or supranational level, while others can be maintained at the national level. In contrast to a "one size fits all" approach to regulation in which each country manages the full regulatory process at the national level, the RVCM encourages leveraging the expertise and capabilities of other MRAs where shared processes strengthen regulation. This value chain approach provides a framework for policymakers to maximize investment impact while striving to reach the goal of safe, affordable, and rapidly accessible medicines for all.

  16. The costs and effects of post-authorisation safety studies for new active substances

    NARCIS (Netherlands)

    Bouvy, J.C.; De Bruin, M.L.; Hoekman, J.; Stolk, P.

    2014-01-01

    Objectives: At market entry, there usually is uncertainty regarding a new medicine's benefit-risk profile. Therefore, regulatory authorities may request additional pharmacovigilance (PhV) activities. Regulatory Authorities can request a Post- Authorisation Safety Study (PASS) such as a registry, dat

  17. The costs and effects of post-authorisation safety studies for new active substances

    NARCIS (Netherlands)

    Bouvy, J.C.; De Bruin, M.L.; Hoekman, J.; Stolk, P.

    2014-01-01

    Objectives: At market entry, there usually is uncertainty regarding a new medicine's benefit-risk profile. Therefore, regulatory authorities may request additional pharmacovigilance (PhV) activities. Regulatory Authorities can request a Post- Authorisation Safety Study (PASS) such as a registry,

  18. 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.

  19. Post-stroke cognitive dysfunctions: A clinical and neuroimaging study

    Directory of Open Access Journals (Sweden)

    Andrei Yuryevich Emelin

    2013-01-01

    Full Text Available Clinical, neuropsychological, and neuroimaging examinations were made in 65 patients (52 men and 13 women aged 65.6±10.1 years who had experienced ischemic stroke. Cognitive impairments (CI were heterogeneous; regulatory functions, attention, and counting were most significantly affected in moderate CI. In mild dementia, mainly poor attention and regulatory dysfunctions were added by clearly-cut impairments of memory, orientation, and visual-spatial function. Brain atrophy, white matter changes, and small focal gray matter damages along with focal post-stroke changes were revealed by neuroimaging in most patients. It was found that besides the volume and location of a damage focus, the signs of impaired integrated mental activity of the brain, regulatory dysfunctions in particular, should be a necessary condition for the verification of post-stroke CI.

  20. 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.

  1. Regulatory processes in Aspergillus niger

    DEFF Research Database (Denmark)

    Poulsen, Lars

    some disadvantages as well, those are byproduct formation, secretion of proteolytic enzymes and formation of mycotoxins. The aim of this project was to reduce these disadvantages, though investigating the regulatory processes. The first objective was to study the regulatory events leading to A. niger......T. The physiological batch characterization showed that the ΔprtT strain had the lowest protease activity (fivefold reduced), but also featured excessive CO2 yield, reduced growth rate and lower biomass yields. The ΔprtB strain had a close to twofold reduced levels of secreted proteases but with additional beneficial...

  2. Post-Concussion Syndrome

    Science.gov (United States)

    Post-concussion syndrome Overview By Mayo Clinic Staff Post-concussion syndrome is a complex disorder in which various symptoms — ... sometimes months after the injury that caused the concussion. Concussion is a mild traumatic brain injury that ...

  3. 75 FR 70757 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    Science.gov (United States)

    2010-11-18

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a... 12, 2010. I. Introduction On August 6, 2010, the Financial Industry Regulatory Authority, Inc... Kimmel, Executive Director, Financial Information Forum, to Elizabeth M. Murphy, Secretary,...

  4. 77 FR 47470 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

    Science.gov (United States)

    2012-08-08

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Withdrawal... FINRA Rulebook August 2, 2012. On April 22, 2009, the Financial Industry Regulatory Authority,...

  5. 77 FR 55517 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    Science.gov (United States)

    2012-09-10

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a.... Introduction On May 24, 2012, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the... General Counsel, Securities Industry and Financial Markets Association, dated June 26, 2012...

  6. 75 FR 62439 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    Science.gov (United States)

    2010-10-08

    ...-2010-043] Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving..., 2010. I. Introduction On August 6, 2010, the Financial Industry Regulatory Authority, Inc. (``FINRA..., 2010 (``Wiesenberg Letter''); Letter from Manisha Kimmel, Executive Director, Financial...

  7. 77 FR 12340 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

    Science.gov (United States)

    2012-02-29

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting... Accounting Support Fee February 23, 2012. I. Introduction On December 20, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission...

  8. 76 FR 20757 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

    Science.gov (United States)

    2011-04-13

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting... February 4, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the...

  9. 75 FR 61793 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2010-10-06

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving... Encrypted September 29, 2010. I. Introduction On June 2, 2010, the Financial Industry Regulatory Authority... Taunt, Chief Executive Officer, Regal Financial Group, to Elizabeth M. Murphy, Secretary,...

  10. Subordinate regulatory mode and leader power: Interpersonal regulatory complementarity predicts task performance

    NARCIS (Netherlands)

    Hamstra, M.R.W.; Orehek, E.; Holleman, M.

    2014-01-01

    This research examines the implications of locomotion regulatory mode (orientation toward making progress on goals) and assessment regulatory mode (orientation toward critically evaluating alternatives) for employees' performance. Regulatory mode theory suggests that, although these are both integra

  11. Reforming Financial Regulatory System in China after the Stock Market Turbulence:Problems and the Responses

    Institute of Scientific and Technical Information of China (English)

    Chen Zhenyun

    2016-01-01

    In an age when modern financial companies have become more and more complex,and if not adequately supervised,they can cause lethal harm to the stability of one’ s financial system. In post-financial crisis era,major developed economies have apparently rein-forced the function of the central bank in a country’ s financial regulatory system. Over the past several years,China has witnessed the huge changes in the financial sector but the financial regulatory framework remains the same as before. The Chinese stock market crash that began on June 12 2015 has urged the domestic regulators to restructure its financial regulatory sys-tem. The issue that which modal China should follow has perplexed Chinese policymakers. The governor of People’ s Bank of China,Zhou Xiaochuan,clearly responded to the problem concerning the current financial regulatory system, and indicated that Chinese regulators and policymakers had still studied the regulatory approach China would adopt during the press of People’s Congress of 2016. This paper reviews the development of China’s banking regulato-ry system,points out the deficiencies in its original system and analyzes the recent trends of fi-nancial regulatory reform in UK to learn the international experience for further reform re-garding financial regulatory system in China.

  12. NEWS: Post-16 update

    Science.gov (United States)

    Campbell, Peter

    2000-07-01

    post16.gif As a teacher of physics it is very easy to become preoccupied with particulars of courses, or topics or even single concepts. Concerned with imminent student audiences and desired learning outcomes, the daily challenge is to summon satisfactory teaching approaches and resources for the job at hand. For the conscientious teacher, assessment outcomes may too often seem a judgment on our own efforts rather than those of our students. From time to time we may step back and think bigger, for example while planning a recruitment event, or while away from work on holiday. We may be successful locally. But why, at a time when books and television documentaries popularizing science have a large following, has physics education been facing declining numbers? Many recognize that physics has an essential contribution to make to the training of science or engineering specialists, but we know that it is also important for the skilled worker, the informed citizen and, in fact, for anyone trying to make sense of the world. So what are the best ways forward for post-16 physics? To make any impact on the bigger picture requires organization, thinking and meeting time among people in diverse roles: teachers and curriculum managers; university lecturers; employers and professional bodies; unitary awarding bodies; regulatory and funding agencies; and even Government. For the past few years, the Institute of Physics post-16 Initiative has created an unrivalled opportunity to address the wider issues. Its Shaping the Future booklets series was designed to stimulate informed discussion and debate, by providing background information and analysis. Taken together, the booklets should help all those concerned with physics education to understand where we are now, and why. Literally dozens of people have contributed to a review and analysis of physics education. Each booklet is a 48-page smorgasbord in A4 landscape format, containing many examples of good practice, basic but

  13. Reducing the cost of post combustion capture technology for pulverized coal power plants by flexible operation

    NARCIS (Netherlands)

    Kler, R.C.F. de; Verbaan, M.; Goetheer, E.L.V.

    2013-01-01

    Currently the low carbon prices, low Spreads and regulatory uncertainties hampers the business cases for coal-fired power plants with post-combustion capture (PCC) in Europe. Improvement of the business case of coal-fired power plants with post combustion capture requires a different approach in

  14. Reducing the cost of Post Combustion Capture technology for Pulverized Coal Power Plants by flexible operation

    NARCIS (Netherlands)

    De Kler, R.C.F.; Verbaan, M.; Goetheer, E.L.V.

    2013-01-01

    Currently the low carbon prices, low Spreads and regulatory uncertainties hampers the business cases for coal-fired power plants with post-combustion capture (PCC) in Europe. Improvement of the business case of coal-fired power plants with post combustion capture requires a different approach in

  15. Reducing the cost of Post Combustion Capture technology for Pulverized Coal Power Plants by flexible operation

    NARCIS (Netherlands)

    De Kler, R.C.F.; Verbaan, M.; Goetheer, E.L.V.

    2013-01-01

    Currently the low carbon prices, low Spreads and regulatory uncertainties hampers the business cases for coal-fired power plants with post-combustion capture (PCC) in Europe. Improvement of the business case of coal-fired power plants with post combustion capture requires a different approach in ter

  16. 后危机时代越南外资银行监管策略分析——以新制度经济学为视角%Analysis of Regulatory Strategy of Vietnam's Foreign-funded Banks in Post-crisis Era

    Institute of Scientific and Technical Information of China (English)

    陈丽平; 陶斌智

    2012-01-01

    Based on a review of the negative role played by foreign-funded banks in Vietnam's economic crisis,this paper applies the dialectic relation between the external institution and internal institution of New Institutional Economics to analyzing the causes for the regulatory failure of the foreign-funded banks.Research findings show that Vietnam's long-time ignorance of the informal institution-building in the internal management of foreign-funded banks and the unbalanced regulatory structure resulted from the absence of ethical management have contributed to the moral hazard.It is therefore concluded that emphasis should be laid on both external and internal management to maintain a stable management structure in foreign-funded banks and ensure a specialized and effective regulation.%基于越南金融危机期间外资银行的负面作用回顾,应用新制度经济学的外在制度与内在制度辩证关系原理,剖析外资银行监管失灵的根源。研究表明,越南长期忽视外资银行内部治理的非正式制度建设,伦理治理机制缺失造成监管结构失衡,从而引发道德风险。因此要强化内外双重治理,重视内部制度建设,才能实现后危机时代外资银行治理结构的稳定,提高监管的专业性和有效性。

  17. A Proteome-wide, Quantitative Survey of In Vivo Ubiquitylation Sites Reveals Widespread Regulatory Roles

    DEFF Research Database (Denmark)

    Wagner, Sebastian Alexander; Beli, Petra; Weinert, Brian Tate;

    2011-01-01

    Post-translational modification of proteins by ubiquitin is a fundamentally important regulatory mechanism. However, proteome-wide analysis of endogenous ubiquitylation remains a challenging task, and almost always has relied on cells expressing affinity tagged ubiquitin. Here we combine single-s...

  18. 78 FR 69468 - Self-Regulatory Organizations; Miami International Securities Exchange LLC; Notice of Filing and...

    Science.gov (United States)

    2013-11-19

    ... Immediate Effectiveness of Proposed Rule Change To Amend Exchange Rule 504, Trading Halts November 13, 2013..., Trading Halts. The text of the proposed rule change is available on the Exchange's Web site at http://www... option class (a ``Post-Halt Notification'') following a regulatory halt, trading pause or...

  19. The Political Economy of Regulatory Risk

    OpenAIRE

    Roland Strausz

    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 ...

  20. The political economy of regulatory risk

    OpenAIRE

    Strausz, Roland

    2009-01-01

    I investigate the argument that, in a twoparty 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 outputexpansion 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 regulatoryriskaverse party is n...

  1. Nuclear Regulatory Commission 1989 Information Digest

    Energy Technology Data Exchange (ETDEWEB)

    None,

    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.

  2. microRNA Decay: Refining microRNA Regulatory Activity.

    Science.gov (United States)

    Pepin, Genevieve; Gantier, Michael P

    2016-01-01

    MicroRNAs (miRNAs) are short 19-25 nucleotide RNA molecules that impact on most biological processes by regulating the efficiency of messenger RNA (mRNA) translation. To date, most research activities have been focused on the control of miRNA expression and its functional consequences. Nonetheless, much remains unknown about the mechanisms affecting the level of specific miRNAs in the cell, a critical feature impacting their regulatory activity. This review focuses on the factors that regulate the abundance of miRNAs, including synthesis, post-transcriptional modifications, nucleases, target binding, and secretion.

  3. Ground rules of the pluripotency gene regulatory network.

    KAUST Repository

    Li, Mo

    2017-01-03

    Pluripotency is a state that exists transiently in the early embryo and, remarkably, can be recapitulated in vitro by deriving embryonic stem cells or by reprogramming somatic cells to become induced pluripotent stem cells. The state of pluripotency, which is stabilized by an interconnected network of pluripotency-associated genes, integrates external signals and exerts control over the decision between self-renewal and differentiation at the transcriptional, post-transcriptional and epigenetic levels. Recent evidence of alternative pluripotency states indicates the regulatory flexibility of this network. Insights into the underlying principles of the pluripotency network may provide unprecedented opportunities for studying development and for regenerative medicine.

  4. 21 CFR 500.88 - Regulatory method.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Regulatory method. 500.88 Section 500.88 Food and... § 500.88 Regulatory method. (a) The sponsor shall submit for evaluation and validation a regulatory method developed to monitor compliance with FDA's operational definition of no residue. (b)...

  5. 77 FR 10351 - Regulatory Review Plan

    Science.gov (United States)

    2012-02-22

    ... XII Regulatory Review Plan AGENCY: Federal Housing Finance Agency. ACTION: Notice of final regulatory review plan. SUMMARY: The Federal Housing Finance Agency (FHFA) is issuing a notice of the final FHFA regulatory review plan for review of existing regulations under Executive Order 13579, ``Regulation...

  6. Regulatory Status of Dissimilar Metal Weld (DMW)

    Energy Technology Data Exchange (ETDEWEB)

    Kim, K. C.; Hong, J. K.; Shin, H. S.; Kang, S. S.; Song, M. H.; Chung, H. D. [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2009-05-15

    In this technical article, the regulatory status for Dissimilar Metal Water (DMW) was discussed. In order to decide the regulatory direction of DMW, the USA's accidents of PWSCC and their regulatory directions were reviewed. By reviewing their experiences, the Korean DMW regulation approach was decided.

  7. 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...

  8. 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...

  9. Regulatory institutions in liberalised electricity markets

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-07-01

    The reform of the electricity supply industry is gathering pace in many countries. Independent regulatory agencies and other regulatory bodies have been created, and regulatory responsibilities redefined. This book reviews the evolving institutional structures to regulate the electricity supply industry in IEA member countries. It is the latest in a series of IEA publications on energy market reform.

  10. Genetic flexibility of regulatory networks.

    Science.gov (United States)

    Hunziker, Alexander; Tuboly, Csaba; Horváth, Péter; Krishna, Sandeep; Semsey, Szabolcs

    2010-07-20

    Gene regulatory networks are based on simple building blocks such as promoters, transcription factors (TFs) and their binding sites on DNA. But how diverse are the functions that can be obtained by different arrangements of promoters and TF binding sites? In this work we constructed synthetic regulatory regions using promoter elements and binding sites of two noninteracting TFs, each sensing a single environmental input signal. We show that simply by combining these three kinds of elements, we can obtain 11 of the 16 Boolean logic gates that integrate two environmental signals in vivo. Further, we demonstrate how combination of logic gates can result in new logic functions. Our results suggest that simple elements of transcription regulation form a highly flexible toolbox that can generate diverse functions under natural selection.

  11. Regulatory T Cells and Parasites

    Directory of Open Access Journals (Sweden)

    TP. Velavan

    2011-01-01

    Full Text Available Human host encounters a wide array of parasites; however, the crucial aspect is the failure of the host immune system to clear these parasites despite antigen recognition. In the recent past, a new immunological concept has emerged, which provides a framework to better understand several aspects of host susceptibility to parasitic infection. It is widely believed that parasites are able to modulate the magnitude of effector responses by inducing regulatory T cell (Tregs population and several studies have investigated whether this cell population plays a role in balancing protective immunity and pathogenesis during parasite infection. This review discusses the several mechanism of Treg-mediated immunosuppression in the human host and focuses on the functional role of Tregs and regulatory gene polymorphisms in infectious diseases.

  12. Reconsidering Styles of Regulatory Enforcement

    DEFF Research Database (Denmark)

    May, Peter J.; Winter, Søren

    2000-01-01

    This study addresses enforcement styles of regulatory inspectors, based on an examination of the municipal enforcement of agro-environmental policies in Denmark. Our findings make three contributions to the regulatory literature. One contribution is to add empirical support for theorizing about...... inspectors’ enforcement styles as consisting of multiple components, rather than a single continuum. We show that inspectors’ enforcement styles comprise the degree of formalism and the degree of coercion that they exercise when carrying out inspections. A second contribution is in showing the relationship...... of different types of enforcement styles to the two underlying dimensions of the concept. A third contribution is an examination of the ways in which inspectors’ enforcement styles relate to their enforcement actions. The consistency of our findings with those of other studies suggests that the dimensions...

  13. Regulatory Changes in Depository Institutions

    OpenAIRE

    Yang, Brian Sejoon

    2016-01-01

    In this dissertation we investigate the effect of monetary policy and regulatory changes on asset pricing and investor behavior. In the first chapter, using unique data on over-the-counter bank stock prices and balance sheet information from 1940 to 1968, we find that the largest commercial bank stocks, ranked by market value or gross deposits, have significant lower risk-adjusted annual returns than do small sized bank stocks even after controlling for standard risk factors including size. ...

  14. Escherichia coli transcriptional regulatory network

    Directory of Open Access Journals (Sweden)

    Agustino Martinez-Antonio

    2011-06-01

    Full Text Available Escherichia coli is the most well-know bacterial model about the function of its molecular components. In this review are presented several structural and functional aspects of their transcriptional regulatory network constituted by transcription factors and target genes. The network discussed here represent to 1531 genes and 3421 regulatory interactions. This network shows a power-law distribution with a few global regulators and most of genes poorly connected. 176 of genes in the network correspond to transcription factors, which form a sub-network of seven hierarchical layers where global regulators tend to be set in superior layers while local regulators are located in the lower ones. There is a small set of proteins know as nucleoid-associated proteins, which are in a high cellular concentrations and reshape the nucleoid structure to influence the running of global transcriptional programs, to this mode of regulation is named analog regulation. Specific signal effectors assist the activity of most of transcription factors in E. coli. These effectors switch and tune the activity of transcription factors. To this type of regulation, depending of environmental signals is named the digital-precise-regulation. The integration of regulatory programs have place in the promoter region of transcription units where it is common to observe co-regulation among global and local TFs as well as of TFs sensing exogenous and endogenous conditions. The mechanistic logic to understand the harmonious operation of regulatory programs in the network should consider the globalism of TFs, their signal perceived, coregulation, genome position, and cellular concentration. Finally, duplicated TFs and their horizontal transfer influence the evolvability of members of the network. The most duplicated and transferred TFs are located in the network periphery.

  15. 77 FR 1524 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2012-01-10

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving..., 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and... effective date of the proposed rule change in a Regulatory Notice to be published no later than 60...

  16. 78 FR 54359 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2013-09-03

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on August 20, 2103, Financial Industry Regulatory.... \\3\\ 15 U.S.C. 78s(b)(3)(A)(i). \\4\\ 17 CFR 240.19b-4(f)(1). ] I. Self-Regulatory...

  17. 78 FR 10655 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    Science.gov (United States)

    2013-02-14

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...) February 8, 2013. I. Introduction On December 20, 2012, Financial Industry Regulatory Authority, Inc... Equity Securities.\\5\\ FINRA may impose a ``Foreign Regulatory Halt'' when a foreign securities...

  18. 77 FR 33527 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2012-06-06

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... hereby given that on May 23, 2012, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with.... 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of...

  19. 77 FR 12092 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2012-02-28

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...\\ notice is hereby given that February 9, 2012, Financial Industry Regulatory Authority, Inc. (``FINRA... interested persons. \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory...

  20. 75 FR 28841 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2010-05-24

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... thereunder,\\2\\ notice is hereby given that on May 18, 2010, Financial Industry Regulatory Authority, Inc.... \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of...

  1. 76 FR 2739 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-01-14

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... is hereby given that on January 5, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA...-Regulatory Organization's Statement of the Terms of Substance of the Proposed Rule Change FINRA is...

  2. 76 FR 20065 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-04-11

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on March 30, 2011, Financial Industry Regulatory... interested persons. \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory...

  3. 75 FR 49542 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2010-08-13

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... 19b-4 thereunder,\\2\\ notice is hereby given that on July 27, 2010, Financial Industry Regulatory... from interested persons. \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory...

  4. 76 FR 70195 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2011-11-10

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...,\\2\\ notice is hereby given that on October 28, 2011, Financial Industry Regulatory Authority, Inc.... \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of...

  5. 78 FR 42581 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2013-07-16

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... thereunder,\\2\\ notice is hereby given that on June 27, 2013, Financial Industry Regulatory Authority, Inc.... 78s(b)(3)(A)(i). \\4\\ 17 CFR 240.19b-4(f)(1). I. Self-Regulatory Organization's Statement of the...

  6. 77 FR 12098 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2012-02-28

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... February 9, 2012, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and...). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of Substance of...

  7. 76 FR 72463 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2011-11-23

    ...-FINRA-2011-044] Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of... is hereby given that on November 8, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA...\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the...

  8. 76 FR 9840 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2011-02-22

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... that on February 4, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the.... 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of...

  9. 78 FR 78451 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2013-12-26

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... thereunder,\\2\\ notice is hereby given that on December 9, 2013, Financial Industry Regulatory Authority, Inc.... \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of...

  10. 78 FR 25331 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

    Science.gov (United States)

    2013-04-30

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Withdrawal.... On January 7, 2013, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the... Regulatory Policy, Wells Fargo Advisors, LLC, dated Feb. 15, 2013; Letter from Tamara K. Salmon,...

  11. 76 FR 67787 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2011-11-02

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... thereunder,\\2\\ notice is hereby given that on October 13, 2011, Financial Industry Regulatory Authority, Inc.... 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of...

  12. 78 FR 76341 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2013-12-17

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... thereunder,\\2\\ notice is hereby given that, on December 2, 2013, Financial Industry Regulatory Authority, Inc... considers the subscriber's financial condition and its regulatory history. FINRA believes that the...

  13. 75 FR 2899 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2010-01-19

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving... January 12, 2010. On November 24, 2009, the Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k...- regulatory organizations.\\6\\ \\6\\ See, e.g., Nasdaq Rule 4761 and NYSE-Arca Rule 7.39. It is therefore...

  14. 78 FR 24261 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2013-04-24

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on April 15, 2013, Financial Industry Regulatory...\\ 17 CFR 240.19b-4(f)(6). I. Self-Regulatory Organization's Statement of the Terms of Substance of...

  15. 75 FR 7532 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2010-02-19

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and...,\\2\\ notice is hereby given that on February 4, 2010, Financial Industry Regulatory Authority, Inc... in Regulatory Notice 09-71 that the new financial responsibility rules will be implemented...

  16. 77 FR 58880 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2012-09-24

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and...,\\2\\ notice is hereby given that on September 17, 2012, Financial Industry Regulatory Authority, Inc...\\ 15 U.S.C. 78s(b)(3)(A). \\4\\ 17 CFR 240.19b-4(f)(6). I. Self-Regulatory Organization's Statement...

  17. 75 FR 58004 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2010-09-23

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... is hereby given that on September 7, 2010, Financial Industry Regulatory Authority, Inc. (``FINRA... Securities Exchange, LLC, Financial Industry Regulatory Authority, Inc., The New York Stock Exchange,...

  18. 76 FR 78706 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    Science.gov (United States)

    2011-12-19

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a... On October 20, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the... advised that it would announce the implementation date of the proposed rule change in a Regulatory...

  19. 75 FR 9459 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2010-03-02

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... hereby given that Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a National Association... National Association of Securities Dealers, Inc., the Financial Industry Regulatory Authority, Inc., or...

  20. 75 FR 39069 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2010-07-07

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on June 30, 2010, Financial Industry Regulatory.... \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of...

  1. 77 FR 33537 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2012-06-06

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... is hereby given that on May 24, 2012, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed.... 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of...

  2. 78 FR 75954 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2013-12-13

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... thereunder,\\2\\ notice is hereby given that on November 25, 2013, Financial Industry Regulatory Authority, Inc.... \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of...

  3. 75 FR 69503 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2010-11-12

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...\\ notice is hereby given that on October 29, 2010, Financial Industry Regulatory Authority, Inc. (``FINRA.... 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of...

  4. 75 FR 15470 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2010-03-29

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... thereunder,\\2\\ notice is hereby given that, on March 9, 2010, Financial Industry Regulatory Authority, Inc...-Regulatory Organization's Statement of the Terms of Substance of the Proposed Rule Change FINRA is...

  5. 75 FR 53998 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2010-09-02

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on August 16, 2010, Financial Industry Regulatory.... \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of...

  6. 77 FR 5611 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    Science.gov (United States)

    2012-02-03

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a..., 2012. I. Introduction On October 13, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA... change in a Regulatory Notice to be published no later than 90 days following Commission approval,...

  7. 76 FR 66344 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2011-10-26

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving.... Introduction On August 31, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a National... Regulatory Notice to be published no later than 90 days following this Commission approval. The...

  8. 75 FR 62901 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2010-10-13

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... thereunder,\\2\\ notice is hereby given that on September 27, 2010, the Financial Industry Regulatory Authority....19b-4(f)(6). I. Self-Regulatory Organization's Statement of the Terms of Substance of the...

  9. 76 FR 50515 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-08-15

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on August 5, 2011, Financial Industry Regulatory...-4(f)(6). I. Self-Regulatory Organization's Statement of the Terms of Substance of the Proposed...

  10. 76 FR 65758 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2011-10-24

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... thereunder,\\2\\ notice is hereby given that on October 5, 2011, Financial Industry Regulatory Authority, Inc.... \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of...

  11. 75 FR 18245 - Public Federal Regulatory Enforcement Fairness Hearing Region IX Regulatory Fairness Board

    Science.gov (United States)

    2010-04-09

    ... ADMINISTRATION Public Federal Regulatory Enforcement Fairness Hearing Region IX Regulatory Fairness Board.... Small Business Administration (SBA) Region IX Regulatory Fairness Board and the SBA Office of the National Ombudsman will hold a National Regulatory Fairness Hearing on Monday, April 26, 2010, at 1:30 p.m...

  12. 78 FR 30384 - Federal Regulatory Enforcement Fairness Hearing; Region X Regulatory Fairness Board

    Science.gov (United States)

    2013-05-22

    ... ADMINISTRATION Federal Regulatory Enforcement Fairness Hearing; Region X Regulatory Fairness Board AGENCY: U.S... Business Regulatory Fairness Board. SUMMARY: The (SBA) Office of the National Ombudsman is issuing this notice to announce the location, date and time of the Regional Small Business Regulatory Fairness hearing...

  13. 75 FR 17793 - Public Federal Regulatory Enforcement Fairness Hearing; Region III Regulatory Fairness Board

    Science.gov (United States)

    2010-04-07

    ... ADMINISTRATION Public Federal Regulatory Enforcement Fairness Hearing; Region III Regulatory Fairness Board.... Small Business Administration (SBA) Region III Regulatory Fairness Board and the SBA Office of the National Ombudsman will hold a National Regulatory Fairness Hearing on Tuesday, May 18, 2010, at 10 a.m...

  14. 78 FR 36011 - Region VII Regulatory Fairness Board; Federal Regulatory Enforcement Fairness Hearing

    Science.gov (United States)

    2013-06-14

    ... ADMINISTRATION Region VII Regulatory Fairness Board; Federal Regulatory Enforcement Fairness Hearing AGENCY: U.S... Business Regulatory Fairness Board. SUMMARY: The (SBA) Office of the National Ombudsman is issuing this notice to announce the location, date and time of the Regional Small Business Regulatory Fairness hearing...

  15. Followers feel valued : When leaders' regulatory focus makes leaders exhibit behavior that fits followers' regulatory focus

    NARCIS (Netherlands)

    Hamstra, Melvyn; Sassenberg, K.; Van Yperen, Nico W.; Wisse, Barbara

    2014-01-01

    When do followers feel valued by their leader? We propose that leaders' regulatory focus can make followers feel valued when leaders' regulatory focus is the same as followers' regulatory focus, that is, when there is regulatory fit between leaders and followers. We further propose that the reason w

  16. 75 FR 11166 - Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission...

    Science.gov (United States)

    2010-03-10

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission; Notice of Joint Meeting of the Nuclear Regulatory Commission and the...

  17. Post cardiac injury syndrome

    DEFF Research Database (Denmark)

    Nielsen, S L; Nielsen, F E

    1991-01-01

    The post-pericardiotomy syndrome is a symptom complex which is similar in many respects to the post-myocardial infarction syndrome and these are summarized under the diagnosis of the Post Cardiac Injury Syndrome (PCIS). This condition, which is observed most frequently after open heart surgery, i...... on the coronary vessels, with cardiac tamponade and chronic pericardial exudate. In the lighter cases, PCIS may be treated with NSAID and, in the more severe cases, with systemic glucocorticoid which has a prompt effect....

  18. 78 FR 79709 - Duke Energy Florida, Inc., Crystal River Unit 3 Nuclear Generating Plant Post-Shutdown...

    Science.gov (United States)

    2013-12-31

    ...] [FR Doc No: 2013-31317] NUCLEAR REGULATORY COMMISSION [Docket No. 50-302; NRC-2013-0283] Duke Energy Florida, Inc., Crystal River Unit 3 Nuclear Generating Plant Post-Shutdown Decommissioning Activities Report AGENCY: Nuclear Regulatory Commission (NRC). ACTION: Notice of receipt; availability; public...

  19. 75 FR 28073 - Draft Regulatory Guide: Issuance, Availability

    Science.gov (United States)

    2010-05-19

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Draft Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Draft Regulatory Guide, DG-3039, ``Standard Format and Content...

  20. 75 FR 48382 - Draft Regulatory Guide: Issuance, Availability

    Science.gov (United States)

    2010-08-10

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Draft Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Draft Regulatory Guide, DG-1228, ``Standard Format and Content...

  1. The core regulatory network in human cells.

    Science.gov (United States)

    Kim, Man-Sun; Kim, Dongsan; Kang, Nam Sook; Kim, Jeong-Rae

    2017-03-04

    In order to discover the common characteristics of various cell types in the human body, many researches have been conducted to find the set of genes commonly expressed in various cell types and tissues. However, the functional characteristics of a cell is determined by the complex regulatory relationships among the genes rather than by expressed genes themselves. Therefore, it is more important to identify and analyze a core regulatory network where all regulatory relationship between genes are active across all cell types to uncover the common features of various cell types. Here, based on hundreds of tissue-specific gene regulatory networks constructed by recent genome-wide experimental data, we constructed the core regulatory network. Interestingly, we found that the core regulatory network is organized by simple cascade and has few complex regulations such as feedback or feed-forward loops. Moreover, we discovered that the regulatory links from genes in the core regulatory network to genes in the peripheral regulatory network are much more abundant than the reverse direction links. These results suggest that the core regulatory network locates at the top of regulatory network and plays a role as a 'hub' in terms of information flow, and the information that is common to all cells can be modified to achieve the tissue-specific characteristics through various types of feedback and feed-forward loops in the peripheral regulatory networks. We also found that the genes in the core regulatory network are evolutionary conserved, essential and non-disease, non-druggable genes compared to the peripheral genes. Overall, our study provides an insight into how all human cells share a common function and generate tissue-specific functional traits by transmitting and processing information through regulatory network.

  2. Post-Polio Syndrome

    Science.gov (United States)

    ... or fatigue, this may overwork already stressed-out motor neurons and increase your risk of post-polio syndrome. Generally, post-polio syndrome is rarely life-threatening, but severe muscle weakness can lead to complications: Falls. Weakness in your leg muscles makes it ...

  3. Commitments by hostage posting

    NARCIS (Netherlands)

    Raub, W.; Baurmann, M.; Lahno, B.

    2009-01-01

    We survey research on incurring commitments by voluntary hostage posting as a mechanism of cooperation. The Trust Game is employed as a paradigmatic example of cooperation problems. We sketch a very simple game-theoretic model that shows how voluntary hostage posting can bind the trustee and thus in

  4. Post-Concussion Syndrome

    Science.gov (United States)

    ... if you're having problems with memory or problem-solving. There is no specific treatment for post-concussion ... for post-concussion syndrome if you have cognitive problems, as most of them ... or other techniques to work around memory deficits and attention skills. ...

  5. Fence Posts and Rails

    Science.gov (United States)

    Turton, Roger

    2016-01-01

    "Mathematical Lens" uses photographs as a springboard for mathematical inquiry and appears in every issue of "Mathematics Teacher." Recently while dismantling an old wooden post-and-rail fence, Roger Turton noticed something very interesting when he piled up the posts and rails together in the shape of a prism. The total number…

  6. Post-Session Authentication

    DEFF Research Database (Denmark)

    Ahmed, Naveed; Jensen, Christian D.

    2012-01-01

    . In this paper, we consider the case of post-session authentication, where parties authenticate each other at the end of their interactive session. This use of authentication is different from session-less authentication (e.g., in RFID) and pre-session authentication (e.g., for access control.) Post...

  7. [Flexible root posts].

    Science.gov (United States)

    Vadachkoriia, N R; Mandzhavidze, N A; Gumberidze, N Sh

    2009-02-01

    The article discusses the current state of restoration techniques of root canal treatment. Nowadays, technical progress allows manufacturers to develop flexible fiberglass posts, aspiring not only to an excellent aesthetics and mechanical properties (first of all, in comparison with metal and cast posts), but also to maintenance of their radio density and a wide range of forms. Growth of fiberglass posts popularity testifies to their clinical efficiency that also is confirmed by results of long-term researches. Introduction of fiberglass posts in a dental practice has rendered huge influence on restoration techniques of root canal treatment. Convincing factors of fiberglass posts superiority provide restoration the appearance similar with the natural dentition; possess close to dentine elasticity; creation of monolithic structure with hard tooth tissues and composite cement, posts, in case of need, can be easily adjusted on length, adhesive linkage of posts gives them additional stability. Modern researches have confirmed that only elastic, namely carbon fiber and the fiberglass posts made of modern technologies possess similar physical properties, as tooth structure. They can create reliable biomimetic design; solve a complex of aesthetic and functional restoration problems.

  8. Post-Stroke Rehabilitation

    Science.gov (United States)

    ... PDF (704 kb) » Spanish Version » Order Materials » Post-Stroke Rehabilitation In the United States more than 700,000 ... best possible long-term outcome. What is post-stroke rehabilitation? Rehabilitation helps stroke survivors relearn skills that are ...

  9. Regulatory control of genetically modified (GM) foods: likely developments.

    Science.gov (United States)

    Schilter, Benoît; Constable, Anne

    2002-02-28

    The placing of genetically modified (GM) crops on the European market requires a regulatory approval supported by a thorough safety evaluation. This approach has been applied to all GM crops presently on the market. Despite this stringent process there has been an increasing public concern about the impact of GM foods on human health and the environment. In this context, regulatory control may develop in several directions. One response to the public concern is to strengthen the data requirements for the risk assessment process. Several avenues have been proposed. They include the application of technologies such as proteomics and metabolomics to assess unintended changes, and the development of predictive methods to evaluate allergenicity. Obligations for post-launch surveillance have appeared in regulations. Criteria are required to define when and why such approaches are necessary. Significant challenges including feasibility and validation of the methods, and safety relevance of the data generated will have to be addressed before any general application of these new approaches. Effective monitoring requires the ability to identify the presence of GM products and trace their origin. Traceability and labeling are therefore important developments in the GM food regulatory arena. Both require the development of reliable analytical detection tools.

  10. Identifying TF-MiRNA Regulatory Relationships Using Multiple Features.

    Directory of Open Access Journals (Sweden)

    Mingyu Shao

    Full Text Available MicroRNAs are known to play important roles in the transcriptional and post-transcriptional regulation of gene expression. While intensive research has been conducted to identify miRNAs and their target genes in various genomes, there is only limited knowledge about how microRNAs are regulated. In this study, we construct a pipeline that can infer the regulatory relationships between transcription factors and microRNAs from ChIP-Seq data with high confidence. In particular, after identifying candidate peaks from ChIP-Seq data, we formulate the inference as a PU learning (learning from only positive and unlabeled examples problem. Multiple features including the statistical significance of the peaks, the location of the peaks, the transcription factor binding site motifs, and the evolutionary conservation are derived from peaks for training and prediction. To further improve the accuracy of our inference, we also apply a mean reciprocal rank (MRR-based method to the candidate peaks. We apply our pipeline to infer TF-miRNA regulatory relationships in mouse embryonic stem cells. The experimental results show that our approach provides very specific findings of TF-miRNA regulatory relationships.

  11. 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.

  12. REGULATORY AGENCIES, CONSUMER AND ENVIROMENT

    Directory of Open Access Journals (Sweden)

    Giseli Valezi Raymundo

    2011-03-01

    Full Text Available The aim of this paper is to present the analysis on the insertion of the consumer in the current model of State in Brazil, considering the nowaday legal system. It is wished to be shown, moreover, the already existing reality on the theme, even if modest, so to in a way to question the responsibility of the consumer, according to its consuming habits and its inertia, takes in today’s technological society. To such proposal, the most effective research method, and, for this reason had been used in this paper, is the extensive bibliography research and legislation consultation. Through it, it had been found that the State model has changed over the past decades in order to delegate the execution of various activities of State ownership to private enterprise, in view of the existence of a minimal State and governor. In this sense, there were created the Regulatory Agencies, which are indirect public administration entities, with the ultimate objective of regulating and supervising the execution of those legal activities, performed by the private sector. The consumer, inserted in this reality, is the direct recipient of the action of the mentioned entities, questioning the legislative and sanction legitimacy of the regulatory entities as well as the possibility of judicial review on the merits of administrative actions of these entities and the applicability of the Brazilian Code of Defense of the Consumer (CDC to the execution of public services, a discipline that affects the administrative law rights. Notwithstanding the above analysis in context, all these social workers, consumers and regulatory agencies are immersed in changing habits, due to the optimization of actions, aimed at preserving the environment, the prospect of achieving sustainable development. Based on this perspective, the results brought by the survey showed that the application of the Brazilian Code of Defense of the Consumer in relations between consumers does not preclude

  13. Utilizing national and international registries to enhance pre-market medical device regulatory evaluation.

    Science.gov (United States)

    Yue, Lilly Q; Campbell, Gregory; Lu, Nelson; Xu, Yunling; Zuckerman, Bram

    2016-01-01

    Regulatory decisions are made based on the assessment of risk and benefit of medical devices at the time of pre-market approval and subsequently, when post-market risk-benefit balance needs reevaluation. Such assessments depend on scientific evidence obtained from pre-market studies, post-approval studies, post-market surveillance studies, patient perspective information, as well as other real world data such as national and international registries. Such registries provide real world evidence and are playing a more and more important role in enhancing the safety and effectiveness evaluation of medical devices. While these registries provide large quantities of data reflecting real world practice and can potentially reduce the cost of clinical trials, challenges arise concerning (1) data quality adequate for regulatory decision-making, (2) bias introduced at every stage and aspect of study, (3) scientific validity of study designs, and (4) reliability and interpretability of study results. This article will discuss related statistical and regulatory challenges and opportunities with examples encountered in medical device regulatory reviews.

  14. Regulatory Issues Surrounding Merchant Interconnection

    Energy Technology Data Exchange (ETDEWEB)

    Kuijlaars, Kees-Jan; Zwart, Gijsbert [Office for Energy Regulation (DTe), The Hague (Netherlands)

    2003-11-01

    We discussed various issues concerning the regulatory perspective on private investment in interconnectors. One might claim that leaving investment in transmission infrastructure to competing market parties is more efficient than relying on regulated investment only (especially in the case of long (DC) lines connecting previously unconnected parts of the grids, so that externalities from e.g. loop flows do not play a significant role). We considered that some aspects of interconnection might reduce these market benefits. In particular, the large fixed costs of interconnection construction may lead to significant under investment (due to both first mover monopoly power and the fact that part of generation cost efficiencies realised by interconnection are not captured by the investor itself, and remain external to the investment decision). Second, merchant ownership restricts future opportunities for adaptation of regulation, as would be required e.g. for introduction of potentially more sophisticated methods of congestion management or market splitting. Some of the disadvantages of merchant investment may be mitigated however by a suitable regulatory framework, and we discussed some views in this direction. The issues we discussed are not intended to give a complete framework, and detailed regulation will certainly involve many more specific requirements. Areas we did not touch upon include e.g. the treatment of deep connection costs, rules for operation and maintenance of the line, and impact on availability of capacity on other interconnections.

  15. Endocrine cells producing regulatory peptides.

    Science.gov (United States)

    Solcia, E; Usellini, L; Buffa, R; Rindi, G; Villani, L; Zampatti, C; Silini, E

    1987-07-15

    Recent data on the immunolocalization of regulatory peptides and related propeptide sequences in endocrine cells and tumors of the gastrointestinal tract, pancreas, lung, thyroid, pituitary (ACTH and opioids), adrenals and paraganglia have been revised and discussed. Gastrin, xenopsin, cholecystokinin (CCK), somatostatin, motilin, secretin, GIP (gastric inhibitory polypeptide), neurotensin, glicentin/glucagon-37 and PYY (peptide tyrosine tyrosine) are the main products of gastrointestinal endocrine cells; glucagon, CRF (corticotropin releasing factor), somatostatin, PP (pancreatic polypeptide) and GRF (growth hormone releasing factor), in addition to insulin, are produced in pancreatic islet cells; bombesin-related peptides are the main markers of pulmonary endocrine cells; calcitonin and CGRP (calcitonin gene-related peptide) occur in thyroid and extrathyroid C cells; ACTH and endorphins in anterior and intermediate lobe pituitary cells, alpha-MSH and CLIP (corticotropin-like intermediate lobe peptide) in intermediate lobe cells; met- and leu-enkephalins and related peptides in adrenal medullary and paraganglionic cells as well as in some gut (enterochromaffin) cells; NPY (neuropeptide Y) in adrenaline-type adrenal medullary cells, etc.. Both tissue-appropriate and tissue-inappropriate regulatory peptides are produced by endocrine tumours, with inappropriate peptides mostly produced by malignant tumours.

  16. [Advanced therapy: from European regulatory framework to national regulatory framework].

    Science.gov (United States)

    Lucas-Samuel, S

    2013-05-01

    The European regulation n(o) 1394/2007/CE published on the 13th of November 2007 defined and harmonized the European regulatory framework for advanced therapy medicinal products. It creates a specialized committee located at the European Medicine Agency, in charge of the assessment of these medicinal products. The consequences of this regulation are introduced in the French regulation by the law n(o) 2011-302 published on the 22nd of March 2011. It detailed notably the possibility for public establishments (except health establishments) and nonprofit organisms to create pharmaceutical establishments. This law defined also a specific category of advanced therapy medicinal products, which fall under the "hospital exemption" framework. The rules regarding the authorizations of the establishments able to prepare these types of medicinal products and the authorization of the products are defined by the n(o) 2012-1236 decree published on the 6th of November 2012.

  17. Global Summit on Regulatory Science 2013.

    Science.gov (United States)

    Howard, Paul C; Tong, Weida; Weichold, Frank; Healy, Marion; Slikker, William

    2014-12-01

    Regulatory science has been defined as the science that is used to develop regulatory decisions by government bodies. Regulatory science encompasses many scientific disciplines that oversee many studies producing a wide array of data. These may include fundamental research into the cellular interaction or response to a particular chemical or substance, hazard-assessment and dose-response studies in animal species, neurophysiological or neurobehavioral studies, best practices for the generation and analysis of genomics data, bioinformatics approaches, and mathematical modeling of risk. The Global Summit on Regulatory Science is an international conference with a mission to explore emerging and innovative technologies, and provide a platform to enhance translation of basic science into regulatory applications. The Third Global Summit on Regulatory Science which focused on nanotechnology is discussed.

  18. Environmental Regulatory Update Table, December 1991

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1992-01-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  19. Environmental Regulatory Update Table, December 1989

    Energy Technology Data Exchange (ETDEWEB)

    Houlbert, L.M.; Langston, M.E. (Tennessee Univ., Knoxville, TN (USA)); Nikbakht, A.; Salk, M.S. (Oak Ridge National Lab., TN (USA))

    1990-01-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  20. Regulatory Risk under Optimal Incentive Regulation

    OpenAIRE

    Strausz, Roland

    2009-01-01

    The paper provides a tractable, analytical framework to study regulatory risk under optimal incentive regulation. Regulatory risk is captured by uncertainty about the policy variables in the regulator’s objective function: weights attached to profits and costs of public funds. Results are as follows: 1) The regulator’s reaction to regulatory risk depends on the curvature of the aggregate demand function. 2) It yields a positive information rent effect exactly when demand is convex. 3) Firms b...

  1. Environmental Regulatory Update Table, November 1991

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1991-12-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  2. Environmental Regulatory Update Table, August 1991

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M., Hawkins, G.T.; Salk, M.S.

    1991-09-01

    This Environmental Regulatory Update Table (August 1991) provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  3. Environmental Regulatory Update Table, September 1991

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1991-10-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  4. Environmental Regulatory Update Table, October 1991

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1991-11-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  5. Environmental Regulatory Update Table, April 1989

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.; Langston, M.E.; Nikbakht, A.; Salk, M.S.

    1989-05-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  6. Environmental Regulatory Update Table, April 1989

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.; Langston, M.E.; Nikbakht, A.; Salk, M.S.

    1989-05-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  7. Environmental regulatory update table, March 1989

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.; Langston, M.E.; Nikbakht, A.; Salk, M.S.

    1989-04-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  8. Environmental Regulatory Update Table, November 1991

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.

    1991-12-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management responsibilities. The table is updated each month with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  9. Post-Approval Studies

    Data.gov (United States)

    U.S. Department of Health & Human Services — The CDRH Post-Approval Studies Program encompasses design, tracking, oversight, and review responsibilities for studies mandated as a condition of approval of a...

  10. Small Regulatory RNAs of Rickettsia conorii

    Science.gov (United States)

    Narra, Hema P.; Schroeder, Casey L. C.; Sahni, Abha; Rojas, Mark; Khanipov, Kamil; Fofanov, Yuriy; Sahni, Sanjeev K.

    2016-01-01

    Small regulatory RNAs comprise critically important modulators of gene expression in bacteria, yet very little is known about their prevalence and functions in Rickettsia species. R. conorii, the causative agent of Mediterranean spotted fever, is a tick-borne pathogen that primarily infects microvascular endothelium in humans. We have determined the transcriptional landscape of R. conorii during infection of Human Microvascular Endothelial Cells (HMECs) by strand-specific RNA sequencing to identify 4 riboswitches, 13 trans-acting (intergenic), and 22 cis-acting (antisense) small RNAs (termed ‘Rc_sR’s). Independent expression of four novel trans-acting sRNAs (Rc_sR31, Rc_sR33, Rc_sR35, and Rc_sR42) and known bacterial sRNAs (6S, RNaseP_bact_a, ffs, and α-tmRNA) was next confirmed by Northern hybridization. Comparative analysis during infection of HMECs vis-à-vis tick AAE2 cells revealed significantly higher expression of Rc_sR35 and Rc_sR42 in HMECs, whereas Rc_sR31 and Rc_sR33 were expressed at similar levels in both cell types. We further predicted a total of 502 genes involved in all important biological processes as potential targets of Rc_sRs and validated the interaction of Rc_sR42 with cydA (cytochrome d ubiquinol oxidase subunit I). Our findings constitute the first evidence of the existence of post-transcriptional riboregulatory mechanisms in R. conorii and interactions between a novel Rc_sR and its target mRNA. PMID:27834404

  11. 75 FR 34962 - Pennsylvania Regulatory Program

    Science.gov (United States)

    2010-06-21

    ... another site is more suitable based upon engineering, geology, economics, transportation systems, and... to the actual language of state regulatory programs and program amendments because each program is...

  12. Exploring associations between self-regulatory mechanisms and neuropsychological functioning and driver behaviour after brain injury.

    Science.gov (United States)

    Rike, Per-Ola; Johansen, Hans J; Ulleberg, Pål; Lundqvist, Anna; Schanke, Anne-Kristine

    2016-04-11

    The objective of this prospective one-year follow-up study was to explore the associations between self-regulatory mechanisms and neuropsychological tests as well as baseline and follow-up ratings of driver behaviour. The participants were a cohort of subjects with stroke and traumatic brain injury (TBI) who were found fit to drive after a multi-disciplinary driver assessment (baseline). Baseline measures included neuropsychological tests and ratings of self-regulatory mechanisms, i.e., executive functions (Behavior Rating Inventory of Executive Function-Adult Version; BRIEF-A) and impulsive personality traits (UPPS Impulsive Behavior Scale). The participants rated pre-injury driving behaviour on the Driver Behaviour Qestionnaire (DBQ) retrospectively at baseline and after one year of post-injury driving (follow-up). Better performance on neuropsychological tests was significantly associated with more post-injury DBQ Violations. The BRIEF-A main indexes were significantly associated with baseline and follow-up ratings of DBQ Mistakes and follow-up DBQ Inattention. UPPS (lack of) Perseverance was significantly associated with baseline DBQ Inattention, whereas UPPS Urgency was significantly associated with baseline DBQ Inexperience and post-injury DBQ Mistakes. There were no significant changes in DBQ ratings from baseline (pre-injury) to follow-up (post-injury). It was concluded that neuropsychological functioning and self-regulatory mechanisms are related to driver behaviour. Some aspects of driver behaviour do not necessarily change after brain injury, reflecting the influence of premorbid driving behaviour or impaired awareness of deficits on post-injury driving behaviour. Further evidence is required to predict the role of self-regulatory mechanisms on driver behaviour and crashes or near misses.

  13. Regulatory T cells as immunotherapy

    Directory of Open Access Journals (Sweden)

    Benjamin David Singer

    2014-02-01

    Full Text Available Regulatory T cells (Tregs suppress exuberant immune system activation and promote immunologic tolerance. Because Tregs modulate both innate and adaptive immunity, the biomedical community has developed intense interest in using Tregs for immunotherapy. Conditions that require clinical tolerance to improve outcomes—autoimmune disease, solid organ transplantation, and hematopoietic stem cell transplantation—may benefit from Treg immunotherapy. Investigators have designed ex vivo strategies to isolate, preserve, expand, and infuse Tregs. Protocols to manipulate Treg populations in vivo have also been considered. Barriers to clinically feasible Treg immunotherapy include Treg stability, off-cell effects, and demonstration of cell preparation purity and potency. Clinical trials involving Treg adoptive transfer to treat graft versus host disease preliminarily demonstrated the safety and efficacy of Treg immunotherapy in humans. Future work will need to confirm the safety of Treg immunotherapy and establish the efficacy of specific Treg subsets for the treatment of immune-mediated disease.

  14. Reduction of regulatory risk: a network economic approach

    OpenAIRE

    Knieps, Günter; Weiß, Hans-Jörg

    2007-01-01

    Several definitions of regulatory risk are known from the literature. From the perspective of regulatory reform it is important to differentiate between the impact of a given regulatory scheme on the firm's risk exposure and the risk arising from discretionary behavior of regulatory agencies. Whereas the conse-quences of effective regulation in principle are known and accepted, excessive regulatory discretion may cause a strong need for regulatory reform. Regulatory reform focussing on the re...

  15. Computer Security: posting and mis-posting

    CERN Multimedia

    Stefan Lueders, Computer Security Team

    2015-01-01

    This is what can happen at CERN if you don't lock your computer screen...   “Hi, I am looking for a partner either male or female to attend salsa lessons. I have a great body and enjoy rubbing it against other people on the dance floor. I would consider dinner after with the right person. If you think you can keep up with me and enjoy getting sweaty send me a reply. Stay sexy…” This is the original text of a recent posting on the CERN Market webpage. Some people might find this appealing, some people think this is funny. Personally, I couldn’t care less. But professionally, we had to follow up as this text can be perceived as inappropriate and, thus, in violation of the Terms of Usage of the CERN Market as well as the CERN Computing Rules and its annex on private usage of the CERN computing facilities. We remind you that the CERN Market is a public website that can be used by people within but also outside CERN. All posts are visible world...

  16. 76 FR 41238 - Post Rock Wind Power Project, LLC; Supplemental Notice That Initial Market-Based Rate Filing...

    Science.gov (United States)

    2011-07-13

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Post Rock Wind Power Project, LLC; Supplemental Notice That Initial Market... in the above-referenced proceeding of Post Rock Wind Power Project, LLC's application for market...

  17. Connecting the Dots...: Information Sharing by Post-Secondary Educational Institutions under the Family Education Rights and Privacy Act (FERPA)

    Science.gov (United States)

    Graham, Richard; Hall, Richard; Gilmer, W. Gerry

    2008-01-01

    Misunderstanding of privacy laws and regulations impedes appropriate information sharing by post-secondary educational institutions under the Family Educational Rights and Privacy Act of 1974 ("FERPA"). Post-Virginia Tech regulatory amendments allow institutions to "connect the dots" regarding a student's behavior and to be…

  18. Regulatory fit messages and physical activity motivation.

    Science.gov (United States)

    Pfeffer, Ines

    2013-04-01

    Targeted communication about health behaviors seems to be more effective than mass communication in which undifferentiated audiences receive identical messages. Regulatory focus is psychological variable that can be used to build two target groups: promotion-focused or prevention-focused people. It is hypothesized that targeting messages to an individual's regulatory focus creates regulatory fit and is more successful to promote a physically active lifestyle than nonfit messages. Two different print messages promoting a physically active lifestyle derived from regulatory focus theory (promotion message vs. prevention message) were randomly assigned to N = 98 participants after measuring their regulatory focus. It was examined whether regulatory fit between the regulatory focus and the assigned print message would lead to more positive evaluations in the dependent variables inclination toward the message (preference for the message), intention to perform the behavior, prospective and retrospective feelings associated with the behavior (positive and negative), and perceived value of the behavior directly after reading the message. Hierarchical linear regression analyses revealed that regulatory fit led to stronger intentions in the prevention-message condition and more prospective positive and retrospective positive feelings associated with the behavior in the promotion-message condition in contrast to the nonfit conditions. Prospective positive feelings associated with the behavior mediated the effect of regulatory fit on intention. The results partly provided support for the regulatory fit concept. Matching print messages to the regulatory focus of individuals seems to be a useful approach to enhance physical activity motivation. Future studies should include an objective measure of physical activity behavior.

  19. 75 FR 17460 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2010-04-06

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and...'') \\1\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on March 26, 2010, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``SEC''...

  20. 78 FR 59995 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2013-09-30

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on September 16, 2013, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``Commission'')...

  1. 75 FR 30457 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2010-06-01

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of Proposed Rule Change Relating to the Restated Certificate of Incorporation of Financial Industry Regulatory...'') \\1\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on May 21, 2010, Financial...

  2. 77 FR 5610 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2012-02-03

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and...\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on January 24, 2012, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``Commission'')...

  3. 78 FR 46652 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2013-08-01

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... thereunder,\\3\\ notice is hereby given that, on July 18, 2013, Financial Industry Regulatory Authority, Inc... as described in Items I, II and III below, which Items have been prepared by the...

  4. 75 FR 27606 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2010-05-17

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... (``Act'') \\1\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on April 27, 2010, the Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a National Association of Securities Dealers,...

  5. 78 FR 37261 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2013-06-20

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on June 3, 2013, Financial Industry Regulatory... rule change from interested persons. \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I....

  6. 77 FR 68181 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2012-11-15

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on November 2, 2012, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``SEC''...

  7. 75 FR 8771 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2010-02-25

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change To Adopt FINRA Rule 2261 (Disclosure of Financial Condition) in the Consolidated FINRA Rulebook February 18, 2010. On November 18, 2009, the Financial Industry Regulatory Authority,...

  8. 76 FR 65307 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2011-10-20

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...''),\\1\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on October 6, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission...

  9. 76 FR 11830 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-03-03

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on February ] 22, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``SEC''...

  10. 77 FR 4599 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2012-01-30

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on January 10, 2012, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``SEC''...

  11. 77 FR 7218 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2012-02-10

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on January 30, 2012, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``SEC''...

  12. 75 FR 36756 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2010-06-28

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on June 17, 2010, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``SEC''...

  13. 75 FR 59300 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2010-09-27

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on September 17, 2010, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``Commission'')...

  14. 75 FR 39610 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2010-07-09

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Amending Financial Industry Regulatory Authority, Inc...'') \\1\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on June 24, 2010, Financial...

  15. 76 FR 29808 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

    Science.gov (United States)

    2011-05-23

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting... Distributions) May 18, 2011. I. Introduction On April 26, 2011, the Financial Industry Regulatory Authority, Inc... 29, 2011. II. Description of the Proposed Rule Change On November 29, 2010, FINRA issued...

  16. 76 FR 11542 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2011-03-02

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving... 24, 2011. I. Introduction On November 10, 2010, the Financial Industry Regulatory Authority, Inc... fidelity bond will be a great financial burden for small firms.\\16\\ The third commenter agrees with...

  17. 76 FR 68240 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2011-11-03

    ...-2011-062] Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on October 20, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``SEC''...

  18. 77 FR 1119 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2012-01-09

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...'') \\1\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on December 19, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission...

  19. 76 FR 77034 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-12-09

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and...''),\\1\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on December 2, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange...

  20. 76 FR 61773 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-10-05

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... Expansion of the Order Audit Trail System to All NMS Stocks September 29, 2011. Pursuant to Section 19(b)(1... given that on September 27, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed...

  1. 76 FR 81551 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2011-12-28

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change Relating to Amendments to the Order Audit Trail System Rules December 21, 2011. I. Introduction On October 28, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with...

  2. 76 FR 25399 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-05-04

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... of the Order Audit Trail System to All NMS Stocks April 29, 2011. Pursuant to Section 19(b)(1) of the... April 26, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities...

  3. 75 FR 69725 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2010-11-15

    ...-2010-058] Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of... the FINRA Trade Reporting and Order Audit Trail System Rules Approved in SR-FINRA-2010-043 November 8... thereunder,\\2\\ notice is hereby given that on November 5, 2010, Financial Industry Regulatory Authority,...

  4. 76 FR 71404 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-11-17

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Relating to the Order Audit Trail System Definitions of... November 4, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities...

  5. 76 FR 37384 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-06-27

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change Relating to Exemptions from the Order Audit Trail System..., Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange...

  6. 78 FR 76973 - Regulatory Capital Rules: Regulatory Capital, Implementation of Basel III, Capital Adequacy...

    Science.gov (United States)

    2013-12-20

    ... #0; Federal Register #0; #0; #0;This section of the FEDERAL REGISTER contains regulatory documents #0..., and 225 Regulations H, Q, and Y RIN 7100-AD 87 Regulatory Capital Rules: Regulatory Capital... Approach for Risk-Weighted Assets, Market Discipline and Disclosure Requirements, Advanced Approaches...

  7. 76 FR 26333 - National Federal Regulatory Enforcement Fairness Hearing Region III Regulatory Fairness Board

    Science.gov (United States)

    2011-05-06

    ... ADMINISTRATION National Federal Regulatory Enforcement Fairness Hearing Region III Regulatory Fairness Board... III) Small Business Regulatory Fairness Board. SUMMARY: The SBA, Office of the National Ombudsman is... Fairness Hearing. This hearing is open to the public. DATES: The hearing will be held on Tuesday, May 24...

  8. 76 FR 74105 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-11-30

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... November 21, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and... significant increase in trading pauses involving rights and warrants since the inclusion of the Phase...

  9. Esthetic Intracanal Posts

    Science.gov (United States)

    Parčina, Ivana; Amižić

    2016-01-01

    The primary function of an endodontic post is to provide retention for the core and enable full sealing of the coronal portion of the root canal. Traditionally used metal posts do not meet the requirements of modern dental medicine due to some fairly significant drawbacks such as color, corrosion potential, non-adhesive bonding and high modulus of elasticity which can lead to root fracture. Recently, esthetic ceramic and fiber reinforced posts have been manufactured in order to avoid such imperfections. Since much attention has been devoted to the esthetic aspects of dental medicine, the use of these posts with composite/ceramic cores is very common in restorative dentistry and it is actually becoming a standard. This is due to the fact that, apart from being an esthetically pleasing material, they are also biocompatible, have good physical properties and the capacity of adhesive bonding to tooth tissue and core buildup. Nonetheless, a good clinician should know how to spot the difference between them in order to select and use the appropriate post system in each specific situation. PMID:27789912

  10. Regulatory Reform: Low Risk, High Promise.

    Science.gov (United States)

    Tanenbaum, Morris

    The press of telecommunication technologies and their progeny have undermined the natural monopoly basis for long distance telecommunications and customer premise products, forced open regulatory doors, toppled barriers to market entry, and led to the reshaping of regulatory philosophy as regulators have seen new, wider horizons for the industry.…

  11. 21 CFR 26.18 - Regulatory collaboration.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Regulatory collaboration. 26.18 Section 26.18 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL MUTUAL... Specific Sector Provisions for Pharmaceutical Good Manufacturing Practices § 26.18 Regulatory...

  12. 78 FR 1646 - Semiannual Regulatory Agenda

    Science.gov (United States)

    2013-01-08

    ...; Organizational Conflicts of Interest. 416 FAR Case 2010-013, Privacy 9000-AM02 Training. 417 Federal Acquisition...: Action Date FR Cite NPRM 12/00/12 Regulatory Flexibility Analysis Required: Yes. Agency Contact: Edward.... L. 110-417). Timetable: Action Date FR Cite NPRM 04/00/13 Regulatory Flexibility Analysis Required...

  13. Meditation and Its Regulatory Role on Sleep

    OpenAIRE

    Nagendra, Ravindra P.; Maruthai, Nirmala; Kutty, Bindu M.

    2012-01-01

    Intense meditation practices help to achieve a harmony between body and mind. Meditation practices influence brain functions, induce various intrinsic neural plasticity events, modulate autonomic, metabolic, endocrine, and immune functions and thus mediate global regulatory changes in various behavioral states including sleep. This brief review focuses on the effect of meditation as a self regulatory phenomenon on sleep.

  14. 49 CFR 355.21 - Regulatory review.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 5 2010-10-01 2010-10-01 false Regulatory review. 355.21 Section 355.21... AND REGULATIONS AFFECTING INTERSTATE MOTOR CARRIER OPERATIONS Requirements § 355.21 Regulatory review... review are provided in the appendix to this part. (b) Responsibility. The State agency designated as...

  15. Genomics in the land of regulatory science.

    Science.gov (United States)

    Tong, Weida; Ostroff, Stephen; Blais, Burton; Silva, Primal; Dubuc, Martine; Healy, Marion; Slikker, William

    2015-06-01

    Genomics science has played a major role in the generation of new knowledge in the basic research arena, and currently question arises as to its potential to support regulatory processes. However, the integration of genomics in the regulatory decision-making process requires rigorous assessment and would benefit from consensus amongst international partners and research communities. To that end, the Global Coalition for Regulatory Science Research (GCRSR) hosted the fourth Global Summit on Regulatory Science (GSRS2014) to discuss the role of genomics in regulatory decision making, with a specific emphasis on applications in food safety and medical product development. Challenges and issues were discussed in the context of developing an international consensus for objective criteria in the analysis, interpretation and reporting of genomics data with an emphasis on transparency, traceability and "fitness for purpose" for the intended application. It was recognized that there is a need for a global path in the establishment of a regulatory bioinformatics framework for the development of transparent, reliable, reproducible and auditable processes in the management of food and medical product safety risks. It was also recognized that training is an important mechanism in achieving internationally consistent outcomes. GSRS2014 provided an effective venue for regulators andresearchers to meet, discuss common issues, and develop collaborations to address the challenges posed by the application of genomics to regulatory science, with the ultimate goal of wisely integrating novel technical innovations into regulatory decision-making.

  16. Meditation and its regulatory role on sleep

    Directory of Open Access Journals (Sweden)

    Ravindra P. Nagendra

    2012-04-01

    Full Text Available Intense meditation practices help to achieve a harmony between body and mind. Meditation practices influence brain functions, induce various intrinsic neural plasticity events, modulate autonomic, metabolic, endocrine and immune functions and thus mediate global regulatory changes in various behavioural states including sleep. This brief review focuses on the effect of meditation as a self regulatory phenomenon on sleep.

  17. Meditation and its regulatory role on sleep.

    Science.gov (United States)

    Nagendra, Ravindra P; Maruthai, Nirmala; Kutty, Bindu M

    2012-01-01

    Intense meditation practices help to achieve a harmony between body and mind. Meditation practices influence brain functions, induce various intrinsic neural plasticity events, modulate autonomic, metabolic, endocrine, and immune functions and thus mediate global regulatory changes in various behavioral states including sleep. This brief review focuses on the effect of meditation as a self regulatory phenomenon on sleep.

  18. CD4-regulatory cells in COPD patients

    DEFF Research Database (Denmark)

    Smyth, Lucy J C; Starkey, Cerys; Vestbo, Jørgen

    2007-01-01

    BACKGROUND: The numbers of airway CD8 and B lymphocytes are increased in COPD patients, suggesting an autoimmune process. CD4-regulatory T cells control autoimmunity but have not been studied in patients with COPD. OBJECTIVE: To compare T-regulatory cell numbers in the BAL from COPD patients, smo...

  19. Collective action : a regulatory focus perspective

    NARCIS (Netherlands)

    Zaal, Maarten Pieter

    2012-01-01

    In this dissertation I investigate how individuals respond to collective disadvantage from the perspective of regulatory focus theory. Regulatory focus theory distinguishes between two motivational systems: promotion focus, the system in charge of the approach of positive end-states, and prevention

  20. 5 CFR 880.102 - Regulatory structure.

    Science.gov (United States)

    2010-01-01

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

  1. 5 CFR 847.102 - Regulatory structure.

    Science.gov (United States)

    2010-01-01

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

  2. 77 FR 47328 - Reducing Regulatory Burden

    Science.gov (United States)

    2012-08-08

    ... health and safety, and other advantages; distributive impacts; and equity). The regulatory process... businesses and the public. Agencies consider low-cost approaches that reduce burdens and maintain flexibility...-regulatory-system . The Department is committed to maintaining a consistent culture of retrospective...

  3. 76 FR 40208 - Regulatory Flexibility Agenda

    Science.gov (United States)

    2011-07-07

    ... Comment Period End 04/04/05 Next Action Undetermined ......... Regulatory Flexibility Analysis Required... FR 10521 NPRM Comment Period End 04/04/05 Next Action Undetermined ......... Regulatory Flexibility... 70 FR 10521 NPRM Comment Period End 04/04/05 Next Action Undetermined ............

  4. Regulatory Competition in Global Financial Markets

    DEFF Research Database (Denmark)

    Ringe, Georg

    2015-01-01

    competition are a reality in today’s global financial market, and the financial sector is different from their traditional fields of application: the ease of arbitrage, the fragility of banking and the risks involved are exceptional. Most importantly, regulatory arbitrage does not or only rarely occurs......The decades-long discussion on the merits of regulatory competition appears in a new light on the global financial market. There are a number of strategies that market participants use to avoid the reach of regulation, in particular by virtue of shifting trading abroad or else relocating activities...... or operations of financial institutions to other jurisdictions. Where this happens, such arbitrage can trigger regulatory competition between jurisdictions that may respond to the relocation of financial services (or threats to relocate) by moderating regulatory standards. Both arbitrage and regulatory...

  5. Adaptive Dynamics of Regulatory Networks: Size Matters

    Directory of Open Access Journals (Sweden)

    2009-03-01

    Full Text Available To accomplish adaptability, all living organisms are constructed of regulatory networks on different levels which are capable to differentially respond to a variety of environmental inputs. Structure of regulatory networks determines their phenotypical plasticity, that is, the degree of detail and appropriateness of regulatory replies to environmental or developmental challenges. This regulatory network structure is encoded within the genotype. Our conceptual simulation study investigates how network structure constrains the evolution of networks and their adaptive abilities. The focus is on the structural parameter network size. We show that small regulatory networks adapt fast, but not as good as larger networks in the longer perspective. Selection leads to an optimal network size dependent on heterogeneity of the environment and time pressure of adaptation. Optimal mutation rates are higher for smaller networks. We put special emphasis on discussing our simulation results on the background of functional observations from experimental and evolutionary biology.

  6. The Political Economy of Regulatory Change

    DEFF Research Database (Denmark)

    Buch-Hansen, Hubert

    2012-01-01

    This article aims to explain the broader evolution of British merger control. To this end it outlines a novel critical political economy perspective on regulation and regulatory change which differs from established political economy approaches, such as the regulatory capitalism/state perspectives......, in three main ways: it places regulatory ideas at the heart of the analysis, it differentiates between different degrees of regulatory change, and it links regulatory change in delineated issue areas with changing power balances between fractions of capital and labor. The application of this perspective...... to the analysis of the evolution of British merger control provides some important new insights, most notably that the content, form, and scope of merger control in Britain have been deeply transformed in accordance with neoliberal ideas since the 1980s and that this process, which was part of a broader...

  7. Adaptive Dynamics of Regulatory Networks: Size Matters

    Directory of Open Access Journals (Sweden)

    Martinetz Thomas

    2009-01-01

    Full Text Available To accomplish adaptability, all living organisms are constructed of regulatory networks on different levels which are capable to differentially respond to a variety of environmental inputs. Structure of regulatory networks determines their phenotypical plasticity, that is, the degree of detail and appropriateness of regulatory replies to environmental or developmental challenges. This regulatory network structure is encoded within the genotype. Our conceptual simulation study investigates how network structure constrains the evolution of networks and their adaptive abilities. The focus is on the structural parameter network size. We show that small regulatory networks adapt fast, but not as good as larger networks in the longer perspective. Selection leads to an optimal network size dependent on heterogeneity of the environment and time pressure of adaptation. Optimal mutation rates are higher for smaller networks. We put special emphasis on discussing our simulation results on the background of functional observations from experimental and evolutionary biology.

  8. The "Post-Post Period" and Environmental Education Research

    Science.gov (United States)

    McKenzie, Marcia

    2005-01-01

    Described as "post-experimental" and of the "post-post period," the current moment in social science research is typified by multi-voiced texts, researcher reflexivity, cultural criticism, and experimental works; characteristics in keeping with post-structurally informed understandings of social science research as contingent, evolving and messy.…

  9. Post-partum pancreatitis.

    Directory of Open Access Journals (Sweden)

    Pai P

    1993-04-01

    Full Text Available Acute pancreatitis in pregnancy and post-partum period, rarely encountered in surgical practice, can have a lethal effect on the mother and the foetus. We report here a case of a 35 year old tertigravida who presented with high grade fever, abdominal pain with distension, tachycardia and tachypnoea. Chest examination and X-rays were suggestive of pneumonia. The abdomen was tense and tender. Peristalsis was absent. Ultrasound revealed presence of fluid in the abdominal cavity which on paracentesis was found to contain Gram positive cocci. Fluid amylase levels were high. On exploratory laparotomy, haemorrhagic oedematous pancreatitis was noticed. The patient expired on the 2nd post operative day.

  10. Post-human Viewing

    DEFF Research Database (Denmark)

    Blaagaard, Bolette

    2013-01-01

    to become part of a global cultural flow, thus calling into question the physical connection between viewer and image. This article analyses what happens to that connection when not only the image but also the physical body is mediated and challenged in post-human relations, and examines the ensuing ethical...... implications. The author takes photojournalism and, in particular, mobile phone footage as a starting point for an exploration of the (post-human) body as evidence and sign of authenticity in the modern age of digital communications and journalism....

  11. Reconstruction of Gene Regulatory Networks Based on Two-Stage Bayesian Network Structure Learning Algorithm

    Institute of Scientific and Technical Information of China (English)

    Gui-xia Liu; Wei Feng; Han Wang; Lei Liu; Chun-guang Zhou

    2009-01-01

    In the post-genomic biology era, the reconstruction of gene regulatory networks from microarray gene expression data is very important to understand the underlying biological system, and it has been a challenging task in bioinformatics. The Bayesian network model has been used in reconstructing the gene regulatory network for its advantages, but how to determine the network structure and parameters is still important to be explored. This paper proposes a two-stage structure learning algorithm which integrates immune evolution algorithm to build a Bayesian network .The new algorithm is evaluated with the use of both simulated and yeast cell cycle data. The experimental results indicate that the proposed algorithm can find many of the known real regulatory relationships from literature and predict the others unknown with high validity and accuracy.

  12. Messenger RNA Fluctuations and Regulatory RNAs Shape the Dynamics of Negative Feedback Loop

    CERN Document Server

    Martínez, María Rodríguez; Tlusty, Tsvi; Pilpel, Yitzhak; Furman, Itay; 10.1103/PhysRevE.81.031924

    2010-01-01

    Single cell experiments of simple regulatory networks can markedly differ from cell population experiments. Such differences arise from stochastic events in individual cells that are averaged out in cell populations. For instance, while individual cells may show sustained oscillations in the concentrations of some proteins, such oscillations may appear damped in the population average. In this paper we investigate the role of RNA stochastic fluctuations as a leading force to produce a sustained excitatory behavior at the single cell level. Opposed to some previous models, we build a fully stochastic model of a negative feedback loop that explicitly takes into account the RNA stochastic dynamics. We find that messenger RNA random fluctuations can be amplified during translation and produce sustained pulses of protein expression. Motivated by the recent appreciation of the importance of non--coding regulatory RNAs in post--transcription regulation, we also consider the possibility that a regulatory RNA transcri...

  13. Multifractal Measure of Post Distribution in Post System

    Institute of Scientific and Technical Information of China (English)

    CHEN Li; HUANG Deng-shi

    2009-01-01

    In order to investigate the true post distribution in the whole society, microelasticity (MIE) and macroelasticity (MAE) were defined by regarding all posts as a system. On this basis, the method for measuring post distribution was proposed. Using the Legendre dual transformation between MIE and MAE to highlight the probabilities of different levels, the post distribution were analyzed hierarchically. The two-scale Cantor model verified that the multifractal measure is applicable to the post distribution evolution process.

  14. 77 FR 34379 - Notice of Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory...

    Science.gov (United States)

    2012-06-11

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Notice of Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission The Federal Energy Regulatory Commission (FERC) and the Nuclear Regulatory...

  15. Regulatory Science in Professional Education.

    Science.gov (United States)

    Akiyama, Hiroshi

    2017-01-01

     In the field of pharmaceutical sciences, the subject of regulatory science (RS) includes pharmaceuticals, food, and living environments. For pharmaceuticals, considering the balance between efficacy and safety is a point required for public acceptance, and in that balance, more importance is given to efficacy in curing disease. For food, however, safety is the most important consideration for public acceptance because food should be essentially free of risk. To ensure food safety, first, any hazard that is an agent in food or condition of food with the potential to cause adverse health effects should be identified and characterized. Then the risk that it will affect public health is scientifically analyzed. This process is called risk assessment. Second, risk management should be conducted to reduce a risk that has the potential to affect public health found in a risk assessment. Furthermore, risk communication, which is the interactive exchange of information and opinions concerning risk and risk management among risk assessors, risk managers, consumers, and other interested parties, should be conducted. Food safety is ensured based on risk analysis consisting of the three components of risk assessment, risk management, and risk communication. RS in the field of food safety supports risk analysis, such as scientific research and development of test methods to evaluate food quality, efficacy, and safety. RS is also applied in the field of living environments because the safety of environmental chemical substances is ensured based on risk analysis, similar to that conducted for food.

  16. Orphan drugs: the regulatory environment.

    Science.gov (United States)

    Franco, Pedro

    2013-02-01

    The definition of a rare disease is not universal and depends on the legislation and policies adopted by each region or country. The main objective of this article is to describe and discuss the legal framework and the regulatory environment of orphan drugs worldwide. Some reflections and discussions on the need for specific orphan drug legislation or policies are described at length. Furthermore, some aspects of the history of each region in respect of the orphan drug legislation evolution are outlined. This article describes and compares the orphan drug legislation or policies of the following countries or regions: United Sates of America (US), European Union (EU), Japan, Australia, Singapore, Taiwan and Canada. The incentives described in the orphan drug legislations or policies, the criteria for designation of orphan status and the authorisation process of an orphan drug are also described and compared. The legislations and policies are to some extent similar but not the same. It is important to understand the main differences among all available legislative systems to improve the international collaboration in the field of orphan drugs and rare diseases.

  17. Tumor eradication after cyclophosphamide depends on concurrent depletion of regulatory T cells: a role for cycling TNFR2-expressing effector-suppressor T cells in limiting effective chemotherapy.

    Science.gov (United States)

    van der Most, Robbert G; Currie, Andrew J; Mahendran, Sathish; Prosser, Amy; Darabi, Anna; Robinson, Bruce W S; Nowak, Anna K; Lake, Richard A

    2009-08-01

    Tumor cell death potentially engages with the immune system. However, the efficacy of anti-tumor chemotherapy may be limited by tumor-driven immunosuppression, e.g., through CD25+ regulatory T cells. We addressed this question in a mouse model of mesothelioma by depleting or reconstituting CD25+ regulatory T cells in combination with two different chemotherapeutic drugs. We found that the efficacy of cyclophosphamide to eradicate established tumors, which has been linked to regulatory T cell depletion, was negated by adoptive transfer of CD25+ regulatory T cells. Analysis of post-chemotherapy regulatory T cell populations revealed that cyclophosphamide depleted cycling (Ki-67(hi)) T cells, including foxp3+ regulatory CD4+ T cells. Ki-67(hi) CD4+ T cells expressed increased levels of two markers, TNFR2 and ICOS, that have been associated with a maximally suppressive phenotype according to recently published studies. This suggest that cyclophosphamide depletes a population of maximally suppressive regulatory T cells, which may explain its superior anti-tumor efficacy in our model. Our data suggest that regulatory T cell depletion could be used to improve the efficacy of anti-cancer chemotherapy regimens. Indeed, we observed that the drug gemcitabine, which does not deplete cycling regulatory T cells, eradicates established tumors in mice only when CD25+ CD4+ T cells are concurrently depleted. Cyclophosphamide could be used to achieve regulatory T cell depletion in combination with chemotherapy.

  18. Registries in European post-marketing surveillance

    DEFF Research Database (Denmark)

    Bouvy, Jacoline C; Blake, Kevin; Slattery, Jim

    2017-01-01

    PURPOSE: Regulatory agencies and other stakeholders increasingly rely on data collected through registries to support their decision-making. Data from registries are a cornerstone of post-marketing surveillance for monitoring the use of medicines in clinical practice. This study was aimed...... for a registry was made as a condition of the marketing authorisation. All centrally authorised products that received a positive opinion of the EMA Committee for Medicinal Products for Human Use between 1 January 2005 and 31 December 2013 were included. Data regarding registry design and experiences were...... registries and 71% of the registries had a primary safety objective. Most commonly reported issues with registries were delayed time to start and low patient accrual rates. CONCLUSIONS: The delays found in getting new registries up and running support the need to improve the timeliness of data collection...

  19. Immune regulation in Chandipura virus infection: characterization of CD4+ T regulatory cells from infected mice

    Directory of Open Access Journals (Sweden)

    Shahir Prajakta

    2011-05-01

    Full Text Available Abstract Back ground Chandipura virus produces acute infection in mice. During infection drastic reduction of CD4+, CD8+ and CD19 + cell was noticed. Depletion of lymphocytes also noticed in spleen. The reduction may be due to the regulatory mechanism of immune system to prevent the bystander host tissue injury. There are several mechanisms like generation of regulatory cells, activation induced cell death (ACID etc were indicated to control the activation and maintain cellular homeostasis. Role of regulatory cells in homeostasis has been described in several viral diseases. This study was undertaken to characterize CD4+T regulatory cells from the infected mice. Method In this study we purified the CD4+ T cells from Chandipura virus infected susceptible Balb/c mice. CD4+ T regulatory cells were identified by expression of cell surface markers CD25, CD127 and CTLA-4 and intracellular markers Foxp3, IL-10 and TGF-beta. Antigen specificity and ability to suppress the proliferation of other lymphocytes were studied in vitro by purified CD4+CD25+T regulatory cells from infected mice. The proliferation was calculated by proliferation module of Flow Jo software. Expression of death receptors on regulatory cells were studied by flowcytometer. Results The CD4+ T cells isolated from infected mice expressed characteristic markers of regulatory phenotype at all post infective hours tested. The CD4+ T regulatory cells were proliferated when stimulated with Chandipura virus antigen. The regulatory cells did not suppress the proliferation of splenocytes stimulated with anti CD3 antibody when co cultured with them. Interesting observation was, while purification of CD4+ T cells by negative selection, the population of cells negative for CD4 also co purified along with CD4+ T cell. Flow cytometry analysis and light microscopy revealed that CD4 negative cells were of different size and shape (atypical compared to the normal lymphocytes. Greater percentage of

  20. Post trauma abdominal cocoon.

    Science.gov (United States)

    Kaur, Supreet; Doley, Rudra Prasad; Chabbhra, Mohinish; Kapoor, Rajeev; Wig, Jaidev

    2015-01-01

    Abdominal cocoon or sclerosing peritonitis refers to a rare cause of intestinal obstruction due to formation of a membrane encasing the bowel. We report a case of abdominal cocoon post blunt trauma abdomen. The patient presented with a history of subacute intestinal obstruction and a mobile abdomen lump. Abdominal cocoon was diagnosed on computed tomography. He underwent adhesiolysis with excision of membrane.

  1. [Post-transfusional AIDS].

    Science.gov (United States)

    Azzini, M; Maccabruni, A; Marcellini, M; Michelone, G; Dei Cas, A

    1987-01-01

    Two cases of post-transfusional AIDS in two premature babies who received blood of the same seropositive donor, are reported. The risk of the susceptibility to HIV infection of these patients, in relation to the immaturity of immune system and to the transfusional treatment often necessary in premature newborns, is stressed.

  2. Teaching Post Keynesian Economics

    DEFF Research Database (Denmark)

    Madsen, Poul Thøis

    2013-01-01

    Denne bog har gør gældende, at post keynesiansk økonomi har sit egen metodiske og didaktiske grundlag, og dens realistisk analyse er tiltrængt i den aktuelle økonomiske og finansielle krise. På et tidspunkt hvor det oprindelige indhold i Keynes 'General Theory ikke længere er til stede i de flest...

  3. Post-duralpunktur hovedpine

    DEFF Research Database (Denmark)

    Dahl, J B; Rosenberg, J

    1990-01-01

    Post dural puncture headache is one of the major complications of spinal anaesthesia. In order to establish this diagnosis, the headache must be dependent on the position of the patient. The symptoms are probably due to leakage of cerebro-spinal fluid from the subarachnoid space to the epidural...

  4. Post Rule of Law

    DEFF Research Database (Denmark)

    Carlson, Kerstin Bree

    2016-01-01

    addresses the practice of hybridity in ICP, drawing examples from the construction and evolution of hybrid procedure at the International Criminal Tribunal for the Former Yugoslavia (ICTY), to argue that the hybridity practiced by international criminal tribunals renders them ‘post rule of law’ institutions...

  5. Teaching Post Keynesian Economics

    DEFF Research Database (Denmark)

    Madsen, Poul Thøis

    2013-01-01

    Denne bog har gør gældende, at post keynesiansk økonomi har sit egen metodiske og didaktiske grundlag, og dens realistisk analyse er tiltrængt i den aktuelle økonomiske og finansielle krise. På et tidspunkt hvor det oprindelige indhold i Keynes 'General Theory ikke længere er til stede i de flest...

  6. 76 FR 72230 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing and Immediate...

    Science.gov (United States)

    2011-11-22

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Adopt a ``Post-Only'' Order Type November 16, 2011. Pursuant to Section 19(b)(1) of the Securities Exchange...

  7. 78 FR 49578 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing and Immediate...

    Science.gov (United States)

    2013-08-14

    ... COMMISSION Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing and Immediate...,\\2\\ notice is hereby given that on August 5, 2013, The NASDAQ Stock Market LLC (``NASDAQ'' or... extensive use of exchange-provided routing facilities and pre- and post-market trading sessions, as compared...

  8. 76 FR 33795 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2011-06-09

    ... filing, the changes will become operative on June 1, 2011. The text of the proposed rule change is... become increasingly irrelevant as a measure of regulatory services required due, among other reasons, to..., please use only one method. The Commission will post all comments on the Commission's Internet Web...

  9. Evolutionary dynamics of prokaryotic transcriptional regulatory networks.

    Science.gov (United States)

    Madan Babu, M; Teichmann, Sarah A; Aravind, L

    2006-04-28

    The structure of complex transcriptional regulatory networks has been studied extensively in certain model organisms. However, the evolutionary dynamics of these networks across organisms, which would reveal important principles of adaptive regulatory changes, are poorly understood. We use the known transcriptional regulatory network of Escherichia coli to analyse the conservation patterns of this network across 175 prokaryotic genomes, and predict components of the regulatory networks for these organisms. We observe that transcription factors are typically less conserved than their target genes and evolve independently of them, with different organisms evolving distinct repertoires of transcription factors responding to specific signals. We show that prokaryotic transcriptional regulatory networks have evolved principally through widespread tinkering of transcriptional interactions at the local level by embedding orthologous genes in different types of regulatory motifs. Different transcription factors have emerged independently as dominant regulatory hubs in various organisms, suggesting that they have convergently acquired similar network structures approximating a scale-free topology. We note that organisms with similar lifestyles across a wide phylogenetic range tend to conserve equivalent interactions and network motifs. Thus, organism-specific optimal network designs appear to have evolved due to selection for specific transcription factors and transcriptional interactions, allowing responses to prevalent environmental stimuli. The methods for biological network analysis introduced here can be applied generally to study other networks, and these predictions can be used to guide specific experiments.

  10. Modeling of hysteresis in gene regulatory networks.

    Science.gov (United States)

    Hu, J; Qin, K R; Xiang, C; Lee, T H

    2012-08-01

    Hysteresis, observed in many gene regulatory networks, has a pivotal impact on biological systems, which enhances the robustness of cell functions. In this paper, a general model is proposed to describe the hysteretic gene regulatory network by combining the hysteresis component and the transient dynamics. The Bouc-Wen hysteresis model is modified to describe the hysteresis component in the mammalian gene regulatory networks. Rigorous mathematical analysis on the dynamical properties of the model is presented to ensure the bounded-input-bounded-output (BIBO) stability and demonstrates that the original Bouc-Wen model can only generate a clockwise hysteresis loop while the modified model can describe both clockwise and counter clockwise hysteresis loops. Simulation studies have shown that the hysteresis loops from our model are consistent with the experimental observations in three mammalian gene regulatory networks and two E.coli gene regulatory networks, which demonstrate the ability and accuracy of the mathematical model to emulate natural gene expression behavior with hysteresis. A comparison study has also been conducted to show that this model fits the experiment data significantly better than previous ones in the literature. The successful modeling of the hysteresis in all the five hysteretic gene regulatory networks suggests that the new model has the potential to be a unified framework for modeling hysteresis in gene regulatory networks and provide better understanding of the general mechanism that drives the hysteretic function.

  11. Regulatory analysis technical evaluation handbook. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-01-01

    The purpose of this Handbook is to provide guidance to the regulatory analyst to promote preparation of quality regulatory analysis documents and to implement the policies of the Regulatory Analysis Guidelines of the US Nuclear Regulatory Commission (NUREG/BR-0058 Rev. 2). This Handbook expands upon policy concepts included in the NRC Guidelines and translates the six steps in preparing regulatory analyses into implementable methodologies for the analyst. It provides standardized methods of preparation and presentation of regulatory analyses, with the inclusion of input that will satisfy all backfit requirements and requirements of NRC`s Committee to Review Generic Requirements. Information on the objectives of the safety goal evaluation process and potential data sources for preparing a safety goal evaluation is also included. Consistent application of the methods provided here will result in more directly comparable analyses, thus aiding decision-makers in evaluating and comparing various regulatory actions. The handbook is being issued in loose-leaf format to facilitate revisions. NRC intends to periodically revise the handbook as new and improved guidance, data, and methods become available.

  12. Regulatory focus and the assignment of punishment

    Directory of Open Access Journals (Sweden)

    Chloe Carmichael

    2007-06-01

    Full Text Available Regulatory Focus has been demonstrated to influence human behavior in a number of domains, such as object valuation and readiness to commit time or money to social projects. It has also been demonstrated to influence an individual’s approach to mistakes; and a person’s preference for global or local processing of information. The present work seeks to consider how regulatory focus might interact with punitive behaviors, specifically, the assignment of legal punishment. In this study, 240 undergraduates completed a series of written instruments that assessed their regulatory focus. They read a vignette that described a target that commits a crime, is detected by the police, and is arrested due to a careless mistake. Participants were asked what level of legal punishment they deemed appropriate. Participants’ punitive evaluations show that there are significant interactions a between the regulatory focus of the participant and the regulatory focus of the target and b between the regulatory focus of the participant and the level of detail used to describe the target and her behavior. In each case, when the regulatory foci matched, causing ‘fit,’ the participant was more lenient than in the non-fit condition.

  13. Finanical Instability, Regulatory Reforms and Bank Governance - Lessons from the East-Asian Financial Crisis

    OpenAIRE

    Srinivas Yanamandra

    2013-01-01

    Purpose – The purpose of this research project is to explore the research question – how does the pursuit of agenda of regulatory reforms, post the crisis, influence governance arrangements at banks and assist them in maintaining resilience during subsequent episodes of crises?Research methodology – The project adopts a comparative case study approach involving a mixture of review of secondary resources and fieldwork interviews across East Asian nations. Findings – The project applied the Min...

  14. FINANCIAL INSTABILITY, REGULATORY REFORMS AND BANK GOVERNANCE - LESSONS FROM THE EAST-ASIAN FINANCIAL CRISIS

    OpenAIRE

    Yanamandra, Srinivas

    2013-01-01

    Purpose – The purpose of this research project is to explore the research question – how does the pursuit of agenda of regulatory reforms, post the crisis, influence governance arrangements at banks and assist them in maintaining resilience during subsequent episodes of crises?Research methodology – The project adopts a comparative case study approach involving a mix of review of secondary resources and fieldwork interviews across East Asian nations. Findings – The project applied the Minskia...

  15. 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

  16. 77 FR 59702 - Promoting U.S. EC Regulatory Compatibility

    Science.gov (United States)

    2012-09-28

    ... Promoting U.S. EC Regulatory Compatibility AGENCY: Office of the United States Trade Representative. ACTION... greater transatlantic regulatory compatibility generally. Concrete ideas on how greater compatibility... and EC invite your views on how to promote greater transatlantic regulatory compatibility...

  17. Regulatory bioinformatics for food and drug safety.

    Science.gov (United States)

    Healy, Marion J; Tong, Weida; Ostroff, Stephen; Eichler, Hans-Georg; Patak, Alex; Neuspiel, Margaret; Deluyker, Hubert; Slikker, William

    2016-10-01

    "Regulatory Bioinformatics" strives to develop and implement a standardized and transparent bioinformatic framework to support the implementation of existing and emerging technologies in regulatory decision-making. It has great potential to improve public health through the development and use of clinically important medical products and tools to manage the safety of the food supply. However, the application of regulatory bioinformatics also poses new challenges and requires new knowledge and skill sets. In the latest Global Coalition on Regulatory Science Research (GCRSR) governed conference, Global Summit on Regulatory Science (GSRS2015), regulatory bioinformatics principles were presented with respect to global trends, initiatives and case studies. The discussion revealed that datasets, analytical tools, skills and expertise are rapidly developing, in many cases via large international collaborative consortia. It also revealed that significant research is still required to realize the potential applications of regulatory bioinformatics. While there is significant excitement in the possibilities offered by precision medicine to enhance treatments of serious and/or complex diseases, there is a clear need for further development of mechanisms to securely store, curate and share data, integrate databases, and standardized quality control and data analysis procedures. A greater understanding of the biological significance of the data is also required to fully exploit vast datasets that are becoming available. The application of bioinformatics in the microbiological risk analysis paradigm is delivering clear benefits both for the investigation of food borne pathogens and for decision making on clinically important treatments. It is recognized that regulatory bioinformatics will have many beneficial applications by ensuring high quality data, validated tools and standardized processes, which will help inform the regulatory science community of the requirements

  18. Dissecting the brown adipogenic regulatory network using integrative genomics

    Science.gov (United States)

    Pradhan, Rachana N.; Bues, Johannes J.; Gardeux, Vincent; Schwalie, Petra C.; Alpern, Daniel; Chen, Wanze; Russeil, Julie; Raghav, Sunil K.; Deplancke, Bart

    2017-01-01

    Brown adipocytes regulate energy expenditure via mitochondrial uncoupling, which makes them attractive therapeutic targets to tackle obesity. However, the regulatory mechanisms underlying brown adipogenesis are still poorly understood. To address this, we profiled the transcriptome and chromatin state during mouse brown fat cell differentiation, revealing extensive gene expression changes and chromatin remodeling, especially during the first day post-differentiation. To identify putatively causal regulators, we performed transcription factor binding site overrepresentation analyses in active chromatin regions and prioritized factors based on their expression correlation with the bona-fide brown adipogenic marker Ucp1 across multiple mouse and human datasets. Using loss-of-function assays, we evaluated both the phenotypic effect as well as the transcriptomic impact of several putative regulators on the differentiation process, uncovering ZFP467, HOXA4 and Nuclear Factor I A (NFIA) as novel transcriptional regulators. Of these, NFIA emerged as the regulator yielding the strongest molecular and cellular phenotypes. To examine its regulatory function, we profiled the genomic localization of NFIA, identifying it as a key early regulator of terminal brown fat cell differentiation. PMID:28181539

  19. Delegation to Independent Regulatory Authorities in the Media Sector: A Paradigm Shift through the Lens of Regulatory Theory

    NARCIS (Netherlands)

    K. Irion; R. Radu

    2014-01-01

    Today, it seems that independent regulatory authorities have almost become a natural institutional form for regulatory governance. This trend has economic and political roots, and numerous normative arguments for creating independent regulatory authorities have been put forward in the international

  20. Comparative Analysis of Regulatory Motif Discovery Tools for Transcription Factor Binding Sites

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In the post-genomic era, identification of specific regulatory motifs or transcription factor binding sites (TFBSs) in non-coding DNA sequences, which is essential to elucidate transcriptional regulatory networks, has emerged as an obstacle that frustrates many researchers. Consequently, numerous motif discovery tools and correlated databases have been applied to solving this problem. However, these existing methods, based on different computational algorithms, show diverse motif prediction efficiency in non-coding DNA sequences. Therefore, understanding the similarities and differences of computational algorithms and enriching the motif discovery literatures are important for users to choose the most appropriate one among the online available tools. Moreover, there still lacks credible criterion to assess motif discovery tools and instructions for researchers to choose the best according to their own projects. Thus integration of the related resources might be a good approach to improve accuracy of the application. Recent studies integrate regulatory motif discovery tools with experimental methods to offer a complementary approach for researchers, and also provide a much-needed model for current researches on transcriptional regulatory networks. Here we present a comparative analysis of regulatory motif discovery tools for TFBSs.

  1. Data Integrity-A Study of Current Regulatory Thinking and Action.

    Science.gov (United States)

    Shafiei, Nader; De Montardy, Regis; Rivera-Martinez, Edwin

    2015-01-01

    In reaction to breaches of data integrity in the pharmaceutical industry, regulatory authorities have introduced inspection approaches or initiatives with the aim of reducing occurrences of data integrity problems. This review article-based on study of 65 cases of regulatory action from 2002 to 2014-provides an overview of current regulatory thinking and action on breaches of data integrity affecting GxP (health-related regulations) processes supporting non-clinical studies, clinical studies, laboratory controls, and production controls. These case studies largely represent position of the U.S. Food and Drug Administration and the regulatory agencies affiliated with the European Medicines Agency. Also discussed is the role of human factors as a potential source of data integrity problems. The article concludes by recommending some remedial controls that could be established to avoid or reduce occurrences of data integrity problems.Lay Abstract: In fulfilling their mission to protect public health, regulatory agencies (e.g., U.S. Food and Drug Administration, European Medicines Agency) must establish confidence that medical products they approve are fit for their intended use. In so doing they rely on scientific and operational data generated during research, development, manufacturing, sales, marketing, distribution, and post-marketing surveillance activities. The level of confidence they build is directly proportional to the scientific validity and integrity of data presented to them by the sponsors of medical products. In this article we present analysis of 65 case studies that document regulatory action taken by various regulatory agencies on breach of data integrity between 2002 and 2014. The ensuing discussion on current trends largely represents position of the U.S. Food and Drug Administration and European Medicines Agency. The article concludes by proposing some remedial controls that could be established by pharmaceutical companies to avoid or reduce

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

    Science.gov (United States)

    Chen, Xiaowei Sylvia; Brown, Chris M

    2012-10-01

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

  3. 78 FR 44331 - Semiannual Regulatory Agenda

    Science.gov (United States)

    2013-07-23

    ... programs as vital tools for creating and preserving American jobs. SBA proposes to strip away regulatory... 500-employee based size standard for NAICS 113310, Logging, but will review it in the near future...

  4. Systemic Risk and Optimal Regulatory Architecture

    NARCIS (Netherlands)

    Espinosa-Vega, M.A.; Kahn, C.; Matta, R.; Sole, J.

    2011-01-01

    Until the recent financial crisis, the safety and soundness of financial institutions was assessed from the perspective of the individual institution. The financial crisis highlighted the need to take systemic externalities seriously when rethinking prudential oversight and the regulatory architectu

  5. Electricity distribution networks: Changing regulatory approaches

    Science.gov (United States)

    Cambini, Carlo

    2016-09-01

    Increasing the penetration of distributed generation and smart grid technologies requires substantial investments. A study proposes an innovative approach that combines four regulatory tools to provide economic incentives for distribution system operators to facilitate these innovative practices.

  6. Safety & Regulatory Strategy : Food Safety and Innovation

    NARCIS (Netherlands)

    Kalk, C.

    2013-01-01

    Food and feed safety is strictly regulated within the EU. Our team of toxicologists, risk assessors and consultants offers strategic advice and valuable expertise in regulatory affairs and health risk assessment.

  7. A study of bacterial gene regulatory mechanisms

    DEFF Research Database (Denmark)

    Hansen, Sabine

    the different regulatory mechanisms affect system dynamics. We have designed a synthetic gene regulatory network (GRN) in bacterial cells that enables us to study the dynamics of GRNs. The results presented in this PhD thesis show that model equations based on the established mechanisms of action of each...... of a particular type of regulatory mechanism. The synthetic system presented in this thesis is, to our knowledge, the first of its kind to allow a direct comparison of the dynamic behaviors of gene regulatory networks that employ different mechanisms of regulation. In addition to studying the dynamic behavior...... of GRNs this thesis also provided the first evidence of the sensor histidine kinase VC1831 being an additional player in the Vibrio cholerae quorum sensing (QS) GRN. Bacteria use a process of cell-cell communication called QS which enable the bacterial cells to collectively control their gene expression...

  8. 77 FR 58975 - Pennsylvania Regulatory Program

    Science.gov (United States)

    2012-09-25

    ... the Pennsylvania statutory scheme via Pennsylvania's Solid Waste Management Act (``SWMA''), the Clean... Office of Surface Mining Reclamation and Enforcement 30 CFR Part 938 Pennsylvania Regulatory Program AGENCY: Office of Surface Mining Reclamation and Enforcement (OSM), Interior. ] ACTION: Proposed rule...

  9. The Political Communication of Independent Regulatory Agencies

    National Research Council Canada - National Science Library

    Puppis, Manuel; Maggetti, Martino; Gilardi, Fabrizio; Biela, Jan; Papadopoulos, Yannis

    2014-01-01

    .... In this context, public communication plays an important role. On the one hand, regulatory agencies might try to use communication to raise their accountability and thereby to mitigate their democratic deficit...

  10. Modernizing the Regulatory System for Biotechnology Products

    Science.gov (United States)

    This Web page describes the continuing effort to modernize the federal regulatory system for biotechnology products as well as clarify various roles of EPA, FDA and USDA in evaluating new biotechnology products.

  11. Mobile Source Emissions Regulatory Compliance Data Inventory

    Data.gov (United States)

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

  12. Communication from La Poste

    CERN Multimedia

    2005-01-01

    We should like to remind users that post sent to the CERN site must be correctly addressed in order to reach the right destination as quickly as possible: Correspondence (goods subject to Swiss VAT): Surname, first name CERN (Department, Building & Mailbox) Route de Meyrin 385 Case Postale 1211 Genève 23 CERN (Switzerland) Official orders (goods not subject to Swiss VAT): CERN Goods Reception Order number ( Ca, Ct, Cl....) For the attention of: (surname, first name) Route de Meyrin 385 Case Postale 1211 Genève 23 CERN (Switzerland) Please inform your suppliers of the above addresses. Last minute Swiss motorway sticker on sale at the POST OFFICE, Main Building (63 R 02) 40.- CHF

  13. Communication from La Poste

    CERN Multimedia

    2005-01-01

    We should like to remind users that post sent to the CERN site must be correctly addressed in order to reach the right destination as quickly as possible: Correspondence (goods subject to Swiss VAT): Surname, first name CERN (Department, Building & Mailbox) Route de Meyrin 385 Case Postale 1211 Genève 23 CERN (Switzerland) Official orders (goods not subject to Swiss VAT): CERN Goods Reception Order number ( Ca, Ct, Cl....) For the attention of: (surname, first name) Route de Meyrin 385 Case Postale 1211 Genève 23 CERN (Switzerland) Please inform your suppliers of the above addresses. Last minute Swiss motorway sticker on sale at the POST OFFICE, Main Building (63 R 02) 40.- CHF

  14. Post trauma abdominal cocoon

    Directory of Open Access Journals (Sweden)

    Supreet Kaur

    2015-01-01

    Full Text Available Abdominal cocoon or sclerosing peritonitis refers to a rare cause of intestinal obstruction due to formation of a membrane encasing the bowel. We report a case of abdominal cocoon post blunt trauma abdomen. The patient presented with a history of subacute intestinal obstruction and a mobile abdomen lump. Abdominal cocoon was diagnosed on computed tomography. He underwent adhesiolysis with excision of membrane.

  15. Post-ATC Reviews

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ Guatemala City,a most populous and prosperous metropolitan in Central America,was once again an eye-catcher for hosting for the second time,on April 16-19,the Council of Representatives'meeting of International Textile andClothing Bureau(ITCB)at the time when it has been already two years post the Agreement on Textiles and Clothing (ATC).

  16. Post-thyroidectomy hemorrhage

    DEFF Research Database (Denmark)

    Godballe, Christian; Madsen, Anders Rørbaek; Pedersen, Henrik Baymler;

    2009-01-01

    risk factors for hemorrhage. Increased hospital stay and infection rates were found in patients treated with drainage. The median time for onset of postoperative hemorrhage was 3 h (range 0-105). Compared with international literature our incidence of post-thyroidectomy hemorrhage is relatively high....... Improvement might be reached by the exchange of experience between departments with focus on adequate surgical technique and careful hemostasis....

  17. Síndrome post

    OpenAIRE

    Avalos, Raquel

    2014-01-01

    ¿Qué sigue luego de que una mujer terminara su relación con el último hombre que amaba? Eso, dicen ellas, depende de cuanto duró el romance o cómo sea la psiquis de cada amante. Lo cierto es que el escenario post convierte a algunas en depresivas, caletas, indiferentes y hasta amnésicas. ¿Qué te parece, varón?

  18. IPTV Market Development and Regulatory Aspects

    DEFF Research Database (Denmark)

    Tadayoni, Reza; Sigurdsson, Halldór Matthias

    2006-01-01

    The aim of this paper is to analyse the development of IPTV technology / market and to discuss major regulatory parameters. A general overview of architectures and the technologies deployed for establishing IPTV services is given and the main stake holder identified, along with, the current service...... architecture, the available content in IPTV platforms, and the current business models. Furthermore the regulatory framework of the TV broadcast and IPTV in Europe is analysed....

  19. Measuring Regulatory Restrictions in Logistics Services

    OpenAIRE

    Claire HOLLWEG; Marn-Heong WONG

    2009-01-01

    This study measures the extent of restrictions on trade in logistics services in the ASEAN+6 economies by constructing a logistics regulatory restrictiveness index for each economy that quantifies the extent of government regulations faced by logistics service providers. This is the first study of its kind to construct a regulatory index of the entire logistics sector, which includes the main modes of international transport and customs restrictions. The indices show that large differences ex...

  20. Mission Risk Reduction Regulatory Change Management

    Science.gov (United States)

    Scroggins, Sharon

    2007-01-01

    NASA Headquarters Environmental Management Division supports NASA's mission to pioneer the future in space exploration, scientific discovery, and aeronautics research by integrating environmental considerations into programs and projects early-on, thereby proactively reducing NASA's exposure to institutional, programmatic and operational risk. As part of this effort, NASA established the Principal Center for Regulatory Risk Analysis and Communication (RRAC PC) as a resource for detecting, analyzing, and communicating environmental regulatory risks to the NASA stakeholder community. The RRAC PC focuses on detecting emerging environmental regulations and other operational change drivers that may pose risks to NASA programs and facilities, and effectively communicating the potential risks. For example, regulatory change may restrict how and where certain activities or operations may be conducted. Regulatory change can also directly affect the ability to use certain materials by mandating a production phase-out or restricting usage applications of certain materials. Regulatory change can result in significant adverse impacts to NASA programs and facilities due to NASA's stringent performance requirements for materials and components related to human-rated space vehicles. Even if a regulation does not directly affect NASA operations, U.S. and international regulations can pose program risks indirectly through requirements levied on manufacturers and vendors of components and materials. For example, manufacturers can change their formulations to comply with new regulatory requirements. Such changes can require time-consuming and costly requalification certification for use in human spaceflight programs. The RRAC PC has implemented a system for proactively managing regulatory change to minimize potential adverse impacts to NASA programs and facilities. This presentation highlights the process utilized by the RRACPC to communicate regulatory change and the associated

  1. A unified architecture of transcriptional regulatory elements

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  2. ATMPs for Cancer Immunotherapy: A Regulatory Overview.

    Science.gov (United States)

    Galli, Maria Cristina

    2016-01-01

    This chapter discusses European regulatory requirements for development of advanced therapy medicinal products (ATMP) for cancer immunotherapy approaches, describing the framework for clinical trials and for marketing authorization.Regulatory critical issues and challenges for developing ATMP are also discussed, with focus on potency determination, long-term follow-up, comparability, and insertional mutagenesis issues. Some of the most critical features of GMP application to ATMP are also described.

  3. LHC support post

    CERN Multimedia

    1995-01-01

    LHC support post prototype, which dates in 1995, in a long development period which started in the early ’90s and continued until the end of the decade. The wires next to the support post are probably wires from strain gauges, which are employed to measure the stress level in the material when the support is mechanically loaded. These supports are mechanically optimized to withstand a weight of up to 100Kn (10 tons) while being as thin as possible to minimize conduction heat to magnets. This is the reason why the stress measurement was extensively done in the prototyping phase. About support posts: The high magnetic fields needed for the LHC can only be reached using superconductors. At very low temperatures, superconductors have no electrical resistance and therefore no power loss. The LHC will be the largest superconducting installation ever built and, at 1.9 degrees above absolute zero (300 degrees below room temperature), one of the the coldest objects in the universe! The magnet supports have to brid...

  4. Cis-regulatory mutations in human disease.

    Science.gov (United States)

    Epstein, Douglas J

    2009-07-01

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

  5. 78 FR 38739 - Standard Format and Content for Post-Shutdown Decommissioning Activities Report

    Science.gov (United States)

    2013-06-27

    ..., DG-1272, in the Federal Register on December 19, 2012 (77 FR 75198), for a 60-day public comment... COMMISSION Standard Format and Content for Post-Shutdown Decommissioning Activities Report AGENCY: Nuclear... (NRC) is issuing Revision 1 of Regulatory Guide (RG) 1.185, ``Standard Format and Content for...

  6. 76 FR 48841 - PJM Interconnection, L.L.C.; Notice Establishing Post-Technical Comment Period

    Science.gov (United States)

    2011-08-09

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission PJM Interconnection, L.L.C.; Notice Establishing Post-Technical Comment Period As indicated in the June 21, 2011 Notice in this docket, comments on the technical conference...

  7. 75 FR 61478 - Mandatory Reliability Standards for the Bulk Power System; Notice Allowing Post-Technical...

    Science.gov (United States)

    2010-10-05

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Mandatory Reliability Standards for the Bulk Power System; Notice Allowing Post-Technical Conference Comments September 24, 2010. On September 23, 2010, the Federal...

  8. 77 FR 14773 - PostRock KPC Pipeline, LLC; Notice of Technical Conference

    Science.gov (United States)

    2012-03-13

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission PostRock KPC Pipeline, LLC; Notice of Technical Conference Take notice that the Commission will convene a technical conference on Tuesday, March 27, 2012, at 10:30 a.m. (EDT), in a room to be designated at the offices...

  9. Freedom of Contract in the Post-Crisis Era: Quo Vadis?

    NARCIS (Netherlands)

    Cherednychenko, O.O.

    2014-01-01

    This article explores to what extent the future development of European financial services contract law will be determined by the information paradigm in the post-crisis era. By using the examples from the field of investment services and consumer credit, it shows that the regulatory measures

  10. KWOC (Key-Word-Out-of-Context) Index of US Nuclear Regulatory Commission Regulatory Guide Series

    Energy Technology Data Exchange (ETDEWEB)

    Jennings, S.D.

    1990-04-01

    To meet the objectives of the program funded by the Department of Energy (DOE)-Nuclear Energy (NE) Technology Support Programs, the Performance Assurance Project Office (PAPO) administers a Performance Assurance Information Program that collects, compiles, and distributes program-related information, reports, and publications for the benefit of the DOE-NE program participants. THE KWOC Index of US Nuclear Regulatory Commission Regulatory Guide Series'' is prepared as an aid in searching for specific topics in the US Nuclear Regulatory Commission, Regulatory Guide Series.

  11. Regulatory T cells ameliorate tissue plasminogen activator-induced brain haemorrhage after stroke.

    Science.gov (United States)

    Mao, Leilei; Li, Peiying; Zhu, Wen; Cai, Wei; Liu, Zongjian; Wang, Yanling; Luo, Wenli; Stetler, Ruth A; Leak, Rehana K; Yu, Weifeng; Gao, Yanqin; Chen, Jun; Chen, Gang; Hu, Xiaoming

    2017-07-01

    Delayed thrombolytic treatment with recombinant tissue plasminogen activator (tPA) may exacerbate blood-brain barrier breakdown after ischaemic stroke and lead to lethal haemorrhagic transformation. The immune system is a dynamic modulator of stroke response, and excessive immune cell accumulation in the cerebral vasculature is associated with compromised integrity of the blood-brain barrier. We previously reported that regulatory T cells, which function to suppress excessive immune responses, ameliorated blood-brain barrier damage after cerebral ischaemia. This study assessed the impact of regulatory T cells in the context of tPA-induced brain haemorrhage and investigated the underlying mechanisms of action. The number of circulating regulatory T cells in stroke patients was dramatically reduced soon after stroke onset (84 acute ischaemic stroke patients with or without intravenous tPA treatment, compared to 115 age and gender-matched healthy controls). Although stroke patients without tPA treatment gradually repopulated the numbers of circulating regulatory T cells within the first 7 days after stroke, post-ischaemic tPA treatment led to sustained suppression of regulatory T cells in the blood. We then used the murine suture and embolic middle cerebral artery occlusion models of stroke to investigate the therapeutic potential of adoptive regulatory T cell transfer against tPA-induced haemorrhagic transformation. Delayed administration of tPA (10 mg/kg) resulted in haemorrhagic transformation in the ischaemic territory 1 day after ischaemia. When regulatory T cells (2 × 106/mouse) were intravenously administered immediately after delayed tPA treatment in ischaemic mice, haemorrhagic transformation was significantly decreased, and this was associated with improved sensorimotor functions. Blood-brain barrier disruption and tight junction damages were observed in the presence of delayed tPA after stroke, but were mitigated by regulatory T cell transfer. Mechanistic

  12. Post-Cruise Questionnaire - Legacy

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Post-Cruise Questionnaire is a mandatory post trip legal document that observers fill out after every trip they have completed.

  13. Post-Cruise Questionnaire - Legacy

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Post-Cruise Questionnaire is a mandatory post trip legal document that observers fill out after every trip they have completed.

  14. 12 CFR 914.1 - Regulatory Report defined.

    Science.gov (United States)

    2010-01-01

    ... Bank. (b) Examples. Regulatory Report includes: (1) Call reports and reports of instrument-level risk... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Regulatory Report defined. 914.1 Section 914.1... DATA AVAILABILITY AND REPORTING § 914.1 Regulatory Report defined. (a) Definition. Regulatory...

  15. 75 FR 20868 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2010-04-21

    ... Issuance and Availability of Regulatory Guide 1.68.2, Revision 2, ``Initial Startup Test Program to... review of applications for permits and licenses. Revision 2 of Regulatory Guide 1.68.2, ``Initial Startup... Regulatory Guide 1.68.2, Revision 2 are available through the NRC's public Web site under ``Regulatory...

  16. 10 CFR 1.45 - Office of Nuclear Regulatory Research.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Office of Nuclear Regulatory Research. 1.45 Section 1.45... Program Offices § 1.45 Office of Nuclear Regulatory Research. The Office of Nuclear Regulatory Research— (a) Plans, recommends, and implements programs of nuclear regulatory research, standards development...

  17. [Post-stripping telangiectasis].

    Science.gov (United States)

    Hutinel, B; Maraval, M

    1985-01-01

    These telangiectasia appear between one and six months after the operation, especially in cases of capillary fragility. The most common localizations are the antero-internal and external sides of the thighs and knees. Unnecessary strippings, of continent saphenous veins, are the most frequent cause of these. Their prevention consists of the least possible traumatising stripping, using a fine stripper, a very rigorous post-operative support, and the wearing of light varicose stockings or tights for between one and three months. The treatment using microsclerosis, often delicate, should not be undertaken before six months.

  18. Post-tonsillectomy hemorrhage

    DEFF Research Database (Denmark)

    Heidemann, Christian; Wallén, Mia; Aakesson, Marie;

    2008-01-01

    Post-tonsillectomy hemorrhage (PTH) is a relatively common and potentially life-threatening complication. The objective of this study was to examine the rate of PTH and identify risk factors. A retrospective cohort study was carried out including all tonsillectomies (430 patients) performed...... as surgical technique" [relative risk (RR) = 5.3], "peritonsillar abscess as indication for surgery" (RR = 0.3) and "age equal to or above 15 years at the time of surgery" (RR = 5.4). It is concluded that patient age, PTA as indication for surgery and the use of coblation significantly affect the occurrence...

  19. Perioperative post graduate education.

    Science.gov (United States)

    Kapnoullas, J

    1997-04-01

    This article describes post-graduate perioperative education in Australia at the Australian Catholic University and St. Vincent's Public Hospital: The Graduate Certificate in Perioperative Practice. The Australian Catholic University operates from eight campuses along the east coast of Australia. There are approximately 9000 students along with 1000 staff. The University consists of major faculties that all have clear relevance to the workplace-namely Arts and Sciences, Education and Health Sciences. Qualifications are offered at Certificate of Doctoral level studies in the areas of business, education, ethics, human movement, management, information systems, music, nursing, religion, social work and theology.

  20. Searching for New Regulatory Frameworks for the Intermediate Financial Structure in Post-Crisis Asia

    OpenAIRE

    Sayuri Shirai

    2001-01-01

    Intermediate Financial Structure 1. In a number of Asian countries, commercial banks are already playing an important role in the corporate bond market as issuers, underwriters, investors, and guarantors. This reflects banks’ already dominant financial positions in their financial markets, good reputation, and informational advantages. Thus, the role of banks for fostering the development of the corporate bond market and their complementary roles should be encouraged. 2. This financial landsc...

  1. 78 FR 40776 - Issuance of Regulatory Guide 1.124 and Regulatory Guide 1.130

    Science.gov (United States)

    2013-07-08

    ...) Boiler and Pressure Vessel Code (B&PVC). Regulatory Guides 1.124 and 1.130 delineates levels of service... 2008 Addenda of the Boiler and Pressure Vessel Code (ASME B&PV Code), Section III, Division 1 (limited... Improvement of Regulatory Guides The NRC typically seeks public comment on a draft version of a...

  2. 76 FR 64419 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-10-18

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Revise the Series 7 Examination Program September...

  3. 78 FR 3925 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2013-01-17

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of Proposed Rule Change Relating to Amendments to the Customer and Industry Codes of Arbitration Procedure To... proposing to amend the Customer and Industry Codes of Arbitration Procedure (``Codes'') to revise the...

  4. 75 FR 42795 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2010-07-22

    ... Disputes (``Customer Code'') and Rule 13602 of the Code of Arbitration Procedure for Industry Disputes (``Industry Code'') (collectively, the ``Codes'') to provide that a non-party witness may be represented by an... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

  5. 77 FR 74712 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2012-12-17

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change To Amend the Customer and Industry Codes of Arbitration Procedure Relating to... and Industry Codes of Arbitration Procedure (collectively, the ``Codes'') (1) to provide that when...

  6. 75 FR 7297 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2010-02-18

    ... Arbitration Procedure for Industry Disputes (``Industry Code'') (together, the ``Codes'') to clarify the... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change To Amend the Postponement Fee and Hearing Session Fee Rules of the Codes of...

  7. 75 FR 8169 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2010-02-23

    ... the Code of Arbitration Procedure for Industry Disputes (``Industry Code'') (together, ``Codes'') to... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of Proposed Rule Change To Amend the Codes of Arbitration Procedure To Provide for Attorney Representation of...

  8. 75 FR 52380 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2010-08-25

    ...-2010-044] Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of Proposed Rule Change Relating to the Expansion of the Order Audit Trail System to All NMS...\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on August 6, 2010, the Financial...

  9. 78 FR 62417 - Regulatory Capital Rules: Regulatory Capital, Implementation of Basel III, Capital Adequacy...

    Science.gov (United States)

    2013-10-22

    ... Part 324 RIN 3064-AD95 Regulatory Capital Rules: Regulatory Capital, Implementation of Basel III, Capital Adequacy, Transition Provisions, Prompt Corrective Action, Standardized Approach for Risk-Weighted Assets, Market Discipline and Disclosure Requirements, Advanced Approaches Risk-Based Capital Rule,...

  10. The foreign experience of regulatory reform implementation and application of «regulatory guillotine»

    Directory of Open Access Journals (Sweden)

    N. M. Litvinova

    2014-09-01

    Full Text Available The foreign experience of regulatory reform implementation is considered. Particular attention is paid to the experience gained and the results of the use of “regulatory guillotine” as one of the kinds of regulatory reforms. The authors analyze the main preconditions and results of regulatory reforms and their impact on improved governance, creation of favorable conditions for business development, creating a positive investment climate. A certain degree of regulatory reform has become the standard for developed markets and for developing countries and are trying to take their place on stage one of the most developed countries. Study abroad experience in regulatory reforms in different countries of the world leads to the conclusion that the foundation for regulatory reform is a special system development and adoption of a special kind of legal acts - regulations. Unlike most legal acts, regulations, at the stage of the project should be accompanied by assessment or regulatory impact analysis, which provides comprehensive information about the possible positive or negative effects of the introduction of state regulation. Such adjustment shall be taken only when the overall benefits of regulation dominate the total cost of its implementation. The authors provide recommendations on the use of foreign experience in Ukraine

  11. 77 FR 8034 - Semiannual Regulatory Agenda and Fiscal Year 2011 Regulatory Plan

    Science.gov (United States)

    2012-02-13

    ... February 13, 2012 Part XXI Bureau of Consumer Financial Protection Semiannual Regulatory Agenda #0;#0;Federal Register / Vol. 77 , No. 29 / Monday, February 13, 2012 / Unified Agenda#0;#0; ] BUREAU OF CONSUMER FINANCIAL PROTECTION 12 CFR Ch. X Semiannual Regulatory Agenda and Fiscal Year 2011...

  12. 78 FR 37267 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2013-06-20

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... 1934 (``Act'') \\1\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on June 3, 2013, Financial... the mandatory inclusion of a non- public arbitrator in a three-arbitrator case raised a...

  13. 76 FR 9838 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2011-02-22

    ... Arbitration Procedure for Industry Disputes (``Industry Code'') to provide that FINRA will appoint a chair... procedures leads FINRA to propose amending the Industry Code to provide that FINRA will appoint a chair... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

  14. 75 FR 41262 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2010-07-15

    ... Arbitration Procedure for Industry Disputes (``Industry Code'') to increase ] the number of arbitrators on.... FINRA also proposed to amend Rule 13403 of the Industry Code to expand the number of arbitrators on... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

  15. 76 FR 20741 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

    Science.gov (United States)

    2011-04-13

    ... the Code of Arbitration Procedure for Industry Disputes (``Industry Code'') to provide that FINRA will... procedures led FINRA to propose amending the Industry Code to provide that FINRA will appoint a chair... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

  16. 75 FR 29594 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2010-05-26

    ... 13404 of the Code of Arbitration Procedure for Industry Disputes (``Industry Code'') to increase the... the Industry Code to expand the number of arbitrators on lists generated through NLSS.\\8\\ For disputes...-2010-022] Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

  17. [Post-abortion contraception].

    Science.gov (United States)

    Ohannessian, A; Jamin, C

    2016-12-01

    To establish guidelines of the French National College of Gynecologists and Obstetricians about post-abortion contraception. A systematic review of the literature about post-abortion contraception was performed on Medline and Cochrane Database between 1978 and March 2016. The guidelines of the French and foreign scientific societies were also consulted. After an abortion, if the woman wishes to use a contraception, it should be started as soon as possible because of the very early ovulation resumption. The contraception choice must be done in accordance with the woman's expectations and lifestyle. The contraindications of each contraception must be respected. The long-acting reversible contraception, intra-uterine device (IUD) and implant, could be preferred (grade C) as the efficacy is not dependent on compliance. Thus, they could better prevent repeat abortion (LE3). In case of surgical abortion, IUD should be proposed and inserted immediately after the procedure (grade A), as well as the implant (grade B). In case of medical abortion, the implant can be inserted from the day of mifépristone, the IUD after an ultrasound examination confirming the success of the abortion (no continuing pregnancy or retained sac) (grade C). Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. Shared consultant physician posts.

    LENUS (Irish Health Repository)

    Cooke, J

    2012-01-31

    Our aim was to assess the acceptability and cost-efficiency of shared consultancy posts. Two consultant physicians worked alternate fortnights for a period of twelve months. Questionnaires were distributed to general practitioners, nurses, consultants and junior doctors affected by the arrangement. Patients or their next of kin were contacted by telephone. 1\\/17 of consultants described the experience as negative. 14\\/19 junior doctors reported a positive experience. 11 felt that training had been improved while 2 felt that it had been adversely affected. 17\\/17 GPs were satisfied with the arrangement. 1\\/86 nurses surveyed reported a negative experience. 1\\/48 patients were unhappy with the arrangement. An extra 2.2 (p<0.001) patients were seen per clinic. Length of stay was shortened by 2.49 days (p<0.001). A saving of 69,212 was made due to decreased locum requirements. We present data suggesting structured shared consultancy posts can be broadly acceptable and cost efficient in Ireland.

  19. [Post-traumatic tics].

    Science.gov (United States)

    Alegre, S; Chacón, J; Redondo, L; Navarro-Busto, C; Solana, B

    1996-10-01

    Secondary tics are those in which an aetiology justifying them can be found, as compared to idiopathic tics, which make up the majority, and the Gilles de la Tourette syndrome (SGT), which is, at the moment, of unknown origin. Of the possible aetiologies described as causing tics, craneo-encephalic trauma has been mentioned on very few occasions. We present a case of post-traumatic tics (verbal and neck) in a young man of 24, and review the published cases which can be considered to be of post-traumatic tics. We have found six cases of tics secondary to traumas, all craneo-encephalic, like ours (the one under study). The time interval between the blow and the appearance of the tic or tics varied between 2 weeks and 3 months. The absence of significant lesions seen in the complementary investigations make it impossible for us to discover the site of the lesion caused by the trauma. However, the presence in some cases of other tics before the trauma, and of family histories of tics, supports the idea of a genetic basis or predisposition to suffer this disorder.

  20. Regulatory focus affects physician risk tolerance.

    Science.gov (United States)

    Veazie, Peter J; McIntosh, Scott; Chapman, Benjamin P; Dolan, James G

    2014-01-01

    Risk tolerance is a source of variation in physician decision-making. This variation, if independent of clinical concerns, can result in mistaken utilization of health services. To address such problems, it will be helpful to identify nonclinical factors of risk tolerance, particularly those amendable to intervention-regulatory focus theory suggests such a factor. This study tested whether regulatory focus affects risk tolerance among primary care physicians. Twenty-seven primary care physicians were assigned to promotion-focused or prevention-focused manipulations and compared on the Risk Taking Attitudes in Medical Decision Making scale using a randomization test. Results provide evidence that physicians assigned to the promotion-focus manipulation adopted an attitude of greater risk tolerance than the physicians assigned to the prevention-focused manipulation (p = 0.01). The Cohen's d statistic was conventionally large at 0.92. Results imply that situational regulatory focus in primary care physicians affects risk tolerance and may thereby be a nonclinical source of practice variation. Results also provide marginal evidence that chronic regulatory focus is associated with risk tolerance (p = 0.05), but the mechanism remains unclear. Research and intervention targeting physician risk tolerance may benefit by considering situational regulatory focus as an explanatory factor.

  1. Functional characterization of variations on regulatory motifs.

    Directory of Open Access Journals (Sweden)

    Michal Lapidot

    2008-03-01

    Full Text Available Transcription factors (TFs regulate gene expression through specific interactions with short promoter elements. The same regulatory protein may recognize a variety of related sequences. Moreover, once they are detected it is hard to predict whether highly similar sequence motifs will be recognized by the same TF and regulate similar gene expression patterns, or serve as binding sites for distinct regulatory factors. We developed computational measures to assess the functional implications of variations on regulatory motifs and to compare the functions of related sites. We have developed computational means for estimating the functional outcome of substituting a single position within a binding site and applied them to a collection of putative regulatory motifs. We predict the effects of nucleotide variations within motifs on gene expression patterns. In cases where such predictions could be compared to suitable published experimental evidence, we found very good agreement. We further accumulated statistics from multiple substitutions across various binding sites in an attempt to deduce general properties that characterize nucleotide substitutions that are more likely to alter expression. We found that substitutions involving Adenine are more likely to retain the expression pattern and that substitutions involving Guanine are more likely to alter expression compared to the rest of the substitutions. Our results should facilitate the prediction of the expression outcomes of binding site variations. One typical important implication is expected to be the ability to predict the phenotypic effect of variation in regulatory motifs in promoters.

  2. Phylogeny based discovery of regulatory elements

    Directory of Open Access Journals (Sweden)

    Cohen Barak A

    2006-05-01

    Full Text Available Abstract Background Algorithms that locate evolutionarily conserved sequences have become powerful tools for finding functional DNA elements, including transcription factor binding sites; however, most methods do not take advantage of an explicit model for the constrained evolution of functional DNA sequences. Results We developed a probabilistic framework that combines an HKY85 model, which assigns probabilities to different base substitutions between species, and weight matrix models of transcription factor binding sites, which describe the probabilities of observing particular nucleotides at specific positions in the binding site. The method incorporates the phylogenies of the species under consideration and takes into account the position specific variation of transcription factor binding sites. Using our framework we assessed the suitability of alignments of genomic sequences from commonly used species as substrates for comparative genomic approaches to regulatory motif finding. We then applied this technique to Saccharomyces cerevisiae and related species by examining all possible six base pair DNA sequences (hexamers and identifying sequences that are conserved in a significant number of promoters. By combining similar conserved hexamers we reconstructed known cis-regulatory motifs and made predictions of previously unidentified motifs. We tested one prediction experimentally, finding it to be a regulatory element involved in the transcriptional response to glucose. Conclusion The experimental validation of a regulatory element prediction missed by other large-scale motif finding studies demonstrates that our approach is a useful addition to the current suite of tools for finding regulatory motifs.

  3. Safeguards inventory and process monitoring regulatory comparison

    Energy Technology Data Exchange (ETDEWEB)

    Cavaluzzi, Jack M. [Texas A & M Univ., College Station, TX (United States); Gibbs, Philip W. [Brookhaven National Lab. (BNL), Upton, NY (United States)

    2013-06-27

    Detecting the theft or diversion of the relatively small amount of fissile material needed to make a nuclear weapon given the normal operating capacity of many of today’s running nuclear production facilities is a difficult task. As throughput increases, the ability of the Material Control and Accountability (MC&A) Program to detect the material loss decreases because the statistical measurement uncertainty also increases. The challenge faced is the ability of current accounting, measurement, and material control programs to detect small yet significant losses under some regulatory approaches can decrease to the point where it is extremely low if not practically non-existent at normal operating capacities. Adding concern to this topic is that there are variations among regulatory bodies as far as what is considered a Significant Quantity (SQ). Some research suggests that thresholds should be lower than those found in any current regulation which if adopted would make meeting detection goals even more difficult. This paper reviews and compares the current regulatory requirements for the MA elements related to physical inventory, uncertainty of the Inventory Difference (ID), and Process Monitoring (PM) in the United States Department of Energy (DOE) and Nuclear Regulatory Commission (NRC), Rosatom of the Russian Federation and the Chinese Atomic Energy Agency (CAEA) of China. The comparison looks at how the regulatory requirements for the implementation of various MA elements perform across a range of operating capacities in example facilities.

  4. 17 CFR 240.17Ad-11 - Reports regarding aged record differences, buy-ins and failure to post certificate detail to...

    Science.gov (United States)

    2010-04-01

    ... differences, buy-ins and failure to post certificate detail to master securityholder and subsidiary files. 240... regarding aged record differences, buy-ins and failure to post certificate detail to master securityholder... appropriate regulatory agency in accordance with § 240.17Ad-2(h), concerning buy-ins of all issues for...

  5. CD4-regulatory cells in COPD patients

    DEFF Research Database (Denmark)

    Smyth, Lucy J C; Starkey, Cerys; Vestbo, Jørgen

    2007-01-01

    BACKGROUND: The numbers of airway CD8 and B lymphocytes are increased in COPD patients, suggesting an autoimmune process. CD4-regulatory T cells control autoimmunity but have not been studied in patients with COPD. OBJECTIVE: To compare T-regulatory cell numbers in the BAL from COPD patients......, smokers with normal lung function, and healthy nonsmokers (HNS). METHODS: BAL and peripheral blood mononuclear cell (PBMC) samples were obtained from 26 COPD patients, 19 smokers, and 8 HNS. Flow cytometry was performed for regulatory phenotypic markers. RESULTS: COPD patients had increased BAL CD8...... numbers compared to smokers and HNS. CD4 numbers were similar between groups. There was increased BAL CD4CD25(bright) expression in smokers (median 28.8%) and COPD patients (median 23.1%) compared to HNS (median 0%). Increased FoxP3 expression was confirmed in BAL CD4CD25(bright) cells. BAL CD4CD25 cells...

  6. Current status of developmental neurotoxicity: regulatory view

    DEFF Research Database (Denmark)

    Hass, Ulla

    2003-01-01

    . Until recently, however, developmental neurotoxicity testing of industrial chemicals has not been a clear regulatory requirement in EU, probably due to the lack of an accepted OECD TG. The revised EU Technical Guidance Document for Risk Assessment (EU-TGD) has now included the OECD draft TG 426...... in the testing strategy for new and existing substances, and biocides. Hopefully, this will lead to an improved database for risk assessment of potential developmental neurotoxicants. However, the regulatory authorities and toxicologists will also be faced with the challenge that decisions have to be made......The need for developmental neurotoxicity testing has been recognized for decades and guidelines are available, as the USEPA guideline and the OECD draft TG 426. Regulatory testing of industrial chemicals for developmental neurotoxicity is required to some extent, especially for pesticides in the US...

  7. Evolutionary rewiring of bacterial regulatory networks

    Directory of Open Access Journals (Sweden)

    Tiffany B. Taylor

    2015-07-01

    Full Text Available Bacteria have evolved complex regulatory networks that enable integration of multiple intracellular and extracellular signals to coordinate responses to environmental changes. However, our knowledge of how regulatory systems function and evolve is still relatively limited. There is often extensive homology between components of different networks, due to past cycles of gene duplication, divergence, and horizontal gene transfer, raising the possibility of cross-talk or redundancy. Consequently, evolutionary resilience is built into gene networks – homology between regulators can potentially allow rapid rescue of lost regulatory function across distant regions of the genome. In our recent study [Taylor, et al. Science (2015, 347(6225] we find that mutations that facilitate cross-talk between pathways can contribute to gene network evolution, but that such mutations come with severe pleiotropic costs. Arising from this work are a number of questions surrounding how this phenomenon occurs.

  8. Transcription regulatory networks analysis using CAGE

    KAUST Repository

    Tegnér, Jesper N.

    2009-10-01

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

  9. Targeting regulatory T cells in cancer.

    LENUS (Irish Health Repository)

    Byrne, William L

    2012-01-31

    Infiltration of tumors by regulatory T cells confers growth and metastatic advantages by inhibiting antitumor immunity and by production of receptor activator of NF-kappaB (RANK) ligand, which may directly stimulate metastatic propagation of RANK-expressing cancer cells. Modulation of regulatory T cells can enhance the efficacy of cancer immunotherapy. Strategies include depletion, interference with function, inhibition of tumoral migration, and exploitation of T-cell plasticity. Problems with these strategies include a lack of specificity, resulting in depletion of antitumor effector T cells or global interruption of regulatory T cells, which may predispose to autoimmune diseases. Emerging technologies, such as RNA interference and tetramer-based targeting, may have the potential to improve selectivity and efficacy.

  10. Current approaches to gene regulatory network modelling

    Directory of Open Access Journals (Sweden)

    Brazma Alvis

    2007-09-01

    Full Text Available Abstract Many different approaches have been developed to model and simulate gene regulatory networks. We proposed the following categories for gene regulatory network models: network parts lists, network topology models, network control logic models, and dynamic models. Here we will describe some examples for each of these categories. We will study the topology of gene regulatory networks in yeast in more detail, comparing a direct network derived from transcription factor binding data and an indirect network derived from genome-wide expression data in mutants. Regarding the network dynamics we briefly describe discrete and continuous approaches to network modelling, then describe a hybrid model called Finite State Linear Model and demonstrate that some simple network dynamics can be simulated in this model.

  11. Statistical significance of cis-regulatory modules

    Directory of Open Access Journals (Sweden)

    Smith Andrew D

    2007-01-01

    Full Text Available Abstract Background It is becoming increasingly important for researchers to be able to scan through large genomic regions for transcription factor binding sites or clusters of binding sites forming cis-regulatory modules. Correspondingly, there has been a push to develop algorithms for the rapid detection and assessment of cis-regulatory modules. While various algorithms for this purpose have been introduced, most are not well suited for rapid, genome scale scanning. Results We introduce methods designed for the detection and statistical evaluation of cis-regulatory modules, modeled as either clusters of individual binding sites or as combinations of sites with constrained organization. In order to determine the statistical significance of module sites, we first need a method to determine the statistical significance of single transcription factor binding site matches. We introduce a straightforward method of estimating the statistical significance of single site matches using a database of known promoters to produce data structures that can be used to estimate p-values for binding site matches. We next introduce a technique to calculate the statistical significance of the arrangement of binding sites within a module using a max-gap model. If the module scanned for has defined organizational parameters, the probability of the module is corrected to account for organizational constraints. The statistical significance of single site matches and the architecture of sites within the module can be combined to provide an overall estimation of statistical significance of cis-regulatory module sites. Conclusion The methods introduced in this paper allow for the detection and statistical evaluation of single transcription factor binding sites and cis-regulatory modules. The features described are implemented in the Search Tool for Occurrences of Regulatory Motifs (STORM and MODSTORM software.

  12. Post-Quantum Cryptography

    DEFF Research Database (Denmark)

    Gauthier Umana, Valérie

    The security of almost all the public-key cryptosystems used in practice depends on the fact that the prime factorization of a number and the discrete logarithm are hard problems to solve. In 1994, Peter Shor found a polynomial-time algorithm which solves these two problems using quantum computers....... The public key cryptosystems that can resist these emerging attacks are called quantum resistant or post-quantum cryptosystems. There are mainly four classes of public-key cryptography that are believed to resist classical and quantum attacks: code-based cryptography, hash-based cryptography, lattice......-cyclic alternant codes and quasi-dyadic codes (joint work with Gregor Leander). We also present a deterministic polynomial-time algorithm to solve the Goppa Code Distinguisher problem for high rate codes (joint work with Jean-Charles Faugere, Ayoub Otmani, Ludovic Perret and Jean-Pierre Tillich). In the second...

  13. Post-representational cartography

    Directory of Open Access Journals (Sweden)

    Rob Kitchin

    2010-03-01

    Full Text Available Over the past decade there has been a move amongst critical cartographers to rethink maps from a post-representational perspective – that is, a vantage point that does not privilege representational modes of thinking (wherein maps are assumed to be mirrors of the world and automatically presumes the ontological security of a map as a map, but rather rethinks and destabilises such notions. This new theorisation extends beyond the earlier critiques of Brian Harley (1989 that argued maps were social constructions. For Harley a map still conveyed the truth of a landscape, albeit its message was bound within the ideological frame of its creator. He thus advocated a strategy of identifying the politics of representation within maps in order to circumnavigate them (to reveal the truth lurking underneath, with the ontology of cartographic practice remaining unquestioned.

  14. Post-streptococcal glomerulonephritis

    Directory of Open Access Journals (Sweden)

    Odalovic A.

    2014-01-01

    Full Text Available Post-streptococcal glomerulonephritis (PSGN is a frequent cause of acute nephritis in children. This case study was done with the aim to point out that the infections caused by Group A streptococci, in spite of antibiotic era, are still present in the population. An 8-year old boy was admitted in our hospital with a two-day history of fewer, tonsillopharyngitis. After hospital admission, patient was treated with penicillin during the period of 10 days, antihypertensive medications (captopril, furosemide, including restricted diet of salt. After the treatment, patient became better. On demission it was found proteinuria and microhematuria PSGN is very serious disease, which leaves severe complications if the valid therapy with penicillin is not used in propriety time, during the recommended period of 10 days.

  15. Post-Positivist Realism

    Institute of Scientific and Technical Information of China (English)

    Barbara; Foley

    2006-01-01

    本文作者对《重申身份》一书中所持的后实证现实主义(post-positivist realism)观点进行了深刻的批评。作者指出,从后实证现实主义立场出发论述身份问题会遭遇到逻辑与政治的难题。它所提供的答案只是症候式,而非实质性的。实际上,后现代主义在身份问题上所处的尴尬也是后实证现实主义所同样面临的。

  16. Post-treatment CIN

    DEFF Research Database (Denmark)

    Bais, Aagje G; Eijkemans, Marinus J C; Rebolj, Mateja;

    2009-01-01

    compared health-care costs and impact of individual hrHPV type on the risk of residual/recurrent CIN. Follow-up by abnormal cytology alone (6, 12 and 24 months after treatment according to the Dutch protocol) showed a lower specificity for detection of residual/recurrent CIN than follow-up by abnormal...... cytology and presence of hrHPV (80 vs. 91%, relative risk 0.87 (95% CI 0.77-0.99)). Both methods showed no significant difference in sensitivity ((86 vs. 100%) RR 0.86 (95% CI 0.63-1.16)). Comparing different post hoc modifications in the strategy of combined testing showed similar test characteristics...

  17. Post-traumatic syringomyelia

    Directory of Open Access Journals (Sweden)

    Agrawal Amit

    2007-01-01

    Full Text Available Progressive post-traumatic cystic syringomyelia is an uncommon and increasingly recognized cause of morbidity following spinal cord injury. We hereby report a 35-year-old gentleman who sustained wedge compression fracture of L-1 vertebral body 15 years back and had complete paraplegia with bowel/bladder involvement. The neurological deficit recovered with minimal residual motor deficits and erectile dysfunction. He presented now with increasing neurological deficits associated with pain and paresthesia. The MRI spine showed a syrinx extending from the site of injury up to the medulla. He underwent a syringo-peritoneal shunt and at follow-up his pain and motor functions had improved but erectile dysfunction was persisting.

  18. Regulatory issues in accreditation of toxicology laboratories.

    Science.gov (United States)

    Bissell, Michael G

    2012-09-01

    Clinical toxicology laboratories and forensic toxicology laboratories operate in a highly regulated environment. This article outlines major US legal/regulatory issues and requirements relevant to accreditation of toxicology laboratories (state and local regulations are not covered in any depth). The most fundamental regulatory distinction involves the purposes for which the laboratory operates: clinical versus nonclinical. The applicable regulations and the requirements and options for operations depend most basically on this consideration, with clinical toxicology laboratories being directly subject to federal law including mandated options for accreditation and forensic toxicology laboratories being subject to degrees of voluntary or state government–required accreditation.

  19. Theory of Regulatory Compliance for Requirements Engineering

    CERN Document Server

    Jureta, Ivan; Mylopoulos, John; Perini, Anna; Susi, Angelo

    2010-01-01

    Regulatory compliance is increasingly being addressed in the practice of requirements engineering as a main stream concern. This paper points out a gap in the theoretical foundations of regulatory compliance, and presents a theory that states (i) what it means for requirements to be compliant, (ii) the compliance problem, i.e., the problem that the engineer should resolve in order to verify whether requirements are compliant, and (iii) testable hypotheses (predictions) about how compliance of requirements is verified. The theory is instantiated by presenting a requirements engineering framework that implements its principles, and is exemplified on a real-world case study.

  20. Gene regulatory mechanisms in infected fish

    DEFF Research Database (Denmark)

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

    2011-01-01

    This talk will highlight the regulatory mechanisms of gene expression especially the programmed form of mRNA decay which is known as RNA interference (RNAi) and how this and other mechanisms contribute to the regulation of genes involved in immunity. In the RNAi mechanism small double stranded RNA...... whole pathways for the fine-tuning of physiological states like immunological reaction. But miRNAs are themselves under control of regulatory sequences for their timed expression. We will give an example of the finding of two rainbow trout microRNAs, which are up-regulated in the liver during infection...

  1. Modular arrangement of regulatory RNA elements

    Science.gov (United States)

    Roßmanith, Johanna; Narberhaus, Franz

    2017-01-01

    ABSTRACT Due to their simple architecture and control mechanism, regulatory RNA modules are attractive building blocks in synthetic biology. This is especially true for riboswitches, which are natural ligand-binding regulators of gene expression. The discovery of various tandem riboswitches inspired the design of combined RNA modules with activities not yet found in nature. Riboswitches were placed in tandem or in combination with a ribozyme or temperature-responsive RNA thermometer resulting in new functionalities. Here, we compare natural examples of tandem riboswitches with recently designed artificial RNA regulators suggesting substantial modularity of regulatory RNA elements. Challenges associated with modular RNA design are discussed. PMID:28010165

  2. Excessive crying in infants with regulatory disorders.

    Science.gov (United States)

    Maldonado-Duran, M; Sauceda-Garcia, J M

    1996-01-01

    The authors point out a correlation between regulatory disorders in infants and the problem of excessive crying. The literature describes other behavioral problems involving excessive crying in very young children, but with little emphasis on this association. The recognition and diagnosis of regulatory disorders in infants who cry excessively can help practitioners design appropriate treatment interventions. Understanding these conditions can also help parents tailor their caretaking style, so that they provide appropriate soothing and stimulation to their child. In so doing, they will be better able to develop and preserve a satisfactory parent-child relationship, as well as to maintain their own sense of competence and self-esteem as parents.

  3. Messenger RNA fluctuations and regulatory RNAs shape the dynamics of a negative feedback loop

    Science.gov (United States)

    Rodríguez Martínez, María; Soriano, Jordi; Tlusty, Tsvi; Pilpel, Yitzhak; Furman, Itay

    2010-03-01

    Single-cell experiments of simple regulatory networks can markedly differ from cell population experiments. Such differences arise from stochastic events in individual cells that are averaged out in cell populations. For instance, while individual cells may show sustained oscillations in the concentrations of some proteins, such oscillations may appear damped in the population average. In this paper we investigate the role of RNA stochastic fluctuations as a leading force to produce a sustained excitatory behavior at the single-cell level. As opposed to some previous models, we build a fully stochastic model of a negative feedback loop that explicitly takes into account the RNA stochastic dynamics. We find that messenger RNA random fluctuations can be amplified during translation and produce sustained pulses of protein expression. Motivated by the recent appreciation of the importance of noncoding regulatory RNAs in post-transcription regulation, we also consider the possibility that a regulatory RNA transcript could bind to the messenger RNA and repress translation. Our findings show that the regulatory transcript helps reducing gene expression variability both at the single-cell level and at the cell population level.

  4. Fatal adverse drug reactions of anticancer drugs detected by all-case post-marketing surveillance in Japan.

    Science.gov (United States)

    Mori, Jinichi; Tanimoto, Tetsuya; Miura, Yuji; Kami, Masahiro

    2015-06-01

    All-case post-marketing surveillance of newly approved anticancer drugs is usually conducted on all patients in Japan. The present study investigates whether all-case post-marketing surveillance identifies fatal adverse drug reactions undetected before market entry. We examined fatal adverse drug reactions identified via all-case post-marketing surveillance by reviewing the disclosed post-marketing surveillance results, and determined the time points in which the fatal adverse drug reactions were initially reported by reviewing drug labels. We additionally scanned emergency alerts on the Japanese regulatory authority website to assess the relationship between all-case post-marketing surveillance and regulatory action. Twenty-five all-case post-marketing surveillances were performed between January 1999 and December 2009. Eight all-case post-marketing surveillances with final results included information on all fatal cases. Of these, the median number of patients was 1287 (range: 106-4998), the median number of fatal adverse drug reactions was 14.5 (range: 4-23). Of the 111 fatal adverse drug reactions detected in the eight post-marketing surveillances, only 28 (25.0%) and 22 (19.6%) were described on the initial global and the initial Japanese drug label, respectively, and 58 (52.3%) fatal adverse drug reactions were first described in the all-case post-marketing surveillance reports. Despite this, the regulatory authority issued only four warning letters, and two of these were prompted by case reports from the all-case post-marketing surveillance. All-case post-marketing surveillance of newly approved anticancer drugs in Japan was useful for the rigorous compilation of non-specific adverse drug reactions, but it rarely detected clinically significant fatal adverse drug reactions. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Post-16 update

    Science.gov (United States)

    1999-01-01

    Post-16 Initiative logo This is the first of a regular series of contributions from the Institute's Post-16 Initiative. The Initiative is taking a hard and searching look at the physics taught in schools and colleges from age 16 to age 19. To start with, it is responding to Government initiatives, but hopes to encourage and stimulate good practice in physics teaching on a longer time scale than can be afforded in making responses to current developments. Here Jon Ogborn writes about what AS courses need to be, while Peter Campbell gives his thoughts about teaching matter. Advanced Subsidiary physics: what should it be? From September 2000 all A-levels will be new. Students can take the first Advanced Subsidiary (AS) year and stop there - or decide to go on. In the Institute of Physics post-16 Initiative, we have been thinking how to provide a satisfying one-year experience of physics at the new AS level, and what it should achieve. The students will decide. So the AS course must give a decent picture of what physics is, what it offers for their futures, what interests it can satisfy. That all says breadth, with enough depth to see what is in store later. And this sounds like the right recipe for someone who is taking a single AS year of physics to broaden their A-level experience. It must also be attractive. A way forward is shown by the Salters - Horners course, attracting interest through leading from applications. Why does that work? It gives physics a story to tell, into which ideas fit and make sense. Our own new A-level, Advancing Physics, must also have interesting stories to tell, which must in addition build up an honest picture of physics. An example: teach electric circuits through modern sensing devices. Sensor instrumentation is a key activity of physicists, full of new ideas, but also simple. It makes essential use of circuits such as the potential divider. Practical work gets better things to do than checking the equation for resistors in parallel

  6. Retention of Root Canal Posts

    DEFF Research Database (Denmark)

    Sahafi, A; Benetti, Ana Raquel; Flury, S;

    2015-01-01

    The aim of this study was to investigate the effect of the cement film thickness of a zinc phosphate or a resin cement on retention of untreated and pretreated root canal posts. Prefabricated zirconia posts (CosmoPost: 1.4 mm) and two types of luting cements (a zinc phosphate cement [DeTrey Zinc......] and a self-etch adhesive resin cement [Panavia F2.0]) were used. After removal of the crowns of 360 extracted premolars, canines, or incisors, the root canals were prepared with a parallel-sided drill system to three different final diameters. Half the posts did not receive any pretreatment. The other half...... received tribochemical silicate coating according to the manufacturer's instructions. Posts were then luted in the prepared root canals (n=30 per group). Following water storage at 37°C for seven days, retention of the posts was determined by the pull-out method. Irrespective of the luting cement...

  7. Post combustion in converter steelmaking

    Energy Technology Data Exchange (ETDEWEB)

    Oghbasilasie, H.; Holappa, L.

    1997-12-31

    The purpose of this work is to study the fundamentals of post combustion and the effect of different process parameters on the post combustion ratio (PCR) and heat transfer efficiency (HTE) in converter steelmaking process. The PCR and HTE have been determined under normal operating conditions. Trials assessed the effect of lance height, vessel volume, foaming slag and pellet additions on PCR and HTE. Based on enthalpy considerations, post combustion of CO gas is regarded as one of the most effective means of increasing the heat supply to the BOP. The thermodynamic study of gas-metal-slag reactions gives the limiting conditions for post combustion inside the converter reactor. Different process parameters influencing both thermodynamic equilibria and kinetic conditions can greatly affect the post combustion ratio. Different features of converter processes as well smelting reduction processes utilizing post combustion have been reviewed. (orig.) SULA 2 Research Programme; 26 refs.

  8. 75 FR 79843 - Fall 2010 Regulatory Agenda

    Science.gov (United States)

    2010-12-20

    ... see our FY 2011 Regulatory Plan. 1. Taking Action on Climate Change: In 2009 EPA finalized an... Supplemental Determinations for Renewable Fuels Produced Under the Final RFS2 Program 2060-AQ36 From Palm Oil... RENEWABLE FUELS PRODUCED UNDER THE FINAL RFS2 PROGRAM FROM PALM OIL Legal Authority: Clean Air Act sec...

  9. Regulatory capital requirements and bail in mechanisms

    NARCIS (Netherlands)

    Joosen, B.P.M.; Haentjens, M.; Wessels, B.

    2015-01-01

    With the introduction of the Capital Requirements Regulation (CRR) in the European Union, the qualitative requirements for bank regulatory capital have changed. These changes aim at implementing in Europe the Basel III principles for better bank capital that is able to absorb losses of banks,

  10. Pre-commercial procurement : regulatory effectiveness?

    NARCIS (Netherlands)

    Apostol, Anca Ramona

    2014-01-01

    Is public procurement of research and development (‘R&D’) services the key to European Union (‘EU’)’s sustainable welfare? Is it being regulated in accordance with economic prescripts for effectiveness? Is the regulatory and policy setting clear and comprehensive in order to stimulate a widespread u

  11. RSAT 2015: Regulatory Sequence Analysis Tools.

    Science.gov (United States)

    Medina-Rivera, Alejandra; Defrance, Matthieu; Sand, Olivier; Herrmann, Carl; Castro-Mondragon, Jaime A; Delerce, Jeremy; Jaeger, Sébastien; Blanchet, Christophe; Vincens, Pierre; Caron, Christophe; Staines, Daniel M; Contreras-Moreira, Bruno; Artufel, Marie; Charbonnier-Khamvongsa, Lucie; Hernandez, Céline; Thieffry, Denis; Thomas-Chollier, Morgane; van Helden, Jacques

    2015-07-01

    RSAT (Regulatory Sequence Analysis Tools) is a modular software suite for the analysis of cis-regulatory elements in genome sequences. Its main applications are (i) motif discovery, appropriate to genome-wide data sets like ChIP-seq, (ii) transcription factor binding motif analysis (quality assessment, comparisons and clustering), (iii) comparative genomics and (iv) analysis of regulatory variations. Nine new programs have been added to the 43 described in the 2011 NAR Web Software Issue, including a tool to extract sequences from a list of coordinates (fetch-sequences from UCSC), novel programs dedicated to the analysis of regulatory variants from GWAS or population genomics (retrieve-variation-seq and variation-scan), a program to cluster motifs and visualize the similarities as trees (matrix-clustering). To deal with the drastic increase of sequenced genomes, RSAT public sites have been reorganized into taxon-specific servers. The suite is well-documented with tutorials and published protocols. The software suite is available through Web sites, SOAP/WSDL Web services, virtual machines and stand-alone programs at http://www.rsat.eu/.

  12. Mutational robustness of gene regulatory networks.

    Directory of Open Access Journals (Sweden)

    Aalt D J van Dijk

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

  13. 75 FR 81112 - Montana Regulatory Program

    Science.gov (United States)

    2010-12-27

    ... organisms. Application of herbicides to control weeds may be necessary in some cases where steep slopes and..., so as to demonstrate the stability of such crossings and that no negative consequences are reasonably... the analysis performed for the counterpart Federal regulation. Executive Order 12866--Regulatory...

  14. 76 FR 76111 - Montana Regulatory Program

    Science.gov (United States)

    2011-12-06

    ...--Regulatory Planning and Review This rule is exempted from review by the Office of Management and Budget (OMB... to and additions of statutory definitions for ``approximate original contour,'' ``in situ coal..., Federal Register (45 FR 21560). You can also find later actions concerning Montana's program and...

  15. 76 FR 37996 - West Virginia Regulatory Program

    Science.gov (United States)

    2011-06-29

    ... significant economic impact on a substantial number of small entities under the Regulatory Flexibility Act (5... making the determination as to whether this rule would have a significant economic impact, the Department... Virginia is amending its Code of State Regulations (CSR) to provide for the establishment of a minimum...

  16. Shaping Formal Networks throug the Regulatory Process

    NARCIS (Netherlands)

    Hall, Thad E.; O'Toole, Laurence J.

    2004-01-01

    Recent research has shown that, at the federal level, new or amended programs typically create networks consisting of multiactor structures spanning governments, sectors, and/or agencies. This study examines the implementation structures created through the regulatory process. We find that in a majo

  17. HIDEN: Hierarchical decomposition of regulatory networks

    Directory of Open Access Journals (Sweden)

    Gülsoy Günhan

    2012-09-01

    Full Text Available Abstract Background Transcription factors regulate numerous cellular processes by controlling the rate of production of each gene. The regulatory relations are modeled using transcriptional regulatory networks. Recent studies have shown that such networks have an underlying hierarchical organization. We consider the problem of discovering the underlying hierarchy in transcriptional regulatory networks. Results We first transform this problem to a mixed integer programming problem. We then use existing tools to solve the resulting problem. For larger networks this strategy does not work due to rapid increase in running time and space usage. We use divide and conquer strategy for such networks. We use our method to analyze the transcriptional regulatory networks of E. coli, H. sapiens and S. cerevisiae. Conclusions Our experiments demonstrate that: (i Our method gives statistically better results than three existing state of the art methods; (ii Our method is robust against errors in the data and (iii Our method’s performance is not affected by the different topologies in the data.

  18. Department of Agriculture Semiannual Regulatory Agenda

    Science.gov (United States)

    2010-04-26

    ... members of the public have advocated for amending the regulations for sourcing dairy replacement animals. They have asserted that the current regulatory language on sourcing dairy replacement animals lacks... Order for dairy product promotion, research, and nutrition education as part of a comprehensive strategy...

  19. 78 FR 42893 - Statement on Regulatory Burden

    Science.gov (United States)

    2013-07-18

    ... serve the credit needs of its customers, i.e., America's farmers, ranchers, aquatic producers and... CREDIT ADMINISTRATION 12 CFR Chapter VI RIN 3052-AC88 Statement on Regulatory Burden AGENCY: Farm Credit Administration. ACTION: Notice of intent; request for comment. SUMMARY: The Farm Credit Administration (FCA,...

  20. Deferred Tax Assests and Bank Regulatory Capital

    NARCIS (Netherlands)

    Gallemore, J.

    2012-01-01

    Abstract: In this study, I examine three issues: (1) whether the probability of bank failure is increasing in the proportion of regulatory capital composed of deferred tax assets (DTA), (2) whether market participants incorporate the increased failure risk associated with the DTA component of capita

  1. 76 FR 18467 - Pennsylvania Regulatory Program

    Science.gov (United States)

    2011-04-04

    ... a partial disapproval of a 1998 submission that included regulations about remining financial... effective regulatory program) relating to incidental extraction of coal under noncoal mining permits.... Section 86.5, Extraction of Coal Incidental to Noncoal Surface Mining Section 86.5(m) is amended to...

  2. Department of Commerce Semiannual Regulatory Agenda

    Science.gov (United States)

    2010-04-26

    ... Part IV Department of Commerce Semiannual Regulatory Agenda ] DEPARTMENT OF COMMERCE (DOC) DEPARTMENT OF COMMERCE Office of the Secretary 13 CFR Ch. III 15 CFR Subtitle A; Subtitle B, Chs. I, II, III..., and VI Spring 2010 Semiannual Agenda of Regulations AGENCY: Office of the Secretary, Commerce....

  3. Independent regulatory authorities in European electricity market

    DEFF Research Database (Denmark)

    Olsen, Ole Jess; Larsen, Anders; Sørensen, Eva Moll

    2006-01-01

    Liberalisation of the electricity market has taken place in most European countries within the last decade. It is considered a precondition of successful liberalisation to establish so-called independent regulatory authorities. In this article, we compare the status and practice of them in 16...

  4. 47 CFR 69.727 - Regulatory relief.

    Science.gov (United States)

    2010-10-01

    ... similarly situated customers; and (ii) The price cap LEC excludes all contract tariff offerings from price... customer. (b) Phase II relief. Upon satisfaction of the Phase II triggers specified in §§ 69.709(c) or 69... Pricing Flexibility § 69.727 Regulatory relief. (a) Phase I relief. Upon satisfaction of the Phase I...

  5. 75 FR 79929 - Semiannual Regulatory Agenda

    Science.gov (United States)

    2010-12-20

    ... be a ``significant regulatory action'' under the definition in Executive Order 12866. Beginning with the fall 2007 edition, the Internet became the basic means for disseminating the Unified Agenda. The... requirements. Additional information on these entries is available in the Unified Agenda published on...

  6. 78 FR 10512 - Wyoming Regulatory Program

    Science.gov (United States)

    2013-02-14

    ... permits a State to assume primacy for the regulation of surface coal mining and reclamation operations on..., among other things, ``a State law which provides for the regulation of surface coal mining and... Office of Surface Mining Reclamation and Enforcement 30 CFR Part 950 Wyoming Regulatory Program AGENCY...

  7. 75 FR 46877 - Pennsylvania Regulatory Program

    Science.gov (United States)

    2010-08-04

    ... permits a State to assume primacy for the regulation of surface coal mining and reclamation operations on... other things, ``a State law which provides for the regulation of surface coal mining and reclamation... Office of Surface Mining Reclamation and Enforcement 30 CFR Part 938 Pennsylvania Regulatory Program...

  8. 77 FR 34894 - Wyoming Regulatory Program

    Science.gov (United States)

    2012-06-12

    ... for the regulation of surface coal mining and reclamation operations on non- Federal and non-Indian... law which provides for the regulation of surface coal mining and reclamation operations in accordance... Office of Surface Mining Reclamation and Enforcement 30 CFR Part 950 Wyoming Regulatory Program AGENCY...

  9. 77 FR 58053 - Kentucky Regulatory Program

    Science.gov (United States)

    2012-09-19

    ... for the regulation of surface coal mining and reclamation operations on non- Federal and non-Indian... which provides for the regulation of surface coal mining and reclamation operations in accordance with... Office of Surface Mining Reclamation and Enforcement 30 CFR Part 917 Kentucky Regulatory Program AGENCY...

  10. 78 FR 13002 - Pennsylvania Regulatory Program

    Science.gov (United States)

    2013-02-26

    ... Section 503(a) of the SMCRA permits a State to assume primacy for the regulation of surface coal mining... Office of Surface Mining Reclamation and Enforcement 30 CFR Part 938 Pennsylvania Regulatory Program AGENCY: Office of Surface Mining Reclamation and Enforcement (``OSM''), Interior. ACTION: Proposed rule...

  11. 78 FR 6062 - North Dakota Regulatory Program

    Science.gov (United States)

    2013-01-29

    ...) of the Act permits a State to assume primacy for the regulation of surface coal mining and... Office of Surface Mining Reclamation and Enforcement 30 CFR Part 934 North Dakota Regulatory Program AGENCY: Office of Surface Mining Reclamation and Enforcement, Interior. ACTION: Proposed rule; public...

  12. 77 FR 18738 - Texas Regulatory Program

    Science.gov (United States)

    2012-03-28

    ... the regulation of surface coal mining and reclamation operations on non- Federal and non-Indian lands... provides for the regulation of surface coal mining and reclamation operations in accordance with the... Office of Surface Mining Reclamation and Enforcement 30 CFR Part 943 Texas Regulatory Program AGENCY...

  13. 76 FR 36040 - Wyoming Regulatory Program

    Science.gov (United States)

    2011-06-21

    ...(a) of the Act permits a State to assume primacy for the regulation of surface coal mining and... Office of Surface Mining Reclamation and Enforcement 30 CFR Part 950 Wyoming Regulatory Program AGENCY: Office of Surface Mining Reclamation and Enforcement, Interior. ACTION: Proposed rule; public comment...

  14. 77 FR 73965 - Montana Regulatory Program

    Science.gov (United States)

    2012-12-12

    ... Section 503(a) of the Act permits a State to assume primacy for the regulation of surface coal mining and... Office of Surface Mining Reclamation and Enforcement 30 CFR Part 926 Montana Regulatory Program AGENCY: Office of Surface Mining Reclamation and Enforcement, Interior. ACTION: Proposed rule; withdrawal...

  15. 75 FR 21534 - Texas Regulatory Program

    Science.gov (United States)

    2010-04-26

    ... a State to assume primacy for the regulation of surface coal mining and reclamation operations on... other things, ``a State law which provides for the regulation of surface coal mining and reclamation... Office of Surface Mining Reclamation and Enforcement 30 CFR Part 943 Texas Regulatory Program AGENCY...

  16. 77 FR 46346 - Ohio Regulatory Program

    Science.gov (United States)

    2012-08-03

    ... state to assume primacy for the regulation of surface coal mining and reclamation operations on non... things, ``* * * a State law which provides for the regulation of surface coal mining and reclamation... Office of Surface Mining Reclamation and Enforcement 30 CFR Part 935 Ohio Regulatory Program AGENCY...

  17. 76 FR 6587 - Pennsylvania Regulatory Program

    Science.gov (United States)

    2011-02-07

    ... regulation of surface coal mining and reclamation operations on non- Federal and non-Indian lands within its... the regulation of surface coal mining and reclamation operations in accordance with the requirements... Office of Surface Mining Reclamation and Enforcement 30 CFR Part 938 Pennsylvania Regulatory Program...

  18. 75 FR 6332 - Wyoming Regulatory Program

    Science.gov (United States)

    2010-02-09

    ... for the regulation of surface coal mining and reclamation operations on non- Federal and non-Indian... law which provides for the regulation of surface coal mining and reclamation operations in accordance... Office of Surface Mining Reclamation and Enforcement 30 CFR Part 950 Wyoming Regulatory Program AGENCY...

  19. 76 FR 36039 - Colorado Regulatory Program

    Science.gov (United States)

    2011-06-21

    ... regulation of surface coal mining and reclamation operations on non- Federal and non-Indian lands within its... for the regulation of surface coal mining and reclamation operations in accordance with the... Office of Surface Mining Reclamation and Enforcement 30 CFR Part 906 Colorado Regulatory Program AGENCY...

  20. 77 FR 66574 - Texas Regulatory Program

    Science.gov (United States)

    2012-11-06

    ... a State to assume primacy for the regulation of surface coal mining and reclamation operations on... other things, ``a State law which provides for the regulation of surface coal mining and reclamation... Office of Surface Mining Reclamation and Enforcement 30 CFR Part 943 Texas Regulatory Program AGENCY...

  1. 75 FR 81122 - Texas Regulatory Program

    Science.gov (United States)

    2010-12-27

    ...) of the Act permits a State to assume primacy for the regulation of surface coal mining and... governments with regard to the regulation of surface coal mining and reclamation operations. One of the... Office of Surface Mining Reclamation and Enforcement 30 CFR Part 943 Texas Regulatory Program AGENCY...

  2. 77 FR 34890 - Oklahoma Regulatory Program

    Science.gov (United States)

    2012-06-12

    ... a State to assume primacy for the regulation of surface coal mining and reclamation operations on... other things, ``* * * State law which provides for the regulation of surface coal mining and reclamation... Office of Surface Mining Reclamation and Enforcement 30 CFR Part 936 Oklahoma Regulatory Program AGENCY...

  3. 77 FR 73966 - Utah Regulatory Program

    Science.gov (United States)

    2012-12-12

    ... regulation of surface coal mining and reclamation operations in accordance with the requirements of this Act... Office of Surface Mining Reclamation and Enforcement 30 CFR Part 944 Utah Regulatory Program AGENCY: Office of Surface Mining Reclamation and Enforcement, Interior. ACTION: Proposed rule; reopening and...

  4. 75 FR 81120 - North Dakota Regulatory Program

    Science.gov (United States)

    2010-12-27

    ... regulation of surface coal mining and reclamation operations in accordance with the requirements of this Act... regard to the regulation of surface coal mining and reclamation operations. One of the purposes of SMCRA... Office of Surface Mining Reclamation and Enforcement 30 CFR Part 934 North Dakota Regulatory Program...

  5. Regulatory capital requirements and bail in mechanisms

    NARCIS (Netherlands)

    Joosen, B.P.M.; Haentjens, M.; Wessels, B.

    2015-01-01

    With the introduction of the Capital Requirements Regulation (CRR) in the European Union, the qualitative requirements for bank regulatory capital have changed. These changes aim at implementing in Europe the Basel III principles for better bank capital that is able to absorb losses of banks, withou

  6. Regulatory Challenges for Cartilage Repair Technologies.

    Science.gov (United States)

    McGowan, Kevin B; Stiegman, Glenn

    2013-01-01

    In the United States, few Food and Drug Administration (FDA)-approved options exist for the treatment of focal cartilage and osteochondral lesions. Developers of products for cartilage repair face many challenges to obtain marketing approval from the FDA. The objective of this review is to discuss the necessary steps for FDA application and approval for a new cartilage repair product. FDA Guidance Documents, FDA Panel Meetings, scientific organization recommendations, and clinicaltrials.gov were reviewed to demonstrate the current thinking of FDA and the scientific community on the regulatory process for cartilage repair therapies. Cartilage repair therapies can receive market approval from FDA as medical devices, drugs, or biologics, and the specific classification of product can affect the nonclinical, clinical, and regulatory strategy to bring the product to market. Recent FDA guidance gives an outline of the required elements to bring a cartilage repair product to market, although these standards are often very general. As a result, companies have to carefully craft their study patient population, comparator group, and clinical endpoint to best showcase their product's attributes. In addition, regulatory strategy and manufacturing process validation need to be considered early in the clinical study process to allow for timely product approval following the completion of clinical study. Although the path to regulatory approval for a cartilage repair therapy is challenging and time-consuming, proper clinical trial planning and attention to the details can eventually save companies time and money by bringing a product to the market in the most expeditious process possible.

  7. FORUM ISSUES IN THE ENFORCEMENT OF REGULATORY ...

    African Journals Online (AJOL)

    1 A Nigerian public company is a corporate entity that is incorporated in accordance .... of self-regulatory organisations in most financial markets who thus far have ...... the ISA, 2007, to the fundamental issue in the appeal, which is whether a.

  8. Inferring latent gene regulatory network kinetics

    NARCIS (Netherlands)

    González, Javier; Vujačić, Ivan; Wit, Ernst

    2013-01-01

    Regulatory networks consist of genes encoding transcription factors (TFs) and the genes they activate or repress. Various types of systems of ordinary differential equations (ODE) have been proposed to model these networks, ranging from linear to Michaelis-Menten approaches. In practice, a serious d

  9. Department of Agriculture Semiannual Regulatory Agenda

    Science.gov (United States)

    2010-12-20

    ...: September 21, 2010. Michael Poe, Chief, Legislative and Regulatory Staff. Agricultural Marketing Service.... Agricultural Marketing Service--Final Rule Stage Regulation Sequence Title Identifier Number Number 178...; Importation of Bovines and Bovine Products 0579-AC68 188 Viral Hemorrhagic Septicemia; Interstate Movement...

  10. Regulatory Proteolysis in Arabidopsis-Pathogen Interactions

    OpenAIRE

    Miklós Pogány; Tamás Dankó; Evelin Kámán-Tóth; Ildikó Schwarczinger; Zoltán Bozsó

    2015-01-01

    Approximately two and a half percent of protein coding genes in Arabidopsis encode enzymes with known or putative proteolytic activity. Proteases possess not only common housekeeping functions by recycling nonfunctional proteins. By irreversibly cleaving other proteins, they regulate crucial developmental processes and control responses to environmental changes. Regulatory proteolysis is also indispensable in interactions between plants and their microbial pathogens. Proteolytic cleavage is s...

  11. 77 FR 28518 - Reducing Regulatory Burden

    Science.gov (United States)

    2012-05-15

    ..., and other advantages; distributive impacts; and equity). The regulatory process encourages public..., simplify, and harmonize regulations to reduce costs and promote certainty for businesses and the public... culture of retrospective review and analysis. DOE will continually engage in review of its rules...

  12. 77 FR 26413 - Promoting International Regulatory Cooperation

    Science.gov (United States)

    2012-05-04

    ...) ``International regulatory cooperation'' refers to a bilateral, regional, or multilateral process, other than... pursuant to section 411 of the Trade Agreements Act of 1979 (19 U.S.C. 2451) and section 141 of the Trade... authorization process for the negotiation and conclusion of international agreements pursuant to 1 U.S.C. 112b(c...

  13. Regulatory guidelines for biosimilars in Malaysia.

    Science.gov (United States)

    Abas, Arpah

    2011-09-01

    The biosimilars sector continues to attract huge interest and controversy. Biosimilars are new biopharmaceuticals that are "similar" but not identical to the innovator product. Characteristics of biopharmaceuticals are closely related to the manufacturing process, which implies that the products cannot be exactly duplicated. Minuscule differences in the product's structure and manufacturing process can result in different clinical outcome. This raises concerns over the safety, efficacy and even pharmacovigilance of biosimilars. Thus, biosimilars are unique - they are not a true chemical generic and are regulated via a distinct regulatory framework. This report discusses the features of Malaysian regulatory oversight of biosimilars and experience acquired in the evaluation of some products from various countries. Ensuring regulatory position adequately reflects scientific advancement, expertise/resources is key. The regulatory situation is an evolving process. Various guidance documents are being prepared with the aim of developing a uniform global framework towards assuring the dual goal of lower costs and patient safety while expediting the availability of important biosimilar products.

  14. Regulatory Promotion of Emergent CCS Technology

    Energy Technology Data Exchange (ETDEWEB)

    Davies, Lincoln; Uchitel, Kirsten; Johnson, David

    2014-01-01

    Despite the growing inevitability of climate change and the attendant need for mitigation strategies, carbon capture and sequestration (CCS) has yet to gain much traction in the United States. Recent regulatory proposals by the U.S. Environmental Protection Agency (EPA), limited in scope to new-build power plants, represent the only significant policy initiative intended to mandate diffusion of CCS technology. Phase I of this Project assessed barriers to CCS deployment as prioritized by the CCS community. That research concluded that there were four primary barriers: (1) cost, (2) lack of a carbon price, (3) liability, and (4) lack of a comprehensive regulatory regime. Phase II of this Project, as presented in this Report, assesses potential regulatory models for CCS and examines where those models address the hurdles to diffusing CCS technology identified in Phase I. It concludes (1) that a CCS-specific but flexible standard, such as a technology performance standard or a very particular type of market-based regulation, likely will promote CCS diffusion, and (2) that these policies cannot work alone, but rather, should be combined with other measures, such as liability limits and a comprehensive CCS regulatory regime.

  15. Department of Commerce Semiannual Regulatory Agenda

    Science.gov (United States)

    2010-12-20

    ... Shrimp Kicker to improve shrimp retention. Timetable: Action Date FR Cite NPRM 05/00/11 Regulatory... camera and other sensors to monitor fishing activity in order to maintain the integrity of the maximized... observers to monitor on board the mothership processors and thereby maintains the integrity of data...

  16. Regulatory T-cells and autoimmunity.

    LENUS (Irish Health Repository)

    Ni Choileain, Niamh

    2012-02-03

    Approximately 20% of the population is affected by autoimmune or inflammatory diseases mediated by an abnormal immune response. A characteristic feature of autoimmune disease is the selective targeting of a single cell type, organ or tissue by certain populations of autoreactive T-cells. Examples of such diseases include rheumatoid arthritis, insulin-dependent diabetes mellitus, and systemic lupus erythematosus (SLE), all of which are characterized by chronic inflammation, tissue destruction and target organ malfunction. Although strong evidence links most autoimmune diseases to specific genes, considerable controversy prevails regarding the role of regulatory T-cell populations in the disease process. These cells are now also believed to play a key role in mediating transplantation tolerance and inhibiting the induction of tumor immunity. Though the concept of therapeutic immune regulation aimed at treating autoimmune pathology has been validated in many animal models, the development of strategies for the treatment of human autoimmune disorders remains in its infancy. The main obstacles to this include the conflicting findings of different model systems, as well as the contrasting functions of regulatory T-cells and cytokines involved in the development of such disorders. This review examines the role of regulatory T-cells in the pathogenesis of autoimmunity and describes the therapeutic potential of these cells for the prevention of immune-mediated pathologies in the future. Although much remains to be learned about such pathologies, a clearer understanding of the mechanisms by which regulatory T-cells function will undoubtedly lead to exciting new possibilities for immunotherapeutics.

  17. 78 FR 44407 - Regulatory Flexibility Agenda

    Science.gov (United States)

    2013-07-23

    ... due diligence services for asset-backed securities, and issuers and underwriters of asset-backed... July 23, 2013 Part XXVII Securities and Exchange Commission Semiannual Regulatory Agenda #0;#0;Federal Register / Vol. 78 , No. 141 / Tuesday, July 23, 2013 / Unified Agenda#0;#0; ] SECURITIES AND EXCHANGE...

  18. 78 FR 1708 - Regulatory Flexibility Agenda

    Science.gov (United States)

    2013-01-08

    ... diligence services for asset-backed securities, and issuers and underwriters of asset-backed securities... January 8, 2013 Part XXV Securities and Exchange Commission Semiannual Regulatory Agenda #0;#0;Federal Register / Vol. 78 , No. 5 / Tuesday, January 8, 2013 / Unified Agenda#0;#0; ] SECURITIES AND EXCHANGE...

  19. Regulatory pathways in the European Union.

    Science.gov (United States)

    Kohler, Manuela

    2011-01-01

    In principle, there are three defined procedures to obtain approval for a medicinal product in the European Union. As discussed in this overview of the procedures, the decision on which regulatory pathway to use will depend on the nature of the active substance, the target indication(s), the history of product and/or the marketing strategy.

  20. Regulatory system reform of occupational health and safety in China.

    Science.gov (United States)

    Wu, Fenghong; Chi, Yan

    2015-01-01

    With the explosive economic growth and social development, China's regulatory system of occupational health and safety now faces more and more challenges. This article reviews the history of regulatory system of occupational health and safety in China, as well as the current reform of this regulatory system in the country. Comprehensive, a range of laws, regulations and standards that promulgated by Chinese government, duties and responsibilities of the regulatory departments are described. Problems of current regulatory system, the ongoing adjustments and changes for modifying and improving regulatory system are discussed. The aim of reform and the incentives to drive forward more health and safety conditions in workplaces are also outlined.

  1. The post-transcriptional operon

    DEFF Research Database (Denmark)

    Tenenbaum, Scott A.; Christiansen, Jan; Nielsen, Henrik

    2011-01-01

    A post-transcriptional operon is a set of monocistronic mRNAs encoding functionally related proteins that are co-regulated by a group of RNA-binding proteins and/or small non-coding RNAs so that protein expression is coordinated at the post-transcriptional level. The post-transcriptional operon...... model (PTO) is used to describe data from an assortment of methods (e.g. RIP-Chip, CLIP-Chip, miRNA profiling, ribosome profiling) that globally address the functionality of mRNA. Several examples of post-transcriptional operons have been documented in the literature and demonstrate the usefulness...

  2. Battery Post-Test Facility

    Data.gov (United States)

    Federal Laboratory Consortium — Post-test diagnostics of aged batteries can provide additional information regarding the cause of performance degradation, which, previously, could be only inferred...

  3. Regulation of voltage gated calcium channels by GPCRs and post-translational modification.

    Science.gov (United States)

    Huang, Junting; Zamponi, Gerald W

    2016-10-18

    Calcium entry via voltage gated calcium channels mediates a wide range of physiological functions, whereas calcium channel dysregulation has been associated with numerous pathophysiological conditions. There are myriad cell signaling pathways that act on voltage gated calcium channels to fine tune their activities and to regulate their cell surface expression. These regulatory mechanisms include the activation of G protein-coupled receptors and downstream phosphorylation events, and their control over calcium channel trafficking through direct physical interactions. Calcium channels also undergo post-translational modifications that alter both function and density of the channels in the plasma membrane. Here we focus on select aspects of these regulatory mechanisms and highlight recent developments.

  4. post-industrial

    Directory of Open Access Journals (Sweden)

    Omar Guerrero

    2005-01-01

    Full Text Available Hoy en día la sociedad postindustrial se manifiesta en cinco dimensiones: un sector económico; una distribución ocupacional; la centralidad del conocimiento teórico; una orientación del futuro con base en el control de la tecnología y una hechura de decisiones orientadas por la nueva tecnología intelectual. De ahí nace la motivación del presente trabajo, el cual consiste en analizar la gerencia pública en la sociedad postindustrial, a través del análisis documental. Así, en consonancia con las condiciones presentes, esta sociedad da cobijo a una administración pública que se consolida en las relaciones de dominación, es decir el gobierno de los hombres; junto a una gerencia que asume la gestión de las cosas. Actualmente, en suma, la administración pública mantiene sus rasgos esenciales, sin menoscabo de convivir una época en la cual los cambios producidos por la post- industrialización provoca el advenimiento de la modalidad d la gerencia de servicios.

  5. Recovery post ICU.

    Science.gov (United States)

    Jones, Christina

    2014-10-01

    Many ICU patients struggle to recovery following critical illness and may be left with physical, cognitive and psychological problems, which have a negative impact on their quality of life. Gross muscle mass loss and weakness can take some months to recover after the patients' Intensive Care Unit (ICU) discharge, in addition critical illness polyneuropathies can further complicate physical recovery. Psychological problems such as anxiety, depression and post traumatic stress disorder (PTSD) are common and have an negative impact on the patients' ability to engage in rehabilitation after ICU discharge. Finally cognitive deficit affecting memory can be a significant problem. The first step in helping patients to recover from such a devastating illness is to recognise those who have the greatest need and target interventions. Research now suggests that there are interventions that can accelerate physical recovery and reduce the incidence of psychological problems such as anxiety, depression and PTSD. Cognitive rehabilitation, however, is still in its infancy. This review will look at the research into patients' recovery and what can be done to improve this where needed.

  6. 75 FR 8772 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2010-02-25

    ... FINRA Rulebook February 18, 2010. I. Introduction On December 31, 2009, Financial Industry Regulatory... rules be designed to prevent fraud and manipulative practices and to promote just and equitable...

  7. 78 FR 62017 - Regulatory Capital Rules: Regulatory Capital, Implementation of Basel III, Capital Adequacy...

    Science.gov (United States)

    2013-10-11

    ... Value Correlation Factor 4. Credit Valuation Adjustments a. Simple Credit Valuation Adjustment Approach... argued that the proposals would have significant negative consequences for the financial services...) portfolio or holding additional regulatory capital solely to mitigate the volatility resulting from...

  8. Predicting miRNA Targets by Integrating Gene Regulatory Knowledge with Expression Profiles.

    Directory of Open Access Journals (Sweden)

    Weijia Zhang

    Full Text Available microRNAs (miRNAs play crucial roles in post-transcriptional gene regulation of both plants and mammals, and dysfunctions of miRNAs are often associated with tumorigenesis and development through the effects on their target messenger RNAs (mRNAs. Identifying miRNA functions is critical for understanding cancer mechanisms and determining the efficacy of drugs. Computational methods analyzing high-throughput data offer great assistance in understanding the diverse and complex relationships between miRNAs and mRNAs. However, most of the existing methods do not fully utilise the available knowledge in biology to reduce the uncertainty in the modeling process. Therefore it is desirable to develop a method that can seamlessly integrate existing biological knowledge and high-throughput data into the process of discovering miRNA regulation mechanisms.In this article we present an integrative framework, CIDER (Causal miRNA target Discovery with Expression profile and Regulatory knowledge, to predict miRNA targets. CIDER is able to utilise a variety of gene regulation knowledge, including transcriptional and post-transcriptional knowledge, and to exploit gene expression data for the discovery of miRNA-mRNA regulatory relationships. The benefits of our framework is demonstrated by both simulation study and the analysis of the epithelial-to-mesenchymal transition (EMT and the breast cancer (BRCA datasets. Our results reveal that even a limited amount of either Transcription Factor (TF-miRNA or miRNA-mRNA regulatory knowledge improves the performance of miRNA target prediction, and the combination of the two types of knowledge enhances the improvement further. Another useful property of the framework is that its performance increases monotonically with the increase of regulatory knowledge.

  9. Isolation of active regulatory elements from eukaryotic chromatin using FAIRE (Formaldehyde Assisted Isolation of Regulatory Elements)

    OpenAIRE

    Giresi, Paul G.; Lieb, Jason D.

    2009-01-01

    The binding of sequence-specific regulatory factors and the recruitment of chromatin remodeling activities cause nucleosomes to be evicted from chromatin in eukaryotic cells. Traditionally, these active sites have been identified experimentally through their sensitivity to nucleases. Here we describe the details of a simple procedure for the genome-wide isolation of nucleosome-depleted DNA from human chromatin, termed FAIRE (Formaldehyde Assisted Isolation of Regulatory Elements). We also pro...

  10. Regulatory element-based prediction identifies new susceptibility regulatory variants for osteoporosis.

    Science.gov (United States)

    Yao, Shi; Guo, Yan; Dong, Shan-Shan; Hao, Ruo-Han; Chen, Xiao-Feng; Chen, Yi-Xiao; Chen, Jia-Bin; Tian, Qing; Deng, Hong-Wen; Yang, Tie-Lin

    2017-08-01

    Despite genome-wide association studies (GWASs) have identified many susceptibility genes for osteoporosis, it still leaves a large part of missing heritability to be discovered. Integrating regulatory information and GWASs could offer new insights into the biological link between the susceptibility SNPs and osteoporosis. We generated five machine learning classifiers with osteoporosis-associated variants and regulatory features data. We gained the optimal classifier and predicted genome-wide SNPs to discover susceptibility regulatory variants. We further utilized Genetic Factors for Osteoporosis Consortium (GEFOS) and three in-house GWASs samples to validate the associations for predicted positive SNPs. The random forest classifier performed best among all machine learning methods with the F1 score of 0.8871. Using the optimized model, we predicted 37,584 candidate SNPs for osteoporosis. According to the meta-analysis results, a list of regulatory variants was significantly associated with osteoporosis after multiple testing corrections and contributed to the expression of known osteoporosis-associated protein-coding genes. In summary, combining GWASs and regulatory elements through machine learning could provide additional information for understanding the mechanism of osteoporosis. The regulatory variants we predicted will provide novel targets for etiology research and treatment of osteoporosis.

  11. Post-Fukushima Probabilistic Safety Enhancements of Industry

    Energy Technology Data Exchange (ETDEWEB)

    Na, Janghwan; Jeon, Ho-Jun; Lee, Hyun-Gyo [Korea Hydro and Nuclear Power Co. Ltd. Central Research Institute, Daejeon (Korea, Republic of)

    2015-05-15

    Nuclear concerned society as well as regulatory agency of Korea also asked several safety measures be included to the existing safety principles. These measures include the post-Fukushima near action items, several mid-long term obligations for severe accidents and rare external hazards which were disregarded due to unlikely event probabilities. This paper illustrates some activities being done or planned in view of probabilistic assessment boundaries; 1) Items currently performed by industry, 2) Regulatory measures which will impact to the industry activities, 3) Activities planned by mid-long bases. After the Fukushima accident, the significance of severe accidents and PSA came to the public as well as the industry itself. Among fifty safety-related plans, in this paper, we showed the implementation strategies and interim insights from LPSD PSA. The plans or activities now underway are further enhancing the safety for operating by introducing PSR and construction plants by inclusion of PSA insights into SAR. The main focus for safety improvement is targeted by not only the hardware improvement, but also systematic structure and effective operational improvement. The results of LPSD PSA implementation strategy will contribute to conforming of regulatory requirement and legislation of PSA which requests the application of extended scope of analysis, new methodology, PSA quality, living PSA through technically sound and application- specific PSA models.

  12. NEWS: Post-16 update

    Science.gov (United States)

    1999-05-01

    (post16) Making physics connect Doesn't Melvyn Bragg do a wonderful job, engaging both scientists and artists in sensitive discussion on Radio 4 about their methods and their purposes? But every week teachers have the chance to show their students that physics is a way of seeing the world that is well-connected with other aspects of knowledge and culture. The stakes are high: students who fail to appreciate this generally choose not to study the subject beyond GCSE. Most students find our preoccupation with technical detail off-putting. Accepting that we have a syllabus to cover, it's still a question of balance. In our teaching we should aim for variety in order to find ways to connect with every student's interests. Also, we can show that we (the nearest embodiment of a physicist some students will experience) are multidimensional and so fully human. Most important, teachers need flexibility to both encourage and respond to student comment and questions. The first booklet in the discussion series Shaping the Future takes up these themes. Rich in ideas for both immediate use and the longer term, it aims to stimulate debate and improve teaching. Copies cost £5.50 including postage and are available from Ingrid Ebeyer, Post-16 Initiative, Institute of Physics, 76 Portland Place, London W1N 3DH. How far is it? This question is asked in many family cars and school minibuses at the start of a journey, and answered by most in terms of hours and minutes rather than miles. What a good idea for introducing a social and historical perspective to a lesson on distance, velocity and time. How far can you actually get in a day? What is the range of human activity? Walking for eight hours will get many people about 25 miles. A pack horse will progress at much the same rate, but fast riding or a coach and team of horses will get further. Motorway driving (when the cones are on holiday) would take you nearly 500 miles. The 05.15 am train from Penzance arrives in Inverness at 7

  13. Post-Laminectomy Wound Infections: Colonized Seromas Mimicking Wound Infections

    Directory of Open Access Journals (Sweden)

    Burke A. Cunha

    2014-02-01

    Full Text Available Objective: Post-operative laminectomy wounds are frequently accompanied by seromas. Post-operative wound drainage may be colonized or infected. The differentiation of wound colonization from infection is difficult for non-infectious disease physicians. Methods: External chart reviewers classified 31/1531 laminectomies (over three years as post-operative wound infections. We re-evaluated these cases using infectious disease criteria, i.e., while pathogens may be cultured from both colonized and infected wounds, only wound infections have a purulent discharge with abundant white blood cells (WBCs on Gram stain. Colonized wounds have positive wound cultures but no/few WBCs on Gram stain. Results: We found only 11/31 actual wound infections, the remainder were not bona fide wound infections, but were colonized seromas. Conclusion: Post-laminectomy colonized seromas that are culture positive for one or more organisms often mimic wound infections. In the era of public reporting of nosocomial infections, it is important that external reviewers differentiate colonization from infection to provide regulatory agencies with accurate data.

  14. Post-Laminectomy Wound Infections: Colonized Seromas Mimicking Wound Infections.

    Science.gov (United States)

    Cunha, Burke A; Abruzzo, Eileen D; Schoch, Paul E

    2014-02-14

    Post-operative laminectomy wounds are frequently accompanied by seromas. Post-operative wound drainage may be colonized or infected. The differentiation of wound colonization from infection is difficult for non-infectious disease physicians. External chart reviewers classified 31/1531 laminectomies (over three years) as post-operative wound infections. We re-evaluated these cases using infectious disease criteria, i.e., while pathogens may be cultured from both colonized and infected wounds, only wound infections have a purulent discharge with abundant white blood cells (WBCs) on Gram stain. Colonized wounds have positive wound cultures but no/few WBCs on Gram stain. We found only 11/31 actual wound infections, the remainder were not bona fide wound infections, but were colonized seromas. Post-laminectomy colonized seromas that are culture positive for one or more organisms often mimic wound infections. In the era of public reporting of nosocomial infections, it is important that external reviewers differentiate colonization from infection to provide regulatory agencies with accurate data.

  15. Mechanisms of post-transcriptional gene regulation in bacterial biofilms

    Directory of Open Access Journals (Sweden)

    Viveka eVadyvaloo

    2014-03-01

    Full Text Available Abstract Biofilms are characterized by a dense multicellular community of microorganisms that can be formed by the attachment of bacteria to an inert surface and to each other. The development of biofilm involves the initial attachment of planktonic bacteria to a surface, followed by replication, cell-to-cell adhesion to form microcolonies, maturation and detachment. Mature biofilms are embedded in a self-produced extracellular polymeric matrix composed primarily of bacterial-derived exopolysaccharides, specialized proteins, adhesins and occasionally DNA. Because the synthesis and assembly of biofilm matrix components is an exceptionally complex process, the transition between its different phases requires the coordinate expression and simultaneous regulation of many genes by complex genetic networks involving all levels of gene regulation. The finely controlled intracellular level of the chemical second messenger molecule, cyclic-di-GMP is central to the post-transcriptional mechanisms governing the switch between the motile planktonic lifestyle and the sessile biofilm forming state in many bacteria. Several other post-transcriptional regulatory mechanisms are known to dictate biofilm development and assembly and these include RNA-binding proteins, small non-coding RNAs, toxin-antitoxin systems, riboswitches and RNases. Post-transcriptional regulation is therefore a powerful molecular mechanism employed by bacteria to rapidly adjust to the changing environment and to fine tune gene expression to the developmental needs of the cell. In this review, we discuss post-transcriptional mechanisms that influence the biofilm developmental cycle in a variety of pathogenic bacteria.

  16. TOR-dependent post-transcriptional regulation of autophagy.

    Science.gov (United States)

    Hu, Guowu; McQuiston, Travis; Bernard, Amélie; Park, Yoon-Dong; Qiu, Jin; Vural, Ali; Zhang, Nannan; Waterman, Scott R; Blewett, Nathan H; Myers, Timothy G; Maraia, Richard J; Kehrl, John H; Uzel, Gulbu; Klionsky, Daniel J; Williamson, Peter R

    2015-01-01

    Regulation of autophagy is required to maintain cellular equilibrium and prevent disease. While extensive study of post-translational mechanisms has yielded important insights into autophagy induction, less is known about post-transcriptional mechanisms that could potentiate homeostatic control. In our study, we showed that the RNA-binding protein, Dhh1 in Saccharomyces cerevisiae and Vad1 in the pathogenic yeast Cryptococcus neoformans is involved in recruitment and degradation of key autophagy mRNAs. In addition, phosphorylation of the decapping protein Dcp2 by the target of rapamycin (TOR), facilitates decapping and degradation of autophagy-related mRNAs, resulting in repression of autophagy under nutrient-replete conditions. The post-transcriptional regulatory process is conserved in both mouse and human cells and plays a role in autophagy-related modulation of the inflammasome product IL1B. These results were then applied to provide mechanistic insight into autoimmunity of a patient with a PIK3CD/p110δ gain-of-function mutation. These results thus identify an important new post-transcriptional mechanism of autophagy regulation that is highly conserved between yeast and mammals.

  17. 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...

  18. Legal principles of regulatory administration and nuclear safety regulation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kyeong Hui; Cheong, Sang Kee [Hannam Univ., Taejon (Korea, Republic of)

    2000-12-15

    This research presents a critical analysis and evaluation of principles of administrative laws in order to provide framework of structural reform on the nuclear safety regulation system. The focus of this analysis and evaluation is centered around the area of origin of regulatory administrative laws; authorities of regulation; procedures of regulatory actions; regulatory enforcement; and administrative relief system. In chapter 2 the concept of regulatory administration is analysed. Chapter 3 identifies the origin of regulatory administration and the principles of administration laws. It also examines legal nature of the nuclear safety standard. In relation to regulatory authorities. Chapter 4 identifies role and responsibility of administration authorities and institutions. It also examines fundamental principles of delegation of power. Then the chapter discusses the nuclear safety regulation authorities and their roles and responsibilities. Chapter 5 classifies and examines regulatory administration actions. Chapter 6 evaluates enforcement measure for effectiveness of regulation. Finally, chapter 7 discusses the administrative relief system for reviewing unreasonable regulatory acts.

  19. 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...

  20. Environmental regulatory and policy framework in China: an overview

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    China has developed one of the most comprehensive environmental regulatory and policy framework in the world. This paper provides a description of the main institutions for environmental management in China, and overviews the regulatory and policy framework in place.

  1. National Strategy for Modernizing the Regulatory System for Biotechnology Products

    Science.gov (United States)

    This National Strategy for Modernizing the Regulatory System for Biotechnology Products sets forth a vision for ensuring that the federal regulatory system is prepared to efficiently assess the risks, if any, of the future products of biotechnology.

  2. What is 'Post-digital?'

    NARCIS (Netherlands)

    F. Cramer

    2014-01-01

    The term "post-digital" was coined in 2000 for electronic music, but reflecting on larger developments in technology and culture, to describe a perspective on digital information technology that is no longer focused on technical innovation or improvement. In the meantime, "post-digital" has acquired

  3. Post-Exposure Prophylaxis (PEP)

    Science.gov (United States)

    ... Pre-Exposure Prophylaxis (PrEP) Post-Exposure Prophylaxis (PEP) HIV Treatment HIV Treatment: The Basics Just Diagnosed: Next Steps After Testing ... HIV HIV and Mental Health How to Find HIV Treatment Services HIV Prevention Post-Exposure Prophylaxis (PEP) (Last ...

  4. Regulatory reform of Finnish environmental policy

    Energy Technology Data Exchange (ETDEWEB)

    Sairinen, R.

    2000-07-01

    The main question of this study concerns the regulatory reform i.e. formation and design of new policy instruments in the Finnish environmental policy. The research question is divided into two parts: (1) How have the new policy instruments evolved and been designed (2) What are the political, administrative, historical and ideological factors underlying the processes of policy instrument formation and design? Three main approaches for analysis are introduced: the model of policy instrument choice by Linder and Peters, the model of policy explanation by Jaenicke, and the concept of governmentality developed by Foucault. Within the developed theoretical framework, the general societal background of regulatory reform is composed of the various features of 'environmental governmentality'. The research questions are divided into two empirical research tasks. (1) Analysis of the historical development of Finnish environmental governing and policy style provides background information about the national institutional settings and policy cultures in order to understand the role of the new policy instruments in the Finnish environmental policy during last two decades. Here, Finnish environmental policy divides into consensual pollution policies and adversial nature conservation. Four main periods of environmental governmentality in Finland is presented: the early nature conservation initiatives (1800-1939), the neglect of environmental issues (1945-1969), the environmental institutionalisation (1970-1986), and the regulatory reform (1987-). (2) The contextual case studies concerns: the drafting of the EIA Act in 1982-1994; the formation of the carbon tax policy in 1989-1996; and the implementation of voluntary environmental agreements in 1987-99. The study shows that regulatory reform has not been an easy policy process in Finland. There has been no common environmental governmentality behind the on-going regulatory reform. The new policy instruments have been

  5. QbD implementation and Post Approval Lifecycle Management (PALM).

    Science.gov (United States)

    Ohage, Ettore; Iverson, Raquel; Krummen, Lynne; Taticek, Ron; Vega, Maria

    2016-09-01

    Quality by design (QbD) is a global regulatory initiative with the goal of enhancing pharmaceutical development through the proactive design of pharmaceutical manufacturing process and controls to consistently deliver the intended performance of the product. The principles of pharmaceutical development relevant to QbD are described in the ICH guidance documents (ICHQ8-11) [1-3]. An integrated set of risk assessments and their related elements developed at Roche/Genentech were designed to provide an overview of product and process knowledge for the production of a recombinant monoclonal antibody. This chapter describes concepts for implementing the control strategy for a monoclonal antibody including a Design Space for routine commercial manufacturing, and the Post Approval Lifecycle Management (PALM) plan that is used to manage any remaining risks during the commercial lifecycle. The PALM plan is part of the submitted dossier in the regional section and serves as a regulatory agreement between the manufacturer and the health authority specifying how process and product attributes are monitored to ensure both remain within a controlled state post-approval, process parameter changes are managed within the design space, and the control system is updated as necessary based on further process and product knowledge.

  6. Social Media Listening for Routine Post-Marketing Safety Surveillance.

    Science.gov (United States)

    Powell, Gregory E; Seifert, Harry A; Reblin, Tjark; Burstein, Phil J; Blowers, James; Menius, J Alan; Painter, Jeffery L; Thomas, Michele; Pierce, Carrie E; Rodriguez, Harold W; Brownstein, John S; Freifeld, Clark C; Bell, Heidi G; Dasgupta, Nabarun

    2016-05-01

    Post-marketing safety surveillance primarily relies on data from spontaneous adverse event reports, medical literature, and observational databases. Limitations of these data sources include potential under-reporting, lack of geographic diversity, and time lag between event occurrence and discovery. There is growing interest in exploring the use of social media ('social listening') to supplement established approaches for pharmacovigilance. Although social listening is commonly used for commercial purposes, there are only anecdotal reports of its use in pharmacovigilance. Health information posted online by patients is often publicly available, representing an untapped source of post-marketing safety data that could supplement data from existing sources. The objective of this paper is to describe one methodology that could help unlock the potential of social media for safety surveillance. A third-party vendor acquired 24 months of publicly available Facebook and Twitter data, then processed the data by standardizing drug names and vernacular symptoms, removing duplicates and noise, masking personally identifiable information, and adding supplemental data to facilitate the review process. The resulting dataset was analyzed for safety and benefit information. In Twitter, a total of 6,441,679 Medical Dictionary for Regulatory Activities (MedDRA(®)) Preferred Terms (PTs) representing 702 individual PTs were discussed in the same post as a drug compared with 15,650,108 total PTs representing 946 individual PTs in Facebook. Further analysis revealed that 26 % of posts also contained benefit information. Social media listening is an important tool to augment post-marketing safety surveillance. Much work remains to determine best practices for using this rapidly evolving data source.

  7. Parameter optimization for constructing competing endogenous RNA regulatory network in glioblastoma multiforme and other cancers

    OpenAIRE

    2015-01-01

    Background In addition to direct targeting and repressing mRNAs, recent studies reported that microRNAs (miRNAs) can bridge up an alternative layer of post-transcriptional gene regulatory networks. The competing endogenous RNA (ceRNA) regulation depicts the scenario where pairs of genes (ceRNAs) sharing, fully or partially, common binding miRNAs (miRNA program) can establish coexpression through competition for a limited pool of the miRNA program. While the dynamics of ceRNA regulation among ...

  8. 40 CFR 73.86 - State regulatory autonomy.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false State regulatory autonomy. 73.86 Section 73.86 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... regulatory autonomy. Nothing in this subpart shall preclude a State or State regulatory authority...

  9. What's the Regulatory Value of a Target Product Profile?

    Science.gov (United States)

    Breder, Christopher D; Du, Wenny; Tyndall, Adria

    2017-07-01

    Target product profiles (TPPs) are used as a regulatory tool for dialog on clinical development or manufacturing plans. Drugs and biologics approved by the FDA that mention TPPs are associated with more efficient regulatory review times, perhaps as a result of increased planning or because the TPP promotes well-organized regulatory dialog. Published by Elsevier Ltd.

  10. 76 FR 59066 - Notice of Regulatory Review Plan

    Science.gov (United States)

    2011-09-23

    ...; ] FEDERAL HOUSING FINANCE AGENCY 12 CFR Chapter XII Notice of Regulatory Review Plan AGENCY: Federal Housing...) is issuing a notice of and requesting comments on the FHFA interim regulatory review plan for review.... Comments FHFA invites comments on all aspects of the interim regulatory review plan, including legal...

  11. Regulatory RNAs in prokaryotes: here, there and everywhere.

    Science.gov (United States)

    Narberhaus, Franz; Vogel, Jörg

    2009-10-01

    A recent meeting on 'Regulatory RNAs in prokaryotes' reflected the growing interest in this research topic. Almost 200 scientists met to discuss the identification, structure, function and mechanistic details of regulatory RNAs in bacteria and archaea. The topics included small regulatory RNAs, riboswitches, RNA thermosensors and CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) elements.

  12. Environmental Regulatory Update Table, January/February 1995

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Bock, R.E.; Mayer, S.J.; Salk, M.S.

    1995-03-01

    The Environmental Regulatory Update Table provides information on regulatory initiatives impacting environmental, health, and safety management responsibilities. the table is updated bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  13. 18 CFR 367.2540 - Account 254, Other regulatory liabilities.

    Science.gov (United States)

    2010-04-01

    ... GAS ACT Balance Sheet Chart of Accounts Deferred Credits § 367.2540 Account 254, Other regulatory... regulatory liabilities. 367.2540 Section 367.2540 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE PUBLIC UTILITY HOLDING COMPANY ACT OF...

  14. Security issues of new innovative payments and their regulatory challenges

    NARCIS (Netherlands)

    Kasiyanto, Safari; Gabriella, Gimigliano

    2016-01-01

    Kasiyanto discusses how the security issues of M-payments and Bitcoin as new forms of innovative payments challenge the existing EU regulatory frameworks, and whether the proposed regulatory frameworks suffice to address such challenges. The regulatory frameworks Kasiyanto discusses mainly focus on

  15. Security issues of new innovative payments and their regulatory challenges

    NARCIS (Netherlands)

    Kasiyanto, Safari; Gabriella, Gimigliano

    2016-01-01

    Kasiyanto discusses how the security issues of M-payments and Bitcoin as new forms of innovative payments challenge the existing EU regulatory frameworks, and whether the proposed regulatory frameworks suffice to address such challenges. The regulatory frameworks Kasiyanto discusses mainly focus on

  16. Genomic regulatory landscapes and chromosomal rearrangements

    DEFF Research Database (Denmark)

    Ladegaard, Elisabete L Engenheiro

    2008-01-01

    The main objectives of the PhD study are to identify and characterise chromosomal rearrangements within evolutionarily conserved regulatory landscapes around genes involved in the regulation of transcription and/or development (trans-dev genes). A frequent feature of trans-dev genes...... the complex spatio-temporal expression of the associated trans-dev gene. Rare chromosomal breakpoints that disrupt the integrity of these regulatory landscapes may be used as a tool, not only to make genotype-phenotype associations, but also to link the associated phenotype with the position and tissue...... specificity of the individual CNEs. In this PhD study I have studied several chromosomal rearrangements with breakpoints in the vicinity of trans-dev genes. This included chromosomal rearrangements compatible with known phenotype-genotype associations (Rieger syndrome-PITX2, Mowat-Wilson syndrome-ZEB2...

  17. Medical research misconduct need regulatory reforms.

    Science.gov (United States)

    Bedi, Neeraj

    2014-10-01

    The medical research misconduct has become a global problem. Except from countries like the USA, China, and Germany the exact figures of misconduct are not available. The research misconduct include fabricating the data, falsifying data, and plagiarism. The irresponsible research practices are publishing research data more than once, conflicts of interest is not declared, selective reporting of data and including an author who has not contributed at all and many more. About 2% of scientists have been found to admit the fabricating the data and 33% researchers were involved in irresponsible research practices. There is no formal regulatory programs available to monitor the research projects. Few developed countries like the USA, Germany, and China tried to develop programs which can monitor the medical research misconduct. There is a need to develop a regulatory system at national and institutional level to regulate the research activity to ensure that good ethical and scientific standards are practiced by medical researchers.

  18. Medical research misconduct need regulatory reforms

    Directory of Open Access Journals (Sweden)

    Neeraj Bedi

    2014-01-01

    Full Text Available The medical research misconduct has become a global problem. Except from countries like the USA, China, and Germany the exact figures of misconduct are not available. The research misconduct include fabricating the data, falsifying data, and plagiarism. The irresponsible research practices are publishing research data more than once, conflicts of interest is not declared, selective reporting of data and including an author who has not contributed at all and many more. About 2% of scientists have been found to admit the fabricating the data and 33% researchers were involved in irresponsible research practices. There is no formal regulatory programs available to monitor the research projects. Few developed countries like the USA, Germany, and China tried to develop programs which can monitor the medical research misconduct. There is a need to develop a regulatory system at national and institutional level to regulate the research activity to ensure that good ethical and scientific standards are practiced by medical researchers.

  19. Emerging regulatory paradigms in glutathione metabolism

    Science.gov (United States)

    Liu, Yilin; Hyde, Annastasia S.; Simpson, Melanie A.; Barycki, Joseph J.

    2015-01-01

    One of the hallmarks of cancer is the ability to generate and withstand unusual levels of oxidative stress. In part, this property of tumor cells is conferred by elevation of the cellular redox buffer glutathione. Though enzymes of the glutathione synthesis and salvage pathways have been characterized for several decades, we still lack a comprehensive understanding of their independent and coordinate regulatory mechanisms. Recent studies have further revealed that overall central metabolic pathways are frequently altered in various tumor types, resulting in significant increases in biosynthetic capacity, and feeding into glutathione synthesis. In this review, we will discuss the enzymes and pathways affecting glutathione flux in cancer, and summarize current models for regulating cellular glutathione through both de novo synthesis and efficient salvage. In addition, we examine the integration of glutathione metabolism with other altered fates of intermediary metabolites, and highlight remaining questions about molecular details of the accepted regulatory modes. PMID:24974179

  20. Regulatory Competition in Global Financial Markets

    DEFF Research Database (Denmark)

    Ringe, Georg

    2016-01-01

    Regulatory arbitrage in financial markets refers to a number of strategies that market participants use to avoid the reach of regulation, in particular by virtue of moving trading abroad or relocating activities or operations of financial institutions to other jurisdictions. Where this happens...... institutions' excessive risk-taking. If such risk-taking would be judged by market discipline instead of posing a risk to global financial stability, the main downside of regulatory competition could be restrained. Within the boundaries of such a system, competition could then operate and contribute...... their standards solely to attract business and thereby impose externalities on the worldwide financial market by undermining financial stability as a global public good. Policymakers worldwide are experimenting with remedies to respond to the phenomenon. I introduce the importance of an effective special...

  1. Papers on the nuclear regulatory dilemma

    Energy Technology Data Exchange (ETDEWEB)

    Barkenbus, J.N.; Freeman, S.D.; Weinberg, A.M.

    1985-10-01

    The four papers contained in this report are titled: (1) From Prescriptive to Performance-Based Regulation of Nuclear Power; (2) Nuclear Regulatory Reform: A Technology-Forcing Approach; (3) Improving the Regulation of Nuclear Power; and (4) Science and Its Limits: The Regulators' Dilemma. These four papers investigate issues relating to the long-term regulation of nuclear energy. They were prepared as part of the Institute for Energy Analysis' project on Nuclear Regulation funded by a grant from the Mellon Foundation and a smaller grant by the MacArthur Foundation. Originally this work was to be supplemented by contributions from the Nuclear Regulatory Commission and from the Department of Energy. These contributions were not forthcoming, and as a result the scope of our investigations was more restricted than we had originally planned.

  2. Modeling Emergence in Neuroprotective Regulatory Networks

    Energy Technology Data Exchange (ETDEWEB)

    Sanfilippo, Antonio P.; Haack, Jereme N.; McDermott, Jason E.; Stevens, S.L.; Stenzel-Poore, Mary

    2013-01-05

    The use of predictive modeling in the analysis of gene expression data can greatly accelerate the pace of scientific discovery in biomedical research by enabling in silico experimentation to test disease triggers and potential drug therapies. Techniques that focus on modeling emergence, such as agent-based modeling and multi-agent simulations, are of particular interest as they support the discovery of pathways that may have never been observed in the past. Thus far, these techniques have been primarily applied at the multi-cellular level, or have focused on signaling and metabolic networks. We present an approach where emergence modeling is extended to regulatory networks and demonstrate its application to the discovery of neuroprotective pathways. An initial evaluation of the approach indicates that emergence modeling provides novel insights for the analysis of regulatory networks that can advance the discovery of acute treatments for stroke and other diseases.

  3. PKA regulatory subunit expression in tooth development.

    Science.gov (United States)

    de Sousa, Sílvia Ferreira; Kawasaki, Katsushige; Kawasaki, Maiko; Volponi, Ana Angelova; Gomez, Ricardo Santiago; Gomes, Carolina Cavaliéri; Sharpe, Paul T; Ohazama, Atsushi

    2014-05-01

    Protein kinase A (PKA) plays critical roles in many biological processes including cell proliferation, cell differentiation, cellular metabolism and gene regulation. Mutation in PKA regulatory subunit, PRKAR1A has previously been identified in odontogenic myxomas, but it is unclear whether PKA is involved in tooth development. The aim of the present study was to assess the expression of alpha isoforms of PKA regulatory subunit (Prkar1a and Prkar2a) in mouse and human odontogenesis by in situ hybridization. PRKAR1A and PRKAR2A mRNA transcription was further confirmed in a human deciduous germ by qRT-PCR. Mouse Prkar1a and human PRKAR2A exhibited a dynamic spatio-temporal expression in tooth development, whereas neither human PRKAR1A nor mouse Prkar2a showed their expression in odontogenesis. These isoforms thus showed different expression pattern between human and mouse tooth germs. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Regulatory norm”: myth or reality?

    Directory of Open Access Journals (Sweden)

    Hugo Alberto Marín Hernández

    2010-06-01

    Full Text Available A controversy has arisen from identifying the nature and position, in the system of sources, of the decisions taken by the regulation commissions of home public service utilities (Spanish acronym crspd. In order to explain our position towards this matter, this document makes reference to (1 the explanatory criteria of the relations between the law and the regulations in the Colombian legal code and (2 the identification of the types of regulations determined by the existence of said criteria; (3 the proposal of distinction between regulation power –regulation- and regulatory faculty –“regulatory norm”- in the national jurisprudence and doctrine, in order to finally (4 outline which are the legal nature of the regulation function and the position, in the administrative law system of sources, of the regulating products derived from the CRSPD.

  5. Attribute Exploration of Gene Regulatory Processes

    CERN Document Server

    Wollbold, Johannes

    2012-01-01

    This thesis aims at the logical analysis of discrete processes, in particular of such generated by gene regulatory networks. States, transitions and operators from temporal logics are expressed in the language of Formal Concept Analysis. By the attribute exploration algorithm, an expert or a computer program is enabled to validate a minimal and complete set of implications, e.g. by comparison of predictions derived from literature with observed data. Here, these rules represent temporal dependencies within gene regulatory networks including coexpression of genes, reachability of states, invariants or possible causal relationships. This new approach is embedded into the theory of universal coalgebras, particularly automata, Kripke structures and Labelled Transition Systems. A comparison with the temporal expressivity of Description Logics is made. The main theoretical results concern the integration of background knowledge into the successive exploration of the defined data structures (formal contexts). Applyi...

  6. Regulatory mechanisms link phenotypic plasticity to evolvability.

    Science.gov (United States)

    van Gestel, Jordi; Weissing, Franz J

    2016-04-18

    Organisms have a remarkable capacity to respond to environmental change. They can either respond directly, by means of phenotypic plasticity, or they can slowly adapt through evolution. Yet, how phenotypic plasticity links to evolutionary adaptability is largely unknown. Current studies of plasticity tend to adopt a phenomenological reaction norm (RN) approach, which neglects the mechanisms underlying plasticity. Focusing on a concrete question - the optimal timing of bacterial sporulation - we here also consider a mechanistic approach, the evolution of a gene regulatory network (GRN) underlying plasticity. Using individual-based simulations, we compare the RN and GRN approach and find a number of striking differences. Most importantly, the GRN model results in a much higher diversity of responsive strategies than the RN model. We show that each of the evolved strategies is pre-adapted to a unique set of unseen environmental conditions. The regulatory mechanisms that control plasticity therefore critically link phenotypic plasticity to the adaptive potential of biological populations.

  7. Regulatory research / Pesquisa regulatória

    Directory of Open Access Journals (Sweden)

    Altair Souza de Assis

    2013-05-01

    Full Text Available We present in this paper the concept, importance, and scope of research into the regulatory framework of regulation and legislation, with a particular focus on legislation related to legal metrology. This study also describes a comparative analysis of the various forms of regulation and the associated regulatory research, with the ultimate goal of better defi ning the concept and to validate the need to have research groups within a country’s regulatory bodies. Based on this work, we conclude that regulatory research is a key factor in the success of any regulatory body’s activities. Such research helps to avoid the creation of absurd or impractical regulatory barriers to a country’s technological development, or worse, to permit “orphans,” that is, technologies that are outside regulatory control, as is currently the case. Indeed, for a country to have a robust technological infrastructure, especially if it is still a developing country, strong and competent regulatory control is essential. However, this must be balanced by an atmosphere that fosters continuous and consistent technological innovation, and such development must also be self-sustainable from economic, social, and environmental viewpoints. ------------------------------------------------ Apresenta-se neste trabalho o conceito, a importância e a abrangência da pesquisa regulatória no âmbito da regulação e da regulamentação, com foco particular na regulamentação relacionada à metrologia legal. Faz-se também uma análise comparativa entre as várias formas de regular e regulamentar, e as suas pesquisas regulatórias afi ns, tendo como meta principal situar melhor o conceito e validar a necessidade de se fazer pesquisa nos órgãos e agências regulatórias do país. Com base neste trabalho, concluímos que a pesquisa regulatória é um fator chave para o sucesso de qualquer plano de ação de regulação para os agentes regulatórios do país. Ela ajuda a

  8. Post-16 update

    Science.gov (United States)

    1999-03-01

    Post-16 Initiative logo Physics in Mathematical Mood Later this year, as part of the post-16 initiative of the Institute of Physics, a booklet with the above title will be published. In draft form, the booklet was discussed at the ASE conference in January. Some of the issues raised are briefly set out here. If you have any views to contribute, please write to Simon Carson at the Institute of Physics or e-mail simon.carson@physics.org. A mathematical view of the world is intrinsically a part of physics and therefore physics should be studied in an appropriately mathematical way. However, we all know that, to some students at least, mathematics proves to be a stumbling block rather than a powerful aid to understanding. So how can we help? Realizing that as physics teachers we need to deliver the mathematics necessary to an understanding of our subject is a start. Its corollary is that we need to find the space within the physics core. We may wish to use supplementary courses such as AS mathematics or QCA's new free-standing mathematics units, but requiring additional courses as a prerequisite to a study of A-level physics may deter students. Teaching the mathematics in context may aid understanding but we also must ensure that techniques are seen in a variety of contexts and that at some point the tool is abstracted from the background. As teachers we need to be aware of the very basic mathematical difficulties that students bring with them: the use of calculators, standard form, simple algebraic manipulation, for example. Mathematical arguments need to be developed fully and carefully. Encouraging cooperation and discussion between students may help the less able to understand and the more able to appreciate and develop their own understanding through making explicit their reasoning by explaining it to others. And what of new technology? Software tools allow students to develop their understanding about graphs, for example, enabling them to investigate the

  9. Regulatory roles of microRNAs in human dental tissues.

    Science.gov (United States)

    Sehic, Amer; Tulek, Amela; Khuu, Cuong; Nirvani, Minou; Sand, Lars Peter; Utheim, Tor Paaske

    2017-01-05

    MicroRNAs (miRNAs) are a class of small, non-coding RNAs that provide an efficient pathway for regulation of gene expression at a post-transcriptional level. Tooth development is regulated by a complex network of cell-cell signaling during all steps of organogenesis. Most of the congenital dental defects in humans are caused by mutations in genes involved in developmental regulatory networks. Whereas the developmental morphological stages of the tooth development already are thoroughly documented, the implicated genetic network is still under investigation. The involvement of miRNAs in the regulation of tooth genetic network was suggested for the first time in 2008. MiRNAs regulate tooth morphogenesis by fine-tuning the signaling networks. Unique groups of miRNAs are expressed in dental epithelium compared with mesenchyme, as well as in molars compared with incisors. The present review focuses on the current state of knowledge on the expression and function of miRNAs in human dental tissues, including teeth and the surrounding structures. Herein, we show that miRNAs exhibit specific roles in human dental tissues and are involved in gingival and periodontal disease, tooth movement and eruption, dental pulp physiology including repair and regeneration, differentiation of dental cells, and enamel mineralization. In light of similarities between the tooth development and other organs originating from the epithelium, further understanding of miRNAs` function in dental tissues may have wide biological relevance. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Population Dynamics of Genetic Regulatory Networks

    Science.gov (United States)

    Braun, Erez

    2005-03-01

    Unlike common objects in physics, a biological cell processes information. The cell interprets its genome and transforms the genomic information content, through the action of genetic regulatory networks, into proteins which in turn dictate its metabolism, functionality and morphology. Understanding the dynamics of a population of biological cells presents a unique challenge. It requires to link the intracellular dynamics of gene regulation, through the mechanism of cell division, to the level of the population. We present experiments studying adaptive dynamics of populations of genetically homogeneous microorganisms (yeast), grown for long durations under steady conditions. We focus on population dynamics that do not involve random genetic mutations. Our experiments follow the long-term dynamics of the population distributions and allow to quantify the correlations among generations. We focus on three interconnected issues: adaptation of genetically homogeneous populations following environmental changes, selection processes on the population and population variability and expression distributions. We show that while the population exhibits specific short-term responses to environmental inputs, it eventually adapts to a robust steady-state, largely independent of external conditions. Cycles of medium-switch show that the adapted state is imprinted in the population and that this memory is maintained for many generations. To further study population adaptation, we utilize the process of gene recruitment whereby a gene naturally regulated by a specific promoter is placed under a different regulatory system. This naturally occurring process has been recognized as a major driving force in evolution. We have recruited an essential gene to a foreign regulatory network and followed the population long-term dynamics. Rewiring of the regulatory network allows us to expose their complex dynamics and phase space structure.

  11. XcisClique: analysis of regulatory bicliques

    Directory of Open Access Journals (Sweden)

    Grene Ruth

    2006-04-01

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

  12. Responding to the changing regulatory scene

    Energy Technology Data Exchange (ETDEWEB)

    Wise, P.

    1995-12-31

    The regulatory approach of the Illinois Environmental Protection Agency (EPA) is discussed in this paper. Three areas receive emphasis: (1) the changing relations between the US EPA and the states, (2) the new emphasis on pollution prevention techniques, and (3) a new environmental amnesty project. Budgetary considerations, performance partnerships, and nonregulatory compliance assistance are briefly outlined in relation to these topics. Results of the environmental amnesty program for small business, called Clean Break, are briefly reported.

  13. Evolution of evolvability in gene regulatory networks.

    Directory of Open Access Journals (Sweden)

    Anton Crombach

    Full Text Available Gene regulatory networks are perhaps the most important organizational level in the cell where signals from the cell state and the outside environment are integrated in terms of activation and inhibition of genes. For the last decade, the study of such networks has been fueled by large-scale experiments and renewed attention from the theoretical field. Different models have been proposed to, for instance, investigate expression dynamics, explain the network topology we observe in bacteria and yeast, and for the analysis of evolvability and robustness of such networks. Yet how these gene regulatory networks evolve and become evolvable remains an open question. An individual-oriented evolutionary model is used to shed light on this matter. Each individual has a genome from which its gene regulatory network is derived. Mutations, such as gene duplications and deletions, alter the genome, while the resulting network determines the gene expression pattern and hence fitness. With this protocol we let a population of individuals evolve under Darwinian selection in an environment that changes through time. Our work demonstrates that long-term evolution of complex gene regulatory networks in a changing environment can lead to a striking increase in the efficiency of generating beneficial mutations. We show that the population evolves towards genotype-phenotype mappings that allow for an orchestrated network-wide change in the gene expression pattern, requiring only a few specific gene indels. The genes involved are hubs of the networks, or directly influencing the hubs. Moreover, throughout the evolutionary trajectory the networks maintain their mutational robustness. In other words, evolution in an alternating environment leads to a network that is sensitive to a small class of beneficial mutations, while the majority of mutations remain neutral: an example of evolution of evolvability.

  14. Adaptation by Plasticity of Genetic Regulatory Networks

    Science.gov (United States)

    Brenner, Naama

    2007-03-01

    Genetic regulatory networks have an essential role in adaptation and evolution of cell populations. This role is strongly related to their dynamic properties over intermediate-to-long time scales. We have used the budding yeast as a model Eukaryote to study the long-term dynamics of the genetic regulatory system and its significance in evolution. A continuous cell growth technique (chemostat) allows us to monitor these systems over long times under controlled condition, enabling a quantitative characterization of dynamics: steady states and their stability, transients and relaxation. First, we have demonstrated adaptive dynamics in the GAL system, a classic model for a Eukaryotic genetic switch, induced and repressed by different carbon sources in the environment. We found that both induction and repression are only transient responses; over several generations, the system converges to a single robust steady state, independent of external conditions. Second, we explored the functional significance of such plasticity of the genetic regulatory network in evolution. We used genetic engineering to mimic the natural process of gene recruitment, placing the gene HIS3 under the regulation of the GAL system. Such genetic rewiring events are important in the evolution of gene regulation, but little is known about the physiological processes supporting them and the dynamics of their assimilation in a cell population. We have shown that cells carrying the rewired genome adapted to a demanding change of environment and stabilized a population, maintaining the adaptive state for hundreds of generations. Using genome-wide expression arrays we showed that underlying the observed adaptation is a global transcriptional programming that allowed tuning expression of the recruited gene to demands. Our results suggest that non-specific properties reflecting the natural plasticity of the regulatory network support adaptation of cells to novel challenges and enhance their evolvability.

  15. Autophagy gets in on the regulatory act

    Institute of Scientific and Technical Information of China (English)

    Steven K. Backues; Daniel J. Klionsky

    2011-01-01

    Autophagy down-regulates the Wnt signal transduction pathway via targeted degradation of a key signaling protein. This may provide an explanation for autophagy's role in tumor suppression.%@@ The eukaryotic cell has at its disposal two primary methods for getting rid of unwanted proteins: the proteasome and autophagy.The proteasome is a large protein complex comprising regulatory and proteolytic subunits whose core function is the degradation of damaged or misfolded proteins.

  16. The regulatory landscape of osteogenic differentiation.

    Science.gov (United States)

    Håkelien, Anne-Mari; Bryne, Jan Christian; Harstad, Kristine G; Lorenz, Susanne; Paulsen, Jonas; Sun, Jinchang; Mikkelsen, Tarjei S; Myklebost, Ola; Meza-Zepeda, Leonardo A

    2014-10-01

    Differentiation of osteoblasts from mesenchymal stem cells (MSCs) is an integral part of bone development and homeostasis, and may when improperly regulated cause disease such as bone cancer or osteoporosis. Using unbiased high-throughput methods we here characterize the landscape of global changes in gene expression, histone modifications, and DNA methylation upon differentiation of human MSCs to the osteogenic lineage. Furthermore, we provide a first genome-wide characterization of DNA binding sites of the bone master regulatory transcription factor Runt-related transcription factor 2 (RUNX2) in human osteoblasts, revealing target genes associated with regulation of proliferation, migration, apoptosis, and with a significant overlap with p53 regulated genes. These findings expand on emerging evidence of a role for RUNX2 in cancer, including bone metastases, and the p53 regulatory network. We further demonstrate that RUNX2 binds to distant regulatory elements, promoters, and with high frequency to gene 3' ends. Finally, we identify TEAD2 and GTF2I as novel regulators of osteogenesis. © 2014 AlphaMed Press.

  17. Regulatory T cells in viral hepatitis

    Institute of Scientific and Technical Information of China (English)

    Eva Billerbeck; Tobias B(o)ttler; Robert Thimme

    2007-01-01

    The pathogenesis and outcome of viral infections are significantly influenced by the host immune response.The immune system is able to eliminate many viruses in the acute phase of infection. However, some viruses,like hepatitis C virus (HCV) and hepatitis B virus (HBV),can evade the host immune responses and establish a persistent infection. HCV and HBV persistence is caused by various mechanisms, like subversion of innate immune responses by viral factors, the emergence of T cell escape mutations, or T cell dysfunction and suppression.Recently, it has become evident that regulatory T cells may contribute to the pathogenesis and outcome of viral infections by suppressing antiviral immune responses.Indeed, the control of HCV and HBV specific immune responses mediated by regulatory T cells may be one mechanism that favors viral persistence, but it may also prevent the host from overwhelming T cell activity and liver damage. This review will focus on the role of regulatory T cells in viral hepatitis.

  18. Small regulatory RNA and Legionella pneumophila

    Directory of Open Access Journals (Sweden)

    Sebastien P Faucher

    2011-05-01

    Full Text Available Legionella pneumophila is a gram-negative bacterial species that is ubiquitous in almost any aqueous environment. It is the agent of Legionnaires’ disease, an acute and often under-reported form of pneumonia. In mammals, L. pneumophila replicates inside macrophages within a modified vacuole. Many protein regulators have been identified that control virulence-related properties, including RpoS, LetA/LetS and PmrA/PmrB. In the past few years, the importance of regulation of virulence factors by small regulatory RNA has been increasingly appreciated. This is also the case in L. pneumophila where three sRNAs (RsmY, RsmZ and 6S RNA were recently shown to be important determinants of virulence regulation and 79 actively transcribed sRNAs were identified. In this review we describe current knowledge about sRNAs and their regulatory properties and how this relates to the known regulatory systems of L. pneumophila. We also provide a model for sRNA-mediated control of gene expression that serves as a framework for understanding the regulation of virulence-related properties of L. pneumophila.

  19. The role of veterinary medicine regulatory agencies.

    Science.gov (United States)

    Smith, M V

    2013-08-01

    An effective animal medicine regulatory programme includes a systematic, evidence-based means of documenting the safety and effectiveness of products before they are produced, marketed or used in a particular country or region. The programme must also include adequate monitoring and controls over the use of these substances. It is clearthat such programmes provide veterinarians, farmers and other animal medicine users with greater assurance that veterinary drugs and biologicals will be safe and effective in preventing and mitigating disease. It is important that these regulatory controls include programmes to ensure that human food obtained from treated animals is safe and that all potential toxicological and microbiological hazards that may be associated with the use of veterinary medicines have been adequately evaluated. There is a great need worldwide for veterinary medicines that provide needed therapies for vast numbers of animals and animal species and, in the case of food-producing animals, for medicinal products that enhance the productivity and efficiency of food production and ensure food safety when they are used in accordance with their approval specifications. The public health mission of regulatory agencies succeeds when they are able to put into the hands of the user an approved, safe and effective, well-manufactured and appropriately labelled medicine, and when there are adequate controls in place to assure proper compliance.

  20. Cooperative or Competitive? Private Regulators and Public Supervisors in the Post-Crisis European Financial Services Landscape

    NARCIS (Netherlands)

    Cherednychenko, Olha O.

    This article explores the interplay between private regulators and public supervisors within principles-based regulation and meta-regulation in the post-crisis European retail financial services landscape. It shows that the way in which the compliance with such regulatory frameworks is supervised