Science.gov

Sample records for cra global regulatory

  1. A global regulatory science agenda for vaccines.

    PubMed

    Elmgren, Lindsay; Li, Xuguang; Wilson, Carolyn; Ball, Robert; Wang, Junzhi; Cichutek, Klaus; Pfleiderer, Michael; Kato, Atsushi; Cavaleri, Marco; Southern, James; Jivapaisarnpong, Teeranart; Minor, Philip; Griffiths, Elwyn; Sohn, Yeowon; Wood, David

    2013-04-18

    The Decade of Vaccines Collaboration and development of the Global Vaccine Action Plan provides a catalyst and unique opportunity for regulators worldwide to develop and propose a global regulatory science agenda for vaccines. Regulatory oversight is critical to allow access to vaccines that are safe, effective, and of assured quality. Methods used by regulators need to constantly evolve so that scientific and technological advances are applied to address challenges such as new products and technologies, and also to provide an increased understanding of benefits and risks of existing products. Regulatory science builds on high-quality basic research, and encompasses at least two broad categories. First, there is laboratory-based regulatory science. Illustrative examples include development of correlates of immunity; or correlates of safety; or of improved product characterization and potency assays. Included in such science would be tools to standardize assays used for regulatory purposes. Second, there is science to develop regulatory processes. Illustrative examples include adaptive clinical trial designs; or tools to analyze the benefit-risk decision-making process of regulators; or novel pharmacovigilance methodologies. Included in such science would be initiatives to standardize regulatory processes (e.g., definitions of terms for adverse events [AEs] following immunization). The aim of a global regulatory science agenda is to transform current national efforts, mainly by well-resourced regulatory agencies, into a coordinated action plan to support global immunization goals. This article provides examples of how regulatory science has, in the past, contributed to improved access to vaccines, and identifies gaps that could be addressed through a global regulatory science agenda. The article also identifies challenges to implementing a regulatory science agenda and proposes strategies and actions to fill these gaps. A global regulatory science agenda will enable

  2. 12 CFR 390.162 - CRA communications.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 5 2012-01-01 2012-01-01 false CRA communications. 390.162 Section 390.162... Agreements § 390.162 CRA communications. (a) Definition of CRA communication. A CRA communication is any of... any CRA affiliate. (b) Discussions or contacts that are not CRA communications—(1) Timing of...

  3. 12 CFR 390.162 - CRA communications.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 5 2014-01-01 2014-01-01 false CRA communications. 390.162 Section 390.162... Agreements § 390.162 CRA communications. (a) Definition of CRA communication. A CRA communication is any of... any CRA affiliate. (b) Discussions or contacts that are not CRA communications. (1) Timing of...

  4. 12 CFR 533.3 - CRA communications.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 6 2013-01-01 2012-01-01 true CRA communications. 533.3 Section 533.3 Banks...-RELATED AGREEMENTS § 533.3 CRA communications. (a) Definition of CRA communication. A CRA communication is... any CRA affiliate. (b) Discussions or contacts that are not CRA communications—(1) Timing of...

  5. 12 CFR 533.3 - CRA communications.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 6 2014-01-01 2012-01-01 true CRA communications. 533.3 Section 533.3 Banks...-RELATED AGREEMENTS § 533.3 CRA communications. (a) Definition of CRA communication. A CRA communication is... any CRA affiliate. (b) Discussions or contacts that are not CRA communications—(1) Timing of...

  6. 12 CFR 133.3 - CRA communications.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 1 2012-01-01 2012-01-01 false CRA communications. 133.3 Section 133.3 Banks...-RELATED AGREEMENTS § 133.3 CRA communications. (a) Definition of CRA communication. A CRA communication is... any CRA affiliate. (b) Discussions or contacts that are not CRA communications—(1) Timing of...

  7. 12 CFR 533.3 - CRA communications.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false CRA communications. 533.3 Section 533.3 Banks...-RELATED AGREEMENTS § 533.3 CRA communications. (a) Definition of CRA communication. A CRA communication is... any CRA affiliate. (b) Discussions or contacts that are not CRA communications—(1) Timing of...

  8. 12 CFR 533.3 - CRA communications.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 6 2012-01-01 2012-01-01 false CRA communications. 533.3 Section 533.3 Banks...-RELATED AGREEMENTS § 533.3 CRA communications. (a) Definition of CRA communication. A CRA communication is... any CRA affiliate. (b) Discussions or contacts that are not CRA communications—(1) Timing of...

  9. 12 CFR 390.162 - CRA communications.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 5 2013-01-01 2013-01-01 false CRA communications. 390.162 Section 390.162... Agreements § 390.162 CRA communications. (a) Definition of CRA communication. A CRA communication is any of... any CRA affiliate. (b) Discussions or contacts that are not CRA communications. (1) Timing of...

  10. 12 CFR 133.3 - CRA communications.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 1 2014-01-01 2014-01-01 false CRA communications. 133.3 Section 133.3 Banks...-RELATED AGREEMENTS § 133.3 CRA communications. (a) Definition of CRA communication. A CRA communication is... any CRA affiliate. (b) Discussions or contacts that are not CRA communications—(1) Timing of...

  11. Global Summit on Regulatory Science 2013.

    PubMed

    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.

  12. 12 CFR 35.3 - CRA communications.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 1 2010-01-01 2010-01-01 false CRA communications. 35.3 Section 35.3 Banks and... AGREEMENTS § 35.3 CRA communications. (a) Definition of CRA communication. A CRA communication is any of the...) Discussions or contacts that are not CRA communications—(1) Timing of contacts with a Federal banking...

  13. 12 CFR 207.3 - CRA communications.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 2 2013-01-01 2013-01-01 false CRA communications. 207.3 Section 207.3 Banks... REPORTING OF CRA-RELATED AGREEMENTS (REGULATION G) § 207.3 CRA communications. (a) Definition of CRA communication. A CRA communication is any of the following— (1) Any written or oral comment or...

  14. 12 CFR 207.3 - CRA communications.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 2 2011-01-01 2011-01-01 false CRA communications. 207.3 Section 207.3 Banks... REPORTING OF CRA-RELATED AGREEMENTS (REGULATION G) § 207.3 CRA communications. (a) Definition of CRA communication. A CRA communication is any of the following— (1) Any written or oral comment or...

  15. 12 CFR 346.3 - CRA communications.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 5 2013-01-01 2013-01-01 false CRA communications. 346.3 Section 346.3 Banks... DISCLOSURE AND REPORTING OF CRA-RELATED AGREEMENTS § 346.3 CRA communications. (a) Definition of CRA communication. A CRA communication is any of the following— (1) Any written or oral comment or...

  16. 12 CFR 346.3 - CRA communications.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 5 2012-01-01 2012-01-01 false CRA communications. 346.3 Section 346.3 Banks... DISCLOSURE AND REPORTING OF CRA-RELATED AGREEMENTS § 346.3 CRA communications. (a) Definition of CRA communication. A CRA communication is any of the following— (1) Any written or oral comment or...

  17. 12 CFR 207.3 - CRA communications.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 2 2010-01-01 2010-01-01 false CRA communications. 207.3 Section 207.3 Banks... REPORTING OF CRA-RELATED AGREEMENTS (REGULATION G) § 207.3 CRA communications. (a) Definition of CRA communication. A CRA communication is any of the following— (1) Any written or oral comment or...

  18. 12 CFR 35.3 - CRA communications.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 1 2012-01-01 2012-01-01 false CRA communications. 35.3 Section 35.3 Banks and... AGREEMENTS § 35.3 CRA communications. (a) Definition of CRA communication. A CRA communication is any of the...) Discussions or contacts that are not CRA communications—(1) Timing of contacts with a Federal banking...

  19. 12 CFR 346.3 - CRA communications.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 4 2011-01-01 2011-01-01 false CRA communications. 346.3 Section 346.3 Banks... DISCLOSURE AND REPORTING OF CRA-RELATED AGREEMENTS § 346.3 CRA communications. (a) Definition of CRA communication. A CRA communication is any of the following— (1) Any written or oral comment or...

  20. 12 CFR 207.3 - CRA communications.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 2 2012-01-01 2012-01-01 false CRA communications. 207.3 Section 207.3 Banks... REPORTING OF CRA-RELATED AGREEMENTS (REGULATION G) § 207.3 CRA communications. (a) Definition of CRA communication. A CRA communication is any of the following— (1) Any written or oral comment or...

  1. 12 CFR 35.3 - CRA communications.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 1 2014-01-01 2014-01-01 false CRA communications. 35.3 Section 35.3 Banks and... AGREEMENTS § 35.3 CRA communications. (a) Definition of CRA communication. A CRA communication is any of the...) Discussions or contacts that are not CRA communications—(1) Timing of contacts with a Federal banking...

  2. 12 CFR 346.3 - CRA communications.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 5 2014-01-01 2014-01-01 false CRA communications. 346.3 Section 346.3 Banks... DISCLOSURE AND REPORTING OF CRA-RELATED AGREEMENTS § 346.3 CRA communications. (a) Definition of CRA communication. A CRA communication is any of the following— (1) Any written or oral comment or...

  3. 12 CFR 207.3 - CRA communications.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 2 2014-01-01 2014-01-01 false CRA communications. 207.3 Section 207.3 Banks... REPORTING OF CRA-RELATED AGREEMENTS (REGULATION G) § 207.3 CRA communications. (a) Definition of CRA communication. A CRA communication is any of the following— (1) Any written or oral comment or...

  4. Global Regulatory Pathways in the Alphaproteobacteria

    SciTech Connect

    2007-04-27

    A major goal for microbiologists in the twenty-first century is to develop an understanding of the microbial cell in all its complexity. In addition to understanding the function of individual gene products we need to focus on how the cell regulates gene expression at a global level to respond to different environmental parameters. Development of genomic technologies such as complete genome sequencing, proteomics, and global comparisons of mRNA expression patterns allows us to begin to address this issue. This proposal focuses on a number of phylogenetically related bacteria that are involved in environmentally important processes such as carbon sequestration and bioremediation. Genome sequencing projects of a number of these bacteria have revealed the presence of a small family of regulatory genes found thus far only in the alpha-proteobacteria. These genes encode proteins that are related to the global regulatory protein RosR in Rhizobium etli, which is involved in determining nodulation competitiveness in this bacterium. Our goal is to examine the function of the proteins encoded by this gene family in several of the bacteria containing homologs to RosR. We will construct gene disruption mutations in a number of these bacteria and characterize the resulting mutant strains using two-dimensional gel electrophoresis and genetic and biochemical techniques. We will thus determine if the other proteins also function as global regulators of gene expression. Using proteomics methods we will identify the specific proteins whose expression varies depending on the presence or absence of the RosR homolog. Over fifty loci regulated by RosR have been identified in R. etli using transposon mutagenesis; this will serve as out benchmark to which we will compare the other regulons. We expect to identify genes regulated by RosR homologs in several bacterial species, including, but not limited to Rhodopseudomonas palustris and Sphingomonas aromaticivorans. In this way we will

  5. Global analysis of photosynthesis transcriptional regulatory networks.

    PubMed

    Imam, Saheed; Noguera, Daniel R; Donohue, Timothy J

    2014-12-01

    Photosynthesis is a crucial biological process that depends on the interplay of many components. This work analyzed the gene targets for 4 transcription factors: FnrL, PrrA, CrpK and MppG (RSP_2888), which are known or predicted to control photosynthesis in Rhodobacter sphaeroides. Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) identified 52 operons under direct control of FnrL, illustrating its regulatory role in photosynthesis, iron homeostasis, nitrogen metabolism and regulation of sRNA synthesis. Using global gene expression analysis combined with ChIP-seq, we mapped the regulons of PrrA, CrpK and MppG. PrrA regulates ∼34 operons encoding mainly photosynthesis and electron transport functions, while CrpK, a previously uncharacterized Crp-family protein, regulates genes involved in photosynthesis and maintenance of iron homeostasis. Furthermore, CrpK and FnrL share similar DNA binding determinants, possibly explaining our observation of the ability of CrpK to partially compensate for the growth defects of a ΔFnrL mutant. We show that the Rrf2 family protein, MppG, plays an important role in photopigment biosynthesis, as part of an incoherent feed-forward loop with PrrA. Our results reveal a previously unrealized, high degree of combinatorial regulation of photosynthetic genes and significant cross-talk between their transcriptional regulators, while illustrating previously unidentified links between photosynthesis and the maintenance of iron homeostasis.

  6. Global Analysis of Photosynthesis Transcriptional Regulatory Networks

    PubMed Central

    Imam, Saheed; Noguera, Daniel R.; Donohue, Timothy J.

    2014-01-01

    Photosynthesis is a crucial biological process that depends on the interplay of many components. This work analyzed the gene targets for 4 transcription factors: FnrL, PrrA, CrpK and MppG (RSP_2888), which are known or predicted to control photosynthesis in Rhodobacter sphaeroides. Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) identified 52 operons under direct control of FnrL, illustrating its regulatory role in photosynthesis, iron homeostasis, nitrogen metabolism and regulation of sRNA synthesis. Using global gene expression analysis combined with ChIP-seq, we mapped the regulons of PrrA, CrpK and MppG. PrrA regulates ∼34 operons encoding mainly photosynthesis and electron transport functions, while CrpK, a previously uncharacterized Crp-family protein, regulates genes involved in photosynthesis and maintenance of iron homeostasis. Furthermore, CrpK and FnrL share similar DNA binding determinants, possibly explaining our observation of the ability of CrpK to partially compensate for the growth defects of a ΔFnrL mutant. We show that the Rrf2 family protein, MppG, plays an important role in photopigment biosynthesis, as part of an incoherent feed-forward loop with PrrA. Our results reveal a previously unrealized, high degree of combinatorial regulation of photosynthetic genes and significant cross-talk between their transcriptional regulators, while illustrating previously unidentified links between photosynthesis and the maintenance of iron homeostasis. PMID:25503406

  7. Topological origin of global attractors in gene regulatory networks

    NASA Astrophysics Data System (ADS)

    Zhang, YunJun; Ouyang, Qi; Geng, Zhi

    2015-02-01

    Fixed-point attractors with global stability manifest themselves in a number of gene regulatory networks. This property indicates the stability of regulatory networks against small state perturbations and is closely related to other complex dynamics. In this paper, we aim to reveal the core modules in regulatory networks that determine their global attractors and the relationship between these core modules and other motifs. This work has been done via three steps. Firstly, inspired by the signal transmission in the regulation process, we extract the model of chain-like network from regulation networks. We propose a module of "ideal transmission chain (ITC)", which is proved sufficient and necessary (under certain condition) to form a global fixed-point in the context of chain-like network. Secondly, by examining two well-studied regulatory networks (i.e., the cell-cycle regulatory networks of Budding yeast and Fission yeast), we identify the ideal modules in true regulation networks and demonstrate that the modules have a superior contribution to network stability (quantified by the relative size of the biggest attraction basin). Thirdly, in these two regulation networks, we find that the double negative feedback loops, which are the key motifs of forming bistability in regulation, are connected to these core modules with high network stability. These results have shed new light on the connection between the topological feature and the dynamic property of regulatory networks.

  8. Fructose 1-Phosphate Is the Preferred Effector of the Metabolic Regulator Cra of Pseudomonas putida*

    PubMed Central

    Chavarría, Max; Santiago, César; Platero, Raúl; Krell, Tino; Casasnovas, José M.; de Lorenzo, Víctor

    2011-01-01

    The catabolite repressor/activator (Cra) protein is a global sensor and regulator of carbon fluxes through the central metabolic pathways of Gram-negative bacteria. To examine the nature of the effector (or effectors) that signal such fluxes to the protein of Pseudomonas putida, the Cra factor of this soil microorganism has been purified and characterized and its three-dimensional structure determined. Analytical ultracentrifugation, gel filtration, and mobility shift assays showed that the effector-free Cra is a dimer that binds an operator DNA sequence in the promoter region of the fruBKA cluster. Furthermore, fructose 1-phosphate (F1P) was found to most efficiently dissociate the Cra-DNA complex. Thermodynamic parameters of the F1P-Cra-DNA interaction calculated by isothermal titration calorimetry revealed that the factor associates tightly to the DNA sequence 5′-TTAAACGTTTCA-3′ (KD = 26.3 ± 3.1 nm) and that F1P binds the protein with an apparent stoichiometry of 1.06 ± 0.06 molecules per Cra monomer and a KD of 209 ± 20 nm. Other possible effectors, like fructose 1,6-bisphosphate, did not display a significant affinity for the regulator under the assay conditions. Moreover, the structure of Cra and its co-crystal with F1P at a 2-Å resolution revealed that F1P fits optimally the geometry of the effector pocket. Our results thus single out F1P as the preferred metabolic effector of the Cra protein of P. putida. PMID:21239488

  9. Fur-mediated global regulatory circuits in pathogenic Neisseria species.

    PubMed

    Yu, Chunxiao; Genco, Caroline Attardo

    2012-12-01

    The ferric uptake regulator (Fur) protein has been shown to function as a repressor of transcription in a number of diverse microorganisms. However, recent studies have established that Fur can function at a global level as both an activator and a repressor of transcription through both direct and indirect mechanisms. Fur-mediated indirect activation occurs via the repression of additional repressor proteins, or small regulatory RNAs, thereby activating transcription of a previously silent gene. Fur mediates direct activation through binding of Fur to the promoter regions of genes. Whereas the repressive mechanism of Fur has been thoroughly investigated, emerging studies on direct and indirect Fur-mediated activation mechanisms have revealed novel global regulatory circuits.

  10. Fur-Mediated Global Regulatory Circuits in Pathogenic Neisseria Species

    PubMed Central

    Yu, Chunxiao

    2012-01-01

    The ferric uptake regulator (Fur) protein has been shown to function as a repressor of transcription in a number of diverse microorganisms. However, recent studies have established that Fur can function at a global level as both an activator and a repressor of transcription through both direct and indirect mechanisms. Fur-mediated indirect activation occurs via the repression of additional repressor proteins, or small regulatory RNAs, thereby activating transcription of a previously silent gene. Fur mediates direct activation through binding of Fur to the promoter regions of genes. Whereas the repressive mechanism of Fur has been thoroughly investigated, emerging studies on direct and indirect Fur-mediated activation mechanisms have revealed novel global regulatory circuits. PMID:22885296

  11. 12 CFR Appendix B to Part 25 - CRA Notice

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 1 2010-01-01 2010-01-01 false CRA Notice B Appendix B to Part 25 Banks and... DEPOSIT PRODUCTION REGULATIONS Pt. 25, App. B Appendix B to Part 25—CRA Notice (a) Notice for main offices...) an announcement of applications covered by the CRA filed by bank holding companies. (b) Notice...

  12. Global regulatory standards for the approval of biosimilars.

    PubMed

    Mounho, Barbara; Phillips, Audrey; Holcombe, Kay; Grampp, Gustavo; Lubiniecki, Tony; Mollerup, Inger; Jones, Carolyn

    2010-01-01

    On March 23, 2010, President Barack Obama signed into law the Patient Protection and Affordable Care Act, which contains the Biologics Price Competition and Innovation Act. Biosimilars have an important role in the United States health care system, and this new law creates an abbreviated approval pathway for biosimilar products in the U.S. A biosimilar is a biologic product demonstrated to be highly similar to an approved innovator biologic product ("reference product"). While the law provides general information on the standards to demonstrate biosimilarity, Congress has authorized the FDA to define the scientific standards and content of biosimilar applications. There is an increasing global interest in the development of biosimilar products, and several regulatory authorities around the world, as well as the World Health Organization (WHO), have established regulatory guidelines for the approval of biosimilars. The scientific standards and requirements in the biosimilar guidelines of the WHO and other health authorities, including the European Union, Canada, Japan, and South Africa, are reviewed in this paper. The similarities as well as the differences among the policies adopted by these regulatory authorities may provide the FDA valuable information as the agency develops its standards and approaches for the approval of biosimilars in the U.S. At the same time, while establishing such approaches, the FDA has the opportunity to demonstrate leadership in addressing significant safety and other issues related to multi-source biologics and biosimilars that remain a global challenge. PMID:24479248

  13. Nanosilver and global public health: international regulatory issues.

    PubMed

    Faunce, Thomas; Watal, Aparna

    2010-06-01

    Silver in nanoparticle form is used extensively worldwide in hospital and general practice settings, in dressings as a treatment for external wounds, burns and ulcers. Nanosilver is also an increasingly important coating over embedded medical devices, inhibiting the development of biofilm. Nanosilver disinfectant sprays and polymer coatings are being widely promoted as protective against viral infections. In addition, nanosilver is widely used for its antibacterial properties in food processing and packaging, as well as in consumer products used for domestic cleaning and clothing. This article argues that medical devices, therapeutic products, and domestic food and goods containing nanosilver, although offering therapeutic benefits, must be subject to precautionary regulation owing to associated public health and environmental risks, particularly from large volumes of nanosilver in waste water. The article first examines the use of nanosilver in a variety of contemporary medical and domestic products, the utilization of which may assist in resolving global public health problems, such as restricted access to safe food, water and medical care. It then discusses the mechanisms of toxicity for nanosilver, whether it should be classified as a new chemical entity for regulatory purposes and whether its increased usage poses significant environmental and public health risks. The article next critically analyses representative international regulatory regimes (the USA, EU, UK and Australia) for medical and domestic use of nanosilver. The conclusion includes a set of recommendations for improving international regulation of nanosilver.

  14. Nanosilver and global public health: international regulatory issues.

    PubMed

    Faunce, Thomas; Watal, Aparna

    2010-06-01

    Silver in nanoparticle form is used extensively worldwide in hospital and general practice settings, in dressings as a treatment for external wounds, burns and ulcers. Nanosilver is also an increasingly important coating over embedded medical devices, inhibiting the development of biofilm. Nanosilver disinfectant sprays and polymer coatings are being widely promoted as protective against viral infections. In addition, nanosilver is widely used for its antibacterial properties in food processing and packaging, as well as in consumer products used for domestic cleaning and clothing. This article argues that medical devices, therapeutic products, and domestic food and goods containing nanosilver, although offering therapeutic benefits, must be subject to precautionary regulation owing to associated public health and environmental risks, particularly from large volumes of nanosilver in waste water. The article first examines the use of nanosilver in a variety of contemporary medical and domestic products, the utilization of which may assist in resolving global public health problems, such as restricted access to safe food, water and medical care. It then discusses the mechanisms of toxicity for nanosilver, whether it should be classified as a new chemical entity for regulatory purposes and whether its increased usage poses significant environmental and public health risks. The article next critically analyses representative international regulatory regimes (the USA, EU, UK and Australia) for medical and domestic use of nanosilver. The conclusion includes a set of recommendations for improving international regulation of nanosilver. PMID:20528456

  15. Project 6: Cumulative Risk Assessment (CRA) Methods and Applications

    EPA Science Inventory

    Project 6: CRA Methods and Applications addresses the need to move beyond traditional risk assessment practices by developing CRA methods to integrate and evaluate impacts of chemical and nonchemical stressors on the environment and human health. Project 6 has three specific obje...

  16. Implementing CRA with Secondary Students with Learning Disabilities in Mathematics

    ERIC Educational Resources Information Center

    Witzel, Bradley S.; Riccomini, Paul J.; Schneider, Elke

    2008-01-01

    Students with learning disabilities struggle to acquire essential mathematical concepts and skills, especially at the secondary level. One effective approach to improving secondary math performance supported by research is the concrete-to-representational-to-abstract (CRA) sequence of instruction. Although CRA is an evidenced-based instructional…

  17. 12 CFR Appendix B to Part 195 - CRA Notice

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Appendix B to Part 195—CRA Notice (a) Notice for main offices and, if an interstate savings association... the savings associations that are scheduled for CRA examination in that quarter. This list is... needs to (name and address of official at savings association) and the . Your letter, together with...

  18. 12 CFR Appendix B to Part 195 - CRA Notice

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Appendix B to Part 195—CRA Notice (a) Notice for main offices and, if an interstate savings association... the savings associations that are scheduled for CRA examination in that quarter. This list is... needs to (name and address of official at savings association) and the . Your letter, together with...

  19. 12 CFR Appendix B to Part 195 - CRA Notice

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Appendix B to Part 195—CRA Notice (a) Notice for main offices and, if an interstate savings association... the savings associations that are scheduled for CRA examination in that quarter. This list is... needs to (name and address of official at savings association) and the . Your letter, together with...

  20. 12 CFR Appendix B to Part 345 - CRA Notice

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... interstate bank, one branch office in each state. Community Reinvestment Act Notice Under the Federal... by the FDIC in evaluating our CRA performance and may be made public. You may ask to look at any... considered by the FDIC in evaluating our CRA performance and may be made public. You may ask to look at...

  1. 12 CFR Appendix B to Part 228 - CRA Notice

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., if an interstate bank, one branch office in each state. Community Reinvestment Act Notice Under the... in evaluating our CRA performance and may be made public. You may ask to look at any comments... evaluating our CRA performance and may be made public. You may ask to look at any comments received by...

  2. Global Hopf bifurcation in the ZIP regulatory system.

    PubMed

    Claus, Juliane; Ptashnyk, Mariya; Bohmann, Ansgar; Chavarría-Krauser, Andrés

    2015-10-01

    Regulation of zinc uptake in roots of Arabidopsis thaliana has recently been modeled by a system of ordinary differential equations based on the uptake of zinc, expression of a transporter protein and the interaction between an activator and inhibitor. For certain parameter choices the steady state of this model becomes unstable upon variation in the external zinc concentration. Numerical results show periodic orbits emerging between two critical values of the external zinc concentration. Here we show the existence of a global Hopf bifurcation with a continuous family of stable periodic orbits between two Hopf bifurcation points. The stability of the orbits in a neighborhood of the bifurcation points is analyzed by deriving the normal form, while the stability of the orbits in the global continuation is shown by calculation of the Floquet multipliers. From a biological point of view, stable periodic orbits lead to potentially toxic zinc peaks in plant cells. Buffering is believed to be an efficient way to deal with strong transient variations in zinc supply. We extend the model by a buffer reaction and analyze the stability of the steady state in dependence of the properties of this reaction. We find that a large enough equilibrium constant of the buffering reaction stabilizes the steady state and prevents the development of oscillations. Hence, our results suggest that buffering has a key role in the dynamics of zinc homeostasis in plant cells.

  3. Circuitry linking the Csr and stringent response global regulatory systems.

    PubMed

    Edwards, Adrianne N; Patterson-Fortin, Laura M; Vakulskas, Christopher A; Mercante, Jeffrey W; Potrykus, Katarzyna; Vinella, Daniel; Camacho, Martha I; Fields, Joshua A; Thompson, Stuart A; Georgellis, Dimitris; Cashel, Michael; Babitzke, Paul; Romeo, Tony

    2011-06-01

    CsrA protein regulates important cellular processes by binding to target mRNAs and altering their translation and/or stability. In Escherichia coli, CsrA binds to sRNAs, CsrB and CsrC, which sequester CsrA and antagonize its activity. Here, mRNAs for relA, spoT and dksA of the stringent response system were found among 721 different transcripts that copurified with CsrA. Many of the transcripts that copurified with CsrA were previously determined to respond to ppGpp and/or DksA. We examined multiple regulatory interactions between the Csr and stringent response systems. Most importantly, DksA and ppGpp robustly activated csrB/C transcription (10-fold), while they modestly activated csrA expression. We propose that CsrA-mediated regulation is relieved during the stringent response. Gel shift assays confirmed high affinity binding of CsrA to relA mRNA leader and weaker interactions with dksA and spoT. Reporter fusions, qRT-PCR and immunoblotting showed that CsrA repressed relA expression, and (p)ppGpp accumulation during stringent response was enhanced in a csrA mutant. CsrA had modest to negligible effects on dksA and spoT expression. Transcription of dksA was negatively autoregulated via a feedback loop that tended to mask CsrA effects. We propose that the Csr system fine-tunes the stringent response and discuss biological implications of the composite circuitry.

  4. Circuitry Linking the Csr and Stringent Response Global Regulatory Systems

    PubMed Central

    Edwards, Adrianne N.; Patterson-Fortin, Laura M.; Vakulskas, Christopher A.; Mercante, Jeffrey W.; Potrykus, Katarzyna; Vinella, Daniel; Camacho, Martha I.; Fields, Joshua A.; Thompson, Stuart A.; Georgellis, Dimitris; Cashel, Michael; Babitzke, Paul; Romeo, Tony

    2011-01-01

    Summary CsrA protein regulates important cellular processes by binding to target mRNAs and altering their translation and/or stability. In Escherichia coli, CsrA binds to sRNAs, CsrB and CsrC, which sequester CsrA and antagonize its activity. Here, mRNAs for relA, spoT and dksA of the stringent response system were found among 721 different transcripts that copurified with CsrA. Many of the transcripts that copurified with CsrA were previously determined to respond to ppGpp and/or DksA. We examined multiple regulatory interactions between the Csr and stringent response systems. Most importantly, DksA and ppGpp robustly activated csrB/C transcription (10-fold), while they modestly activated csrA expression. We propose that CsrA-mediated regulation is relieved during the stringent response. Gel shift assays confirmed high affinity binding of CsrA to relA mRNA leader and weaker interactions with dksA and spoT. Reporter fusions, qRT-PCR, and immunoblotting showed that CsrA repressed relA expression, and (p)ppGpp accumulation during stringent response was enhanced in a csrA mutant. CsrA had modest to negligible effects on dksA and spoT expression. Transcription of dksA was negatively autoregulated via a feedback loop that tended to mask CsrA effects. We propose that the Csr system fine-tunes the stringent response and discuss biological implications of the composite circuitry. PMID:21488981

  5. 12 CFR Appendix B to Part 563e - CRA Notice

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Appendix B to Part 563e—CRA Notice (a) Notice for main offices and, if an interstate savings association... each quarter, the OTS publishes a nationwide list of the savings associations that are scheduled for... address of official at savings association) and OTS (address). Your letter, together with any response...

  6. 12 CFR Appendix B to Part 563e - CRA Notice

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Appendix B to Part 563e—CRA Notice (a) Notice for main offices and, if an interstate savings association... each quarter, the OTS publishes a nationwide list of the savings associations that are scheduled for... address of official at savings association) and OTS (address). Your letter, together with any response...

  7. 12 CFR Appendix B to Part 563e - CRA Notice

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Appendix B to Part 563e—CRA Notice (a) Notice for main offices and, if an interstate savings association... each quarter, the OTS publishes a nationwide list of the savings associations that are scheduled for... address of official at savings association) and OTS (address). Your letter, together with any response...

  8. 12 CFR Appendix B to Part 563e - CRA Notice

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Appendix B to Part 563e—CRA Notice (a) Notice for main offices and, if an interstate savings association... each quarter, the OTS publishes a nationwide list of the savings associations that are scheduled for... address of official at savings association) and OTS (address). Your letter, together with any response...

  9. Education Opportunities Using the CRaTER Instrument

    NASA Astrophysics Data System (ADS)

    Case, A. W.; Gross, N. A.; Spence, H. E.; Instrument Team, C.

    2009-12-01

    The Cosmic Ray Telescope for the Effects of Radiation (CRaTER) instrument on the Lunar Reconnaissance Orbiter (LRO) will quantify the effects of both solar energetic particles (SEP’s) and galactic cosmic rays (GCR’s) on living tissue. A number of education and public outreach opportunities for this project have presented themselves, including work with librarians in Massachusetts and presentations at the Museum of Science, Boston. These opportunities have allowed the CRaTER team to explain, in both formal and informal settings, what radiation is, what its effects are on living tissue, and what can be done to protect astronauts and instruments on the Moon. In addition, the CRaTER instrument is simple enough that the working engineering model can be shown to the public and the CRaTER team can describe the design process for development of an instrument that will fly on a spacecraft. This provides the public with important insight into the process of science.

  10. 12 CFR Appendix B to Part 25 - CRA Notice

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... and, if an interstate bank, one branch office in each state. Community Reinvestment Act Notice Under... performance and may be made public. You may ask to look at any comments received by the Deputy Comptroller... considered by the Comptroller in evaluating our CRA performance and may be made public. You may ask to...

  11. 12 CFR Appendix B to Part 25 - CRA Notice

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... and, if an interstate bank, one branch office in each state. Community Reinvestment Act Notice Under... performance and may be made public. You may ask to look at any comments received by the Deputy Comptroller... considered by the Comptroller in evaluating our CRA performance and may be made public. You may ask to...

  12. Regulatory Underpinnings of Global Health Security: FDA's Roles in Preventing, Detecting, and Responding to Global Health Threats

    PubMed Central

    Bond, Katherine C.; Maher, Carmen

    2014-01-01

    In February 2014, health officials from around the world announced the Global Health Security Agenda, a critical effort to strengthen national and global systems to prevent, detect, and respond to infectious disease threats and to foster stronger collaboration across borders. With its increasing global roles and broad range of regulatory responsibilities in ensuring the availability, safety, and security of medical and food products, the US Food and Drug Administration (FDA) is engaged in a range of efforts in support of global health security. This article provides an overview of FDA's global health security roles, focusing on its responsibilities related to the development and use of medical countermeasures (MCMs) for preventing, detecting, and responding to global infectious disease and other public health emergency threats. The article also discusses several areas—antimicrobial resistance, food safety, and supply chain integrity—in which FDA's global health security roles continue to evolve and extend beyond MCMs and, in some cases, beyond traditional infectious disease threats. PMID:25254912

  13. Regulatory underpinnings of Global Health security: FDA's roles in preventing, detecting, and responding to global health threats.

    PubMed

    Courtney, Brooke; Bond, Katherine C; Maher, Carmen

    2014-01-01

    In February 2014, health officials from around the world announced the Global Health Security Agenda, a critical effort to strengthen national and global systems to prevent, detect, and respond to infectious disease threats and to foster stronger collaboration across borders. With its increasing global roles and broad range of regulatory responsibilities in ensuring the availability, safety, and security of medical and food products, the US Food and Drug Administration (FDA) is engaged in a range of efforts in support of global health security. This article provides an overview of FDA's global health security roles, focusing on its responsibilities related to the development and use of medical countermeasures (MCMs) for preventing, detecting, and responding to global infectious disease and other public health emergency threats. The article also discusses several areas-antimicrobial resistance, food safety, and supply chain integrity-in which FDA's global health security roles continue to evolve and extend beyond MCMs and, in some cases, beyond traditional infectious disease threats. PMID:25254912

  14. An experimentally supported model of the Bacillus subtilis global transcriptional regulatory network.

    PubMed

    Arrieta-Ortiz, Mario L; Hafemeister, Christoph; Bate, Ashley Rose; Chu, Timothy; Greenfield, Alex; Shuster, Bentley; Barry, Samantha N; Gallitto, Matthew; Liu, Brian; Kacmarczyk, Thadeous; Santoriello, Francis; Chen, Jie; Rodrigues, Christopher D A; Sato, Tsutomu; Rudner, David Z; Driks, Adam; Bonneau, Richard; Eichenberger, Patrick

    2015-11-01

    Organisms from all domains of life use gene regulation networks to control cell growth, identity, function, and responses to environmental challenges. Although accurate global regulatory models would provide critical evolutionary and functional insights, they remain incomplete, even for the best studied organisms. Efforts to build comprehensive networks are confounded by challenges including network scale, degree of connectivity, complexity of organism-environment interactions, and difficulty of estimating the activity of regulatory factors. Taking advantage of the large number of known regulatory interactions in Bacillus subtilis and two transcriptomics datasets (including one with 38 separate experiments collected specifically for this study), we use a new combination of network component analysis and model selection to simultaneously estimate transcription factor activities and learn a substantially expanded transcriptional regulatory network for this bacterium. In total, we predict 2,258 novel regulatory interactions and recall 74% of the previously known interactions. We obtained experimental support for 391 (out of 635 evaluated) novel regulatory edges (62% accuracy), thus significantly increasing our understanding of various cell processes, such as spore formation. PMID:26577401

  15. De Novo Evolution of Complex, Global and Hierarchical Gene Regulatory Mechanisms

    PubMed Central

    Jenkins, Dafyd J.

    2010-01-01

    Gene regulatory networks exhibit complex, hierarchical features such as global regulation and network motifs. There is much debate about whether the evolutionary origins of such features are the results of adaptation, or the by-products of non-adaptive processes of DNA replication. The lack of availability of gene regulatory networks of ancestor species on evolutionary timescales makes this a particularly difficult problem to resolve. Digital organisms, however, can be used to provide a complete evolutionary record of lineages. We use a biologically realistic evolutionary model that includes gene expression, regulation, metabolism and biosynthesis, to investigate the evolution of complex function in gene regulatory networks. We discover that: (i) network architecture and complexity evolve in response to environmental complexity, (ii) global gene regulation is selected for in complex environments, (iii) complex, inter-connected, hierarchical structures evolve in stages, with energy regulation preceding stress responses, and stress responses preceding growth rate adaptations and (iv) robustness of evolved models to mutations depends on hierarchical level: energy regulation and stress responses tend not to be robust to mutations, whereas growth rate adaptations are more robust and non-lethal when mutated. These results highlight the adaptive and incremental evolution of complex biological networks, and the value and potential of studying realistic in silico evolutionary systems as a way of understanding living systems. Electronic supplementary material The online version of this article (doi:10.1007/s00239-010-9369-4) contains supplementary material, which is available to authorized users. PMID:20680619

  16. Global regulatory developments for clinical stem cell research: diversification and challenges to collaborations.

    PubMed

    Rosemann, Achim; Bortz, Gabriela; Vasen, Federico; Sleeboom-Faulkner, Margaret

    2016-10-01

    In this article, we explore regulatory developments in stem cell medicine in seven jurisdictions: Japan, China, India, Argentina, Brazil, the USA and the EU. We will show that the research methods, ethical standards and approval procedures for the market use of clinical stem cell interventions are undergoing an important process of global diversification. We will discuss the implications of this process for international harmonization and the conduct of multicountry clinical research collaborations. It will become clear that the increasing heterogeneity of research standards and regulations in the stem cell field presents a significant challenge to international clinical trial partnerships, especially with countries that diverge from the regulatory models that have been developed in the USA and the EU. PMID:27622527

  17. CsrA and Cra influence Shigella flexneri pathogenesis.

    PubMed

    Gore, Aja L; Payne, Shelley M

    2010-11-01

    Shigella flexneri is a facultative intracellular pathogen that invades and disrupts the colonic epithelium. In order to thrive in the host, S. flexneri must adapt to environmental conditions in the gut and within the eukaryotic cytosol, including variability in the available carbon sources and other nutrients. We examined the roles of the carbon consumption regulators CsrA and Cra in a cell culture model of S. flexneri virulence. CsrA is an activator of glycolysis and a repressor of gluconeogenesis, and a csrA mutant had decreased attachment and invasion of cultured cells. Conversely, Cra represses glycolysis and activates gluconeogenesis, and the cra mutant had an increase in both attachment and invasion compared to the wild-type strain. Both mutants were defective in plaque formation. The importance of the glycolytic pathway in invasion and plaque formation was confirmed by testing the effect of a mutation in the glycolysis gene pfkA. The pfkA mutant was noninvasive and had cell surface alterations as indicated by decreased sensitivity to SDS and an altered lipopolysaccharide profile. The loss of invasion by the csrA and pfkA mutants was due to decreased expression of the S. flexneri virulence factor regulators virF and virB, resulting in decreased production of Shigella invasion plasmid antigens (Ipa). These data indicate that regulation of carbon metabolism and expression of the glycolysis gene pfkA are critical for synthesis of the virulence gene regulators VirF and VirB, and both the glycolytic and gluconeogenic pathways influence steps in S. flexneri invasion and plaque formation. PMID:20713625

  18. [Future Regulatory Science through a Global Product Development Strategy to Overcome the Device Lag].

    PubMed

    Tsuchii, Isao

    2016-01-01

    Environment that created "medical device lag (MDL)" has changed dramatically, and currently that term is not heard often. This was mainly achieved through the leadership of three groups: government, which determined to overcome MDL and took steps to do so; medical societies, which exhibited accountability in trial participation; and MD companies, which underwent a change in mindset that allowed comprehensive tripartite cooperation to reach the current stage. In particular, the global product development strategy (GPDS) of companies in a changing social environment has taken a new-turn with international harmonization trends, like Global Harmonization Task Force and International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. As a result, this evolution has created opportunities for treatment with cutting-edge MDs in Japanese society. Simultaneously, it has had a major impact on the planning process of GPDS of companies. At the same time, the interest of global companies has shifted to emerging economies for future potential profit since Japan no longer faces MDL issue. This economic trend makes MDLs a greater problem for manufacturers. From the regulatory science viewpoint, this new environment has not made it easy to plan a global strategy that will be adaptable to local societies. Without taking hasty action, flexible thinking from the global point of view is necessary to enable the adjustment of local strategies to fit the situation on the ground so that the innovative Japanese medical technology can be exported to a broad range of societies. PMID:27040334

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

    PubMed

    Crager, Sara Eve

    2014-11-01

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

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

    PubMed

    Crager, Sara Eve

    2015-01-01

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

  1. Improving Global Access to New Vaccines: Intellectual Property, Technology Transfer, and Regulatory Pathways

    PubMed Central

    2014-01-01

    The 2012 World Health Assembly Global Vaccine Action Plan called for global access to new vaccines within 5 years of licensure. Current approaches have proven insufficient to achieve sustainable vaccine pricing within such a timeline. Paralleling the successful strategy of generic competition to bring down drug prices, a clear consensus is emerging that market entry of multiple suppliers is a critical factor in expeditiously bringing down prices of new vaccines. In this context, key target objectives for improving access to new vaccines include overcoming intellectual property obstacles, streamlining regulatory pathways for biosimilar vaccines, and reducing market entry timelines for developing-country vaccine manufacturers by transfer of technology and know-how. I propose an intellectual property, technology, and know-how bank as a new approach to facilitate widespread access to new vaccines in low- and middle-income countries by efficient transfer of patented vaccine technologies to multiple developing-country vaccine manufacturers. PMID:25211753

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

    PubMed

    Crager, Sara Eve

    2014-11-01

    The 2012 World Health Assembly Global Vaccine Action Plan called for global access to new vaccines within 5 years of licensure. Current approaches have proven insufficient to achieve sustainable vaccine pricing within such a timeline. Paralleling the successful strategy of generic competition to bring down drug prices, a clear consensus is emerging that market entry of multiple suppliers is a critical factor in expeditiously bringing down prices of new vaccines. In this context, key target objectives for improving access to new vaccines include overcoming intellectual property obstacles, streamlining regulatory pathways for biosimilar vaccines, and reducing market entry timelines for developing-country vaccine manufacturers by transfer of technology and know-how. I propose an intellectual property, technology, and know-how bank as a new approach to facilitate widespread access to new vaccines in low- and middle-income countries by efficient transfer of patented vaccine technologies to multiple developing-country vaccine manufacturers. PMID:25211753

  3. Coronal Activity in the R CrA T Association

    NASA Technical Reports Server (NTRS)

    Patten, Brian M.; Oliversen, Ronald J. (Technical Monitor)

    2005-01-01

    Brian Patten is the Principal Investigator of the NASA ROSS-ADP project Coronal Activity in the R CrA T Association. For this project we have extracted net counts and variability information for all of the X-ray sources found in 23 archival ROSAT PSPC and HRI images in the region of the R CrA T association. These data have been merged with an extensive database of optical and near-infrared photometry, optical spectroscopy, and parallax data. These data have been used to (1) identify new association members and clarify the membership status of a number of previously suspected members of the association, and (2) derive, for the first time, an accurate coronal luminosity function for the T Tauri members of this T association and make direct comparisons between the coronal luminosity functions for other T associations and those of large clusters. We have used our survey data to assess (a) the importance of the star-formation environment in initial coronal activity levels, (b) the effects of PMS evolution on dynamo activity as a function of mass and age, and (c) the level of contamination by field post-T Tauri stars on association membership surveys.

  4. 38 CFR 1.916 - Disclosure of debt information to consumer reporting agencies (CRA).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... order to conduct program evaluation studies as required by 38 U.S.C. 527 or any other law. (b... information to consumer reporting agencies (CRA). 1.916 Section 1.916 Pensions, Bonuses, and Veterans' Relief... debt information to consumer reporting agencies (CRA). (a) The Department of Veterans Affairs...

  5. 38 CFR 1.916 - Disclosure of debt information to consumer reporting agencies (CRA).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... order to conduct program evaluation studies as required by 38 U.S.C. 527 or any other law. (b... information to consumer reporting agencies (CRA). 1.916 Section 1.916 Pensions, Bonuses, and Veterans' Relief... debt information to consumer reporting agencies (CRA). (a) The Department of Veterans Affairs...

  6. 38 CFR 1.916 - Disclosure of debt information to consumer reporting agencies (CRA).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... order to conduct program evaluation studies as required by 38 U.S.C. 527 or any other law. (b... information to consumer reporting agencies (CRA). 1.916 Section 1.916 Pensions, Bonuses, and Veterans' Relief... debt information to consumer reporting agencies (CRA). (a) The Department of Veterans Affairs...

  7. 38 CFR 1.916 - Disclosure of debt information to consumer reporting agencies (CRA).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... information to consumer reporting agencies (CRA). 1.916 Section 1.916 Pensions, Bonuses, and Veterans' Relief... debt information to consumer reporting agencies (CRA). (a) The Department of Veterans Affairs may... Affairs file number, Social Security number, and date of birth, to consumer reporting agencies for...

  8. The global regulatory landscape regarding micronutrient fortification of condiments and seasonings.

    PubMed

    Mejia, Luis A; Bower, Allyson M

    2015-11-01

    Fortification of staple foods has been a successful strategy for combatting micronutrient deficiency. Recently, fortification of condiments and seasonings has been considered as a new approach to mitigate micronutrient deficiencies worldwide. The regulatory environment of already existing programs must be examined to assess their safety, efficacy, and sustainability as this strategy expands globally. The objective of this review is to summarize the global regulatory landscape for the fortification of condiments and seasonings. Presently, legislation regarding the fortification of condiments and seasonings is primarily voluntary and limited to a few nations in Asia. The only dietary vehicles addressed are salt, soy sauce, and fish sauce, and the micronutrients addressed are iron and iodine. A marketing-driven introduction of fortified seasoning powders with iron, and indirectly with iodine, is also gaining popularity in Africa, Central America, and Caribbean countries. It is recommended that legislation regarding food fortification be mandatory in nature and follow established CODEX and World Trade Organization principles as well as World Health Organization/Food and Agriculture Organization of the United Nations fortification guidelines to ensure that these programs are safe, effective, and sustainable. PMID:26251126

  9. 13 CFR 107.1640 - SBA access to records of the CRA, Brokers, Dealers and Pool or Trust assemblers.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false SBA access to records of the CRA, Brokers, Dealers and Pool or Trust assemblers. 107.1640 Section 107.1640 Business Credit and Assistance... records of the CRA, Brokers, Dealers and Pool or Trust assemblers. The CRA and any broker, dealer and...

  10. 13 CFR 107.1640 - SBA access to records of the CRA, Brokers, Dealers and Pool or Trust assemblers.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false SBA access to records of the CRA, Brokers, Dealers and Pool or Trust assemblers. 107.1640 Section 107.1640 Business Credit and Assistance... records of the CRA, Brokers, Dealers and Pool or Trust assemblers. The CRA and any broker, dealer and...

  11. 13 CFR 107.1640 - SBA access to records of the CRA, Brokers, Dealers and Pool or Trust assemblers.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false SBA access to records of the CRA, Brokers, Dealers and Pool or Trust assemblers. 107.1640 Section 107.1640 Business Credit and Assistance... records of the CRA, Brokers, Dealers and Pool or Trust assemblers. The CRA and any broker, dealer and...

  12. 13 CFR 107.1640 - SBA access to records of the CRA, Brokers, Dealers and Pool or Trust assemblers.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false SBA access to records of the CRA, Brokers, Dealers and Pool or Trust assemblers. 107.1640 Section 107.1640 Business Credit and Assistance... records of the CRA, Brokers, Dealers and Pool or Trust assemblers. The CRA and any broker, dealer and...

  13. 13 CFR 107.1640 - SBA access to records of the CRA, Brokers, Dealers and Pool or Trust assemblers.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false SBA access to records of the CRA, Brokers, Dealers and Pool or Trust assemblers. 107.1640 Section 107.1640 Business Credit and Assistance... records of the CRA, Brokers, Dealers and Pool or Trust assemblers. The CRA and any broker, dealer and...

  14. The Global Regulatory Architecture of Transcription during the Caulobacter Cell Cycle

    PubMed Central

    Zhou, Bo; Schrader, Jared M.; Kalogeraki, Virginia S.; Abeliuk, Eduardo; Dinh, Cong B.; Pham, James Q.; Cui, Zhongying Z.; Dill, David L.; McAdams, Harley H.; Shapiro, Lucy

    2015-01-01

    Each Caulobacter cell cycle involves differentiation and an asymmetric cell division driven by a cyclical regulatory circuit comprised of four transcription factors (TFs) and a DNA methyltransferase. Using a modified global 5′ RACE protocol, we globally mapped transcription start sites (TSSs) at base-pair resolution, measured their transcription levels at multiple times in the cell cycle, and identified their transcription factor binding sites. Out of 2726 TSSs, 586 were shown to be cell cycle-regulated and we identified 529 binding sites for the cell cycle master regulators. Twenty-three percent of the cell cycle-regulated promoters were found to be under the combinatorial control of two or more of the global regulators. Previously unknown features of the core cell cycle circuit were identified, including 107 antisense TSSs which exhibit cell cycle-control, and 241 genes with multiple TSSs whose transcription levels often exhibited different cell cycle timing. Cumulatively, this study uncovered novel new layers of transcriptional regulation mediating the bacterial cell cycle. PMID:25569173

  15. Global Mapping of Open Chromatin Regulatory Elements by Formaldehyde-Assisted Isolation of Regulatory Elements Followed by Sequencing (FAIRE-seq).

    PubMed

    Bianco, Stéphanie; Rodrigue, Sébastien; Murphy, Bruce D; Gévry, Nicolas

    2015-01-01

    Genetic information is organized in a complex structure composed of DNA and proteins together designated chromatin. Chromatin plays a dynamic role in transcriptional processes in that alteration of the interaction between its components results in the deregulation of cellular transcriptional program. Modification of epigenetic marks, variation in the precise positioning of nucleosomes, and consequent mobilization of nucleosomes regulate the access of various transcriptional factors to its underlying DNA template. Nucleosome-depleted regions, also designated open chromatin domains, are associated with active DNA regulatory elements, including promoters, enhancers, silencers, and insulators. Here, we describe the protocol of a rapid and simple technique entitled FAIRE (formaldehyde-assisted isolation of regulatory elements). Combined with high-throughput sequencing (FAIRE-seq), this procedure allows isolation of nucleosome-free regions and their mapping along the genome, thereby providing a global view of cell-specific regulatory elements.

  16. Autoimmune Hepatitis: Progress from Global Immunosuppression to Personalised Regulatory T Cell Therapy

    PubMed Central

    Than, Nwe Ni; Jeffery, Hannah C.; Oo, Ye H.

    2016-01-01

    Autoimmune hepatitis (AIH) is an immune mediated liver injury. The precise aetiology of AIH is still unknown but current evidence suggests both genetic and environmental factors are involved. Breakdown in peripheral self-tolerance, and impaired functions of FOXP3+ regulatory T cell along with effector cell resistance to suppression at the tissue level seem to play an important role in AIH immunopathogenesis. AIH is predominantly a T lymphocytes driven disease but B lymphocytes are also involved in the immunopathology. Innate immune cells are crucial in the initial onset of disease and their response is followed by adaptive T (Th1, Th17, and cytotoxic T cells) and B cell responses evidenced by liver histology and peripheral blood serology. Standard treatment regimens involving steroid and immunosuppressive medications lead to global immune suppression requiring life-long therapy with many side effects. Biologic therapies have been attempted but duration of remission is short-lived. Future direction of diagnosis and treatment for AIH should be guided by “omics” and the immunology profile of the individual patient and clinicians should aim to deliver personalised medicine for their patients. Cell therapy such as infusion of autologous, antigen-specific, and liver-homing regulatory T cells to restore hepatic immune tolerance may soon be a potential future treatment for AIH patients. PMID:27446862

  17. Global and robust stability analysis of genetic regulatory networks with time-varying delays and parameter uncertainties.

    PubMed

    Fang-Xiang Wu

    2011-08-01

    The study of stability is essential for designing or controlling genetic regulatory networks. This paper addresses global and robust stability of genetic regulatory networks with time delays and parameter uncertainties. Most existing results on this issue are based on the linear matrix inequalities (LMIs) approach, which results in checking the existence of a feasible solution to high dimensional LMIs. Based on M-matrix theory, we will present several novel global stability conditions for genetic regulatory networks with time-varying and time-invariant delays. All of these stability conditions are given in terms of M-matrices, for which there are many and very easy ways to be verified. Then, we extend these results to genetic regulatory networks with time delays and parameter uncertainties. To illustrate the effectiveness of our theoretical results, several genetic regulatory networks are analyzed. Compared with existing results in the literature, we also show that our results are less conservative than existing ones with these illustrative genetic regulatory networks.

  18. Grouping of Diverse Stressors for Cumulative Risk Analysis (CRA) by Media, Time and Toxicity

    EPA Science Inventory

    CRAs may address multiple chemical, physical, biological or psychosocial stressors. Approaches for grouping diverse stressors prior to risk analysis can simplify some complexities associated with CRAs. For CRAs involving chemical mixtures, this entails developing CRA exposure gr...

  19. Transcriptional Analysis of the Global Regulatory Networks Active in Pseudomonas syringae during Leaf Colonization

    PubMed Central

    Yu, Xilan; Lund, Steven P.; Greenwald, Jessica W.; Records, Angela H.; Scott, Russell A.; Nettleton, Dan; Lindow, Steven E.; Gross, Dennis C.

    2014-01-01

    ABSTRACT The plant pathogen Pseudomonas syringae pv. syringae B728a grows and survives on leaf surfaces and in the leaf apoplast of its host, bean (Phaseolus vulgaris). To understand the contribution of distinct regulators to B728a fitness and pathogenicity, we performed a transcriptome analysis of strain B728a and nine regulatory mutants recovered from the surfaces and interior of leaves and exposed to environmental stresses in culture. The quorum-sensing regulators AhlR and AefR influenced few genes in planta or in vitro. In contrast, GacS and a downstream regulator, SalA, formed a large regulatory network that included a branch that regulated diverse traits and was independent of plant-specific environmental signals and a plant signal-dependent branch that positively regulated secondary metabolite genes and negatively regulated the type III secretion system. SalA functioned as a central regulator of iron status based on its reciprocal regulation of pyoverdine and achromobactin genes and also sulfur uptake, suggesting a role in the iron-sulfur balance. RetS functioned almost exclusively to repress secondary metabolite genes when the cells were not on leaves. Among the sigma factors examined, AlgU influenced many more genes than RpoS, and most AlgU-regulated genes depended on RpoN. RpoN differentially impacted many AlgU- and GacS-activated genes in cells recovered from apoplastic versus epiphytic sites, suggesting differences in environmental signals or bacterial stress status in these two habitats. Collectively, our findings illustrate a central role for GacS, SalA, RpoN, and AlgU in global regulation in B728a in planta and a high level of plasticity in these regulators’ responses to distinct environmental signals. PMID:25182327

  20. Drug policy and global regulatory capitalism: the case of new psychoactive substances (NPS).

    PubMed

    Seddon, Toby

    2014-09-01

    The recent emergence of vibrant markets in 'new psychoactive substances' or 'legal highs' has posed significant new challenges for drug policy. These partly concern what to do about them but the speed and complexity of change has also raised difficulties for how policy responses should be developed. Existing drug policy systems appear too slow and cumbersome to keep up with the pace of change, remaining locked in large part within 'old' ways of thinking that centre almost exclusively around the deployment (or not) of the criminal law and its related enforcement apparatus. In this paper, it is argued that we need to rethink the problem through the lens of regulation, in order to learn lessons from other sectors where more agile responses to changing markets and business innovation have often proved possible. By examining examples drawn from these other areas, an alternative policy-making framework can be developed, involving a more flexible mix of state regulation, civil society action and private law mechanisms. This new approach is founded on a recognition of the networked and polycentric character of effective market governance in an era of global regulatory capitalism. PMID:24768473

  1. Global Regulatory T-Cell Research from 2000 to 2015: A Bibliometric Analysis.

    PubMed

    Zongyi, Yin; Dongying, Chen; Baifeng, Li

    2016-01-01

    We aimed to analyze the global scientific output of regulatory T-cell (Treg) research and built a model to qualitatively and quantitatively evaluate publications from 2000 to 2015. Data were obtained from the Web of Science Core Collection (WoSCC) of Thomson Reuters on January 1, 2016. The bibliometric method and Citespace III were used to analyze authors, journals, publication outputs, institutions, countries, research areas, research hotspots, and trends. In total, we identified 35,741 publications on Treg research from 2000 to 2015, and observed that the annual publication rate increased with time. The Journal of Immunology published the highest number of articles, the leading country was the USA, and the leading institute was Harvard University. Sakaguchi, Hori, Fontenot, and Wang were the top authors in Treg research. Immunology accounted for the highest number of publications, followed by oncology, experimental medicine, cell biology, and hematology. Keyword analysis indicated that autoimmunity, inflammation, cytokine, gene expression, foxp3, and immunotherapy were the research hotspots, whereas autoimmune inflammation, gene therapy, granzyme B, RORγt, and th17 were the frontiers of Treg research. This bibliometric analysis revealed that Treg-related studies are still research hotspots, and that Treg-related clinical therapies are the research frontiers; however, further study and collaborations are needed worldwide. Overall, our findings provide valuable information for the editors of immunology journals to identify new perspectives and shape future research directions. PMID:27611317

  2. Global Regulatory T-Cell Research from 2000 to 2015: A Bibliometric Analysis

    PubMed Central

    Zongyi, Yin; Dongying, Chen

    2016-01-01

    We aimed to analyze the global scientific output of regulatory T-cell (Treg) research and built a model to qualitatively and quantitatively evaluate publications from 2000 to 2015. Data were obtained from the Web of Science Core Collection (WoSCC) of Thomson Reuters on January 1, 2016. The bibliometric method and Citespace III were used to analyze authors, journals, publication outputs, institutions, countries, research areas, research hotspots, and trends. In total, we identified 35,741 publications on Treg research from 2000 to 2015, and observed that the annual publication rate increased with time. The Journal of Immunology published the highest number of articles, the leading country was the USA, and the leading institute was Harvard University. Sakaguchi, Hori, Fontenot, and Wang were the top authors in Treg research. Immunology accounted for the highest number of publications, followed by oncology, experimental medicine, cell biology, and hematology. Keyword analysis indicated that autoimmunity, inflammation, cytokine, gene expression, foxp3, and immunotherapy were the research hotspots, whereas autoimmune inflammation, gene therapy, granzyme B, RORγt, and th17 were the frontiers of Treg research. This bibliometric analysis revealed that Treg-related studies are still research hotspots, and that Treg-related clinical therapies are the research frontiers; however, further study and collaborations are needed worldwide. Overall, our findings provide valuable information for the editors of immunology journals to identify new perspectives and shape future research directions. PMID:27611317

  3. Drug policy and global regulatory capitalism: the case of new psychoactive substances (NPS).

    PubMed

    Seddon, Toby

    2014-09-01

    The recent emergence of vibrant markets in 'new psychoactive substances' or 'legal highs' has posed significant new challenges for drug policy. These partly concern what to do about them but the speed and complexity of change has also raised difficulties for how policy responses should be developed. Existing drug policy systems appear too slow and cumbersome to keep up with the pace of change, remaining locked in large part within 'old' ways of thinking that centre almost exclusively around the deployment (or not) of the criminal law and its related enforcement apparatus. In this paper, it is argued that we need to rethink the problem through the lens of regulation, in order to learn lessons from other sectors where more agile responses to changing markets and business innovation have often proved possible. By examining examples drawn from these other areas, an alternative policy-making framework can be developed, involving a more flexible mix of state regulation, civil society action and private law mechanisms. This new approach is founded on a recognition of the networked and polycentric character of effective market governance in an era of global regulatory capitalism.

  4. Disruption of a global regulatory gene to enhance central carbon flux into phenylalanine biosynthesis in Escherichia coli.

    PubMed

    Tatarko, M; Romeo, T

    2001-07-01

    Genetic engineering of microbes for commercial metabolite production traditionally has sought to alter the levels and/or intrinsic activities of key enzymes in relevant biosynthetic pathway(s). Microorganisms exploit similar strategies for flux control, but also coordinate flux through sets of related pathways by using global regulatory circuits. We have engineered a global regulatory system of Escherichia coli, Csr (carbon storage regulator), to increase precursor for aromatic amino acid biosynthesis. Disruption of csrA increases gluconeogenesis, decreases glycolysis, and thus elevates phosphoenolpyruvate, a limiting precursor of aromatics. A strain in which the aromatic (shikimate) pathway had been optimized produced twofold more phenylalanine when csrA was disrupted. Overexpression of tktA (transketolase) to increase the other precursor, erythrose-4-phosphate, yielded approximately 1.4-fold enhancement, while both changes were additive. These effects of csrA were not mediated by increasing the regulatory enzymes of phenylalanine biosynthesis. This study introduces the concept of "global metabolic engineering" for second-generation strain improvement. PMID:11375660

  5. A comprehensive study on regulatory requirements for development and filing of generic drugs globally

    PubMed Central

    Handoo, Shweta; Arora, Vandana; Khera, Deepak; Nandi, Prafulla Kumar; Sahu, Susanta Kumar

    2012-01-01

    The regulatory requirements of various countries of the world vary from each other. Therefore, it is challenging for the companies to develop a single drug which can be simultaneously submitted in all the countries for approval. The regulatory strategy for product development is essentially to be established before commencement of developmental work in order to avoid major surprises after submission of the application. The role of the regulatory authorities is to ensure the quality, safety, and efficacy of all medicines in circulation in their country. It not only includes the process of regulating and monitoring the drugs but also the process of manufacturing, distribution, and promotion of it. One of the primary challenges for regulatory authority is to ensure that the pharmaceutical products are developed as per the regulatory requirement of that country. This process involves the assessment of critical parameters during product development. PMID:23373001

  6. A comprehensive study on regulatory requirements for development and filing of generic drugs globally.

    PubMed

    Handoo, Shweta; Arora, Vandana; Khera, Deepak; Nandi, Prafulla Kumar; Sahu, Susanta Kumar

    2012-07-01

    The regulatory requirements of various countries of the world vary from each other. Therefore, it is challenging for the companies to develop a single drug which can be simultaneously submitted in all the countries for approval. The regulatory strategy for product development is essentially to be established before commencement of developmental work in order to avoid major surprises after submission of the application. The role of the regulatory authorities is to ensure the quality, safety, and efficacy of all medicines in circulation in their country. It not only includes the process of regulating and monitoring the drugs but also the process of manufacturing, distribution, and promotion of it. One of the primary challenges for regulatory authority is to ensure that the pharmaceutical products are developed as per the regulatory requirement of that country. This process involves the assessment of critical parameters during product development.

  7. The Lunar Radiation Environment: LRO/CRaTER Observations and Geant4 Modeling

    NASA Astrophysics Data System (ADS)

    Looper, M. D.; Mazur, J.; Blake, J. B.; Spence, H. E.; Golightly, M.; Case, A. W.

    2010-12-01

    The Cosmic Ray Telescope for the Effects of Radiation (CRaTER) has been in orbit around the moon aboard the Lunar Reconnaissance Orbiter (LRO) for over a year. The purpose of CRaTER is to measure the radiation environment that will be experienced, in particular, by astronauts on and near the lunar surface; to that end, CRaTER consists of a "telescope" of six silicon solid state detectors arranged in three pairs, with two large blocks of Tissue-Equivalent Plastic between pairs to represent the shielding provided by the human body. The data we have collected to date are complex, and to understand our observations we have performed extensive modeling of the "albedo" particles produced by interactions of primary cosmic rays with the lunar surface and with the spacecraft itself, and of the response of the sensor to both primary and albedo particles. We will present measurements of the Linear Energy Transfer (LET) and dose from CRaTER, and will show more generic LET and dose spectra, using our models to remove the effects specific to the CRaTER sensor geometry and spacecraft environment (shielding, locally-produced albedo), for lunar orbit and at the lunar surface.

  8. 7 CFR 4290.1640 - Secretary's access to records of the CRA, Brokers, Dealers and Pool or Trust assemblers.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., Dealers and Pool or Trust assemblers. 4290.1640 Section 4290.1640 Agriculture Regulations of the... to records of the CRA, Brokers, Dealers and Pool or Trust assemblers. The CRA and any broker, dealer and Pool or Trust assembler operating under the regulations in this part shall make all books,...

  9. 7 CFR 4290.1640 - Secretary's access to records of the CRA, Brokers, Dealers and Pool or Trust assemblers.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., Dealers and Pool or Trust assemblers. 4290.1640 Section 4290.1640 Agriculture Regulations of the... to records of the CRA, Brokers, Dealers and Pool or Trust assemblers. The CRA and any broker, dealer and Pool or Trust assembler operating under the regulations in this part shall make all books,...

  10. 7 CFR 4290.1640 - Secretary's access to records of the CRA, Brokers, Dealers and Pool or Trust assemblers.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., Dealers and Pool or Trust assemblers. 4290.1640 Section 4290.1640 Agriculture Regulations of the... to records of the CRA, Brokers, Dealers and Pool or Trust assemblers. The CRA and any broker, dealer and Pool or Trust assembler operating under the regulations in this part shall make all books,...

  11. 13 CFR 108.1640 - SBA access to records of the CRA, Brokers, Dealers and Pool or Trust assemblers.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., Brokers, Dealers and Pool or Trust assemblers. 108.1640 Section 108.1640 Business Credit and Assistance....1640 SBA access to records of the CRA, Brokers, Dealers and Pool or Trust assemblers. The CRA and any broker, dealer and Pool or Trust assembler operating under the regulations in this part shall make...

  12. 13 CFR 108.1640 - SBA access to records of the CRA, Brokers, Dealers and Pool or Trust assemblers.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., Brokers, Dealers and Pool or Trust assemblers. 108.1640 Section 108.1640 Business Credit and Assistance....1640 SBA access to records of the CRA, Brokers, Dealers and Pool or Trust assemblers. The CRA and any broker, dealer and Pool or Trust assembler operating under the regulations in this part shall make...

  13. 7 CFR 4290.1640 - Secretary's access to records of the CRA, Brokers, Dealers and Pool or Trust assemblers.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., Dealers and Pool or Trust assemblers. 4290.1640 Section 4290.1640 Agriculture Regulations of the... to records of the CRA, Brokers, Dealers and Pool or Trust assemblers. The CRA and any broker, dealer and Pool or Trust assembler operating under the regulations in this part shall make all books,...

  14. 13 CFR 108.1640 - SBA access to records of the CRA, Brokers, Dealers and Pool or Trust assemblers.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., Brokers, Dealers and Pool or Trust assemblers. 108.1640 Section 108.1640 Business Credit and Assistance....1640 SBA access to records of the CRA, Brokers, Dealers and Pool or Trust assemblers. The CRA and any broker, dealer and Pool or Trust assembler operating under the regulations in this part shall make...

  15. 13 CFR 108.1640 - SBA access to records of the CRA, Brokers, Dealers and Pool or Trust assemblers.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., Brokers, Dealers and Pool or Trust assemblers. 108.1640 Section 108.1640 Business Credit and Assistance....1640 SBA access to records of the CRA, Brokers, Dealers and Pool or Trust assemblers. The CRA and any broker, dealer and Pool or Trust assembler operating under the regulations in this part shall make...

  16. 7 CFR 4290.1640 - Secretary's access to records of the CRA, Brokers, Dealers and Pool or Trust assemblers.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., Dealers and Pool or Trust assemblers. 4290.1640 Section 4290.1640 Agriculture Regulations of the... to records of the CRA, Brokers, Dealers and Pool or Trust assemblers. The CRA and any broker, dealer and Pool or Trust assembler operating under the regulations in this part shall make all books,...

  17. NatB Domain-Containing CRA-1 Antagonizes Hydrolase ACER-1 Linking Acetyl-CoA Metabolism to the Initiation of Recombination during C. elegans Meiosis

    PubMed Central

    Gao, Jinmin; Kim, Hyun-Min; Elia, Andrew E.; Elledge, Stephen J.; Colaiácovo, Monica P.

    2015-01-01

    The formation of DNA double-strand breaks (DSBs) must take place during meiosis to ensure the formation of crossovers, which are required for accurate chromosome segregation, therefore avoiding aneuploidy. However, DSB formation must be tightly regulated to maintain genomic integrity. How this regulation operates in the context of different chromatin architectures and accessibility, and how it is linked to metabolic pathways, is not understood. We show here that global histone acetylation levels undergo changes throughout meiotic progression. Moreover, perturbations to global histone acetylation levels are accompanied by changes in the frequency of DSB formation in C. elegans. We provide evidence that the regulation of histone acetylation requires CRA-1, a NatB domain-containing protein homologous to human NAA25, which controls the levels of acetyl-Coenzyme A (acetyl-CoA) by antagonizing ACER-1, a previously unknown and conserved acetyl-CoA hydrolase. CRA-1 is in turn negatively regulated by XND-1, an AT-hook containing protein. We propose that this newly defined protein network links acetyl-CoA metabolism to meiotic DSB formation via modulation of global histone acetylation. PMID:25768301

  18. Molecular characterization of the CRa gene conferring clubroot resistance in Brassica rapa.

    PubMed

    Ueno, Hiroki; Matsumoto, Etsuo; Aruga, Daisuke; Kitagawa, Satoshi; Matsumura, Hideo; Hayashida, Nobuaki

    2012-12-01

    Clubroot disease is one of the major diseases affecting Brassicaceae crops, and a number of these crops grown commercially, such as Chinese cabbage (Brassica rapa L. ssp. pekinensis), are known to be highly susceptible to clubroot disease. To provide protection from this disease, plant breeders have introduced genes for resistance to clubroot from the European turnip into susceptible lines. The CRa gene confers specific resistance to the clubroot pathogen Plasmodiophora brassicae isolate M85. Fine mapping of the CRa locus using synteny to the Arabidopsis thaliana genome and partial genome sequences of B. rapa revealed a candidate gene encoding a TIR-NBS-LRR protein. Several structural differences in this candidate gene were found between susceptible and resistant lines, and CRa expression was observed only in the resistant line. Four mutant lines lacking clubroot resistance were obtained by the UV irradiation of pollen from a resistant line, and all of these mutant lines carried independent mutations in the candidate TIR-NBS-LRR gene. This genetic and molecular evidence strongly suggests that the identified gene is CRa. This is the first report on the molecular characterization of a clubroot Resistance gene in Brassicaceae and of the disease resistance gene in B. rapa.

  19. University Faculty Value the CRA Designation--They Just Don't Realize It Yet!

    ERIC Educational Resources Information Center

    Cole, Kimberley W.

    2013-01-01

    The Certified Research Administrator (CRA) certification has enjoyed success and recognition among research administration professionals. However, this recognition is parochial and does not extend much past the walls of research administration. Results of a recent research study showed that Principal Investigators value and expect certain aspects…

  20. 12 CFR 345.29 - Effect of CRA performance on applications.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... OF GENERAL POLICY COMMUNITY REINVESTMENT Standards for Assessing Performance § 345.29 Effect of CRA... assumption of liabilities; and (4) Deposit insurance for a newly chartered financial institution. (b) New financial institutions. A newly chartered financial institution shall submit with its application...

  1. VizieR Online Data Catalog: RASS young sources around R CrA (Neuhaeuser+, 2000)

    NASA Astrophysics Data System (ADS)

    Neuhaeuser, R.; Walter, F. M.; Covino, E.; Alcala, J. M.; Wolk, S. J.; Frink, S.; Guillout, P.; Sterzik, M. F.; Comeron, F.

    2000-11-01

    We present the ROSAT All-Sky Survey data in a 126 deg2 area around the CrA star forming region. With low-resolution spectroscopy of unidentified ROSAT sources we could find 19 new pre-main sequence stars, two of which are classical T Tauri stars, the others being weak-lined. The spectral types of these new T Tauri stars range from F7 to M6. The two new classical T Tauri stars are located towards two small cloud-lets outside of the main CrA cloud. They appear to be ~10 Myrs old, by comparing their location in the H-R diagram with isochrones for an assumed distance of 130 pc, the distance of the main CrA dark cloud. The new off-cloud weak-line T Tauri stars may have formed in similar cloudlets, which have dispersed recently. High-resolution spectra of our new T Tauri stars show that they have significantly more lithium absorption than zero-age main-sequence stars of the same spectral type, so that they are indeed young. From those spectra we also obtained rotational and radial velocities. For some stars we found the proper motion in published catalogs. The direction and velocity of the 3D space motion - south relative to the galactic plane - of the CrA T Tauri stars is consistent with the dark cloud being formed originally by a high-velocity cloud impact onto the galactic plane, which triggered the star formation in CrA. We also present VRIJHK photometry for most of the new T Tauri stars to derive their luminosities, ages, and masses. (4 data files).

  2. Biosafety, biosecurity and internationally mandated regulatory regimes: compliance mechanisms for education and global health security

    PubMed Central

    Sture, Judi; Whitby, Simon; Perkins, Dana

    2015-01-01

    This paper highlights the biosafety and biosecurity training obligations that three international regulatory regimes place upon states parties. The duty to report upon the existence of such provisions as evidence of compliance is discussed in relation to each regime. We argue that such mechanisms can be regarded as building blocks for the development and delivery of complementary biosafety and biosecurity teaching and training materials. We show that such building blocks represent foundations upon which life and associated scientists – through greater awareness of biosecurity concerns – can better fulfil their responsibilities to guard their work from misuse in the future. PMID:24494580

  3. Forbush Decrease events in Lunar Radiation Environment observed by the LRO/CRaTER

    NASA Astrophysics Data System (ADS)

    Sohn, J.; Oh, S.; Yi, Y.; Kim, E.; Lee, J.; Spence, H. E.

    2012-12-01

    The Lunar Reconnaissance Orbiter (LRO) launched on June 16, 2009 has six experiments including of the Cosmic Ray Telescope for the Effects of Radiation (CRaTER) onboard. The CRaTER instrument characterizes the radiation environment to be experienced by humans during future lunar missions. The CRaTER instrument measures the effects of ionizing energy loss in matter specifically in silicon solid-state detectors due to penetrating solar energetic protons (SEP) and galactic cosmic rays (GCR) after interactions with tissue-equivalent plastic (TEP), a synthetic analog of human tissue. The CRaTER instrument houses a compact and highly precise microdosimeter. It measures dose rates below one micro-Rad/sec in lunar radiation environment. Forbush decrease (FD) event is the sudden decrease of galactic cosmic ray (GCR) flux. The FD event is considered to be caused by exclusion of GCR due to intense interplanetary magnetic field (IMF) structures of interplanetary shock (IP) sheath region and/or the interplanetary coronal mass ejection (CME) following the IP shocks as a shock driver. We use the data of cosmic ray flux and dose rates observed by the CRaTER instrument. We also use the CME list of STEREO SECCHI inner, outer coronagraph and the IMF (Interplanetary CME) data of the ACE/MAG instrument. We examine the origins and the characteristics of the FD-like events in lunar radiation environment. We also compare these events with the FD events on the Earth. We find that whenever the FD events are recorded at ground Neutron Monitor stations, the FD-like events also occur on the lunar environments. The flux variation amplitude of FD-like events on the Moon is approximately two times larger than that of FD events on the Earth. We compare time profiles of GCR flux with of the dose rate of FD-like events in the lunar environment. We figure out that the distinct FD-like events correspond to dose rate events in the CRaTER on lunar environment during the event period.

  4. Global Risk Assessment of Aflatoxins in Maize and Peanuts: Are Regulatory Standards Adequately Protective?

    PubMed Central

    Wu, Felicia

    2013-01-01

    The aflatoxins are a group of fungal metabolites that contaminate a variety of staple crops, including maize and peanuts, and cause an array of acute and chronic human health effects. Aflatoxin B1 in particular is a potent liver carcinogen, and hepatocellular carcinoma (HCC) risk is multiplicatively higher for individuals exposed to both aflatoxin and chronic infection with hepatitis B virus (HBV). In this work, we sought to answer the question: do current aflatoxin regulatory standards around the world adequately protect human health? Depending upon the level of protection desired, the answer to this question varies. Currently, most nations have a maximum tolerable level of total aflatoxins in maize and peanuts ranging from 4 to 20ng/g. If the level of protection desired is that aflatoxin exposures would not increase lifetime HCC risk by more than 1 in 100,000 cases in the population, then most current regulatory standards are not adequately protective even if enforced, especially in low-income countries where large amounts of maize and peanuts are consumed and HBV prevalence is high. At the protection level of 1 in 10,000 lifetime HCC cases in the population, however, almost all aflatoxin regulations worldwide are adequately protective, with the exception of several nations in Africa and Latin America. PMID:23761295

  5. Global risk assessment of aflatoxins in maize and peanuts: are regulatory standards adequately protective?

    PubMed

    Wu, Felicia; Stacy, Shaina L; Kensler, Thomas W

    2013-09-01

    The aflatoxins are a group of fungal metabolites that contaminate a variety of staple crops, including maize and peanuts, and cause an array of acute and chronic human health effects. Aflatoxin B1 in particular is a potent liver carcinogen, and hepatocellular carcinoma (HCC) risk is multiplicatively higher for individuals exposed to both aflatoxin and chronic infection with hepatitis B virus (HBV). In this work, we sought to answer the question: do current aflatoxin regulatory standards around the world adequately protect human health? Depending upon the level of protection desired, the answer to this question varies. Currently, most nations have a maximum tolerable level of total aflatoxins in maize and peanuts ranging from 4 to 20ng/g. If the level of protection desired is that aflatoxin exposures would not increase lifetime HCC risk by more than 1 in 100,000 cases in the population, then most current regulatory standards are not adequately protective even if enforced, especially in low-income countries where large amounts of maize and peanuts are consumed and HBV prevalence is high. At the protection level of 1 in 10,000 lifetime HCC cases in the population, however, almost all aflatoxin regulations worldwide are adequately protective, with the exception of several nations in Africa and Latin America.

  6. Global trade and assisted reproductive technologies: regulatory challenges in international surrogacy.

    PubMed

    Nelson, Erin

    2013-01-01

    International surrogacy is an increasingly common phenomenon and an important global health challenge. Legal rules are a key consideration for the participants in international surrogacy arrangements. In some cases the law can help to resolve the complex issues that arise in this context, but it is important to consider the role played by law in contributing to the complex conflicts that such arrangements can generate.

  7. Can the FDA improve oversight of foreign clinical trials?: Closing the information gap and moving towards a globalized regulatory scheme.

    PubMed

    Ourso, André

    2012-01-01

    Currently, pharmaceutical companies' utilization of foreign clinical trial data is a ubiquitous and indispensable aspect of gaining approval to market drugs in the United States. Cost benefits, a larger pool of ready volunteer subjects, and greater efficiency in clinical testing are some of the reasons for conducting clinical trials overseas. Despite these advantages, lack of proper oversight may have serious public health implications regarding the integrity of clinical research, ethical treatment of human subjects, and drug safety. Due to the expansive global nature of foreign clinical trials, there are concerns with the FDA's ability to monitor and regulate these trials. This article examines the FDA's oversight of foreign clinical trials and the agency's limitations regulating these trials. In addition to looking at steps the FDA is taking to address these limitations, the article examines other potential regulatory and cooperative actions that can be taken to effectively monitor foreign clinical trials and to ensure data integrity and patient safety. PMID:22606923

  8. Can the FDA improve oversight of foreign clinical trials?: Closing the information gap and moving towards a globalized regulatory scheme.

    PubMed

    Ourso, André

    2012-01-01

    Currently, pharmaceutical companies' utilization of foreign clinical trial data is a ubiquitous and indispensable aspect of gaining approval to market drugs in the United States. Cost benefits, a larger pool of ready volunteer subjects, and greater efficiency in clinical testing are some of the reasons for conducting clinical trials overseas. Despite these advantages, lack of proper oversight may have serious public health implications regarding the integrity of clinical research, ethical treatment of human subjects, and drug safety. Due to the expansive global nature of foreign clinical trials, there are concerns with the FDA's ability to monitor and regulate these trials. This article examines the FDA's oversight of foreign clinical trials and the agency's limitations regulating these trials. In addition to looking at steps the FDA is taking to address these limitations, the article examines other potential regulatory and cooperative actions that can be taken to effectively monitor foreign clinical trials and to ensure data integrity and patient safety.

  9. Medición de Ecos de Luz en R CrA

    NASA Astrophysics Data System (ADS)

    Calandra, M. F.; Gil-Hutton, R.

    2015-08-01

    After confirmation of the existence of Light Echoes in S CrA, it was decided to evaluate the behavior of nearby stars in that region and discuss the possibility for them to also show this phenomenon. In this work, Light Echoes around R CrA were measured from observations made between July and November 2007 at the Complejo Astronómico El Leoncito (CASLEO). We find the distance to the dust structure that causes the echo by adjusting various models available in the literature and, using this estimation of the distance and the particular characteristics of the star, it is possible to conclude that the observed dust structure would be at a distance that is similar to that of the Oort cloud in the Solar System.

  10. Final Report: Contractor Readiness Assessment (CRA) for TREAT Fuel Movement and Control Rod Drives Isolation

    SciTech Connect

    Rowsell, David Leon

    2015-06-01

    This report documents the Contractor Readiness Assessment (CRA) for TREAT Fuel Movement and Control Rod Drives Isolation. The review followed the approved Plan of Action (POA) and Implementation Plan (IP) using the identified core requirements. The activity was limited scope focusing on the control rod drives functional isolation and fuel element movement. The purpose of this review is to ensure the facility's readiness to move fuel elements thus supporting inspection and functionally isolate the control rod drives to maintain the required shutdown margin.

  11. The global regulatory system Csr senses glucose through the phosphoenolpyruvate: carbohydrate phosphotransferase system.

    PubMed

    Pérez-Morales, Deyanira; Bustamante, Víctor H

    2016-02-01

    A novel connection between two regulatory systems controlling crucial biological processes in bacteria, the carbon storage regulator (Csr) system and the glucose-specific phosphotransferase system (PTS), is reported by Leng et al. in this issue. This involves the interaction of unphosphorylated EIIA(Glc), a component of the glucose-specific PTS, with the CsrD protein, which accelerates the decay of the CsrB and CsrC small RNAs via RNase E in Escherichia coli. As unphosphorylated EIIA(G) (lc) is generated in the presence of glucose, the PTS thus acts as a sensor of glucose for the Csr system. Interestingly, another pathway can operate for communication between the Csr system and the glucose-specific PTS. The absence of glucose generates phosphorylated EIIA(Glc) , which activates the enzyme adenylate cyclase to produce cyclic adenosine monophosphate (cAMP) that, in turn, binds to the regulator cAMP receptor protein (CRP). Leng et al. show that the complex cAMP-CRP modestly reduces CsrB decay independently of CsrD. On the other hand, a previous study indicates that the complex cAMP-CRP positively regulates the transcription of CsrB and CsrC in Salmonella enterica. Therefore, EIIA(G) (lc) could work as a molecular switch that regulates the activity of the Csr system, in response to its phosphorylation state determined by the presence or absence of glucose, in order to control gene expression.

  12. Proteomics analysis of global regulatory cascades involved in clavulanic acid production and morphological development in Streptomyces clavuligerus.

    PubMed

    Ferguson, Nicole L; Peña-Castillo, Lourdes; Moore, Marcus A; Bignell, Dawn R D; Tahlan, Kapil

    2016-04-01

    The genus Streptomyces comprises bacteria that undergo a complex developmental life cycle and produce many metabolites of importance to industry and medicine. Streptomyces clavuligerus produces the β-lactamase inhibitor clavulanic acid, which is used in combination with β-lactam antibiotics to treat certain β-lactam resistant bacterial infections. Many aspects of how clavulanic acid production is globally regulated in S. clavuligerus still remains unknown. We conducted comparative proteomics analysis using the wild type strain of S. clavuligerus and two mutants (ΔbldA and ΔbldG), which are defective in global regulators and vary in their ability to produce clavulanic acid. Approximately 33.5 % of the predicted S. clavuligerus proteome was detected and 192 known or putative regulatory proteins showed statistically differential expression levels in pairwise comparisons. Interestingly, the expression of many proteins whose corresponding genes contain TTA codons (predicted to require the bldA tRNA for translation) was unaffected in the bldA mutant.

  13. The US regulatory and pharmacopeia response to the global heparin contamination crisis.

    PubMed

    Szajek, Anita Y; Chess, Edward; Johansen, Kristian; Gratzl, Gyöngyi; Gray, Elaine; Keire, David; Linhardt, Robert J; Liu, Jian; Morris, Tina; Mulloy, Barbara; Nasr, Moheb; Shriver, Zachary; Torralba, Pearle; Viskov, Christian; Williams, Roger; Woodcock, Janet; Workman, Wesley; Al-Hakim, Ali

    2016-06-01

    The contamination of the widely used lifesaving anticoagulant drug heparin in 2007 has drawn renewed attention to the challenges that are associated with the characterization, quality control and standardization of complex biological medicines from natural sources. Heparin is a linear, highly sulfated polysaccharide consisting of alternating glucosamine and uronic acid monosaccharide residues. Heparin has been used successfully as an injectable antithrombotic medicine since the 1930s, and its isolation from animal sources (primarily porcine intestine) as well as its manufacturing processes have not changed substantially since its introduction. The 2007 heparin contamination crisis resulted in several deaths in the United States and hundreds of adverse reactions worldwide, revealing the vulnerability of a complex global supply chain to sophisticated adulteration. This Perspective discusses how the US Food and Drug Administration (FDA), the United States Pharmacopeial Convention (USP) and international stakeholders collaborated to redefine quality expectations for heparin, thus making an important natural product better controlled and less susceptible to economically motivated adulteration. PMID:27281424

  14. Global small RNA chaperone Hfq and regulatory small RNAs are important virulence regulators in Erwinia amylovora.

    PubMed

    Zeng, Quan; McNally, R Ryan; Sundin, George W

    2013-04-01

    Hfq is a global small RNA (sRNA) chaperone that interacts with Hfq-regulated sRNAs and functions in the posttranscriptional regulation of gene expression. In this work, we identified Hfq to be a virulence regulator in the Gram-negative fire blight pathogen Erwinia amylovora. Deletion of hfq in E. amylovora Ea1189 significantly reduced bacterial virulence in both immature pear fruits and apple shoots. Analysis of virulence determinants in strain Ea1189Δhfq showed that Hfq exerts pleiotropic regulation of amylovoran exopolysaccharide production, biofilm formation, motility, and the type III secretion system (T3SS). Further characterization of biofilm regulation by Hfq demonstrated that Hfq limits bacterial attachment to solid surfaces while promoting biofilm maturation. Characterization of T3SS regulation by Hfq revealed that Hfq positively regulates the translocation and secretion of the major type III effector DspE and negatively controls the secretion of the putative translocator HrpK and the type III effector Eop1. Lastly, 10 Hfq-regulated sRNAs were identified using a computational method, and two of these sRNAs, RprA and RyhA, were found to be required for the full virulence of E. amylovora.

  15. Lunar radiation environment and space weathering from the Cosmic Ray Telescope for the Effects of Radiation (CRaTER)

    NASA Astrophysics Data System (ADS)

    Schwadron, N. A.; Baker, T.; Blake, B.; Case, A. W.; Cooper, J. F.; Golightly, M.; Jordan, A.; Joyce, C.; Kasper, J.; Kozarev, K.; Mislinski, J.; Mazur, J.; Posner, A.; Rother, O.; Smith, S.; Spence, H. E.; Townsend, L. W.; Wilson, J.; Zeitlin, C.

    2012-03-01

    The Cosmic Ray Telescope for the Effects of Radiation (CRaTER) measures linear energy transfer by Galactic Cosmic Rays (GCRs) and Solar Energetic Particles (SEPs) on the Lunar Reconnaissance Orbiter (LRO) Mission in a circular, polar lunar orbit. GCR fluxes remain at the highest levels ever observed during the space age. One of the largest SEP events observed by CRaTER during the LRO mission occurred on June 7, 2011. We compare model predictions by the Earth-Moon-Mars Radiation Environment Module (EMMREM) for both dose rates from GCRs and SEPs during this event with results from CRaTER. We find agreement between these models and the CRaTER dose rates, which together demonstrate the accuracy of EMMREM, and its suitability for a real-time space weather system. We utilize CRaTER to test forecasts made by the Relativistic Electron Alert System for Exploration (REleASE), which successfully predicts the June 7th event. At the maximum CRaTER-observed GCR dose rate (˜11.7 cGy/yr where Gy is a unit indicating energy deposition per unit mass, 1 Gy = 1 J/kg), GCRs deposit ˜88 eV/molecule in water over 4 billion years, causing significant change in molecular composition and physical structure (e.g., density, color, crystallinity) of water ice, loss of molecular hydrogen, and production of more complex molecules linking carbon and other elements in the irradiated ice. This shows that space weathering by GCRs may be extremely important for chemical evolution of ice on the Moon. Thus, we show comprehensive observations from the CRaTER instrument on the Lunar Reconnaissance Orbiter that characterizes the radiation environment and space weathering on the Moon.

  16. Genome-wide Annotation, Identification, and Global Transcriptomic Analysis of Regulatory or Small RNA Gene Expression in Staphylococcus aureus

    PubMed Central

    Weiss, Andy; Broach, William H.; Wiemels, Richard E.; Mogen, Austin B.; Rice, Kelly C.

    2016-01-01

    ABSTRACT In Staphylococcus aureus, hundreds of small regulatory or small RNAs (sRNAs) have been identified, yet this class of molecule remains poorly understood and severely understudied. sRNA genes are typically absent from genome annotation files, and as a consequence, their existence is often overlooked, particularly in global transcriptomic studies. To facilitate improved detection and analysis of sRNAs in S. aureus, we generated updated GenBank files for three commonly used S. aureus strains (MRSA252, NCTC 8325, and USA300), in which we added annotations for >260 previously identified sRNAs. These files, the first to include genome-wide annotation of sRNAs in S. aureus, were then used as a foundation to identify novel sRNAs in the community-associated methicillin-resistant strain USA300. This analysis led to the discovery of 39 previously unidentified sRNAs. Investigating the genomic loci of the newly identified sRNAs revealed a surprising degree of inconsistency in genome annotation in S. aureus, which may be hindering the analysis and functional exploration of these elements. Finally, using our newly created annotation files as a reference, we perform a global analysis of sRNA gene expression in S. aureus and demonstrate that the newly identified tsr25 is the most highly upregulated sRNA in human serum. This study provides an invaluable resource to the S. aureus research community in the form of our newly generated annotation files, while at the same time presenting the first examination of differential sRNA expression in pathophysiologically relevant conditions. PMID:26861020

  17. Transcriptional and translational regulatory responses to iron limitation in the globally distributed marine bacterium Candidatus Pelagibacter ubique

    SciTech Connect

    Smith, Daniel P.; Kitner, J. B.; Norbeck, Angela D.; Clauss, Therese RW; Lipton, Mary S.; Schwalbach, M. S.; Steindler, L.; Nicora, Carrie D.; Smith, Richard D.; Giovannoni, Stephen J.

    2010-05-05

    Abstract Background: Iron is recognized as an important micronutrient that limits microbial plankton productivity over vast regions of the oceans. We investigated the gene expression responses of Candidatus Pelagibacter ubique cultures to iron limitation in natural seawater media supplemented with a siderophore to chelate iron. Methodology/Principal Findings: Microarray data indicated transcription of the periplasmic iron binding protein sfuC increased by 16-fold, and iron transporter subunits, iron-sulfur center assembly genes, and the putative ferroxidase rubrerythrin transcripts increased to a lesser extent. Quantitative peptide mass spectrometry revealed that sfuC protein abundance increased 27-fold, despite an average decrease of 59% across the global proteome. Two RNA-binding proteins, CspE and CspL, correlated well with iron availability, suggesting that they may contribute to the observed differences between the transcriptome and proteome. Conclusions/Significance: We propose sfuC as a marker gene for indicating iron limitation in marine metatranscriptomic and metaproteomic ecological surveys. The marked proteome reduction was not directly correlated to changes in the transcriptome, implicating post-transcriptional regulatory mechanisms as modulators of protein expression. We propose a model in which the RNA-binding activity of cspE and cspL selectively enables protein synthesis of the iron acquisition protein sfuC during transient growth-limiting episodes of iron scarcity.

  18. Integration of a complex regulatory cascade involving the SirA/BarA and Csr global regulatory systems that controls expression of the Salmonella SPI-1 and SPI-2 virulence regulons through HilD.

    PubMed

    Martínez, Luary C; Yakhnin, Helen; Camacho, Martha I; Georgellis, Dimitris; Babitzke, Paul; Puente, José L; Bustamante, Víctor H

    2011-06-01

    Salmonella pathogenicity islands 1 and 2 (SPI-1 and SPI-2) play key roles in the pathogenesis of Salmonella enterica. Previously, we showed that when Salmonella grows in Luria-Bertani medium, HilD, encoded in SPI-1, first induces the expression of hilA, located in SPI-1, and subsequently of the ssrAB operon, located in SPI-2. These genes code for HilA and the SsrA/B two-component system, the positive regulators of the SPI-1 and SPI-2 regulons respectively. In this study, we demonstrate that CsrA, a global regulatory RNA binding protein, post-transcriptionally regulates hilD expression by directly binding near the Shine-Dalgarno and translation initiation codon sequences of the hilD mRNA, preventing its translation and leading to its accelerated turnover. Negative regulation is counteracted by the global SirA/BarA two-component system, which directly activates the expression of CsrB and CsrC, two non-coding regulatory RNAs that sequester CsrA, thereby preventing it from binding to its target mRNAs. Our results illustrate the integration of global and specific regulators into a multifactorial regulatory cascade controlling the expression of virulence genes acquired by horizontal transfer events.

  19. CraMs: Craniometric Analysis Application Using 3D Skull Models.

    PubMed

    Dias, Paulo; Neves, Luis; Santos, Daniel; Coelho, Catarina; Ferreira, Maria Teresa; Santos, Helder; Silva, Samuel; Santos, Beatriz Sousa

    2015-01-01

    Craniometric analysis plays an important role in anthropology studies and forensics. This paper presents CraMs, an application using a new craniometric approach based on 3D models of the skull. The main objective is to obtain, through a process supervised by anthropologists, the main points of interest used to compute craniometric measurements. The application aids this process by analyzing the skull geometry and automatically providing points of interest. The application also allows for semiautomatic point detection, where the user provides an initial guess that might be refined based on the curvature of the skull, as well as the manual selection of any other points of interest. Moreover, results comparing measurements obtained with CraMs and traditional craniometry methods on eight skulls suggest that the application provides comparable craniometric measurements and lower inter-observer variability. This approach offers advantages such as an easier access to skulls with no risk of bone damage and the possibility of defining new measurements based on morphology or other skull characteristics, which are not possible using traditional methods. PMID:26594956

  20. Secondary-Particle Production in Organic Material by Cosmic Rays: Simulations and CRaTER Observations

    NASA Astrophysics Data System (ADS)

    Looper, M. D.; Blake, J. B.; Mazur, J. E.; Spence, H. E.

    2009-12-01

    It is well known that material between a radiation environment and a sensitive target, whether the target is an electronic device or living tissue, can enhance the dose received by the target instead of shielding it, depending on the characteristics of the material and of the radiation. The Cosmic Ray Telescope for the Effects of Radiation (CRaTER) aboard the Lunar Reconnaissance Orbiter (LRO) is designed to measure this effect on the dose that would be received from the space radiation environment by an astronaut on or near the lunar surface. In between its silicon solid-state detectors are two pieces of Tissue-Equivalent Plastic (TEP) with a density and composition similar to muscle tissue, in which interacting primary cosmic-ray nuclei will produce secondary particles that increase dose in an underlying target beyond the base LET of the cosmic-ray particle itself. We will present results of Geant4 simulations of this effect given an incident cosmic-ray spectrum, and will compare those results with observations from CRaTER's first months in lunar orbit.

  1. CraMs: Craniometric Analysis Application Using 3D Skull Models.

    PubMed

    Dias, Paulo; Neves, Luis; Santos, Daniel; Coelho, Catarina; Ferreira, Maria Teresa; Santos, Helder; Silva, Samuel; Santos, Beatriz Sousa

    2015-01-01

    Craniometric analysis plays an important role in anthropology studies and forensics. This paper presents CraMs, an application using a new craniometric approach based on 3D models of the skull. The main objective is to obtain, through a process supervised by anthropologists, the main points of interest used to compute craniometric measurements. The application aids this process by analyzing the skull geometry and automatically providing points of interest. The application also allows for semiautomatic point detection, where the user provides an initial guess that might be refined based on the curvature of the skull, as well as the manual selection of any other points of interest. Moreover, results comparing measurements obtained with CraMs and traditional craniometry methods on eight skulls suggest that the application provides comparable craniometric measurements and lower inter-observer variability. This approach offers advantages such as an easier access to skulls with no risk of bone damage and the possibility of defining new measurements based on morphology or other skull characteristics, which are not possible using traditional methods.

  2. Mentoring Literacy Professionals: Continuing the Spirit of CRA/ALER after 50 Years. The Thirty-First Yearbook: A Doubled Peer Reviewed Publication of the College Reading Association

    ERIC Educational Resources Information Center

    Szabo, Susan, Ed.; Sampson, Mary Beth, Ed.; Foote, Martha M., Ed.; Falk-Ross, Francine, Ed.

    2010-01-01

    This volume is a milestone year for the Yearbook, the conference, and the College Reading Association (CRA). At this conference, CRA celebrated its 50th year. The title of this thirty-first yearbook mirrors the theme of the 2008 conference--"Mentoring Literacy Professionals for 50 Years." The title "Mentoring Literacy Professionals: Continuing the…

  3. 13 CFR 108.1640 - SBA access to records of the CRA, Brokers, Dealers and Pool or Trust assemblers.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false SBA access to records of the CRA, Brokers, Dealers and Pool or Trust assemblers. 108.1640 Section 108.1640 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION NEW MARKETS VENTURE CAPITAL (âNMVCâ) PROGRAM SBA Financial Assistance...

  4. The WebCam vs. the Particle Beam: A CRaTER Visualization of the Effects of Radiation

    NASA Astrophysics Data System (ADS)

    Case, A. W.; Gross, N. A.; Spence, H. E.

    2008-12-01

    The term "radiation" can cause significant anxiety to a general audience in part because of the associated health risks, but also because of lack of a conceptual framework about the nature of radiation. A visual depiction of radiation may go a long way towards providing just such a framework. The CRaTER Team had an opportunity to create just such a video. The Cosmic Ray Telescope for the Effects of Radiation (CRaTER) is a radiation instrument that will fly on the Lunar Reconnaissance Orbiter (LRO) and is designed to determine the effects of energetic particles on living tissue. In order to calibrate CRaTER and characterize its reaction to various radiation environments, the CRaTER team has used particle beam facilities include the Proton Radiation Therapy Facility at Massachusetts General Hospital (MGH). During one of the sessions at MGH, the team placed an off the shelf web camera into the beam and recorded the visual effects. This video recording was used as the basis for an edited video describing what was done and the results. The hope is that this video will provide a general audience with a visual framework for the nature and effects of radiation

  5. LRO Cosmic Ray Telescope for the Effects of Radiation (CRaTER): Instrument Overviw and Computer Simulations of Detector Response to SEPs and GCRs

    NASA Astrophysics Data System (ADS)

    Charara, Y.; Towsend, L.; Spence, H.; Blake, J. B.; Golightly, M.; Kepko, E.; Kasper, J.; Looper, M.; Mazur, J.

    2006-12-01

    The Lunar Reconnaissance Orbiter (LRO) Mission, scheduled to be launched by the end of 2008, will carry six instruments to serve several exploratory objectives for a return of astronauts to the Moon. One of the six instruments, the Cosmic Ray Telescope for the Effects of Radiation (CRaTER), will characterize the lunar radiation environment and its biological impacts on humans. In this presentation, we provide an overview of CRaTER measurement objectives and implementation. CRaTER has two Tissue Equivalent Plastic volumes embedded between three pairs of solid-state detectors. We present preliminary computer calculations of expected CRaTER detector responses to Solar Energetic Particles (SEPs) and Galactic Cosmic Rays (GCRs) by simulating several SEPs and energetic, heavy, GCR particle spectra using two state-of-the-art Monte Carlo Codes, HETC-HEDS and BBFRAG.

  6. Different Pathways Act Downstream of the CEP Peptide Receptor CRA2 to Regulate Lateral Root and Nodule Development.

    PubMed

    Mohd-Radzman, Nadiatul A; Laffont, Carole; Ivanovici, Ariel; Patel, Neha; Reid, Dugald; Stougaard, Jens; Frugier, Florian; Imin, Nijat; Djordjevic, Michael A

    2016-08-01

    C-TERMINALLY ENCODED PEPTIDEs (CEPs) control root system architecture in a non-cell-autonomous manner. In Medicago truncatula, MtCEP1 affects root development by increasing nodule formation and inhibiting lateral root emergence by unknown pathways. Here, we show that the MtCEP1 peptide-dependent increase in nodulation requires the symbiotic signaling pathway and ETHYLENE INSENSITIVE2 (EIN2)/SICKLE (SKL), but acts independently of SUPER NUMERIC NODULES. MtCEP1-dependent inhibition of lateral root development acts through an EIN2-independent mechanism. MtCEP1 increases nodulation by promoting rhizobial infections, the developmental competency of roots for nodulation, the formation of fused nodules, and an increase in frequency of nodule development that initiates at proto-phloem poles. These phenotypes are similar to those of the ein2/skl mutant and support that MtCEP1 modulates EIN2-dependent symbiotic responses. Accordingly, MtCEP1 counteracts the reduction in nodulation induced by increasing ethylene precursor concentrations, and an ethylene synthesis inhibitor treatment antagonizes MtCEP1 root phenotypes. MtCEP1 also inhibits the development of EIN2-dependent pseudonodule formation. Finally, mutants affecting the COMPACT ROOT ARCHITECTURE2 (CRA2) receptor, which is closely related to the Arabidopsis CEP Receptor1, are unresponsive to MtCEP1 effects on lateral root and nodule formation, suggesting that CRA2 is a CEP peptide receptor mediating both organogenesis programs. In addition, an ethylene inhibitor treatment counteracts the cra2 nodulation phenotype. These results indicate that MtCEP1 and its likely receptor, CRA2, mediate nodulation and lateral root development through different pathways. PMID:27342310

  7. Different Pathways Act Downstream of the CEP Peptide Receptor CRA2 to Regulate Lateral Root and Nodule Development1[OPEN

    PubMed Central

    Mohd-Radzman, Nadiatul A.; Ivanovici, Ariel; Frugier, Florian; Djordjevic, Michael A.

    2016-01-01

    C-TERMINALLY ENCODED PEPTIDEs (CEPs) control root system architecture in a non-cell-autonomous manner. In Medicago truncatula, MtCEP1 affects root development by increasing nodule formation and inhibiting lateral root emergence by unknown pathways. Here, we show that the MtCEP1 peptide-dependent increase in nodulation requires the symbiotic signaling pathway and ETHYLENE INSENSITIVE2 (EIN2)/SICKLE (SKL), but acts independently of SUPER NUMERIC NODULES. MtCEP1-dependent inhibition of lateral root development acts through an EIN2-independent mechanism. MtCEP1 increases nodulation by promoting rhizobial infections, the developmental competency of roots for nodulation, the formation of fused nodules, and an increase in frequency of nodule development that initiates at proto-phloem poles. These phenotypes are similar to those of the ein2/skl mutant and support that MtCEP1 modulates EIN2-dependent symbiotic responses. Accordingly, MtCEP1 counteracts the reduction in nodulation induced by increasing ethylene precursor concentrations, and an ethylene synthesis inhibitor treatment antagonizes MtCEP1 root phenotypes. MtCEP1 also inhibits the development of EIN2-dependent pseudonodule formation. Finally, mutants affecting the COMPACT ROOT ARCHITECTURE2 (CRA2) receptor, which is closely related to the Arabidopsis CEP Receptor1, are unresponsive to MtCEP1 effects on lateral root and nodule formation, suggesting that CRA2 is a CEP peptide receptor mediating both organogenesis programs. In addition, an ethylene inhibitor treatment counteracts the cra2 nodulation phenotype. These results indicate that MtCEP1 and its likely receptor, CRA2, mediate nodulation and lateral root development through different pathways. PMID:27342310

  8. 76 FR 32364 - Collaboration in Regulatory Science and Capacity To Advance Global Access to Safe Vaccines and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-06

    ... pandemic influenza vaccines). Expected outputs ] could include analyses, reports and data-driven strategy... sustainable global influenza vaccines production capacity. These financial and intellectual investments in... influenza and other vaccines, biological products and technologies. These norms and standards are based...

  9. An Overview of First-Year Results from the Lunar Reconnaissance Orbiter (LRO) Cosmic Ray Telescope for the Effects of Radiation (CRaTER) (Invited)

    NASA Astrophysics Data System (ADS)

    Spence, H. E.; Golightly, M.; Schwadron, N. A.; Wilson, J. K.; Case, A.; Kasper, J. C.; Blake, J.; Looper, M. D.; Mazur, J.; Townsend, L.; Zeitlin, C.; Stubbs, T. J.; Crater Science Team

    2010-12-01

    We present an overview of science results from the Cosmic Ray Telescope for the Effects of Radiation (CRaTER) obtained during its first year of operations aboard the Lunar Reconnaissance Orbiter (LRO) at the Moon. CRaTER has been immersed in the ionizing radiation environment of the Moon since its launch on NASA’s LRO in June 2009. CRaTER measures the linear energy transfer (LET) of energetic particles traversing the instrument, a quantity that describes the rate at which particles lose kinetic energy as they pass through matter. A significant portion of the kinetic energy converts into deleterious ionizing radiation through the interactions with matter, thus posing a major radiation risk for human and robotic space explorers subjected to deep space energetic particles. CRaTER employs strategically placed solid-state detectors and tissue equivalent plastic (TEP), a synthetic analog for human tissue, to quantify radiation effects pertinent to astronaut safety. In this talk, we present science highlights resulting from CRaTER studies. These CRaTER science results include: radiation dose rate estimates during the recent deep, prolonged solar minimum; lunar orbit dose rate comparisons with Apollo-era estimates; assessment of variability of galactic cosmic rays and their sources; first direct observations of albedo protons from the lunar regolith and comparison with models; and detection of first, weak solar-related energetic particle events of the new solar cycle.

  10. Galactic Cosmic Rays and Lunar Secondary Particles from Solar Minimum to Maximum: CRaTER Observations and Geant4 Modeling

    NASA Astrophysics Data System (ADS)

    Looper, M. D.; Mazur, J. E.; Blake, J. B.; Spence, H. E.; Schwadron, N.; Golightly, M. J.; Case, A. W.; Kasper, J. C.; Townsend, L. W.; Wilson, J. K.

    2014-12-01

    The Lunar Reconnaissance Orbiter mission was launched in 2009 during the recent deep and extended solar minimum, with the highest galactic cosmic ray (GCR) fluxes observed since the beginning of the space era. Its Cosmic Ray Telescope for the Effects of Radiation (CRaTER) instrument was designed to measure the spectra of energy deposits in silicon detectors shielded behind pieces of tissue equivalent plastic, simulating the self-shielding provided by an astronaut's body around radiation-sensitive organs. The CRaTER data set now covers the evolution of the GCR environment near the moon during the first five years of development of the present solar cycle. We will present these observations, along with Geant4 modeling to illustrate the varying particle contributions to the energy-deposit spectra. CRaTER has also measured protons traveling up from the lunar surface after their creation during GCR interactions with surface material, and we will report observations and modeling of the energy and angular distributions of these "albedo" protons.

  11. CRA/EPRI coal market analysis system: integration and other improvements. Final report

    SciTech Connect

    Press, J.

    1981-12-01

    Current models of the coal market assume demand to be exogenous and, effectively, unresponsive to price. At the same time models of electric utility capacity expansion assume the prices of fuels to be exogenous. In fact the coal market and utility planning are interdependent. Integration of a coal model with a utility capacity planning model would allow investigation of the simultaneous operation of the two areas of activity. Modifications to the CRA/EPRI Coal Market Analysis System (CMAS) to enable such integration with the Gordian Utility Capacity Expansion Model have been designed and partially implemented. Some modifications were required to accomplish the interface and some to keep the CMAS to a reasonable size for computer implementation. In addition, other improvements were made to the CMAS apart from the requirements of integration. The theory and mechanics of integration using linear programming decomposition techniques have been developed with special application to the CMAS. Several alternative methods are discussed with one chosen for this particular investigation.

  12. Global identification of the genetic networks and cis-regulatory elements of the cold response in zebrafish.

    PubMed

    Hu, Peng; Liu, Mingli; Zhang, Dong; Wang, Jinfeng; Niu, Hongbo; Liu, Yimeng; Wu, Zhichao; Han, Bingshe; Zhai, Wanying; Shen, Yu; Chen, Liangbiao

    2015-10-30

    The transcriptional programs of ectothermic teleosts are directly influenced by water temperature. However, the cis- and trans-factors governing cold responses are not well characterized. We profiled transcriptional changes in eight zebrafish tissues exposed to mildly and severely cold temperatures using RNA-Seq. A total of 1943 differentially expressed genes (DEGs) were identified, from which 34 clusters representing distinct tissue and temperature response expression patterns were derived using the k-means fuzzy clustering algorithm. The promoter regions of the clustered DEGs that demonstrated strong co-regulation were analysed for enriched cis-regulatory elements with a motif discovery program, DREME. Seventeen motifs, ten known and seven novel, were identified, which covered 23% of the DEGs. Two motifs predicted to be the binding sites for the transcription factors Bcl6 and Jun, respectively, were chosen for experimental verification, and they demonstrated the expected cold-induced and cold-repressed patterns of gene regulation. Protein interaction modeling of the network components followed by experimental validation suggested that Jun physically interacts with Bcl6 and might be a hub factor that orchestrates the cold response in zebrafish. Thus, the methodology used and the regulatory networks uncovered in this study provide a foundation for exploring the mechanisms of cold adaptation in teleosts.

  13. A direct link between the global regulator PhoP and the Csr regulon in Y. pseudotuberculosis through the small regulatory RNA CsrC.

    PubMed

    Nuss, Aaron M; Schuster, Franziska; Kathrin Heroven, Ann; Heine, Wiebke; Pisano, Fabio; Dersch, Petra

    2014-01-01

    In this study we investigated the influence of the global response regulator PhoP on the complex regulatory cascade controlling expression of early stage virulence genes of Yersinia pseudotuberculosis via the virulence regulator RovA. Our analysis revealed the following novel features: (1) PhoP activates expression of the CsrC RNA in Y. pseudotuberculosis, leading to activation of RovA synthesis through the CsrABC-RovM cascade, (2) activation of csrC transcription is direct and PhoP is shown to bind to two separate PhoP box-like sites, (3) PhoP-mediated activation results in transcription from two different promoters closely downstream of the PhoP binding sites, leading to two distinct CsrC RNAs, and (4) the stability of the CsrC RNAs differs significantly between the Y. pseudotuberculosis strains YPIII and IP32953 due to a 20 nucleotides insertion in CsrC(IP32953), which renders the transcript more susceptible to degradation. In summary, our study showed that PhoP-mediated influence on the regulatory cascade controlling the Csr system and RovA in Y. pseudotuberculosis varies within the species, suggesting that the Csr system is a focal point to readjust and adapt the genus to different hosts and reservoirs.

  14. Corrosion behavior of CRA`s in high density packer fluids at high temperature

    SciTech Connect

    Scoppio, L.; Barteri, M.; Cheldi, T.; Ke, M.; Massi, S.

    1999-11-01

    Results from an experimental investigation carried out in high density brine packer fluids are presented. Different variables were examined, namely temperature, time of exposure, chemical inhibition and brine composition and density. Tests to compare the performance of different classes of stainless steels were carried out by autoclave exposure under different deaerated brines solutions: NaCl/NaBr, CaCl{sub 2}/CaBr{sub 2} and CaBr{sub 3}/ZnBr{sub 2}, CaCl{sub 2}, CaCl{sub 2}/CaBr{sub 2}/ZnBr{sub 2}. General corrosion, localized corrosion (pitting and crevice), galvanic corrosion and resistance to environmental cracking were evaluated both in absence of corrosion inhibitor and with the addition of two different commercial inhibitors. Duplex steels were very resistant to the localized corrosion, although pitting and crevice were present in some combination of brine and temperature. The martensitic steel was very sensitive to the general and the localized corrosion. Brine CaCl{sub 2}/CaBr{sub 2} {rho} = 1.75 g/cm{sup 3}, showed at 200 C, a pitting on 13%Cr lower than expected. This is probably due to the general corrosion which show a mechanism competitive with localized corrosion. As a result, pitting corrosion is a matter of big concern when applications in heavy brine are considered. In fact only the most alloyed materials at temperature below 200 C can be considered as immune. As a consequence, the effect of commercially available corrosion inhibitors is sometime lower than expected and there is a need of further improvements of corrosion inhibitors for the application to the CRA`S (Corrosion Resistant Alloys) in brine environments at 200 C.

  15. Acetyl-Phosphate Is Not a Global Regulatory Bridge between Virulence and Central Metabolism in Borrelia burgdorferi

    PubMed Central

    Richards, Crystal L.; Lawrence, Kevin A.; Su, Hua; Yang, Youyun; Yang, X. Frank; Dulebohn, Daniel P.; Gherardini, Frank C.

    2015-01-01

    In B. burgdorferi, the Rrp2-RpoN-RpoS signaling cascade is a distinctive system that coordinates the expression of virulence factors required for successful transition between its arthropod vector and mammalian hosts. Rrp2 (BB0763), an RpoN specific response regulator, is essential to activate this regulatory pathway. Previous investigations have attempted to identify the phosphate donor of Rrp2, including the cognate histidine kinase, Hk2 (BB0764), non-cognate histidine kinases such as Hk1, CheA1, and CheA2, and small molecular weight P-donors such as carbamoyl-phosphate and acetyl-phosphate (AcP). In a report by Xu et al., exogenous sodium acetate led to increased expression of RpoS and OspC and it was hypothesized this effect was due to increased levels of AcP via the enzyme AckA (BB0622). Genome analyses identified only one pathway that could generate AcP in B. burgdorferi: the acetate/mevalonate pathway that synthesizes the lipid, undecaprenyl phosphate (C55-P, lipid I), which is essential for cell wall biogenesis. To assess the role of AcP in Rrp2–dependent regulation of RpoS and OspC, we used a unique selection strategy to generate mutants that lacked ackA (bb0622: acetate to AcP) or pta (bb0589: AcP to acetyl-CoA). These mutants have an absolute requirement for mevalonate and demonstrate that ackA and pta are required for cell viability. When the ΔackA or Δpta mutant was exposed to conditions (i.e., increased temperature or cell density) that up-regulate the expression of RpoS and OspC, normal induction of those proteins was observed. In addition, adding 20mM acetate or 20mM benzoate to the growth media of B. burgdorferi strain B31 ΔackA induced the expression of RpoS and OspC. These data suggest that AcP (generated by AckA) is not directly involved in modulating the Rrp2-RpoN-RpoS regulatory pathway and that exogenous acetate or benzoate are triggering an acid stress response in B. burgdorferi. PMID:26681317

  16. Quality in health care and globalization of health services: accreditation and regulatory oversight of medical tourism companies.

    PubMed

    Turner, Leigh G

    2011-02-01

    Patients are crossing national borders in search of affordable and timely health care. Many medical tourism companies are now involved in organizing cross-border health services. Despite the rapid expansion of the medical tourism industry, few standards exist to ensure that these businesses organize high-quality, competent international health care. Addressing the regulatory vacuum, 10 standards are proposed as a framework for regulating the medical tourism industry. Medical tourism companies should have to undergo accreditation review. Care should be arranged only at accredited international health-care facilities. Standards should be established to ensure that clients of medical tourism companies make informed choices. Continuity of care needs to become an integral feature of cross-border care. Restrictions should be placed on the use of waiver of liability forms by medical tourism companies. Medical tourism companies must ensure that they conform to relevant legislation governing privacy and confidentiality of patient information. Restrictions must be placed on the types of health services marketed by medical tourism companies. Representatives of medical tourism agencies should have to undergo training and certification. Medical travel insurance and medical complications insurance should be included in the health-care plans of patients traveling for care. To protect clients from financial losses, medical tourism companies should be mandated to contribute to compensation funds. Establishing high standards for the operation of medical tourism companies should reduce risks facing patients when they travel abroad for health care.

  17. Corrosion caused by elevator and spider marks on CRA pipe: Comparison of conventional inserts and a new gripping system

    SciTech Connect

    1997-05-01

    Corrosion-resistant alloys (CRA) are used to reduce corrosion damage to casing and tubing strings and prolong the life span of the well pipe. An analysis of various corrosion mechanisms shows that surface integrity is an important factor in corrosion prevention. Surface damage caused by inappropriate handling or conventional slip markings contribute directly to the development and propagation of corrosion. A newly developed gripping system distributes the load equally onto a large number of small peaks, minimizing the indentation of each single peak. The new gripping system does not damage the surface integrity of the pipe, virtually eliminating the corrosion potential.

  18. In Bacillus subtilis LutR is part of the global complex regulatory network governing the adaptation to the transition from exponential growth to stationary phase.

    PubMed

    Irigül-Sönmez, Öykü; Köroğlu, Türkan E; Öztürk, Büşra; Kovács, Ákos T; Kuipers, Oscar P; Yazgan-Karataş, Ayten

    2014-02-01

    The lutR gene, encoding a product resembling a GntR-family transcriptional regulator, has previously been identified as a gene required for the production of the dipeptide antibiotic bacilysin in Bacillus subtilis. To understand the broader regulatory roles of LutR in B. subtilis, we studied the genome-wide effects of a lutR null mutation by combining transcriptional profiling studies using DNA microarrays, reverse transcription quantitative PCR, lacZ fusion analyses and gel mobility shift assays. We report that 65 transcriptional units corresponding to 23 mono-cistronic units and 42 operons show altered expression levels in lutR mutant cells, as compared with lutR(+) wild-type cells in early stationary phase. Among these, 11 single genes and 25 operons are likely to be under direct control of LutR. The products of these genes are involved in a variety of physiological processes associated with the onset of stationary phase in B. subtilis, including degradative enzyme production, antibiotic production and resistance, carbohydrate utilization and transport, nitrogen metabolism, phosphate uptake, fatty acid and phospholipid biosynthesis, protein synthesis and translocation, cell-wall metabolism, energy production, transfer of mobile genetic elements, induction of phage-related genes, sporulation, delay of sporulation and cannibalism, and biofilm formation. Furthermore, an electrophoretic mobility shift assay performed in the presence of both SinR and LutR revealed a close overlap between the LutR and SinR targets. Our data also revealed a significant overlap with the AbrB regulon. Together, these findings reveal that LutR is part of the global complex, interconnected regulatory systems governing adaptation of bacteria to the transition from exponential growth to stationary phase. PMID:24196425

  19. Microbial modeling of thermal resistance of Alicyclobacillus acidoterrestris CRA7152 spores in concentrated orange juice with nisin addition

    PubMed Central

    Peña, Wilmer Edgard Luera; de Massaguer, Pilar Rodriguez; Teixeira, Luciano Quintão

    2009-01-01

    The nisin effect on thermal death of Alicyclobacillus acidoterrestris CRA 7152 spores in concentrated orange juice (64°Brix) was studied. Concentrations of 0, 50, 75 and 100 IU of nisin/ml juice, at temperatures of 92, 95, 98 and 102°C were evaluated. The quadratic polynomial model was used to analyze the effects of the factors and their interaction. Verification of surviving spores was carried out through plating in K medium (pH 3.7). The results showed that the D values without nisin addition were 25.5, 12.9, 6.1 and 2.3 min for 92, 95, 98 and 102°C respectively. With addition of nisin into the juice there was a drop of heat resistance as the concentration was increased at a same temperature. With 30, 50, 75, 100 and 150 IU/ml at 95°C, the D values were 12.34, 11.38, 10.49, 9.49 and 9.42 min respectively, showing that a decrease in the D value up to 27% can be obtained. The second order polynomial model established with r2 = 0.995 showed that the microorganism resistance was affected by the action of temperature followed by the nisin concentration. Nisin therefore is an alternative for reducing the rigor of the A. acidoterrestris CRA 7152 thermal treatment. PMID:24031405

  20. Assessing Nonchemical factors in Cumulative Risk Assessment (CRA): A Case Study of the Association between Lower Heart Rate Variability and Particulate Matter

    EPA Science Inventory

    There has been increased interest in the integration of chemicals (e.g. particulate matter, lead) and nonchemicals (e.g., genetics, gender, lifestyle) in cumulative risk assessment (CRA). Because few toxicological or epidemiological studies on these complex mixtures have been con...

  1. Analysis of the potential radiation hazard of the 23 July 2012 SEP event observed by STEREO A using the EMMREM model and LRO/CRaTER

    NASA Astrophysics Data System (ADS)

    Joyce, C. J.; Schwadron, N. A.; Townsend, L. W.; Mewaldt, R. A.; Cohen, C. M. S.; Rosenvinge, T. T.; Case, A. W.; Spence, H. E.; Wilson, J. K.; Gorby, M.; Quinn, M.; Zeitlin, C. J.

    2015-09-01

    We present a study of the potential radiation hazard of the powerful, superfast interplanetary coronal mass ejection (ICME) observed by STEREO A on 23 July 2012. Using energetic proton flux data from the High Energy Telescope and Low Energy Telescope instruments aboard STEREO A together with the Earth-Moon-Mars Radiation Environment Module, we compute dose rates and accumulated doses during the event for both skin/eye and blood forming organs using four physically relevant levels of shielding. For spacesuit equivalent shielding, we compute a peak skin/eye dose rate of 1970 cGy-Eq/d, a value far greater than those of the 2003 Halloween storms or the January and March solar energetic particle events of 2012. However, due to the relative brevity of the event, the resulting accumulated dose was just 383 cGy-Eq, which is more aligned with the total doses of the 2003 Halloween and 2012 January/March events. Additionally, we use dose rates at STEREO B and Lunar Reconnaissance Orbiter/Cosmic Ray Telescope for the Effects of Radiation (LRO/CRaTER) during the event to show how the radiation impact is affected by the position of the ICME relative to the observer. Specifically, we find that the energetic particle event associated with the local shock and ICME passage at STEREO A caused greatly enhanced dose rates when compared to STEREO B and LRO/CRaTER, which were longitudinally distant from the ICME. The STEREO A/B dose rates used here will soon be made available to the community as a tool for studying the energetic particle radiation of solar events from different longitudes as a part of NASA's Heliophysics Virtual Observatories and on the Predictions of radiation from REleASE, EMMREM, and Data Incorporating CRaTER, COSTEP, and other SEP measurements (PREDICCS) and CRaTER websites.

  2. PREDICCS: Predictions of Radiation from REleASE, EMMREM, and Data Incorporating CRaTER, COSTEP (EPHIN), and other SEP measurements

    NASA Astrophysics Data System (ADS)

    Mislinski, J. F.; Schwadron, N. A.; Townsend, L.; Spence, H. E.; Rother, O. M.; Posner, A.; Squier, R.; Wilson, J. K.; Jordan, A.; Anderson, R.; Baker, T.; Kozarev, K. A.; Joyce, C. J.

    2011-12-01

    Accurate models for the radiation environment through the heliosphere are necessary for future manned missions. PREDICCS will be an on-line system - available for scientists and the public - to predict and forecast the radiation environment through interplanetary space. It integrates two radiation environment models with Solar Energetic Particle (SEP) measurements: the Earth-Moon-Mars Radiation Environment Module (EMMREM) and the Relativistic Electron Alert System for Exploration (REleASE) and incorporates data from the CRaTER and COSTEP (EPHIN) instruments, and other SEP measurements. REleASE very accurately forecasts SEP events up to one and a half hours ahead of the event itself [1]. The EMMREM model predicts the real-time radiation environment using two modules: the Energetic Particle Radiation Environment Module (EPREM) and the Baryon Transport Module (BRYNTRN) [2]. We combine these two models to nowcast and forecast the radiation environment at various observers (Earth, Moon, Mars, and at specific target observers such as comets and asteroids) and for future SEP events. Validation of these models requires data from CRaTER, COSTEP (EPHIN), and other SEP measurements. CRaTER characterizes the lunar radiation environment and its biological impacts with LET (Linear Energy Transfer) spectra of galactic and solar cosmic rays [3] and COSTEP (EPHIN) measures relativistic electrons and deka-MeV protons and helium [4]. We have done preliminary comparisons of a recent, albeit small, SEP event from early June 2011 that has shown excellent agreement with EMMREM predictions. This event has been well observed by CRaTER and a number of other instruments and is the first "significant" event as we come out of the longest and deepest solar minimum in the space age. Additional observations of SEP events in the near future will help to fine tune the models in order to predict the radiation environment with more confidence. This will be an invaluable resource for all that are

  3. Search for young stars among ROSAT All-Sky Survey X-ray sources in and around the R CrA dark cloud

    NASA Astrophysics Data System (ADS)

    Neuhäuser, R.; Walter, F. M.; Covino, E.; Alcalá, J. M.; Wolk, S. J.; Frink, S.; Guillout, P.; Sterzik, M. F.; Comerón, F.

    2000-10-01

    We present the ROSAT All-Sky Survey data in a 126 deg2 area in and around the CrA star forming region. With low-resolution spectroscopy of unidentified ROSAT sources we could find 19 new pre-main sequence stars, two of which are classical T Tauri stars, the others being weak-lined. The spectral types of these new T Tauri stars range from F7 to M6. The two new classical T Tauri stars are located towards two small cloud-lets outside of the main CrA cloud. They appear to be ~ 10 Myrs old, by comparing their location in the H-R diagram with isochrones for an assumed distance of 130 pc, the distance of the main CrA dark cloud. The new off-cloud weak-line T Tauri stars may have formed in similar cloudlets, which have dispersed recently. High-resolution spectra of our new T Tauri stars show that they have significantly more lithium absorption than zero-age main-sequence stars of the same spectral type, so that they are indeed young. From those spectra we also obtained rotational and radial velocities. For some stars we found the proper motion in published catalogs. The direction and velocity of the 3D space motion - south relative to the galatic plane - of the CrA T Tauri stars is consistent with the dark cloud being formed originally by a high-velocity cloud impact onto the galactic plane, which triggered the star formation in CrA. We also present VRIJHK photometry for most of the new T Tauri stars to derive their luminosities, ages, and masses. Partly based on observations collected at the 1.52 m and 3.5 m telescopes of the European Southern Observatory, Chile, in programs 55.E-0549, 57.E-0646, and 63.L-0023, and on observations collected at the 0.9 m, 1.5 m, and 4.0 m CTIO telescope.

  4. Does the worsening galactic cosmic radiation environment observed by CRaTER preclude future manned deep space exploration?

    NASA Astrophysics Data System (ADS)

    Schwadron, N. A.; Blake, J. B.; Case, A. W.; Joyce, C. J.; Kasper, J.; Mazur, J.; Petro, N.; Quinn, M.; Porter, J. A.; Smith, C. W.; Smith, S.; Spence, H. E.; Townsend, L. W.; Turner, R.; Wilson, J. K.; Zeitlin, C.

    2014-11-01

    The Sun and its solar wind are currently exhibiting extremely low densities and magnetic field strengths, representing states that have never been observed during the space age. The highly abnormal solar activity between cycles 23 and 24 has caused the longest solar minimum in over 80 years and continues into the unusually small solar maximum of cycle 24. As a result of the remarkably weak solar activity, we have also observed the highest fluxes of galactic cosmic rays in the space age and relatively small solar energetic particle events. We use observations from the Cosmic Ray Telescope for the Effects of Radiation (CRaTER) on the Lunar Reconnaissance Orbiter to examine the implications of these highly unusual solar conditions for human space exploration. We show that while these conditions are not a show stopper for long-duration missions (e.g., to the Moon, an asteroid, or Mars), galactic cosmic ray radiation remains a significant and worsening factor that limits mission durations. While solar energetic particle events in cycle 24 present some hazard, the accumulated doses for astronauts behind 10 g/cm2 shielding are well below current dose limits. Galactic cosmic radiation presents a more significant challenge: the time to 3% risk of exposure-induced death (REID) in interplanetary space was less than 400 days for a 30 year old male and less than 300 days for a 30 year old female in the last cycle 23-24 minimum. The time to 3% REID is estimated to be ˜20% lower in the coming cycle 24-25 minimum. If the heliospheric magnetic field continues to weaken over time, as is likely, then allowable mission durations will decrease correspondingly. Thus, we estimate exposures in extreme solar minimum conditions and the corresponding effects on allowable durations.

  5. Experiences in the design of CRA`s for erosion/corrosion control in the production facilities of eastern Venezuela oil fields

    SciTech Connect

    Romero, N.; Palacios, C.A.

    1997-08-01

    It is a well known fact that CRA`s are used in the oil industry as one way to control erosion/corrosion effects. Many fields in the eastern region of Venezuela are considered corrosive due to the presence of CO{sub 2} (5 to 20%), H{sub 2}S (up to 5 ppm), and water (50% water cut) contained in the produced hydrocarbons (condensated). For some areas, the hydrocarbon is accompanied by sand, making them erosive as well. These conditions and frequent failures experienced in the field, led to the use of CRA`s. For the wells, 13% Cr and bimetallic (carbon steel/13% Cr) tubing was used for 51 condensate wells containing 5 to 20% CO{sub 2}. For the surface equipment (valves, reducers, expanders and other types of fittings) tungsten carbide hard facing were used, for some of the valves, a epoxi-phenolic coating was used. This article describes the different design criteria used for the installation of the tubing, the logistics involved during field inspections and handling tips to avoid galling during workovers. It also, presents results from the bi-metallic tubing and the hard facings used for the surface equipment.

  6. The Culture Repopulation Ability (CRA) Assay and Incubation in Low Oxygen to Test Antileukemic Drugs on Imatinib-Resistant CML Stem-Like Cells.

    PubMed

    Cheloni, Giulia; Tanturli, Michele

    2016-01-01

    Chronic myeloid leukemia (CML) is a stem cell-driven disorder caused by the BCR/Abl oncoprotein, a constitutively active tyrosine kinase (TK). Chronic-phase CML patients are treated with impressive efficacy with TK inhibitors (TKi) such as imatinib mesylate (IM). However, rather than definitively curing CML, TKi induces a state of minimal residual disease, due to the persistence of leukemia stem cells (LSC) which are insensitive to this class of drugs. LSC persistence may be due to different reasons, including the suppression of BCR/Abl oncoprotein. It has been shown that this suppression follows incubation in low oxygen under appropriate culture conditions and incubation times.Here we describe the culture repopulation ability (CRA) assay, a non-clonogenic assay capable - together with incubation in low oxygen - to reveal in vitro stem cells endowed with marrow repopulation ability (MRA) in vivo. The CRA assay can be used, before moving to animal tests, as a simple and reliable method for the prescreening of drugs potentially active on CML and other leukemias with respect to their activity on the more immature leukemia cell subsets. PMID:27581140

  7. Impact of the Staphylococcus epidermidis LytSR two-component regulatory system on murein hydrolase activity, pyruvate utilization and global transcriptional profile

    PubMed Central

    2010-01-01

    Background Staphylococcus epidermidis has emerged as one of the most important nosocomial pathogens, mainly because of its ability to colonize implanted biomaterials by forming a biofilm. Extensive studies are focused on the molecular mechanisms involved in biofilm formation. The LytSR two-component regulatory system regulates autolysis and biofilm formation in Staphylococcus aureus. However, the role of LytSR played in S. epidermidis remained unknown. Results In the present study, we demonstrated that lytSR knock-out in S. epidermidis did not alter susceptibility to Triton X-100 induced autolysis. Quantitative murein hydrolase assay indicated that disruption of lytSR in S. epidermidis resulted in decreased activities of extracellular murein hydrolases, although zymogram showed no apparent differences in murein hydrolase patterns between S. epidermidis strain 1457 and its lytSR mutant. Compared to the wild-type counterpart, 1457ΔlytSR produced slightly more biofilm, with significantly decreased dead cells inside. Microarray analysis showed that lytSR mutation affected the transcription of 164 genes (123 genes were upregulated and 41 genes were downregulated). Specifically, genes encoding proteins responsible for protein synthesis, energy metabolism were downregulated, while genes involved in amino acid and nucleotide biosynthesis, amino acid transporters were upregulated. Impaired ability to utilize pyruvate and reduced activity of arginine deiminase was observed in 1457ΔlytSR, which is consistent with the microarray data. Conclusions The preliminary results suggest that in S. epidermidis LytSR two-component system regulates extracellular murein hydrolase activity, bacterial cell death and pyruvate utilization. Based on the microarray data, it appears that lytSR inactivation induces a stringent response. In addition, LytSR may indirectly enhance biofilm formation by altering the metabolic status of the bacteria. PMID:21073699

  8. A Csr-type regulatory system, including small non-coding RNAs, regulates the global virulence regulator RovA of Yersinia pseudotuberculosis through RovM.

    PubMed

    Heroven, Ann Kathrin; Böhme, Katja; Rohde, Manfred; Dersch, Petra

    2008-06-01

    The MarR-type regulator RovA controls expression of virulence genes of Yersinia pseudotuberculosis in response to environmental signals. Using a genetic strategy to discover components that influence rovA expression, we identified new regulatory factors with homology to components of the carbon storage regulator system (Csr). We showed that overexpression of a CsrB- or a CsrC-type RNA activates rovA, whereas a CsrA-like protein represses RovA synthesis. We further demonstrate that influence of the Csr system on rovA is indirect and occurs through control of the LysR regulator RovM, which inhibits rovA transcription. The CsrA protein had also a major influence on the motility of Yersinia, which was independent of RovM. The CsrB and CsrC RNAs are differentially expressed in Yersinia. CsrC is highly induced in complex but not in minimal media, indicating that medium-dependent rovM expression is mediated through CsrC. CsrB synthesis is generally very low. However, overexpression of the response regulator UvrY was found to activate CsrB production, which in turn represses CsrC synthesis independent of the growth medium. In summary, the post-transcriptional Csr-type components were shown to be key regulators in the co-ordinated environmental control of physiological processes and virulence factors, which are crucial for the initiation of Yersinia infections.

  9. Global Analysis of DNA Methylation Variation in Adipose Tissue from Twins Reveals Links to Disease-Associated Variants in Distal Regulatory Elements

    PubMed Central

    Grundberg, Elin; Meduri, Eshwar; Sandling, Johanna K.; Hedman, Åsa K.; Keildson, Sarah; Buil, Alfonso; Busche, Stephan; Yuan, Wei; Nisbet, James; Sekowska, Magdalena; Wilk, Alicja; Barrett, Amy; Small, Kerrin S.; Ge, Bing; Caron, Maxime; Shin, So-Youn; Ahmadi, Kourosh R.; Ainali, Chrysanthi; Barrett, Amy; Bataille, Veronique; Bell, Jordana T.; Buil, Alfonso; Deloukas, Panos; Dermitzakis, Emmanouil T.; Dimas, Antigone S.; Durbin, Richard; Glass, Daniel; Grundberg, Elin; Hassanali, Neelam; Hedman, Åsa K.; Ingle, Catherine; Knowles, David; Krestyaninova, Maria; Lindgren, Cecilia M.; Lowe, Christopher E.; McCarthy, Mark I.; Meduri, Eshwar; di Meglio, Paola; Min, Josine L.; Montgomery, Stephen B.; Nestle, Frank O.; Nica, Alexandra C.; Nisbet, James; O’Rahilly, Stephen; Parts, Leopold; Potter, Simon; Sandling, Johanna; Sekowska, Magdalena; Shin, So-Youn; Small, Kerrin S.; Soranzo, Nicole; Spector, Tim D.; Surdulescu, Gabriela; Travers, Mary E.; Tsaprouni, Loukia; Tsoka, Sophia; Wilk, Alicja; Yang, Tsun-Po; Zondervan, Krina T.; Lathrop, Mark; Dermitzakis, Emmanouil T.; McCarthy, Mark I.; Spector, Timothy D.; Bell, Jordana T.; Deloukas, Panos

    2013-01-01

    Epigenetic modifications such as DNA methylation play a key role in gene regulation and disease susceptibility. However, little is known about the genome-wide frequency, localization, and function of methylation variation and how it is regulated by genetic and environmental factors. We utilized the Multiple Tissue Human Expression Resource (MuTHER) and generated Illumina 450K adipose methylome data from 648 twins. We found that individual CpGs had low variance and that variability was suppressed in promoters. We noted that DNA methylation variation was highly heritable (h2median = 0.34) and that shared environmental effects correlated with metabolic phenotype-associated CpGs. Analysis of methylation quantitative-trait loci (metQTL) revealed that 28% of CpGs were associated with nearby SNPs, and when overlapping them with adipose expression quantitative-trait loci (eQTL) from the same individuals, we found that 6% of the loci played a role in regulating both gene expression and DNA methylation. These associations were bidirectional, but there were pronounced negative associations for promoter CpGs. Integration of metQTL with adipose reference epigenomes and disease associations revealed significant enrichment of metQTL overlapping metabolic-trait or disease loci in enhancers (the strongest effects were for high-density lipoprotein cholesterol and body mass index [BMI]). We followed up with the BMI SNP rs713586, a cg01884057 metQTL that overlaps an enhancer upstream of ADCY3, and used bisulphite sequencing to refine this region. Our results showed widespread population invariability yet sequence dependence on adipose DNA methylation but that incorporating maps of regulatory elements aid in linking CpG variation to gene regulation and disease risk in a tissue-dependent manner. PMID:24183450

  10. Antagonistic control of the turnover pathway for the global regulatory sRNA CsrB by the CsrA and CsrD proteins

    PubMed Central

    Vakulskas, Christopher A.; Leng, Yuanyuan; Abe, Hazuki; Amaki, Takumi; Okayama, Akihiro; Babitzke, Paul; Suzuki, Kazushi; Romeo, Tony

    2016-01-01

    The widely conserved protein CsrA (carbon storage regulator A) globally regulates bacterial gene expression at the post-transcriptional level. In many species, CsrA activity is governed by untranslated sRNAs, CsrB and CsrC in Escherichia coli, which bind to multiple CsrA dimers, sequestering them from lower affinity mRNA targets. Both the synthesis and turnover of CsrB/C are regulated. Their turnover requires the housekeeping endonuclease RNase E and is activated by the presence of a preferred carbon source via the binding of EIIAGlc of the glucose transport system to the GGDEF-EAL domain protein CsrD. We demonstrate that the CsrB 3′ segment contains the features necessary for CsrD-mediated decay. RNase E cleavage in an unstructured segment located immediately upstream from the intrinsic terminator is necessary for subsequent degradation to occur. CsrA stabilizes CsrB against RNase E cleavage by binding to two canonical sites adjacent to the necessary cleavage site, while CsrD acts by overcoming CsrA-mediated protection. Our genetic, biochemical and structural studies establish a molecular framework for sRNA turnover by the CsrD-RNase E pathway. We propose that CsrD evolution was driven by the selective advantage of decoupling Csr sRNA decay from CsrA binding, connecting it instead to the availability of a preferred carbon source. PMID:27235416

  11. 77 FR 26413 - Promoting International Regulatory Cooperation

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-04

    ... global economy, international regulatory cooperation, consistent with domestic law and prerogatives and U... HOUSE, May 1, 2012. [FR Doc. 2012-10968 Filed 5-3-12; 8:45 am] Billing code 3295-F2-P...

  12. Post-translational Serine/Threonine Phosphorylation and Lysine Acetylation: A Novel Regulatory Aspect of the Global Nitrogen Response Regulator GlnR in S. coelicolor M145.

    PubMed

    Amin, Rafat; Franz-Wachtel, Mirita; Tiffert, Yvonne; Heberer, Martin; Meky, Mohamed; Ahmed, Yousra; Matthews, Arne; Krysenko, Sergii; Jakobi, Marco; Hinder, Markus; Moore, Jane; Okoniewski, Nicole; Maček, Boris; Wohlleben, Wolfgang; Bera, Agnieszka

    2016-01-01

    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. This study clearly

  13. Post-translational Serine/Threonine Phosphorylation and Lysine Acetylation: A Novel Regulatory Aspect of the Global Nitrogen Response Regulator GlnR in S. coelicolor M145

    PubMed Central

    Amin, Rafat; Franz-Wachtel, Mirita; Tiffert, Yvonne; Heberer, Martin; Meky, Mohamed; Ahmed, Yousra; Matthews, Arne; Krysenko, Sergii; Jakobi, Marco; Hinder, Markus; Moore, Jane; Okoniewski, Nicole; Maček, Boris; Wohlleben, Wolfgang; Bera, Agnieszka

    2016-01-01

    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. This study clearly

  14. Meditation and its regulatory role on sleep.

    PubMed

    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.

  15. Regulatory Anatomy

    PubMed Central

    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, legal documents, technological devices, organizational structures, and work practices aimed at minimizing risk. I use this term to reorient the analytical attention with respect to safety regulation. Instead of evaluating whether safety is achieved, the point is to explore the types of “safety” produced through these logics as well as to consider the sometimes unintended consequences of such safety work. In fact, the EU rules have been giving rise to complaints from practitioners finding the directives problematic and inadequate. In this article, I explore the problems practitioners face and why they arise. In short, I expose the regulatory anatomy of the policy landscape. PMID:26139952

  16. Regulatory RNAs

    PubMed Central

    Vazquez-Anderson, Jorge; Contreras, Lydia M

    2013-01-01

    RNAs have many important functional properties, including that they are independently controllable and highly tunable. As a result of these advantageous properties, their use in a myriad of sophisticated devices has been widely explored. Yet, the exploitation of RNAs for synthetic applications is highly dependent on the ability to characterize the many new molecules that continue to be discovered by large-scale sequencing and high-throughput screening techniques. In this review, we present an exhaustive survey of the most recent synthetic bacterial riboswitches and small RNAs while emphasizing their virtues in gene expression management. We also explore the use of these RNA components as building blocks in the RNA synthetic biology toolbox and discuss examples of synthetic RNA components used to rewire bacterial regulatory circuitry. We anticipate that this field will expand its catalog of smart devices by mimicking and manipulating natural RNA mechanisms and functions. PMID:24356572

  17. Regulatory Physiology

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

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

  18. Genomics in the land of regulatory science.

    PubMed

    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.

  19. Regulatory pathways for vaccines for developing countries.

    PubMed

    Milstien, Julie; Belgharbi, Lahouari

    2004-02-01

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

  20. Regulatory pathways for vaccines for developing countries.

    PubMed Central

    Milstien, Julie; Belgharbi, Lahouari

    2004-01-01

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

  1. The binarity of Herbig Ae/Be stars observed with Adaptive Optics and spectroscopy. A study of the triple system TY CrA

    NASA Astrophysics Data System (ADS)

    Corporon, Patrice

    1998-03-01

    mass stars (A--F). Companions usually have no infrared excess, nor do primaries with massive companions. Furthermore, X-ray emission in some HAeBe stars may well be explained by the presence of a T Tauri companion. However, because of bias effects, great care must be taken about these issues, and complementary observations are needed. Our observations provide clues for binary formation theories, but while fragmentation and capture via a circumstellar disk seem plausible mechanisms, disk instabilities and stellar capture scenarios cannot be ruled out. The second part of the thesis is devoted to the study of TY CrA, the unique triple spectroscopic system among Herbig Ae/Be stars. We found this previously known eclipsing binary to be also a spectroscopic binary of SB2 type (P = 2.9 days), and we obtained the first direct mass determination of an HAeBe star. The orbital motion of a third companion around the central binary has been monitored, and a complete dynamical model of the triple system has been made. Our theoretical investigations show that the stability of the hierarchical system is insured by tidal effects inside the central eclipsing binary. To explain the puzzling subsynchroneous rotation of the primary star, a peculiar orientation, in which the primary is seen pole-on and its rotational axis is perpendicular to its orbital axis, is proposed. The circumstellar environment of TY CrA has been studied. SWS, LWS--ISO data show polycyclic aromatic hydrocarbon emissions (some of them never observed from the ground in TY CrA), and O sc i 63, 146 microns and [C II] 158 micron emission lines. These features may well be explained by the presence of a compact HII region and a photodissociation region associated with TY CrA. Adaptive Optics images in the near infrared obtained with and without coronograph show that the dusty environment must be confined very close to the star (< 0.5'' = 65 AU at 130pc).

  2. Regulatory bioinformatics for food and drug safety.

    PubMed

    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

  3. Regulatory bioinformatics for food and drug safety.

    PubMed

    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

  4. Globalization, global health, and access to healthcare.

    PubMed

    Collins, Téa

    2003-01-01

    It is now commonly realized that the globalization of the world economy is shaping the patterns of global health, and that associated morbidity and mortality is affecting countries' ability to achieve economic growth. The globalization of public health has important implications for access to essential healthcare. The rise of inequalities among and within countries negatively affects access to healthcare. Poor people use healthcare services less frequently when sick than do the rich. The negative impact of globalization on access to healthcare is particularly well demonstrated in countries of transitional economies. No longer protected by a centralized health sector that provided free universal access to services for everyone, large segments of the populations in the transition period found themselves denied even the most basic medical services. Only countries where regulatory institutions are strong, domestic markets are competitive and social safety nets are in place, have a good chance to enjoy the health benefits of globalization.

  5. Determinants of Effective Information Transfer in International Regulatory Standards Adoption

    ERIC Educational Resources Information Center

    Popescu, Denisa

    2010-01-01

    The role of international regulatory standards within the current global environment has become of the most importance. The age of the global system and free market capitalism carried us into the unprecedented age of regulations, and standard setting. Regulations are now becoming the emerging mode of global governance. This study focuses on…

  6. Globalization and emerging governance modalities.

    PubMed

    Neubauer, Deane Edward

    2005-09-01

    This paper explores the possibilities for global governance effectively dealing with the international transmission of disease. First, zoonotic regulation and control pose a special case for public health agencies, and this paper proposes a propositional model for an effective public health stance. Second, globalization dynamics are briefly reviewed in terms of an emerging consensus on the need for global governance in public health. Third, a brief examination of global governance modalities suggests that a strong global governance case has distinct limitations (despite its possible justification); an exploration of contemporary directions in global governance follows. Finally, the paper examines the phenomenon of contemporary zoonotic control within the conditions of an effective regulatory regime.

  7. Global Sales Training's Balancing Act

    ERIC Educational Resources Information Center

    Boehle, Sarah

    2010-01-01

    A one-size-fits-all global sales strategy that fails to take into account the cultural, regulatory, geographic, and economic differences that exist across borders is a blueprint for failure. For training organizations tasked with educating globally dispersed sales forces, the challenge is adapting to these differences while simultaneously…

  8. Influence of the hot-fill water-spray-cooling process after continuous pasteurization on the number of decimal reductions and on Alicyclobacillus acidoterrestris CRA 7152 growth in orange juice stored at 35 degrees C.

    PubMed

    Spinelli, Ana Cláudia N F; Sant'Ana, Anderson S; Pacheco-Sanchez, Cristiana P; Massaguer, Pilar R

    2010-02-28

    In this study, the influence of the hot-fill water-spray-cooling process after continuous pasteurization on the number of decimal reductions (gamma) and growth parameters (lag time; lambda, ratio N(f)/N(o); kappa, maximum growth rate; mu) of Alicyclobacillus acidoterrestris CRA 7152 in orange juice stored at 35 degrees C were investigated. Two different inoculum levels of A. acidoterrestris CRA 7152 (10(2) and 10(3) spores/mL) in orange juice (11(0)Brix, pH 3.7) and a Microthermics UHT-HTST pilot plant were used to simulate industrial conditions. Results have shown that regardless of the inoculum level (10(2) or 10(3) spores/mL), the pasteurization processes were unable to cause even 1 gamma. Predictive modeling using the Baranyi model showed that only kappa and time to reach 10(4)spores/mL (t10(4) - time to juice spoilage) were affected by the spore inoculum used (p<0.05). It has been concluded that A. acidoterrestris was able to survive the hot-fill process and to grow and spoil orange juice in 5-6 days when the final storage temperature was 35 degrees C.

  9. Ospemifene: first global approval.

    PubMed

    Elkinson, Shelley; Yang, Lily P H

    2013-05-01

    Ospemifene (Osphena™) is an oral selective estrogen receptor modulator (SERM), with tissue-specific estrogenic agonist/antagonist effects. QuatRx Pharmaceuticals conducted the global development of the agent before licensing it to Shionogi for regulatory filing and commercialization worldwide. Ospemifene is the first non-estrogen treatment approved for moderate to severe dyspareunia in women with menopause-related vulvar and vaginal atrophy. The drug is approved in the USA, and application for EU regulatory approval is underway. This article summarizes the milestones in the development of ospemifene leading to this first approval for moderate to severe dyspareunia, a symptom of postmenopausal vulvar and vaginal atrophy.

  10. Environmental regulatory update table

    SciTech Connect

    Brown, K.J.; Langston, M.E.; Tucker, C.S.; Reed, R.M.

    1987-06-01

    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.

  11. The Regulatory Framework for Privacy and Security

    NASA Astrophysics Data System (ADS)

    Hiller, Janine S.

    The internet enables the easy collection of massive amounts of personally identifiable information. Unregulated data collection causes distrust and conflicts with widely accepted principles of privacy. The regulatory framework in the United States for ensuring privacy and security in the online environment consists of federal, state, and self-regulatory elements. New laws have been passed to address technological and internet practices that conflict with privacy protecting policies. The United States and the European Union approaches to privacy differ significantly, and the global internet environment will likely cause regulators to face the challenge of balancing privacy interests with data collection for many years to come.

  12. Nuclear Regulatory Commission Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-20

    ... agenda on April 26, 2010 (75 FR 21960). For this edition of the NRC's regulatory agenda, the most... publication of the last NRC semiannual agenda on April 26, 2010 (75 FR 21960). Within each group, the rules... regulations to improve the control over the distribution of source material to exempt persons and to...

  13. Programmed Death-1 Antibody Blocks Therapeutic Effects of T-Regulatory Cells in Cockroach Antigen-Induced Allergic Asthma

    PubMed Central

    McGee, Halvor S.; Yagita, Hideo; Shao, Zhifei; Agrawal, Devendra K.

    2010-01-01

    We recently reported that the adoptive transfer of T-regulatory cells (Tregs) isolated from lung and spleen tissue of green fluorescent protein–transgenic mice reversed airway hyperresponsiveness and airway inflammation. Because Programmed Death-1 (PD-1) is a pivotal receptor regulating effector T-cell activation by Tregs, we evaluated whether PD-1 is involved in the therapeutic effect of naturally occurring Tregs (NTregs) and inducible Tregs (iTregs) in cockroach (CRA)-sensitized and challenged mice. The CD4+CD25+ NTregs and CD4+CD25− iTregs isolated from the lungs and spleens of BALB/c mice were adoptively transferred into CRA-sensitized and CRA-challenged mice with and without anti–PD-1 antibody (100 μg/mice). The CD4+CD25+ T cells in the lung were phenotyped after adoptive transfer. Concentrations of IL-4, IL-5, IL-10, IFN-γ, and IL-13 in bronchoalveolar lavage fluid (BALF) were measured using ELISA. The NTregs and iTregs from either lung or spleen tissue reversed airway hyperresponsiveness for at least 4 wk. However, the therapeutic effect was blocked by administering the anti–PD-1 antibody. The administration of Tregs-recipient mice with anti–PD-1 antibody significantly decreased cytotoxic T-lymphocyte antigen-4 expression, with low concentrations of Forkhead-winged transcriptional factor box 3 (Foxp3) mRNA transcripts in lung CD4+CD25+ T cells. These mice had substantially higher concentrations of BALF IL-4, IL-5, and IL-13, but significantly decreased levels of BALF IL-10. Adoptive therapy recipients without the anti–PD-1 antibody exhibited high levels of CTLA-4 expression and Foxp3 transcripts in lung CD4+CD25+ T cells, with a significant decrease in BALF IL-4, IL-5, and IL-13 concentrations and a substantial increase in BALF IL-10 concentrations. These data suggest that the reversal of airway hyperresponsiveness and airway inflammation by Tregs is mediated in part by PD-1, because other costimulatory molecules (e.g., inducible costimulatory

  14. Regulatory guidance document

    SciTech Connect

    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.

  15. Regulatory sequence analysis tools.

    PubMed

    van Helden, Jacques

    2003-07-01

    The web resource Regulatory Sequence Analysis Tools (RSAT) (http://rsat.ulb.ac.be/rsat) offers a collection of software tools dedicated to the prediction of regulatory sites in non-coding DNA sequences. These tools include sequence retrieval, pattern discovery, pattern matching, genome-scale pattern matching, feature-map drawing, random sequence generation and other utilities. Alternative formats are supported for the representation of regulatory motifs (strings or position-specific scoring matrices) and several algorithms are proposed for pattern discovery. RSAT currently holds >100 fully sequenced genomes and these data are regularly updated from GenBank.

  16. Global Fluency.

    ERIC Educational Resources Information Center

    Tosti, Donald T.

    1999-01-01

    Defines global fluency as a facility with cultural behaviors that help an organization thrive in an ever-changing global business environment; and discusses business culture, global culture, an example of a change effort at a global company, leadership values, company values, and defining global values and practices. (Author/LRW)

  17. 3 CFR - Regulatory Review

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... been learned since that time. Far more is now known about regulation—not only about when it is... interests of future generations; identify methods of ensuring that regulatory review does not produce...

  18. Assessing the regulatory picture

    SciTech Connect

    Not Available

    1994-02-01

    This article addresses the safety of the nation's drinking water supply and discusses compliance of the Clean Water Act. Right now, the shape of the regulatory future is uncertain. The results of the D-DBP regulatory negotiation are imminent. Congress is ready to begin debating reauthorization of the Safe Drinking Water Act, and utilities are trying to comply with the regulations while trying not to price water out of the reach of some of their customers.

  19. NRC regulatory initiatives

    SciTech Connect

    Johnson, T.C.

    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.

  20. Regulatory Fit Effects on Stimulus Identification

    PubMed Central

    Glass, Brian D.; Maddox, W. Todd; Markmana, Arthur B.

    2010-01-01

    This article examines the effects of a fit between a person's global regulatory focus and the local task reward structure on perceptual processing and judgment. On each trial, participants were presented with one of two briefly presented stimuli and were asked to identify it. Participants were placed in a promotion focus (a situationally induced sensitivity to gains) or a prevention focus (a situationally induced sensitivity to losses) and were asked to maximize gains or minimize losses. An asymmetric payoff ratio biased the overall reward toward one identification response over the other. Two experiments tested the role of regulatory fit when internal familiarity and perceptual sensitivity was low or high. When familiarity and sensitivity were low, participants in a regulatory fit (promotion focus with gains or a prevention focus with losses) showed greater perceptual sensitivity, but no response bias differences relative to participants in a regulatory mismatch. When familiarity and sensitivity were high, participants in a regulatory fit showed a response bias toward the high payoff stimulus, but no differences in perceptual sensitivity. Speculation on the neurobiological basis of this effect, as well as implications of this work for clinical disorders, such as depression, is offered. PMID:21264696

  1. Regulatory principles governing Salmonella and Yersinia virulence

    PubMed Central

    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

  2. Globalization and global health.

    PubMed

    Berlinguer, G

    1999-01-01

    Along with the positive or negative consequences of the globalization of health, we can consider global health as a goal, responding to human rights and to common interests. History tells us that after the "microbial unification" of the world, which began in 1492, over three centuries elapsed before the recognition of common risks and attempts to cope with them in a cross-boundary effort. In the 19th and 20th centuries, the struggle against epidemics united countries, world health became a common goal, and considerable results were achieved. However, in recent decades the notion of health as a cornerstone of economic development has been replaced by the idea that public health and health services are an obstacle to the wealth of nations. Meanwhile, new common threats are growing: among them, the exacerbation of old infections and emergence of new ones, the impact of environmental changes, drug traffic on a world scale, and destructive and self-destructive violence. New and stronger empirical motives relate the interests of peoples to universal rights and to global health. The author concludes with some proposals for policies.

  3. Regulatory challenges to global harmonization and expanded access to concentrates: how will regulators balance the increasing cost of new safety requirements with the desire to increase the availability of affordable product?

    PubMed

    Farrugia, A

    2004-10-01

    The provision of concentrates of the deficient coagulation factors is an essential component of the provision of comprehensive haemophilia care. Their safety, quality and efficacy need to be assured independently of the measures dictated by the market and the individual manufacturers. Over the past 20 years, this assurance has become the role of regulatory authorities, which in the developed world have generated a framework that assesses haemophilia products as medicines in the highest category of risk relative to other therapeutic agents. Systems of official regulation mandating standards and other measures are now coupled with voluntary standards adopted by industry bodies as additional features of a comprehensive nexus of arrangements contributing to product quality and risk minimization. Currently, the regulation of products for haemophilia in less developed economies relies on reference to decisions in the first-world authorities. This may not always result in optimal outcomes as most of the haemophilia care in the developing world is through local plasma and cryoprecipitate, which are not subject to the oversight of mainstream regulators. Furthermore, the emergence of companies based outside the developed world and seeking to supply the emerging economies of the developing world with haemophilia concentrates has necessitated new strategies for regulation that are independent of the established frameworks. Overall, the principles used by mainstream agencies may be applied in all environments seeking to assure the quality of haemophilia care. Applied properly, they can contribute to maintaining the delivery of a form of therapy that is nowadays amongst the safest in therapeutic practice. A rigid interpretation can seriously impede access to treatment, and therefore the development of independent expertise and appropriate strategies in assuring product safety and quality in the developing world is essential if patient safety and access to products can be assured.

  4. Predicting the impact of promoter variability on regulatory outputs

    PubMed Central

    Kreamer, Naomi N.; Phillips, Rob; Newman, Dianne K.; Boedicker, James Q.

    2015-01-01

    The increased availability of whole genome sequences calls for quantitative models of global gene expression, yet predicting gene expression patterns directly from genome sequence remains a challenge. We examine the contributions of an individual regulator, the ferrous iron-responsive regulatory element, BqsR, on global patterns of gene expression in Pseudomonas aeruginosa. The position weight matrix (PWM) derived for BqsR uncovered hundreds of likely binding sites throughout the genome. Only a subset of these potential binding sites had a regulatory consequence, suggesting that BqsR/DNA interactions were not captured within the PWM or that the broader regulatory context at each promoter played a greater role in setting promoter outputs. The architecture of the BqsR operator was systematically varied to understand how binding site parameters influence expression. We found that BqsR operator affinity was predicted by the PWM well. At many promoters the surrounding regulatory context, including overlapping operators of BqsR or the presence of RhlR binding sites, were influential in setting promoter outputs. These results indicate more comprehensive models that include local regulatory contexts are needed to develop a predictive understanding of global regulatory outputs. PMID:26675057

  5. Viral complement regulatory proteins.

    PubMed

    Rosengard, A M; Ahearn, J M

    1999-05-01

    The inactivation of complement provides cells and tissues critical protection from complement-mediated attack and decreases the associated recruitment of other inflammatory mediators. In an attempt to evade the host immune response, viruses have evolved two mechanisms to acquire complement regulatory proteins. They can directly seize the host cell complement regulators onto their outer envelope and/or they can produce their own proteins which are either secreted into the neighboring intercellular space or expressed as membrane-bound proteins on the infected host cell. The following review will concentrate on the viral homologues of the mammalian complement regulatory proteins, specifically those containing complement control protein (CCP) repeats. PMID:10408371

  6. Rationales for regulatory activity

    SciTech Connect

    Perhac, R.M.

    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.

  7. Pembrolizumab: first global approval.

    PubMed

    Poole, Raewyn M

    2014-10-01

    Pembrolizumab [Keytruda(®) (US)], a humanized monoclonal antibody against the programmed death receptor-1 (PD-1) protein, has been developed by Merck & Co for the treatment of cancer. Pembrolizumab has received its first global approval for the treatment of advanced, unresectable or metastatic malignant melanoma in the US, for use in patients with disease progression after prior treatment with ipilimumab and, for BRAF V600 mutation-positive patients, a BRAF inhibitor. It is the first anti-PD-1 therapy to receive regulatory approval in the US, and is currently under regulatory review in the EU. This article summarizes the milestones in the development of pembrolizumab leading to this first approval for the treatment of malignant melanoma.

  8. Delay-independent stability of genetic regulatory networks.

    PubMed

    Wu, Fang-Xiang

    2011-11-01

    Genetic regulatory networks can be described by nonlinear differential equations with time delays. In this paper, we study both locally and globally delay-independent stability of genetic regulatory networks, taking messenger ribonucleic acid alternative splicing into consideration. Based on nonnegative matrix theory, we first develop necessary and sufficient conditions for locally delay-independent stability of genetic regulatory networks with multiple time delays. Compared to the previous results, these conditions are easy to verify. Then we develop sufficient conditions for global delay-independent stability for genetic regulatory networks. Compared to the previous results, this sufficient condition is less conservative. To illustrate theorems developed in this paper, we analyze delay-independent stability of two genetic regulatory networks: a real-life repressilatory network with three genes and three proteins, and a synthetic gene regulatory network with five genes and seven proteins. The simulation results show that the theorems developed in this paper can effectively determine the delay-independent stability of genetic regulatory networks.

  9. EPAct Transportation Regulatory Activities

    SciTech Connect

    2011-11-21

    The U.S. Department of Energy's (DOE) Vehicle Technologies Program manages several transportation regulatory activities established by the Energy Policy Act of 1992 (EPAct), as amended by the Energy Conservation Reauthorization Act of 1998, EPAct 2005, and the Energy Independence and Security Act of 2007 (EISA).

  10. The regulatory horizon

    NASA Technical Reports Server (NTRS)

    Cook, ED

    1987-01-01

    The author briefly discusses the FAA's position as it relates to cockpit resource management. For example, if Cockpit Resource Management (CRM) is a positive concept, why isn't everyone required to implement it? The regulatory practice of the FAA is discussed and questions and answers are presented.

  11. Regulatory guidelines for biosimilars in Malaysia.

    PubMed

    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.

  12. Global change and mercury

    USGS Publications Warehouse

    Krabbenhoft, David P.; Sunderland, Elsie M.

    2013-01-01

    More than 140 nations recently agreed to a legally binding treaty on reductions in human uses and releases of mercury that will be signed in October of this year. This follows the 2011 rule in the United States that for the first time regulates mercury emissions from electricity-generating utilities. Several decades of scientific research preceded these important regulations. However, the impacts of global change on environmental mercury concentrations and human exposures remain a major uncertainty affecting the potential effectiveness of regulatory activities.

  13. Efinaconazole: first global approval.

    PubMed

    Patel, Trina; Dhillon, Sohita

    2013-11-01

    A non-lacquer 10% topical solution of efinaconazole, developed by Valeant Pharmaceuticals International, received its first global approval in Canada in October 2013 for the treatment of onychomycosis. The product is under regulatory review in the US and Japan. The mechanism of anti-fungal activity of efinaconazole, a small-molecule triazole compound, appears to be similar to that of other anti-fungal triazoles, namely ergosterol synthesis inhibition. In particular, it appears to inhibit 14α demethylase, an enzyme involved in the conversion of lanosterol to ergosterol, resulting in secondary degenerative changes. This article summarizes the milestones in the development of efinaconazole leading to this first approval for onychomycosis.

  14. Global HRD.

    ERIC Educational Resources Information Center

    1997

    This document contains four papers from a symposium on global human resource development (HRD). "Globalization of Human Resource Management (HRM) in Government: A Cross-Cultural Perspective" (Pan Suk Kim) relates HRM to national cultures and addresses its specific functional aspects with a unique dimension in a global organization. "An…

  15. Global Education.

    ERIC Educational Resources Information Center

    Berkley, June, Ed.

    1982-01-01

    The articles in this collection deal with various methods of global education--education to prepare students to function as understanding and informed citizens of the world. Topics discussed in the 26 articles include: (1) the necessity of global education; (2) global education in the elementary school language arts curriculum; (3) science fiction…

  16. Global Education.

    ERIC Educational Resources Information Center

    Longstreet, Wilma S., Ed.

    1988-01-01

    This issue contains an introduction ("The Promise and Perplexity of Globalism," by W. Longstreet) and seven articles dedicated to exploring the meaning of global education for today's schools. "Global Education: An Overview" (J. Becker) develops possible definitions, identifies objectives and skills, and addresses questions and issues in this…

  17. Medical Research Misconduct Need Regulatory Reforms

    PubMed Central

    Bedi, Neeraj

    2014-01-01

    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. PMID:25364140

  18. Toxicogenomics and the Regulatory Framework

    EPA Science Inventory

    Toxicogenomics presents regulatory agencies with the opportunity to revolutionize their analyses by enabling the collection of information on a broader range of responses than currently considered in traditional regulatory decision making. Analyses of genomic responses are expec...

  19. Nuclear Regulatory Commission information digest

    SciTech Connect

    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.

  20. 12 CFR 562.2 - Regulatory reports.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... of the special supervisory, regulatory, and economic policy needs served by such reports. Regulatory... reflects the underlying economic substance of the transaction at issue. Regulatory reporting...

  1. 78 FR 44329 - Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-23

    ....nasa.gov/open . Timetable: Action Date FR Cite NPRM 10/00/13 Regulatory Flexibility Analysis Required... Administration (NASA). ACTION: Semiannual regulatory agenda. SUMMARY: NASA's regulatory agenda describes those regulations being considered for development or amendment by NASA, the need and legal basis for the...

  2. 75 FR 79759 - Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-20

    ... Action 04/16/10 75 FR 2012 Regulatory Flexibility Analysis Required: Yes Agency Contact: Mohammed Khan... ``Regulatory Planning and Review,'' 58 FR 51735, and the Regulatory Flexibility Act, 5 U.S.C. 601 et seq... use throughout the rulemaking process. Timetable: Action Date FR Cite Notice: Public Meeting...

  3. Establishing regulatory priorities

    SciTech Connect

    Pontius, F.W.

    1995-12-01

    Statutory deadlines for setting regulations under the 1986 Safe Drinking Water Act (SDWA) have not been met. Faced with limited resources, the US Environmental Protection Agency (USEPA) has historically set regulatory priorities based on perceived need, politics, and legal deadlines. This has resulted in a fragmented regulatory program and confusion on the part of the regulated community and on the part of other stakeholders. Even though the agency has been subject to court-imposed deadlines for most new regulations, resource limitations have caused these deadlines to be missed, resulting in new court-imposed deadlines. In 1994, the agency began considering a new approach for determining how many regulations can be developed and in what order. A draft strategic plan was prepared in December 1994. Based on discussion of this plan, USEPA requested the US District Court for Oregon to extend certain regulatory deadlines so that new priorities could be set for the highest-risk substances. An extension was granted until Aug. 1, 1995, and was subsequently extended to Dec. 15, 1995.

  4. Regulatory aspects on nanomedicines.

    PubMed

    Sainz, Vanessa; Conniot, João; Matos, Ana I; Peres, Carina; Zupancic, Eva; Moura, Liane; Silva, Liana C; Florindo, Helena F; Gaspar, Rogério S

    2015-12-18

    Nanomedicines have been in the forefront of pharmaceutical research in the last decades, creating new challenges for research community, industry, and regulators. There is a strong demand for the fast development of scientific and technological tools to address unmet medical needs, thus improving human health care and life quality. Tremendous advances in the biomaterials and nanotechnology fields have prompted their use as promising tools to overcome important drawbacks, mostly associated to the non-specific effects of conventional therapeutic approaches. However, the wide range of application of nanomedicines demands a profound knowledge and characterization of these complex products. Their properties need to be extensively understood to avoid unpredicted effects on patients, such as potential immune reactivity. Research policy and alliances have been bringing together scientists, regulators, industry, and, more frequently in recent years, patient representatives and patient advocacy institutions. In order to successfully enhance the development of new technologies, improved strategies for research-based corporate organizations, more integrated research tools dealing with appropriate translational requirements aiming at clinical development, and proactive regulatory policies are essential in the near future. This review focuses on the most important aspects currently recognized as key factors for the regulation of nanomedicines, discussing the efforts under development by industry and regulatory agencies to promote their translation into the market. Regulatory Science aspects driving a faster and safer development of nanomedicines will be a central issue for the next years.

  5. Alternatives to animal experimentation: The regulatory background

    SciTech Connect

    Garthoff, Bernward . E-mail: bernward.garthoff@bayercropscience.com

    2005-09-01

    The framework, in which alternatives to animal experiments can be developed, standardized, respectively formally validated, has to be seen in a global context. The ever increasing demand of testing for hazard and risk assessment in health and environment, exemplified by the EU REACH program, subsequently triggers laboratory animal testing. This holds especially true, if no valid alternative methods agreed to by the regulatory authorities and the scientific community are available. At least for regulatory toxicity testing, the global frame and network are given by institutions such as OECD, ICH, and alike. However, due to the necessity of global consent of states, organizations, and stakeholders, the time gap between availability of a novel alternative test method and its final acceptance by authorities and implementation thereafter is widening. The lack of new technologies or opportunities for alternative method application such as, for example, the broad use of transgenic animals for refinement of existing tests, adds to the problem. The bare existence of certain in vivo tests increases also the gap between public demands for testing versus availability of alternative tests. Industries operating on a worldwide basis support the alternative test development in their respective area of research and operational business. However, a more coordinating approach such as that of the ecopa-organization (European Consensus Platform on Alternatives) is needed to exploit the existing possibilities within the current regulatory framework. This will speed up the process of acceptance and challenge the political worldto feel responsible for the sequels of their demanding more testing, that is, by funding alternative method development in academia and industry.

  6. Alternatives to animal experimentation: the regulatory background.

    PubMed

    Garthoff, Bernward

    2005-09-01

    The framework, in which alternatives to animal experiments can be developed, standardized, respectively formally validated, has to be seen in a global context. The ever increasing demand of testing for hazard and risk assessment in health and environment, exemplified by the EU REACH program, subsequently triggers laboratory animal testing. This holds especially true, if no valid alternative methods agreed to by the regulatory authorities and the scientific community are available. At least for regulatory toxicity testing, the global frame and network are given by institutions such as OECD, ICH, and alike. However, due to the necessity of global consent of states, organizations, and stakeholders, the time gap between availability of a novel alternative test method and its final acceptance by authorities and implementation thereafter is widening. The lack of new technologies or opportunities for alternative method application such as, for example, the broad use of transgenic animals for refinement of existing tests, adds to the problem. The bare existence of certain in vivo tests increases also the gap between public demands for testing versus availability of alternative tests. Industries operating on a worldwide basis support the alternative test development in their respective area of research and operational business. However, a more coordinating approach such as that of the ecopa-organization (European Consensus Platform on Alternatives) is needed to exploit the existing possibilities within the current regulatory framework. This will speed up the process of acceptance and challenge the political world to feel responsible for the sequels of their demanding more testing, that is, by funding alternative method development in academia and industry.

  7. Alternatives to animal experimentation: the regulatory background.

    PubMed

    Garthoff, Bernward

    2005-09-01

    The framework, in which alternatives to animal experiments can be developed, standardized, respectively formally validated, has to be seen in a global context. The ever increasing demand of testing for hazard and risk assessment in health and environment, exemplified by the EU REACH program, subsequently triggers laboratory animal testing. This holds especially true, if no valid alternative methods agreed to by the regulatory authorities and the scientific community are available. At least for regulatory toxicity testing, the global frame and network are given by institutions such as OECD, ICH, and alike. However, due to the necessity of global consent of states, organizations, and stakeholders, the time gap between availability of a novel alternative test method and its final acceptance by authorities and implementation thereafter is widening. The lack of new technologies or opportunities for alternative method application such as, for example, the broad use of transgenic animals for refinement of existing tests, adds to the problem. The bare existence of certain in vivo tests increases also the gap between public demands for testing versus availability of alternative tests. Industries operating on a worldwide basis support the alternative test development in their respective area of research and operational business. However, a more coordinating approach such as that of the ecopa-organization (European Consensus Platform on Alternatives) is needed to exploit the existing possibilities within the current regulatory framework. This will speed up the process of acceptance and challenge the political world to feel responsible for the sequels of their demanding more testing, that is, by funding alternative method development in academia and industry. PMID:15982684

  8. 77 FR 35944 - Renewal of the Global Markets Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-15

    ... determine how it can avoid unnecessary regulatory or operational impediments to global business while still... COMMISSION Renewal of the Global Markets Advisory Committee AGENCY: Commodity Futures Trading Commission... has determined to renew the charter of its Global Markets Advisory Committee. FOR FURTHER...

  9. Compartmentalized gene regulatory network of the pathogenic fungus Fusarium graminearum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Head blight caused by Fusarium graminearum (Fg) is a major limiting factor of wheat production with both yield loss and mycotoxin contamination. Here we report a model for global Fg gene regulatory networks (GRNs) inferred from a large collection of transcriptomic data using a machine-learning appro...

  10. Riociguat: first global approval.

    PubMed

    Conole, Daniel; Scott, Lesley J

    2013-11-01

    Riociguat (Adempas(®)), an oral first-in-class soluble guanylate cyclase (sGC) stimulator, is under global development by Bayer Healthcare Pharmaceuticals Inc. for the treatment of adult patients with inoperable or chronic/persistent chronic thromboembolic pulmonary hypertension (CTEPH) and for the treatment of adult patients with pulmonary arterial hypertension (PAH). The drug directly stimulates sGC in a nitric oxide independent manner, thereby increasing the sensitivity of sGC to nitric oxide, leading to increased cyclic guanosine monophosphate generation (a key signalling molecule involved in regulating vascular tone, proliferation, fibrosis and inflammation). Riociguat is the world's first approved pharmacotherapy for CTEPH, with its first global approval in this indication occurring in Canada. It has subsequently been approved in the USA for the treatment of patients with CTEPH and also received its first global approval in patients with PAH in the USA. It is undergoing regulatory review for these indications in Europe and for use in patients with CTEPH in Japan. This article summarizes the milestones in the development of riociguat, leading to its first global approvals in patients with CTEPH and PAH.

  11. Standardization of SOPs to Evaluations: Impacts on Regulatory Decisions using Learning and Memory as Case Studies

    EPA Science Inventory

    In an era of global trade and regulatory cooperation, consistent and scientifically based interpretation of developmental neurotoxicity (DNT) studies is essential, particularly for non­ standard assays and variable endpoints. Because there is flexibility in the selection of ...

  12. 76 FR 34007 - Draft Regulatory Basis for a Potential Rulemaking on Spent Nuclear Fuel Reprocessing Facilities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-10

    ... sought to expand the use of civilian nuclear power globally and close the nuclear fuel cycle through... COMMISSION 10 CFR Part 50 Draft Regulatory Basis for a Potential Rulemaking on Spent Nuclear Fuel... development of a draft regulatory basis document for a potential rulemaking on spent nuclear fuel...

  13. 78 FR 20325 - 2013 Parenteral Drug Association/Food and Drug Administration Joint Regulatory Conference...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-04

    ... Administration Joint Regulatory Conference: Driving Quality and Compliance Throughout the Product Life Cycle in a... Life Cycle in a Global Regulatory Environment.'' The conference will cover current issues affecting the... Innovations. Life Cycle Management. Process Validation. Validation FDA Guidance. Challenges of...

  14. Proceedings: international regulatory considerations on development pathways for cell therapies.

    PubMed

    Feigal, Ellen G; Tsokas, Katherine; Viswanathan, Sowmya; Zhang, Jiwen; Priest, Catherine; Pearce, Jonathan; Mount, Natalie

    2014-08-01

    Regenerative medicine is a rapidly evolving field that faces novel scientific and regulatory challenges. In September 2013, the International Workshop on Regulatory Pathways for Cell Therapies was convened to discuss the nature of these challenges and potential solutions and to highlight opportunities for potential convergence between different regulatory bodies that might assist the field's development. The workshop discussions generated potentially actionable steps in five main areas that could mitigate cell therapy development pathway risk and accelerate moving promising therapies to patients. These included the need for convergence of regulatory guidelines on donor eligibility and suitability of lines for use in clinical trials and subsequent commercialization for cell therapies to move forward on a global basis; the need to challenge and encourage investigators in the regenerative medicine field to share information and provide examples of comparability studies related to master cell banks; the need for convergence of guidelines across regulatory jurisdictions on requirements for tumorigenicity studies, based on particular cell types and on biodistribution studies; the need to increase transparency in sharing clinical trial information more broadly and disseminating results more rapidly; and the need to establish a forum for sharing the experiences of various approaches being developed to expedite regulatory approvals and access for patients to innovative cell and regenerative therapies in the different regulatory jurisdictions and to assess their potential strengths and weaknesses.

  15. Proceedings: International Regulatory Considerations on Development Pathways for Cell Therapies

    PubMed Central

    Tsokas, Katherine; Viswanathan, Sowmya; Zhang, Jiwen; Priest, Catherine; Pearce, Jonathan; Mount, Natalie

    2014-01-01

    Regenerative medicine is a rapidly evolving field that faces novel scientific and regulatory challenges. In September 2013, the International Workshop on Regulatory Pathways for Cell Therapies was convened to discuss the nature of these challenges and potential solutions and to highlight opportunities for potential convergence between different regulatory bodies that might assist the field’s development. The workshop discussions generated potentially actionable steps in five main areas that could mitigate cell therapy development pathway risk and accelerate moving promising therapies to patients. These included the need for convergence of regulatory guidelines on donor eligibility and suitability of lines for use in clinical trials and subsequent commercialization for cell therapies to move forward on a global basis; the need to challenge and encourage investigators in the regenerative medicine field to share information and provide examples of comparability studies related to master cell banks; the need for convergence of guidelines across regulatory jurisdictions on requirements for tumorigenicity studies, based on particular cell types and on biodistribution studies; the need to increase transparency in sharing clinical trial information more broadly and disseminating results more rapidly; and the need to establish a forum for sharing the experiences of various approaches being developed to expedite regulatory approvals and access for patients to innovative cell and regenerative therapies in the different regulatory jurisdictions and to assess their potential strengths and weaknesses. PMID:25038248

  16. Relationships between regulatory temperament dimensions and self-regulatory behaviors at 4 and 6 months of age.

    PubMed

    Aureli, Tiziana; Coppola, Gabrielle; Picconi, Laura; Grazia, Annalisa; Ponzetti, Silvia

    2015-02-01

    The present study focused on relationships between temperament and behavior in early regulation development. Unlike most studies on the topic, we observed infant behavior in a naturalistic playful situation rather than in experimental stressful procedure, and employed temperament measures uniquely reflecting regulatory dispositions rather than a global measure of reactivity. The infant's self-regulatory behaviors were observed at 4 and 6 months during face-to-face interactions and regulatory dimensions were assessed at 4 months. We found that low intensity pleasure and soothability dimensions, related to the infant physical and social experience, respectively, significantly affected regulatory behavior and their influence showed to depend on the infant's age, with the former dimension being influential at the earlier age and the latter being influential when the behavior was observed at the later age. Results are interpreted on the light of a dynamic view of regulation development.

  17. Intrinsic limits to gene regulation by global crosstalk

    PubMed Central

    Friedlander, Tamar; Prizak, Roshan; Guet, Călin C.; Barton, Nicholas H.; Tkačik, Gašper

    2016-01-01

    Gene regulation relies on the specificity of transcription factor (TF)–DNA interactions. Limited specificity may lead to crosstalk: a regulatory state in which a gene is either incorrectly activated due to noncognate TF–DNA interactions or remains erroneously inactive. As each TF can have numerous interactions with noncognate cis-regulatory elements, crosstalk is inherently a global problem, yet has previously not been studied as such. We construct a theoretical framework to analyse the effects of global crosstalk on gene regulation. We find that crosstalk presents a significant challenge for organisms with low-specificity TFs, such as metazoans. Crosstalk is not easily mitigated by known regulatory schemes acting at equilibrium, including variants of cooperativity and combinatorial regulation. Our results suggest that crosstalk imposes a previously unexplored global constraint on the functioning and evolution of regulatory networks, which is qualitatively distinct from the known constraints that act at the level of individual gene regulatory elements. PMID:27489144

  18. Regulatory considerations for global transfer of cryopreserved fish gametes

    USGS Publications Warehouse

    Jenkins, Jill A.; Tiersch, Terrence R.; Green, Christopher C.

    2011-01-01

    Federal and state resource managers, scientists, lawmakers, business and development investors, and the general public all struggle with issues surrounding the conservation of our biological heritage, especially in the face of increased population growth and consequent anthropogenic disturbances. Conservation interests include recovering exploited aquatic populations, decreasing the loss of genetic diversity, and reintroducing locally depleted species. However, research on husbandry and other techniques critical to implementing conservation strategies is often not started until few individuals remain. A program in the cryopreservation of gametes and embryos from aquatic species would address several of these conservation concerns by allowing the establishment of gene banks

  19. [A current and global review of sweeteners. Regulatory aspects].

    PubMed

    García-Almeida, J M; Casado Fdez, Gracia M; García Alemán, J

    2013-07-01

    In this chapter we review the role and potential benefits of non-caloric sweeteners, as part of the diet. After appearing and interest in the beneficial effects attributed to them, face different situations and conditions (obesity, diabetes...), more and more numerous studies, show their ineffective use. In conclusion, further research and results are needed to provide convincing evidence of their long-term effectiveness and the absence of negative effects from their use. The interest of the chapter lies in examining the distinctive aspects of sweeteners compared with sugar, measured as the standard of comparison. We will focus then on the other substances that are commonly used to sweeten foods instead of sugar.

  20. The regulatory landscape of osteogenic differentiation.

    PubMed

    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. PMID:24898411

  1. Toxicogenomics in regulatory ecotoxicology

    USGS Publications Warehouse

    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.

  2. The Regulatory Network of Pseudomonas aeruginosa

    PubMed Central

    2011-01-01

    Background Pseudomonas aeruginosa is an important bacterial model due to its metabolic and pathogenic abilities, which allow it to interact and colonize a wide range of hosts, including plants and animals. In this work we compile and analyze the structure and organization of an experimentally supported regulatory network in this bacterium. Results The regulatory network consists of 690 genes and 1020 regulatory interactions between their products (12% of total genes: 54% sigma and 16% of transcription factors). This complex interplay makes the third largest regulatory network of those reported in bacteria. The entire network is enriched for activating interactions and, peculiarly, self-activation seems to occur more prominent for transcription factors (TFs), which contrasts with other biological networks where self-repression is dominant. The network contains a giant component of 650 genes organized into 11 hierarchies, encompassing important biological processes, such as, biofilms formation, production of exopolysaccharide alginate and several virulence factors, and of the so-called quorum sensing regulons. Conclusions The study of gene regulation in P. aeruginosa is biased towards pathogenesis and virulence processes, all of which are interconnected. The network shows power-law distribution -input degree -, and we identified the top ten global regulators, six two-element cycles, the longest paths have ten steps, six biological modules and the main motifs containing three and four elements. We think this work can provide insights for the design of further studies to cover the many gaps in knowledge of this important bacterial model, and for the design of systems strategies to combat this bacterium. PMID:22587778

  3. Adaptation by Plasticity of Genetic Regulatory Networks

    NASA Astrophysics Data System (ADS)

    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.

  4. Regulatory Considerations for Biosimilars

    PubMed Central

    Nellore, Ranjani

    2010-01-01

    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. PMID:21829775

  5. Regulatory Streamlining and Improvement

    SciTech Connect

    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 Development: This area

  6. Global Composite

    Atmospheric Science Data Center

    2013-04-19

    article title:  MISR Global Images See the Light of Day     View Larger Image ... than its nadir counterpart due to enhanced reflection of light by atmospheric particulates. MISR data are processed at the ...

  7. Global Albedo

    Atmospheric Science Data Center

    2013-04-19

    ... estimation of crop yields and disease outbreaks) and land management. Global MISR DHR maps are also available for all other parts of the ... of Directional Hemispherical Reflectance. project:  MISR category:  gallery date:  ...

  8. Asymptotic stability of delayed stochastic genetic regulatory networks with impulses

    NASA Astrophysics Data System (ADS)

    Sakthivel, R.; Raja, R.; Anthoni, S. Marshal

    2010-11-01

    In this paper, the asymptotic stability analysis problem is considered for a class of delayed stochastic genetic regulatory networks with impulses. Based on the Lyapunov stability technique and stochastic analysis theory, stability criteria are proposed in terms of linear matrix inequalities (LMI). It is shown that the addressed stochastic genetic regulatory networks are globally asymptotically stable if four LMIs are feasible, where the feasibility of LMIs can be readily checked by Matlab LMI toolbox. Finally, a numerical example is given to demonstrate the usefulness of the proposed result.

  9. 77 FR 7972 - Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-13

    ... agenda pursuant to Executive Order 12866, ``Regulatory Planning and Review,'' 58 FR 51735, and the... Identifier No. 396 National Standards to 1105-AB34 Prevent, Detect, and Respond to Prison Rape (Reg Plan Seq... Prevent, Detect, and Respond to Prison Rape Regulatory Plan: This entry is Seq. No. 85 in part II of...

  10. 78 FR 1634 - Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-08

    ... Administration (NASA). ACTION: Semiannual regulatory agenda. SUMMARY: NASA's regulatory agenda describes those regulations being considered for development or amendment by NASA, the need and legal basis for the actions... Controls and Management Systems, Office of Management Systems Division, NASA Headquarters, Washington,...

  11. 78 FR 1574 - Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-08

    ... and stability to receive opioid addiction treatment medication. Timetable: Action Date FR Cite NPRM 06/19/09 74 FR 29153 NPRM Comment Period End 08/18/09 Final Action 12/06/12 77 FR 72752 Regulatory... FR Cite NPRM 03/00/13 Regulatory Flexibility Analysis Required: Yes. Agency Contact: Charles...

  12. Regulatory Foci and Organizational Commitment

    ERIC Educational Resources Information Center

    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…

  13. Olodaterol: first global approval.

    PubMed

    Gibb, Andrew; Yang, Lily P H

    2013-11-01

    Olodaterol (Striverdi(®) Respimat(®)) is a novel, long-acting, β2-adrenergic receptor agonist developed by Boehringer Ingelheim for the treatment of chronic obstructive pulmonary disease (COPD). The drug is delivered via the Respimat(®) Soft Mist™ inhaler. Olodaterol received its first global approval for the once-daily maintenance treatment of COPD in Canada and Russia, and submissions for regulatory approval have also been made in the USA, the EU and elsewhere. Phase II trials have been conducted in patients with asthma. The company is also developing a fixed-dose combination of olodaterol with tiotropium bromide, a long-acting anti-muscarinic agent, for the treatment of COPD. This article summarizes the milestones in the development of olodaterol leading to this first approval for COPD.

  14. Canagliflozin: first global approval.

    PubMed

    Elkinson, Shelley; Scott, Lesley J

    2013-06-01

    Canagliflozin (Invokana™), an oral selective sodium-glucose co-transporter 2 (SGLT2) inhibitor, is under global development with Mitsubishi Tanabe Pharma and Janssen Pharmaceuticals, a subsidiary of Johnson and Johnson, for the treatment of type 2 diabetes mellitus. SGLT2 are mainly located in the proximal tubule of the kidney and are involved in the reabsorption of filtered glucose from the glomeruli into the body. Inhibition of SGLT2 lowers blood glucose in an insulin independent manner as a consequence of blocking reabsorption of filtered glucose in the glomeruli, thereby increasing urinary excretion of glucose and, in turn, potentially reducing bodyweight. Canagliflozin is the first SGLT2 inhibitor to be approved in the USA and is under regulatory review in the EU. This article summarizes the milestones in the development of canagliflozin, leading to its first approval for use in adults with type 2 diabetes.

  15. Olodaterol: first global approval.

    PubMed

    Gibb, Andrew; Yang, Lily P H

    2013-11-01

    Olodaterol (Striverdi(®) Respimat(®)) is a novel, long-acting, β2-adrenergic receptor agonist developed by Boehringer Ingelheim for the treatment of chronic obstructive pulmonary disease (COPD). The drug is delivered via the Respimat(®) Soft Mist™ inhaler. Olodaterol received its first global approval for the once-daily maintenance treatment of COPD in Canada and Russia, and submissions for regulatory approval have also been made in the USA, the EU and elsewhere. Phase II trials have been conducted in patients with asthma. The company is also developing a fixed-dose combination of olodaterol with tiotropium bromide, a long-acting anti-muscarinic agent, for the treatment of COPD. This article summarizes the milestones in the development of olodaterol leading to this first approval for COPD. PMID:24158691

  16. The African Health Profession Regulatory Collaborative for Nurses and Midwives

    PubMed Central

    2012-01-01

    Background More than thirty-five sub-Saharan African countries have severe health workforce shortages. Many also struggle with a mismatch between the knowledge and competencies of health professionals and the needs of the populations they serve. Addressing these workforce challenges requires collaboration among health and education stakeholders and reform of health worker regulations. Health professional regulatory bodies, such as nursing and midwifery councils, have the mandate to reform regulations yet often do not have the resources or expertise to do so. In 2011, the United States of America Centers for Disease Control and Prevention began a four-year initiative to increase the collaboration among national stakeholders and help strengthen the capacity of health professional regulatory bodies to reform national regulatory frameworks. The initiative is called the African Health Regulatory Collaborative for Nurses and Midwives. This article describes the African Health Regulatory Collaborative for Nurses and Midwives and discusses its importance in implementing and sustaining national, regional, and global workforce initiatives. Discussion The African Health Profession Regulatory Collaborative for Nurses and Midwives convenes leaders responsible for regulation from 14 countries in East, Central and Southern Africa. It provides a high profile, south-to-south collaboration to assist countries in implementing joint approaches to problems affecting the health workforce. Implemented in partnership with Emory University, the Commonwealth Secretariat, and the East, Central and Southern African College of Nursing, this initiative also supports four to five countries per year in implementing locally-designed regulation improvement projects. Over time, the African Health Regulatory Collaborative for Nurses and Midwives will help to increase the regulatory capacity of health professional organizations and ultimately improve regulation and professional standards in this

  17. Regulatory Monitoring of Fortified Foods: Identifying Barriers and Good Practices

    PubMed Central

    Rowe, Laura A; Vossenaar, Marieke; Garrett, Greg S

    2015-01-01

    While fortification of staple foods and condiments has gained enormous global traction, poor performance persists throughout many aspects of implementation, most notably around the critical element of regulatory monitoring, which is essential for ensuring foods meet national fortification standards. Where coverage of fortified foods is high, limited nutritional impact of fortification programs largely exists due to regulatory monitoring that insufficiently identifies and holds producers accountable for underfortified products. Based on quality assurance data from 20 national fortification programs in 12 countries, we estimate that less than half of the samples are adequately fortified against relevant national standards. In this paper, we outline key findings from a literature review, key informant interviews with 11 fortification experts, and semi-quantitative surveys with 39 individuals from regulatory agencies and the food fortification industry in 17 countries on the perceived effectiveness of regulatory monitoring systems and barriers to compliance against national fortification standards. Findings highlight that regulatory agencies and industry disagree on the value that enforcement mechanisms have in ensuring compliance against standards. Perceived political risk of enforcement and poorly resourced inspectorate capacity appear to adversely reinforce each other within an environment of unclear legislation to create a major hurdle for improving overall compliance of fortification programs against national standards. Budget constraints affect the ability of regulatory agencies to create a well-trained inspector cadre and improve the detection and enforcement of non-compliant and underfortified products. Recommendations to improve fortification compliance include improving technical capacity; ensuring sustained leadership, accountability, and funding in both the private and the public sectors; and removing political barriers to ensure consistent detection of

  18. Regulatory Monitoring of Fortified Foods: Identifying Barriers and Good Practices.

    PubMed

    Luthringer, Corey L; Rowe, Laura A; Vossenaar, Marieke; Garrett, Greg S

    2015-09-01

    While fortification of staple foods and condiments has gained enormous global traction, poor performance persists throughout many aspects of implementation, most notably around the critical element of regulatory monitoring, which is essential for ensuring foods meet national fortification standards. Where coverage of fortified foods is high, limited nutritional impact of fortification programs largely exists due to regulatory monitoring that insufficiently identifies and holds producers accountable for underfortified products. Based on quality assurance data from 20 national fortification programs in 12 countries, we estimate that less than half of the samples are adequately fortified against relevant national standards. In this paper, we outline key findings from a literature review, key informant interviews with 11 fortification experts, and semi-quantitative surveys with 39 individuals from regulatory agencies and the food fortification industry in 17 countries on the perceived effectiveness of regulatory monitoring systems and barriers to compliance against national fortification standards. Findings highlight that regulatory agencies and industry disagree on the value that enforcement mechanisms have in ensuring compliance against standards. Perceived political risk of enforcement and poorly resourced inspectorate capacity appear to adversely reinforce each other within an environment of unclear legislation to create a major hurdle for improving overall compliance of fortification programs against national standards. Budget constraints affect the ability of regulatory agencies to create a well-trained inspector cadre and improve the detection and enforcement of non-compliant and underfortified products. Recommendations to improve fortification compliance include improving technical capacity; ensuring sustained leadership, accountability, and funding in both the private and the public sectors; and removing political barriers to ensure consistent detection of

  19. T follicular regulatory cells.

    PubMed

    Sage, Peter T; Sharpe, Arlene H

    2016-05-01

    Pathogen exposure elicits production of high-affinity antibodies stimulated by T follicular helper (Tfh) cells in the germinal center reaction. Tfh cells provide both costimulation and stimulatory cytokines to B cells to facilitate affinity maturation, class switch recombination, and plasma cell differentiation within the germinal center. Under normal circumstances, the germinal center reaction results in antibodies that precisely target foreign pathogens while limiting autoimmunity and excessive inflammation. In order to have this degree of control, the immune system ensures Tfh-mediated B-cell help is regulated locally in the germinal center. The recently identified T follicular regulatory (Tfr) cell subset can migrate to the germinal center and inhibit Tfh-mediated B-cell activation and antibody production. Although many aspects of Tfr cell biology are still unclear, recent data have begun to delineate the specialized roles of Tfr cells in controlling the germinal center reaction. Here we discuss the current understanding of Tfr-cell differentiation and function and how this knowledge is providing new insights into the dynamic regulation of germinal centers, and suggesting more efficacious vaccine strategies and ways to treat antibody-mediated diseases.

  20. Internationalization of regulatory requirements.

    PubMed

    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.

  1. The Global Information Infrastructure: Agenda for Cooperation.

    ERIC Educational Resources Information Center

    Microcomputers for Information Management, 1995

    1995-01-01

    Amplifies five principles set forth at the 1994 World Telecommunication Development Conference held in Buenos Aires (Argentina) to identify the U.S. government role in developing a global information infrastructure. Highlights include private sector investment, competition, open access, flexible regulatory environment, universal service, and a…

  2. Regulatory and clinical considerations for biosimilar oncology drugs

    PubMed Central

    Bennett, Charles L; Chen, Brian; Hermanson, Terhi; Wyatt, Michael D; Schulz, Richard M; Georgantopoulos, Peter; Kessler, Samuel; Raisch, Dennis W; Qureshi, Zaina P; Lu, Z Kevin; Love, Bryan L; Noxon, Virginia; Bobolts, Laura; Armitage, Melissa; Bian, John; Ray, Paul; Ablin, Richard J; Hrushesky, William J; Macdougall, Iain C; Sartor, Oliver; Armitage, James O

    2015-01-01

    Biological oncology products are integral to cancer treatment, but their high costs pose challenges to patients, families, providers, and insurers. The introduction of biosimilar agents—molecules that are similar in structure, function, activity, immunogenicity, and safety to the original biological drugs—provide opportunities both to improve healthcare access and outcomes, and to reduce costs. Several international regulatory pathways have been developed to expedite entry of biosimilars into global marketplaces. The first wave of oncology biosimilar use was in Europe and India in 2007. Oncology biosimilars are now widely marketed in several countries in Europe, and in Australia, Japan, China, Russia, India, and South Korea. Their use is emerging worldwide, with the notable exception of the USA, where several regulatory and cost barriers to biosimilar approval exist. In this Review, we discuss oncology biosimilars and summarise their regulatory frameworks, clinical experiences, and safety concerns. PMID:25456378

  3. Regulatory framework for access to safe, effective quality medicines.

    PubMed

    Rägo, Lembit; Sillo, Hiiti; 't Hoen, Ellen; Zweygarth, Monika

    2014-01-01

    Medicines of uncertain quality, safety and efficacy can be worse than no treatment at all. It is the responsibility of national medicines regulatory authorities to protect patients from harm. Yet, there are great disparities in regulatory capacity globally, preventing large populations from accessing the benefits of advances in the pharmaceutical field. This article describes the main regulatory functions and how they are applied to assure the quality, safety and efficacy of different types of medicines in different environments. It gives examples of initiatives that have increased access to good quality medicines worldwide and - more importantly - are laying the groundwork for collaborative approaches aiming to ensure that pharmaceutical products meet the same, stringent quality standards in all parts of the world. PMID:25310085

  4. Regulatory and clinical considerations for biosimilar oncology drugs.

    PubMed

    Bennett, Charles L; Chen, Brian; Hermanson, Terhi; Wyatt, Michael D; Schulz, Richard M; Georgantopoulos, Peter; Kessler, Samuel; Raisch, Dennis W; Qureshi, Zaina P; Lu, Z Kevin; Love, Bryan L; Noxon, Virginia; Bobolts, Laura; Armitage, Melissa; Bian, John; Ray, Paul; Ablin, Richard J; Hrushesky, William J; Macdougall, Iain C; Sartor, Oliver; Armitage, James O

    2014-12-01

    Biological oncology products are integral to cancer treatment, but their high costs pose challenges to patients, families, providers, and insurers. The introduction of biosimilar agents-molecules that are similar in structure, function, activity, immunogenicity, and safety to the original biological drugs-provide opportunities both to improve health-care access and outcomes, and to reduce costs. Several international regulatory pathways have been developed to expedite entry of biosimilars into global marketplaces. The first wave of oncology biosimilar use was in Europe and India in 2007. Oncology biosimilars are now widely marketed in several countries in Europe, and in Australia, Japan, China, Russia, India, and South Korea. Their use is emerging worldwide, with the notable exception of the USA, where several regulatory and cost barriers to biosimilar approval exist. In this Review, we discuss oncology biosimilars and summarise their regulatory frameworks, clinical experiences, and safety concerns.

  5. Healthcare regulatory concepts in Brazil.

    PubMed

    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.

  6. Global Education.

    ERIC Educational Resources Information Center

    McCoubrey, Sharon

    1994-01-01

    This theme issue focuses on topics related to global issues. (1) "Recycling for Art Projects" (Wendy Stephenson) gives an argument for recycling in the art classroom; (2) "Winds of Change: Tradition and Innovation in Circumpolar Art" (Bill Zuk and Robert Dalton) includes profiles of Alaskan Yupik artist, Larry Beck, who creates art from recycled…

  7. Global Warming.

    ERIC Educational Resources Information Center

    Hileman, Bette

    1989-01-01

    States the foundations of the theory of global warming. Describes methodologies used to measure the changes in the atmosphere. Discusses steps currently being taken in the United States and the world to slow the warming trend. Recognizes many sources for the warming and the possible effects on the earth. (MVL)

  8. Global Warming?

    ERIC Educational Resources Information Center

    Eichman, Julia Christensen; Brown, Jeff A.

    1994-01-01

    Presents information and data on an experiment designed to test whether different atmosphere compositions are affected by light and temperature during both cooling and heating. Although flawed, the experiment should help students appreciate the difficulties that researchers face when trying to find evidence of global warming. (PR)

  9. Global Change

    USGS Publications Warehouse

    ,

    1993-01-01

    Global change is a relatively new area of scientific study using research from many disciplines to determine how Earth systems change, and to assess the influence of human activity on these changes. This teaching packet consists of a poster and three activity sheets. In teaching these activities four themes are important: time, change, cycles, and Earth as home.

  10. 12 CFR 35.3 - CRA communications.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... employee who approves, directs, authorizes, or negotiates the agreement with the NGEP; or (B) An employee... member of the NGEP who approves, directs, authorizes, or negotiates the agreement with the insured... time period as described in paragraph (b)(1) or (b)(2) of this section and the...

  11. 12 CFR 133.3 - CRA communications.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... or any affiliate has knowledge of the communication— (A) An employee who approves, directs... knowledge of the communication— (i) A director, employee, or member of the NGEP who approves, directs... and assume that the communication occurs within the relevant time period as described in paragraph...

  12. 12 CFR 346.3 - CRA communications.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... institution or any affiliate has knowledge of the communication— (A) An employee who approves, directs... knowledge of the communication— (i) A director, employee, or member of the NGEP who approves, directs... and assume that the communication occurs within the relevant time period as described in paragraph...

  13. 12 CFR 35.3 - CRA communications.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... employee who approves, directs, authorizes, or negotiates the agreement with the NGEP; or (B) An employee... member of the NGEP who approves, directs, authorizes, or negotiates the agreement with the insured... time period as described in paragraph (b)(1) or (b)(2) of this section and the...

  14. 12 CFR 533.3 - CRA communications.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... or any affiliate has knowledge of the communication— (A) An employee who approves, directs... knowledge of the communication— (i) A director, employee, or member of the NGEP who approves, directs... and assume that the communication occurs within the relevant time period as described in paragraph...

  15. The CRaZy Calcium Cycle.

    PubMed

    Espeso, Eduardo A

    2016-01-01

    Calcium is an essential cation for a cell. This cation participates in the regulation of numerous processes in either prokaryotes or eukaryotes, from bacteria to humans. Saccharomyces cerevisiae has served as a model organism to understand calcium homeostasis and calcium-dependent signaling in fungi. In this chapter it will be reviewed known and predicted transport mechanisms that mediate calcium homeostasis in the yeast. How and when calcium enters the cell, how and where it is stored, when is reutilized, and finally secreted to the environment to close the cycle. As a second messenger, maintenance of a controlled free intracellular calcium concentration is important for mediating transcriptional regulation. Many environmental stimuli modify the concentration of cytoplasmic free calcium generating the "calcium signal". This is sensed and transduced through the calmodulin/calcineurin pathway to a transcription factor, named calcineurin-responsive zinc finger, CRZ, also known as "crazy", to mediate transcriptional regulation of a large number of genes of diverse pathways including a negative feedback regulation of the calcium homeostasis system.

  16. Transcriptional Regulatory Networks in Saccharomyces cerevisiae

    NASA Astrophysics Data System (ADS)

    Lee, Tong Ihn; Rinaldi, Nicola J.; Robert, François; Odom, Duncan T.; Bar-Joseph, Ziv; Gerber, Georg K.; Hannett, Nancy M.; Harbison, Christopher T.; Thompson, Craig M.; Simon, Itamar; Zeitlinger, Julia; Jennings, Ezra G.; Murray, Heather L.; Gordon, D. Benjamin; Ren, Bing; Wyrick, John J.; Tagne, Jean-Bosco; Volkert, Thomas L.; Fraenkel, Ernest; Gifford, David K.; Young, Richard A.

    2002-10-01

    We have determined how most of the transcriptional regulators encoded in the eukaryote Saccharomyces cerevisiae associate with genes across the genome in living cells. Just as maps of metabolic networks describe the potential pathways that may be used by a cell to accomplish metabolic processes, this network of regulator-gene interactions describes potential pathways yeast cells can use to regulate global gene expression programs. We use this information to identify network motifs, the simplest units of network architecture, and demonstrate that an automated process can use motifs to assemble a transcriptional regulatory network structure. Our results reveal that eukaryotic cellular functions are highly connected through networks of transcriptional regulators that regulate other transcriptional regulators.

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

    PubMed

    Gonçalves, Joana P; Aires, Ricardo S; Francisco, Alexandre P; Madeira, Sara C

    2012-01-01

    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 functionally enriched

  18. Regulatory insight into the European human pluripotent stem cell registry.

    PubMed

    Kurtz, Andreas; Stacey, Glyn; Kidane, Luam; Seriola, Anna; Stachelscheid, Harald; Veiga, Anna

    2014-12-01

    The European pluripotent stem cell registry aims at listing qualified pluripotent stem cell (PSC) lines that are available globally together with relevant information for each cell line. Specific emphasis is being put on documenting ethical procurement of the cells and providing evidence of pluripotency. The report discusses the tasks and challenges for a global PSC registry as an instrument to develop collaboration, to access cells from diverse resources and banks, and to implement standards, and as a means to follow up usage of cells and support adherence to regulatory and scientific standards and transparency for stakeholders. PMID:25457963

  19. Regulatory insight into the European human pluripotent stem cell registry.

    PubMed

    Kurtz, Andreas; Stacey, Glyn; Kidane, Luam; Seriola, Anna; Stachelscheid, Harald; Veiga, Anna

    2014-12-01

    The European pluripotent stem cell registry aims at listing qualified pluripotent stem cell (PSC) lines that are available globally together with relevant information for each cell line. Specific emphasis is being put on documenting ethical procurement of the cells and providing evidence of pluripotency. The report discusses the tasks and challenges for a global PSC registry as an instrument to develop collaboration, to access cells from diverse resources and banks, and to implement standards, and as a means to follow up usage of cells and support adherence to regulatory and scientific standards and transparency for stakeholders.

  20. Regulatory facility guide for Ohio

    SciTech Connect

    Anderson, S.S.; Bock, R.E.; Francis, M.W.; Gove, R.M.; Johnson, P.E.; Kovac, F.M.; Mynatt, J.O.; Rymer, A.C.

    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.

  1. Panwapa: Global Kids, Global Connections

    ERIC Educational Resources Information Center

    Berson, Ilene R.; Berson, Michael J.

    2009-01-01

    Panwapa, created by the Sesame Street Workshop of PBS, is an example of an initiative on the Internet designed to enhance students' learning by exposing them to global communities. Panwapa means "Here on Earth" in Tshiluba, a Bantu language spoken in the Democratic Republic of Congo. At the Panwapa website, www.panwapa.org, children aged four to…

  2. The limits of regulatory toxicology

    SciTech Connect

    Carrington, Clark D.; Bolger, P. Michael

    2010-03-01

    The Acceptable Daily Intake (ADI) has been used by regulatory and public health organizations (e.g., the U.S. Food and Drug and Administration, and the World Health Organization) for chemicals for more than 50 years. The ADI concept was also initially employed at the U.S. Environmental Protection Agency at its inception in 1971, although with the adoption of newer terminology, it later became known as the Reference Dose (RfD). It is clear from the literature that both were first devised as instruments of regulatory policy. In the intervening years, it has become common to use language that implies that these standards are statements of scientific fact. Similarly, some of the discretionary or default values that are used to derive regulatory standards are represented as scientific assumptions when in fact they also represent regulatory policy. This confusion impedes both the best use of the available science and informed public participation in policy making. In addition, the misconception of the ADI or the RfD as statements of scientific fact may impede the consideration of alternative means to reduce exposure to chemicals that may be harmful, including regulatory measures that do not involve prescribing a regulatory concentration limit.

  3. Going Global

    ERIC Educational Resources Information Center

    Boulard, Garry

    2010-01-01

    In a move to increase its out-of-state and international student enrollment, officials at the University of Iowa are stepping up their global recruitment efforts--even in the face of criticism that the school may be losing sight of its mission. The goal is to increase enrollment across the board, with both in-state as well as out-of-state and…

  4. Global Arrays

    2006-02-23

    The Global Arrays (GA) toolkit provides an efficient and portable “shared-memory” programming interface for distributed-memory computers. Each process in a MIMD parallel program can asynchronously access logical blocks of physically distributed dense multi-dimensional arrays, without need for explicit cooperation by other processes. Unlike other shared-memory environments, the GA model exposes to the programmer the non-uniform memory access (NUMA) characteristics of the high performance computers and acknowledges that access to a remote portion of the sharedmore » data is slower than to the local portion. The locality information for the shared data is available, and a direct access to the local portions of shared data is provided. Global Arrays have been designed to complement rather than substitute for the message-passing programming model. The programmer is free to use both the shared-memory and message-passing paradigms in the same program, and to take advantage of existing message-passing software libraries. Global Arrays are compatible with the Message Passing Interface (MPI).« less

  5. [The global harmonization task force : successes and challenges].

    PubMed

    Rotter, R G

    2009-06-01

    With the move towards globalized international commerce and trade, a call for harmonization of medical device regulatory requirements and practices has evolved. The purpose of the Global Harmonization Task Force (GHTF) is to encourage convergence of regulatory requirements and practices at a global level through consensus to achieve four principle goals: promote safety, quality and performance/effectiveness of medical devices; encourage technological innovation; foster international trade; and serve as a forum of information exchange - all in the interests of protecting and promoting public health. The GHTF is governed by a Steering Committee, and the principle development of the GHTF regulatory model has been, and continues to be, done through five working groups known as Study Groups and supplemented recently by the creation of several Ad Hoc Working Groups. Since its creation in 1992, the members of the GHTF have worked collaboratively to develop what is now ready to be called a global model for the regulation of medical devices.

  6. 75 FR 79929 - Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-20

    ... Commission ###Semiannual Regulatory Agenda### ] FEDERAL TRADE COMMISSION (FTC) FEDERAL TRADE COMMISSION 16 CFR Ch. I Semiannual Regulatory Agenda AGENCY: Federal Trade Commission. ACTION: Semiannual regulatory... 22(d)(1) of the Federal Trade Commission Act, 15 U.S.C. 57b-3(d)(1), and the Regulatory......

  7. Department of Energy Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-20

    ... Semiannual Regulatory Agenda 10 CFR Chs. II, III, and X 48 CFR Ch. 9 Regulatory Agenda AGENCY: Department of... ``Regulatory Planning and Review,'' 58 FR 51735, and the Regulatory Flexibility Act, 5 U.S.C. 601 et seq... use throughout the rulemaking process. Timetable: Action Date FR Cite Notice: Public Meeting...

  8. Global Arrays

    SciTech Connect

    Krishnamoorthy, Sriram; Daily, Jeffrey A.; Vishnu, Abhinav; Palmer, Bruce J.

    2015-11-01

    Global Arrays (GA) is a distributed-memory programming model that allows for shared-memory-style programming combined with one-sided communication, to create a set of tools that combine high performance with ease-of-use. GA exposes a relatively straightforward programming abstraction, while supporting fully-distributed data structures, locality of reference, and high-performance communication. GA was originally formulated in the early 1990’s to provide a communication layer for the Northwest Chemistry (NWChem) suite of chemistry modeling codes that was being developed concurrently.

  9. Regulatory physiology discipline science plan

    NASA Technical Reports Server (NTRS)

    1991-01-01

    The focus of the Regulatory Physiology discipline of the Space Physiology and Countermeasures Program is twofold. First, to determine and study how microgravity and associated factors of space flight affect the regulatory mechanisms by which humans adapt and achieve homeostasis and thereby regulate their ability to respond to internal and external signals; and, second, to study selected physiological systems that have been demonstrated to be influenced by gravity. The Regulatory Physiology discipline, as defined here, is composed of seven subdisciplines: (1) Circadian Rhythms, (2) Endocrinology, (3) Fluid and Electrolyte Regulation, (4) Hematology, (5) Immunology, (6) Metabolism and Nutrition, and (7) Temperature Regulation. The purpose of this Discipline Science Plan is to provide a conceptual strategy for NASA's Life Sciences Division research and development activities in the area of regulatory physiology. It covers the research areas critical to NASA's programmatic requirements for the Extended-Duration Orbiter, Space Station Freedom, and exploration mission science activities. These science activities include ground-based and flight; basic, applied, and operational; and animal and human research and development. This document summarizes the current status of the program, outlines available knowledge, establishes goals and objectives, identifies science priorities, and defines critical questions in regulatory physiology. It contains a general plan that will be used by both NASA Headquarters Program Offices and the field centers to review and plan basic, applied, and operational intramural and extramural research and development activities in this area.

  10. Reverse Engineering of Genome-wide Gene Regulatory Networks from Gene Expression Data.

    PubMed

    Liu, Zhi-Ping

    2015-02-01

    Transcriptional regulation plays vital roles in many fundamental biological processes. Reverse engineering of genome-wide regulatory networks from high-throughput transcriptomic data provides a promising way to characterize the global scenario of regulatory relationships between regulators and their targets. In this review, we summarize and categorize the main frameworks and methods currently available for inferring transcriptional regulatory networks from microarray gene expression profiling data. We overview each of strategies and introduce representative methods respectively. Their assumptions, advantages, shortcomings, and possible improvements and extensions are also clarified and commented.

  11. Finding regulatory elements and regulatory motifs: a general probabilistic framework

    PubMed Central

    van Nimwegen, Erik

    2007-01-01

    Over the last two decades a large number of algorithms has been developed for regulatory motif finding. Here we show how many of these algorithms, especially those that model binding specificities of regulatory factors with position specific weight matrices (WMs), naturally arise within a general Bayesian probabilistic framework. We discuss how WMs are constructed from sets of regulatory sites, how sites for a given WM can be discovered by scanning of large sequences, how to cluster WMs, and more generally how to cluster large sets of sites from different WMs into clusters. We discuss how 'regulatory modules', clusters of sites for subsets of WMs, can be found in large intergenic sequences, and we discuss different methods for ab initio motif finding, including expectation maximization (EM) algorithms, and motif sampling algorithms. Finally, we extensively discuss how module finding methods and ab initio motif finding methods can be extended to take phylogenetic relations between the input sequences into account, i.e. we show how motif finding and phylogenetic footprinting can be integrated in a rigorous probabilistic framework. The article is intended for readers with a solid background in applied mathematics, and preferably with some knowledge of general Bayesian probabilistic methods. The main purpose of the article is to elucidate that all these methods are not a disconnected set of individual algorithmic recipes, but that they are just different facets of a single integrated probabilistic theory. PMID:17903285

  12. The rise of regulatory RNA

    PubMed Central

    Morris, K.V.; Mattick, J.S.

    2015-01-01

    Discoveries over the last decade portend a paradigm shift in molecular biology. Evidence suggests that RNA is not only functional as a messenger between DNA and protein but also in the regulation of genome organization and gene expression, which is increasingly elaborated in complex organisms. Regulatory RNAs appear to operate at many levels, but in particular to play an important role in the epigenetic processes that control differentiation and development. These discoveries suggest a central role for RNA in human evolution and ontogeny. Here we survey the emergence of the previously unsuspected world of regulatory RNAs from an historical perspective. PMID:24776770

  13. Below Regulatory Concern Owners Group:

    SciTech Connect

    Smith, C.F.; Phillips, L.B.; Williams, W.J.

    1988-03-01

    The US Nuclear Regulatory Commission has indicated that Below Regulatory Concern (BRC) exemption of waste streams from the disposal requirements for low level radioactive waste should be based on actual expected nuclide concentration and variability. Because of variations in the importance and relative abundance of nuclides in waste, one or a small number of nuclides may control the detemination of a waste steam as BRC. This study wasconducted to evaluate the relative importance of the major radionucldies in dose assessments for the disposal options and geographic regions under consideration for BRC waste. 6 refs., 25 tabs.

  14. Glycoconjugate Vaccines: The Regulatory Framework.

    PubMed

    Jones, Christopher

    2015-01-01

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

  15. Global teaching of global seismology

    NASA Astrophysics Data System (ADS)

    Stein, S.; Wysession, M.

    2005-12-01

    Our recent textbook, Introduction to Seismology, Earthquakes, & Earth Structure (Blackwell, 2003) is used in many countries. Part of the reason for this may be our deliberate attempt to write the book for an international audience. This effort appears in several ways. We stress seismology's long tradition of global data interchange. Our brief discussions of the science's history illustrate the contributions of scientists around the world. Perhaps most importantly, our discussions of earthquakes, tectonics, and seismic hazards take a global view. Many examples are from North America, whereas others are from other areas. Our view is that non-North American students should be exposed to North American examples that are type examples, and that North American students should be similarly exposed to examples elsewhere. For example, we illustrate how the Euler vector geometry changes a plate boundary from spreading, to strike-slip, to convergence using both the Pacific-North America boundary from the Gulf of California to Alaska and the Eurasia-Africa boundary from the Azores to the Mediterranean. We illustrate diffuse plate boundary zones using western North America, the Andes, the Himalayas, the Mediterranean, and the East Africa Rift. The subduction zone discussions examine Japan, Tonga, and Chile. We discuss significant earthquakes both in the U.S. and elsewhere, and explore hazard mitigation issues in different contexts. Both comments from foreign colleagues and our experience lecturing overseas indicate that this approach works well. Beyond the specifics of our text, we believe that such a global approach is facilitated by the international traditions of the earth sciences and the world youth culture that gives students worldwide common culture. For example, a video of the scene in New Madrid, Missouri that arose from a nonsensical earthquake prediction in 1990 elicits similar responses from American and European students.

  16. Global Geomorphology

    NASA Technical Reports Server (NTRS)

    Douglas, I.

    1985-01-01

    Any global view of landforms must include an evaluation of the link between plate tectonics and geomorphology. To explain the broad features of the continents and ocean floors, a basic distinction between the tectogene and cratogene part of the Earth's surface must be made. The tectogene areas are those that are dominated by crustal movements, earthquakes and volcanicity at the present time and are essentially those of the great mountain belts and mid ocean ridges. Cratogene areas comprise the plate interiors, especially the old lands of Gondwanaland and Laurasia. Fundamental as this division between plate margin areas and plate interiors is, it cannot be said to be a simple case of a distinction between tectonically active and stable areas. Indeed, in terms of megageomorphology, former plate margins and tectonic activity up to 600 million years ago have to be considered.

  17. 76 FR 30325 - Application to Export Electric Energy; E-T Global Energy, LLC

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-25

    ... Energy Regulatory Commission Application to Export Electric Energy; E-T Global Energy, LLC AGENCY: Office... Global Energy, LLC (E-T Global) has applied for authority to transmit electric energy from the United... authority to transmit electric energy from the United States to Mexico for five years as a power...

  18. Global warming

    NASA Astrophysics Data System (ADS)

    Houghton, John

    2005-06-01

    'Global warming' is a phrase that refers to the effect on the climate of human activities, in particular the burning of fossil fuels (coal, oil and gas) and large-scale deforestation, which cause emissions to the atmosphere of large amounts of 'greenhouse gases', of which the most important is carbon dioxide. Such gases absorb infrared radiation emitted by the Earth's surface and act as blankets over the surface keeping it warmer than it would otherwise be. Associated with this warming are changes of climate. The basic science of the 'greenhouse effect' that leads to the warming is well understood. More detailed understanding relies on numerical models of the climate that integrate the basic dynamical and physical equations describing the complete climate system. Many of the likely characteristics of the resulting changes in climate (such as more frequent heat waves, increases in rainfall, increase in frequency and intensity of many extreme climate events) can be identified. Substantial uncertainties remain in knowledge of some of the feedbacks within the climate system (that affect the overall magnitude of change) and in much of the detail of likely regional change. Because of its negative impacts on human communities (including for instance substantial sea-level rise) and on ecosystems, global warming is the most important environmental problem the world faces. Adaptation to the inevitable impacts and mitigation to reduce their magnitude are both necessary. International action is being taken by the world's scientific and political communities. Because of the need for urgent action, the greatest challenge is to move rapidly to much increased energy efficiency and to non-fossil-fuel energy sources.

  19. Global gamesmanship.

    PubMed

    MacMillan, Ian C; van Putten, Alexander B; McGrath, Rita Gunther

    2003-05-01

    Competition among multinationals these days is likely to be a three-dimensional game of global chess: The moves an organization makes in one market are designed to achieve goals in another in ways that aren't immediately apparent to its rivals. The authors--all management professors-call this approach "competing under strategic interdependence," or CSI. And where this interdependence exists, the complexity of the situation can quickly overwhelm ordinary analysis. Indeed, most business strategists are terrible at anticipating the consequences of interdependent choices, and they're even worse at using interdependency to their advantage. In this article, the authors offer a process for mapping the competitive landscape and anticipating how your company's moves in one market can influence its competitive interactions in others. They outline the six types of CSI campaigns--onslaughts, contests, guerrilla campaigns, feints, gambits, and harvesting--available to any multiproduct or multimarket corporation that wants to compete skillfully. They cite real-world examples such as the U.S. pricing battle Philip Morris waged with R.J. Reynolds--not to gain market share in the domestic cigarette market but to divert R.J. Reynolds's resources and attention from the opportunities Philip Morris was pursuing in Eastern Europe. And, using data they collected from their studies of consumer-products companies Procter & Gamble and Unilever, the authors describe how to create CSI tables and bubble charts that present a graphical look at the competitive landscape and that may uncover previously hidden opportunities. The CSI mapping process isn't just for global corporations, the authors explain. Smaller organizations that compete with a portfolio of products in just one national or regional market may find it just as useful for planning their next business moves.

  20. 75 FR 79799 - Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-20

    ... Hinchman, Senior Counsel, Office of Legal Policy, Department of Justice, Room 4252, 950 Pennsylvania Avenue... Department of Justice and the Access Board have each gathered a great deal of information regarding the... Justice ###Semiannual Regulatory Agenda### ] DEPARTMENT OF JUSTICE (DOJ) DEPARTMENT OF JUSTICE 8 CFR Ch....

  1. 78 FR 44279 - Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-23

    ... agenda pursuant to Executive Order 12866, ``Regulatory Planning and Review,'' 58 FR 51735, and the... destruction of controlled substances consistent with the Controlled Substances Act. Timetable: Action Date FR Cite ANPRM 01/21/09 74 FR 3480 ANPRM Comment Period End 03/23/09 Notice of Public Meeting 12/22/10...

  2. Insights into the regulatory landscape of the lysine riboswitch

    PubMed Central

    Garst, Andrew D.; Porter, Ely B.; Batey, Robert T.

    2012-01-01

    A prevalent means of regulating gene expression in bacteria is by riboswitches found within mRNA leader sequences. Like protein repressors these RNA elements must bind an effector molecule with high specificity against a background of other cellular metabolites of similar chemical structure to elicit the appropriate regulatory response. Current crystal structures of the lysine riboswitch do not provide a complete understanding of selectivity as recognition is substantially mediated through main chain atoms of the amino acid. Using a directed set of lysine analogs and other amino acids, the relative contributions of the polar functional groups to binding affinity and the regulatory response have been determined. Our results reveal that the lysine riboswitch has >1,000-fold specificity for lysine over other amino acids. To achieve this specificity, the aptamer is highly sensitive to the precise placement of the ε-amino group and relatively tolerant of alterations to the main chain functional groups. At low NTP concentrations, we observe good agreement between the half-maximal regulatory activity (T50) and the affinity of the receptor for lysine (KD) as well many of its analogs. However, above 400 µM [NTP] the concentration of lysine required to elicit transcription termination rises, moving into the riboswitch into a kinetic control regime. These data demonstrate that under physiologically relevant conditions riboswitches can integrate both effector and NTP concentrations to generate a regulatory response appropriate for global metabolic state of the cell. PMID:22771573

  3. Insights into the regulatory landscape of the lysine riboswitch.

    PubMed

    Garst, Andrew D; Porter, Ely B; Batey, Robert T

    2012-10-12

    A prevalent means of regulating gene expression in bacteria is by riboswitches found within mRNA leader sequences. Like protein repressors, these RNA elements must bind an effector molecule with high specificity against a background of other cellular metabolites of similar chemical structure to elicit the appropriate regulatory response. Current crystal structures of the lysine riboswitch do not provide a complete understanding of selectivity as recognition is substantially mediated through main-chain atoms of the amino acid. Using a directed set of lysine analogs and other amino acids, we have determined the relative contributions of the polar functional groups to binding affinity and the regulatory response. Our results reveal that the lysine riboswitch has >1000-fold specificity for lysine over other amino acids. The aptamer is highly sensitive to the precise placement of the ε-amino group and relatively tolerant of alterations to the main-chain functional groups in order to achieve this specificity. At low nucleotide triphosphate (NTP) concentrations, we observe good agreement between the half-maximal regulatory activity (T(50)) and the affinity of the receptor for lysine (K(d)), as well as many of its analogs. However, above 400 μM [NTP], the concentration of lysine required to elicit transcription termination rises, moving into the riboswitch into a kinetic control regime. These data demonstrate that, under physiologically relevant conditions, riboswitches can integrate both effector and NTP concentrations to generate a regulatory response appropriate for global metabolic state of the cell. PMID:22771573

  4. Assessing potential future environmental legislative, regulatory, and judicial events

    SciTech Connect

    Tonn, B.; Schweitzer, M.; Godfrey, G.; Wagner, C.; MacGregor, D.G.

    1998-03-01

    This report describes a methodology to proactively and methodically assess future potential environmental legislative, regulatory, and judicial events. This is an important endeavor because new, revised, and reauthorized legislation, proposed and final regulations, and outcomes of judicial proceedings have the potential to impose new actions, directions, and costs of many organizations in the United States (related to capital investments, operating approaches, and research and development) and to affect the quality of life. The electric power industry is particularly impacted by environmental regulatory events (the term `regulatory` is used to cover all the types of legal events listed above), as the generation, transmission, and distribution of electricity affects air and water quality, require disposal of solid, hazardous, and radioactive wastes, and at times, impacts wetlands and endangered species. Numerous potential regulatory events, such as the reauthorization of the Clean Water Act and new regulations associated with global climate change, can greatly affect the power industry. Organizations poised to respond proactively to such events will improve their competitive positions, reduce their costs in the long-term, and improve their public images.

  5. Macitentan: first global approval.

    PubMed

    Patel, Trina; McKeage, Kate

    2014-01-01

    Macitentan (Opsumit®) is a novel dual endothelin receptor antagonist (ERA) with sustained receptor binding properties developed by Actelion Pharmaceuticals Ltd. In October 2013, oral macitentan 10 mg once daily received its first global approval in the US, followed closely by Canada, for the treatment of pulmonary arterial hypertension (PAH). The drug has also received a positive opinion in the EU from the Committee for Medicinal Products for Human Use for the treatment of PAH, and is under regulatory review in several other countries for the same indication. Endothelin (ET)-1 influences pathological changes via two ET receptor subtypes (ETA and ETB), to which it binds with high affinity. ET-1 is implicated in several forms of vascular disease making it a valid target for the treatment of pulmonary vascular diseases such as PAH. Clinical development is underway for other indications, including Eisenmenger syndrome, ischaemic digital ulcers secondary to systemic sclerosis, and glioblastoma. Macitentan was also evaluated in idiopathic pulmonary fibrosis; however, a phase 2 trial did not meet its primary endpoint and further investigation in this indication was discontinued. Macitentan was developed by modifying the structure of bosentan in the search for an optimal dual ERA with improved efficacy and tolerability compared with other ERAs. This article summarizes the milestones in the development of macitentan leading to this first approval for PAH.

  6. Vortioxetine: first global approval.

    PubMed

    Gibb, Andrew; Deeks, Emma D

    2014-01-01

    Vortioxetine is an orally administered small molecule developed by Lundbeck A/S for the once-daily treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD). Vortioxetine received its first global approval for MDD in the USA in September 2013 and regulatory approval for its use in this indication in the EU (where it has received a positive opinion) and Canada is awaited. The drug is a bis-aryl-sulphanyl amine compound that combines serotonin (5-HT) reuptake inhibition with other characteristics, including receptor activity modulation. In vitro studies indicate that vortioxetine is an inhibitor of the 5-HT transporter and is a 5-HT(1D), 5-HT₃ and 5-HT₇ receptor antagonist, a 5-HT(1A) receptor agonist and a 5-HT(1B) receptor partial agonist. Animal and in vitro studies indicate that several neurotransmitter systems may be impacted by vortioxetine, with the drug enhancing levels of 5-HT, noradrenaline, dopamine, acetylcholine and histamine in certain areas of the brain, as well as modulating γ-aminobutyric acid and glutamate neurotransmission. Phase III trials of vortioxetine in both MDD and GAD have been conducted worldwide. This article summarizes the milestones in the development of vortioxetine leading to this first approval for MDD.

  7. Modeling human cancer-related regulatory modules by GA-RNN hybrid algorithms

    PubMed Central

    Chiang, Jung-Hsien; Chao, Shih-Yi

    2007-01-01

    Background Modeling cancer-related regulatory modules from gene expression profiling of cancer tissues is expected to contribute to our understanding of cancer biology as well as developments of new diagnose and therapies. Several mathematical models have been used to explore the phenomena of transcriptional regulatory mechanisms in Saccharomyces cerevisiae. However, the contemplating on controlling of feed-forward and feedback loops in transcriptional regulatory mechanisms is not resolved adequately in Saccharomyces cerevisiae, nor is in human cancer cells. Results In this study, we introduce a Genetic Algorithm-Recurrent Neural Network (GA-RNN) hybrid method for finding feed-forward regulated genes when given some transcription factors to construct cancer-related regulatory modules in human cancer microarray data. This hybrid approach focuses on the construction of various kinds of regulatory modules, that is, Recurrent Neural Network has the capability of controlling feed-forward and feedback loops in regulatory modules and Genetic Algorithms provide the ability of global searching of common regulated genes. This approach unravels new feed-forward connections in regulatory models by modified multi-layer RNN architectures. We also validate our approach by demonstrating that the connections in our cancer-related regulatory modules have been most identified and verified by previously-published biological documents. Conclusion The major contribution provided by this approach is regarding the chain influences upon a set of genes sequentially. In addition, this inverse modeling correctly identifies known oncogenes and their interaction genes in a purely data-driven way. PMID:17359522

  8. Global trends

    NASA Technical Reports Server (NTRS)

    Megie, G.; Chanin, M.-L.; Ehhalt, D.; Fraser, P.; Frederick, J. F.; Gille, J. C.; Mccormick, M. P.; Schoebert, M.; Bishop, L.; Bojkov, R. D.

    1990-01-01

    Measuring trends in ozone, and most other geophysical variables, requires that a small systematic change with time be determined from signals that have large periodic and aperiodic variations. Their time scales range from the day-to-day changes due to atmospheric motions through seasonal and annual variations to 11 year cycles resulting from changes in the sun UV output. Because of the magnitude of all of these variations is not well known and highly variable, it is necessary to measure over more than one period of the variations to remove their effects. This means that at least 2 or more times the 11 year sunspot cycle. Thus, the first requirement is for a long term data record. The second related requirement is that the record be consistent. A third requirement is for reasonable global sampling, to ensure that the effects are representative of the entire Earth. The various observational methods relevant to trend detection are reviewed to characterize their quality and time and space coverage. Available data are then examined for long term trends or recent changes in ozone total content and vertical distribution, as well as related parameters such as stratospheric temperature, source gases and aerosols.

  9. Global cooling?

    PubMed

    Damon, P E; Kunen, S M

    1976-08-01

    The world's inhabitants, including Scientists, live primarily in the Northern Hemisphere. It is quite natural to be concerned about events that occur close to home and neglect faraway events. Hence, it is not surprising that so little attention has been given to the Southern Hemisphere. Evidence for global cooling has been based, in large part, on a severe cooling trend at high northern latitudes. This article points out that the Northern Hemisphere cooling trend appears to be out of phase with a warming trend at high latitudes in the Southern Hemisphere. The data are scanty. We cannot be sure that these temperature fluctuations are be not the result of natural causes. How it seems most likely that human activity has already significantly perturbed the atmospheric weather system. The effect of particulate matter pollution should be most severe in the highly populated and industrialized Northern Hemisphere. Because of the rapid diffusion of CO(2) molecules within the atmosphere, both hemispheres will be subject to warming due to the atmospheric (greenhouse) effect as the CO(2) content of the atmosphere builds up from the combustion of fossil fuels. Because of the differential effects of the two major sources of atmospheric pollution, the CO(2) greenhouse effect warming trend should first become evident in the Southern Hemisphere. The socioeconomic and political consequences of climate change are profound. We need an early warning system such as would be provided by a more intensive international world weather watch, particularly at high northern and southern latitudes.

  10. Physiologically based pharmacokinetic modeling: from regulatory science to regulatory policy.

    PubMed

    Sinha, V; Zhao, P; Huang, S M; Zineh, I

    2014-05-01

    Assessment of controllable sources of intra- and interpatient variability in drug response is of critical importance in the regulatory evaluation of new drugs.(1) Although determinants of response variability would ideally be understood and accounted for before approval of a new pharmaceutical product, this is rarely the case for all; clinical trials in specific populations that definitively test optimal dosing in patient management strategies are not routinely performed prior to drug approval.

  11. Aphis and the accredited veterinarian. A partnership in regulatory medicine.

    PubMed

    Heamon, J A

    1993-09-01

    APHIS has a long history of partnership with the private practitioner in the veterinary accreditation program. The accreditation program is truly the backbone of the nation's regulatory programs for the prevention, control, and eradication of domestic livestock diseases. The United States' animal export program also relies heavily on the expertise, diligence, and integrity of the accredited practitioner. Accredited veterinarians provide assurance to regulatory officials, and clients, both within the United States and internationally that newly acquired animals will not introduce disease into the livestock population. With the approach of the twenty-first century and the continuing trend toward a global agricultural economy, it becomes even more imperative that APHIS and the accredited veterinarian work together to develop and maintain an active and sound partnership to enhance American agriculture. PMID:8236615

  12. Dynamic Gene Regulatory Networks Drive Hematopoietic Specification and Differentiation.

    PubMed

    Goode, Debbie K; Obier, Nadine; Vijayabaskar, M S; Lie-A-Ling, Michael; Lilly, Andrew J; Hannah, Rebecca; Lichtinger, Monika; Batta, Kiran; Florkowska, Magdalena; Patel, Rahima; Challinor, Mairi; Wallace, Kirstie; Gilmour, Jane; Assi, Salam A; Cauchy, Pierre; Hoogenkamp, Maarten; Westhead, David R; Lacaud, Georges; Kouskoff, Valerie; Göttgens, Berthold; Bonifer, Constanze

    2016-03-01

    Metazoan development involves the successive activation and silencing of specific gene expression programs and is driven by tissue-specific transcription factors programming the chromatin landscape. To understand how this process executes an entire developmental pathway, we generated global gene expression, chromatin accessibility, histone modification, and transcription factor binding data from purified embryonic stem cell-derived cells representing six sequential stages of hematopoietic specification and differentiation. Our data reveal the nature of regulatory elements driving differential gene expression and inform how transcription factor binding impacts on promoter activity. We present a dynamic core regulatory network model for hematopoietic specification and demonstrate its utility for the design of reprogramming experiments. Functional studies motivated by our genome-wide data uncovered a stage-specific role for TEAD/YAP factors in mammalian hematopoietic specification. Our study presents a powerful resource for studying hematopoiesis and demonstrates how such data advance our understanding of mammalian development. PMID:26923725

  13. Biomarkers for Alzheimer's disease: academic, industry and regulatory perspectives.

    PubMed

    Hampel, Harald; Frank, Richard; Broich, Karl; Teipel, Stefan J; Katz, Russell G; Hardy, John; Herholz, Karl; Bokde, Arun L W; Jessen, Frank; Hoessler, Yvonne C; Sanhai, Wendy R; Zetterberg, Henrik; Woodcock, Janet; Blennow, Kaj

    2010-07-01

    Advances in therapeutic strategies for Alzheimer's disease that lead to even small delays in onset and progression of the condition would significantly reduce the global burden of the disease. To effectively test compounds for Alzheimer's disease and bring therapy to individuals as early as possible there is an urgent need for collaboration between academic institutions, industry and regulatory organizations for the establishment of standards and networks for the identification and qualification of biological marker candidates. Biomarkers are needed to monitor drug safety, to identify individuals who are most likely to respond to specific treatments, to stratify presymptomatic patients and to quantify the benefits of treatments. Biomarkers that achieve these characteristics should enable objective business decisions in portfolio management and facilitate regulatory approval of new therapies.

  14. Principles of dynamical modularity in biological regulatory networks

    PubMed Central

    Deritei, Dávid; Aird, William C.; Ercsey-Ravasz, Mária; Regan, Erzsébet Ravasz

    2016-01-01

    Intractable diseases such as cancer are associated with breakdown in multiple individual functions, which conspire to create unhealthy phenotype-combinations. An important challenge is to decipher how these functions are coordinated in health and disease. We approach this by drawing on dynamical systems theory. We posit that distinct phenotype-combinations are generated by interactions among robust regulatory switches, each in control of a discrete set of phenotypic outcomes. First, we demonstrate the advantage of characterizing multi-switch regulatory systems in terms of their constituent switches by building a multiswitch cell cycle model which points to novel, testable interactions critical for early G2/M commitment to division. Second, we define quantitative measures of dynamical modularity, namely that global cell states are discrete combinations of switch-level phenotypes. Finally, we formulate three general principles that govern the way coupled switches coordinate their function. PMID:26979940

  15. Dynamic Gene Regulatory Networks Drive Hematopoietic Specification and Differentiation

    PubMed Central

    Goode, Debbie K.; Obier, Nadine; Vijayabaskar, M.S.; Lie-A-Ling, Michael; Lilly, Andrew J.; Hannah, Rebecca; Lichtinger, Monika; Batta, Kiran; Florkowska, Magdalena; Patel, Rahima; Challinor, Mairi; Wallace, Kirstie; Gilmour, Jane; Assi, Salam A.; Cauchy, Pierre; Hoogenkamp, Maarten; Westhead, David R.; Lacaud, Georges; Kouskoff, Valerie; Göttgens, Berthold; Bonifer, Constanze

    2016-01-01

    Summary Metazoan development involves the successive activation and silencing of specific gene expression programs and is driven by tissue-specific transcription factors programming the chromatin landscape. To understand how this process executes an entire developmental pathway, we generated global gene expression, chromatin accessibility, histone modification, and transcription factor binding data from purified embryonic stem cell-derived cells representing six sequential stages of hematopoietic specification and differentiation. Our data reveal the nature of regulatory elements driving differential gene expression and inform how transcription factor binding impacts on promoter activity. We present a dynamic core regulatory network model for hematopoietic specification and demonstrate its utility for the design of reprogramming experiments. Functional studies motivated by our genome-wide data uncovered a stage-specific role for TEAD/YAP factors in mammalian hematopoietic specification. Our study presents a powerful resource for studying hematopoiesis and demonstrates how such data advance our understanding of mammalian development. PMID:26923725

  16. Regulatory applications of sediment criteria. Final report

    SciTech Connect

    Not Available

    1987-06-23

    The report briefly describes the development of sediment criteria, discusses their utility and appropriate regulatory applications, and recommends steps to enhance the acceptance of sediment criteria by the regulatory and regulated communities.

  17. Plant Evolution: Evolving Antagonistic Gene Regulatory Networks.

    PubMed

    Cooper, Endymion D

    2016-06-20

    Developing a structurally complex phenotype requires a complex regulatory network. A new study shows how gene duplication provides a potential source of antagonistic interactions, an important component of gene regulatory networks. PMID:27326708

  18. Small Business Administration Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    ... businesses. Timetable: Action Date FR Cite NPRM 08/00/10 Regulatory Flexibility Analysis Required: Yes Agency... Manufacturing Assistance Act of 2004 (Reauthorization Act) to regulate Small Business Lending Companies (SBLCs... Part XVI Small Business Administration Semiannual Regulatory Agenda ] SMALL...

  19. 75 FR 61531 - Issuance of Regulatory Guide

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-05

    ... E. Norris, Component Integrity Branch, Division of Engineering, Office of Nuclear Regulatory... acceptable alternatives to requirements in the American Society of Mechanical Engineers (ASME) Boiler and.... Harriet Karagiannis, Acting Chief, Regulatory Guide Development Branch, Division of Engineering, Office...

  20. Plant Evolution: Evolving Antagonistic Gene Regulatory Networks.

    PubMed

    Cooper, Endymion D

    2016-06-20

    Developing a structurally complex phenotype requires a complex regulatory network. A new study shows how gene duplication provides a potential source of antagonistic interactions, an important component of gene regulatory networks.

  1. Nuclear Regulatory Commission 1989 Information Digest

    SciTech Connect

    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. Genetic flexibility of regulatory networks.

    PubMed

    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.

  3. Regulatory cells and transplantation tolerance.

    PubMed

    Cobbold, Stephen P; Waldmann, Herman

    2013-06-01

    Transplantation tolerance is a continuing therapeutic goal, and it is now clear that a subpopulation of T cells with regulatory activity (Treg) that express the transcription factor foxp3 are crucial to this aspiration. Although reprogramming of the immune system to donor-specific transplantation tolerance can be readily achieved in adult mouse models, it has yet to be successfully translated in human clinical practice. This requires that we understand the fundamental mechanisms by which donor antigen-specific Treg are induced and function to maintain tolerance, so that we can target therapies to enhance rather than impede these regulatory processes. Our current understanding is that Treg act via numerous molecular mechanisms, and critical underlying components such as mTOR inhibition, are only now emerging. PMID:23732858

  4. 21 CFR 500.88 - Regulatory method.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 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. 78 FR 44399 - Semiannual Regulatory Flexibility Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-23

    ... Capital, Implementation of Basel III, Minimum Regulatory Capital Ratios, Capital Adequacy, and Transition... leverage capital requirements. Timetable: Action Date FR Cite Board Requested Comment 08/30/12 77 FR 53059... Capital Rules: Regulatory Capital, Implementation of Basel III, Minimum Regulatory Capital Ratios,......

  6. Department of Energy Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    ... OF ENERGY Semiannual Regulatory Agenda 10 CFR Chs. II, III, and X 48 CFR Ch. 9 Regulatory Agenda... Review,'' 58 FR 51735, and the Regulatory Flexibility Act, 5 U.S.C. 601 et seq. SUPPLEMENTARY INFORMATION... and direct heating equipment. This is the second review for water heaters. Timetable: Action Date...

  7. 78 FR 1624 - Fall 2012 Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-08

    ... and not to existing residential wood-heating appliances. Timetable: Action Date FR Cite NPRM 06/00/13... that start up after the regulatory agenda is signed? H. What tools are available for mining regulatory..., ``Regulatory Planning and Review'' (58 FR 51735, Oct. 4, 1993), as supplemented by Executive Order (EO)...

  8. 78 FR 1594 - Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-08

    .... Timetable: Action Date FR Cite ANPRM 01/00/13 Regulatory Flexibility Analysis Required: Yes. Agency Contact...: Action Date FR Cite Final Action 12/00/12 Regulatory Flexibility Analysis Required: Yes. Agency Contact... idle facilities. Completed: Reason Date FR Cite Withdrawn 10/18/12 Regulatory Flexibility...

  9. 78 FR 23507 - Notice of Regulatory Review

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-19

    ... regulations may be made more effective and less burdensome. \\1\\ Regulatory Review Plan, 77 FR 10351 (Feb. 22...'s Director. \\2\\ Notice of Regulatory Review Plan, 76 FR 59066 (Sept. 23, 2011). \\3\\ Regulatory Review Plan, 77 FR 10351 (Feb. 22, 2012). This Notice initiates the first such review. II. Request...

  10. 21 CFR 500.88 - Regulatory method.

    Code of Federal Regulations, 2010 CFR

    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)...

  11. Securities and Exchange Commission Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    .... Timetable: Action Date FR Cite NPRM 03/00/11 Regulatory Flexibility Analysis Required: Yes Agency Contact...: Action Date FR Cite NPRM 12/00/10 Regulatory Flexibility Analysis Required: Yes Agency Contact: Jennifer... Date FR Cite NPRM 09/00/10 Regulatory Flexibility Analysis Required: Yes Agency Contact: Anthony...

  12. Summation from a regulatory perspective

    SciTech Connect

    Ohanian, E.V.; Cotruvo, J.A.

    1986-11-01

    There is an urgent need to discuss the Office of Drinking Water's standard-setting or rule making process since most of the researchers whose papers are presented here directly or indirectly play a crucial role in this complex undertaking. Therefore, this paper will address the research data required to support policy making and regulatory decisions pertaining to health effects of disinfectants and disinfection by-products.

  13. Regulatory motifs in Chk1

    PubMed Central

    Caparelli, Michael L.; O’Connell, Matthew J.

    2013-01-01

    Chk1 is the effector kinase of the G2 DNA damage checkpoint. Chk1 homologs possess a highly conserved N-terminal kinase domain and a less conserved C-terminal regulatory domain. In response to DNA damage, Chk1 is recruited to mediator proteins assembled at lesions on replication protein A (RPA)-coated single-stranded DNA (ssDNA). Chk1 is then activated by phosphorylation on S345 in the C-terminal regulatory domain by the PI3 kinase-related kinases ATM and ATR to enforce a G2 cell cycle arrest to allow time for DNA repair. Models have emerged in which this C-terminal phosphorylation relieves auto-inhibitory regulation of the kinase domain by the regulatory domain. However, experiments in fission yeast have shown that deletion of this putative auto-inhibitory domain actually inactivates Chk1 function. We show here that Chk1 homologs possess a kinase-associated 1 (KA1) domain that possesses residues previously implicated in Chk1 auto-inhibition. In addition, all Chk1 homologs have a small and highly conserved C-terminal extension (CTE domain). In fission yeast, both of these motifs are essential for Chk1 activation through interaction with the mediator protein Crb2, the homolog of human 53BP1. Thus, through different intra- and intermolecular interactions, these motifs explain why the regulatory domain exerts both positive and negative control over Chk1 activation. Such motifs may provide alternative targets to the ATP-binding pocket on which to dock Chk1 inhibitors as anticancer therapeutics. PMID:23422000

  14. Regulatory aspects of neutron radiography

    NASA Astrophysics Data System (ADS)

    Hammer, J.

    1999-11-01

    While full legislation for industrial radiography with gamma and X-rays already exists in many countries, the situation is different for neutron radiography. Therefore, the licensing for equipment and procedures in this field has to be based on basic principles of national and international rules. This contribution will explain how the regulatory body in Switzerland deals with neutron radiography installations in order to maintain national standards of health and safety.

  15. 77 FR 56686 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-13

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... interested persons. \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's... FINRA and at the Commission's Public Reference Room. II. Self-Regulatory Organization's Statement of...

  16. 78 FR 70602 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-26

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of Substance of the Proposed Rule... of the rules in accordance with the requirements of Form 19b-4. II. Self-Regulatory...

  17. A medical device regulatory framework - case study: South Africa.

    PubMed

    Poluta, Mladen A

    2006-01-01

    The regulation of medical devices is well-established in industrialized countries, with increasing global standardization and harmonization. In developing and resource-poor countries, however, there is a much greater degree of variability and implementation. For such countries, this paper suggests a comprehensive and integrated regulatory framework approach using the South African health technology policy framework as a basis for comparison and benchmarking. It is hoped that this compact model, which covers a wide range of HTM-related aspects, will be useful to governments and their partners, amongst other role-players.

  18. CONCEPT OF OPERATIONS PLANS for Phase I the INTERNATIONAL PILOT FOR Global Radiological source SORTING, Tracking, AND MONITORING (GradSStraM) Using eMERGING RFID AND WEB 2.0 TECHNOLOGIES TO PROVIDE TOTAL ASSET AND INFORMATION VISUALIZATIONA United states- European Union Lighthouse Priority Project for fostering trade and reducing regulatory burden

    SciTech Connect

    Walker, Randy M

    2009-01-01

    Thousands of shipments of radioisotopes developed in the United States (US) are transported domestically and internationally for medical and industrial applications, including to partner laboratories in European Union (EU) countries. Over the past five years, the Environmental Protection Agency (EPA), the Department of Energy (DOE), and Oak Ridge National Laboratory (ORNL) have worked with state regulatory compliance personnel, key private sector shippers and carriers, the Department of Homeland Security (DHS), the Department of Transportation (DOT), the Department of Defense (DoD) and the Nuclear Regulatory Commission (NRC) on Radio Frequency Identification (RFID) tracking and monitoring of medical and industrial radioisotopes in commerce. The EPA Radiological Source Tracking and Monitoring (RadSTraM) project tested, evaluated, and integrated RFID technologies in laboratory settings, and at multiple private-sector shipping and distribution facilities (Perkin Elmer and DHL) using common radioisotopes used in everyday commerce. The RFID tracking was also tested in association with other deployed technologies including radiation detection, chemical/explosives detection, advanced imaging, lasers, and infrared scanning. At the 2007 EU-US Summit, the leaders of the US Department of Commerce (DOC) and EU European Commission (EC) committed to pursue jointly directed Lighthouse Priority Projects. These projects are intended to 'foster cooperation' and 'reduce regulatory burdens' with respect to transatlantic commerce. The Transatlantic Economic Council (TEC) Lighthouse Project on Radio Frequency Identification (RFID) has been directed to 'develop a joint framework for cooperation on identification and development of best practices for Radio Frequency Identification (RFID) technologies.' The RFID Lighthouse Priority Project commits both sides to endeavor to align U.S. and EU regulatory and policy approaches on RFID technologies, including pilot projects in the public sector

  19. Global power: The big picture

    SciTech Connect

    Poirier, J.L.

    1996-12-31

    In this presentation, the author reviews the current activity in global power (GP) based on the most recent data gathered by Hagler Bailly which has maintained for the last five years a very comprehensive data base on global power transactions and project announcements. The firm has also worked with dozens of global power companies since 1990. The presentation reviews the trends in the number of GP closings for 1992-1995 and gives a preview of what the worldwide pipeline of activities looks like for the next 4-5 years. The analysis covers all GP activities (i.e., generation, distribution and transmission) as well as the various types of transactions that are taking place (i.e., greenfield projects, privatizations, secondary purchases). Key country markets are also highlighted. The author also presents a review of recent positive and negative developments in terms of regulatory changes, project cost trends, developers` project experiences, and financing issues. This systematic review serves as a preamble to the author`s projection of future GP market activity (e.g., number of closings by type of project through 2000). Finally, the author presents an updated view of the competition in the GP market including the number and various types of competitors; the newcomers; the winners and the losers; and the changes in leaders` market shares.

  20. 75 FR 28073 - Draft Regulatory Guide: Issuance, Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  1. 75 FR 48382 - Draft Regulatory Guide: Issuance, Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  2. 78 FR 44165 - Nuclear Regulatory Commission Enforcement Policy

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-23

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Nuclear Regulatory Commission Enforcement Policy AGENCY: Nuclear Regulatory Commission. ACTION: Enforcement policy; request for comment. SUMMARY: The U.S. Nuclear Regulatory Commission (NRC) is...

  3. 75 FR 16525 - Notice of Issuance of Regulatory Guide

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-01

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of... Branch, Division of Engineering, Office of Nuclear Regulatory Research, U.S. Nuclear...

  4. 75 FR 36715 - Final Regulatory Guide: Issuance, Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-28

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Final Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION.... Sturzebecher, U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001, telephone: (301) 251- 7494 or...

  5. Globalization and health: results and options.

    PubMed Central

    Cornia, G. A.

    2001-01-01

    The last two decades have witnessed the emergence and consolidation of an economic paradigm which emphasizes domestic deregulation and the removal of barriers to international trade and finance. If properly managed, such an approach can lead to perceptible gains in health status. Where markets are non-exclusionary, regulatory institutions strong and safety nets in place, globalization enhances the performance of countries with a good human and physical infrastructure but narrow domestic markets. Health gains in China, Costa Rica, the East Asian "tiger economies" and Viet Nam can be attributed in part to their growing access to global markets, savings and technology. However, for most of the remaining countries, many of them in Africa, Latin America and Eastern Europe, globalization has not lived up to its promises due to a combination of poor domestic conditions, an unequal distribution of foreign investments and the imposition of new conditions further limiting the access of their exports to the OECD markets. In these developing countries, the last twenty years have brought about a slow, unstable and unequal pattern of growth and stagnation in health indicators. Autarky is not the answer to this situation, but neither is premature, unconditional and unselective globalization. Further unilateral liberalization is unlikely to help them to improve their economic performance and health conditions. For them, a gradual and selective integration into the world economy linked to the removal of asymmetries in global markets and to the creation of democratic institutions of global governance is preferable to instant globalization. PMID:11584731

  6. Wetlands: The changing regulatory landscape

    SciTech Connect

    Glick, R.M. )

    1993-05-01

    Protection of wetlands became a national issue in 1988 when President George Bush pledged no net loss of wetlands in the US under his [open quotes]environmental presidency.[close quotes] As wetlands became a national issue, the job of protecting them became an obligation for many groups, including hydro-power developers. Now, when a site selected for development includes an area that may be classified as a wetland, the developer quickly discovers the importance of recognizing and protecting these natural habitats. Federal legislation severely limits development of wetland, and most states increase the restrictions with their own wetlands regulations. The difficulty of defining wetlands complicates federal and state enforcement. Land that appears to be dry may in fact be classified as a wetland. So, even if a site appears dry, potential hydro developers must confirm whether or not any jurisdictional wetlands are present. Regulated lands include much more than marshes and swamps. Further complicating the definition of wetlands, a recent court decision found that even artificially created wetlands, such as man-made ponds, may be subject to regulation. Hydro developers must be aware of current regulatory requirements before they consider development of any site that may contain wetlands. To be certain that a site is [open quotes]buildable[close quotes] from the standpoint of wetlands regulation, a developer must verify (with the help of state agencies) that the property does not contain any jurisdictional wetlands. If it does, the regulatory process before development becomes much more complicated. For the short term, uncertainty abounds and extreme caution is in order. Because the regulatory process has become so complex and an agreeable definition of wetlands so elusive, the trend among the Corps and collaborating agencies is to constrict nationwide permits in favor of narrowing the jurisdictional definition of wetlands.

  7. Human System Integration: Regulatory Analysis

    NASA Technical Reports Server (NTRS)

    2005-01-01

    This document was intended as an input to the Access 5 Policy Integrated Product team. Using a Human System Integration (HIS) perspective, a regulatory analyses of the FARS (specifically Part 91), the Airman s Information Manual (AIM) and the FAA Controllers Handbook (7110.65) was conducted as part of a front-end approach needed to derive HSI requirements for Unmanned Aircraft Systems (UAS) operations in the National Airspace System above FL430. The review of the above aviation reference materials yielded eighty-four functions determined to be necessary or highly desirable for flight within the Air Traffic Management System. They include categories for Flight, Communications, Navigation, Surveillance, and Hazard Avoidance.

  8. An estimation of the global burden of disease due to skin lesions caused by arsenic in drinking water.

    PubMed

    Fewtrell, Lorna; Fuge, Ron; Kay, David

    2005-06-01

    The global burden of disease due to skin lesions caused by arsenic in drinking water was estimated by combining country-based exposure data with selected exposure-response relationships derived from the literature. Populations were considered to be exposed to elevated arsenic levels if their drinking water contained arsenic concentrations of 50 microg I(-1) or greater. Elevated arsenic concentrations in drinking water result in a significant global burden of disease, even when confining the health outcome to skin lesions. The burden of disease was particularly marked in the World Health Organization (WHO) comparative risk assessment (CRA) 'Sear D' region, which includes Bangladesh, India and Nepal. Unsurprisingly, Bangladesh was the worst affected country with 143 disability adjusted life years (DALYs) per 1,000 population. Although this initial estimate is subject to a large degree of uncertainty, it does represent an important first step in allowing the comparison of the problem relating to elevated arsenic in drinking water to other environmental health outcomes.

  9. Drug-device combination products: regulatory landscape and market growth.

    PubMed

    Bayarri, L

    2015-08-01

    Combination products are therapeutic and diagnostic products that combine drugs, devices and/or biological products, leading to safer and more effective treatments thanks to careful and precise drug targeting, local administration and individualized therapy. These technologies can especially benefit patients suffering from serious diseases and conditions such as cancer, heart disease, multiple sclerosis and diabetes, among others. On the other hand, drug-device combination products have also introduced a new dynamic in medical product development, regulatory approval and corporate interaction. Due to the increasing integration of drugs and devices observed in the latest generation of combination products, regulatory agencies have developed specific competences and regulations over the last decade. Manufacturers are required to fully understand the specific requirements in each country in order to ensure timely and accurate market access of new combination products, and the development of combination products involves a very specific pattern of interactions between manufacturers and regulatory agencies. The increased sophistication of the products brought to market over the last couple of decades has accentuated the need to develop drugs and devices collaboratively using resources from both industries, fostering the need of business partnering and technology licensing. This review will provide a global overview of the market trends, as well as (in the last section) an analysis of the drug-device combination products approved by the FDA during the latest 5 years.

  10. Regulatory Match Effects on a Modified Wisconsin Card Sort Task

    PubMed Central

    Maddox, W. Todd; Filoteo, J. Vincent; Glass, Brian D.; Markman, Arthur B.

    2009-01-01

    The Wisconsin Card Sorting Task (WCST; Heaton, 1980) is commonly used to assess concept formation and set shifting. Cognitive research suggests that set shifting performance is enhanced by a match between a person’s regulatory focus (promotion focus: attempting to earn an entry into a cash drawing; prevention focus: attempting to avoid losing an entry into the drawing) and the task reward structure (gains: attempting to maximize points gained; losses: attempting to minimize points lost). A regulatory match results when attempting to earn an entry by maximizing points or attempting to avoid losing an entry by minimizing losses. We test the hypothesis that performance on a modified WCST is accentuated in younger, healthy participants when there is a match between the global performance incentive and the local task reward structure. As predicted, participants in a match showed better set shifting but equivalent initial concept formation when compared to participants in a mismatch. Further, relative to a baseline control group, mismatch participants were significantly worse at set shifting than were participants in a regulatory match. These results suggest that set shifting performance might be impacted by incentive and task reward factors in ways that have not been considered previously. PMID:20128935

  11. Drug-device combination products: regulatory landscape and market growth.

    PubMed

    Bayarri, L

    2015-08-01

    Combination products are therapeutic and diagnostic products that combine drugs, devices and/or biological products, leading to safer and more effective treatments thanks to careful and precise drug targeting, local administration and individualized therapy. These technologies can especially benefit patients suffering from serious diseases and conditions such as cancer, heart disease, multiple sclerosis and diabetes, among others. On the other hand, drug-device combination products have also introduced a new dynamic in medical product development, regulatory approval and corporate interaction. Due to the increasing integration of drugs and devices observed in the latest generation of combination products, regulatory agencies have developed specific competences and regulations over the last decade. Manufacturers are required to fully understand the specific requirements in each country in order to ensure timely and accurate market access of new combination products, and the development of combination products involves a very specific pattern of interactions between manufacturers and regulatory agencies. The increased sophistication of the products brought to market over the last couple of decades has accentuated the need to develop drugs and devices collaboratively using resources from both industries, fostering the need of business partnering and technology licensing. This review will provide a global overview of the market trends, as well as (in the last section) an analysis of the drug-device combination products approved by the FDA during the latest 5 years. PMID:26380388

  12. A dynamic and intricate regulatory network determines Pseudomonas aeruginosa virulence

    PubMed Central

    Balasubramanian, Deepak; Schneper, Lisa; Kumari, Hansi; Mathee, Kalai

    2013-01-01

    Pseudomonas aeruginosa is a metabolically versatile bacterium that is found in a wide range of biotic and abiotic habitats. It is a major human opportunistic pathogen causing numerous acute and chronic infections. The critical traits contributing to the pathogenic potential of P. aeruginosa are the production of a myriad of virulence factors, formation of biofilms and antibiotic resistance. Expression of these traits is under stringent regulation, and it responds to largely unidentified environmental signals. This review is focused on providing a global picture of virulence gene regulation in P. aeruginosa. In addition to key regulatory pathways that control the transition from acute to chronic infection phenotypes, some regulators have been identified that modulate multiple virulence mechanisms. Despite of a propensity for chaotic behaviour, no chaotic motifs were readily observed in the P. aeruginosa virulence regulatory network. Having a ‘birds-eye’ view of the regulatory cascades provides the forum opportunities to pose questions, formulate hypotheses and evaluate theories in elucidating P. aeruginosa pathogenesis. Understanding the mechanisms involved in making P. aeruginosa a successful pathogen is essential in helping devise control strategies. PMID:23143271

  13. U.S. perspective on mycotoxin regulatory issues.

    PubMed

    Park, Douglas L; Troxell, Terry C

    2002-01-01

    Control programs set up by the Food and Drug Administration (FDA) for aflatoxin, an unavoidable natural contaminant produced by specific molds that invade a number of feedstuffs and basic foods, provide an example of forces that affect risk assessment and management strategies by a regulatory agency. More recently, on an international scale, efforts to establish international food standards for fumonisin, deoxynivalenol, ochratoxin A, zearalenone, and patulin, as well as for aflatoxin, demonstrate the complexity of developing regulations and/or standards designed to protect consumer health and ensure fair trade practices on a global scale. Current FDA regulations for aflatoxins address public health concerns for potential contamination in basic foods, residues in milk, and animal feeds for numerous commodities and applications. Regulatory limits, sampling and analytical procedures, decontamination and/or diversion to less risk uses for contaminated product are components of mycotoxin control programs. Current efforts by FDA to establish regulatory controls for deoxynivalenol, fumonisin, and patulin add further insight on the role that safety and risk assessment procedures play in the development of action levels and advisories for mycotoxins.

  14. Regulatory RNAs in photosynthetic cyanobacteria.

    PubMed

    Kopf, Matthias; Hess, Wolfgang R

    2015-05-01

    Regulatory RNAs play versatile roles in bacteria in the coordination of gene expression during various physiological processes, especially during stress adaptation. Photosynthetic bacteria use sunlight as their major energy source. Therefore, they are particularly vulnerable to the damaging effects of excess light or UV irradiation. In addition, like all bacteria, photosynthetic bacteria must adapt to limiting nutrient concentrations and abiotic and biotic stress factors. Transcriptome analyses have identified hundreds of potential regulatory small RNAs (sRNAs) in model cyanobacteria such as Synechocystis sp. PCC 6803 or Anabaena sp. PCC 7120, and in environmentally relevant genera such as Trichodesmium, Synechococcus and Prochlorococcus. Some sRNAs have been shown to actually contain μORFs and encode short proteins. Examples include the 40-amino-acid product of the sml0013 gene, which encodes the NdhP subunit of the NDH1 complex. In contrast, the functional characterization of the non-coding sRNA PsrR1 revealed that the 131 nt long sRNA controls photosynthetic functions by targeting multiple mRNAs, providing a paradigm for sRNA functions in photosynthetic bacteria. We suggest that actuatons comprise a new class of genetic elements in which an sRNA gene is inserted upstream of a coding region to modify or enable transcription of that region.

  15. RSAT: regulatory sequence analysis tools.

    PubMed

    Thomas-Chollier, Morgane; Sand, Olivier; Turatsinze, Jean-Valéry; Janky, Rekin's; Defrance, Matthieu; Vervisch, Eric; Brohée, Sylvain; van Helden, Jacques

    2008-07-01

    The regulatory sequence analysis tools (RSAT, http://rsat.ulb.ac.be/rsat/) is a software suite that integrates a wide collection of modular tools for the detection of cis-regulatory elements in genome sequences. The suite includes programs for sequence retrieval, pattern discovery, phylogenetic footprint detection, pattern matching, genome scanning and feature map drawing. Random controls can be performed with random gene selections or by generating random sequences according to a variety of background models (Bernoulli, Markov). Beyond the original word-based pattern-discovery tools (oligo-analysis and dyad-analysis), we recently added a battery of tools for matrix-based detection of cis-acting elements, with some original features (adaptive background models, Markov-chain estimation of P-values) that do not exist in other matrix-based scanning tools. The web server offers an intuitive interface, where each program can be accessed either separately or connected to the other tools. In addition, the tools are now available as web services, enabling their integration in programmatic workflows. Genomes are regularly updated from various genome repositories (NCBI and EnsEMBL) and 682 organisms are currently supported. Since 1998, the tools have been used by several hundreds of researchers from all over the world. Several predictions made with RSAT were validated experimentally and published.

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

    PubMed

    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. Writing Technical Documents for the Global Pharmaceutical Industry.

    ERIC Educational Resources Information Center

    Bonk, Robert J.

    1998-01-01

    States that technical writers in the global pharmaceutical industry write for two audiences: regulatory agencies and healthcare practitioners. Contends that information products that address these audiences must balance the competing forces of business interests, market penetration, and the cultural variables of products so tied to people's…

  18. IMPACTS OF GLOBAL CLIMATE CHANGE ADAPTION ON SUSTAINABILITY

    EPA Science Inventory

    This presentation presents the potential impacts that global climate change may have on the quality and quantity of water available to drinking water and wastewater treatment systems and the adaptations these systems might have to employ in order to remain in regulatory complianc...

  19. Mechanistic Toxicology in the Face of Global Climate Change

    EPA Science Inventory

    To incorporate effects of global climate change (GCC) into regulatory assessments of chemical risk, damage and restoration needs, an understanding is needed of GCC effects on mechanisms of chemical toxicity and the implications of those effects when placed in context with GCC eff...

  20. The evolution of the regulatory framework for antibacterial agents.

    PubMed

    Rex, John H; Goldberger, Mark; Eisenstein, Barry I; Harney, Carrie

    2014-09-01

    The rising tide of antibacterial resistance and the lack of a diverse, vibrant pipeline of novel antibacterial agents is a global crisis that impairs our ability to treat life-threatening infections. The recent introduction of a tiered approach to the regulatory framework in this area offers one path to resolving some of the challenges. By drawing heavily on the predictive power of the related sciences of pharmacokinetics and pharmacodynamics, smaller, focused clinical trial programs have become possible for agents that might not otherwise have been possible to progress. There are limitations to these pathways, and they are not easy to implement, but making reliable noninferiority-based approaches available is critical to reinvigorating the global antibiotic pipeline. With the recognition of these ideas by key regulatory authorities in recent guidance, the next challenges in this area will focus on interpretive breakpoints, the extent of data in the prescribing information, ensuring that multiple agents can be progressed, and the challenge of the antibiotic business model.

  1. The evolution of the regulatory framework for antibacterial agents

    PubMed Central

    Rex, John H; Goldberger, Mark; Eisenstein, Barry I; Harney, Carrie

    2014-01-01

    The rising tide of antibacterial resistance and the lack of a diverse, vibrant pipeline of novel antibacterial agents is a global crisis that impairs our ability to treat life-threatening infections. The recent introduction of a tiered approach to the regulatory framework in this area offers one path to resolving some of the challenges. By drawing heavily on the predictive power of the related sciences of pharmacokinetics and pharmacodynamics, smaller, focused clinical trial programs have become possible for agents that might not otherwise have been possible to progress. There are limitations to these pathways, and they are not easy to implement, but making reliable noninferiority-based approaches available is critical to reinvigorating the global antibiotic pipeline. With the recognition of these ideas by key regulatory authorities in recent guidance, the next challenges in this area will focus on interpretive breakpoints, the extent of data in the prescribing information, ensuring that multiple agents can be progressed, and the challenge of the antibiotic business model. PMID:24797794

  2. MicroRNA and transcription factor mediated regulatory network for ovarian cancer: regulatory network of ovarian cancer.

    PubMed

    Ying, Huanchun; Lv, Jing; Ying, Tianshu; Li, Jun; Yang, Qing; Ma, Yuan

    2013-10-01

    A better understanding on the regulatory interactions of microRNA (miRNA) target genes and transcription factor (TF) target genes in ovarian cancer may be conducive for developing early diagnosis strategy. Thus, gene expression data and miRNA expression data were downloaded from The Cancer Genome Atlas in this study. Differentially expressed genes and miRNAs were selected out with t test, and Gene Ontology enrichment analysis was performed with DAVID tools. Regulatory interactions were retrieved from miRTarBase, TRED, and TRANSFAC, and then networks for miRNA target genes and TF target genes were constructed to globally present the mechanisms. As a result, a total of 1,939 differentially expressed genes were identified, and they were enriched in 28 functions, among which cell cycle was affected to the most degree. Besides, 213 differentially expressed miRNAs were identified. Two regulatory networks for miRNA target genes and TF target genes were established and then both were combined, in which E2F transcription factor 1, cyclin-dependent kinase inhibitor 1A, cyclin E1, and miR-16 were the hub genes. These genes may be potential biomarkers for ovarian cancer.

  3. An Attainable Global Perspective.

    ERIC Educational Resources Information Center

    de Castaneda, Viann Pedersen

    Concordia College (Minnesota) has established a global studies curriculum that encourages the development of a global perspective in future business leaders. Global perspective is seen as having five dimensions: (1) perspective consciousness; (2) "state of the planet" awareness; (3) cross-cultural awareness; (4) knowledge of global dynamics; and…

  4. Environmental Regulatory Update Table, January 1991

    SciTech Connect

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

    1991-02-01

    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, March 1989

    SciTech Connect

    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.

  6. Environmental regulatory update table, July 1991

    SciTech Connect

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

    1991-08-01

    This Environmental Regulatory Update Table (July 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.

  7. Environmental Regulatory Update Table, December 1990

    SciTech Connect

    Hawkins, G.T.; Houlberg, L.M.; Noghrei-Nikbakht, P.A.; Salk, M.S.

    1991-01-01

    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.

  8. Environmental Regulatory Update Table, November 1990

    SciTech Connect

    Hawkins, G.T.; Houlberg, L.M.; Noghrei-Nikbakht, P.A.; Salk, M.S.

    1990-12-01

    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. Environmental Regulatory Update Table, September 1990

    SciTech Connect

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

    1990-10-01

    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.

  10. Environmental Regulatory Update Table, October 1991

    SciTech Connect

    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.

  11. Environmental Regulatory Update Table, October 1990

    SciTech Connect

    Houlberg, L.M.; Noghrei-Nikbakht, P.A.; Salk, M.S.

    1990-11-01

    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.

  12. Environmental Regulatory Update Table, April 1989

    SciTech Connect

    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.

  13. Environmental Regulatory Update Table, December 1989

    SciTech Connect

    Houlbert, L.M.; Langston, M.E. ); Nikbakht, A.; Salk, M.S. )

    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.

  14. Environmental Regulatory Update Table, August 1991

    SciTech Connect

    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.

  15. Environmental Regulatory Update Table, December 1991

    SciTech Connect

    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.

  16. Environmental Regulatory Update Table, November 1991

    SciTech Connect

    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.

  17. Environmental Regulatory Update Table, September 1991

    SciTech Connect

    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.

  18. 21 CFR 26.18 - Regulatory collaboration.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... RECOGNITION OF PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE QUALITY SYSTEM AUDIT REPORTS... Specific Sector Provisions for Pharmaceutical Good Manufacturing Practices § 26.18 Regulatory...

  19. A genomic regulatory network for development

    NASA Technical Reports Server (NTRS)

    Davidson, Eric H.; Rast, Jonathan P.; Oliveri, Paola; Ransick, Andrew; Calestani, Cristina; Yuh, Chiou-Hwa; Minokawa, Takuya; Amore, Gabriele; Hinman, Veronica; Arenas-Mena, Cesar; Otim, Ochan; Brown, C. Titus; Livi, Carolina B.; Lee, Pei Yun; Revilla, Roger; Rust, Alistair G.; Pan, Zheng jun; Schilstra, Maria J.; Clarke, Peter J C.; Arnone, Maria I.; Rowen, Lee; Cameron, R. Andrew; McClay, David R.; Hood, Leroy; Bolouri, Hamid

    2002-01-01

    Development of the body plan is controlled by large networks of regulatory genes. A gene regulatory network that controls the specification of endoderm and mesoderm in the sea urchin embryo is summarized here. The network was derived from large-scale perturbation analyses, in combination with computational methodologies, genomic data, cis-regulatory analysis, and molecular embryology. The network contains over 40 genes at present, and each node can be directly verified at the DNA sequence level by cis-regulatory analysis. Its architecture reveals specific and general aspects of development, such as how given cells generate their ordained fates in the embryo and why the process moves inexorably forward in developmental time.

  20. Transcriptome Sequencing from Diverse Human Populations Reveals Differentiated Regulatory Architecture

    PubMed Central

    Lappalainen, Tuuli; Henn, Brenna M.; Kidd, Jeffrey M.; Yee, Muh-Ching; Grubert, Fabian; Cann, Howard M.; Snyder, Michael; Montgomery, Stephen B.; Bustamante, Carlos D.

    2014-01-01

    Large-scale sequencing efforts have documented extensive genetic variation within the human genome. However, our understanding of the origins, global distribution, and functional consequences of this variation is far from complete. While regulatory variation influencing gene expression has been studied within a handful of populations, the breadth of transcriptome differences across diverse human populations has not been systematically analyzed. To better understand the spectrum of gene expression variation, alternative splicing, and the population genetics of regulatory variation in humans, we have sequenced the genomes, exomes, and transcriptomes of EBV transformed lymphoblastoid cell lines derived from 45 individuals in the Human Genome Diversity Panel (HGDP). The populations sampled span the geographic breadth of human migration history and include Namibian San, Mbuti Pygmies of the Democratic Republic of Congo, Algerian Mozabites, Pathan of Pakistan, Cambodians of East Asia, Yakut of Siberia, and Mayans of Mexico. We discover that approximately 25.0% of the variation in gene expression found amongst individuals can be attributed to population differences. However, we find few genes that are systematically differentially expressed among populations. Of this population-specific variation, 75.5% is due to expression rather than splicing variability, and we find few genes with strong evidence for differential splicing across populations. Allelic expression analyses indicate that previously mapped common regulatory variants identified in eight populations from the International Haplotype Map Phase 3 project have similar effects in our seven sampled HGDP populations, suggesting that the cellular effects of common variants are shared across diverse populations. Together, these results provide a resource for studies analyzing functional differences across populations by estimating the degree of shared gene expression, alternative splicing, and regulatory genetics

  1. Immunometabolism of regulatory T cells

    PubMed Central

    Newton, Ryan; Priyadharshini, Bhavana; Turka, Laurence A

    2016-01-01

    The bidirectional interaction between the immune system and whole-body metabolism has been well recognized for many years. Via effects on adipocytes and hepatocytes, immune cells can modulate whole-body metabolism (in metabolic syndromes such as type 2 diabetes and obesity) and, reciprocally, host nutrition and commensal-microbiota-derived metabolites modulate immunological homeostasis. Studies demonstrating the metabolic similarities of proliferating immune cells and cancer cells have helped give birth to the new field of immunometabolism, which focuses on how the cell-intrinsic metabolic properties of lymphocytes and macrophages can themselves dictate the fate and function of the cells and eventually shape an immune response. We focus on this aspect here, particularly as it relates to regulatory T cells. PMID:27196520

  2. Regulatory Analysis of Reactivity Transients

    SciTech Connect

    Beyer, Carl E.; Clifford, Paul M.; Geelhood, Kenneth J.; Voglewede, John C.

    2009-08-01

    This paper will describe modifications made to the FRAPCON-3 and FRAPTRAN fuel performance codes and models that impact reactivity initiated accident (RIA) analyses. The modified models include an upper bound empirical and best estimate release models for fast transients, and a revised fuel failure model that accounts for ductile and brittle failure. Because experimental data exists for discrete test conditions, the codes and models are used to interpolate and to some extent, to extrapolate these test conditions. An upper bound empirical model for release is used to establish new recommended release fractions for long-lived and short lived (radioactive) isotopes for RIA events in Regulatory Guide 1.183. A best estimate release model is used in FRAPTRAN 1.4 based on grain boundary gas concentrations from FRAPCON-3.4 to predict release for RIA events. Code and model predictions will be compared to failure and release data from RIA tests to demonstrate accuracy.

  3. Regulatory aspects of clinical xenotransplantation.

    PubMed

    Schuurman, Henk-Jan

    2015-11-01

    Xenotransplantation attracted interest from regulatory authorities, particularly after the demonstration of pig-to-human transmission of porcine endogenous retrovirus (1996). This added to the risk of a product, resulting in a Guidance of the US Food and Drug Administration (2003). This addresses the full flow chart in product manufacturing, starting with the designated pathogen-free status of the source animal; and special aspects regarding the recipient like informed consent and monitoring for infectious pathogens. Also archiving of records from the donor and recipient, as well as storage of samples is described. The European Medicines Agency issued a Guideline on xenogeneic cell therapy products (2009). Cell-based medicinal products are subject to specific regulations and directives, which apply also to xenogeneic products: the xenotransplant guidances/guidelines are an addition to these regulations. Noteworthy, acellular products like heart valves and decellularized cornea are not considered a cell therapy product, but rather a medical device with its own regulation. WHO issued relevant documents, especially about safety, and the International Xenotransplantation Association published consensus documents, a.o., addressing preclinical efficacy requirements before entering clinical trials. This manuscript presents an overview of the regulatory framework, with special focus on cell therapy products necause these are expected to reach the market first (i.e., pancreatic islets, hepatocytes and cellularized cornea); major illustrations are from the European situation. Albeit being complex, the regulation of xenotransplant products does not form a block in product development, but rather supports the introduction of efficacious and safe products to meet the medical need.

  4. Small regulatory RNAs in Archaea.

    PubMed

    Babski, Julia; Maier, Lisa-Katharina; Heyer, Ruth; Jaschinski, Katharina; Prasse, Daniela; Jäger, Dominik; Randau, Lennart; Schmitz, Ruth A; Marchfelder, Anita; Soppa, Jörg

    2014-01-01

    Small regulatory RNAs (sRNAs) are universally distributed in all three domains of life, Archaea, Bacteria, and Eukaryotes. In bacteria, sRNAs typically function by binding near the translation start site of their target mRNAs and thereby inhibit or activate translation. In eukaryotes, miRNAs and siRNAs typically bind to the 3'-untranslated region (3'-UTR) of their target mRNAs and influence translation efficiency and/or mRNA stability. In archaea, sRNAs have been identified in all species investigated using bioinformatic approaches, RNomics, and RNA-Seq. Their size can vary significantly between less than 50 to more than 500 nucleotides. Differential expression of sRNA genes has been studied using northern blot analysis, microarrays, and RNA-Seq. In addition, biological functions have been unraveled by genetic approaches, i.e., by characterization of designed mutants. As in bacteria, it was revealed that archaeal sRNAs are involved in many biological processes, including metabolic regulation, adaptation to extreme conditions, stress responses, and even in regulation of morphology and cellular behavior. Recently, the first target mRNAs were identified in archaea, including one sRNA that binds to the 5'-region of two mRNAs in Methanosarcina mazei Gö1 and a few sRNAs that bind to 3'-UTRs in Sulfolobus solfataricus, three Pyrobaculum species, and Haloferax volcanii, indicating that archaeal sRNAs appear to be able to target both the 5'-UTR or the 3'-UTRs of their respective target mRNAs. In addition, archaea contain tRNA-derived fragments (tRFs), and one tRF has been identified as a major ribosome-binding sRNA in H. volcanii, which downregulates translation in response to stress. Besides regulatory sRNAs, archaea contain further classes of sRNAs, e.g., CRISPR RNAs (crRNAs) and snoRNAs.

  5. Globalization and human cooperation.

    PubMed

    Buchan, Nancy R; Grimalda, Gianluca; Wilson, Rick; Brewer, Marilynn; Fatas, Enrique; Foddy, Margaret

    2009-03-17

    Globalization magnifies the problems that affect all people and that require large-scale human cooperation, for example, the overharvesting of natural resources and human-induced global warming. However, what does globalization imply for the cooperation needed to address such global social dilemmas? Two competing hypotheses are offered. One hypothesis is that globalization prompts reactionary movements that reinforce parochial distinctions among people. Large-scale cooperation then focuses on favoring one's own ethnic, racial, or language group. The alternative hypothesis suggests that globalization strengthens cosmopolitan attitudes by weakening the relevance of ethnicity, locality, or nationhood as sources of identification. In essence, globalization, the increasing interconnectedness of people worldwide, broadens the group boundaries within which individuals perceive they belong. We test these hypotheses by measuring globalization at both the country and individual levels and analyzing the relationship between globalization and individual cooperation with distal others in multilevel sequential cooperation experiments in which players can contribute to individual, local, and/or global accounts. Our samples were drawn from the general populations of the United States, Italy, Russia, Argentina, South Africa, and Iran. We find that as country and individual levels of globalization increase, so too does individual cooperation at the global level vis-à-vis the local level. In essence, "globalized" individuals draw broader group boundaries than others, eschewing parochial motivations in favor of cosmopolitan ones. Globalization may thus be fundamental in shaping contemporary large-scale cooperation and may be a positive force toward the provision of global public goods. PMID:19255433

  6. Globalization and human cooperation.

    PubMed

    Buchan, Nancy R; Grimalda, Gianluca; Wilson, Rick; Brewer, Marilynn; Fatas, Enrique; Foddy, Margaret

    2009-03-17

    Globalization magnifies the problems that affect all people and that require large-scale human cooperation, for example, the overharvesting of natural resources and human-induced global warming. However, what does globalization imply for the cooperation needed to address such global social dilemmas? Two competing hypotheses are offered. One hypothesis is that globalization prompts reactionary movements that reinforce parochial distinctions among people. Large-scale cooperation then focuses on favoring one's own ethnic, racial, or language group. The alternative hypothesis suggests that globalization strengthens cosmopolitan attitudes by weakening the relevance of ethnicity, locality, or nationhood as sources of identification. In essence, globalization, the increasing interconnectedness of people worldwide, broadens the group boundaries within which individuals perceive they belong. We test these hypotheses by measuring globalization at both the country and individual levels and analyzing the relationship between globalization and individual cooperation with distal others in multilevel sequential cooperation experiments in which players can contribute to individual, local, and/or global accounts. Our samples were drawn from the general populations of the United States, Italy, Russia, Argentina, South Africa, and Iran. We find that as country and individual levels of globalization increase, so too does individual cooperation at the global level vis-à-vis the local level. In essence, "globalized" individuals draw broader group boundaries than others, eschewing parochial motivations in favor of cosmopolitan ones. Globalization may thus be fundamental in shaping contemporary large-scale cooperation and may be a positive force toward the provision of global public goods.

  7. Health, globalization and developing countries.

    PubMed

    Cilingiroglu, Nesrin

    2005-02-01

    In health care today, scientific and technological frontiers are expanding at unprecedented rates, even as economic and financial pressures shrink profit margins, intensify competition, and constrain the funds available for investment. Therefore, the world today has more economic, and social opportunities for people than 10 or 100 years since globalization has created a new ground somewhat characterized by rapid economic transformation, deregulation of national markets by new trade regimes, amazing transport, electronic communication possibilities and high turnover of foreign investment and capital flow as well as skilled labor. These trends can easily mask great inequalities in developing countries such as importation and spreading of infectious and non-communicable diseases; miniaturization of movement of medical technology; health sector trades management driven by economics without consideration to the social and health aspects and its effects, increasing health inequalities and their economic and social burden creation; multinational companies' cheap labor employment promotion in widening income differentials; and others. As a matter of fact, all these factors are major determinants of ill health. Health authorities of developing countries have to strengthen their regulatory framework in order to ensure that national health systems derive maximum benefit in terms of equity, quality and efficiency, while reducing potential social cost to a minimum generated risky side of globalization. PMID:15770290

  8. Health, globalization and developing countries.

    PubMed

    Cilingiroglu, Nesrin

    2005-02-01

    In health care today, scientific and technological frontiers are expanding at unprecedented rates, even as economic and financial pressures shrink profit margins, intensify competition, and constrain the funds available for investment. Therefore, the world today has more economic, and social opportunities for people than 10 or 100 years since globalization has created a new ground somewhat characterized by rapid economic transformation, deregulation of national markets by new trade regimes, amazing transport, electronic communication possibilities and high turnover of foreign investment and capital flow as well as skilled labor. These trends can easily mask great inequalities in developing countries such as importation and spreading of infectious and non-communicable diseases; miniaturization of movement of medical technology; health sector trades management driven by economics without consideration to the social and health aspects and its effects, increasing health inequalities and their economic and social burden creation; multinational companies' cheap labor employment promotion in widening income differentials; and others. As a matter of fact, all these factors are major determinants of ill health. Health authorities of developing countries have to strengthen their regulatory framework in order to ensure that national health systems derive maximum benefit in terms of equity, quality and efficiency, while reducing potential social cost to a minimum generated risky side of globalization.

  9. Regulatory fit messages and physical activity motivation.

    PubMed

    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.

  10. 77 FR 42419 - Airworthiness Directives; Honeywell International, Inc. Global Navigation Satellite Sensor Units

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-19

    ... ``significant rule'' under DOT Regulatory Policies and Procedures (44 FR 11034, February 26, 1979), (3) Will not... International, Inc. Global Navigation Satellite Sensor Units AGENCY: Federal Aviation Administration (FAA), DOT... augmentation system (WAAS) global navigation satellite sensor units (GNSSU). This AD requires you cease...

  11. Proceedings of GLOBAL 2013: International Nuclear Fuel Cycle Conference - Nuclear Energy at a Crossroads

    SciTech Connect

    2013-07-01

    The Global conference is a forum for the discussion of the scientific, technical, social and regulatory aspects of the nuclear fuel cycle. Relevant topics include global utilization of nuclear energy, current fuel cycle technologies, advanced reactors, advanced fuel cycles, nuclear nonproliferation and public acceptance.

  12. Power and Networks in Worldwide Knowledge Coordination: The Case of Global Science

    ERIC Educational Resources Information Center

    King, Roger

    2011-01-01

    The article considers the global governance of knowledge systems, exploring concepts of power, networks, standards (defined as normative practices), and structuration. The focus is on science as a form of predominantly private global governance, particularly the self-regulatory and collaborative processes stretching across time and space. These…

  13. E-Business Reporting: Towards a Global Standard for Financial Reporting Systems Using XBRL

    ERIC Educational Resources Information Center

    Long, Margaret J.

    2013-01-01

    Reporting systems can provide transparency into financial markets necessary for a sustainable, prosperous global economy. The most widely used global platform for exchanging electronic information about companies to regulatory bodies is XBRL. Standards for this platform are in the process of becoming legally harmonized, but not all countries are…

  14. Regulatory Compliance Requirements for an Open Source Electronic Image Trial Management System

    PubMed Central

    Rhodes, Colin; Moore, Steve; Clark, Ken; Maffitt, David; Perry, John; Handzel, Toni; Prior, Fred

    2015-01-01

    There is a global need for software to manage imaging based clinical trials to speed basic research and drug development. Such a system must comply with regulatory requirements. The U.S. Food and Drug Administration (FDA) has regulations regarding software development process controls and data provenance tracking. A key unanswered problem is the identification of which data changes are significant given a workflow model for image trial management. We report on the results of our study of provenance tracking requirements and define an architecture and software development process that meets U.S. regulatory requirements using open source software components. PMID:21097264

  15. 75 FR 71166 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-22

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... thereunder,\\2\\ notice is hereby given that on November 1, 2010, Financial Industry Regulatory Authority, Inc... similar status or performing similar functions, or a natural person engaged in the investment banking...

  16. 76 FR 59751 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-27

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... thereunder,\\2\\ notice is hereby given that on September 7, 2011, Financial Industry Regulatory Authority, Inc...), or are subject to a separate registration and qualification requirement, Investment...

  17. 77 FR 61647 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-10

    ... turn transactions in security futures. \\12\\ 15 U.S.C. 78o-3(b)(5). B. Self-Regulatory Organization's... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... in Security Futures October 3, 2012. Pursuant to Section 19(b)(1) of the Securities Exchange Act...

  18. 75 FR 53998 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-02

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Amend the Security Futures Risk Disclosure Statement.... \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of...

  19. 76 FR 37384 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  20. 76 FR 60567 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-29

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... Reporting Rules for Certain Alternative Trading Systems September 23, 2011. Pursuant to Section 19(b)(1) of... that on September 16, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed...

  1. 76 FR 71404 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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...

  2. 78 FR 30384 - Federal Regulatory Enforcement Fairness Hearing; Region X Regulatory Fairness Board

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-22

    ... ADMINISTRATION Federal Regulatory Enforcement Fairness Hearing; Region X Regulatory Fairness Board AGENCY: U.S. Small Business Administration (SBA). ACTION: Notice of open meeting of the Regional (Region X) Small... requested. Anyone wishing to attend and/or make a presentation to the Region X Regulatory Fairness...

  3. 77 FR 14052 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-08

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... Change in Ownership, Control, or Business Operations) To Adopt New Standardized Electronic Form CMA March.... 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of...

  4. 75 FR 39603 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-09

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving... Exchange Act Release No. 61189 (December 17, 2009), 74 FR 68648 (``Notice''). \\4\\ See Letter to Elizabeth M... obligations, if applicable, to the Commission or other regulatory authority; (3) FINRA has actual...

  5. 75 FR 49542 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    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... members in a timely fashion to facilitate its Regulation M compliance program. Rule 5190(d) sets forth...

  6. 75 FR 74766 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-01

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and..., Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission...\\ See Exchange Act Release No. 62434 (July 1, 2010; 75 FR 39603 (July 9, 2010); SR-FINRA-2009-089...

  7. Transforming Academic Globalization into Globalization for All

    ERIC Educational Resources Information Center

    Ramalhoto, M. F.

    2006-01-01

    Driving innovation and continuous improvement with regard to ecological, environmental and human sustainability is essential for win-win globalization. That calls for research on strategic and monitoring planning to manage globalization and technological and scientific change. This paper describes a new basic function of the university institution…

  8. Large-scale modeling of condition-specific gene regulatory networks by information integration and inference

    PubMed Central

    Ellwanger, Daniel Christian; Leonhardt, Jörn Florian; Mewes, Hans-Werner

    2014-01-01

    Understanding how regulatory networks globally coordinate the response of a cell to changing conditions, such as perturbations by shifting environments, is an elementary challenge in systems biology which has yet to be met. Genome-wide gene expression measurements are high dimensional as these are reflecting the condition-specific interplay of thousands of cellular components. The integration of prior biological knowledge into the modeling process of systems-wide gene regulation enables the large-scale interpretation of gene expression signals in the context of known regulatory relations. We developed COGERE (http://mips.helmholtz-muenchen.de/cogere), a method for the inference of condition-specific gene regulatory networks in human and mouse. We integrated existing knowledge of regulatory interactions from multiple sources to a comprehensive model of prior information. COGERE infers condition-specific regulation by evaluating the mutual dependency between regulator (transcription factor or miRNA) and target gene expression using prior information. This dependency is scored by the non-parametric, nonlinear correlation coefficient η2 (eta squared) that is derived by a two-way analysis of variance. We show that COGERE significantly outperforms alternative methods in predicting condition-specific gene regulatory networks on simulated data sets. Furthermore, by inferring the cancer-specific gene regulatory network from the NCI-60 expression study, we demonstrate the utility of COGERE to promote hypothesis-driven clinical research.

  9. Large-scale modeling of condition-specific gene regulatory networks by information integration and inference.

    PubMed

    Ellwanger, Daniel Christian; Leonhardt, Jörn Florian; Mewes, Hans-Werner

    2014-12-01

    Understanding how regulatory networks globally coordinate the response of a cell to changing conditions, such as perturbations by shifting environments, is an elementary challenge in systems biology which has yet to be met. Genome-wide gene expression measurements are high dimensional as these are reflecting the condition-specific interplay of thousands of cellular components. The integration of prior biological knowledge into the modeling process of systems-wide gene regulation enables the large-scale interpretation of gene expression signals in the context of known regulatory relations. We developed COGERE (http://mips.helmholtz-muenchen.de/cogere), a method for the inference of condition-specific gene regulatory networks in human and mouse. We integrated existing knowledge of regulatory interactions from multiple sources to a comprehensive model of prior information. COGERE infers condition-specific regulation by evaluating the mutual dependency between regulator (transcription factor or miRNA) and target gene expression using prior information. This dependency is scored by the non-parametric, nonlinear correlation coefficient η(2) (eta squared) that is derived by a two-way analysis of variance. We show that COGERE significantly outperforms alternative methods in predicting condition-specific gene regulatory networks on simulated data sets. Furthermore, by inferring the cancer-specific gene regulatory network from the NCI-60 expression study, we demonstrate the utility of COGERE to promote hypothesis-driven clinical research.

  10. Department of Labor Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    ... Date FR Cite ANPRM 12/00/10 Regulatory Flexibility Analysis Required: Undetermined Government Levels...: Action Date FR Cite NPRM 12/00/10 Regulatory Flexibility Analysis Required: Undetermined Government..., 202, 205, 211, 301, 302, and 303 of EO 11246, as amended; 30 FR 12319; 32 FR 14303, as amended by...

  11. 47 CFR 101.533 - Regulatory status.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false Regulatory status. 101.533 Section 101.533 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES 24 GHz Service and Digital Electronic Message Service § 101.533 Regulatory status. (a)...

  12. 47 CFR 101.533 - Regulatory status.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 5 2011-10-01 2011-10-01 false Regulatory status. 101.533 Section 101.533 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES 24 GHz Service and Digital Electronic Message Service § 101.533 Regulatory status. (a)...

  13. 47 CFR 27.10 - Regulatory status.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 2 2011-10-01 2011-10-01 false Regulatory status. 27.10 Section 27.10 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Applications and Licenses § 27.10 Regulatory status. The following rules apply...

  14. 47 CFR 27.10 - Regulatory status.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 2 2014-10-01 2014-10-01 false Regulatory status. 27.10 Section 27.10 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Applications and Licenses § 27.10 Regulatory status. The following rules apply...

  15. 47 CFR 27.10 - Regulatory status.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 2 2013-10-01 2013-10-01 false Regulatory status. 27.10 Section 27.10 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Applications and Licenses § 27.10 Regulatory status. The following rules apply...

  16. 47 CFR 90.1309 - Regulatory status.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 5 2012-10-01 2012-10-01 false Regulatory status. 90.1309 Section 90.1309 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES PRIVATE LAND MOBILE RADIO SERVICES Wireless Broadband Services in the 3650-3700 MHz Band § 90.1309 Regulatory...

  17. 47 CFR 27.10 - Regulatory status.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Regulatory status. 27.10 Section 27.10 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Applications and Licenses § 27.10 Regulatory status. The following rules apply...

  18. 47 CFR 27.10 - Regulatory status.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 2 2012-10-01 2012-10-01 false Regulatory status. 27.10 Section 27.10 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES MISCELLANEOUS WIRELESS COMMUNICATIONS SERVICES Applications and Licenses § 27.10 Regulatory status. The following rules apply...

  19. Department of Transportation Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    ... continues to have a SEIOSNOSE. Amendment No. 125-10 Amendment No. 125-10 required digital flight data... with Executive Order 12866 ``Regulatory Planning and Review'' (58 FR 51735; October 4, 1993) and the Department's Regulatory Policies and Procedures (44 FR 11034; February 26, 1979), the Department prepares...

  20. Federal Trade Commission Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-20

    ... and Review'' of September 30, 1993, 58 FR 51735 (Oct. 4, 1993). This edition of the Unified Agenda of..., ``Federalism,'' of August 4, 1999, 64 FR 43255 (Aug. 10, 1999), which does not apply to independent regulatory...'s Telemarketing Sales Rule (TSR or Rule) to address the sale of debt relief services (74 FR...

  1. 5 CFR 340.201 - Regulatory requirements.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 340.201 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS OTHER THAN FULL-TIME CAREER EMPLOYMENT (PART-TIME, SEASONAL, ON-CALL, AND INTERMITTENT) Regulatory Requirements-Part-Time Employment § 340.201 Regulatory requirements. This subpart contains the regulations of...

  2. 5 CFR 340.201 - Regulatory requirements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 340.201 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS OTHER THAN FULL-TIME CAREER EMPLOYMENT (PART-TIME, SEASONAL, ON-CALL, AND INTERMITTENT) Regulatory Requirements-Part-Time Employment § 340.201 Regulatory requirements. This subpart contains the regulations of...

  3. Department of Defense Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    ... American Act. Timetable: Action Date FR Cite NPRM 06/00/10 Regulatory Flexibility Analysis Required: Yes... DoD oversight of contractor business systems. Timetable: Action Date FR Cite NPRM 01/15/10 75 FR 2457... Part V Department of Defense Semiannual Regulatory Agenda ] DEPARTMENT OF DEFENSE (DOD)...

  4. Environmental Protection Agency Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    ...:// Not in FR www.epa.gov/lawsregs/search/regagenda.html Semiannual Regulatory Flexibility Agenda www....html issue ] Monthly Action Initiation List http://www.regulations.gov/fdmspublic/component/ Not in FR... Rulemaking Gateway www.epa.gov/rulemaking/ Not in FR B. What Are EPA's Regulatory Goals, and What...

  5. 75 FR 79843 - Fall 2010 Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-20

    ... Locations Location Semiannual Regulatory Agenda www.reginfo.gov/, www.regulations.gov, and http:// Not in FR.../component/ Not in FR main?main=DocketDetail& d=EPA-HQ-OA-2008-0265 and http:// www.epa.gov/lawsregs/ search/ail.html Rulemaking Gateway www.epa.gov/rulemaking/ Not in FR B. What Are EPA's Regulatory...

  6. 5 CFR 847.102 - Regulatory structure.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 2 2012-01-01 2012-01-01 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...

  7. 40 CFR 92.6 - Regulatory structure.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... and locomotive engines for which the regulations of this part (i.e., 40 CFR part 92) apply are... 40 Protection of Environment 20 2014-07-01 2013-07-01 true Regulatory structure. 92.6 Section 92.6... Locomotives and Locomotive Engines § 92.6 Regulatory structure. This section provides an overview of...

  8. 5 CFR 847.102 - Regulatory structure.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 2 2011-01-01 2011-01-01 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...

  9. 40 CFR 92.6 - Regulatory structure.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... locomotives and locomotive engines for which the regulations of this part (i.e., 40 CFR part 92) apply are... 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...

  10. 5 CFR 880.102 - Regulatory structure.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 2 2014-01-01 2014-01-01 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...

  11. 5 CFR 880.102 - Regulatory structure.

    Code of Federal Regulations, 2010 CFR

    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...

  12. 40 CFR 94.6 - Regulatory structure.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... emissions from in-use marine engines. (b) The engines for which the regulations of this part (i.e., 40 CFR... 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...

  13. 5 CFR 880.102 - Regulatory structure.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 2 2012-01-01 2012-01-01 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...

  14. 40 CFR 94.6 - Regulatory structure.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... emissions from in-use marine engines. (b) The engines for which the regulations of this part (i.e., 40 CFR... 40 Protection of Environment 20 2011-07-01 2011-07-01 false Regulatory structure. 94.6 Section 94... for Compression-Ignition Marine Engines § 94.6 Regulatory structure. This section provides an...

  15. 5 CFR 847.102 - Regulatory structure.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 2 2014-01-01 2014-01-01 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...

  16. 40 CFR 94.6 - Regulatory structure.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... emissions from in-use marine engines. (b) The engines for which the regulations of this part (i.e., 40 CFR... 40 Protection of Environment 21 2013-07-01 2013-07-01 false Regulatory structure. 94.6 Section 94... for Compression-Ignition Marine Engines § 94.6 Regulatory structure. This section provides an...

  17. 5 CFR 847.102 - Regulatory structure.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 2 2013-01-01 2013-01-01 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...

  18. 5 CFR 847.102 - Regulatory structure.

    Code of Federal Regulations, 2010 CFR

    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...

  19. 40 CFR 94.6 - Regulatory structure.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... emissions from in-use marine engines. (b) The engines for which the regulations of this part (i.e., 40 CFR... 40 Protection of Environment 21 2012-07-01 2012-07-01 false Regulatory structure. 94.6 Section 94... for Compression-Ignition Marine Engines § 94.6 Regulatory structure. This section provides an...

  20. 5 CFR 880.102 - Regulatory structure.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 2 2013-01-01 2013-01-01 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. 40 CFR 94.6 - Regulatory structure.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... in-use marine engines. (b) The engines for which the regulations of this part (i.e., 40 CFR part 94... 40 Protection of Environment 20 2014-07-01 2013-07-01 true Regulatory structure. 94.6 Section 94.6... Compression-Ignition Marine Engines § 94.6 Regulatory structure. This section provides an overview of...

  2. 5 CFR 880.102 - Regulatory structure.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 2 2011-01-01 2011-01-01 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...

  3. 40 CFR 92.6 - Regulatory structure.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... locomotives and locomotive engines for which the regulations of this part (i.e., 40 CFR part 92) apply are... 40 Protection of Environment 20 2011-07-01 2011-07-01 false Regulatory structure. 92.6 Section 92... Regulations for Locomotives and Locomotive Engines § 92.6 Regulatory structure. This section provides...

  4. 40 CFR 92.6 - Regulatory structure.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... locomotives and locomotive engines for which the regulations of this part (i.e., 40 CFR part 92) apply are... 40 Protection of Environment 21 2012-07-01 2012-07-01 false Regulatory structure. 92.6 Section 92... Regulations for Locomotives and Locomotive Engines § 92.6 Regulatory structure. This section provides...

  5. 40 CFR 92.6 - Regulatory structure.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... locomotives and locomotive engines for which the regulations of this part (i.e., 40 CFR part 92) apply are... 40 Protection of Environment 21 2013-07-01 2013-07-01 false Regulatory structure. 92.6 Section 92... Regulations for Locomotives and Locomotive Engines § 92.6 Regulatory structure. This section provides...

  6. 78 FR 1698 - Semiannual Regulatory Flexibility Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-08

    ..., Implementation of Basel III, Minimum Regulatory Capital Ratios, Capital Adequacy, and Transition Provisions..., Capital Adequacy, and Transition Provisions (Docket No. R-1442) Legal Authority: 12 U.S.C. 24; 12 U.S.C... disclosures related to regulatory capital instruments. Timetable: Action Date FR Cite Merged With 7100 AD87...

  7. 5 CFR 340.201 - Regulatory requirements.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 340.201 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS OTHER THAN FULL-TIME CAREER EMPLOYMENT (PART-TIME, SEASONAL, ON-CALL, AND INTERMITTENT) Regulatory Requirements-Part-Time Employment § 340.201 Regulatory requirements. This subpart contains the regulations of...

  8. 5 CFR 340.201 - Regulatory requirements.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 340.201 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS OTHER THAN FULL-TIME CAREER EMPLOYMENT (PART-TIME, SEASONAL, ON-CALL, AND INTERMITTENT) Regulatory Requirements-Part-Time Employment § 340.201 Regulatory requirements. This subpart contains the regulations of...

  9. 5 CFR 340.201 - Regulatory requirements.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 340.201 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS OTHER THAN FULL-TIME CAREER EMPLOYMENT (PART-TIME, SEASONAL, ON-CALL, AND INTERMITTENT) Regulatory Requirements-Part-Time Employment § 340.201 Regulatory requirements. This subpart contains the regulations of...

  10. 47 CFR 101.1309 - Regulatory status.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 5 2012-10-01 2012-10-01 false Regulatory status. 101.1309 Section 101.1309 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Multiple Address Systems General Provisions § 101.1309 Regulatory status. (a) The Commission...

  11. 47 CFR 101.1309 - Regulatory status.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 5 2014-10-01 2014-10-01 false Regulatory status. 101.1309 Section 101.1309 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Multiple Address Systems General Provisions § 101.1309 Regulatory status. (a) The Commission...

  12. 12 CFR 1010.14 - Regulatory exemptions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 8 2014-01-01 2014-01-01 false Regulatory exemptions. 1010.14 Section 1010.14 Banks and Banking BUREAU OF CONSUMER FINANCIAL PROTECTION LAND REGISTRATION (REGULATION J) General Requirements § 1010.14 Regulatory exemptions. (a) Eligibility requirements. The following transactions...

  13. 12 CFR 233.7 - Regulatory enforcement.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Regulatory enforcement. 233.7 Section 233.7 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM PROHIBITION ON FUNDING OF UNLAWFUL INTERNET GAMBLING (REGULATION GG) § 233.7 Regulatory enforcement....

  14. 31 CFR 132.7 - Regulatory enforcement.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Regulatory enforcement. 132.7 Section 132.7 Money and Finance: Treasury Regulations Relating to Money and Finance PROHIBITION ON FUNDING OF UNLAWFUL INTERNET GAMBLING § 132.7 Regulatory enforcement. The requirements under this part are subject...

  15. 12 CFR 233.7 - Regulatory enforcement.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 3 2011-01-01 2011-01-01 false Regulatory enforcement. 233.7 Section 233.7 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM PROHIBITION ON FUNDING OF UNLAWFUL INTERNET GAMBLING (REGULATION GG) § 233.7 Regulatory enforcement....

  16. 47 CFR 69.727 - Regulatory relief.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 3 2013-10-01 2013-10-01 false Regulatory relief. 69.727 Section 69.727 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) ACCESS CHARGES Pricing Flexibility § 69.727 Regulatory relief. (a) Phase I relief. Upon satisfaction of the Phase...

  17. 47 CFR 69.727 - Regulatory relief.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 3 2011-10-01 2011-10-01 false Regulatory relief. 69.727 Section 69.727 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) ACCESS CHARGES Pricing Flexibility § 69.727 Regulatory relief. (a) Phase I relief. Upon satisfaction of the Phase...

  18. 47 CFR 69.727 - Regulatory relief.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 3 2012-10-01 2012-10-01 false Regulatory relief. 69.727 Section 69.727 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) ACCESS CHARGES Pricing Flexibility § 69.727 Regulatory relief. (a) Phase I relief. Upon satisfaction of the Phase...

  19. 47 CFR 69.727 - Regulatory relief.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 3 2014-10-01 2014-10-01 false Regulatory relief. 69.727 Section 69.727 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) ACCESS CHARGES Pricing Flexibility § 69.727 Regulatory relief. (a) Phase I relief. Upon satisfaction of the Phase...

  20. 47 CFR 69.727 - Regulatory relief.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Regulatory relief. 69.727 Section 69.727 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) ACCESS CHARGES Pricing Flexibility § 69.727 Regulatory relief. (a) Phase I relief. Upon satisfaction of the Phase...

  1. 77 FR 58025 - Texas Regulatory Program

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-19

    ... Office of Surface Mining Reclamation and Enforcement 30 CFR Part 943 Texas Regulatory Program AGENCY... the Texas regulatory program (Texas program) under the Surface Mining Control and Reclamation Act of 1977 (SMCRA or the Act). Texas proposed revisions to its regulations regarding annual permit...

  2. Federal Trade Commission Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    ... Part XX Federal Trade Commission Semiannual Regulatory Agenda ] FEDERAL TRADE COMMISSION (FTC) FEDERAL TRADE COMMISSION 16 CFR Ch. I Semiannual Regulatory Agenda AGENCY: Federal Trade Commission... published in accordance with section 22(d)(1) of the Federal Trade Commission Act, 15 U.S.C.......

  3. 75 FR 61530 - Issuance of Regulatory Guides

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-05

    ... Guides 1.84, Rev. 35, ``Design, Fabrication, and Materials Code Case Acceptability, ASME Section III... Engineering, Office of Nuclear Regulatory Research, U.S. Nuclear Regulatory Commission, Washington, DC 20555..., Revision 16, on June 2, 2009, 74 FR 26303. On the same date, the NRC published a parallel notice...

  4. Department of Interior Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    ...: Action Date FR Cite Final Action 04/00/10 Regulatory Flexibility Analysis Required: Yes Agency Contact... idle facilities. Timetable: Action Date FR Cite NPRM 12/00/10 NPRM Comment Period End 02/00/11... Part IX Department of the Interior Semiannual Regulatory Agenda ] DEPARTMENT OF THE INTERIOR...

  5. Environmental regulatory update table, November 1987

    SciTech Connect

    Langston, M.E.; Sharples, F.E.; Tucker, C.S.

    1987-11-01

    This report 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, September 1987

    SciTech Connect

    Langston, M.E.; Sharples, F.E.; Tucker, C.S.

    1987-10-01

    This report 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, May 1987

    SciTech Connect

    Brown, K.J.; Tucker, C.S.; Reed, R.M.

    1987-06-01

    Information on regulatory initiatives of interest to DOE operations and contractor staff with environmental management oversight 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. 78 FR 44315 - Spring 2013 Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-23

    ... Agenda and the E-Agenda? G. How can you find out about rulemakings that start up after the Regulatory... requirements contained in numerous executive orders: 12866, ``Regulatory Planning and Review'' (58 FR 51735...'' (76 FR 3821, Jan. 21, 2011); 12898, ``Environmental Justice'' (59 FR 7629, Feb. 16, 1994);...

  9. 78 FR 1708 - Regulatory Flexibility Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-08

    ... section 4(6) of the Securities Act. Timetable: Action Date FR Cite NPRM 12/00/12 Regulatory Flexibility... Expansion) of the JOBS Act. Timetable: Action Date FR Cite NPRM 01/00/13 Regulatory Flexibility Analysis... on existing exemptions under the Securities Act. Timetable: Action Date FR Cite Interim Final Rule...

  10. [Regulatory B cells in human autoimmune diseases].

    PubMed

    Miyagaki, Tomomitsu

    2015-01-01

    B cells have been generally considered to be positive regulators of immune responses because of their ability to produce antigen-specific antibodies and to activate T cells through antigen presentation. Impairment of B cell development and function may cause autoimmune diseases. Recently, specific B cell subsets that can negatively regulate immune responses have been described in mouse models of a wide variety of autoimmune diseases. The concept of those B cells, termed regulatory B cells, is now recognized as important in the murine immune system. Among several regulatory B cell subsets, IL-10-producing regulatory B cells are the most widely investigated. On the basis of discoveries from studies of such mice, human regulatory B cells that produce IL-10 in most cases are becoming an active area of research. There have been emerging data suggesting the importance of human regulatory B cells in various diseases. Revealing the immune regulation mechanisms of human regulatory B cells in human autoimmune diseases could lead to the development of novel B cell targeted therapies. This review highlights the current knowledge on regulatory B cells, mainly IL-10-producing regulatory B cells, in clinical research using human samples. PMID:26725860

  11. Weight of evidence: regulatory toxicology in Canada

    SciTech Connect

    Somers, E.

    1986-12-01

    The legislative application of regulatory toxicology in Canada is reviewed, together with the sources of experimental evidence used for action. Examples are given of the critical toxicological information that led to a regulatory decision. Risk numbers have only been used to a limited extent in Canada. Some possibilities for future research are offered.

  12. 76 FR 40208 - Regulatory Flexibility Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-07

    ... Date FR Cite NPRM 03/00/12 Regulatory Flexibility Analysis Required: Yes. Agency Contact: Sean Harrison... Rule 506 of Regulation D. Timetable: Action Date FR Cite NPRM 06/01/11 76 FR 31518 NPRM Comment Period... by registrants. Timetable: Action Date FR Cite NPRM 03/00/12 Regulatory Flexibility Analysis...

  13. 76 FR 40050 - Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-07

    ... July 7, 2011 Part VII Department of Energy Semiannual Regulatory Agenda #0;#0;Federal Register / Vol. 76 , No. 130 / Thursday, July 7, 2011 / Unified Agenda#0;#0; ] DEPARTMENT OF ENERGY 10 CFR Chs. II, III, and X 48 CFR Ch. 9 Semiannual Regulatory Agenda AGENCY: Department of Energy. ACTION: Notice...

  14. 78 FR 1570 - Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-08

    ... January 8, 2013 Part VII Department of Energy Semiannual Regulatory Agenda #0;#0;Federal Register / Vol. 78 , No. 5 / Tuesday, January 8, 2013 / Unified Agenda#0;#0; ] DEPARTMENT OF ENERGY 10 CFR Chs. II, III, and X 48 CFR Ch. 9 Semiannual Regulatory Agenda AGENCY: Department of Energy. ACTION: Notice...

  15. Regulatory Reform: Low Risk, High Promise.

    ERIC Educational Resources Information Center

    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.…

  16. Department of Transportation Agency Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-20

    ... accordance with Executive Order 12866 ``Regulatory Planning and Review'' (58 FR 51735; October 4, 1993) and the Department's Regulatory Policies and Procedures (44 FR 11034; February 26, 1979), the Department... last agenda was published in the Federal Register on April 26, 2010 (75 FR 21840). The next one...

  17. 76 FR 33181 - Regulatory Review Schedule

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-08

    ... processes. (76 FR 18457, April 4, 2011). The Commission's regulatory review process establishes a detailed... National Indian Gaming Commission 25 CFR Chapter III Regulatory Review Schedule AGENCY: National Indian... Notice of Consultation advising the public that the NIGC was conducting a comprehensive review of all...

  18. 49 CFR 355.21 - Regulatory review.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 5 2011-10-01 2011-10-01 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...

  19. 76 FR 54408 - Regulatory Review Schedule

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-01

    .... (76 FR 18457, April 4, 2011). The Commission's regulatory review process established a tribal... National Indian Gaming Commission 25 CFR Chapter III Regulatory Review Schedule AGENCY: National Indian..., 1441 L Street, NW., Suite 9100, Washington, DC 20005. Telephone: 202-632-7003; e-mail:...

  20. 77 FR 10351 - Regulatory Review Plan

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-22

    ... plan and requested comments on the plan. 76 FR 59066 (September 23, 2011). FHFA received no comments... 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...

  1. 76 FR 26967 - Regulatory Review Schedule

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-10

    ... National Indian Gaming Commission 25 CFR Chapter III Regulatory Review Schedule AGENCY: National Indian... advising the public that the NIGC was conducting a comprehensive review of its regulations and requesting public comment on the process for conducting the regulatory review. On April 4, 2011, after holding...

  2. 49 CFR 355.21 - Regulatory review.

    Code of Federal Regulations, 2010 CFR

    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...

  3. 75 FR 79925 - Semiannual Regulatory Flexibility Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-20

    ... FR Cite Board Issued Final Rule on 02/22/10 75 FR 7658 Regulatory Flexibility Analysis Required: Yes... FR 37526 Regulatory Flexibility Analysis Required: Yes Agency Contact: Amy Henderson, Senior Attorney... similar to the proposed rule. Timetable: Action Date FR Cite Board Requested Comment 08/26/09 74 FR...

  4. The global epidemiology of waterpipe smoking

    PubMed Central

    Maziak, Wasim; Taleb, Ziyad Ben; Bahelah, Raed; Islam, Farahnaz; Jaber, Rana; Auf, Rehab; Salloum, Ramzi G

    2015-01-01

    Objectives In the past decade, waterpipe smoking (a.k.a. hookah, shisha, narghile) has become a global phenomenon. In this review, we provide an updated picture of the main epidemiological trends in waterpipe smoking globally. Data sources Peer-reviewed publications indexed in major biomedical databases between 2004 and 2014. Search keywords included a combination of: waterpipe, hookah, shisha along with epidemiology, patterns, prevalence and predictors. We also used different spellings of waterpipe terms commonly used. Study selection The focus was on studies with large representative samples, national data or high-quality reports that illuminated aspects of the epidemiology and trends in waterpipe smoking. Data extraction Multiple researchers extracted the data independently and collectively decided on the most important and pertinent studies to include in the review. Data synthesis Waterpipe smoking has become a global phenomenon among youth. The global waterpipe epidemic is likely driven by (1) the introduction of manufactured flavoured tobacco (Maassel); (2) the intersection between waterpipe's social dimension and thriving café culture; (3) the evolution of mass communication media; (4) the lack of regulatory/policy framework specific to the waterpipe. Waterpipe smoking is becoming the most popular tobacco use method among youth in the Middle East, and is quickly gaining popularity elsewhere. Important patterns of waterpipe smoking include the predominance among younger, male, high socioeconomic, and urban groups. Intermittent and social use are also noted patterns. Conclusions Waterpipe smoking has become a global public health problem. Developing surveillance, intervention and regulatory/policy frameworks specific to the waterpipe has become a public health priority. PMID:25298368

  5. Global health diplomacy.

    PubMed

    Adams, Vincanne; Novotny, Thomas E; Leslie, Hannah

    2008-01-01

    A variety of shifts emergent with globalization, which are reflected in part by nascent programs in "Global Public Health," "Global Health Sciences," and "Global Health," are redefining international public health. We explore three of these shifts as a critical discourse and intervention in global health diplomacy: the expansion in non-governmental organization participation in international health programs, the globalization of science and pharmaceutical research, and the use of militarized languages of biosecurity to recast public health programs. Using contemporary anthropological and international health literature, we offer a critical yet hopeful exploration of the implications of these shifts for critical inquiry, health, and the health professions.

  6. Beyond offshoring: assess your company's global potential.

    PubMed

    Farrell, Diana

    2004-12-01

    In the past few years, companies have become aware that they can slash costs by offshoring: moving jobs to lower-wage locations. But this practice is just the tip of the iceberg in terms of how globalization can transform industries, according to research by the McKinsey Global Institute (MGI). The institute's yearlong study suggests that by streamlining their production processes and supply chains globally, rather than just nationally or regionally, companies can lower their costs-as we've seen in the consumer-electronics and PC industries. Companies can save as much as 70% of their total costs through globalization--50% from offshoring, 5% from training and business-task redesign, and 15% from process improvements. But they don't have to stop there. The cost reductions make it possible to lower prices and expand into new markets, attracting whole new classes of customers. To date, however, few businesses have recognized the full scope of performance improvements that globalization makes possible, much less developed sound strategies for capturing those opportunities. In this article, Diana Farrell, director of MGI, offers a step-by-step approach to doing both things. Among her suggestions: Assess where your industry falls along the globalization spectrum, because not all sectors of the economy face the same challenges and opportunities at the same time. Also, pay attention to production, regulatory, and organizational barriers to globalization. If any of these can be changed, size up the cost-saving (and revenue-generating) opportunities that will emerge for your company as a result of those changes. Farrell also defines the five stages of globalization-market entry, product specialization, value chain disaggregation, value chain reengineering, and the creation of new markets-and notes the different levers for cutting costs and creating value that companies can use in each phase. PMID:15605568

  7. Mediation: Sanity in the regulatory process

    SciTech Connect

    Cohen, D.S.

    1993-01-15

    The regulatory process is in need of change. The adversarial model used by most regulatory agencies is an inefficient, expensive, and conflict-producing procedure. Ill-adapted to resolving issues of great public policy concern, regulation calls out for non-adversarial alternative processes to address the resolution of public policy disputes between the players in the regulatory process. The adversarial model of regulation mimics traditional courtroom procedures. It is designed to determine issues of fact, not issues of public policy with legal maneuvering used to shroud the development of facts. Conflict maintenance and not conflict resolution has become the hallmark of the adversarial process in the regulatory arena. Unlike the courtroom process which provides a certain finality to conflicts, the adversarial process in the regulatory process is perpetual.

  8. Global solidarity, migration and global health inequity.

    PubMed

    Eckenwiler, Lisa; Straehle, Christine; Chung, Ryoa

    2012-09-01

    The grounds for global solidarity have been theorized and conceptualized in recent years, and many have argued that we need a global concept of solidarity. But the question remains: what can motivate efforts of the international community and nation-states? Our focus is the grounding of solidarity with respect to global inequities in health. We explore what considerations could motivate acts of global solidarity in the specific context of health migration, and sketch briefly what form this kind of solidarity could take. First, we argue that the only plausible conceptualization of persons highlights their interdependence. We draw upon a conception of persons as 'ecological subjects' and from there illustrate what such a conception implies with the example of nurses migrating from low and middle-income countries to more affluent ones. Next, we address potential critics who might counter any such understanding of current international politics with a reference to real-politik and the insights of realist international political theory. We argue that national governments--while not always or even often motivated by moral reasons alone--may nevertheless be motivated to acts of global solidarity by prudential arguments. Solidarity then need not be, as many argue, a function of charitable inclination, or emergent from an acknowledgment of injustice suffered, but may in fact serve national and transnational interests. We conclude on a positive note: global solidarity may be conceptualized to helpfully address global health inequity, to the extent that personal and transnational interdependence are enough to motivate national governments into action.

  9. Harmonization of regulatory guidelines on efficacy of ectoparasiticides for companion animals: status and missing points.

    PubMed

    Curet Bobey, Marianne

    2015-02-28

    Ectoparasites of major clinical significance in companion animals include fleas, ticks, lice, mange, mite, mosquitoes and sandflies, as well as biting flies. Obtaining a marketing authorization (or licence) for an ectoparasiticide relies on the assessment by regulatory agencies of a comprehensive data package to confirm the quality, safety and efficacy of the product when used in the target animal species for the proposed claims. Such approval is done under a highly regulated system. However, the global regulatory framework for pet ectoparasiticides is complex, since these products may be classified either as pesticides or as pharmaceuticals depending on the country or even within a given country, based on the presentation or mode of action. Within each jurisdiction, regulatory guidelines provide standards relating to study designs, relevant parasite species, efficacy calculation and acceptable thresholds, and define the corresponding acceptable label claims. Despite some similarities, there is no formal international harmonization for development requirements. In some areas, gaps and/or inconsistencies are more marked than others. Published recommendations from scientific expert groups (e.g. W.A.A.V.P. guidelines) are therefore a useful tool for regulatory bodies, researchers, developers and animal health companies. These expert recommendations reflect the current position of the scientific community and potentially address aspects not covered satisfactorily by regulatory texts while taking into account the latest advancements in experimental methodologies. Since the changes to official regulatory texts generally occur at a slower pace than the scientific state-of-the-art, and because of the lack of a harmonized approach, both scientific and regulatory guidance documents are necessary. The main objective of this review is to explore the complexity of the international regulatory framework for pet ectoparasiticides and to highlight some areas that are

  10. Harmonization of regulatory guidelines on efficacy of ectoparasiticides for companion animals: status and missing points.

    PubMed

    Curet Bobey, Marianne

    2015-02-28

    Ectoparasites of major clinical significance in companion animals include fleas, ticks, lice, mange, mite, mosquitoes and sandflies, as well as biting flies. Obtaining a marketing authorization (or licence) for an ectoparasiticide relies on the assessment by regulatory agencies of a comprehensive data package to confirm the quality, safety and efficacy of the product when used in the target animal species for the proposed claims. Such approval is done under a highly regulated system. However, the global regulatory framework for pet ectoparasiticides is complex, since these products may be classified either as pesticides or as pharmaceuticals depending on the country or even within a given country, based on the presentation or mode of action. Within each jurisdiction, regulatory guidelines provide standards relating to study designs, relevant parasite species, efficacy calculation and acceptable thresholds, and define the corresponding acceptable label claims. Despite some similarities, there is no formal international harmonization for development requirements. In some areas, gaps and/or inconsistencies are more marked than others. Published recommendations from scientific expert groups (e.g. W.A.A.V.P. guidelines) are therefore a useful tool for regulatory bodies, researchers, developers and animal health companies. These expert recommendations reflect the current position of the scientific community and potentially address aspects not covered satisfactorily by regulatory texts while taking into account the latest advancements in experimental methodologies. Since the changes to official regulatory texts generally occur at a slower pace than the scientific state-of-the-art, and because of the lack of a harmonized approach, both scientific and regulatory guidance documents are necessary. The main objective of this review is to explore the complexity of the international regulatory framework for pet ectoparasiticides and to highlight some areas that are

  11. IMERG Global Precipitation Rates

    NASA Video Gallery

    NASA's Global Precipitation Measurement mission has produced its first global map of rainfall and snowfall. The GPM Core Observatory launched one year ago on Feb. 27, 2014 as a collaboration betwee...

  12. Global Health Observatory (GHO)

    MedlinePlus

    ... repository Reports Country statistics Map gallery Standards Global Health Observatory (GHO) data Monitoring health for the SDGs ... relevant web pages on the theme. Monitoring the health goal: indicators of overall progress Mortality and global ...

  13. Global Tuberculosis Report 2015

    MedlinePlus

    ... Feed Youtube Twitter Facebook Google + iTunes Play Store Tuberculosis (TB) Menu Tuberculosis The End TB Strategy Areas ... data News, events and features About us Global tuberculosis report 2015 This is the twentieth global report ...

  14. Global climate change

    NASA Technical Reports Server (NTRS)

    Levine, Joel S.

    1991-01-01

    Present processes of global climate change are reviewed. The processes determining global temperature are briefly described and the concept of effective temperature is elucidated. The greenhouse effect is examined, including the sources and sinks of greenhouse gases.

  15. Boolean Modelingof Genetic Regulatory Networks

    NASA Astrophysics Data System (ADS)

    Albert, Réka

    Biological systems form complex networks of interaction on several scales, ranging from the molecular to the ecosystem level. On the subcellular scale, interaction between genes and gene products (mRNAs, proteins) forms the basis of essential processes like signal transduction, cell metabolism or embryonic development. Recent experimental advances helped uncover the qualitative structure of many gene control networks, creating a surge of interest in the quantitative description of gene regulation. We give a brief description of the main frameworks and methods used in modeling gene regulatory networks, then focus on a recent model of the segment polarity genes of the fruit fly Drosophila melanogaster. The basis of this model is the known interactions between the products of the segment polarity genes, and the network topology these interactions form. The interactions between mRNAs and proteins are described as logical (Boolean) functions. The success in reproducing both wild type and mutant gene expression patterns suggests that the kinetic details of the interactions are not essential as long as the network of interactions is unperturbed. The model predicts the gene patterns for cases that were not yet studied experimentally, and implies a remarkable robustness toward changes in internal parameters, initial conditions and even some mutations.

  16. Evolving Robust Gene Regulatory Networks

    PubMed Central

    Noman, Nasimul; Monjo, Taku; Moscato, Pablo; Iba, Hitoshi

    2015-01-01

    Design and implementation of robust network modules is essential for construction of complex biological systems through hierarchical assembly of ‘parts’ and ‘devices’. The robustness of gene regulatory networks (GRNs) is ascribed chiefly to the underlying topology. The automatic designing capability of GRN topology that can exhibit robust behavior can dramatically change the current practice in synthetic biology. A recent study shows that Darwinian evolution can gradually develop higher topological robustness. Subsequently, this work presents an evolutionary algorithm that simulates natural evolution in silico, for identifying network topologies that are robust to perturbations. We present a Monte Carlo based method for quantifying topological robustness and designed a fitness approximation approach for efficient calculation of topological robustness which is computationally very intensive. The proposed framework was verified using two classic GRN behaviors: oscillation and bistability, although the framework is generalized for evolving other types of responses. The algorithm identified robust GRN architectures which were verified using different analysis and comparison. Analysis of the results also shed light on the relationship among robustness, cooperativity and complexity. This study also shows that nature has already evolved very robust architectures for its crucial systems; hence simulation of this natural process can be very valuable for designing robust biological systems. PMID:25616055

  17. Orphan drugs: the regulatory environment.

    PubMed

    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.

  18. Global Atmospheric Aerosol Modeling

    NASA Technical Reports Server (NTRS)

    Hendricks, Johannes; Aquila, Valentina; Righi, Mattia

    2012-01-01

    Global aerosol models are used to study the distribution and properties of atmospheric aerosol particles as well as their effects on clouds, atmospheric chemistry, radiation, and climate. The present article provides an overview of the basic concepts of global atmospheric aerosol modeling and shows some examples from a global aerosol simulation. Particular emphasis is placed on the simulation of aerosol particles and their effects within global climate models.

  19. Mapping Global Citizenship

    ERIC Educational Resources Information Center

    Stein, Sharon

    2015-01-01

    The demand to cultivate global citizenship is frequently invoked as central to colleges' and universities' internationalization efforts. However, the term "global citizenship" remains undertheorized in the context of U.S. higher education. This article maps and engages three common global citizenship positions--entrepreneurial, liberal…

  20. Globalization: Myths and Realities.

    ERIC Educational Resources Information Center

    McMichael, Philip

    1996-01-01

    Nationally oriented institutions of the developmentalist era are being replaced by globally oriented institutions under the legitimizing cloak of efficiency and financial credibility. Meanwhile, producing communities either seek niches in the global economy or resist global pressures, thereby newly emphasizing the local. Explores the conjunction…

  1. Globalization and American Education

    ERIC Educational Resources Information Center

    Merriman, William; Nicoletti, Augustine

    2008-01-01

    Globalization is a potent force in today's world. The welfare of the United States is tied to the welfare of other countries by economics, the environment, politics, culture, information, and technology. This paper identifies the implications of globalization for education, presents applications of important aspects of globalization that teachers…

  2. Developing Successful Global Leaders

    ERIC Educational Resources Information Center

    Training, 2011

    2011-01-01

    Everyone seems to agree the world desperately needs strong leaders who can manage a global workforce and all the inherent challenges that go with it. That's a big part of the raison d'etre for global leadership development programs. But are today's organizations fully utilizing these programs to develop global leaders, and, if so, are they…

  3. Regulatory analysis technical evaluation handbook. Final report

    SciTech Connect

    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.

  4. Global social identity and global cooperation.

    PubMed

    Buchan, Nancy R; Brewer, Marilynn B; Grimalda, Gianluca; Wilson, Rick K; Fatas, Enrique; Foddy, Margaret

    2011-06-01

    This research examined the question of whether the psychology of social identity can motivate cooperation in the context of a global collective. Our data came from a multinational study of choice behavior in a multilevel public-goods dilemma conducted among samples drawn from the general populations of the United States, Italy, Russia, Argentina, South Africa, and Iran. Results demonstrate that an inclusive social identification with the world community is a meaningful psychological construct that plays a role in motivating cooperation that transcends parochial interests. Self-reported identification with the world as a whole predicts behavioral contributions to a global public good beyond what is predicted from expectations about what other people are likely to contribute. Furthermore, global social identification is conceptually distinct from general attitudes about global issues, and has unique effects on cooperative behavior.

  5. Global social identity and global cooperation.

    PubMed

    Buchan, Nancy R; Brewer, Marilynn B; Grimalda, Gianluca; Wilson, Rick K; Fatas, Enrique; Foddy, Margaret

    2011-06-01

    This research examined the question of whether the psychology of social identity can motivate cooperation in the context of a global collective. Our data came from a multinational study of choice behavior in a multilevel public-goods dilemma conducted among samples drawn from the general populations of the United States, Italy, Russia, Argentina, South Africa, and Iran. Results demonstrate that an inclusive social identification with the world community is a meaningful psychological construct that plays a role in motivating cooperation that transcends parochial interests. Self-reported identification with the world as a whole predicts behavioral contributions to a global public good beyond what is predicted from expectations about what other people are likely to contribute. Furthermore, global social identification is conceptually distinct from general attitudes about global issues, and has unique effects on cooperative behavior. PMID:21586763

  6. Global Health and the Global Economic Crisis

    PubMed Central

    Gill, Stephen; Bakker, Isabella

    2011-01-01

    Although the resources and knowledge for achieving improved global health exist, a new, critical paradigm on health as an aspect of human development, human security, and human rights is needed. Such a shift is required to sufficiently modify and credibly reduce the present dominance of perverse market forces on global health. New scientific discoveries can make wide-ranging contributions to improved health; however, improved global health depends on achieving greater social justice, economic redistribution, and enhanced democratization of production, caring social institutions for essential health care, education, and other public goods. As with the quest for an HIV vaccine, the challenge of improved global health requires an ambitious multidisciplinary research program. PMID:21330597

  7. Global temperatures and the global warming ``debate''

    NASA Astrophysics Data System (ADS)

    Aubrecht, Gordon

    2009-04-01

    Many ordinary citizens listen to pronouncements on talk radio casting doubt on anthropogenic global warming. Some op-ed columnists likewise cast doubts, and are read by credulous citizens. For example, on 8 March 2009, the Boston Globe published a column by Jeff Jacoby, ``Where's global warming?'' According to Jacoby, ``But it isn't such hints of a planetary warming trend that have been piling up in profusion lately. Just the opposite.'' He goes on to write, ``the science of climate change is not nearly as important as the religion of climate change,'' and blamed Al Gore for getting his mistaken views accepted. George Will at the Washington Post also expressed denial. As a result, 44% of U.S. voters, according to the January 19 2009 Rasmussen Report, blame long-term planetary trends for global warming, not human beings. Is there global cooling, as skeptics claim? We examine the temperature record.

  8. Beyond global warming: Ecology and global change

    SciTech Connect

    Vitousek, P.M. )

    1994-10-01

    While ecologists involved in management or policy often are advised to learn to deal with uncertainty, some components of global environmental change are certainly occurring and are certainly human-caused. All have important ecological consequences. Well-documented global changes include: Increasing concentrations of carbon dioxide in the atmosphere; alterations in the biogeochemistry of the global nitrogen cycle; and ongoing land use/land cover change. Human activity - now primarily fossil fuel combustion - has increased carbon dioxide concentrations from [approximately] 280 to 355 [mu]L/L since 1800 and is likely to have climatic consequences and direct effects on biota in all terrestrial ecosystems. The global nitrogen cycle has been altered so that more nitrogen is fixed annually by humanity than by all natural pathways combined. Altering atmospheric chemistry and aquatic ecosystems, contributes to eutrophication of the biosphere, and has substantial regional effects on biological diversity. Finally, human land use/land cover change has transformed one-third to one-half of Earth's ice-free surface, representing the most important component of global change now. Any clear dichotomy between pristine ecosystems and human-altered areas that may have existed in the past has vanished, and ecological research should account for this reality. Certain components of global environmental change are the primary causes of anticipated changes in climate, and of ongoing losses of biological diversity. They are caused by the extraordinary growth in size and resource use of the human population. On a broad scale, there is little uncertainty about any of these components of change or their causes. However, much of the public believes the causes of global change to be uncertain and contentious. By speaking out effectively,the focus of public discussion towards what can and should be done about global environmental change can be shifted. 135 refs., 13 figs., 1 tab.

  9. 75 FR 62436 - Notice of Issuance of Regulatory Guide

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-08

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of... Coatings Applied to Nuclear Power Plants.'' FOR FURTHER INFORMATION CONTACT: Bruce P. Lin, Division...

  10. 76 FR 31382 - Notice of Issuance of Regulatory Guide

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-31

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of... Surveys and Monitoring.'' FOR FURTHER INFORMATION CONTACT: Harriet Karagiannis, U.S. Nuclear...

  11. Global perspectives: A new global ethic, a new global partnership

    SciTech Connect

    Brundtland, G.H.

    1990-06-01

    In her keynote address at the opening plenary session of the Globe '90 Conference held in Vancouver in March, Mrs. Brundtland called for a new global partnership of government, industry, producers and consumers to meet present and future environmental challenges. This partnership would require help to developing countries to help free them from their handicaps of debt, overpopulation and poverty; that improvements made to the environment would not be offset by ecological damage in other areas. She was encouraged that the policy of sustainable development has been widely adapted as the only viable strategy for global change.

  12. Regulatory T cells: balancing protection versus pathology.

    PubMed

    Rakebrandt, Nikolas; Littringer, Katharina; Joller, Nicole

    2016-01-01

    Foxp3+ regulatory T cells (Tregs) maintain immune tolerance, prevent autoimmunity and modulate immune responses during infection and cancer. Recent studies have revealed considerable heterogeneity and plasticity within the Treg compartment, depending on the immunological context, which may result in Tregs losing their suppressive function in inflammatory environments. We review how dysfunctional Tregs contribute to disease pathogenesis in inflammatory conditions and how inappropriate regulatory responses may hamper protective immunity in the context of infection and cancer. We also discuss how Tregs might be targeted therapeutically to re-establish a proper balance between regulatory and effector responses in autoimmunity, infections, and cancer. PMID:27497235

  13. REGULATORY T CELLS AND VASECTOMY

    PubMed Central

    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

  14. Global Collaborative STEM Education

    NASA Astrophysics Data System (ADS)

    Meabh Kelly, Susan; Smith, Walter

    2016-04-01

    Global Collaborative STEM Education, as the name suggests, simultaneously supports two sets of knowledge and skills. The first set is STEM -- science, technology, engineering and math. The other set of content knowledge and skills is that of global collaboration. Successful global partnerships require awareness of one's own culture, the biases embedded within that culture, as well as developing awareness of the collaborators' culture. Workforce skills fostered include open-mindedness, perseverance when faced with obstacles, and resourceful use of technological "bridges" to facilitate and sustain communication. In respect for the 2016 GIFT Workshop focus, Global Collaborative STEM Education projects dedicated to astronomy research will be presented. The projects represent different benchmarks within the Global Collaborative STEM Education continuum, culminating in an astronomy research experience that fully reflects how the global STEM workforce collaborates. To facilitate wider engagement in Global Collaborative STEM Education, project summaries, classroom resources and contact information for established international collaborative astronomy research projects will be disseminated.

  15. Adiposity-Dependent Regulatory Effects on Multi-tissue Transcriptomes.

    PubMed

    Glastonbury, Craig A; Viñuela, Ana; Buil, Alfonso; Halldorsson, Gisli H; Thorleifsson, Gudmar; Helgason, Hannes; Thorsteinsdottir, Unnur; Stefansson, Kari; Dermitzakis, Emmanouil T; Spector, Tim D; Small, Kerrin S

    2016-09-01

    Obesity is a global epidemic that is causally associated with a range of diseases, including type 2 diabetes and cardiovascular disease, at the population-level. However, there is marked heterogeneity in obesity-related outcomes among individuals. This might reflect genotype-dependent responses to adiposity. Given that adiposity, measured by BMI, is associated with widespread changes in gene expression and regulatory variants mediate the majority of known complex trait loci, we sought to identify gene-by-BMI (G × BMI) interactions on the regulation of gene expression in a multi-tissue RNA-sequencing (RNA-seq) dataset from the TwinsUK cohort (n = 856). At a false discovery rate of 5%, we identified 16 cis G × BMI interactions (top cis interaction: CHURC1, rs7143432, p = 2.0 × 10(-12)) and one variant regulating 53 genes in trans (top trans interaction: ZNF423, rs3851570, p = 8.2 × 10(-13)), all in adipose tissue. The interactions were adipose-specific and enriched for variants overlapping adipocyte enhancers, and regulated genes were enriched for metabolic and inflammatory processes. We replicated a subset of the interactions in an independent adipose RNA-seq dataset (deCODE genetics, n = 754). We also confirmed the interactions with an alternate measure of obesity, dual-energy X-ray absorptiometry (DXA)-derived visceral-fat-volume measurements, in a subset of TwinsUK individuals (n = 682). The identified G × BMI regulatory effects demonstrate the dynamic nature of gene regulation and reveal a functional mechanism underlying the heterogeneous response to obesity. Additionally, we have provided a web browser allowing interactive exploration of the dataset, including of association between expression, BMI, and G × BMI regulatory effects in four tissues. PMID:27588447

  16. Global solidarity, migration and global health inequity.

    PubMed

    Eckenwiler, Lisa; Straehle, Christine; Chung, Ryoa

    2012-09-01

    The grounds for global solidarity have been theorized and conceptualized in recent years, and many have argued that we need a global concept of solidarity. But the question remains: what can motivate efforts of the international community and nation-states? Our focus is the grounding of solidarity with respect to global inequities in health. We explore what considerations could motivate acts of global solidarity in the specific context of health migration, and sketch briefly what form this kind of solidarity could take. First, we argue that the only plausible conceptualization of persons highlights their interdependence. We draw upon a conception of persons as 'ecological subjects' and from there illustrate what such a conception implies with the example of nurses migrating from low and middle-income countries to more affluent ones. Next, we address potential critics who might counter any such understanding of current international politics with a reference to real-politik and the insights of realist international political theory. We argue that national governments--while not always or even often motivated by moral reasons alone--may nevertheless be motivated to acts of global solidarity by prudential arguments. Solidarity then need not be, as many argue, a function of charitable inclination, or emergent from an acknowledgment of injustice suffered, but may in fact serve national and transnational interests. We conclude on a positive note: global solidarity may be conceptualized to helpfully address global health inequity, to the extent that personal and transnational interdependence are enough to motivate national governments into action. PMID:22827320

  17. Asymmetric Regulation of Peripheral Genes by Two Transcriptional Regulatory Networks

    PubMed Central

    Li, Jing-Ru; Suzuki, Takahiro; Nishimura, Hajime; Kishima, Mami; Maeda, Shiori; Suzuki, Harukazu

    2016-01-01

    Transcriptional regulatory network (TRN) reconstitution and deconstruction occur simultaneously during reprogramming; however, it remains unclear how the starting and targeting TRNs regulate the induction and suppression of peripheral genes. Here we analyzed the regulation using direct cell reprogramming from human dermal fibroblasts to monocytes as the platform. We simultaneously deconstructed fibroblastic TRN and reconstituted monocytic TRN; monocytic and fibroblastic gene expression were analyzed in comparison with that of fibroblastic TRN deconstruction only or monocytic TRN reconstitution only. Global gene expression analysis showed cross-regulation of TRNs. Detailed analysis revealed that knocking down fibroblastic TRN positively affected half of the upregulated monocytic genes, indicating that intrinsic fibroblastic TRN interfered with the expression of induced genes. In contrast, reconstitution of monocytic TRN showed neutral effects on the majority of fibroblastic gene downregulation. This study provides an explicit example that demonstrates how two networks together regulate gene expression during cell reprogramming processes and contributes to the elaborate exploration of TRNs. PMID:27483142

  18. Early Biomarkers and Regulatory Innovation in Multidrug-Resistant Tuberculosis.

    PubMed

    Wallis, Robert S; Peppard, Thomas

    2015-10-15

    Biomarkers play an essential role in accelerating drug development. Sputum culture conversion using solid medium is the best-characterized tuberculosis biomarker, having been examined at the patient and trial levels in studies with thousands of subjects, and having recently been validated using data from 3 unsuccessful phase 3 trials. We presently are poised at the threshold of regulatory innovation for antibacterials to treat drug-resistant infections, in which Special Medical Use authorization restricted to patients with limited options could be based on the results of small clinical trials. Patients worldwide would be well served by licensing of new regimens for multidrug-resistant tuberculosis based on biomarker evidence commensurate with the urgency of the current global crisis. PMID:26409278

  19. Generic antibiotic industries: Challenges and implied strategies with regulatory perspectives.

    PubMed

    Venkatesh, M; Bairavi, V G; Sasikumar, K C

    2011-01-01

    Ever since the discovery of antibiotics, the quality of human life greatly improved in the 20(th) century. The discovery of penicillin transformed the medicine industry and initiated a search for a better antibiotic every time resulting in several synthetic and semi-synthetic antibiotics. Beginning with the 1937 sulfa drug tragedy, the drug regulations had a parallel growth along with the antibiotics and the antibiotic-based generic Pharma industries. This review article is focused on the scenario depicting current global Pharma industries based on generic antibiotics. Several regulatory aspects involved with these industries have been discussed along with the complexity of the market, issues that could affect their growth, their struggle for quality, and their compliance with the tightened regulations. With the skyrocketing commercialization of antibiotics through generics and the leveraging technologic renaissance, generic industries are involved in providing maximum safer benefits for the welfare of the people, highlighting its need today..

  20. BIOSENSORS FOR ENVIRONMENTAL MONITORING: A REGULATORY PERSPECTIVE

    EPA Science Inventory

    Biosensors show the potential to complement laboratory-based analytical methods for environmental applications. Although biosensors for potential environmental-monitoring applications have been reported for a wide range of environmental pollutants, from a regulatory perspective, ...