Science.gov

Sample records for cra global regulatory

  1. 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 and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY DISCLOSURE AND REPORTING OF CRA-RELATED AGREEMENTS § 346.3 CRA communications. (a) Definition of CRA communication. A CRA communication is any of...

  2. 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. PMID:25128336

  3. 12 CFR 133.3 - CRA communications.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...-RELATED AGREEMENTS § 133.3 CRA communications. (a) Definition of CRA communication. A CRA communication is... with a Federal banking agency. An oral or written communication with a Federal banking agency is not a CRA communication if it occurred more than 3 years before the parties entered into the agreement....

  4. 12 CFR 533.3 - CRA communications.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...-RELATED AGREEMENTS § 533.3 CRA communications. (a) Definition of CRA communication. A CRA communication is... with a Federal banking agency. An oral or written communication with a Federal banking agency is not a CRA communication if it occurred more than 3 years before the parties entered into the agreement....

  5. 12 CFR 35.3 - CRA communications.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... AGREEMENTS § 35.3 CRA communications. (a) Definition of CRA communication. A CRA communication is any of the.... An oral or written communication with a Federal banking agency is not a CRA communication if it... insured depository institutions and affiliates. A communication with an insured depository institution...

  6. 12 CFR 533.3 - CRA communications.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...-RELATED AGREEMENTS § 533.3 CRA communications. (a) Definition of CRA communication. A CRA communication is... with a Federal banking agency. An oral or written communication with a Federal banking agency is not a CRA communication if it occurred more than 3 years before the parties entered into the agreement....

  7. 12 CFR 390.162 - CRA communications.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Agreements § 390.162 CRA communications. (a) Definition of CRA communication. A CRA communication is any of... with a Federal banking agency. An oral or written communication with a Federal banking agency is not a CRA communication if it occurred more than 3 years before the parties entered into the agreement....

  8. 12 CFR 390.162 - CRA communications.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Agreements § 390.162 CRA communications. (a) Definition of CRA communication. A CRA communication is any of... with a Federal banking agency. An oral or written communication with a Federal banking agency is not a CRA communication if it occurred more than 3 years before the parties entered into the agreement....

  9. 12 CFR 35.3 - CRA communications.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AGREEMENTS § 35.3 CRA communications. (a) Definition of CRA communication. A CRA communication is any of the.... An oral or written communication with a Federal banking agency is not a CRA communication if it... insured depository institutions and affiliates. A communication with an insured depository institution...

  10. 12 CFR 390.162 - CRA communications.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Agreements § 390.162 CRA communications. (a) Definition of CRA communication. A CRA communication is any of... with a Federal banking agency. An oral or written communication with a Federal banking agency is not a CRA communication if it occurred more than 3 years before the parties entered into the agreement....

  11. 12 CFR 133.3 - CRA communications.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...-RELATED AGREEMENTS § 133.3 CRA communications. (a) Definition of CRA communication. A CRA communication is... with a Federal banking agency. An oral or written communication with a Federal banking agency is not a CRA communication if it occurred more than 3 years before the parties entered into the agreement....

  12. 12 CFR 35.3 - CRA communications.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... AGREEMENTS § 35.3 CRA communications. (a) Definition of CRA communication. A CRA communication is any of the.... An oral or written communication with a Federal banking agency is not a CRA communication if it... insured depository institutions and affiliates. A communication with an insured depository institution...

  13. 12 CFR 35.3 - CRA communications.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AGREEMENTS § 35.3 CRA communications. (a) Definition of CRA communication. A CRA communication is any of the.... An oral or written communication with a Federal banking agency is not a CRA communication if it... insured depository institutions and affiliates. A communication with an insured depository institution...

  14. 12 CFR 133.3 - CRA communications.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...-RELATED AGREEMENTS § 133.3 CRA communications. (a) Definition of CRA communication. A CRA communication is... with a Federal banking agency. An oral or written communication with a Federal banking agency is not a CRA communication if it occurred more than 3 years before the parties entered into the agreement....

  15. 12 CFR 533.3 - CRA communications.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...-RELATED AGREEMENTS § 533.3 CRA communications. (a) Definition of CRA communication. A CRA communication is... with a Federal banking agency. An oral or written communication with a Federal banking agency is not a CRA communication if it occurred more than 3 years before the parties entered into the agreement....

  16. 12 CFR 533.3 - CRA communications.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...-RELATED AGREEMENTS § 533.3 CRA communications. (a) Definition of CRA communication. A CRA communication is... with a Federal banking agency. An oral or written communication with a Federal banking agency is not a CRA communication if it occurred more than 3 years before the parties entered into the agreement....

  17. 12 CFR 207.3 - CRA communications.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... provided to a Federal banking agency concerning the adequacy of the performance under the CRA of the... performance under the CRA of the institution and must be included in the institution's CRA public file. (3... concerning the adequacy of the performance under the CRA of the insured depository institution,...

  18. 12 CFR 346.3 - CRA communications.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... provided to a Federal banking agency concerning the adequacy of the performance under the CRA of the... performance under the CRA of the institution and must be included in the institution's CRA public file. (3... concerning the adequacy of the performance under the CRA of the insured depository institution,...

  19. 12 CFR 533.3 - CRA communications.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... agency concerning the adequacy of the performance under the CRA of the insured depository institution... to the insured depository institution that discusses the adequacy of the performance under the CRA of... the performance under the CRA of the insured depository institution, any affiliated insured...

  20. 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

  1. 12 CFR 207.3 - CRA communications.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... communication. A CRA communication is any of the following— (1) Any written or oral comment or testimony... contacts with a Federal banking agency. An oral or written communication with a Federal banking agency is not a CRA communication if it occurred more than 3 years before the parties entered into the...

  2. 12 CFR 207.3 - CRA communications.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... communication. A CRA communication is any of the following— (1) Any written or oral comment or testimony... contacts with a Federal banking agency. An oral or written communication with a Federal banking agency is not a CRA communication if it occurred more than 3 years before the parties entered into the...

  3. 12 CFR 346.3 - CRA communications.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... communication. A CRA communication is any of the following— (1) Any written or oral comment or testimony... contacts with a Federal banking agency. An oral or written communication with a Federal banking agency is not a CRA communication if it occurred more than 3 years before the parties entered into the...

  4. 12 CFR 207.3 - CRA communications.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... communication. A CRA communication is any of the following— (1) Any written or oral comment or testimony... contacts with a Federal banking agency. An oral or written communication with a Federal banking agency is not a CRA communication if it occurred more than 3 years before the parties entered into the...

  5. 12 CFR 207.3 - CRA communications.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... communication. A CRA communication is any of the following— (1) Any written or oral comment or testimony... contacts with a Federal banking agency. An oral or written communication with a Federal banking agency is not a CRA communication if it occurred more than 3 years before the parties entered into the...

  6. 12 CFR 346.3 - CRA communications.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... communication. A CRA communication is any of the following— (1) Any written or oral comment or testimony... contacts with a Federal banking agency. An oral or written communication with a Federal banking agency is not a CRA communication if it occurred more than 3 years before the parties entered into the...

  7. 12 CFR 346.3 - CRA communications.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... communication. A CRA communication is any of the following— (1) Any written or oral comment or testimony... contacts with a Federal banking agency. An oral or written communication with a Federal banking agency is not a CRA communication if it occurred more than 3 years before the parties entered into the...

  8. 12 CFR 35.3 - CRA communications.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... adequacy of the performance under the CRA of the insured depository institution, any affiliated insured... institution that discusses the adequacy of the performance under the CRA of the institution and must be... comments or testimony to any Federal banking agency concerning the adequacy of the performance under...

  9. 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

  10. 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. PMID:25503406

  11. 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.

  12. 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...

  13. 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

  14. 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

  15. [Role of Academia in Regulatory Science for Global Drug Development].

    PubMed

    Tsukamoto, Katsura; Takenaka, Toichi

    2016-01-01

    As diseases know no national boundaries, drug development must be designed at a global level. Drugs are highly regulated to maximize the benefits to public health, which is assessed on a regional basis. The complexity and diversity of stakeholders increase dramatically once multiple international regions are involved. Each stakeholder in drug development depends on customized criteria to make decisions for its own benefit. Thus, a huge gap exists among drug discovery researchers, developers, clinicians, patients, and regulatory bodies. With reasonable scientific evidence gathered and analyzed, mutual agreement can be reached. We believe that this important role of regulatory science and academic involvement will create harmony. By practicing diverse, innovative regulatory scientific research, academia has the potential to become the core of communication among various stakeholder groups. Furthermore, another important responsibility of academia, i.e., knowledge, provides additional aspects to the field of drug development. Those who understand regulatory science can contribute to the efficient achievement of innovative, effective, safe drugs. Thus, research and education are essential roles of academia to allow a better understanding of the balance between benefits and risks. Communication and knowledge will promote the prompt delivery of better medical products to patients in need. PMID:27040336

  16. 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...

  17. 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

  18. 12 CFR Appendix B to Part 345 - CRA Notice

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY COMMUNITY... interstate bank, one branch office in each state. Community Reinvestment Act Notice Under the Federal Community Reinvestment Act (CRA), the Federal Deposit Insurance Corporation (FDIC) evaluates our record...

  19. 12 CFR Appendix B to Part 228 - CRA Notice

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... under the CRA, including, for example, information about our branches, such as their location and... comments. If we are operating under an approved strategic plan, you may also have access to a copy of...

  20. 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.

  1. Regulatory challenges for in vitro diagnostics in a global environment.

    PubMed

    Longwell, A

    1994-06-01

    U.S. medical products are marketed globally and are designed to meet needs of medical practitioners and their patients throughout the world. However, differences in how these products are regulated in different countries can pose challenges for the global marketer. This paper explores some of the differences between proposed and extant U.S. and European regulations for in vitro diagnostic products in terms of documentation, records, and labelling. It will describe some of the practical implications of these differences. PMID:7804632

  2. Reviewing the regulatory barriers for nanomedicine: global questions and challenges.

    PubMed

    Bowman, Diana M; Gatof, Jake

    2015-01-01

    Nanomedicine will play an increasing role in prevention and treatment across the entire healthcare spectrum. However, their precise market size, economic value and areas of application remain unclear. This opacity, including the question of what constitutes nanomedicine matters, especially when considered alongside the key regulatory questions and concerns. This article begins by placing these key questions into context in relation to the current scientific state of the art, focusing particular attention on the human health and safety context. In exploring these central questions surrounding the regulation of nanomedicine, this perspective also explores existing and suggested frameworks that aim to deal with emerging technologies more generally. It then outlines priority areas for action and general conclusions specific to nanomedicine. PMID:26470990

  3. 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. PMID:25312412

  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. Structural Analysis of the Global Multimedia Scenario: Technological, Market, Environmental, and Regulatory Issues.

    ERIC Educational Resources Information Center

    Nicolo, Enrico; Sapio, Bartolomeo

    1996-01-01

    Presents a strategic evaluation of the global multimedia scenario, considering both stand-alone workstations and distributed multimedia in the worldwide interactive network, including educational databases on the Internet. Discusses 50 technological, market, environmental, and regulatory factors and estimates their impacts on each other using WISE…

  6. Re-engineering cellular physiology by rewiring high-level global regulatory genes

    PubMed Central

    Fitzgerald, Stephen; Dillon, Shane C.; Chao, Tzu-Chiao; Wiencko, Heather L.; Hokamp, Karsten; Cameron, Andrew D. S.; Dorman, Charles J.

    2015-01-01

    Knowledge of global regulatory networks has been exploited to rewire the gene control programmes of the model bacterium Salmonella enterica serovar Typhimurium. The product is an organism with competitive fitness that is superior to that of the wild type but tuneable under specific growth conditions. The paralogous hns and stpA global regulatory genes are located in distinct regions of the chromosome and control hundreds of target genes, many of which contribute to stress resistance. The locations of the hns and stpA open reading frames were exchanged reciprocally, each acquiring the transcription control signals of the other. The new strain had none of the compensatory mutations normally associated with alterations to hns expression in Salmonella; instead it displayed rescheduled expression of the stress and stationary phase sigma factor RpoS and its regulon. Thus the expression patterns of global regulators can be adjusted artificially to manipulate microbial physiology, creating a new and resilient organism. PMID:26631971

  7. Re-engineering cellular physiology by rewiring high-level global regulatory genes.

    PubMed

    Fitzgerald, Stephen; Dillon, Shane C; Chao, Tzu-Chiao; Wiencko, Heather L; Hokamp, Karsten; Cameron, Andrew D S; Dorman, Charles J

    2015-01-01

    Knowledge of global regulatory networks has been exploited to rewire the gene control programmes of the model bacterium Salmonella enterica serovar Typhimurium. The product is an organism with competitive fitness that is superior to that of the wild type but tuneable under specific growth conditions. The paralogous hns and stpA global regulatory genes are located in distinct regions of the chromosome and control hundreds of target genes, many of which contribute to stress resistance. The locations of the hns and stpA open reading frames were exchanged reciprocally, each acquiring the transcription control signals of the other. The new strain had none of the compensatory mutations normally associated with alterations to hns expression in Salmonella; instead it displayed rescheduled expression of the stress and stationary phase sigma factor RpoS and its regulon. Thus the expression patterns of global regulators can be adjusted artificially to manipulate microbial physiology, creating a new and resilient organism. PMID:26631971

  8. 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

  9. 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

  10. 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.

  11. An Investigation of the Effects of CRA Instruction and Students with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Stroizer, Shaunita; Hinton, Vanessa; Flores, Margaret; Terry, LaTonya

    2015-01-01

    Students with Autism Spectrum Disorders (ASD) have unique educational needs. The concrete representational abstract (CRA) instructional sequence has been shown effective in teaching students with mathematical difficulties. The purpose of this study was to examine the effects of the CRA sequence in teaching students with ASD. A multiple baseline…

  12. 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

  13. 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

    ...The Food and Drug Administration (FDA) announces its intention to accept and consider a single source application for award of a cooperative agreement to the World Health Organization (WHO) in support of collaboration in regulatory science and capacity of National Regulatory Authorities (NRAs) to advance global access to safe and effective vaccines and other biologicals that meet international......

  14. 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

  15. 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

  16. [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. PMID:25791189

  17. 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

  18. Global analysis of p53-regulated transcription identifies its direct targets and unexpected regulatory mechanisms

    PubMed Central

    Allen, Mary Ann; Andrysik, Zdenek; Dengler, Veronica L; Mellert, Hestia S; Guarnieri, Anna; Freeman, Justin A; Sullivan, Kelly D; Galbraith, Matthew D; Luo, Xin; Kraus, W Lee; Dowell, Robin D; Espinosa, Joaquin M

    2014-01-01

    The p53 transcription factor is a potent suppressor of tumor growth. We report here an analysis of its direct transcriptional program using Global Run-On sequencing (GRO-seq). Shortly after MDM2 inhibition by Nutlin-3, low levels of p53 rapidly activate ∼200 genes, most of them not previously established as direct targets. This immediate response involves all canonical p53 effector pathways, including apoptosis. Comparative global analysis of RNA synthesis vs steady state levels revealed that microarray profiling fails to identify low abundance transcripts directly activated by p53. Interestingly, p53 represses a subset of its activation targets before MDM2 inhibition. GRO-seq uncovered a plethora of gene-specific regulatory features affecting key survival and apoptotic genes within the p53 network. p53 regulates hundreds of enhancer-derived RNAs. Strikingly, direct p53 targets harbor pre-activated enhancers highly transcribed in p53 null cells. Altogether, these results enable the study of many uncharacterized p53 target genes and unexpected regulatory mechanisms. DOI: http://dx.doi.org/10.7554/eLife.02200.001 PMID:24867637

  19. Capacity for a global vaccine safety system: the perspective of national regulatory authorities.

    PubMed

    Graham, Janice E; Borda-Rodriguez, Alexander; Huzair, Farah; Zinck, Emily

    2012-07-13

    Confidence in vaccine safety is critical to national immunization strategies and to global public health. To meet the Millenium Development Goals, and buoyed by the success of new vaccines produced in developing countries, the World Health Organization has been developing a strategy to establish a global system for effective vaccine pharmacovigilance in all countries. This paper reports the findings of a qualitative survey, conducted for the WHO Global Vaccine Safety Blueprint project, on the perspectives of national regulatory authorities responsible for vaccine safety in manufacturing and procuring countries. Capacity and capabilities of detecting, reporting and responding to adverse events following immunization (AEFI), and expectations of minimum capacity necessary for vaccine pharmacovigilance were explored. Key barriers to establishing a functional national vaccine safety system in developing countries were identified. The lack of infrastructure, information technology for stable communications and data exchange, and human resources affect vaccine safety monitoring in developing countries. A persistent "fear of reporting" in several low and middle income countries due to insufficient training and insecure employment underlies a perceived lack of political will in many governments for vaccine pharmacovigilance. Regulators recommended standardized and internationally harmonized safety reporting forms, improved surveillance mechanisms, and a global network for access and exchange of safety data independent of industry. PMID:22658930

  20. Measurements of galactic cosmic ray shielding with the CRaTER instrument

    NASA Astrophysics Data System (ADS)

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

    2013-05-01

    The Cosmic Ray Telescope for the Effects of Radiation (CRaTER) instrument aboard the Lunar Reconnaissance Orbiter has been measuring energetic charged particles from the galactic cosmic rays (GCRs) and solar particle events in lunar orbit since 2009. CRaTER includes three pairs of silicon detectors, separated by pieces of tissue-equivalent plastic that shield two of the three pairs from particles incident at the zenith-facing end of the telescope. Heavy-ion beams studied in previous ground-based work have been shown to be reasonable proxies for the GCRs when their energies are sufficiently high. That work, which included GCR simulations, led to predictions for the amount of dose reduction that would be observed by CRaTER. Those predictions are compared to flight data obtained by CRaTER in 2010-2011.

  1. 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...

  2. 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

  3. Integrated biclustering of heterogeneous genome-wide datasets for the inference of global regulatory networks

    PubMed Central

    Reiss, David J; Baliga, Nitin S; Bonneau, Richard

    2006-01-01

    Background The learning of global genetic regulatory networks from expression data is a severely under-constrained problem that is aided by reducing the dimensionality of the search space by means of clustering genes into putatively co-regulated groups, as opposed to those that are simply co-expressed. Be cause genes may be co-regulated only across a subset of all observed experimental conditions, biclustering (clustering of genes and conditions) is more appropriate than standard clustering. Co-regulated genes are also often functionally (physically, spatially, genetically, and/or evolutionarily) associated, and such a priori known or pre-computed associations can provide support for appropriately grouping genes. One important association is the presence of one or more common cis-regulatory motifs. In organisms where these motifs are not known, their de novo detection, integrated into the clustering algorithm, can help to guide the process towards more biologically parsimonious solutions. Results We have developed an algorithm, cMonkey, that detects putative co-regulated gene groupings by integrating the biclustering of gene expression data and various functional associations with the de novo detection of sequence motifs. Conclusion We have applied this procedure to the archaeon Halobacterium NRC-1, as part of our efforts to decipher its regulatory network. In addition, we used cMonkey on public data for three organisms in the other two domains of life: Helicobacter pylori, Saccharomyces cerevisiae, and Escherichia coli. The biclusters detected by cMonkey both recapitulated known biology and enabled novel predictions (some for Halobacterium were subsequently confirmed in the laboratory). For example, it identified the bacteriorhodopsin regulon, assigned additional genes to this regulon with apparently unrelated function, and detected its known promoter motif. We have performed a thorough comparison of cMonkey results against other clustering methods, and find that

  4. 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

  5. Selection and installation of CRA-clad flowlines in the Madden Deep Unit

    SciTech Connect

    Craig, B.D.; Eckroth, J.J.

    1997-05-01

    This paper describes the selection and installation of corrosion-resistant-alloy (CRA)-clad flowlines and solid Alloy 625 piping well-head tie-ins for hookup of wells in the Madden Deep Unit of Wyoming. The highly corrosive nature of the gas, coupled with the anticipated production of elemental sulfur and the close proximity to populated areas, dictated the use of these specialty materials. The special fabrication and installation requirements for CRA-clad flowlines, including some of the difficulties, are presented. The completion and production of high-pressure, high-temperature gas wells in the Madden Deep Unit of Wyoming has required the extensive use of CRA`s downhole because of the extremely corrosive conditions anticipated from the high H{sub 2}S and CO{sub 2} content of the gas.

  6. 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

  7. 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

  8. 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

  9. 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…

  10. 38 CFR 1.916 - Disclosure of debt information to consumer reporting agencies (CRA).

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2011-07-01 2011-07-01 false Disclosure of debt information to consumer reporting agencies (CRA). 1.916 Section 1.916 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS GENERAL PROVISIONS Standards for Collection of Claims § 1.916 Disclosure of debt information to consumer...

  11. 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

  12. Consistent Robustness Analysis (CRA) Identifies Biologically Relevant Properties of Regulatory Network Models

    PubMed Central

    Saithong, Treenut; Painter, Kevin J.; Millar, Andrew J.

    2010-01-01

    Background A number of studies have previously demonstrated that “goodness of fit” is insufficient in reliably classifying the credibility of a biological model. Robustness and/or sensitivity analysis is commonly employed as a secondary method for evaluating the suitability of a particular model. The results of such analyses invariably depend on the particular parameter set tested, yet many parameter values for biological models are uncertain. Results Here, we propose a novel robustness analysis that aims to determine the “common robustness” of the model with multiple, biologically plausible parameter sets, rather than the local robustness for a particular parameter set. Our method is applied to two published models of the Arabidopsis circadian clock (the one-loop [1] and two-loop [2] models). The results reinforce current findings suggesting the greater reliability of the two-loop model and pinpoint the crucial role of TOC1 in the circadian network. Conclusions Consistent Robustness Analysis can indicate both the relative plausibility of different models and also the critical components and processes controlling each model. PMID:21179566

  13. Validation of PREDICCS using LRO/CRaTER observations during three major solar events in 2012

    NASA Astrophysics Data System (ADS)

    Joyce, C. J.; Schwadron, N. A.; Wilson, J. K.; Spence, H. E.; Kasper, J. C.; Golightly, M.; Blake, J. B.; Mazur, J.; Townsend, L. W.; Case, A. W.; Semones, E.; Smith, S.; Zeitlin, C. J.

    2013-06-01

    (Predictions of Radiation from Release, EMMREM, and Data Incorporating the CRaTER, COSTEP and other SEP measurements, prediccs.sr.unh.edu) is an online system designed to provide a near real-time characterization of the radiation environment of the inner heliosphere. PREDICCS utilizes data from various satellites in conjunction with numerical models such as the Earth-Moon-Mars Radiation Environment Module (EMMREM) to produce dose rate and particle flux data at the Earth, Moon and Mars. The Cosmic Ray Telescope for the Effects of Radiation (CRaTER) instrument launched aboard the Lunar Reconnaissance Orbiter (LRO) spacecraft in 2009 and designed to measure energetic particle radiation, offers an opportunity to test the capability of PREDICCS to accurately describe the lunar radiation environment. We provide comparisons between dose rates produced by PREDICCS with those measured by CRaTER during three major solar energetic particle (SEP) events that occurred in 2012. In addition, using EMMREM data products together with our archive of measured CRaTER dose rates, we compute the modulation potential at the Moon throughout the LRO mission and, using this, compute the background GCR dose rate during each event. We demonstrate reasonable agreement between PREDICCS and CRaTER dose rates and come to the conclusion that PREDICCS provides credible characterization of the lunar radiation environment. This study represents the first multi-event validation, via in situ measurement, of radiation models such as EMMREM, which should prove to be valuable in future efforts in risk assessment and in the study of radiation in the inner heliosphere.

  14. Fructose 1-phosphate is the one and only physiological effector of the Cra (FruR) regulator of Pseudomonas putida

    PubMed Central

    Chavarría, Max; Durante-Rodríguez, Gonzalo; Krell, Tino; Santiago, César; Brezovsky, Jan; Damborsky, Jiri; de Lorenzo, Víctor

    2014-01-01

    Fructose-1-phosphate (F1P) is the preferred effector of the catabolite repressor/activator (Cra) protein of the soil bacterium Pseudomonas putida but its ability to bind other metabolic intermediates in vivo is unclear. The Cra protein of this microorganism (CraPP) was submitted to mobility shift assays with target DNA sequences (the PfruB promoter) and candidate effectors fructose-1,6-bisphosphate (FBP), glucose 6-phosphate (G6P), and fructose-6-phosphate (F6P). 1 mM F1P was sufficient to release most of the Cra protein from its operators but more than 10 mM of FBP or G6P was required to free the same complex. However, isothermal titration microcalorimetry failed to expose any specific interaction between CraPP and FBP or G6P. To solve this paradox, transcriptional activity of a PfruB-lacZ fusion was measured in wild-type and ΔfruB cells growing on substrates that change the intracellular concentrations of F1P and FBP. The data indicated that PfruB activity was stimulated by fructose but not by glucose or succinate. This suggested that CraPP represses expression in vivo of the cognate fruBKA operon in a fashion dependent just on F1P, ruling out any other physiological effector. Molecular docking and dynamic simulations of the Cra-agonist interaction indicated that both metabolites can bind the repressor, but the breach in the relative affinity of CraPP for F1P vs FBP is three orders of magnitude larger than the equivalent distance in the Escherichia coli protein. This assigns the Cra protein of P. putida the sole role of transducing the presence of fructose in the medium into a variety of direct and indirect physiological responses. PMID:24918052

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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. PMID:23761295

  1. 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

  2. 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. PMID:23581668

  3. 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. PMID:26593223

  4. 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. PMID:26790415

  5. 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

  6. 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

  7. 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.

  8. 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. PMID:23378513

  9. 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…

  10. Global characterization of interferon regulatory factor (IRF) genes in vertebrates: Glimpse of the diversification in evolution

    PubMed Central

    2010-01-01

    Background Interferon regulatory factors (IRFs), which can be identified based on a unique helix-turn-helix DNA-binding domain (DBD) are a large family of transcription factors involved in host immune response, haemotopoietic differentiation and immunomodulation. Despite the identification of ten IRF family members in mammals, and some recent effort to identify these members in fish, relatively little is known in the composition of these members in other classes of vertebrates, and the evolution and probably the origin of the IRF family have not been investigated in vertebrates. Results Genome data mining has been performed to identify any possible IRF family members in human, mouse, dog, chicken, anole lizard, frog, and some teleost fish, mainly zebrafish and stickleback, and also in non-vertebrate deuterostomes including the hemichordate, cephalochordate, urochordate and echinoderm. In vertebrates, all ten IRF family members, i.e. IRF-1 to IRF-10 were identified, with two genes of IRF-4 and IRF-6 identified in fish and frog, respectively, except that in zebrafish exist three IRF-4 genes. Surprisingly, an additional member in the IRF family, IRF-11 was found in teleost fish. A range of two to ten IRF-like genes were detected in the non-vertebrate deuterostomes, and they had little similarity to those IRF family members in vertebrates as revealed in genomic structure and in phylogenetic analysis. However, the ten IRF family members, IRF-1 to IRF-10 showed certain degrees of conservation in terms of genomic structure and gene synteny. In particular, IRF-1, IRF-2, IRF-6, IRF-8 are quite conserved in their genomic structure in all vertebrates, and to a less degree, some IRF family members, such as IRF-5 and IRF-9 are comparable in the structure. Synteny analysis revealed that the gene loci for the ten IRF family members in vertebrates were also quite conservative, but in zebrafish conserved genes were distributed in a much longer distance in chromosomes. Furthermore

  11. 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.

  12. Analyses of Primary and Secondary Ion Contributions to LET Spectra for the CRaTER Instrument on LRO

    NASA Astrophysics Data System (ADS)

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

    2012-12-01

    The Cosmic Ray Telescope for the Effects of Radiation (CRaTER), an instrument on the Lunar Reconnaissance Orbiter (LRO) spacecraft, measures the energy depositions by solar and galactic cosmic radiations in its silicon detectors. These energy depositions are converted to linear energy transfer (LET) spectra, which forms the basis for the derivation of biological impact through calculation of quality factors, and dose equivalents based on observed charge distributions. In this work the Monte Carlo transport code HETC-HEDS (High Energy Transport Code - Human Exploration and Development in Space) and the NASA space radiation transport code HZETRN2010 are used to estimate LET contributions from the incident primary ions and their charged secondaries produced in nuclear collisions within the components of the CRaTER instrument. Comparisons of the calculated spectra with measurements of LET from the CRaTER instrument are made. Contributions of the primary ions and their charged secondaries to the LET are separately analyzed using the HETC-HEDS results. Energetic delta rays escaping from the instrument will lower the measured LET values below estimates using Bethe-Bloch theory. Estimates of LET contributions from primaries will be corrected for the delta ray escapes using methods developed by Badhwar (Christie et al, Nuclear Instruments and Methods A, 1987). The resulting predictions for LET spectra are compared to CRaTER observations to validate the model and for use in deriving biological impact factors.

  13. 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

  14. VizieR Online Data Catalog: Extinction toward CrA and Lup (Andreazza+, 1996)

    NASA Astrophysics Data System (ADS)

    Andreazza, C. M.; Vilas-Boas, J. W. S.

    1996-01-01

    Star counts technique is used towards southern dark globular filaments situated in the cloud complexes of Corona Australis and Lupus. Tables and maps of the distribution of visual extinction are presented for each filament. Lower limit masses for the filaments and condensations have been estimated and the central coordinates of the condensations are also given. R CrA is the most active star forming region among the filaments studied in this work whereas Lupus 1, with almost the same lower limit of mass, has only a few T Tauri stars and just one young embedded object. The distribution of direction of the magnetic field in the condensations of Lupus, suggests that the condensation morphologies does not have any apparent relation with the magnetic field orientation. (5 data files).

  15. High-niobium bearing steel for base material of CRA clad UOE pipe

    SciTech Connect

    Terada, Y.; Tamehiro, H.; Uemori, R.; Maruyama, N.; Ogawa, H.; Takahashi, A.

    1994-12-31

    The manufacturing technology of corrosion resistant alloy (CRA) clad UOE pipe by applying thermomechanical control process (TMCP) has been studied. In order to obtain good pitting corrosion resistance in the Incoloy 825 layer, it is necessary to ensure complete recrystallization and suppress the precipitation of chromium carbides in the Incoloy 825 layer after rolling. To this end the clad plate was finish-rolled at high temperature and water-cooled after appropriate air cooling. However, in conventional steel, high temperature rolling considerably deteriorates the low-temperature toughness, therefore, it was found that increasing the niobium content causes the microstructure to refine remarkably and provides an excellent balance of strength and low-temperature toughness at a niobium content of about 0.1% even in high temperature rolling. The grain refinement by adding high niobium is attributable to suppression of austenite grain coarsening during slab-reheating by Nb(CN) particles, a rise in recrystallization stop temperature of austenite.

  16. Assessment of Technology Readiness Level of a Carbon Dioxide Reduction Assembly (CRA) for use on International Space Station

    NASA Technical Reports Server (NTRS)

    Murdoch, Karen; Smith, Fred; Perry, Jay; Green, Steve

    2004-01-01

    When technologies are traded for incorporation into vehicle systems to support a specific mission scenario, they are often assessed in terms of Technology Readiness Level (TRL). TRL is based on three major categories of Core Technology Components, Ancillary Hardware and System Maturity, and Control and Control Integration. This paper describes the Technology Readiness Level assessment of the Carbon Dioxide Reduction Assembly (CRA) for use on the International Space Station. A team comprising of the NASA Johnson Space Center, Marshall Space Flight Center, Southwest Research Institute and Hamilton Sundstrand Space Systems International have been working on various aspects of the CRA to bring its TRL from 4/5 up to 6. This paper describes the work currently being done in the three major categories. Specific details are given on technology development of the Core Technology Components including the reactor, phase separator and CO2 compressor.

  17. 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

  18. 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

  19. The spectroscopic orbit and subsynchronous rotation of the Herbig Ae/Be star TY CrA

    NASA Astrophysics Data System (ADS)

    Casey, Brian W.; Mathieu, Robert D.; Suntzeff, Nicholas B.; Lee, Chi-Wai; Cardelli, Jason A.

    1993-06-01

    High-resolution spectra of the Herbig Ae/Be eclipsing binary TY CrA are obtained and used to measure high-precision radial velocities. We find TY CrA to be a single-lined spectroscopic binary having a circular orbit with a period of 2.88873 days, supporting a previous photometric period of 2.888777 days. We also place an upper limit of 15 km/s on the v sin i of the primary. Such a low rotational velocity corresponds to highly subsynchronous rotation, presuming the stellar rotation axis to have an inclination angle near 90. We argue that this remarkably slow rotation velocity in a circular orbit cannot be explained in the context of stellar evolution and tidal interactions alone. Presuming TY CrA to be a pre-main-sequence star, the origin of its subsynchronism must lie in a braking mechanism early in the life of the primary. Finally, we note that the lack of NIR excess emission indicates that no optically thick disk material is present within a few orbital separations of the binary.

  20. Solar modulation of the deep space galactic cosmic ray lineal energy spectrum measured by CRaTER, 2009-2014

    NASA Astrophysics Data System (ADS)

    Zeitlin, C.; Case, A. W.; Schwadron, N. A.; Spence, H. E.; Mazur, J. E.; Joyce, C. J.; Looper, M. D.; Jordan, A.; Rios, R. R.; Townsend, L. W.; Kasper, J. C.; Blake, J. B.; Smith, S.; Wilson, J.; Iwata, Y.

    2016-03-01

    The Cosmic Ray Telescope for the Effects of Radiation (CRaTER) is an energetic particle detector flying aboard the Lunar Reconnaissance Orbiter. Since arriving at the Moon in 2009, CRaTER has observed the deep solar minimum of solar cycle 23, the ascending phase of cycle 24, the very weak maximum of cycle 24, and in recent months, what appears to be the start of the descending phase of cycle 24. In earlier work, we presented lineal energy spectra of galactic cosmic rays (GCRs) at solar minimum for different shielding depths. The long period of CRaTER observations allows us to study the evolution of these spectra as a function of solar modulation. As solar modulation increases, the total flux of GCRs decreases, and lower-energy ions are preferentially removed from the spectrum of ions that arrive in the inner heliosphere. These effects lead to modest variations in the lineal energy spectrum as a function of time. GCR fluxes at the 2009/2010 solar minimum were high by historical standards and at solar maximum remained high compared to earlier maxima.

  1. 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.

  2. Early Results from the LRO Cosmic Ray Telescope for the Effects of Radiation (CRaTER) During this Historic Solar Minimum (Invited)

    NASA Astrophysics Data System (ADS)

    Spence, H. E.; Kasper, J. C.; Golightly, M. J.; Blake, J. B.; Mazur, J. E.; Townsend, L. W.; Case, A. W.; Looper, M. D.; Larsen, B. A.; Stubbs, T. J.; Zeitlin, C. J.; Semones, E.; Onsager, T. G.; Huang, C.; Jordan, A.

    2009-12-01

    We describe early results from a new instrument, the Cosmic Ray Telescope for the Effects of Radiation (CRaTER), which is providing measurements of energetic particles while in orbit around the Moon onboard the Lunar Reconnaissance Orbiter (LRO) mission. CRaTER measures the effects of ionizing energy loss in matter due to penetrating solar energetic protons (SEP) and galactic cosmic rays (GCR), specifically in six silicon solid-state detectors and after interactions with tissue-equivalent plastic (TEP), a synthetic analog of human tissue. The CRaTER investigation quantifies the linear energy transfer (LET) spectrum in these materials through direct measurements with the lunar space radiation environment, particularly the interactions of ions with energies above 10 MeV. Combined with models of radiation transport through materials, CRaTER LET measurements constrain models of the biological effects of ionizing radiation in the lunar environment as well as provide valuable information on radiation effects on electronic systems in deep space. In addition to these human exploration goals, CRaTER measurement capabilities provide new insights on the spatial and temporal variability of the SEP and GCR populations and their interactions with the lunar surface. We present an overview of the CRaTER instrument, its exploration and science goals, and early results from flight observations obtained since LRO’s launch in June 2009 until present, an interesting interval during this historic solar minimum accompanied by record high GCR intensity.

  3. CRA-W's committee of intervention: analyse of catchments polluted with pesticides.

    PubMed

    Noel, S; Bah, B B; Collinet, G; Buffet, D; Sorel, A; Hallet, V

    2008-01-01

    In the Walloon Region of Belgium, a committee of intervention has been created to investigate problems of pesticide contamination of various catchments use for drinking water production. This committee involves the Agricultural Research centre--Wallonia (CRA-W, project coordinator) and some University experts. It is funded by the Société Publique de Gestion des Eaux (SPGE). The diagnosis method, base on the AQUAPLAINE method (Arvatis-France), consists of 4 steps. The first step is the preparation of diagnosis (at the office) that takes into account the paper risk of active ingredients. and their uses, the identification of the agricultural parcels, the collection of cartographic and numeric data, the description of the hydrogeological and pedological contexts and the study of the meteorological data in relation with the period of pollution. The second step consists of making a plot diagnosis (on the field) to identify the way of transfer inside the plot and collecting data. At the third step, the people who can apply PPP treatment close to the catchment are met (farmers and city services). Information are collected on treatments applied and on the state of parcels. Based on the hypothesis of pollution cause, the committee proposes solution to solve the problem. One of the catchment that has been investigated by the committee is located at Biesmerée, (Namur province, in Belgium). A temporally contamination was caused by 4 pesticides : chlortoluron, isoproturon, trifluralin and diflufenican. After investigations, it seems that the pollution was probably due to the hydrogeological context. As the river is locally perched over the aquifer, the presence of Poly-aromatic hydrocarbons (PAHs) could be due to the infiltration of surface water inside the catchment or/and to the presence of a sinkhole temporally activated during river flood period. Infiltration rate has to be assessed and river bank impermeabilization is recommended. PMID:19226832

  4. SB242084, flumazenil, and CRA1000 block ethanol withdrawal-induced anxiety in rats.

    PubMed

    Knapp, Darin J; Overstreet, David H; Moy, Sheryl S; Breese, George R

    2004-02-01

    Anxiety-like behaviors are integral features of withdrawal from chronic ethanol exposure. In the experiments in the current study, we tested the hypothesis that anxiety can be regulated independently of other withdrawal signs and thus may be responsive to selective pharmacological agents. For 17 days, rats were fed ethanol (8-12 g/kg/day) in a liquid diet. Between 5 and 6 h after cessation of ethanol treatment, rats were tested in either the social interaction or plus-maze test of anxiety-like behavior after treatment with drugs hypothesized to have anxiolytic action. SB242084, flumazenil, and CRA1000-antagonists for 5-hydroxytryptamine (serotonin) (5-HT) 2C (5-HT(2C)), benzodiazepine, and corticotropin-releasing factor type 1 (CRF(1)) receptors, respectively-attenuated decreased social interaction without concomitant effects on activity measures. In contrast, ifenprodil, MDL 72222, and zolpidem-antagonists for N-methyl-d-aspartate (NMDA) and 5-HT(3) receptors, and agonist for benzodiazepine type 1 receptors, respectively-did not share this effect. Results for SB242084, flumazenil, and ifenprodil in the elevated plus-maze test were comparable to those in the social interaction test. These results support the suggestion that multiple neuronal systems (CRF(1), 5-HT(2C), and benzodiazepine receptors) contribute to the ethanol withdrawal sign of decreased social interaction. Furthermore, the selective effects of pharmacological agents on social interaction seem to indicate that this behavior can be dissociated from other signs. Because anxiety may be a complicating factor in alcohol withdrawal and relapse, future studies of this type are needed to provide focus for the effort to define selective and novel antianxiety agents for these disorders. PMID:15163561

  5. Analyses of the ONeMg Novae in the IUE Archives II: Nova V693 CrA 1981

    NASA Astrophysics Data System (ADS)

    Vanlandingham, K. M.; Starrfield, S.; Wagner, R. M.; Shore, S. N.; Sonneborn, G.

    1996-12-01

    We have begun a study of the subclass of novae known as `neon' or ONeMg novae (Starrfield, Sparks & Truran 1986). Novae of this type are characterized by strong neon emission lines in their spectra and high ejecta velocities. These novae are thought to occur on ONeMg white dwarfs with masses near the Chandrasekhar limit. Our study includes Nova Herculis 1991, Nova Corona Austrinae 1981, and Nova LMC 1990 #1. Analysis of Her 91 (Vanlandingham et al. 1996 MNRAS 282 563) is complete and we are currently working on LMC 90 #1. Here we present our recent results for Corona Austrinae 1981. Nova V693 Corona Austrinae (CrA81) was discovered on April 2.75 UT 1981. Observations with IUE began on 1981 April 10 and continued through 1981 November 14. CrA81 was a fast ONeMg nova, with t_2 =~ 8 days and t_3 =~ 14 days. By matching the SWP and LWR spectra together at 2000 Angstroms and adjusting the value of the reddening until the continuum had a roughly constant slope we find E(B-V) =~ 0.2+/-0.1 for the nova. Using maximum magnitude-decay rate relationships (Della Valle 1995; Livio 1992) we find the distance to CrA81 to be 14.3+/-0.2 kpc. We used the photoionization code CLOUDY 84 and the minimization routine MINUIT to determine elemental abundances for the nova. Our results show all of the elements to be enhanced relative to solar material. While helium, carbon, and magnesium are only marginally enhanced, oxygen and silicon are about 20 times solar, and nitrogen and neon are 140 and 287 times solar, respectively. The high neon abundance supports the fact that CrA81 is an ONeMg nova. These results are based on independent fits to three different observations, spanning over six months. Williams et al (1985) and Andrea et al (1994) also performed abundance analyses on CrA81. Andrea's values are 2 to 5 times larger than those of Williams. Our abundance values are lower than both Williams and Andrea for He, C, O, Mg, and Al, with our values being closer to Williams for N, Ne, and Si

  6. 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.

  7. Radiation environment at the Moon: Comparisons of transport code modeling and measurements from the CRaTER instrument

    NASA Astrophysics Data System (ADS)

    Porter, Jamie A.; Townsend, Lawrence W.; Spence, Harlan; Golightly, Michael; Schwadron, Nathan; Kasper, Justin; Case, Anthony W.; Blake, John B.; Zeitlin, Cary

    2014-06-01

    The Cosmic Ray Telescope for the Effects of Radiation (CRaTER), an instrument carried on the Lunar Reconnaissance Orbiter spacecraft, directly measures the energy depositions by solar and galactic cosmic radiations in its silicon wafer detectors. These energy depositions are converted to linear energy transfer (LET) spectra. High LET particles, which are mainly high-energy heavy ions found in the incident cosmic ray spectrum, or target fragments and recoils produced by protons and heavier ions, are of particular importance because of their potential to cause significant damage to human tissue and electronic components. Aside from providing LET data useful for space radiation risk analyses for lunar missions, the observed LET spectra can also be used to help validate space radiation transport codes, used for shielding design and risk assessment applications, which is a major thrust of this work. In this work the Monte Carlo transport code HETC-HEDS (High-Energy Transport Code-Human Exploration and Development in Space) is used to estimate LET contributions from the incident primary ions and their charged secondaries produced by nuclear collisions as they pass through the three pairs of silicon detectors. Also in this work, the contributions to the LET of the primary ions and their charged secondaries are analyzed and compared with estimates obtained using the deterministic space radiation code HZETRN 2010, developed at NASA Langley Research Center. LET estimates obtained from the two transport codes are compared with measurements of LET from the CRaTER instrument during the mission. Overall, a comparison of the LET predictions of the HETC-HEDS code to the predictions of the HZETRN code displays good agreement. The code predictions are also in good agreement with the CRaTER LET measurements above 15 keV/µm but differ from the measurements for smaller values of LET. A possible reason for this disagreement between measured and calculated spectra below 15 keV/µm is an

  8. Unraveling the regulatory network in Streptococcus pyogenes: the global response regulator CovR represses rivR directly.

    PubMed

    Roberts, Samantha A; Churchward, Gordon G; Scott, June R

    2007-02-01

    The response regulator CovR acts as a master regulator of virulence in Streptococcus pyogenes by repressing transcription of approximately 15% of the group A streptococcus genome directly or indirectly. We demonstrate that phosphorylated CovR represses transcription of rivR directly by binding to conserved sequences located downstream from the promoter to block procession of RNA polymerase. This establishes the first link in a regulatory network where CovR interacts directly with other proteins that modulate gene expression. PMID:16963575

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

    PubMed Central

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

    2015-01-01

    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. PMID:26227973

  10. Radiation modeling in the Earth and Mars atmospheres using LRO/CRaTER with the EMMREM Module

    NASA Astrophysics Data System (ADS)

    Joyce, C. J.; Schwadron, N. A.; Wilson, J. K.; Spence, H. E.; Kasper, J. C.; Golightly, M.; Blake, J. B.; Townsend, L. W.; Case, A. W.; Semones, E.; Smith, S.; Zeitlin, C. J.

    2014-02-01

    We expand upon the efforts of Joyce et al. (2013), who computed the modulation potential at the Moon using measurements from the Cosmic Ray Telescope for the Effects of Radiation (CRaTER) instrument on the Lunar Reconnaissance Orbiter (LRO) spacecraft along with data products from the Earth-Moon-Mars Radiation Environment Module (EMMREM). Using the computed modulation potential, we calculate galactic cosmic ray (GCR) dose and dose equivalent rates in the Earth and Mars atmospheres for various altitudes over the course of the LRO mission. While we cannot validate these predictions by directly comparable measurement, we find that our results conform to expectations and are in good agreement with the nearest available measurements and therefore may be used as reasonable estimates for use in efforts in risk assessment in the planning of future space missions as well as in the study of GCRs. PREDICCS (Predictions of radiation from REleASE, EMMREM, and Data Incorporating the CRaTER, COSTEP, and other solar energetic particles measurements) is an online system designed to provide the scientific community with a comprehensive resource on the radiation environments of the inner heliosphere. The data products shown here will be incorporated into PREDICCS in order to further this effort and daily updates will be made available on the PREDICCS website (http://prediccs.sr.unh.edu).

  11. Parameterizations of the linear energy transfer spectrum for the CRaTER instrument during the LRO mission

    NASA Astrophysics Data System (ADS)

    Townsend, L. W.; Charara, Y. M.; Delauder, N.; Pourarsalan, M.; Anderson, J. A.; Fisher, C. M.; Spence, H. E.; Schwadron, N. A.; Golightly, M. J.; Cucinotta, F. A.

    2010-03-01

    The Cosmic Ray Telescope for the Effects of Radiation (CRaTER) instrument was launched as part of the Lunar Reconnaissance Orbiter (LRO) spacecraft in June 2009. Its purpose is to measure the linear energy transfer (LET) spectrum in lunar orbit as an aid in determining risks to human crews on future lunar missions. Part of the preparations for the mission involved estimating the LET spectrum for the anticipated environment that the instrument is likely to see during the 1 year operational phase of the LRO mission. Detailed estimates of LET spectra in the six silicon detectors and two tissue equivalent plastic segments were made using the beta version of the HETC-HEDS Monte Carlo transport code. Tables of LET in each detector component, for incident particle elemental species from hydrogen through iron, were carried out at incident particle energies from 20 MeV per nucleon to 3 GeV per nucleon. The LET values in these tables have been parameterized by elemental species and energy for ease in quickly and accurately estimating the LET response for any input solar or galactic cosmic ray spectrum likely to be encountered during the lifetime of the instrument. The parameterized LET values are in excellent agreement with the HETC-HEDS calculations. Typical differences are on the order of a few percent. These parameterizations will also be useful in validation studies of the Earth-Moon-Mars Radiation Environment Module using CRaTER measurements in lunar orbit.

  12. CovS/CovR of group B streptococcus: a two-component global regulatory system involved in virulence.

    PubMed

    Lamy, Marie-Cécile; Zouine, Mohammed; Fert, Juliette; Vergassola, Massimo; Couve, Elisabeth; Pellegrini, Elisabeth; Glaser, Philippe; Kunst, Frank; Msadek, Tarek; Trieu-Cuot, Patrick; Poyart, Claire

    2004-12-01

    In this study, we carried out a detailed structural and functional analysis of a Streptococcus agalactiae (GBS) two-component system which is orthologous to the CovS/CovR (CsrS/CsrR) regulatory system of Streptococcus pyogenes. In GBS, covR and covS are part of a seven gene operon transcribed from two promoters that are not regulated by CovR. A DeltacovSR mutant was found to display dramatic phenotypic changes such as increased haemolytic activity and reduced CAMP activity on blood agar. Adherence of the DeltacovSR mutant to epithelial cells was greatly increased and analysis by transmission electron microscopy revealed the presence at its surface of a fibrous extracellular matrix that might be involved in these intercellular interactions. However, the DeltacovSR mutant was unable to initiate growth in RPMI and its viability in human normal serum was greatly impaired. A major finding of this phenotypic analysis was that the CovS/CovR system is important for GBS virulence, as a 3 log increase of the LD(50) of the mutant strain was observed in the neonate rat sepsis model. The pleiotropic phenotype of the DeltacovSR mutant is in full agreement with the large number of genes controlled by CovS/CovR as seen by expression profiling analysis, many of which encode potentially secreted or cell surface-associated proteins: 76 genes are repressed whereas 63 were positively regulated. CovR was shown to bind directly to the regulatory regions of several of these genes and a consensus CovR recognition sequence was proposed using both DNase I footprinting and computational analyses. PMID:15554966

  13. Involvement of Regulatory Interactions among Global Regulators GlxR, SugR, and RamA in Expression of ramA in Corynebacterium glutamicum

    PubMed Central

    Toyoda, Koichi; Teramoto, Haruhiko; Gunji, Wataru; Inui, Masayuki

    2013-01-01

    The central carbon metabolism genes in Corynebacterium glutamicum are under the control of a transcriptional regulatory network composed of several global regulators. It is known that the promoter region of ramA, encoding one of these regulators, interacts with its gene product, RamA, as well as with the two other regulators, GlxR and SugR, in vitro and/or in vivo. Although RamA has been confirmed to repress its own expression, the roles of GlxR and SugR in ramA expression have remained unclear. In this study, we examined the effects of GlxR binding site inactivation on expression of the ramA promoter-lacZ fusion in the genetic background of single and double deletion mutants of sugR and ramA. In the wild-type background, the ramA promoter activity was reduced to undetectable levels by the introduction of mutations into the GlxR binding site but increased by sugR deletion, indicating that GlxR and SugR function as the transcriptional activator and repressor, respectively. The marked repression of ramA promoter activity by the GlxR binding site mutations was largely compensated for by deletions of sugR and/or ramA. Furthermore, ramA promoter activity in the ramA-sugR double mutant was comparable to that in the ramA mutant but was significantly higher than that in the sugR mutant. Taken together, it is likely that the level of ramA expression is dynamically balanced by GlxR-dependent activation and repression by RamA along with SugR in response to perturbation of extracellular and/or intracellular conditions. These findings add multiple regulatory loops to the transcriptional regulatory network model in C. glutamicum. PMID:23396909

  14. 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. PMID:24786463

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

    PubMed

    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. 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

  17. Global Identification of SMAD2 Target Genes Reveals a Role for Multiple Co-regulatory Factors in Zebrafish Early Gastrulas*

    PubMed Central

    Liu, Zhaoting; Lin, Xiwen; Cai, Zhaoping; Zhang, Zhuqiang; Han, Chunsheng; Jia, Shunji; Meng, Anming; Wang, Qiang

    2011-01-01

    Nodal and Smad2/3 signals play pivotal roles in mesendoderm induction and axis determination during late blastulation and early gastrulation in vertebrate embryos. However, Smad2/3 direct target genes during those critical developmental stages have not been systematically identified. Here, through ChIP-chip assay, we show that the promoter/enhancer regions of 679 genes are bound by Smad2 in the zebrafish early gastrulas. Expression analyses confirm that a significant proportion of Smad2 targets are indeed subjected to Nodal/Smad2 regulation at the onset of gastrulation. The co-existence of DNA-binding sites of other transcription factors in the Smad2-bound regions allows the identification of well known Smad2-binding partners, such as FoxH1 and Lef1/β-catenin, as well as many previously unknown Smad2 partners, including Oct1 and Gata6, during embryogenesis. We demonstrate that Oct1 physically associates with and enhances the transcription and mesendodermal induction activity of Smad2, whereas Gata6 exerts an inhibitory role in Smad2 signaling and mesendodermal induction. Thus, our study systemically uncovers a large number of Smad2 targets in early gastrulas and suggests cooperative roles of Smad2 and other transcription factors in controlling target gene transcription, which will be valuable for studying regulatory cascades during germ layer formation and patterning of vertebrate embryos. PMID:21669877

  18. 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...

  19. 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

  20. Molecular characterization of global regulatory RNA species that control pathogenicity factors in Erwinia amylovora and Erwinia herbicola pv. gypsophilae.

    PubMed

    Ma, W; Cui, Y; Liu, Y; Dumenyo, C K; Mukherjee, A; Chatterjee, A K

    2001-03-01

    rsmB(Ecc) specifies a nontranslatable RNA regulator that controls exoprotein production and pathogenicity in soft rot-causing Erwinia carotovora subsp. carotovora. This effect of rsmB(Ecc) RNA is mediated mostly by neutralizing the function of RsmA(Ecc), an RNA-binding protein of E. carotovora subsp. carotovora, which acts as a global negative regulator. To determine the occurrence of functional homologs of rsmB(Ecc) in non-soft-rot-causing Erwinia species, we cloned the rsmB genes of E. amylovora (rsmB(Ea)) and E. herbicola pv. gypsophilae (rsmB(Ehg)). We show that rsmB(Ea) in E. amylovora positively regulates extracellular polysaccharide (EPS) production, motility, and pathogenicity. In E. herbicola pv. gypsophilae, rsmB(Ehg) elevates the levels of transcripts of a cytokinin (etz) gene and stimulates the production of EPS and yellow pigment as well as motility. RsmA(Ea) and RsmA(Ehg) have more than 93% identity to RsmA(Ecc) and, like the latter, function as negative regulators by affecting the transcript stability of the target gene. The rsmB genes reverse the negative effects of RsmA(Ea), RsmA(Ehg), and RsmA(Ecc), but the extent of reversal is highest with homologous combinations of rsm genes. These observations and findings that rsmB(Ea) and rsmB(Ehg) RNA bind RsmA(Ecc) indicate that the rsmB effect is channeled via RsmA. Additional support for this conclusion comes from the observation that the rsmB genes are much more effective as positive regulators in a RsmA(+) strain of E. carotovora subsp. carotovora than in its RsmA(-) derivative. E. herbicola pv. gypsophilae produces a 290-base rsmB transcript that is not subject to processing. By contrast, E. amylovora produces 430- and 300-base rsmB transcripts, the latter presumably derived by processing of the primary transcript as previously noted with the transcripts of rsmB(Ecc). Southern blot hybridizations revealed the presence of rsmB homologs in E. carotovora, E. chrysanthemi, E. amylovora, E. herbicola, E

  1. A Dynamical Mass Measurement for the Pre-Main-Sequence Secondary of the Eclipsing Binary TY CrA

    NASA Astrophysics Data System (ADS)

    Mathieu, R. D.; Casey, B.; Vaz, L. P.; Andersen, J.; Suntzeff, N.; Walter, F.

    1994-05-01

    Using the Danish 50cm telescope at La Silla we have obtained simultaneous uvby light curves of the eclipsing binary TY CrA, located in the Corona Australis star-forming region. We have securely detected the secondary eclipse (2% depth in y). We have also obtained high-resolution (R=15000) echelle spectra in the red. Along with the primary spectrum, absorption lines of the secondary and a previously unknown tertiary component have been found. In particular, both the secondary and tertiary are detected at the Lithium 6708 Angstroms line. Based on temperature insensitive lines the tertiary/secondary luminosity ratio at ~ 6400 Angstroms is ~ 1.5. When combined with our previous single-lined orbital solution for the primary (Casey, B.W., Mathieu, R.D., Suntzeff, N.B., Lee, C.W., and Cardelli, J.A. 1993, Astron. Journal, 105, 2276) the secondary radial-velocity measurements provide a mass ratio of 0.521+/-0.007. Using a modified form of the Wilson-Devinney formalism, our light curve solution gives an inclination angle of 81°, masses and radii of (3.2 M_sun, 1.8 R_sun) and (1.7 M_sun, 2.3 R_sun) for the primary and secondary respectively. Based on both spectral classification and uvby colors we adopt a primary effective temperature of 12,000 +/- 500 K. Using Kurucz atmosphere models for both stars in the WD solution, we derive a temperature of 5,000 K for the secondary, thus fully specifying the system. The primary lies on the ZAMS, while the secondary lies at the base of the Hayashi tracks. The secondary provides the first dynamical mass calibration with which to test theoretical calculations of Hayashi tracks. We will evaluate several modern theoretical pre-main sequence evolutionary models with respect to TY CrA. The vsin i of the secondary spectrum is 40 km/sec, making the secondary rotation synchronous with the orbital motion. Given that the primary is remarkably subsynchronous (Casey et al. 1993 and new spectra), we conclude that the orbit was tidally circularized

  2. Theoretical investigation of the neutron star in low-mass X-ray binary X1822-371 (V691 CrA)

    NASA Astrophysics Data System (ADS)

    Monowar Hossein, Sk.; Farhad, Nur; Molla, Sajahan; Kalam, Mehedi

    2016-06-01

    We propose a model for the neutron star in low-mass X-ray binary (LMXB) X1822-371 (V691 CrA) (Muñoz-Darius et al. in Astrophys. J. 635:502, 2005). Here we investigate the physical phenomena of the neutron star in LMXB X1822-371 (V691 CrA) by using the Tolman-IV solution (Tolman in Phys. Rev. 55:364, 1939). Using our model, we evaluate central density (ρ0), surface density (ρb), central pressure (p 0), surface redshift (Z s) and probable radius of the above mentioned neutron star, which is very much consistent with reported data. We also obtain a possible equation of state (EoS) of the star which is physically acceptable.

  3. 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.

  4. FliZ is a global regulatory protein affecting the expression of flagellar and virulence genes in individual Xenorhabdus nematophila bacterial cells.

    PubMed

    Jubelin, Grégory; Lanois, Anne; Severac, Dany; Rialle, Stéphanie; Longin, Cyrille; Gaudriault, Sophie; Givaudan, Alain

    2013-10-01

    Heterogeneity in the expression of various bacterial genes has been shown to result in the presence of individuals with different phenotypes within clonal bacterial populations. The genes specifying motility and flagellar functions are coordinately regulated and form a complex regulon, the flagellar regulon. Complex interplay has recently been demonstrated in the regulation of flagellar and virulence gene expression in many bacterial pathogens. We show here that FliZ, a DNA-binding protein, plays a key role in the insect pathogen, Xenorhabdus nematophila, affecting not only hemolysin production and virulence in insects, but efficient swimming motility. RNA-Seq analysis identified FliZ as a global regulatory protein controlling the expression of 278 Xenorhabdus genes either directly or indirectly. FliZ is required for the efficient expression of all flagellar genes, probably through its positive feedback loop, which controls expression of the flhDC operon, the master regulator of the flagellar circuit. FliZ also up- or downregulates the expression of numerous genes encoding non-flagellar proteins potentially involved in key steps of the Xenorhabdus lifecycle. Single-cell analysis revealed the bimodal expression of six identified markers of the FliZ regulon during exponential growth of the bacterial population. In addition, a combination of fluorescence-activated cell sorting and RT-qPCR quantification showed that this bimodality generated a mixed population of cells either expressing ("ON state") or not expressing ("OFF state") FliZ-dependent genes. Moreover, studies of a bacterial population exposed to a graded series of FliZ concentrations showed that FliZ functioned as a rheostat, controlling the rate of transition between the "OFF" and "ON" states in individuals. FliZ thus plays a key role in cell fate decisions, by transiently creating individuals with different potentials for motility and host interactions. PMID:24204316

  5. VizieR Online Data Catalog: YSOs candidates and knots in CrA cloud (Peterson+, 2011)

    NASA Astrophysics Data System (ADS)

    Peterson, D. E.; Caratti o Garatti, A.; Bourke, T. L.; Forbrich, J.; Gutermuth, R. A.; Jorgensen, J. K.; Allen, L. E.; Patten, B. M.; Dunham, M. M.; Harvey, P. M.; Merin, B.; Chapman, N. L.; Cieza, L. A.; Huard, T. L.; Knez, C.; Prager, B.; Evans, N. J.

    2011-10-01

    Corona Australis was observed with the Spitzer Infrared Array Camera (IRAC) at 3.6, 4.5, 5.8, and 8.0um and the Multiband Imaging Photometer for Spitzer (MIPS) at 24, 70, and 160um as part of two guaranteed time observation (GTO) programs (PID 6 (2004 Apr 20), 30784 (2006 Sep 25; 2007 May 29-30); PI: Fazio) as well as the Gould Belt Legacy Survey (PID 30574 (2008 May 10 & Oct 23); PI: Allen). The regions around the previously identified YSOs IRS 5, IRS 7, and IRAS 32 (IRAS 18595-3712) were observed with the SMA (Submillimeter Array) in the dust continuum near 225GHz (~1.3mm). Observations of the IRS 7 region were made on 2006 August 20 (program 2006-03-S046), while IRAS 32 and IRS 5 were observed on 2008 June 10 and 14 (program 2008A-S074). As a complement to the Spitzer and SMA data, we make use of multi-epoch H2 (2.12um) maps to detect jets and outflows in the CrA star-forming region to study their proper motions and identify the exciting sources. (8 data files).

  6. 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.

  7. Enhancement of the Synthesis of RpoN, Cra, and H-NS by Polyamines at the Level of Translation in Escherichia coli Cultured with Glucose and Glutamate▿ †

    PubMed Central

    Terui, Yusuke; Higashi, Kyohei; Taniguchi, Shiho; Shigemasa, Ai; Nishimura, Kazuhiro; Yamamoto, Kaneyoshi; Kashiwagi, Keiko; Ishihama, Akira; Igarashi, Kazuei

    2007-01-01

    Proteins whose synthesis is enhanced by polyamines at the level of translation were identified in a polyamine-requiring mutant cultured in the presence of 0.1% glucose and 0.02% glutamate instead of 0.4% glucose as an energy source. Under these conditions, enhancement of cell growth by polyamines was almost the same as that in the presence of 0.4% glucose. It was found that synthesis of RpoN, Cra, and H-NS was enhanced by polyamines at the level of translation at the early logarithmic phase of growth (A540 of 0.15). The effects of polyamines on synthesis of RpoN, H-NS, and Cra were due to the existence of unusual Shine-Dalgarno sequences (RpoN and H-NS) and an inefficient GUG initiation codon (Cra) in their mRNAs. Thus, rpoN, cra, and hns genes were identified as new members of the polyamine modulon. Because most of the polyamine modulon genes thus far identified encode transcription factors (RpoS [σ38], Cya, FecI [σ18], Fis, RpoN [σ54], Cra, and H-NS), DNA microarray analysis of mRNA expressed in cells was performed. At the early logarithmic phase of growth, a total of 97 species of mRNAs that were up-regulated by polyamines more than twofold were under the control of seven polyamine modulon genes mentioned above. PMID:17220219

  8. 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.

  9. 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

  10. Genome-wide Distribution of AdpA, a Global Regulator for Secondary Metabolism and Morphological Differentiation in Streptomyces, Revealed the Extent and Complexity of the AdpA Regulatory Network

    PubMed Central

    Higo, Akiyoshi; Hara, Hirofumi; Horinouchi, Sueharu; Ohnishi, Yasuo

    2012-01-01

    AdpA is a global transcriptional activator triggering morphological differentiation and secondary metabolism in Streptomyces griseus. AdpA influences the expression of >1000 genes; however, the overall picture of the AdpA regulon remains obscure. Here, we took snapshots of the distribution of AdpA across the chromosome in living S. griseus cells using chromatin immunoprecipitation/chromatin affinity precipitation-seq analysis. In both liquid and solid cultures, AdpA bound to >1200 similar sites, which were located on not only in putative regulatory regions (65%), but also in regions (35%) that appeared not to affect transcription. Transcriptome analysis indicated that ∼40% of the AdpA-binding sites in putative regulatory regions were involved in gene regulation. AdpA was indicated to act as a transcriptional repressor as well as an activator. Expression profiles of AdpA-target genes were very different between liquid and solid cultures, despite their similar AdpA-binding profiles. We concluded that AdpA directly controls >500 genes in cooperation with other regulatory proteins. A comprehensive competitive gel mobility shift assay of AdpA with 304 selected AdpA-binding sites revealed several unique characteristics of the DNA-binding property of AdpA. This study provides the first experimental insight into the extent of the AdpA regulon, indicating that many genes are under the direct control of AdpA. PMID:22449632

  11. Virulence control in group A Streptococcus by a two-component gene regulatory system: global expression profiling and in vivo infection modeling.

    PubMed

    Graham, Morag R; Smoot, Laura M; Migliaccio, Cristi A Lux; Virtaneva, Kimmo; Sturdevant, Daniel E; Porcella, Stephen F; Federle, Michael J; Adams, Gerald J; Scott, June R; Musser, James M

    2002-10-15

    Two-component gene regulatory systems composed of a membrane-bound sensor and cytoplasmic response regulator are important mechanisms used by bacteria to sense and respond to environmental stimuli. Group A Streptococcus, the causative agent of mild infections and life-threatening invasive diseases, produces many virulence factors that promote survival in humans. A two-component regulatory system, designated covRS (cov, control of virulence; csrRS), negatively controls expression of five proven or putative virulence factors (capsule, cysteine protease, streptokinase, streptolysin S, and streptodornase). Inactivation of covRS results in enhanced virulence in mouse models of invasive disease. Using DNA microarrays and quantitative RT-PCR, we found that CovR influences transcription of 15% (n = 271) of all chromosomal genes, including many that encode surface and secreted proteins mediating host-pathogen interactions. CovR also plays a central role in gene regulatory networks by influencing expression of genes encoding transcriptional regulators, including other two-component systems. Differential transcription of genes influenced by covR also was identified in mouse soft-tissue infection. This analysis provides a genome-scale overview of a virulence gene network in an important human pathogen and adds insight into the molecular mechanisms used by group A Streptococcus to interact with the host, promote survival, and cause disease. PMID:12370433

  12. 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. PMID:18430141

  13. 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

  14. 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

  15. Phosphorylation of the AfsR product, a global regulatory protein for secondary-metabolite formation in Streptomyces coelicolor A3(2).

    PubMed Central

    Hong, S K; Kito, M; Beppu, T; Horinouchi, S

    1991-01-01

    The AfsR protein is essential for the biosynthesis at the wild-type level of A-factor, actinorhodin, and undecylprodigiosin in Streptomyces coelicolor A3(2) and Streptomyces lividans. Because overexpression of the afsR gene caused some deleterious effect on these strains, a multicopy plasmid carrying the whole afsR gene was introduced into Streptomyces griseus, from which a crude cell lysate was prepared as a protein source. The AfsR protein was purified to homogeneity from the cytoplasmic fraction through several steps of chromatography, including affinity column chromatography with ATP-agarose and use of anti-AfsR antibody for its detection. The molecular weight of AfsR was estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by gel filtration to be 105,300, which is in good agreement with that deduced from the nucleotide sequence of afsR. The purified AfsR protein was found to be phosphorylated through the transfer of the gamma-phosphate group of ATP in the presence of the cell extracts of S. coelicolor A3(2) and S. lividans. This phosphorylation proceeded very rapidly, and no competition was observed with CTP, GTP, UTP, or cyclic AMP. In the cell extract of S. griseus, no activity phosphorylating the AfsR protein was detected, suggesting that this activity is not generally present in Streptomyces spp. but is specific to certain species. It is conceivable that the extent of phosphorylation of the AfsR protein modulates its regulatory activity which, in turn, regulates expression of some target gene(s) involved in the secondary-metabolite formation in S. coelicolor A3(2). Images PMID:2007554

  16. 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

  17. 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

  18. 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

  19. 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.

  20. 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

  1. 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. PMID:25796433

  2. 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

  3. 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. PMID:20015562

  4. 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…

  5. 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…

  6. 3 CFR - Regulatory Review

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 3 The President 1 2010-01-01 2010-01-01 false Regulatory Review Presidential Documents Other Presidential Documents Memorandum of January 30, 2009 Regulatory Review Memorandum for the Heads of Executive Departments and Agencies For well over two decades, the Office of Information and Regulatory Affairs (OIRA) at the Office of Management...

  7. Regulatory affairs administration as regulatory policy determinant

    SciTech Connect

    Forcier, J.R.

    1984-05-10

    It is the thesis of this article that the processing of a utility company's regulation-related work, the supporting tasks and the manner in which they are completed, can and does have a significant impact on the final results or work product of the regulatory affairs function, including even, potentially, the action of the regulatory agency. The article is therefore full of practical pointers on how the interface with the regulatory authority can best be organized, managed, and carried through to the attainment of optimum results for the utility. 2 references.

  8. [Systemic lupus erythematosus and regulatory T cells].

    PubMed

    Miyara, M; Amoura, Z; Piette, J-C; Gorochov, G

    2008-09-01

    A global depletion of FoxP3+ CD25(bright) CD4+ regulatory T cell is observed during lupus flares. This phenomenon is not the consequence of the relocalization of Tregs in diseased organs but could be related to their specific sensitivity to Fas mediated apoptosis. Several therapeutic perspectives can be drawn taking into account these pathophysiological insights. PMID:18538896

  9. Chromatin insulators: regulatory mechanisms and epigenetic inheritance

    PubMed Central

    Bushey, Ashley M.; Dorman, Elizabeth R.; Corces, Victor G.

    2008-01-01

    Enhancer-blocking insulators are DNA elements that disrupt the communication between a regulatory sequence, such as an enhancer or a silencer, and a promoter. Insulators participate in both transcriptional regulation and global nuclear organization, two features of chromatin that are thought to be maintained from one generation to the next through epigenetic mechanisms. Furthermore, there are many regulatory mechanisms in place that enhance or hinder insulator activity. These modes of regulation could be used to establish cell-type specific insulator activity that is epigenetically inherited along a cell and/or organismal lineage. This review will discuss the evidence for epigenetic inheritance and regulation of insulator function. PMID:18851828

  10. 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.

  11. Nuclear Regulatory Commission Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-20

    ...) 2010, less the amounts appropriated from the Nuclear Waste Fund, amounts appropriated for Waste... 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...

  12. NRC regulatory agenda

    SciTech Connect

    Not Available

    1991-04-01

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

  13. NRC regulatory agenda

    SciTech Connect

    Not Available

    1992-05-01

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

  14. NRC Regulatory Agenda

    SciTech Connect

    Not Available

    1991-10-01

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

  15. NRC Regulatory Agenda

    SciTech Connect

    Not Available

    1991-08-01

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

  16. NRC regulatory agenda

    SciTech Connect

    Not Available

    1993-04-01

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

  17. NRC regulatory agenda

    SciTech Connect

    Not Available

    1990-07-01

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

  18. Plant Regulatory Organizations

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The chapter on Plant Regulatory Organizations is part of a book titled Pest Management and Phytosanitary Trade Barriers authored by Neil Heather (Australia) and Guy Hallman. It covers the role of plant regulatory organizations from the international to state level in protecting plant health. At on...

  19. 78 FR 20325 - 2013 Parenteral Drug Association/Food and Drug Administration Joint Regulatory Conference...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-04

    ... Global Regulatory Environment AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public... Life Cycle in a Global Regulatory Environment.'' The conference will cover current issues affecting the... facilitate the development and continuous improvement of safe and effective medical products. The...

  20. Regulatory analysis of the C. elegans genome with spatiotemporal resolution

    PubMed Central

    Araya, Carlos L.; Kawli, Trupti; Kundaje, Anshul; Jiang, Lixia; Wu, Beijing; Vafeados, Dionne; Terrell, Robert; Weissdepp, Peter; Gevirtzman, Louis; Mace, Daniel; Niu, Wei; Boyle, Alan P.; Xie, Dan; Ma, Lijia; Murray, John I.; Reinke, Valerie; Waterston, Robert H.; Snyder, Michael

    2015-01-01

    Summary Discovering the structure and dynamics of transcriptional regulatory events in the genome with cellular and temporal resolution is crucial to understanding the regulatory underpinnings of development and disease. We determined the genomic distribution of binding sites for 92 transcription factors (TFs) and regulatory proteins across multiple stages of C. elegans development by performing 241 ChIP-seq experiments. Integrating regulatory binding and cellular-resolution expression data yielded a spatiotemporally-resolved metazoan TF binding map. Using this map, we explore developmental regulatory circuits that encode combinatorial logic at the levels of co-binding and co-expression of TFs, characterizing (1) the genomic coverage and clustering of regulatory binding, (2) the binding preferences of and biological processes regulated by TFs, (3) the global TF co-associations and genomic subdomains that suggest shared patterns of regulation, and (4) key TFs and TF co-associations for fate specification of individual lineages and cell-types. PMID:25164749

  1. Regulatory considerations in oncologic biosimilar drug development

    PubMed Central

    Macdonald, Judith C; Hartman, Helen; Jacobs, Ira A

    2015-01-01

    Biosimilar monoclonal antibodies are being developed globally for patients with different types of solid tumors and hematologic malignancies. Applications for proposed biosimilar monoclonal antibodies are being submitted to the regulatory authorities around the world and may increase patient access to key treatment options upon approval. An understanding among stakeholders (e.g., physicians, patients and their caregivers, pharmacists, payers) of the approval criteria, as well as the similarities and differences in regulatory pathways involved in biosimilar approval in different countries, as presented in this review, will facilitate identification of high-quality, safe, monoclonal antibodies that have been developed according to strict, biosimilar regulatory standards. Further guidance and resolution of the ongoing discussions on biosimilar labeling, naming, automatic substitution, and indication extrapolation may ensure, in the future, an effective and appropriate use of biosimilar monoclonal antibodies by oncologists and other stakeholders in daily clinical practice. PMID:25961747

  2. 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.

  3. 78 FR 44279 - Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-23

    ...The Department of Justice is publishing its spring 2013 regulatory agenda pursuant to Executive Order 12866, ``Regulatory Planning and Review,'' 58 FR 51735, and the Regulatory Flexibility Act, 5 U.S.C. sections 601 to 612...

  4. The ensembl regulatory build.

    PubMed

    Zerbino, Daniel R; Wilder, Steven P; Johnson, Nathan; Juettemann, Thomas; Flicek, Paul R

    2015-01-01

    Most genomic variants associated with phenotypic traits or disease do not fall within gene coding regions, but in regulatory regions, rendering their interpretation difficult. We collected public data on epigenetic marks and transcription factor binding in human cell types and used it to construct an intuitive summary of regulatory regions in the human genome. We verified it against independent assays for sensitivity. The Ensembl Regulatory Build will be progressively enriched when more data is made available. It is freely available on the Ensembl browser, from the Ensembl Regulation MySQL database server and in a dedicated track hub. PMID:25887522

  5. Stabilizing gene regulatory networks through feedforward loops

    NASA Astrophysics Data System (ADS)

    Kadelka, C.; Murrugarra, D.; Laubenbacher, R.

    2013-06-01

    The global dynamics of gene regulatory networks are known to show robustness to perturbations in the form of intrinsic and extrinsic noise, as well as mutations of individual genes. One molecular mechanism underlying this robustness has been identified as the action of so-called microRNAs that operate via feedforward loops. We present results of a computational study, using the modeling framework of stochastic Boolean networks, which explores the role that such network motifs play in stabilizing global dynamics. The paper introduces a new measure for the stability of stochastic networks. The results show that certain types of feedforward loops do indeed buffer the network against stochastic effects.

  6. NRC regulatory agenda

    SciTech Connect

    Not Available

    1990-10-01

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

  7. NRC Regulatory Agenda

    SciTech Connect

    Not Available

    1989-10-01

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

  8. NRC regulatory agenda

    SciTech Connect

    Not Available

    1990-04-01

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

  9. Canadian drug regulatory framework.

    PubMed

    Kelly, L; Lazzaro, M; Petersen, C

    2007-03-01

    The role of regulatory drug submission evaluators in Canada is to critically assess both the data submitted and the sponsor's interpretation of the data in order to reach an evidence-, and context-based recommendation as to the potential benefits and potential harms (i.e., risks) associated with taking the drug under the proposed conditions of use. The purpose of this document is to outline the regulatory framework in which this assessment occurs, including: defining what "authorization to market a drug in Canada" means, in terms of the role of the sponsor, the responsibility of Health Canada in applying the Food and Drugs Act prior to and after marketing authorization, and the distinction between regulatory authorization versus physician authorization; highlighting organizational, process and legal factors within Health Canada related to authorization of clinical trials and authorization to market a drug; considerations during the review process, such as regulatory and scientific issues related to the drug, patient populations and trial designs; application of international guidelines, and decisions from other jurisdictions; regulatory realities regarding drug authorization, including the requirement for wording in the Product Monograph to accurately reflect the information currently available on the safe and effective use of a drug, and that hypothesis-confirming studies are essential to regulatory endorsement; current issues related to the review of therapies for dementia, such as assessing preventative treatments, and therapies that have symptomatic versus disease-modifying effects, statistical issues regarding missing data, and trial design issues. PMID:17469674

  10. 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

  11. Structure-Based Network Analysis of Activation Mechanisms in the ErbB Family of Receptor Tyrosine Kinases: The Regulatory Spine Residues Are Global Mediators of Structural Stability and Allosteric Interactions

    PubMed Central

    James, Kevin A.; Verkhivker, Gennady M.

    2014-01-01

    The ErbB protein tyrosine kinases are among the most important cell signaling families and mutation-induced modulation of their activity is associated with diverse functions in biological networks and human disease. We have combined molecular dynamics simulations of the ErbB kinases with the protein structure network modeling to characterize the reorganization of the residue interaction networks during conformational equilibrium changes in the normal and oncogenic forms. Structural stability and network analyses have identified local communities integrated around high centrality sites that correspond to the regulatory spine residues. This analysis has provided a quantitative insight to the mechanism of mutation-induced “superacceptor” activity in oncogenic EGFR dimers. We have found that kinase activation may be determined by allosteric interactions between modules of structurally stable residues that synchronize the dynamics in the nucleotide binding site and the αC-helix with the collective motions of the integrating αF-helix and the substrate binding site. The results of this study have pointed to a central role of the conserved His-Arg-Asp (HRD) motif in the catalytic loop and the Asp-Phe-Gly (DFG) motif as key mediators of structural stability and allosteric communications in the ErbB kinases. We have determined that residues that are indispensable for kinase regulation and catalysis often corresponded to the high centrality nodes within the protein structure network and could be distinguished by their unique network signatures. The optimal communication pathways are also controlled by these nodes and may ensure efficient allosteric signaling in the functional kinase state. Structure-based network analysis has quantified subtle effects of ATP binding on conformational dynamics and stability of the EGFR structures. Consistent with the NMR studies, we have found that nucleotide-induced modulation of the residue interaction networks is not limited to the

  12. 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

  13. Predicting the impact of promoter variability on regulatory outputs.

    PubMed

    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

  14. Effects of the two-component system comprising GacA and GacS of Erwinia carotovora subsp. carotovora on the production of global regulatory rsmB RNA, extracellular enzymes, and harpinEcc.

    PubMed

    Cui, Y; Chatterjee, A; Chatterjee, A K

    2001-04-01

    Posttranscriptional regulation mediated by the regulator of secondary metabolites (RSM) RsmA-rsmB pair is the most important factor in the expression of genes for extracellular enzymes and HarpinEcc in Erwinia carotovora subsp. carotovora. RsmA is a small RNA-binding protein, which acts by lowering the half-life of a mRNA species. rsmB specifies an untranslated regulatory RNA and neutralizes the RsmA effect. It has been speculated that GacA-GacS, members of a two-component system, may affect gene expression via RsmA. Because expA, a gacA homolog, and expS (or rpfA), a gacS homolog, have been identified in E. carotovora subsp. carotovora, we examined the effects of these gacA and gacS homologs on the expression of rsmA, rsmB, and an assortment of exoprotein genes. The gacA gene of E. carotovora subsp. carotovora strain 71 stimulated transcription of genes for several extracellular enzymes (pel-1, a pectate lyase gene; peh-1, a polygalacturonase gene; and celV, a cellulase gene), hrpNEcc (an E. carotovora subsp. carotovora gene specifying the elicitor of hypersensitive reaction), and rsmB in GacA+ and GacS+ E. carotovora subsp. carotovora strains. Similarly, the E. carotovora subsp. carotovora gacA gene stimulated csrB (rsmB) transcription in Escherichia coli. A GacS- mutant of E. carotovora subsp. carotovora strain AH2 and a GacA- mutant of E. carotovora subsp. carotovora strain Ecc71 compared with their parent strains produced very low levels of rsmB, pel-1, peh-1, celV, and hrpNEcc transcripts but produced similar levels of rsmA RNA and RsmA protein as well as transcripts of hyperproduction of extracellular enzymes (Hex) hexA, kdgR (repressor of genes for uronate and pectate catabolism), rsmC, and rpoS (gene for Sigma-S, an alternate Sigma factor). The levels of rsmB, pel-1, peh-1, celV, and hrpNEcc transcripts as well as production of pectate lyase, polygalacturonase, cellulase, protease, and HarpinEcc proteins were stimulated in GacS- and GacA- mutants by Gac

  15. 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.

  16. 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.

  17. 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…

  18. Global Science.

    ERIC Educational Resources Information Center

    Brophy, Michael

    1991-01-01

    Approaches taken by a school science department to implement a global science curriculum using a range of available resources are outlined. Problems with current curriculum approaches, alternatives to an ethnocentric curriculum, advantages of global science, and possible strategies for implementing a global science policy are discussed. (27…

  19. 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…

  20. 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…

  1. Toxicogenomics in Regulatory Ecotoxicology

    EPA Science Inventory

    The potential utility of toxicogenomics in toxicological research and regulatory activities has been the subject of scientific discussions, and as with any new technology, there is a wide range of opinion. The purpose of this feature article is to consider roles of toxicogenomic...

  2. 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.

  3. 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).

  4. REFINE WETLAND REGULATORY PROGRAM

    EPA Science Inventory

    The Tribes will work toward refining a regulatory program by taking a draft wetland conservation code with permitting incorporated to TEB for review. Progress will then proceed in developing a permit tracking system that will track both Tribal and fee land sites within reservati...

  5. REGULATORY AIR QUALITY MODELS

    EPA Science Inventory

    Appendix W to 40CFR Part 51 (Guideline on Air Quality Models) specifies the models to be used for purposes of permitting, PSD, and SIPs. Through a formal regulatory process this modeling guidance is periodically updated to reflect current science. In the most recent action, thr...

  6. NRC regulatory agenda

    SciTech Connect

    Not Available

    1993-02-01

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

  7. NRC regulatory agenda

    SciTech Connect

    Not Available

    1992-11-01

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

  8. NRC Regulatory Agenda

    SciTech Connect

    Not Available

    1992-07-01

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

  9. 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. PMID:21784655

  10. 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...

  11. 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.

  12. 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. PMID:26260323

  13. 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.

  14. Learning regulatory programs by threshold SVD regression

    PubMed Central

    Ma, Xin; Xiao, Luo; Wong, Wing Hung

    2014-01-01

    We formulate a statistical model for the regulation of global gene expression by multiple regulatory programs and propose a thresholding singular value decomposition (T-SVD) regression method for learning such a model from data. Extensive simulations demonstrate that this method offers improved computational speed and higher sensitivity and specificity over competing approaches. The method is used to analyze microRNA (miRNA) and long noncoding RNA (lncRNA) data from The Cancer Genome Atlas (TCGA) consortium. The analysis yields previously unidentified insights into the combinatorial regulation of gene expression by noncoding RNAs, as well as findings that are supported by evidence from the literature. PMID:25331876

  15. 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...

  16. 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 ...

  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. Intrinsic limits to gene regulation by global crosstalk.

    PubMed

    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

  19. Securities and Exchange Commission Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    ... [Securities and Exchange Commission Semiannual Regulatory Agenda ] Part XXIII Securities and Exchange Commission Semiannual Regulatory Agenda ] SECURITIES AND EXCHANGE COMMISSION (SEC) SECURITIES AND EXCHANGE COMMISSION 17 CFR Ch. II Regulatory Flexibility Agenda AGENCY: Securities and Exchange Commission. ACTION: Semiannual regulatory...

  20. 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

  1. 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. PMID:25667170

  2. [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. PMID:23834089

  3. The core to regulatory reform

    SciTech Connect

    Partridge, J.W. Jr.

    1993-06-15

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

  4. 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.

  5. Global trends, needs, issues.

    PubMed

    Kieffer, R G

    1998-01-01

    Worldwide, Pharmaceutical Plant Management struggles with the competing priorities of lowering costs, rising customer expectations, more demanding government regulations, and the need to reduce cycle times especially in the introduction of new products. All of this takes place in an environment of global competition, regulatory harmonization, mergers and downsizing, and employee insecurity. Employees are expected to do more with less, work with more sophisticated equipment and processes, take more personal responsibility for quality and productivity, work in teams, etc. In summary, we are talking about CHANGE, the speed of which will accelerate in the years to come. This presentation will discuss how some pharmaceutical plants are addressing these challenges. Examples will be given in the areas of validation, process reengineering, risk analysis, role of the quality function and people. It is my contention that most of the global trends today are insufficient to meet the challenges that we face. I hope that this presentation will generate some ideas on what the global trends should be. PMID:9752708

  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. Japanese pharmaceutical and regulatory environment.

    PubMed

    Nagata, Ryoichi; Rafizadeh-Kabe, Jean-David

    2002-12-01

    Drastic regulatory changes in Japan since 1997 have had a considerable impact on the way new medicines are developed. The regulatory authority itself has been transformed. Clinical trials are now performed according to international guidelines. Clinical data generated in one area are acceptable in the rest of the world in some cases through a bridging process that is viewed as only temporary. The future of drug development lies in multinational clinical trials and simultaneous submission to the major regulatory authorities. PMID:22034129

  8. 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.

  9. 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

  10. Building Developmental Gene Regulatory Networks

    PubMed Central

    Li, Enhu; Davidson, Eric H.

    2009-01-01

    Animal development is an elaborate process programmed by genomic regulatory instructions. Regulatory genes encode transcription factors and signal molecules, and their expression is under the control of cis-regulatory modules that define the logic of transcriptional responses to the inputs of other regulatory genes. The functional linkages amongst regulatory genes constitute the gene regulatory networks (GRNs) that govern cell specification and patterning in development. Constructing such networks requires identification of the regulatory genes involved and characterization of their temporal and spatial expression patterns. Interactions (activation/repression) among transcription factors or signals can be investigated by large-scale perturbation analysis, in which the function of each gene is specifically blocked. Resultant expression changes are then integrated to identify direct linkages, and to reveal the structure of the GRN. Predicted GRN linkages can be tested and verified by cis-regulatory analysis. The explanatory power of the GRN was shown in the lineage specification of sea urchin endomesoderm. Acquiring such networks is essential for a systematic and mechanistic understanding of the developmental process. PMID:19530131

  11. 75 FR 79759 - Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-20

    ... use throughout the rulemaking process. Timetable: Action Date FR Cite Notice: Public Meeting Framework... heating equipment. This is the second review for water heaters. Completed: Reason Date FR Cite Final... ``Regulatory Planning and Review,'' 58 FR 51735, and the Regulatory Flexibility Act, 5 U.S.C. 601 et...

  12. 76 FR 3825 - Regulatory Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-21

    ..., Washington, January 18, 2011 [FR Doc. 2011-1386 Filed 1-20-11; 8:45 am] Billing code 3110-01-P ... Documents#0;#0; ] Memorandum of January 18, 2011 Regulatory Compliance Memorandum for the Heads of Executive... accessible to the public, information concerning their regulatory compliance and enforcement activities,...

  13. Citizen participation on regulatory boards.

    PubMed

    Chesney, J D

    1984-01-01

    This article examines the relationship between regulatory board function and citizen participation. The research indicates that public members generally prefer advisory boards, while provider members prefer quasi-judicial bodies. Implications of these findings for structuring citizen participation in the regulatory process are examined. PMID:6736596

  14. 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...

  15. 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…

  16. 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...

  17. 75 FR 22889 - Self-Regulatory Organizations; International Securities Exchange, LLC; Notice of Filing and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-30

    ... interested persons. \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's... began listing options on the First Trust ISE Global Copper Index Fund (``CU'') and the First Trust ISE Global Platinum Index Fund (``PLTM''). As of the date of this filing, CU and PLTM are both singly...

  18. Understanding genetic regulatory networks

    NASA Astrophysics Data System (ADS)

    Kauffman, Stuart

    2003-04-01

    Random Boolean networks (RBM) were introduced about 35 years ago as first crude models of genetic regulatory networks. RBNs are comprised of N on-off genes, connected by a randomly assigned regulatory wiring diagram where each gene has K inputs, and each gene is controlled by a randomly assigned Boolean function. This procedure samples at random from the ensemble of all possible NK Boolean networks. The central ideas are to study the typical, or generic properties of this ensemble, and see 1) whether characteristic differences appear as K and biases in Boolean functions are introducted, and 2) whether a subclass of this ensemble has properties matching real cells. Such networks behave in an ordered or a chaotic regime, with a phase transition, "the edge of chaos" between the two regimes. Networks with continuous variables exhibit the same two regimes. Substantial evidence suggests that real cells are in the ordered regime. A key concept is that of an attractor. This is a reentrant trajectory of states of the network, called a state cycle. The central biological interpretation is that cell types are attractors. A number of properties differentiate the ordered and chaotic regimes. These include the size and number of attractors, the existence in the ordered regime of a percolating "sea" of genes frozen in the on or off state, with a remainder of isolated twinkling islands of genes, a power law distribution of avalanches of gene activity changes following perturbation to a single gene in the ordered regime versus a similar power law distribution plus a spike of enormous avalanches of gene changes in the chaotic regime, and the existence of branching pathway of "differentiation" between attractors induced by perturbations in the ordered regime. Noise is serious issue, since noise disrupts attractors. But numerical evidence suggests that attractors can be made very stable to noise, and meanwhile, metaplasias may be a biological manifestation of noise. As we learn more

  19. 78 FR 1636 - Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-08

    ...This Regulatory Agenda is a semiannual summary of all current and projected rulemakings, existing regulations, and completed actions of the Small Business Administration (SBA). For this fall edition of the SBA's Regulatory Agenda, a Regulatory Plan that contains a list of the Agency's most important and significant regulatory actions and a Statement of Regulatory Priorities is also included.......

  20. Department of Justice Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-20

    ... [The Regulatory Plan and Unified Agenda of Federal Regulatory and Deregulatory Actions] Part XI Department of Justice Semiannual Regulatory Agenda ] DEPARTMENT OF JUSTICE (DOJ) DEPARTMENT OF JUSTICE 8 CFR Ch. V 21 CFR Ch. I 27 CFR Ch. II 28 CFR Ch. I, V Regulatory Agenda AGENCY: Department of Justice. ACTION: Semiannual regulatory agenda....

  1. 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

  2. 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

  3. Global militarization

    SciTech Connect

    Wallensteen, P.; Galtung, J.; Portales, C.

    1985-01-01

    This book contains 10 chapters. Some of the titles are: Military Formations and Social Formations: A Structural Analysis; Global Conflict Formations: Present Developments and Future Directions; War and the Power of Warmakers in Western Europe and Elsewhere, 1600-1980; and The Urban Type of Society and International War.

  4. 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)

  5. 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…

  6. Campus Global.

    ERIC Educational Resources Information Center

    Sort, Josep

    2003-01-01

    Describes the development of the Campus Global portal at a public university in Spain. The project aimed to change the ways in which the university community worked, taught, and learned. Examines how the project was carried out, the transformations it instigated inside the organization, the improvements it has brought about, and the current state…

  7. 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. PMID:27088919

  8. 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. PMID:25456378

  9. 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

  10. 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…

  11. 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…

  12. Global Arrays

    SciTech Connect

    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 shared 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).

  13. Global Arrays

    Energy Science and Technology Software Center (ESTSC)

    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

  14. Regulatory Insight into the European Human Pluripotent Stem Cell Registry

    PubMed Central

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

    2014-01-01

    Abstract 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

  15. 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

  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. Homotypic Regulatory Clusters in Drosophila

    PubMed Central

    Lifanov, Alexander P.; Makeev, Vsevolod J.; Nazina, Anna G.; Papatsenko, Dmitri A.

    2003-01-01

    Cis-regulatory modules (CRMs) are transcription regulatory DNA segments (∼1 Kb range) that control the expression of developmental genes in higher eukaryotes. We analyzed clustering of known binding motifs for transcription factors (TFs) in over 60 known CRMs from 20 Drosophila developmental genes, and we present evidence that each type of recognition motif forms significant clusters within the regulatory regions regulated by the corresponding TF. We demonstrate how a search with a single binding motif can be applied to explore gene regulatory networks and to discover coregulated genes in the genome. We also discuss the potential of the clustering method in interpreting the differential response of genes to various levels of transcriptional regulators. PMID:12670999

  19. International regulatory aspects of clinical periodontal research.

    PubMed

    Cooley, W E; Castellion, A W

    1997-03-01

    The Food and Drug Administration (FDA) was the pioneer regulatory agency to set standards for clinical studies aimed at approval of new drugs. For years the FDA's rules represented the most thorough, stringent, and consistent policy. Now most other developed countries have comparable requirements for the conduct of clinical trials. The European Community (EC). Canadian, and Japanese regulations are most important for United States (US) scientists attempting to globalize their research. Regulations in Eastern Europe, some Asian countries, and Latin America are of growing importance. The Pacific-Rim appears to be the fastest growing pharmaceutical market in the next decade. Currently, the EC and Japan's Good Clinical Practice (GCP) regulations are more detailed than those of the US. Moreover, the World Health Organization recently published GCP recommendations similar to the EC requirements. Well-designed and well-controlled studies done in the EC, US, and other developed countries are generally accepted throughout the world. Japan and some other countries require studies in local patients. American scientists cannot expect to conduct studies in other countries as principal investigators, but many are associated with national clinicians. Mutual recognition of marketing approvals is the ultimate goal for the globalization of drug research. While it is the objective of the Scheme for the Mutual Recognition of Evaluation Reports on Pharmaceutical Products and the EC Decentralized Procedure, it is not apparent when the FDA will totally accept another regulatory body's approval decision. The International Conference on Harmonization involves the EC, Japan, and the US. This most important series of meetings will finally align the major countries more closely in regulating clinical studies and the production of safe, effective, and quality products, especially in these times of worldwide economic considerations and health care reform. It is imperative that US dental

  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. Global power: Markets and strategies

    SciTech Connect

    Poirer, J.L.

    1998-07-01

    The author will first present an updated view of the global power market activity, including opportunities in power generation, transmission and distribution. This will include a review of the trends in closings and transaction flowed by type of activity and geographic area. Estimates will be based on Hagler Bailly's comprehensive database on global power transactions and project announcements. The firm has also worked with dozens of global power companies since 1990. Second, the author will review trends in terms of regulatory changes, project cost trends, developers' project experiences, and financing issues. This systematic review will be the foundation for projection of future market activity (e.g., number of closing by type of project through 2000). A forecast of future greenfield and privatization activity will be provided and the key markets will be highlighted. Third, the author will present an updated view of the competition in the global power market (including the various types of competitors and changes in their respective market posture). Finally, the author will discuss the various types of strategies and business models that are followed by key global power players.

  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. Regulatory RNAs in Bacteria

    PubMed Central

    Waters, Lauren S.; Storz, Gisela

    2011-01-01

    RNA regulators in bacteria are a heterogenous group of molecules that act by various mechanisms to modulate a wide range of physiological responses. One class comprises riboswitches, which are parts of the mRNAs they regulate. These leader sequences fold into structures amenable to conformational changes upon the binding of small molecules. Riboswitches thus sense and respond to the availability of various nutrients in the cell. Other small transcripts bind to proteins, among them global regulators, and antagonize their functions. The largest and most extensively studied set of small RNA regulators act through base pairing with RNAs, usually modulating the translation and stability of mRNAs. The majority of these small RNAs regulate responses to changes in environmental conditions. Finally, a recently discovered group of RNA regulators, known as the CRISPR RNAs, contain short regions of homology to bacteriophage and plasmid sequences. CRISPR RNAs interfere with bacteriophage infection and plasmid conjugation by targeting the homologous foreign DNA through an unknown mechanism. Here we discuss what is known about these RNA regulators, as well as the many intriguing questions that remain to be addressed. PMID:19239884

  4. Securities and Exchange Commission Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-20

    ... [The Regulatory Plan and Unified Agenda of Federal Regulatory and Deregulatory Actions] Part XXIV Securities and Exchange Commission Semiannual Regulatory Agenda ] SECURITIES AND EXCHANGE COMMISSION (SEC) SECURITIES AND EXCHANGE COMMISSION 17 CFR Ch. II Regulatory Flexibility Agenda AGENCY: Securities and Exchange Commission. ACTION:...

  5. 7 CFR 1773.40 - Regulatory assets.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 12 2010-01-01 2010-01-01 false Regulatory assets. 1773.40 Section 1773.40... § 1773.40 Regulatory assets. The CPA's workpapers must document whether all regulatory assets comply with... whether all regulatory assets have received RUS approval....

  6. 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.

  7. 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.

  8. 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.

  9. 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. PMID:12747163

  10. 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.

  11. 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...

  12. 75 FR 11166 - Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-10

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission; Notice of Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission March 2,...

  13. Noncoding Regulatory RNAs in Hematopoiesis.

    PubMed

    Jeong, M; Goodell, M A

    2016-01-01

    Hematopoiesis is a dynamic process in which blood cells are continuously generated from hematopoietic stem cells (HSCs). The regulatory mechanisms controlling HSC fate have been studied extensively over the past several decades. Although many protein-coding genes have been shown to regulate hematopoietic differentiation, additional levels of HSC regulation are not well studied. Advances in deep sequencing have revealed many new classes of regulatory noncoding RNAs (ncRNAs), such as enhancer RNAs and antisense ncRNAs. Functional analysis of some of these ncRNAs has provided insights into the molecular mechanisms that regulate hematopoietic development and disease. In this review, we summarize recent advances in our understanding of functional regulatory ncRNAs associated with hematopoietic self-renewal and differentiation, as well as those dysregulated ncRNAs involved in hematologic malignancies. PMID:27137659

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

    PubMed Central

    Liu, Zhi-Ping

    2015-01-01

    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. PMID:25937810

  15. Negative cooperativity in regulatory enzymes.

    PubMed

    Levitzki, A; Koshland, D E

    1969-04-01

    Negative cooperativity has been observed in CTP synthetase, an allosteric enzyme which contains a regulatory site. Thus, the same enzyme exhibits negative cooperativity for GTP (an effector) and glutamine (a substrate) and positive cooperativity for ATP and UTP (both substrates). In the process of the delineation of these phenomena, diagnostic procedures for negative cooperativity were developed. Application of these procedures to other enzymes indicates that negative cooperativity is a characteristic of many of them. These findings add strong support for the sequential model of subunit interactions which postulates that ligand-induced conformational changes are responsible for regulatory and cooperative phenomena in enzymes. PMID:5256410

  16. 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

  17. 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. PMID:24311349

  18. 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.

  19. 75 FR 18245 - Public Federal Regulatory Enforcement Fairness Hearing Region IX Regulatory Fairness Board

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-09

    ... From the Federal Register Online via the Government Publishing Office SMALL BUSINESS ADMINISTRATION Public Federal Regulatory Enforcement Fairness Hearing Region IX Regulatory Fairness Board.... Small Business Administration (SBA) Region IX Regulatory Fairness Board and the SBA Office of...

  20. 77 FR 74712 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-17

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change To Amend the Customer and Industry Codes of Arbitration Procedure Relating to... Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange...

  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... analysis is required, and the status of regulations previously reported. ADDRESSES: Acting Assistant... the new accessibility standards. Other amendments include updates to organizational information,...

  2. 78 FR 1634 - Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-08

    ... Date FR Cite NPRM 02/00/13 Regulatory Flexibility Analysis Required: No. Agency Contact: Robert W... analysis is required, and the status of regulations previously reported. ADDRESSES: Director, for Internal... accessibility standards. Other amendments include updates to organizational information, use of the...

  3. 75 FR 79799 - Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-20

    ... agenda pursuant to Executive Order 12866 ``Regulatory Planning and Review,'' 58 FR 51735, and the... rulemaking that was published in the Federal Register on September 30, 2004, at 69 FR 58768, issued under... Enforcement Fairness Act of 1996 (SBREFA). Completed: Reason Date FR Cite Final Action 09/15/10 75 FR...

  4. 75 FR 79763 - Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-20

    ... e mail communications. Timetable: Action Date FR Cite NPRM 04/00/11 NPRM Comment Period End 06/00/11... Medicaid EHR Incentive Programs. Timetable: Action Date FR Cite Interim Final Rule 01/13/10 75 FR 2014... 75 FR 44590 Regulatory Flexibility Analysis Required: No Agency Contact: Steven Posnack,...

  5. Wildlife trade and global disease emergence.

    PubMed

    Karesh, William B; Cook, Robert A; Bennett, Elizabeth L; Newcomb, James

    2005-07-01

    The global trade in wildlife provides disease transmission mechanisms that not only cause human disease outbreaks but also threaten livestock, international trade, rural livelihoods, native wildlife populations, and the health of ecosystems. Outbreaks resulting from wildlife trade have caused hundreds of billions of dollars of economic damage globally. Rather than attempting to eradicate pathogens or the wild species that may harbor them, a practical approach would include decreasing the contact rate among species, including humans, at the interface created by the wildlife trade. Since wildlife marketing functions as a system of scale-free networks with major hubs, these points provide control opportunities to maximize the effects of regulatory efforts. PMID:16022772

  6. 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.

  7. 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

  8. 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

  9. 78 FR 62726 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing and Immediate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-22

    ... COMMISSION Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing and Immediate...\\, and Rule 19b-4 \\2\\ thereunder, notice is hereby given that on October 2, 2013, The NASDAQ Stock Market... transfer from the NASDAQ Global or Global Select Market to the NASDAQ Capital Market. Finally,...

  10. 77 FR 52791 - Regulatory Capital Rules: Regulatory Capital, Implementation of Basel III, Minimum Regulatory...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-30

    ... approaches capital rules, a supplementary leverage ratio that incorporates a broader set of exposures in the... regulatory capital buffer. B. Leverage Ratio 1. Minimum Tier 1 Leverage Ratio. A description of the minimum tier 1 leverage ratio, including the calculation of the numerator and the denominator. 2....

  11. 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

  12. 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

  13. 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

  14. 21 CFR 26.34 - Regulatory authorities.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... RECOGNITION OF PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE QUALITY SYSTEM AUDIT REPORTS, AND CERTAIN MEDICAL DEVICE PRODUCT EVALUATION REPORTS: UNITED STATES AND THE EUROPEAN COMMUNITY Specific Sector Provisions for Medical Devices § 26.34 Regulatory authorities. The regulatory...

  15. 21 CFR 26.34 - Regulatory authorities.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... RECOGNITION OF PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE QUALITY SYSTEM AUDIT REPORTS, AND CERTAIN MEDICAL DEVICE PRODUCT EVALUATION REPORTS: UNITED STATES AND THE EUROPEAN COMMUNITY Specific Sector Provisions for Medical Devices § 26.34 Regulatory authorities. The regulatory...

  16. 21 CFR 26.34 - Regulatory authorities.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... RECOGNITION OF PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE QUALITY SYSTEM AUDIT REPORTS, AND CERTAIN MEDICAL DEVICE PRODUCT EVALUATION REPORTS: UNITED STATES AND THE EUROPEAN COMMUNITY Specific Sector Provisions for Medical Devices § 26.34 Regulatory authorities. The regulatory...

  17. 76 FR 6123 - Reducing Regulatory Burden

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-03

    ... achieving its regulatory objectives. DATES: Written comments and information are requested on or before... the least burden on society, consistent with obtaining the regulatory objectives, taking into account... approaches that reduce burdens and maintain flexibility. Regulations be guided by objective...

  18. 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

  19. 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.

  20. [Regulatory requirements for topical preparations].

    PubMed

    Wohlrab, J; Klauck, D; Savtcheva, E

    2014-03-01

    Professional use of topical treatment in dermatological practice requires not only knowledge about the pharmacological properties, efficacy, safety and pharmaceutical quality of a preparation, but also about its regulatory classification. The latter essentially determines the physician's prescription practice and therapeutic freedom. The regulatory framework with which one is confronted unfortunately lacks transparency. It regulates not only the prescribability and reimbursability of proprietary medicinal products and extemporaneous preparations, but also the obligation to give information as well as the details of liability of both the prescriber (physician) and the manufacturer (pharmaceutical company or pharmacist). The prescriber needs to be aware of to what extent the pharmacist has the possibility and even obligation to change the prescribed preparation. In some cases this can directly affect the therapeutic concept of the physician and even impair the effectiveness and safety of the chosen therapy. PMID:24622851

  1. 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.

  2. 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)...

  3. 75 FR 61531 - Issuance of Regulatory Guide

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-05

    ... COMMISSION Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice. SUMMARY: The... Guide 1.193, Rev. 3, ``ASME Code Cases Not Approved for Use.'' FOR FURTHER INFORMATION CONTACT: Wallace... Wallace.Norris@nrc.gov . SUPPLEMENTARY INFORMATION: I. Introduction The NRC is issuing Regulatory...

  4. Department of Commerce Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-20

    ... [The Regulatory Plan and Unified Agenda of Federal Regulatory and Deregulatory Actions] Part IV Department of Commerce Semiannual Regulatory Agenda ] DEPARTMENT OF COMMERCE (DOC) DEPARTMENT OF COMMERCE Office of the Secretary 13 CFR Ch. III 15 CFR Subtitle A; Subtitle B, Chs. I, II, III, VII, VIII, IX, and XI 19 CFR Ch. III 37 CFR Chs. I, IV,...

  5. 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)...

  6. 21 CFR 500.88 - Regulatory method.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 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)...

  7. 21 CFR 500.88 - Regulatory method.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 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)...

  8. 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.

  9. Regulatory strategies and market entry

    SciTech Connect

    Russo, M.V.

    1988-01-01

    This paper discusses the intertwining influence of regulation, the pursuit of social goals, and market entry. The authors focus on the California natural gas distribution system, showing how the California Public Utilies Commission increasingly exercised its authority to set rates so as to meet social goals. Among these goals were lower fuel oil use, lower residential rates, and greater small power production. However, by calling on large users to pay substantially above their costs to subsidize these programs, the system was left open to cream-skimming entry. When a major new market for natural gas in the Kern County oil fields arose, several groups applied to the Federanl Energy Regulatory Commission to build an interstate gas pipeline - Califronia's first- dedicated to serving those customers. The proposals are being considered because of past pricing trends, because of the desire to avoid state regulatory oversight of their operations, and because they can be used to evade federal price regulations on natural gas. However, from a societal economic standpoint, all of the pipelines would be exceedingly expensive. The case demonstrates the unexpected and often the perverse consequences of pursuing social goals within a regulatory framework.

  10. 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

  11. 75 FR 39069 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-07

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

  12. 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

  13. Statistical Inference and Reverse Engineering of Gene Regulatory Networks from Observational Expression Data

    PubMed Central

    Emmert-Streib, Frank; Glazko, Galina V.; Altay, Gökmen; de Matos Simoes, Ricardo

    2012-01-01

    In this paper, we present a systematic and conceptual overview of methods for inferring gene regulatory networks from observational gene expression data. Further, we discuss two classic approaches to infer causal structures and compare them with contemporary methods by providing a conceptual categorization thereof. We complement the above by surveying global and local evaluation measures for assessing the performance of inference algorithms. PMID:22408642

  14. 76 FR 32878 - Draft Regulatory Guide: Issuance, Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-07

    ...; ] NUCLEAR REGULATORY COMMISSION 10 CFR Part 50 Draft Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Draft Regulatory Guide, DG-1253, ``Preoperational Testing of Emergency Core Cooling Systems for Pressurized-Water Reactors''....

  15. 75 FR 41241 - Draft Regulatory Guide; Issuance, Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-15

    ... COMMISSION Draft Regulatory Guide; Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Issuance, availability of Draft Regulatory Guide (DG)-1234. ADDRESSES: You may submit comments by any one... and licenses. The draft regulatory guide, entitled, ``Water Sources for Long-Term...

  16. 75 FR 62893 - Draft Regulatory Guide: Issuance, Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-13

    ... COMMISSION Draft Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Draft Regulatory Guide, DG-1196, ``Qualification for Cement... Commission (NRC) is issuing for public comment a draft guide in the agency's ``Regulatory Guide''...

  17. 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...

  18. 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...

  19. 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...

  20. 77 FR 2573 - International Product Change-Global Plus 1C and 2C Negotiated Service Agreements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-18

    ... International Product Change--Global Plus 1C and 2C Negotiated Service Agreements AGENCY: Postal Service TM... Regulatory Commission to add Global Plus 1C and 2C Negotiated Service Agreements to the Competitive Products... of United States Postal Service to Add Global Plus 1C and 2C Negotiated Service Agreements to...

  1. 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.

  2. 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.

  3. Bacteriophage therapy: a regulatory perspective.

    PubMed

    Pelfrene, Eric; Willebrand, Elsa; Cavaleiro Sanches, Ana; Sebris, Zigmars; Cavaleri, Marco

    2016-08-01

    Despite the recognized problem of antibiotic multidrug resistance, very few antibacterial agents with new mechanisms of action are under development. Bacteriophage therapy could offer one alternative strategy to mitigate this challenge. Although widely used throughout the 20th century in Eastern Europe and the former Soviet Union, this potential therapy has not yet been investigated according to rigorous scientific standards. This paper reports on a multistakeholder meeting held at the EMA, which outlined the existing regulatory framework to which such therapy should adhere and reviewed the current obstacles and shortcomings in scientific development for bacteriophage therapy. PMID:27068400

  4. Broadband-ISDN: Personal Connections to Global Resources.

    ERIC Educational Resources Information Center

    Kaman, Geradine M.

    1993-01-01

    Discusses the development and impact of broadband ISDN (Integrated Services Digital Network) on global telecommunications and society. Issues covered include regulatory policies, ownership and control, content regulation, home access, rural versus urban access, pricing, user groups, barriers, and privacy. The need for greater public involvement is…

  5. 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...

  6. 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…

  7. 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…

  8. 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

  9. 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. PMID:11922095

  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. 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

  12. 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. PMID:18495751

  13. 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

  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, 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  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. Conservation of DNA curvature signals in regulatory regions of prokaryotic genes

    PubMed Central

    Jáuregui, Ruy; Abreu-Goodger, Cei; Moreno-Hagelsieb, Gabriel; Collado-Vides, Julio; Merino, Enrique

    2003-01-01

    DNA curvature plays a well-characterized role in many transcriptional regulation mechanisms. We present evidence for the conservation of curvature signals in putative regulatory regions of several archaeal and eubacterial genomes. Genes with highly curved upstream regions were identified in orthologous groups, based on the annotations of the Cluster of Orthologous Groups of proteins (COG) database. COGs possessing a significant number of genes with curvature signals were analyzed, and conserved properties were found in several cases. Curvature signals related to regulatory sites, previously described in single organisms, were located in a broad spectrum of bacterial genomes. Global regulatory proteins, such as HU, IHF and FIS, known to bind to curved DNA and to be autoregulated, were found to present conserved DNA curvature signals in their regulatory regions, emphasizing the fact that structural parameters of the DNA molecule are conserved elements in the process of transcriptional regulation of some systems. It is currently an open question whether these diverse systems are part of an integrated global regulatory response in different microorganisms. PMID:14627810

  9. The Inferelator: an algorithm for learning parsimonious regulatory networks from systems-biology data sets de novo

    PubMed Central

    2006-01-01

    We present a method (the Inferelator) for deriving genome-wide transcriptional regulatory interactions, and apply the method to predict a large portion of the regulatory network of the archaeon Halobacterium NRC-1. The Inferelator uses regression and variable selection to identify transcriptional influences on genes based on the integration of genome annotation and expression data. The learned network successfully predicted Halobacterium's global expression under novel perturbations with predictive power similar to that seen over training data. Several specific regulatory predictions were experimentally tested and verified. PMID:16686963

  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. 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…

  12. 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.

  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. 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…

  15. 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.

  16. 21 CFR 26.18 - Regulatory collaboration.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  17. Regulatory T cells: stability revisited

    PubMed Central

    Bailey-Bucktrout, Samantha L.; Bluestone, Jeffrey A.

    2011-01-01

    Breakdown in self-tolerance is due, in part, to a loss of regulatory T (Treg) cells. Recently, a controversy has surfaced about whether Treg cells are overwhelmingly stable, or if they can be reprogrammed in inflammatory and autoimmune environments. Those in the instability “camp” have shown that a fraction of Treg cells lose Foxp3 and acquire effector arm activities. Instability is coupled with IL-2 insufficiency and the inflammatory milieu that promote reprogramming. Here, we highlight the basic tenets of each viewpoint and discuss technical, biological and environmental differences in the models that may help yield a unifying hypothesis. Also considered is how Treg cell instability could link to development of autoimmune disease and the implications for Treg cell-based cellular therapy trials. PMID:21620768

  18. Immunometabolism of regulatory T cells.

    PubMed

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

    2016-05-19

    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

  19. 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.

  20. 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

  1. 75 FR 4596 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-28

    ..., RECORDS AND REPORTS * * * * * 4520. Financial Records and Reporting Requirements 4521. Notifications... Financial Responsibility). See also Securities Exchange Act Release No. 60933 (November 4, 2009), 74 FR... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

  2. 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. PMID:26408947

  3. Spanish regulatory approach for Biobanking

    PubMed Central

    Arias-Diaz, Javier; Martín-Arribas, María C; García del Pozo, Javier; Alonso, Carlos

    2013-01-01

    The Spanish regulatory framework for storage of samples for research responds to most issues raised by both researchers and society regarding biobanking. The Spanish regulation currently foresees three possible ways in which these samples are to be handled: (a) gathering for use in a specific project, (b) storage in a collection, and (c) storage in a Biobank. Samples incorporated into a ‘collection' can only be used by the investigator who requested them and cannot be transferred to third parties or used in research projects outside the particular research line foreseen in the original consent. On the other hand, the legal entity ‘Biobank' refers not only to a set of physical facilities but to the management of the samples stored under that label, and particularly to the requirements for their cession. An approach based on putting most of the regulatory weight on the biobank side has been chosen in order to guaranty the rights of the donors as well as to ease the task of the researchers. A Biobank requires both to be authorized and to be registered in a public Registry. The requirements are quite stringent, allowing for the consent to be given as ‘broad' in scope without implying being ‘blank.' In this regard, for Biobanks to justify the taking on of some of the donors' rights, a key requirement is to have an external ethics committee supervising the adequacy of samples cession and use, notwithstanding the need for a previous bioethical supervision of the target protocol. PMID:23188043

  4. Regulatory T cells: a review.

    PubMed

    Dasgupta, Alakananda; Saxena, Renu

    2012-01-01

    Regulatory T cells (Tregs) play a pivotal role in the homeostasis of the immune system and in the modulation of the immune response. Tregs have emerged as key players in the development and maintenance of peripheral immune tolerance. Broadly speaking, CD4+ T cells possessing the ability to suppress immune responses can be divided into two types: naturally occurring (nTreg) and inducible (iTreg) or adaptive regulatory cells. Naturally occurring thymus-derived CD4+CD25+ Tregs are a subset of T cells which have immunosuppressive properties and are 5%-10% of the total peripheral CD4+ T cells. In normal conditions, Tregs regulate ongoing immune responses and prevent autoimmunity. Imbalanced function or number of these cells, either enhanced or decreased, might lead to tumour development and autoimmunity, respectively. These cells thus play a major role in autoimmune diseases, transplantation tolerance, infectious diseases, allergic disease and tumour immunity. These natural properties make Tregs attractive tools for novel immunotherapeutic approaches. The in vivo manipulation or depletion of Tregs may help devise effective immunotherapy for patients with cancer, autoimmunity, graftversus-host disease, infectious diseases and allergic diseases. It is crucial to understand the biology of Tregs before attempting therapies, including (i) the injection of expanded Tregs to cure autoimmune disease or prevent graft-versus-host disease or (ii) the depletion or inhibition of Tregs in cancer therapy. Recent findings in murine models and studies in humans have opened new avenues to study the biology of Tregs and their therapeutic potential. This overview provides a framework for integrating these concepts of basic and translational research. PMID:23998865

  5. 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

  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. 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

  8. Toward a Genome-Wide Reconstruction of Cis-Regulatory Networks in the Human Genome

    PubMed Central

    Cecchini, Katharine R.; Banerjee, A. Raja; Kim, Tae Hoon

    2009-01-01

    The vast amount of recent progress made on the sequence of the human genome has allowed an unprecedented examination of cis-regulatory networks. These networks consist of functional elements such as promoters, enhancers, silencers, and insulators, and their coordinated activity is responsible for regulation of gene expression. Recent studies surveyed the entire genome, identifying novel elements and evaluating functional differences in respect to development. These investigations present the first steps towards a global regulatory map for expression in the human genome. PMID:19560550

  9. Regulatory compliance requirements for an open source electronic image trial management system.

    PubMed

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

    2010-01-01

    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

  10. Association of Inhalation Toxicologists' (AIT) review of regulatory aspects for inhalation toxicology studies.

    PubMed

    Jones, David R; Baldrick, Paul

    2013-02-01

    Regulatory guidelines are intended to provide recommendations on ways to achieve greater harmonization in the interpretation and application of technical procedures and requirements for product registration in order to reduce or obviate replication of the testing carried out during the research and development of new products. The objectives of such harmonization are more economical use of human, animal and material resources; the elimination of unnecessary delay in the global development and availability of new products while maintaining safeguards on quality, safety and efficacy; and the fulfillment of regulatory obligations to protect public health. PMID:23363040

  11. 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...

  12. 77 FR 43885 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-26

    ... Release No. 65025 (August 3, 2011), 76 FR 48937 (August 9, 2011) (SEC order approving SR-FINRA- 2011-027... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and...\\ notice is hereby given that on July 11, 2012, Financial Industry Regulatory Authority, Inc....

  13. 78 FR 62417 - Regulatory Capital Rules: Regulatory Capital, Implementation of Basel III, Capital Adequacy...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-22

    ... comments that appeared in the Federal Register of September 10, 2013 (78 FR 55340), regarding Regulatory... NW., Washington, DC 20429. SUPPLEMENTARY INFORMATION: In FR Doc. 2013-21357, appearing on page 55518... Part 324 RIN 3064-AD95 Regulatory Capital Rules: Regulatory Capital, Implementation of Basel...

  14. 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...

  15. 78 FR 36011 - Region VII Regulatory Fairness Board; Federal Regulatory Enforcement Fairness Hearing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-14

    ... ADMINISTRATION Region VII Regulatory Fairness Board; Federal Regulatory Enforcement Fairness Hearing AGENCY: U.S. Small Business Administration (SBA). ACTION: Notice of open meeting of the Regional (Region VII) Small... Region VII Regulatory Fairness Board must contact Jeanna Trenkamp by June 17, 2013 in writing, by fax...

  16. 77 FR 8938 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-15

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... 1, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and... financial or operational schedules or reports as FINRA may deem necessary as a supplement to the...

  17. 78 FR 17975 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-25

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

  18. 75 FR 30453 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-01

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change To Amend the By- Laws of NASD Dispute Resolution May 24, 2010. On January 22, 2010, Financial Industry Regulatory Authority,...

  19. 78 FR 62831 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-22

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... FINRA Rulebook October 4, 2013. I. Introduction On June 21, 2013, the Financial Industry Regulatory... Securities Exchange Act Release No. 64736 (June 23, 2011), 76 FR 38245 (June 29, 2011) (File No. SR-...

  20. 78 FR 40792 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-08

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... 19b-4 thereunder,\\2\\ notice is hereby given that on June 21, 2013, Financial Industry Regulatory... (Customer Complaints), and Incorporated NYSE Rule 342.21 (Trade Review and Investigation); (3) replace...

  1. 77 FR 3515 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Instituting...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-24

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Instituting..., the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange... designed to simplify the Rule's price and size tiers; facilitate the display of customer limit orders...

  2. 75 FR 55842 - Self-Regulatory Organizations; Financial Industry Regulatory Authority; Order Granting Approval...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-14

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority; Order Granting Approval of... FINRA Rulebook September 3, 2010. I. Introduction On June 14, 2010, Financial Industry Regulatory...), 75 FR 39715 (July 12, 2010). II. Description As part of the process of developing a new...

  3. 76 FR 15012 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-18

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of..., 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a National Association of... the growing complexity of the financial services industry and the importance of services provided...

  4. 77 FR 26340 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-03

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... January 10, 2012, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and... Industry and Financial Markets Association (``SIFMA''), on the proposal.\\5\\ On April 23, 2012,...

  5. 77 FR 58880 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-24

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and...,\\2\\ notice is hereby given that on September 17, 2012, Financial Industry Regulatory Authority,...

  6. 78 FR 55322 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-10

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... 19b-4 thereunder,\\2\\ notice is hereby given that on August 23, 2013, Financial Industry Regulatory... investment banking business, or as consideration for investment banking business previously awarded...

  7. 75 FR 35105 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-21

    ... Release No. 17371 (December 12, 1980), 45 FR 83707 (December 19, 1980) (Order Approving Proposed Rule... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a National Association of Securities Dealers,...

  8. 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...

  9. 76 FR 10629 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-25

    ... No. 63316 (Nov. 15, 2010), 75 FR 71166 (Nov. 22, 2010) (``Notice''). \\4\\ See letter from Board of... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a... November 1, 2010, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities...

  10. 76 FR 45883 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-01

    ... certain changes. See Securities Exchange Act Release No. 64687 (June 16, 2011), 76 FR 36586 (June 22, 2011... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... July 15, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities...

  11. 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...

  12. 76 FR 24076 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-29

    ... 27, 2011.\\4\\ \\3\\ See Securities Exchange Act Release No. 63010 (September 29, 2010), 75 FR 61541... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...,\\2\\ notice is hereby given that on April 18, 2011, Financial Industry Regulatory Authority,...

  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 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 ...

  15. 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...

  16. 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.

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 5 CFR 838.102 - Regulatory structure.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 2 2014-01-01 2014-01-01 false Regulatory structure. 838.102 Section 838... (CONTINUED) COURT ORDERS AFFECTING RETIREMENT BENEFITS Court Orders Generally Organization and Structure of Regulations on Court Orders § 838.102 Regulatory structure. (a) This part is organized as follows: (1)...

  2. 5 CFR 838.102 - Regulatory structure.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 2 2013-01-01 2013-01-01 false Regulatory structure. 838.102 Section 838... (CONTINUED) COURT ORDERS AFFECTING RETIREMENT BENEFITS Court Orders Generally Organization and Structure of Regulations on Court Orders § 838.102 Regulatory structure. (a) This part is organized as follows: (1)...

  3. 47 CFR 90.1309 - Regulatory status.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 5 2013-10-01 2013-10-01 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...

  4. 47 CFR 90.1309 - Regulatory status.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 5 2011-10-01 2011-10-01 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...

  5. 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...

  6. 47 CFR 90.1309 - Regulatory status.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 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...

  7. 47 CFR 90.1309 - Regulatory status.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 5 2014-10-01 2014-10-01 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...

  8. 78 FR 1624 - Fall 2012 Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-08

    ..., ``Regulatory Planning and Review'' (58 FR 51735, Oct. 4, 1993), as supplemented by Executive Order (EO) 13563, ``Improving Regulation and Regulatory Review'' (76 FR 3821, Jan. 21, 2011); 12898, ``Federal Actions to Address Environmental Justice in Minority Populations and Low-income Populations'' (59 FR 7629, Feb....

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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:...

  14. 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...

  15. 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...

  16. 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...

  17. Department of Labor Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-20

    ..., including the detail required to be reported. Timetable: Action Date FR Cite NPRM 07/00/11 Regulatory... 1 of the order. Timetable: Action Date FR Cite NPRM 08/03/09 74 FR 38488 NPRM Comment Period End 09/02/09 Final Action 05/20/10 75 FR 28368 Final Action Effective 06/21/10 Regulatory...

  18. 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...

  19. 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...

  20. 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....

  1. Small Business Administration Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    ... PROGRAM Legal Authority: 15 USC 636(a)(31) Abstract: SBA plans to issue regulations for the SBA Express... eligibility determinations. Timetable: Action Date FR Cite NPRM 08/00/10 Regulatory Flexibility Analysis... program. ] Timetable: Action Date FR Cite NPRM 08/00/10 Regulatory Flexibility Analysis Required:...

  2. 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... for Compression-Ignition Marine Engines § 94.6 Regulatory structure. This section provides an overview... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Regulatory structure. 94.6 Section...

  3. Environment, safety, and health regulatory implementation plan

    SciTech Connect

    Not Available

    1993-10-21

    To identify, document, and maintain the Uranium Mill Tailings Remedial Action (UMTRA) Project`s environment, safety, and health (ES&H) regulatory requirements, the US Department of Energy (DOE) UMTRA Project Office tasked the Technical Assistance Contractor (TAC) to develop a regulatory operating envelope for the UMTRA Project. The system selected for managing the UMTRA regulatory operating envelope data bass is based on the Integrated Project Control/Regulatory Compliance System (IPC/RCS) developed by WASTREN, Inc. (WASTREN, 1993). The IPC/RCS is a tool used for identifying regulatory and institutional requirements and indexing them to hardware, personnel, and program systems on a project. The IPC/RCS will be customized for the UMTRA Project surface remedial action and groundwater restoration programs. The purpose of this plan is to establish the process for implementing and maintaining the UMTRA Project`s regulatory operating envelope, which involves identifying all applicable regulatory and institutional requirements and determining compliance status. The plan describes how the Project will identify ES&H regulatory requirements, analyze applicability to the UMTRA Project, and evaluate UMTRA Project compliance status.

  4. Federal Trade Commission Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    ... No. 12866 ``Regulatory Planning and Review'' of September 30, 1993, 58 FR 51735 (Oct. 4, 1993). Since... Final Rule, which the Commission issued jointly with the Federal Reserve on January 15, 2010 (75 FR 2724... Regulatory Plan narrative. 74 FR 64137, 64366. The Commission has also responded to the optional...

  5. 75 FR 79929 - 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...

  6. 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...

  7. 5 CFR 838.102 - Regulatory structure.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Regulatory structure. 838.102 Section 838... (CONTINUED) COURT ORDERS AFFECTING RETIREMENT BENEFITS Court Orders Generally Organization and Structure of Regulations on Court Orders § 838.102 Regulatory structure. (a) This part is organized as follows: (1)...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 77 FR 8020 - Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-13

    ... Agenda for the agency. SBA's last semiannual regulatory agenda was published on July 7, 2011, at 76 FR... Administration--Completed Actions Regulation Sequence No. Title Identifier No. 474 Implementation of Military... individual SBDC client data. Timetable: Action Date FR Cite ANPRM 06/00/12 Regulatory Flexibility...

  13. 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....

  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. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 5 CFR 838.102 - Regulatory structure.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 2 2012-01-01 2012-01-01 false Regulatory structure. 838.102 Section 838... (CONTINUED) COURT ORDERS AFFECTING RETIREMENT BENEFITS Court Orders Generally Organization and Structure of Regulations on Court Orders § 838.102 Regulatory structure. (a) This part is organized as follows: (1)...

  20. 5 CFR 838.102 - Regulatory structure.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Regulatory structure. 838.102 Section 838... (CONTINUED) COURT ORDERS AFFECTING RETIREMENT BENEFITS Court Orders Generally Organization and Structure of Regulations on Court Orders § 838.102 Regulatory structure. (a) This part is organized as follows: (1)...

  1. 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...

  2. 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...

  3. 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...

  4. Department of Energy Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-20

    ... ``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 Framework Document Availibility 09/20/10 75 FR 59657 Comment Period End 11/24/10 NPRM 04/00/12 Final Action...

  5. 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...

  6. 78 FR 44331 - Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-23

    ...This Regulatory Agenda is a semiannual summary of all current and projected rulemakings and completed actions of the Small Business Administration (SBA). SBA expects that this summary information will enable the public to be more aware of, and effectively participate in, SBA's regulatory activity. SBA invites the public to submit comments on any aspect of this...

  7. 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...

  8. 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...

  9. 12 CFR 562.2 - Regulatory reports.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... defined herein. A regulatory report is any report that the OTS prepares, or is submitted to, or is used by... condition and operation of savings associations. The Report of Examination and the Thrift Financial Report... of the special supervisory, regulatory, and economic policy needs served by such reports....

  10. 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...

  11. 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...

  12. 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)...

  13. 76 FR 75798 - Reducing Regulatory Burden

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-05

    ...; ] DEPARTMENT OF ENERGY 5 CFR Chapter XXIII 10 CFR Chapters II, III, X Reducing Regulatory Burden AGENCY: Office... its implementation of Executive Order 13563, ``Improving Regulation and Regulatory Review,'' issued by... General Counsel for Legislation, Regulation, and Energy Efficiency, U.S. Department of Energy, Office...

  14. Department of Justice Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    ...,'' 58 FR 51735, and the Regulatory Flexibility Act, 5 U.S.C. sections 601 to 612 (1988). FOR FURTHER... proposed rulemaking that was published in the Federal Register on September 30, 2004, at 69 FR 58768... Business Regulatory Enforcement Fairness Act of 1996 (SBREFA). Timetable: Action Date FR Cite ANPRM...

  15. 78 FR 1646 - Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-08

    ...This agenda provides summary descriptions of regulations being developed by the Civilian Agency Acquisition Council and the Defense Acquisition Regulations Council in compliance with Executive Order 12866 ``Regulatory Planning and Review.'' This agenda is being published to allow interested persons an opportunity to participate in the rulemaking process. The Regulatory Secretariat Division has......

  16. Department of Transportation Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    ..., and Plain Language Review Plan. Our latest review notice was published November 15, 2007 (72 FR 64170... 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...

  17. 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...

  18. 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...

  19. 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...

  20. 78 FR 1698 - Semiannual Regulatory Flexibility Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-08

    ... whether a deposited check has been returned unpaid. Timetable: Action Date FR Cite Board Requested Comment 03/25/11 76 FR 16862 Board Expects Further Action........ 12/00/12 Regulatory Flexibility Analysis... by their Federal regulatory authority. Timetable: Action Date FR Cite Board Requested Comment...

  1. 49 CFR 355.21 - Regulatory review.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 5 2013-10-01 2013-10-01 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...

  2. 49 CFR 355.21 - Regulatory review.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 5 2012-10-01 2012-10-01 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. 49 CFR 355.21 - Regulatory review.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 5 2014-10-01 2014-10-01 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...

  4. 76 FR 40050 - Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-07

    ...) pursuant to Executive Order 12866, ``Regulatory Planning and Review,'' 58 FR 51735, and the Regulatory... FR Cite Notice: Public Meeting Framework 09/28/10 75 FR 59657 Document Availibility. Comment Period... Commercial and Industrial Electric Motors. Issued in Washington, DC, on March 1, 2011. Scott Blake...

  5. 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...

  6. 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...

  7. 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...

  8. 78 FR 44349 - Semiannual Regulatory Agenda

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-23

    ... purposes of HMDA. Timetable: Action Date FR Cite Prerule Activities 09/00/13 Regulatory Flexibility...). Timetable: ] Action Date FR Cite NPRM 08/23/12 77 FR 51116 NPRM Comment Period Extended........ 09/06/12 77 FR 54843 NPRM Comment Period End 11/06/12 Final Rule 10/00/13 Regulatory Flexibility...

  9. The Psychology of Globalization.

    ERIC Educational Resources Information Center

    Arnett, Jeffrey Jensen

    2002-01-01

    Examines the influence of globalization on psychological functioning, describing globalization worldwide and its psychological consequences. Notes that most people now develop bicultural identities that combine local identity with global culture-related identity. Identity confusion is increasing among young people in non-western cultures because…

  10. 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…

  11. 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…

  12. 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…

  13. Computational architecture of the yeast regulatory network

    NASA Astrophysics Data System (ADS)

    Maslov, Sergei; Sneppen, Kim

    2005-12-01

    The topology of regulatory networks contains clues to their overall design principles and evolutionary history. We find that while in- and out-degrees of a given protein in the regulatory network are not correlated with each other, there exists a strong negative correlation between the out-degree of a regulatory protein and in-degrees of its targets. Such correlation positions large regulatory modules on the periphery of the network and makes them rather well separated from each other. We also address the question of relative importance of different classes of proteins quantified by the lethality of null-mutants lacking one of them as well as by the level of their evolutionary conservation. It was found that in the yeast regulatory network highly connected proteins are in fact less important than their low-connected counterparts.

  14. 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.

  15. Global sea level linked to global temperature

    PubMed Central

    Vermeer, Martin; Rahmstorf, Stefan

    2009-01-01

    We propose a simple relationship linking global sea-level variations on time scales of decades to centuries to global mean temperature. This relationship is tested on synthetic data from a global climate model for the past millennium and the next century. When applied to observed data of sea level and temperature for 1880–2000, and taking into account known anthropogenic hydrologic contributions to sea level, the correlation is >0.99, explaining 98% of the variance. For future global temperature scenarios of the Intergovernmental Panel on Climate Change's Fourth Assessment Report, the relationship projects a sea-level rise ranging from 75 to 190 cm for the period 1990–2100. PMID:19995972

  16. 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

  17. 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

  18. Small regulatory RNAs in Archaea

    PubMed Central

    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. PMID:24755959

  19. 76 FR 2725 - Draft Regulatory Guide: Issuance, Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-14

    ... From the Federal Register Online via the Government Publishing Office NUCLEAR REGULATORY COMMISSION Draft Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Issuance, Availability of Draft Regulatory Guide (DG)-1245. FOR FURTHER INFORMATION CONTACT: Mark P. Orr, U.S. Nuclear Regulatory Commission,...

  20. 76 FR 16017 - Withdrawal of Regulatory Guide 8.5

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-22

    ... COMMISSION Withdrawal of Regulatory Guide 8.5 AGENCY: Nuclear Regulatory Commission. ACTION: Withdrawal of Regulatory Guide 8.5, ``Criticality and Other Interior Evacuation Signals.'' FOR FURTHER INFORMATION CONTACT... The U.S. Nuclear Regulatory Commission (NRC) is withdrawing Regulatory Guide 8.5, ``Criticality...

  1. 75 FR 20645 - Draft Regulatory Guide: Issuance, Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-20

    ... COMMISSION Draft Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Draft Regulatory Guide, DG-4018. FOR FURTHER INFORMATION CONTACT... Regulatory Commission (NRC) is issuing for public comment a draft guide in the agency's ``Regulatory...

  2. 76 FR 6086 - Draft Regulatory Guide: Issuance, Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-03

    ... COMMISSION 10 CFR Part 73 RIN 3150-AI49 Draft Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Availability of Draft Regulatory Guide. SUMMARY: The U.S. Nuclear Regulatory Commission (Commission or NRC) is issuing for public comment Draft Regulatory Guide,...

  3. 75 FR 36715 - Final Regulatory Guide: Issuance, Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-28

    ... COMMISSION Final Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide, RG 1.62. FOR FURTHER INFORMATION CONTACT: Karl J... Regulatory Commission (NRC or Commission) is issuing a revision of a guide in the agency's ``Regulatory...

  4. 76 FR 27924 - Draft Regulatory Guide, Guidance for ITAAC Closure

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-13

    ... COMMISSION 10 CFR Parts 2 and 52 RIN 3150-AI77 Draft Regulatory Guide, Guidance for ITAAC Closure AGENCY: Nuclear Regulatory Commission. ACTION: Draft regulatory guide; request for comment. SUMMARY: The U.S. Nuclear Regulatory Commission (NRC) is issuing for public comment Draft Regulatory Guide...

  5. 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.

  6. 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

  7. 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.

  8. T regulatory cells in allergy.

    PubMed

    Braga, M; Quecchia, C; Cavallucci, E; Di Giampaolo, L; Schiavone, C; Petrarca, C; Di Gioacchino, M

    2011-01-01

    The progressive understanding of the nature and mechanisms of T regulatory (Treg) cells in the last decade has changed the concept of immune tolerance, that is no longer considered as a mere lack of immune reactivity but as a finely regulated process that requires specific activity of cells, adhesion and secreted molecules. Tregs play a key role in maintenance of self-tolerance and induction of tolerance against ubiquitous innocuous non-self antigens, so preventing the onset of autoimmune diseases and allergies. This review will focus on the Treg response in allergy that is characterized by a down-regulation of allergen specific T cell proliferation and inhibition of both Th1 and Th2 cytokines production. Hence, Treg cells suppress allergen-specific Th1 and Th2 cell responses playing an important role in the physiological immune response to allergens. Further, Treg cells are able to suppress IgE production by B lymphocytes and directly or indirectly inhibit the activity of allergic inflammation effector cells, namely eosinophils, basophils and mastcells. Finally, increasing evidence suggests that Treg cells are also implicated in chronicity development of inflammatory diseases. This appears to happen through a fine interaction they entertain with resident tissue cells and has been particularly highlighted in the study of airways remodeling in asthma. The understanding of the mechanisms underlying allergen tolerance has brought new interest in the development of new allergy treatment, able to target Treg cells, both in allergy prevention and in the therapy of established allergy. PMID:21329567

  9. 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

  10. 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.

  11. 77 FR 34379 - Notice of Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-11

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

  12. In Vitro Testing for Orally Inhaled Products: Developments in Science-Based Regulatory Approaches.

    PubMed

    Forbes, Ben; Bäckman, Per; Christopher, David; Dolovich, Myrna; Li, Bing V; Morgan, Beth

    2015-07-01

    This article is part of a series of reports from the "Orlando Inhalation Conference-Approaches in International Regulation" which was held in March 2014, and coorganized by the University of Florida and the International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS). The goal of the conference was to foster the exchange of ideas and knowledge across the global scientific and regulatory community in order to identify and help move towards strategies for internationally harmonized, science-based regulatory approaches for the development and marketing approval of inhalation medicines, including innovator and second entry products. This article provides an integrated perspective of case studies and discussion related to in vitro testing of orally inhaled products, including in vitro-in vivo correlations and requirements for in vitro data and statistical analysis that support quality or bioequivalence for regulatory applications. PMID:25940082

  13. The unfolded protein response triggers site-specific regulatory ubiquitylation of 40S ribosomal proteins

    PubMed Central

    Rising, Lisa; Mak, Raymond; Webb, Kristofor; Kaiser, Stephen E.; Zuzow, Nathan; Riviere, Paul; Yang, Bing; Fenech, Emma; Tang, Xin; Lindsay, Scott A.; Christianson, John C.; Hampton, Randolph Y.; Wasserman, Steven A.; Bennett, Eric J.

    2015-01-01

    Summary Insults to endoplasmic reticulum (ER) homeostasis activate the unfolded protein response (UPR), which elevates protein folding and degradation capacity and attenuates protein synthesis. While a role for ubiquitin in regulating the degradation of misfolded ER-resident proteins is well described, ubiquitin-dependent regulation of translational reprogramming during the UPR remains uncharacterized. Using global quantitative ubiquitin proteomics, we identify evolutionarily conserved, site-specific regulatory ubiquitylation of 40S ribosomal proteins. We demonstrate that these events occur on assembled cytoplasmic ribosomes and are stimulated by both UPR activation and translation inhibition. We further show that ER stress-stimulated regulatory 40S ribosomal ubiquitylation occurs on a timescale similar to eIF2α phosphorylation, is dependent upon PERK signaling, and is required for optimal cell survival during chronic UPR activation. In total, these results reveal regulatory 40S ribosomal ubiquitylation as a previously uncharacterized and important facet of eukaryotic translational control. PMID:26051182

  14. Modeling of hysteresis in gene regulatory networks.

    PubMed

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

    2012-08-01

    Hysteresis, observed in many gene regulatory networks, has a pivotal impact on biological systems, which enhances the robustness of cell functions. In this paper, a general model is proposed to describe the hysteretic gene regulatory network by combining the hysteresis component and the transient dynamics. The Bouc-Wen hysteresis model is modified to describe the hysteresis component in the mammalian gene regulatory networks. Rigorous mathematical analysis on the dynamical properties of the model is presented to ensure the bounded-input-bounded-output (BIBO) stability and demonstrates that the original Bouc-Wen model can only generate a clockwise hysteresis loop while the modified model can describe both clockwise and counter clockwise hysteresis loops. Simulation studies have shown that the hysteresis loops from our model are consistent with the experimental observations in three mammalian gene regulatory networks and two E.coli gene regulatory networks, which demonstrate the ability and accuracy of the mathematical model to emulate natural gene expression behavior with hysteresis. A comparison study has also been conducted to show that this model fits the experiment data significantly better than previous ones in the literature. The successful modeling of the hysteresis in all the five hysteretic gene regulatory networks suggests that the new model has the potential to be a unified framework for modeling hysteresis in gene regulatory networks and provide better understanding of the general mechanism that drives the hysteretic function. PMID:22588784

  15. 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.

  16. 77 FR 21785 - Medical Countermeasures Initiative Regulatory Science Symposium

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-11

    ... HUMAN SERVICES Food and Drug Administration Medical Countermeasures Initiative Regulatory Science... Administration (FDA) is announcing the following meeting: Medical Countermeasures Initiative Regulatory Science... development, highlight work on regulatory science as it applies to the development and advancement of...

  17. Evolution of transcriptional regulatory circuits in bacteria

    PubMed Central

    Perez, J. Christian; Groisman, Eduardo A.

    2009-01-01

    Related organisms typically respond to a given cue by altering the level or activity of orthologous transcription factors, which, paradoxically, often regulate expression of distinct gene sets. Although promoter rewiring of shared genes is primarily responsible for regulatory differences among related eukaryotic species, in bacteria, species-specific genes are often controlled by ancestral transcription factors and regulatory circuit evolution has been further shaped by horizontal gene transfer. Modifications in transcription factors and in promoter structure also contribute to divergence in bacterial regulatory circuits. PMID:19632175

  18. Global warming without global mean precipitation increase?

    PubMed

    Salzmann, Marc

    2016-06-01

    Global climate models simulate a robust increase of global mean precipitation of about 1.5 to 2% per kelvin surface warming in response to greenhouse gas (GHG) forcing. Here, it is shown that the sensitivity to aerosol cooling is robust as well, albeit roughly twice as large. This larger sensitivity is consistent with energy budget arguments. At the same time, it is still considerably lower than the 6.5 to 7% K(-1) decrease of the water vapor concentration with cooling from anthropogenic aerosol because the water vapor radiative feedback lowers the hydrological sensitivity to anthropogenic forcings. When GHG and aerosol forcings are combined, the climate models with a realistic 20th century warming indicate that the global mean precipitation increase due to GHG warming has, until recently, been completely masked by aerosol drying. This explains the apparent lack of sensitivity of the global mean precipitation to the net global warming recently found in observations. As the importance of GHG warming increases in the future, a clear signal will emerge. PMID:27386558

  19. Global warming without global mean precipitation increase?

    PubMed Central

    Salzmann, Marc

    2016-01-01

    Global climate models simulate a robust increase of global mean precipitation of about 1.5 to 2% per kelvin surface warming in response to greenhouse gas (GHG) forcing. Here, it is shown that the sensitivity to aerosol cooling is robust as well, albeit roughly twice as large. This larger sensitivity is consistent with energy budget arguments. At the same time, it is still considerably lower than the 6.5 to 7% K−1 decrease of the water vapor concentration with cooling from anthropogenic aerosol because the water vapor radiative feedback lowers the hydrological sensitivity to anthropogenic forcings. When GHG and aerosol forcings are combined, the climate models with a realistic 20th century warming indicate that the global mean precipitation increase due to GHG warming has, until recently, been completely masked by aerosol drying. This explains the apparent lack of sensitivity of the global mean precipitation to the net global warming recently found in observations. As the importance of GHG warming increases in the future, a clear signal will emerge. PMID:27386558

  20. 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

  1. Strategies of bringing drug product marketing applications to meet current regulatory standards.

    PubMed

    Wu, Yan; Freed, Anita; Lavrich, David; Raghavachari, Ramesh; Huynh-Ba, Kim; Shah, Ketan; Alasandro, Mark

    2015-08-01

    In the past decade, many guidance documents have been issued through collaboration of global organizations and regulatory authorities. Most of these are applicable to new products, but there is a risk that currently marketed products will not meet the new compliance standards during audits and inspections while companies continue to make changes through the product life cycle for continuous improvement or market demands. This discussion presents different strategies to bringing drug product marketing applications to meet current and emerging standards. It also discusses stability and method designs to meet process validation and global development efforts. PMID:26024722

  2. Stability of genetic regulatory networks based on switched systems and mixed time-delays.

    PubMed

    Wang, Lan; Luo, Zong-Ping; Yang, Hui-Lin; Cao, Jinde

    2016-08-01

    In this paper, the switched genetic regulatory networks (GRNs) are modeled from a real biological system, based on switched systems, noise and mixed time-delays. Global asymptotical stability for the proposed switched GRNs are studied by the Lyapunov method and the matrix inequality techniques. Some new sufficient conditions are obtained to ensure the global asymptotical stability of the proposed switched GRNs. Furthermore, the proposed LMI results are computationally efficient as it can be solved numerically with standard commercial software. Finally, an example is provided to illustrate the usefulness of the results. PMID:27326659

  3. 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.. PMID:21430959

  4. 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

  5. Regulatory T Cells in Allogeneic Stem Cell Transplantation

    PubMed Central

    Nagler, Arnon

    2013-01-01

    Growing evidence suggests that cellular adoptive immunotherapy is becoming an attractive though challenging approach in regulating tumor immunity and alloresponses in clinical transplantation. Naturally arising CD4+CD25+Foxp3+ regulatory T cells (Treg) have emerged as a key component in this regard. Over the last decade, a large body of evidence from preclinical models has demonstrated their crucial role in auto- and tumor immunity and has opened the door to their “first-in-man” clinical application. Initial studies in clinical allogeneic stem cell transplantation are very encouraging and may pave the way for other applications. Further improvements in Treg ex vivo or in vivo expansion technologies will simplify their global clinical application. In this review, we discuss the current knowledge of Treg biology and their potential for cell-based immunotherapy in allogeneic stem cell transplantation. PMID:23737813

  6. The New Global Health

    PubMed Central

    Simone, Patricia M.; Davison, Veronica; Slutsker, Laurence

    2013-01-01

    Global health reflects the realities of globalization, including worldwide dissemination of infectious and noninfectious public health risks. Global health architecture is complex and better coordination is needed between multiple organizations. Three overlapping themes determine global health action and prioritization: development, security, and public health. These themes play out against a background of demographic change, socioeconomic development, and urbanization. Infectious diseases remain critical factors, but are no longer the major cause of global illness and death. Traditional indicators of public health, such as maternal and infant mortality rates no longer describe the health status of whole societies; this change highlights the need for investment in vital registration and disease-specific reporting. Noncommunicable diseases, injuries, and mental health will require greater attention from the world in the future. The new global health requires broader engagement by health organizations and all countries for the objectives of health equity, access, and coverage as priorities beyond the Millennium Development Goals are set. PMID:23876365

  7. Globalization, culture and psychology.

    PubMed

    Melluish, Steve

    2014-10-01

    This article outlines the cultural and psychological effects of globalization. It looks at the impact of globalization on identity; ideas of privacy and intimacy; the way we understand and perceive psychological distress; and the development of the profession of psychology around the world. The article takes a critical perspective on globalization, seeing it as aligned with the spread of neoliberal capitalism, a tendency towards cultural homogenization, the imposition of dominant 'global north' ideas and the resultant growing inequalities in health and well-being. However, it also argues that the increased interconnectedness created by globalization allows for greater acknowledgement of our common humanity and for collective efforts to be developed to tackle what are increasingly global problems. This requires the development of more nuanced understandings of cultural differences and of indigenous psychologies. PMID:25343628

  8. 76 FR 59462 - Self-Regulatory Organizations; BATS Y-Exchange, Inc.; Notice of Filing of Proposed Rule Change To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-26

    ... COMMISSION Self-Regulatory Organizations; BATS Y-Exchange, Inc.; Notice of Filing of Proposed Rule Change To Amend and Restate the Amended and Restated Bylaws of BATS Global Markets, Inc. September 19, 2011... thereunder,\\2\\ notice is hereby given that on September 7, 2011, BATS Y-Exchange, Inc. (the ``Exchange''...

  9. 76 FR 59472 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing of Proposed Rule Change To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-26

    ... COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing of Proposed Rule Change To Amend and Restate the Amended and Restated Bylaws of BATS Global Markets, Inc. September 19, 2011... thereunder,\\2\\ notice is hereby given that on September 7, 2011, BATS Exchange, Inc. (the ``Exchange''...

  10. 75 FR 9982 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing and Immediate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-04

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Adopt a Round Lot Holder Initial Listing Requirement for Listing of Warrants on the Nasdaq Global and...

  11. 76 FR 71396 - Self-Regulatory Organizations; BATS Y-Exchange, Inc.; Order Approving Proposed Rule Change, as...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-17

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; BATS Y-Exchange, Inc.; Order Approving Proposed Rule Change, as Modified by Partial Amendment No. 1, To Amend and Restate the Amended and Restated Bylaws of BATS Global Markets, Inc. November 10, 2011....

  12. 78 FR 75607 - Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing of a Proposed Rule Change in...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-12

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; BATS Exchange, Inc.; Notice of Filing of a Proposed Rule Change in Connection With the Proposed Business Combination Involving BATS Global Markets, Inc. and Direct Edge Holdings LLC December 6, 2013. Pursuant...

  13. 78 FR 75585 - Self-Regulatory Organizations; BATS Y-Exchange, Inc.; Notice of Filing of a Proposed Rule Change...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-12

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; BATS Y-Exchange, Inc.; Notice of Filing of a Proposed Rule Change in Connection With the Proposed Business Combination Involving BATS Global Markets, Inc. and Direct Edge Holdings LLC December 6, 2013....

  14. 78 FR 62834 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Granting Approval of Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-22

    ... From the Federal Register Online via the Government Publishing Office SECURITIES AND EXCHANGE COMMISSION Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Granting Approval of Proposed Rule Change Relating to the Listing and Trading of the Shares of the First Trust Global Tactical Commodity Strategy Fund of First...

  15. Structural basis for regulation of rhizobial nodulation and symbiosis gene expression by the regulatory NolR

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The symbiosis between rhizobial microbes and host plants involves the coordinated expression of multiple genes, which leads to nodule formation and nitrogen fixation. As part of the transcriptional machinery for nodulation and symbiosis across a range of Rhizobium, NolR serves as a global regulatory...

  16. Global health for a globally minded president.

    PubMed

    Daulaire, Nils

    2009-01-01

    President-elect Barack Obama can build on historic initiatives championed by his predecessor in global AIDS and malaria. These should serve as the platform for a more comprehensive and evidence-based set of activities aimed at addressing the major causes of ill health and instability in low-income countries. Obama should launch a new Global Family Health Action Plan aimed at saving the lives of six million children and women annually in impoverished nations. Existing policies driven by U.S. domestic ideological battles, particularly those relating to sexual and reproductive health, should be revised and brought into line with solid science and evidence from the field. PMID:19151008

  17. Genomic analysis of regulatory network dynamics reveals large topological changes

    NASA Astrophysics Data System (ADS)

    Luscombe, Nicholas M.; Madan Babu, M.; Yu, Haiyuan; Snyder, Michael; Teichmann, Sarah A.; Gerstein, Mark

    2004-09-01

    Network analysis has been applied widely, providing a unifying language to describe disparate systems ranging from social interactions to power grids. It has recently been used in molecular biology, but so far the resulting networks have only been analysed statically. Here we present the dynamics of a biological network on a genomic scale, by integrating transcriptional regulatory information and gene-expression data for multiple conditions in Saccharomyces cerevisiae. We develop an approach for the statistical analysis of network dynamics, called SANDY, combining well-known global topological measures, local motifs and newly derived statistics. We uncover large changes in underlying network architecture that are unexpected given current viewpoints and random simulations. In response to diverse stimuli, transcription factors alter their interactions to varying degrees, thereby rewiring the network. A few transcription factors serve as permanent hubs, but most act transiently only during certain conditions. By studying sub-network structures, we show that environmental responses facilitate fast signal propagation (for example, with short regulatory cascades), whereas the cell cycle and sporulation direct temporal progression through multiple stages (for example, with highly inter-connected transcription factors). Indeed, to drive the latter processes forward, phase-specific transcription factors inter-regulate serially, and ubiquitously active transcription factors layer above them in a two-tiered hierarchy. We anticipate that many of the concepts presented here-particularly the large-scale topological changes and hub transience-will apply to other biological networks, including complex sub-systems in higher eukaryotes.

  18. Comparative studies of gene regulatory mechanisms.

    PubMed

    Pai, Athma A; Gilad, Yoav

    2014-12-01

    It has become increasingly clear that changes in gene regulation have played an important role in adaptive evolution both between and within species. Over the past five years, comparative studies have moved beyond simple characterizations of differences in gene expression levels within and between species to studying variation in regulatory mechanisms. We still know relatively little about the precise chain of events that lead to most regulatory adaptations, but we have taken significant steps towards understanding the relative importance of changes in different mechanisms of gene regulatory evolution. In this review, we first discuss insights from comparative studies in model organisms, where the available experimental toolkit is extensive. We then focus on a few recent comparative studies in primates, where the limited feasibility of experimental manipulation dictates the approaches that can be used to study gene regulatory evolution. PMID:25215415

  19. REGULATORY APPLICATIONS OF POREWATER TOXICITY TESTING

    EPA Science Inventory

    The purpose of this chapter is to evaluate the use of porewater toxicity tests in regulatory applications, including their potential use in the development of sediment quality guideline (SQG) values. Specifically, the following discussion focuses on the appropriateness and readin...

  20. 47 CFR 69.727 - Regulatory relief.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... customer. (b) Phase II relief. Upon satisfaction of the Phase II triggers specified in §§ 69.709(c) or 69... Pricing Flexibility § 69.727 Regulatory relief. (a) Phase I relief. Upon satisfaction of the Phase...