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  1. Antigen-presenting cells exposed to Lactobacillus acidophilus NCFM, Bifidobacterium bifidum BI-98, and BI-504 reduce regulatory T cell activity

    DEFF Research Database (Denmark)

    Schmidt, Esben Gjerløff Wedebye; Claesson, Mogens Helweg; Jensen, Simon Skjøde

    2010-01-01

    BACKGROUND:: The effect in vitro of six different probiotic strains including Lactobacillus acidophilus NCFM, Lactobacillus salivarius Ls-33, Lactobacillus paracasei subsp. paracasei YS8866441, Lactobacillus plantarum Lp-115, Bifidobacterium bifidum BI-504 and BI-98 was studied on splenic...

  2. 77 FR 47328 - Reducing Regulatory Burden

    Science.gov (United States)

    2012-08-08

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

  3. 77 FR 28518 - Reducing Regulatory Burden

    Science.gov (United States)

    2012-05-15

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

  4. Microinterventions targeting regulatory focus and regulatory fit selectively reduce dysphoric and anxious mood.

    Science.gov (United States)

    Strauman, Timothy J; Socolar, Yvonne; Kwapil, Lori; Cornwell, James F M; Franks, Becca; Sehnert, Steen; Higgins, E Tory

    2015-09-01

    Depression and generalized anxiety, separately and as comorbid states, continue to represent a significant public health challenge. Current cognitive-behavioral treatments are clearly beneficial but there remains a need for continued development of complementary interventions. This manuscript presents two proof-of-concept studies, in analog samples, of "microinterventions" derived from regulatory focus and regulatory fit theories and targeting dysphoric and anxious symptoms. In Study 1, participants with varying levels of dysphoric and/or anxious mood were exposed to a brief intervention either to increase or to reduce engagement in personal goal pursuit, under the hypothesis that dysphoria indicates under-engagement of the promotion system whereas anxiety indicates over-engagement of the prevention system. In Study 2, participants with varying levels of dysphoric and/or anxious mood received brief training in counterfactual thinking, under the hypothesis that inducing individuals in a state of promotion failure to generate subtractive counterfactuals for past failures (a non-fit) will lessen their dejection/depression-related symptoms, whereas inducing individuals in a state of prevention failure to generate additive counterfactuals for past failures (a non-fit) will lessen their agitation/anxiety-related symptoms. In both studies, we observed discriminant patterns of reduction in distress consistent with the hypothesized links between dysfunctional states of the two motivational systems and dysphoric versus anxious symptoms.

  5. Reducing the Effect of Stereotype Threat: The Role of Coaction Contexts and Regulatory Fit

    Science.gov (United States)

    Wen, Fangfang; Zuo, Bin; Wu, Yang; Dong, Xuanhao; Wang, Wei

    2016-01-01

    Two experiments examined the effects of competition and cooperation contexts, as well as regulatory fit, on reducing the negative influence of stereotype threat. Experiment 1 demonstrated that in high stereotype threat conditions, participants in the cooperation context scored significantly higher on a math test than those in the competition…

  6. Regulatory risk assessments: Is there a need to reduce uncertainty and enhance robustness?

    Science.gov (United States)

    Snodin, D J

    2015-12-01

    A critical evaluation of several recent regulatory risk assessments has been undertaken. These relate to propyl paraben (as a food additive, cosmetic ingredient or pharmaceutical excipient), cobalt (in terms of a safety-based limit for pharmaceuticals) and the cancer Threshold of Toxicological Concern as applied to food contaminants and pharmaceutical impurities. In all cases, a number of concerns can be raised regarding the reliability of the current assessments, some examples being absence of data audits, use of single-dose and/or non-good laboratory practice studies to determine safety metrics, use of a biased data set and questionable methodology and lack of consistency with precedents and regulatory guidance. Drawing on these findings, a set of recommendations is provided to reduce uncertainty and improve the quality and robustness of future regulatory risk assessments.

  7. Dietary gluten reduces the number of intestinal regulatory T cells in mice

    DEFF Research Database (Denmark)

    Ejsing-Duun, Maria; Josephsen, Jytte; Aasted, Bent

    2008-01-01

    It is well established that gluten-free diet reduces the incidence of type 1 diabetes mellitus (T1D) in non-obese diabetic (NOD) mice, though the mechanism is not known. However, regulatory T cells (Treg) are likely to play an important role. Also, it is known that dietary gluten induces...... an intestinal increase in the bacterium Lactococcus garvieae, but the importance of this phenomenon for T1D development is doubtful. Our hypothesis is that gluten is responsible for mediating its effect on T1D through the influence on Treg development independent of gluten-induced Lactococci. Four groups...... of female NOD and BALB / c mice of 3 week old were fed either a gluten-free diet or a standard diet. Lactococcus garvieae or saline water was administered per oral to one of each dietary group. Spleen and Peyer's patches were sampled from BALB / c mice for flow cytometric monitoring of IL-10 and Treg. NOD...

  8. Chloroquine treatment enhances regulatory T cells and reduces the severity of experimental autoimmune encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Rodolfo Thomé

    Full Text Available BACKGROUND: The modulation of inflammatory processes is a necessary step, mostly orchestrated by regulatory T (Treg cells and suppressive Dendritic Cells (DCs, to prevent the development of deleterious responses and autoimmune diseases. Therapies that focused on adoptive transfer of Treg cells or their expansion in vivo achieved great success in controlling inflammation in several experimental models. Chloroquine (CQ, an anti-malarial drug, was shown to reduce inflammation, although the mechanisms are still obscure. In this context, we aimed to access whether chloroquine treatment alters the frequency of Treg cells and DCs in normal mice. In addition, the effects of the prophylactic and therapeutic treatment with CQ on Experimental Autoimmune Encephalomyelitis (EAE, an experimental model for human Multiple Sclerosis, was investigated as well. METHODOLOGY/PRINCIPAL FINDINGS: EAE was induced in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein (MOG35-55 peptide. C57BL/6 mice were intraperitoneally treated with chloroquine. Results show that the CQ treatment provoked an increase in Treg cells frequency as well as a decrease in DCs. We next evaluated whether prophylactic CQ administration is capable of reducing the clinical and histopathological signs of EAE. Our results demonstrated that CQ-treated mice developed mild EAE compared to controls that was associated with lower infiltration of inflammatory cells in the central nervous system CNS and increased frequency of Treg cells. Also, proliferation of MOG35-55-reactive T cells was significantly inhibited by chloroquine treatment. Similar results were observed when chloroquine was administrated after disease onset. CONCLUSION: We show for the first time that CQ treatment promotes the expansion of Treg cells, corroborating previous reports indicating that chloroquine has immunomodulatory properties. Our results also show that CQ treatment suppress the inflammation in the CNS of

  9. Docosahexaenoic acid reduces suppressive and migratory functions of CD4CD25 regulatory T-cells

    Science.gov (United States)

    Yessoufou, Akadiri; Plé, Aude; Moutairou, Kabirou; Hichami, Aziz; Khan, Naim Akhtar

    2009-01-01

    Immunological tolerance is one of the fundamental aspects of the immune system. The CD4+CD25+ regulatory T (Treg) cells have emerged as key players in the development of tolerance to self and foreign antigens. However, little is known about the endogenous factors and mechanisms controlling their suppressive capacity on immune response. In this study, we observed that docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, diminished, in a dose-dependent manner, the capacity of Treg cells to inhibit the CD4+CD25− effector T-cell proliferation. DHA not only reduced the migration of Treg cells toward chemokines but also downregulated the mRNA expression of CCR-4 and CXCR-4 in Treg cells. DHA also curtailed ERK1/2 and Akt phosphorylation and downregulated the Smad7 levels in these cells. Contradictorily, DHA upregulated the mRNA expression of Foxp3, CTLA-4, TGF-β, and IL-10; nonetheless, this fatty acid increased the expression of p27KIP1 mRNA, known to be involved in Treg cell unresponsiveness. In Foxp3-immunoprepitated nuclear proteins, DHA upregulated histone desacetylase 7 levels that would again participate in the unresposnsiveness of these cells. Finally, a DHA-enriched diet also diminished, ex vivo, the suppressive capacity of Treg cells. Altogether, these results suggest that DHA, by diminishing Treg cell functions, may play a key role in health and disease. PMID:19561360

  10. Reduced Numbers and Impaired Function of Regulatory T Cells in Peripheral Blood of Ischemic Stroke Patients

    Directory of Open Access Journals (Sweden)

    Johanna Ruhnau

    2016-01-01

    Full Text Available Background and Purpose. Regulatory T cells (Tregs have been suggested to modulate stroke-induced immune responses. However, analyses of Tregs in patients and in experimental stroke have yielded contradictory findings. We performed the current study to assess the regulation and function of Tregs in peripheral blood of stroke patients. Age dependent expression of CD39 on Tregs was quantified in mice and men. Methods. Total FoxP3+ Tregs and CD39+FoxP3+ Tregs were quantified by flow cytometry in controls and stroke patients on admission and on days 1, 3, 5, and 7 thereafter. Treg function was assessed by quantifying the inhibition of activation-induced expression of CD69 and CD154 on T effector cells (Teffs. Results. Total Tregs accounted for 5.0% of CD4+ T cells in controls and <2.8% in stroke patients on admission. They remained below control values until day 7. CD39+ Tregs were most strongly reduced in stroke patients. On day 3 the Treg-mediated inhibition of CD154 upregulation on CD4+ Teff was impaired in stroke patients. CD39 expression on Treg increased with age in peripheral blood of mice and men. Conclusion. We demonstrate a loss of active FoxP3+CD39+ Tregs from stroke patient’s peripheral blood. The suppressive Treg function of remaining Tregs is impaired after stroke.

  11. Transformational-transactional leadership styles and follower's regulatory focus: Fit reduces followers' turnover intentions

    NARCIS (Netherlands)

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

    2011-01-01

    Individuals' willingness to remain in their organizations contributes to workforce stability and organizational effectiveness. Working from the notion that different leadership styles encourage followers to self-regulate in distinct ways, we propose regulatory fit between leadership styles and follo

  12. Regulatory T cells reduce acute lung injury fibroproliferation by decreasing fibrocyte recruitment.

    Science.gov (United States)

    Garibaldi, Brian T; D'Alessio, Franco R; Mock, Jason R; Files, D Clark; Chau, Eric; Eto, Yoshiki; Drummond, M Bradley; Aggarwal, Neil R; Sidhaye, Venkataramana; King, Landon S

    2013-01-01

    Acute lung injury (ALI) causes significant morbidity and mortality. Fibroproliferation in ALI results in worse outcomes, but the mechanisms governing fibroproliferation remain poorly understood. Regulatory T cells (Tregs) are important in lung injury resolution. Their role in fibroproliferation is unknown. We sought to identify the role of Tregs in ALI fibroproliferation, using a murine model of lung injury. Wild-type (WT) and lymphocyte-deficient Rag-1(-/-) mice received intratracheal LPS. Fibroproliferation was characterized by histology and the measurement of lung collagen. Lung fibrocytes were measured by flow cytometry. To dissect the role of Tregs in fibroproliferation, Rag-1(-/-) mice received CD4(+)CD25(+) (Tregs) or CD4(+)CD25(-) Tcells (non-Tregs) at the time of LPS injury. To define the role of the chemokine (C-X-C motif) ligand 12 (CXCL12)-CXCR4 pathway in ALI fibroproliferation, Rag-1(-/-) mice were treated with the CXCR4 antagonist AMD3100 to block fibrocyte recruitment. WT and Rag-1(-/-) mice demonstrated significant collagen deposition on Day 3 after LPS. WT mice exhibited the clearance of collagen, but Rag-1(-/-) mice developed persistent fibrosis. This fibrosis was mediated by the sustained epithelial expression of CXCL12 (or stromal cell-derived factor 1 [SDF-1]) that led to increased fibrocyte recruitment. The adoptive transfer of Tregs resolved fibroproliferation by decreasing CXCL12 expression and subsequent fibrocyte recruitment. Blockade of the CXCL12-CXCR4 axis with AMD3100 also decreased lung fibrocytes and fibroproliferation. These results indicate a central role for Tregs in the resolution of ALI fibroproliferation by reducing fibrocyte recruitment along the CXCL12-CXCR4 axis. A dissection of the role of Tregs in ALI fibroproliferation may inform the design of new therapeutic tools for patients with ALI.

  13. Photo(chemotherapy reduces circulating Th17 cells and restores circulating regulatory T cells in psoriasis.

    Directory of Open Access Journals (Sweden)

    Takuya Furuhashi

    Full Text Available BACKGROUND: Photo(chemotherapy is widely used to treat psoriasis, the pathogenesis of which might be caused by an imbalance of Th17 cells/regulatory T cells (Treg. In the present study, we evaluated the effects of photo(chemotherapy on the Th17/Treg balance and Treg function. METHODS: Peripheral blood was obtained from psoriasis patients treated with bath-psoralen ultraviolet A (UVA, n = 50 or narrowband ultraviolet B (UVB, n = 18, and age-matched healthy volunteers (n = 20. CD3(+CD4(+IL-17A(+ or CD4(+CD25(+Foxp3(+cells were analyzed to estimate Th17 or Treg number by fluorescence-activated cell sorting. Moreover, CD4(+ CD25(- T cells from patients treated with PUVA(n = 14 were incubated in CFSE and activated with or without CD4(+ CD25(+T cells, and the suppressive function of CD4(+ CD25(+T cells were analyzed. RESULTS: Photo(chemotherapy significantly reduced Th17 levels from 5.66 ± 3.15% to 2.96 ± 2.89% in patients with increased Th17 (Th17/CD4>3.01% [mean+SD of controls]. In contrast, photo(chemotherapy significantly increased Treg levels from 2.77 ± 0.75 to 3.40 ± 1.88% in patients with less than 4.07% Treg level, defined as the mean of controls. Furthermore, while Treg suppressed the CD4(+CD25(- T cell proliferation to a greater extent in controls (Treg Functional Ratio 94.4 ± 4.28% than in patients (70.3±25.1%, PUVA significantly increased Treg Functional Ratio to 88.1 ± 6.47%. Th17 levels in severe patients (>30 PASI were significantly higher as compared to controls. Th17 levels that were left after treatment in the patients not achieving PASI 50 (3.78 ± 4.18% were significantly higher than those in the patients achieving PASI 75 (1.83±1.87%. Treg levels in patients achieving PASI 90 (4.89 ± 1.70% were significantly higher than those in the patients not achieving PASI 90 (3.90 ± 1.66%. Treg levels prior to treatment with Th17 high decreased group (5.16 ± 2.20% was significantly higher than that with Th17 high increased group

  14. FOXP3+ regulatory T cells in autoimmune hepatitis are fully functional and not reduced in frequency

    NARCIS (Netherlands)

    Peiseler, M.; Sebode, M.; Franke, B.; Wortmann, F.; Schwinge, D.; Quaas, A.; Baron, U.; Olek, S.; Wiegard, C.; Lohse, A.W.; Weiler-Normann, C.; Schramm, C.; Herkel, J.

    2012-01-01

    BACKGROUND & AIMS: The pathogenesis of autoimmune hepatitis (AIH) is not understood, but it was suggested that AIH may be related to a numerical or functional impairment of CD4+CD25+FOXP3+ regulatory T cells (Treg), which are important mediators of immune tolerance to self-antigens. However, the rol

  15. Paricalcitol reduces peritoneal fibrosis in mice through the activation of regulatory T cells and reduction in IL-17 production.

    Directory of Open Access Journals (Sweden)

    Guadalupe T González-Mateo

    Full Text Available Fibrosis is a significant health problem associated with a chronic inflammatory reaction. The precise mechanisms involved in the fibrotic process are still poorly understood. However, given that inflammation is a major causative factor, immunomodulation is a possible therapeutic approach to reduce fibrosis. The vitamin D receptor (VDR that is present in all hematopoietic cells has been associated with immunomodulation. We investigated whether the intraperitoneal administration of paricalcitol, a specific activator of the VDR, modulates peritoneal dialysis fluid (PDF-induced peritoneal fibrosis. We characterized the inflammatory process in the peritoneal cavity of mice treated or not treated with paricalcitol and analyzed the ensuing fibrosis. The treatment reduced peritoneal IL-17 levels, which strongly correlated with a significantly lower peritoneal fibrotic response. In vitro studies demonstrate that both CD4+ and CD8+ regulatory T cells appear to impact the regulation of IL-17. Paricalcitol treatment resulted in a significantly increased frequency of CD8+ T cells showing a regulatory phenotype. The frequency of CD4+ Tregs tends to be increased, but it did not achieve statistical significance. However, paricalcitol treatment increased the number of CD4+ and CD8+ Treg cells in vivo. In conclusion, the activation of immunological regulatory mechanisms by VDR signaling could prevent or reduce fibrosis, as shown in peritoneal fibrosis induced by PDF exposure in mice.

  16. Reducing uncertainty in regulatory decision-making for transgenic crops: more ecological research or clearer environmental risk assessment?

    Science.gov (United States)

    Raybould, Alan

    2010-01-01

    Ecological research and environmental risk assessment are similar in that they address interesting problems by formulating and testing hypotheses. They differ in the types of problems that are interesting, the characteristics of good hypotheses to solve those problems, and the methods for rigorous testing of hypotheses. It is important to recognize the differences between environmental risk assessment and basic ecological research because confusing them can lead to ineffective risk assessment and missed opportunities to advance ecological theory. Uncertainty in regulatory decision-making about transgenic crops may be reduced more effectively by clarifying the purpose and structure of environmental risk assessments than by further research on the ecology of the crops.

  17. Ionizing radiation selectively reduces skin regulatory T cells and alters immune function.

    Directory of Open Access Journals (Sweden)

    Yu Zhou

    Full Text Available The skin serves multiple functions that are critical for life. The protection from pathogens is achieved by a complicated interaction between aggressive effectors and controlling functions that limit damage. Inhomogeneous radiation with limited penetration is used in certain types of therapeutics and is experienced with exposure to solar particle events outside the protection of the Earth's magnetic field. This study explores the effect of ionizing radiation on skin immune function. We demonstrate that radiation, both homogeneous and inhomogeneous, induces inflammation with resultant specific loss of regulatory T cells from the skin. This results in a hyper-responsive state with increased delayed type hypersensitivity in vivo and CD4+ T cell proliferation in vitro. The effects of inhomogeneous radiation to the skin of astronauts or as part of a therapeutic approach could result in an unexpected enhancement in skin immune function. The effects of this need to be considered in the design of radiation therapy protocols and in the development of countermeasures for extended space travel.

  18. Ionizing Radiation Selectively Reduces Skin Regulatory T Cells and Alters Immune Function

    Science.gov (United States)

    Zhou, Yu; Ni, Houping; Balint, Klara; Sanzari, Jenine K.; Dentchev, Tzvete; Diffenderfer, Eric S.; Wilson, Jolaine M.; Cengel, Keith A.; Weissman, Drew

    2014-01-01

    The skin serves multiple functions that are critical for life. The protection from pathogens is achieved by a complicated interaction between aggressive effectors and controlling functions that limit damage. Inhomogeneous radiation with limited penetration is used in certain types of therapeutics and is experienced with exposure to solar particle events outside the protection of the Earth’s magnetic field. This study explores the effect of ionizing radiation on skin immune function. We demonstrate that radiation, both homogeneous and inhomogeneous, induces inflammation with resultant specific loss of regulatory T cells from the skin. This results in a hyper-responsive state with increased delayed type hypersensitivity in vivo and CD4+ T cell proliferation in vitro. The effects of inhomogeneous radiation to the skin of astronauts or as part of a therapeutic approach could result in an unexpected enhancement in skin immune function. The effects of this need to be considered in the design of radiation therapy protocols and in the development of countermeasures for extended space travel. PMID:24959865

  19. Reconciling Estimates of the Value to Firms of Reduced Regulatory Delay in the Marketing of Their New Drugs.

    Science.gov (United States)

    Wilmoth, Daniel R

    2015-12-01

    The prescription drug user fee program provides additional resources to the U.S. Food and Drug Administration at the expense of regulated firms. Those resources accelerate the review of new drugs. Faster approvals allow firms to realize profits sooner, and the program is supported politically by industry. However, published estimates of the value to firms of reduced regulatory delay vary dramatically. It is shown here that this variation is driven largely by differences in methods that correspond to differences in implicit assumptions about the effects of reduced delay. Theoretical modeling is used to derive an equation describing the relationship between estimates generated using different methods. The method likely to yield the most accurate results is identified. A reconciliation of published estimates yields a value to a firm for a one-year reduction in regulatory delay at the time of approval of about $60 million for a typical drug. Published 2015. This article is a U.S. Government work and is in the public domain in the U.S.A.

  20. 76 FR 17572 - Reducing Regulatory Burden; Retrospective Review Under E.O. 13563

    Science.gov (United States)

    2011-03-30

    ... disclosure. FOR FURTHER INFORMATION CONTACT: Office of the Assistant General Counsel for General Law, Ethics..., and harmonize regulations to reduce costs and promote certainty for businesses and the public... related to the submission. George W. Madison, General Counsel, Department of the Treasury. BILLING...

  1. Mutations of the Drosophila myosin regulatory light chain affect courtship song and reduce reproductive success.

    Science.gov (United States)

    Chakravorty, Samya; Vu, Hien; Foelber, Veronica; Vigoreaux, Jim O

    2014-01-01

    The Drosophila indirect flight muscles (IFM) rely on an enhanced stretch-activation response to generate high power output for flight. The IFM is neurally activated during the male courtship song, but its role, if any, in generating the small amplitude wing vibrations that produce the song is not known. Here, we examined the courtship song properties and mating behavior of three mutant strains of the myosin regulatory light chain (DMLC2) that are known to affect IFM contractile properties and impair flight: (i) Dmlc2(Δ2-46) (Ext), an N-terminal extension truncation; (ii) Dmlc2(S66A,S67A) (Phos), a disruption of two MLC kinase phosphorylation sites; and (iii) Dmlc2(Δ2-46;S66A,S67A) (Dual), expressing both mutations. Our results show that the Dmlc2 gene is pleiotropic and that mutations that have a profound effect on flight mechanics (Phos and Dual) have minimal effects on courtship song. None of the mutations affect interpulse interval (IPI), a determinant of species-specific song, and intrapulse frequency (IPF) compared to Control (Dmlc2 (+) rescued null strain). However, abnormalities in the sine song (increased frequency) and the pulse song (increased cycles per pulse and pulse length) evident in Ext males are not apparent in Dual males suggesting that Ext and Phos interact differently in song and flight mechanics, given their known additive effect on the latter. All three mutant males produce a less vigorous pulse song and exhibit impaired mating behavior compared to Control males. As a result, females are less receptive to Ext, Phos, and Dual males when a Control male is present. These results open the possibility that DMLC2, and perhaps contractile protein genes in general, are partly under sexual selection. That mutations in DMLC2 manifest differently in song and flight suggest that this protein fulfills different roles in song and flight and that stretch activation plays a smaller role in song production than in flight.

  2. Maraviroc decreases CCL8-mediated migration of CCR5(+) regulatory T cells and reduces metastatic tumor growth in the lungs.

    Science.gov (United States)

    Halvorsen, E C; Hamilton, M J; Young, A; Wadsworth, B J; LePard, N E; Lee, H N; Firmino, N; Collier, J L; Bennewith, K L

    2016-06-01

    Regulatory T cells (Tregs) play a crucial physiological role in the regulation of immune homeostasis, although recent data suggest Tregs can contribute to primary tumor growth by suppressing antitumor immune responses. Tregs may also influence the development of tumor metastases, although there is a paucity of information regarding the phenotype and function of Tregs in metastatic target organs. Herein, we demonstrate that orthotopically implanted metastatic mammary tumors induce significant Treg accumulation in the lungs, which is a site of mammary tumor metastasis. Tregs in the primary tumor and metastatic lungs express high levels of C-C chemokine receptor type 5 (CCR5) relative to Tregs in the mammary fat pad and lungs of tumor-free mice, and Tregs in the metastatic lungs are enriched for CCR5 expression in comparison to other immune cell populations. We also identify that C-C chemokine ligand 8 (CCL8), an endogenous ligand of CCR5, is produced by F4/80(+) macrophages in the lungs of mice with metastatic primary tumors. Migration of Tregs toward CCL8 ex vivo is reduced in the presence of the CCR5 inhibitor Maraviroc. Importantly, treatment of mice with Maraviroc (MVC) reduces the level of CCR5(+) Tregs and metastatic tumor burden in the lungs. This work provides evidence of a CCL8/CCR5 signaling axis driving Treg recruitment to the lungs of mice bearing metastatic primary tumors, representing a potential therapeutic target to decrease Treg accumulation and metastatic tumor growth.

  3. Antigen-specific regulatory T-cell subsets in transplantation tolerance regulatory T-cell subset quality reduces the need for quantity.

    NARCIS (Netherlands)

    Koenen, H.J.P.M.; Joosten, I.

    2006-01-01

    Regulatory T cells (Treg) are critical controllers of the immune response. Disturbed Treg function results in autoimmunity, whereas in transplantation Treg are crucial in graft survival and transplant tolerance. Hence therapeutic modalities that influence Treg numbers or function hold great clinical

  4. MapReduce Algorithms for Inferring Gene Regulatory Networks from Time-Series Microarray Data Using an Information-Theoretic Approach

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    Yasser Abduallah

    2017-01-01

    Full Text Available Gene regulation is a series of processes that control gene expression and its extent. The connections among genes and their regulatory molecules, usually transcription factors, and a descriptive model of such connections are known as gene regulatory networks (GRNs. Elucidating GRNs is crucial to understand the inner workings of the cell and the complexity of gene interactions. To date, numerous algorithms have been developed to infer gene regulatory networks. However, as the number of identified genes increases and the complexity of their interactions is uncovered, networks and their regulatory mechanisms become cumbersome to test. Furthermore, prodding through experimental results requires an enormous amount of computation, resulting in slow data processing. Therefore, new approaches are needed to expeditiously analyze copious amounts of experimental data resulting from cellular GRNs. To meet this need, cloud computing is promising as reported in the literature. Here, we propose new MapReduce algorithms for inferring gene regulatory networks on a Hadoop cluster in a cloud environment. These algorithms employ an information-theoretic approach to infer GRNs using time-series microarray data. Experimental results show that our MapReduce program is much faster than an existing tool while achieving slightly better prediction accuracy than the existing tool.

  5. MapReduce Algorithms for Inferring Gene Regulatory Networks from Time-Series Microarray Data Using an Information-Theoretic Approach.

    Science.gov (United States)

    Abduallah, Yasser; Turki, Turki; Byron, Kevin; Du, Zongxuan; Cervantes-Cervantes, Miguel; Wang, Jason T L

    2017-01-01

    Gene regulation is a series of processes that control gene expression and its extent. The connections among genes and their regulatory molecules, usually transcription factors, and a descriptive model of such connections are known as gene regulatory networks (GRNs). Elucidating GRNs is crucial to understand the inner workings of the cell and the complexity of gene interactions. To date, numerous algorithms have been developed to infer gene regulatory networks. However, as the number of identified genes increases and the complexity of their interactions is uncovered, networks and their regulatory mechanisms become cumbersome to test. Furthermore, prodding through experimental results requires an enormous amount of computation, resulting in slow data processing. Therefore, new approaches are needed to expeditiously analyze copious amounts of experimental data resulting from cellular GRNs. To meet this need, cloud computing is promising as reported in the literature. Here, we propose new MapReduce algorithms for inferring gene regulatory networks on a Hadoop cluster in a cloud environment. These algorithms employ an information-theoretic approach to infer GRNs using time-series microarray data. Experimental results show that our MapReduce program is much faster than an existing tool while achieving slightly better prediction accuracy than the existing tool.

  6. Regulatory T cell expansion in HTLV-1 and strongyloidiasis co-infection is associated with reduced IL-5 responses to Strongyloides stercoralis antigen.

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    Martin Montes

    Full Text Available BACKGROUND: Human strongyloidiasis varies from a chronic but limited infection in normal hosts to hyperinfection in patients treated with corticosteroids or with HTLV-1 co-infection. Regulatory T cells dampen immune responses to infections. How human strongyloidiasis is controlled and how HTLV-1 infection affects this control are not clear. We hypothesize that HTLV-1 leads to dissemination of Strongyloides stercoralis infection by augmenting regulatory T cell numbers, which in turn down regulate the immune response to the parasite. OBJECTIVE: To measure peripheral blood T regulatory cells and Strongyloides stercoralis larval antigen-specific cytokine responses in strongyloidiasis patients with or without HTLV-1 co-infection. METHODS: Peripheral blood mononuclear cells (PBMCs were isolated from newly diagnosed strongyloidiasis patients with or without HTLV-1 co-infection. Regulatory T cells were characterized by flow cytometry using intracellular staining for CD4, CD25 and FoxP3. PBMCs were also cultured with and without Strongyloides larval antigens. Supernatants were analyzed for IL-5 production. RESULTS: Patients with HTLV-1 and Strongyloides co-infection had higher parasite burdens. Eosinophil counts were decreased in the HTLV-1 and Strongyloides co-infected subjects compared to strongyloidiasis-only patients (70.0 vs. 502.5 cells/mm(3, p = 0.09, Mann-Whitney test. The proportion of regulatory T cells was increased in HTLV-1 positive subjects co-infected with strongyloidiasis compared to patients with only strongyloidiasis or asymptomatic HTLV-1 carriers (median = 17.9% vs. 4.3% vs. 5.9 p<0.05, One-way ANOVA. Strongyloides antigen-specific IL-5 responses were reduced in strongyloidiasis/HTLV-1 co-infected patients (5.0 vs. 187.5 pg/ml, p = 0.03, Mann-Whitney test. Reduced IL-5 responses and eosinophil counts were inversely correlated to the number of CD4+CD25+FoxP3+ cells. CONCLUSIONS: Regulatory T cell counts are increased in patients with

  7. Regulatory approval of cancer risk-reducing (chemopreventive) drugs: moving what we have learned into the clinic.

    Science.gov (United States)

    Meyskens, Frank L; Curt, Gregory A; Brenner, Dean E; Gordon, Gary; Herberman, Ronald B; Finn, Olivera; Kelloff, Gary J; Khleif, Samir N; Sigman, Caroline C; Szabo, Eva

    2011-03-01

    This article endeavors to clarify the current requirements and status of regulatory approval for chemoprevention (risk reduction) drugs and discusses possible improvements to the regulatory pathway for chemoprevention. Covering a wide range of topics in as much depth as space allows, this report is written in a style to facilitate the understanding of nonscientists and to serve as a framework for informing the directions of experts engaged more deeply with this issue. Key topics we cover here are as follows: a history of definitive cancer chemoprevention trials and their influence on the evolution of regulatory assessments; a brief review of the long-standing success of pharmacologic risk reduction of cardiovascular diseases and its relevance to approval for cancer risk reduction drugs; the use and limitations of biomarkers for developing and the approval of cancer risk reduction drugs; the identification of individuals at a high(er) risk for cancer and who are appropriate candidates for risk reduction drugs; business models that should incentivize pharmaceutical industry investment in cancer risk reduction; a summary of scientific and institutional barriers to development of cancer risk reduction drugs; and a summary of major recommendations that should help facilitate the pathway to regulatory approval for pharmacologic cancer risk reduction drugs.

  8. Reduced FOXP3(+) regulatory T cells in patients with primary sclerosing cholangitis are associated with IL2RA gene polymorphisms

    NARCIS (Netherlands)

    Sebode, M.; Peiseler, M.; Franke, B.; Schwinge, D.; Schoknecht, T.; Wortmann, F.; Quaas, A.; Petersen, B.S.; Ellinghaus, E.; Baron, U.; Olek, S.; Wiegard, C.; Weiler-Normann, C.; Lohse, A.W.; Herkel, J.; Schramm, C.

    2014-01-01

    BACKGROUND & AIMS: Recently, genome wide association studies in primary sclerosing cholangitis (PSC) revealed associations with gene polymorphisms that potentially could affect the function of regulatory T cells (Treg). The aim of this study was to investigate Treg in patients with PSC and to associ

  9. Oral treatment with laquinimod augments regulatory T-cells and brain-derived neurotrophic factor expression and reduces injury in the CNS of mice with experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Aharoni, Rina; Saada, Ravit; Eilam, Raya; Hayardeny, Liat; Sela, Michael; Arnon, Ruth

    2012-10-15

    Laquinimod is an orally active molecule that showed efficacy in clinical trials in multiple sclerosis. We studied its effects in the CNS, when administered by therapeutic regimen to mice inflicted with experimental autoimmune encephalomyelitis (EAE). Laquinimod reduced clinical and inflammatory manifestations and elevated the prevalence of T-regulatory cells in the brain. In untreated mice, in the chronic disease stage, brain derived neurotrophic factor (BDNF) expression was impaired. Laquinimod treatment restored BDNF expression to its level in healthy controls. Furthermore, CNS injury, manifested by astrogliosis, demyelination and axonal damages, was significantly reduced following laquinimod treatment, indicating its immunomodulatory and neuroprotective activity.

  10. Dietary Apigenin Exerts Immune-Regulatory Activity in Vivo by Reducing NF-κB Activity, Halting Leukocyte Infiltration and Restoring Normal Metabolic Function.

    Science.gov (United States)

    Cardenas, Horacio; Arango, Daniel; Nicholas, Courtney; Duarte, Silvia; Nuovo, Gerard J; He, Wei; Voss, Oliver H; Gonzalez-Mejia, M Elba; Guttridge, Denis C; Grotewold, Erich; Doseff, Andrea I

    2016-03-01

    The increasing prevalence of inflammatory diseases and the adverse effects associated with the long-term use of current anti-inflammatory therapies prompt the identification of alternative approaches to reestablish immune balance. Apigenin, an abundant dietary flavonoid, is emerging as a potential regulator of inflammation. Here, we show that apigenin has immune-regulatory activity in vivo. Apigenin conferred survival to mice treated with a lethal dose of Lipopolysaccharide (LPS) restoring normal cardiac function and heart mitochondrial Complex I activity. Despite the adverse effects associated with high levels of splenocyte apoptosis in septic models, apigenin had no effect on reducing cell death. However, we found that apigenin decreased LPS-induced apoptosis in lungs, infiltration of inflammatory cells and chemotactic factors' accumulation, re-establishing normal lung architecture. Using NF-κB luciferase transgenic mice, we found that apigenin effectively modulated NF-κB activity in the lungs, suggesting the ability of dietary compounds to exert immune-regulatory activity in an organ-specific manner. Collectively, these findings provide novel insights into the underlying immune-regulatory mechanisms of dietary nutraceuticals in vivo.

  11. Bacterial β-(1,3)-glucan prevents DSS-induced IBD by restoring the reduced population of regulatory T cells.

    Science.gov (United States)

    Lee, Kwang-Ho; Park, Min; Ji, Kon-Young; Lee, Hwa-Youn; Jang, Ji-Hun; Yoon, Il-Joo; Oh, Seung-Su; Kim, Su-Man; Jeong, Yun-Hwa; Yun, Chul-Ho; Kim, Mi-Kyoung; Lee, In-Young; Choi, Ha-Rim; Ko, Ki-sung; Kang, Hyung-Sik

    2014-10-01

    Bacterial β-(1,3)-glucan has more advantages in terms of cost, yield and efficiency than that derived from mushrooms, plants, yeasts and fungi. We have previously developed a novel and high-yield β-(1,3)-glucan produced by Agrobacterium sp. R259. This study aimed to elucidate the functional mechanism and therapeutic efficacy of bacterial β-(1,3)-glucan in dextran sulfate sodium (DSS)-induced inflammatory bowel disease (IBD).Mice were orally pretreated with bacterial β-(1,3)-glucan at daily doses of 2.5 or 5mg/kg for 2 weeks. After 6 days of DSS treatment, clinical assessment of IBD severity and expression of pro-inflammatory cytokines were evaluated. In vivo cell proliferation was examined by immunohistochemistry using Ki-67 and ER-TR7 antibodies. The frequency of regulatory T cells (Tregs) was analyzed by flow cytometry. Natural killer (NK) activity and IgA level were evaluated using NK cytotoxicity assay and ELISA.The deterioration of body weight gain, colonic architecture, disease score and histological score was recovered in DSS-induced IBD mice when pretreated with bacterial β-(1,3)-glucan. The recruitment of macrophages and the gene expression of proinflammatory cytokines, such as IL-1β, IL-6 and IL-17A/F, were markedly decreased in the colon of β-(1,3)-glucan-pretreated mice. β-(1,3)-Glucan induced the recovery of Tregs in terms of their frequency in DSS-induced IBD mice. Intriguingly, β-(1,3)-glucan reversed the functional defects of NK cells and excessive IgA production in DSS-induced IBD mice.We conclude that bacterial β-(1,3)-glucan prevented the progression of DSS-induced IBD by recovering the reduction of Tregs, functional defect of NK cells and excessive IgA production.

  12. Assessing the Benefits of U.S. Customs and Border Protection Regulatory Actions to Reduce Terrorism Risks

    Science.gov (United States)

    2012-01-01

    nonlinear use of probabilities) – Self -control problems ( procrastination ) Model is wrong? – Omits important attributes (type of mortality risk...impacts of major regulations prior to promulgation. For regulations intended to confer benefits under circumstances of extreme uncertainty, such as...alternative approaches for estimating the benefits of regulations designed to reduce the risks of terrorist attacks on U.S. soil. The observations

  13. Exposure of FVIII in the Presence of Phosphatidyl Serine Reduces Generation of Memory B-Cells and Induces Regulatory T-Cell-Mediated Hyporesponsiveness in Hemophilia A Mice.

    Science.gov (United States)

    Ramakrishnan, Radha; Davidowitz, Andrew; Balu-Iyer, Sathy V

    2015-08-01

    A major complication of replacement therapy with Factor VIII (FVIII) for hemophilia A (HA) is the development of unwanted immune responses. Previous studies showed that administration of FVIII in the presence of phosphatidyl serine (PS) reduced the development of anti-FVIII antibodies in HA mice. However, the impact of PS-mediated effects on immunological memory, such as generation of memory B-cells, is not clear. The effect of PS on memory B-cells was therefore investigated using adoptive transfer approach in FVIII(-/-) HA mice. Adoptive transfer of memory B-cells from a PS-FVIII-treated group to naïve mice followed by challenge of the recipient mice with FVIII showed a significantly reduced anti-FVIII antibody response in the recipient mice, compared with animals that received memory B-cells from free FVIII and FVIII-charge matched phosphatidyl glycerol (PG) group. The decrease in memory B-cell response is accompanied by an increase in FoxP3 expressing regulatory T-cells (Tregs). Flow cytometry studies showed that the generation of Tregs is higher in PS-treated animals as compared with FVIII and FVIII-PG treated animals. The PS-mediated hyporesponsiveness was found to be antigen-specific. The PS-FVIII immunization showed hyporesponsiveness toward FVIII rechallenge but not against ovalbumin (OVA) rechallenge, an unrelated antigen. This demonstrates that PS reduces immunologic memory of FVIII and induces antigen-specific peripheral tolerance in HA mice.

  14. Early graft failure of GalTKO pig organs in baboons is reduced by expression of a human complement pathway-regulatory protein.

    Science.gov (United States)

    Azimzadeh, Agnes M; Kelishadi, Sean S; Ezzelarab, Mohamed B; Singh, Avneesh K; Stoddard, Tiffany; Iwase, Hayato; Zhang, Tianshu; Burdorf, Lars; Sievert, Evelyn; Avon, Chris; Cheng, Xiangfei; Ayares, David; Horvath, Keith A; Corcoran, Philip C; Mohiuddin, Muhammad M; Barth, Rolf N; Cooper, David K C; Pierson, Richard N

    2015-01-01

    We describe the incidence of early graft failure (EGF, defined as loss of function from any cause within 3 days after transplant) in a large cohort of GalTKO pig organs transplanted into baboons in three centers, and the effect of additional expression of a human complement pathway-regulatory protein, CD46 or CD55 (GalTKO.hCPRP). Baboon recipients of life-supporting GalTKO kidney (n = 7) or heterotopic heart (n = 14) grafts received either no immunosuppression (n = 4), or one of several partial or full immunosuppressive regimens (n = 17). Fourteen additional baboons received a GalTKO.hCPRP kidney (n = 5) or heart (n = 9) and similar treatment regimens. Immunologic, pathologic, and coagulation parameters were measured at frequent intervals. EGF of GalTKO organs occurred in 9/21 baboons (43%). hCPRP expression reduced the GalTKO EGF incidence to 7% (1/14; P organs in which EGF developed (P organ failure, and (iii) the expression of a hCPRP reduces EGF but does not prevent systemic coagulation activation. Additional strategies will be required to control coagulation activation.

  15. Regulatory agencies and regulatory risk

    OpenAIRE

    Knieps, Günter; Weiß, Hans-Jörg

    2007-01-01

    The aim of this paper is to show that regulatory risk is due to the discretionary behaviour of regulatory agencies, caused by a too extensive regulatory mandate provided by the legislator. The normative point of reference and a behavioural model of regulatory agencies based on the positive theory of regulation are presented. Regulatory risk with regard to the future behaviour of regulatory agencies is modelled as the consequence of the ex ante uncertainty about the relative influence of inter...

  16. Activation of the aryl hydrocarbon receptor reduces the number of precursor and effector T cells, but preserves thymic CD4(+)CD25(+)Foxp3(+) regulatory T cells

    NARCIS (Netherlands)

    Schulz, V.J.; Smit, J.J.; Bol-Schoenmakers, M.; van Duursen, M.B.M.; van den Berg, M.; Pieters, R.H.H.

    2012-01-01

    Aryl hydrocarbon receptor (AhR) activation suppresses immune responses, including allergic sensitization, by increasing the percentage of regulatory (Treg) cells. Furthermore, AhR activation is known to affect thymic precursor T cells. However, the effect of AhR activation on intrathymic CD4(+)CD25(

  17. Transiently reduced PI3K/Akt activity drives the development of regulatory function in antigen-stimulated Naive T-cells.

    Directory of Open Access Journals (Sweden)

    Eloho Etemire

    Full Text Available Regulatory T-cells (Tregs are central for immune homeostasis and divided in thymus-derived natural Tregs and peripherally induced iTreg. However, while phenotype and function of iTregs are well known, a remarkable lack exists in knowledge about signaling mechanisms leading to their generation from naïve precursors in peripheral tissues. Using antigen specific naïve T-cells from mice, we investigated CD4+ CD25+ FoxP3- iTreg induction during antigen-specific T-cell receptor (TCR stimulation with weak antigen presenting cells (APC. We show that early signaling pathways such as ADAM-17-activation appeared similar in developing iTreg and effector cells (Teff and both initially shedded CD62-L. But iTreg started reexpressing CD62-L after 24 h while Teff permanently downmodulated it. Furthermore, between 24 and 72 hours iTreg presented with significantly lower phosphorylation levels of Akt-S473 suggesting lower activity of the PI3K/Akt-axis. This was associated with a higher expression of the Akt hydrophobic motif-specific phosphatase PHLPP1 in iTreg. Importantly, the lack of costimulatory signals via CD28 from weak APC was central for the development of regulatory function in iTreg but not for the reappearance of CD62-L. Thus, T-cells display a window of sensitivity after onset of TCR triggering within which the intensity of the PI3K/Akt signal controls entry into either effector or regulatory pathways.

  18. Therapeutic immunization with HIV-1 Tat reduces immune activation and loss of regulatory T-cells and improves immune function in subjects on HAART.

    Directory of Open Access Journals (Sweden)

    Barbara Ensoli

    Full Text Available UNLABELLED: Although HAART suppresses HIV replication, it is often unable to restore immune homeostasis. Consequently, non-AIDS-defining diseases are increasingly seen in treated individuals. This is attributed to persistent virus expression in reservoirs and to cell activation. Of note, in CD4(+ T cells and monocyte-macrophages of virologically-suppressed individuals, there is continued expression of multi-spliced transcripts encoding HIV regulatory proteins. Among them, Tat is essential for virus gene expression and replication, either in primary infection or for virus reactivation during HAART, when Tat is expressed, released extracellularly and exerts, on both the virus and the immune system, effects that contribute to disease maintenance. Here we report results of an ad hoc exploratory interim analysis (up to 48 weeks on 87 virologically-suppressed HAART-treated individuals enrolled in a phase II randomized open-label multicentric clinical trial of therapeutic immunization with Tat (ISS T-002. Eighty-eight virologically-suppressed HAART-treated individuals, enrolled in a parallel prospective observational study at the same sites (ISS OBS T-002, served for intergroup comparison. Immunization with Tat was safe, induced durable immune responses, and modified the pattern of CD4(+ and CD8(+ cellular activation (CD38 and HLA-DR together with reduction of biochemical activation markers and persistent increases of regulatory T cells. This was accompanied by a progressive increment of CD4(+ T cells and B cells with reduction of CD8(+ T cells and NK cells, which were independent from the type of antiretroviral regimen. Increase in central and effector memory and reduction in terminally-differentiated effector memory CD4(+ and CD8(+ T cells were accompanied by increases of CD4(+ and CD8(+ T cell responses against Env and recall antigens. Of note, more immune-compromised individuals experienced greater therapeutic effects. In contrast, these changes

  19. The Regulatory Plan

    Science.gov (United States)

    2010-12-20

    ... reduce obesity. In support of these activities in 2011, the Food and Nutrition Service (FNS) will propose... regulatory choices are based on careful analysis of the evidence, and if opportunities are provided for... billions of dollars while increasing energy security; combating childhood obesity; and creating a ``race...

  20. Impaired coronary microcirculation in type 2 diabetic patients is associated with elevated circulating regulatory T cells and reduced number of IL-21R⁺ T cells

    DEFF Research Database (Denmark)

    von Scholten, Bernt Johan; Rosendahl, Alexander; Hasbak, Philip

    2016-01-01

    BACKGROUND: Low-grade systemic inflammation is considered to participate in the progression of type 2 diabetes (T2D) and in diabetic complications. METHODS: To determine if circulating leukocytes were abnormally regulated in T2D patients, 8-color flow-cytometry (FACS) analysis was performed...... characterized by reduced overall T cell, Th17, IL-21R(+), Treg's and TLR4(+) T cells, while the monocyte population showed enhanced TLR4 expression. Further, our data revealed reduced M1-like CD11c expression in T2D which was associated with impaired CFR. In contrast, we show, for the first time in T2D...

  1. Reduced Dendritic Cells Expressing CD200R1 in Children with Inflammatory Bowel Disease: Correlation with Th17 and Regulatory T Cells.

    Science.gov (United States)

    Elshal, Mohamed F; Aldahlawi, Alia M; Saadah, Omar I; McCoy, J Philip

    2015-12-04

    Loss of tolerance of the adaptive immune system towards indigenous flora contributes to the development of inflammatory bowel diseases (IBD). Defects in dendritic cell (DC)-mediated innate and adoptive immune responses are conceivable. The aim of this study was to investigate the expression of the inhibitory molecules CD200R1 and their ligand CD200 on DCs, to clarify the role of the DCs in the pathogenesis of IBD. Thirty-seven pediatric IBD patients (23 with Crohn's disease (CD) and 14 with ulcerative colitis (UC)) with mean age 13.25 ± 2.9 years were included. Fourteen age-matched healthy pediatric volunteers (five males and nine females) served as a control group (HC). The percentage of CD11c⁺ myeloid dendritic cells (mDCs) and CD123⁺ plasmacytoid DCs (pDCs) expressing CD200R1 and CD200 were evaluated in peripheral blood using flow cytometry and were correlated with routine biochemical, serological markers, serum levels of cytokines and with the percentages of circulating regulatory T cells (Treg) and CD4⁺ producing IL-17 (Th17). IBD patients showed a significant decrease in the percentage of pDCs and mDCs expressing CD200R1 compared to that of HC. Patients with UC showed increased expressions of the CD200 molecule on pDCs as compared to HC. DCs expressing CD200R1 were found to be correlated positively with Treg and negatively with TH17 and erythrocyte sedimentation rate (ESR). Our findings suggest that IBD is associated with dysregulation in the CD200R1/CD200 axis and that the decrease in DCs expressing CD200R1 may contribute to the imbalance of Th17 and Treg cells and in the pathogenesis of IBD.

  2. Regulatory Anatomy

    DEFF Research Database (Denmark)

    Hoeyer, Klaus

    2015-01-01

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

  3. Freeze and Thaw of CD4+CD25+Foxp3+ Regulatory T Cells Results in Loss of CD62L Expression and a Reduced Capacity to Protect against Graft-versus-Host Disease.

    Directory of Open Access Journals (Sweden)

    Mareike Florek

    Full Text Available The adoptive transfer of CD4+CD25+Foxp3+ regulatory T cells (Tregs in murine models of allogeneic hematopoietic cell transplantation (HCT has been shown to protect recipient mice from lethal acute graft-versus-host disease (GVHD and this approach is being actively investigated in human clinical trials. Here, we examined the effects of cryopreservation on Tregs. We found that freeze and thaw of murine and human Tregs is associated with reduced expression of L-selectin (CD62L, which was previously established to be an important factor that contributes to the in vivo protective effects of Tregs. Frozen and thawed murine Tregs showed a reduced capacity to bind to the CD62L binding partner MADCAM1 in vitro as well as an impaired homing to secondary lymphoid organs in vivo. Upon adoptive transfer frozen and thawed Tregs failed to protect against lethal GVHD compared with fresh Tregs in a murine model of allogeneic HCT across major histocompatibility barriers. In summary, the direct administration of adoptively transferred frozen and thawed Tregs adversely affects their immunosuppressive potential which is an important factor to consider in the clinical implementation of Treg immunotherapies.

  4. Upregulation of CD19⁺CD24(hi)CD38(hi) regulatory B cells is associated with a reduced risk of acute lung injury in elderly pneumonia patients.

    Science.gov (United States)

    Song, Haihan; Xi, Jianjun; Li, Guang-Gang; Xu, Shumin; Wang, Chunmei; Cheng, Tingting; Li, Hongqiang; Zhang, Ying; Liu, Xiandong; Bai, Jianwen

    2016-04-01

    Acute lung injury (ALI) is a common complication in elderly pneumonia patients who have a rapid progression, and is accompanied by a high mortality rate. Because the treatment options of ALI are limited to supportive care, identifying pneumonia patients who are at higher risk of ALI development is the emphasis of many studies. Here, we approach this problem from an immunological perspective by examining CD19(+)CD24(hi)CD38(hi) B cells, an important participant in acute and chronic inflammation. We find that elderly pneumonia patients have elevated CD19(+)CD24(hi)CD38(hi) B cell frequency compared to healthy individuals. This B cell population may express a higher level of IL-10, which has been was shown to suppress CD4(+) T cell-mediated proinflammatory cytokine interferon gamma (IFNg) and tumor necrosis factor alpha (TNFa) production, through an IL-10-dependent mechanism. We also observe that the frequency of CD19(+)CD24(hi)CD38(hi) B cell is positively correlated with the frequency of CD4(+)CD25(+)Foxp3(+)Tregs in peripheral blood. Moreover, consistent with CD19(+)CD24(hi)CD38(hi) B cell's anti-inflammatory role, we find that pneumonia patients who later developed ALI have reduced level of CD19(+)CD24(hi)CD38(hi) B cells. Together, our results demonstrated that CD19(+)CD24(hi)CD38(hi) B cells in pneumonia patients possess regulatory function in vivo, and are associated with a reduced ALI risk.

  5. Development of regulatory policy for SMART-P

    Energy Technology Data Exchange (ETDEWEB)

    Lee, S. H.; Lee, Y. H.; Moo, Philip; Koh, B. J.; Son, M. K.; Han, G. H.; Kim, D. H. [Korea Association for Nuclear Technology, Daejeon (Korea, Republic of)

    2004-06-15

    KAERI promoted the construction of a research reactor, SMART-P, the reduced scale of SMART, with intent to demonstrate the safety and performance of SMART. According to this progress, the development of regulatory process for SMART-P became necessary. The establishment of regulatory policy, based on the current regulatory guidelines as well as technical aspect, became essential matters. Considering the on-going small and medium size reactors in near future, the selection of the appropriate measure in the existing regulatory process to SMART-P is very important. Thus the schematic study for the applicable licensing procedure and regulatory requirements suitable for SMART-P is required.

  6. Development of regulatory policy for SMART-P

    Energy Technology Data Exchange (ETDEWEB)

    Lee, S. H.; Moon, S. H.; Lee, Y. H.; Son, M. K.; Han, K. H.; Kim, D. H. [Korea Association for Nuclear Technology, Taejon (Korea, Republic of)

    2003-06-15

    KAERI promoted the construction of a research reactor, SMART-P, the reduced scale of SMART, with intent to demonstrate the safety and performance of SMART. According to this progress, the development of regulatory process for SMART-P became necessary. The establishment of regulatory policy, based on the current regulatory guidelines as well as technical aspect, became essential matters. Considering the on-going small and medium size reactors m near future, the selection of the appropriate measure in the existing regulatory process to SMART-P is very important. Thus the schematic study for the applicable licensing procedure and regulatory requirements suitable for SMART-P is required.

  7. Regulating regulatory T cells.

    Science.gov (United States)

    Le, N T; Chao, N

    2007-01-01

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

  8. Regulatory Streamlining and Improvement

    Energy Technology Data Exchange (ETDEWEB)

    Mark A. Carl

    2006-07-11

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

  9. Regulatory guidance document

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1994-05-01

    The Office of Civilian Radioactive Waste Management (OCRWM) Program Management System Manual requires preparation of the OCRWM Regulatory Guidance Document (RGD) that addresses licensing, environmental compliance, and safety and health compliance. The document provides: regulatory compliance policy; guidance to OCRWM organizational elements to ensure a consistent approach when complying with regulatory requirements; strategies to achieve policy objectives; organizational responsibilities for regulatory compliance; guidance with regard to Program compliance oversight; and guidance on the contents of a project-level Regulatory Compliance Plan. The scope of the RGD includes site suitability evaluation, licensing, environmental compliance, and safety and health compliance, in accordance with the direction provided by Section 4.6.3 of the PMS Manual. Site suitability evaluation and regulatory compliance during site characterization are significant activities, particularly with regard to the YW MSA. OCRWM`s evaluation of whether the Yucca Mountain site is suitable for repository development must precede its submittal of a license application to the Nuclear Regulatory Commission (NRC). Accordingly, site suitability evaluation is discussed in Chapter 4, and the general statements of policy regarding site suitability evaluation are discussed in Section 2.1. Although much of the data and analyses may initially be similar, the licensing process is discussed separately in Chapter 5. Environmental compliance is discussed in Chapter 6. Safety and Health compliance is discussed in Chapter 7.

  10. Lithium, an inhibitor of cAMP-induced inositol 1,4,5-trisphosphate accumulation in Dictyostelium discoideum, inhibits activation of guanine-nucleotide-binding regulatory proteins, reduces activation of adenylylcyclase, but potentiates activation of guanyl

    NARCIS (Netherlands)

    Peters, Dorien J.M.; Snaar-Jagalska, B. Ewa; Haastert, Peter J.M. van; Schaap, Pauline

    1992-01-01

    Li+ drastically alters pattern formation in Dictyostelium by inhibiting cAMP-induced prespore-gene expression and promoting cAMP-induced prestalk-gene expression. We reported previously that Li+ inhibits inositol monophosphatases in this organism and strongly reduces basal and cAMP-stimulated inosit

  11. NRC regulatory initiatives

    Energy Technology Data Exchange (ETDEWEB)

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

    1989-11-01

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

  12. The T box regulatory element controlling expression of the class I lysyl-tRNA synthetase of Bacillus cereus strain 14579 is functional and can be partially induced by reduced charging of asparaginyl-tRNAAsn

    LENUS (Irish Health Repository)

    Foy, Niall

    2010-07-22

    Abstract Background Lysyl-tRNA synthetase (LysRS) is unique within the aminoacyl-tRNA synthetase family in that both class I (LysRS1) and class II (LysRS2) enzymes exist. LysRS1 enzymes are found in Archaebacteria and some eubacteria while all other organisms have LysRS2 enzymes. All sequenced strains of Bacillus cereus (except AH820) and Bacillus thuringiensis however encode both a class I and a class II LysRS. The lysK gene (encoding LysRS1) of B. cereus strain 14579 has an associated T box element, the first reported instance of potential T box control of LysRS expression. Results A global study of 891 completely sequenced bacterial genomes identified T box elements associated with control of LysRS expression in only four bacterial species: B. cereus, B. thuringiensis, Symbiobacterium thermophilum and Clostridium beijerinckii. Here we investigate the T box element found in the regulatory region of the lysK gene in B. cereus strain 14579. We show that this T box element is functional, responding in a canonical manner to an increased level of uncharged tRNALys but, unusually, also responding to an increased level of uncharged tRNAAsn. We also show that B. subtilis strains with T box regulated expression of the endogenous lysS or the heterologous lysK genes are viable. Conclusions The T box element controlling lysK (encoding LysRS1) expression in B. cereus strain 14579 is functional, but unusually responds to depletion of charged tRNALys and tRNAAsn. This may have the advantage of making LysRS1 expression responsive to a wider range of nutritional stresses. The viability of B. subtilis strains with a single LysRS1 or LysRS2, whose expression is controlled by this T box element, makes the rarity of the occurrence of such control of LysRS expression puzzling.

  13. Mission Risk Reduction Regulatory Change Management

    Science.gov (United States)

    Scroggins, Sharon

    2007-01-01

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

  14. Induction of mitochondrial uncoupling enhances VEGF₁₂₀ but reduces MCP-1 release in mature 3T3-L1 adipocytes: possible regulatory mechanism through endogenous ER stress and AMPK-related pathways.

    Science.gov (United States)

    Miyokawa-Gorin, Kaoru; Takahashi, Kazuto; Handa, Keiko; Kitahara, Atsuko; Sumitani, Yoshikazu; Katsuta, Hidenori; Tanaka, Toshiaki; Nishida, Susumu; Yoshimoto, Katsuhiko; Ohno, Hideki; Ishida, Hitoshi

    2012-03-01

    Although white adipocytes contain a larger number of mitochondria per cytoplasmic volume, adipocyte mitochondrial uncoupling to reduce the efficiency of ATP production on cellular function including secretory regulation of bioactive molecules such as VEGF and MCP-1 remains to be elucidated. Here we induce mitochondrial uncoupling under hypoxia-independent conditions in mature 3T3-L1 adipocytes using a metabolic uncoupler, dinitrophenol (DNP). MCP-1 release was significantly decreased by 26% (poxidative stress was observed. Treatment with thapsigargin, which can induce exogenous endoplasmic reticulum (ER) stress, clearly attenuated MCP-1 release (pmetabolic syndrome and type 2 diabetes.

  15. Rationales for regulatory activity

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-02-01

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

  16. Prediction of regulatory elements

    DEFF Research Database (Denmark)

    Sandelin, Albin

    2008-01-01

    Finding the regulatory mechanisms responsible for gene expression remains one of the most important challenges for biomedical research. A major focus in cellular biology is to find functional transcription factor binding sites (TFBS) responsible for the regulation of a downstream gene. As wet-lab...

  17. Regulatory Issues Surrounding Merchant Interconnection

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-11-01

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

  18. Legislation analysis on reducing GHG in Australia

    Institute of Scientific and Technical Information of China (English)

    Yiqi Mao; Li Chen

    2014-01-01

    ‘Greenhouse Effect’ derived from human activities has caused many concerns. This dissertation mainly analysis existing GHG reduction regulations in Australia, the relationship between those regulations, and the effectiveness of the regulatory framework to see whether the CPR Scheme and other complementary strategies can effectively improve the regulatory outcomes, namely reduces GHG emissions.

  19. Nuclear Regulatory Commission information digest

    Energy Technology Data Exchange (ETDEWEB)

    None,

    1990-03-01

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

  20. 77 FR 28467 - Identifying and Reducing Regulatory Burdens

    Science.gov (United States)

    2012-05-14

    ... to conduct a single exercise, but to engage in ``periodic review of existing significant regulations... in periodic review of existing regulations prior to the issuance of Executive Order 13563. But.... Policy. Regulations play an indispensable role in protecting public health, welfare, safety, and...

  1. Analysis and proposals of regulatory issues aimed at reducing emissions of greenhouse gases in the thermoelectric generation of isolated systems; Analise e propostas de aspectos regulatorios visando a reducao de emissoes de gases de efeito estufa na geracao termoeletrica dos sistemas isolados

    Energy Technology Data Exchange (ETDEWEB)

    Magalhaes, Pedro Coelho de Souza Monteiro [Universidade Salvador (UNIFACS), BA (Brazil)

    2008-07-01

    Restricted access to electricity, the existence of an energy matrix based on fossil fueled electricity plants and the lack of financial means by the population living in the Northern region of Brazil to afford the costs with electricity generation, transmission and distribution in the region created the need to implement cross subsidies in the country's electric sector isolated system. The subsidy policies have aimed at allowing the access to electricity for the population and industries in the north of Brazil and at promoting the economic development of this region, but have brought a great cost to society, particularly the Fuel Consumption Account (CCC), considering the environmental impacts of the fossil fuel use. This paper evaluates the current structure and the regulatory norms of the electricity sector's subsidies granted to the Isolated Systems, and intend to propose measures to reduce emissions of greenhouse gases in the thermoelectric generation plants in the isolated systems with the implementation of governmental incentives to power plants efficiency. (author)

  2. Politically Induced Regulatory Risk and Independent Regulatory Agencies

    OpenAIRE

    Strausz, Roland

    2015-01-01

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

  3. Clinical research: regulatory issues.

    Science.gov (United States)

    Wermeling, D P

    1999-02-01

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

  4. Toxicogenomics in regulatory ecotoxicology

    Science.gov (United States)

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

    2006-01-01

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

  5. 75 FR 54210 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

    Science.gov (United States)

    2010-09-03

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

  6. Regulatory mark; Marco regulatorio

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-10-15

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

  7. Regulatory considerations for biosimilars

    Directory of Open Access Journals (Sweden)

    Ranjani Nellore

    2010-01-01

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

  8. Regulatory Foci and Organizational Commitment

    Science.gov (United States)

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

    2008-01-01

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

  9. Regulatory focus in groupt contexts

    NARCIS (Netherlands)

    Faddegon, Krispijn Johannes

    2009-01-01

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

  10. Disclosure as a regulatory tool

    DEFF Research Database (Denmark)

    2006-01-01

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

  11. 75 FR 30453 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2010-06-01

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

  12. 75 FR 40000 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2010-07-13

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

  13. 75 FR 11166 - Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission...

    Science.gov (United States)

    2010-03-10

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

  14. Internationalization of regulatory requirements.

    Science.gov (United States)

    Juillet, Y

    2003-02-01

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

  15. Carbon Capture and Storage Legal and Regulatory Review. Edition 3

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2012-07-01

    The International Energy Agency (IEA) considers carbon capture and storage (CCS) a crucial part of worldwide efforts to limit global warming by reducing greenhouse-gas emissions. The IEA estimates that emissions can be reduced to a level consistent with a 2°C global temperature increase through the broad deployment of low-carbon energy technologies – and that CCS would contribute about one-fifth of emission reductions in this scenario. Achieving this level of deployment will require that regulatory frameworks – or rather a lack thereof – do not unnecessarily impede environmentally safe demonstration and deployment of CCS, so in October 2010 the IEA launched the IEA Carbon Capture and Storage Legal and Regulatory Review. The CCS Review is a regular review of CCS regulatory progress worldwide. Produced annually, it collates contributions by national and regional governments, as well as leading organisations engaged in CCS regulatory activities, to provide a knowledge-sharing forum to support CCS framework development. Each two page contribution provides a short summary of recent and anticipated CCS regulatory developments and highlights a particular, pre-nominated regulatory theme. To introduce each edition, the IEA provides a brief analysis of key advances and trends, based on the contributions submitted. The theme for this third edition is stakeholder engagement in the development of CO2 storage projects. Other issues addressed include: regulating CO2-EOR, CCS and CO2-EOR for storage; CCS incentive policy; key, substantive issues being addressed by jurisdictions taking steps to finalise CCS regulatory framework development; and CCS legal and regulatory developments in the context of the Clean Energy Ministerial Carbon Capture, Use and Storage Action Group.

  16. Healthcare regulatory concepts in Brazil.

    Science.gov (United States)

    Oliveira, Robson Rocha de; Elias, Paulo Eduardo Mangeon

    2012-06-01

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

  17. The Danish Regulatory Reform of Telecommunications

    DEFF Research Database (Denmark)

    Skouby, Knud Erik

    1998-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Joana P Gonçalves

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

  19. Current Regulations and Regulatory Actions

    Science.gov (United States)

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

  20. Anti-regulatory T cells

    DEFF Research Database (Denmark)

    Andersen, Mads Hald

    2017-01-01

    Our initial understanding of immune-regulatory cells was based on the discovery of suppressor cells that assure peripheral T-cell tolerance and promote immune homeostasis. Research has particularly focused on the importance of regulatory T cells (Tregs) for immune modulation, e.g. directing host...... responses to tumours or inhibiting autoimmunity development. However, recent studies report the discovery of self-reactive pro-inflammatory T cells—termed anti-regulatory T cells (anti-Tregs)—that target immune-suppressive cells. Thus, regulatory cells can now be defined as both cells that suppress immune......-reactive T cells that recognize such targets may be activated due to the strong activation signal given by their cognate targets. The current review describes the existing knowledge regarding these self-reactive anti-Tregs, providing examples of antigen-specific anti-Tregs and discussing their possible roles...

  1. Electronic Commerce Removing Regulatory Impediments

    Science.gov (United States)

    1992-05-01

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

  2. Regulatory facility guide for Ohio

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-02-28

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

  3. MicroRNAs targeting TGFβ signalling underlie the regulatory T cell defect in multiple sclerosis.

    Science.gov (United States)

    Severin, Mary E; Lee, Priscilla W; Liu, Yue; Selhorst, Amanda J; Gormley, Matthew G; Pei, Wei; Yang, Yuhong; Guerau-de-Arellano, Mireia; Racke, Michael K; Lovett-Racke, Amy E

    2016-06-01

    Transforming growth factor beta (TGFβ) signalling is critical for regulatory T cell development and function, and regulatory T cell dysregulation is a common observation in autoimmune diseases, including multiple sclerosis. In a comprehensive miRNA profiling study of patients with multiple sclerosis naïve CD4 T cells, 19 differentially expressed miRNAs predicted to target the TGFβ signalling pathway were identified, leading to the hypothesis that miRNAs may be responsible for the regulatory T cell defect observed in patients with multiple sclerosis. Patients with multiple sclerosis had reduced levels of TGFβ signalling components in their naïve CD4 T cells. The differentially expressed miRNAs negatively regulated the TGFβ pathway, resulting in a reduced capacity of naïve CD4 T cells to differentiate into regulatory T cells. Interestingly, the limited number of regulatory T cells, that did develop when these TGFβ-targeting miRNAs were overexpressed, were capable of suppressing effector T cells. As it has previously been demonstrated that compromising TGFβ signalling results in a reduced regulatory T cell repertoire insufficient to control autoimmunity, and patients with multiple sclerosis have a reduced regulatory T cell repertoire, these data indicate that the elevated expression of multiple TGFβ-targeting miRNAs in naïve CD4 T cells of patients with multiple sclerosis impairs TGFβ signalling, and dampens regulatory T cell development, thereby enhancing susceptibility to developing multiple sclerosis.

  4. Reducing sedentarism

    DEFF Research Database (Denmark)

    Brown, Wendy; Andersen, Lars Bo; Sigmund, Anderssen

    Reducing Sedentarism Brown, WJ*1; Brown, WJ*1; Andersen, LB*2; Anderssen, SA*3 1The University of Queensland, Australia; 2University of Southern Denmark, Denmark; 3Norwegian School of Sports Medicine, Norway Western lifestyles have changed remarkably over the last century, with decreasing levels...... between 7 and 10 hours each day sitting, with about half this time spent sitting at work. This paper will examine the hypothesis that too much sitting is a risk factor for poor health, even in those who meet the current physical activity guidelines. First, the biological plausibility of too much sitting...

  5. Regulatory Expectations for Safety Culture

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Su Jin; Oh, Jang Jin; Choi, Young Sung [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2014-05-15

    The oversight of licensee's safety culture becomes an important issue that attracts great public and political concerns recently in Korea. Beginning from the intended violation of rules, a series of corruptions, documents forgery and disclosure of wrong-doings made the public think that the whole mindset of nuclear workers has been inadequate. Thus, they are demanding that safety culture shall be improved and that regulatory body shall play more roles and responsibilities for the improvements and oversight for them. This paper introduces, as an effort of regulatory side, recent changes in the role of regulators in safety culture, regulatory expectations on the desired status of licensee's safety culture, the pilot inspection program for safety culture and research activity for the development of oversight system. After the Fukushima accident in Japan 2011, many critics has searched for cultural factors that caused the unacceptable negligence pervaded in Japan nuclear society and the renewed emphasis has been placed on rebuilding safety culture by operators, regulators, and relevant institutions globally. Significant progress has been made in how to approach safety culture and led to a new perspective different from the existing normative assessment method both in operators and regulatory side. Regulatory expectations and oversight of them are based on such a new holistic concept for human, organizational and cultural elements to maintain and strengthen the integrity of defense in depth and consequently nuclear safety.

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  7. 75 FR 70757 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    Science.gov (United States)

    2010-11-18

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

  8. 77 FR 47470 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

    Science.gov (United States)

    2012-08-08

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

  9. 76 FR 72736 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

    Science.gov (United States)

    2011-11-25

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting... September 22, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities... Killian, Vice President, Securities Industry and Financial Markets Association (``SIFMA''), to Elizabeth...

  10. 77 FR 55517 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    Science.gov (United States)

    2012-09-10

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

  11. 75 FR 62439 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    Science.gov (United States)

    2010-10-08

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

  12. 77 FR 12340 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

    Science.gov (United States)

    2012-02-29

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

  13. 76 FR 20757 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

    Science.gov (United States)

    2011-04-13

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

  14. 75 FR 61793 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2010-10-06

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

  15. Regulatory treatment of allowances and compliance costs

    Energy Technology Data Exchange (ETDEWEB)

    Rose, K. [National Regulatory Research Institute, Columbus, OH (United States)

    1993-07-01

    The Clean Air Act Amendments of 1990 (CAAA) established a national emission allowance trading system, a market-based form of environmental regulation designed to reduce and limit sulfur dioxide emissions. However, the allowance trading system is being applied primarily to an economically regulated electric utility industry. The combining of the new form of environmental regulation and economic regulation of electric utilities has raised a number of questions including what the role should be of the federal and state utility regulating commissions and how those actions will affect the decision making process of the utilities and the allowance market. There are several dimensions to the regulatory problems that commissions face. Allowances and utility compliance expenditures have implications for least-cost/IPR (integrated resource planning), prudence review procedures, holding company and multistate utility regulation and ratemaking treatment. The focus of this paper is on the ratemaking treatment. The following topics are covered: ratemaking treatment of allowances and compliance costs; Traditional cost-recovery mechanisms; limitations to the traditional approach; traditional approach and the allowance trading market; market-based cost recovery mechanisms; methods of determining the benchmark; determining the split between ratepayers and the utility; other regulatory approaches; limitations of incentive mechanisms.

  16. Nuclear Regulatory Commission 1989 Information Digest

    Energy Technology Data Exchange (ETDEWEB)

    None,

    1989-03-01

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

  17. The Political Economy of Regulatory Risk

    OpenAIRE

    Roland Strausz

    2009-01-01

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

  18. The political economy of regulatory risk

    OpenAIRE

    Strausz, Roland

    2009-01-01

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

  19. 40 CFR 94.6 - Regulatory structure.

    Science.gov (United States)

    2010-07-01

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

  20. 40 CFR 92.6 - Regulatory structure.

    Science.gov (United States)

    2010-07-01

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

  1. 21 CFR 500.88 - Regulatory method.

    Science.gov (United States)

    2010-04-01

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

  2. 77 FR 10351 - Regulatory Review Plan

    Science.gov (United States)

    2012-02-22

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

  3. Genetic flexibility of regulatory networks.

    Science.gov (United States)

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

    2010-07-20

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  5. 77 FR 1524 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2012-01-10

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

  6. 76 FR 20741 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

    Science.gov (United States)

    2011-04-13

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting... On February 4, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the... implementation of New Rule 13806 (Promissory Note Proceedings) in Regulatory Notice 09-48 (August 2009)....

  7. 78 FR 54359 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2013-09-03

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

  8. 78 FR 10655 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    Science.gov (United States)

    2013-02-14

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

  9. 75 FR 17810 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2010-04-07

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on March 12, 2010, Financial Industry Regulatory...-Regulatory Organization's Statement of the Terms of Substance of the Proposed Rule Change FINRA is...

  10. 77 FR 33527 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2012-06-06

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

  11. 77 FR 12092 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2012-02-28

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

  12. 75 FR 28841 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2010-05-24

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

  13. 76 FR 2739 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-01-14

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

  14. 76 FR 62128 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2011-10-06

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... is hereby given that on September 22, 2011, the Financial Industry Regulatory Authority, Inc.... \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of...

  15. 78 FR 5542 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2013-01-25

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...,\\2\\ notice is hereby given that on January 7, 2013, Financial Industry Regulatory Authority, Inc.... \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of...

  16. 77 FR 74249 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2012-12-13

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...,\\2\\ notice is hereby given that on November 30, 2012, Financial Industry Regulatory Authority, Inc.... \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of...

  17. 76 FR 77283 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2011-12-12

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... hereby given that on November 21, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA...\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the...

  18. 76 FR 20065 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-04-11

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

  19. 75 FR 49542 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2010-08-13

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

  20. 76 FR 70195 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2011-11-10

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

  1. 78 FR 42581 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2013-07-16

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

  2. 77 FR 12098 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2012-02-28

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

  3. 76 FR 72463 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2011-11-23

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

  4. 76 FR 9840 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2011-02-22

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

  5. 78 FR 78451 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2013-12-26

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

  6. 78 FR 25331 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

    Science.gov (United States)

    2013-04-30

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

  7. 76 FR 67787 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2011-11-02

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

  8. 78 FR 76341 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2013-12-17

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

  9. 75 FR 2899 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2010-01-19

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

  10. 78 FR 24261 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2013-04-24

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

  11. 75 FR 7532 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2010-02-19

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

  12. 77 FR 58880 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2012-09-24

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

  13. 75 FR 58004 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2010-09-23

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

  14. 76 FR 78706 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    Science.gov (United States)

    2011-12-19

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

  15. 75 FR 9459 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2010-03-02

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

  16. 75 FR 39069 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2010-07-07

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

  17. 77 FR 33537 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2012-06-06

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

  18. 78 FR 75954 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2013-12-13

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

  19. 75 FR 69503 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2010-11-12

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

  20. 76 FR 9838 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2011-02-22

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... given that on February 4, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with.... \\1\\ 15 U.S.C. 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of...

  1. 75 FR 15470 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2010-03-29

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

  2. 75 FR 53998 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2010-09-02

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

  3. 77 FR 5611 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    Science.gov (United States)

    2012-02-03

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

  4. 76 FR 66344 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2011-10-26

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

  5. 75 FR 62901 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2010-10-13

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

  6. 76 FR 50515 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-08-15

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

  7. 76 FR 65758 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2011-10-24

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

  8. Escherichia coli transcriptional regulatory network

    Directory of Open Access Journals (Sweden)

    Agustino Martinez-Antonio

    2011-06-01

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

  9. 75 FR 28073 - Draft Regulatory Guide: Issuance, Availability

    Science.gov (United States)

    2010-05-19

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

  10. 75 FR 48382 - Draft Regulatory Guide: Issuance, Availability

    Science.gov (United States)

    2010-08-10

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

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

    Directory of Open Access Journals (Sweden)

    Mantas Barčys

    2013-06-01

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

  12. The core regulatory network in human cells.

    Science.gov (United States)

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

    2017-03-04

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

  13. Innovative approaches to reduce animal testing : replace whenever possible, reduce through refinement and mechanistic understanding

    NARCIS (Netherlands)

    Ravenzwaay, van B.

    2013-01-01

    'Many of the in vitro toxicological studies have not been sufficiently validated to determine their applicability domain, even less have gained regulatory acceptance. Major advantage of in vitro testing today is the early identification of significant hazards in compound development and reduced and

  14. Food irradiation--US regulatory considerations

    Energy Technology Data Exchange (ETDEWEB)

    Morehouse, Kim M. E-mail: kim.morehouse@cfsan.fda.gov

    2002-03-01

    The use of ionizing radiation in food processing has received increased interest as a means of reducing the level of foodborne pathogens. This overview discusses the regulatory issues connected with the use of this technology in the United States. Several recent changes in the FDA's review process are discussed. These include the current policy that utilizes an expedited review process for petitions seeking approval of additives and technologies intended to reduce pathogen levels in food, and the recent USDA rule that eliminates the need for a separate rulemaking process by USDA for irradiation of meat and poultry. Recently promulgated rules and pending petitions before the FDA associated with the use of ionizing radiation for the treatment of foods are also discussed along with the current FDA labeling requirements for irradiated foods and the 1999 advanced notice of proposed rule on labeling. Another issue that is presented is the current status of the approval of packaging materials intended for food contact during irradiation treatment of foods.

  15. REGULATORY AGENCIES, CONSUMER AND ENVIROMENT

    Directory of Open Access Journals (Sweden)

    Giseli Valezi Raymundo

    2011-03-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Tonn, B.; Schweitzer, M.; Godfrey, G. [Oak Ridge National Lab., TN (United States); Wagner, C. [Univ. of Tennessee, Knoxville (United States); MacGregor, D.G. [MacGregor-Bates, Inc. (United States)

    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.

  17. Endocrine cells producing regulatory peptides.

    Science.gov (United States)

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

    1987-07-15

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

  18. Global Summit on Regulatory Science 2013.

    Science.gov (United States)

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

    2014-12-01

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

  19. The Effect of Regulatory Harmonization on Cross-border Labor Migration: Evidence from the Accounting Profession

    OpenAIRE

    2015-01-01

    The paper examines whether international regulatory harmonization increases cross-border labor migration. To study this question, we analyze European Union (EU) initiatives that harmonized accounting and auditing standards. Regulatory harmonization should reduce economic mobility barriers, essentially making it easier for accounting professionals to move across countries. Our research design compares the cross-border migration of accounting professionals relative to tightly-matched other prof...

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

    Science.gov (United States)

    Lucas-Samuel, S

    2013-05-01

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

  1. Environmental Regulatory Update Table, December 1991

    Energy Technology Data Exchange (ETDEWEB)

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

    1992-01-01

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

  2. Environmental Regulatory Update Table, April 1989

    Energy Technology Data Exchange (ETDEWEB)

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

    1989-05-01

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

  3. Environmental Regulatory Update Table, October 1991

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-11-01

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

  4. Environmental Regulatory Update Table, September 1991

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-10-01

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

  5. Environmental Regulatory Update Table, August 1991

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-09-01

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

  6. Regulatory Risk under Optimal Incentive Regulation

    OpenAIRE

    Strausz, Roland

    2009-01-01

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

  7. Environmental Regulatory Update Table, December 1989

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-01-01

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

  8. Environmental Regulatory Update Table, November 1991

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-12-01

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

  9. Environmental regulatory update table, March 1989

    Energy Technology Data Exchange (ETDEWEB)

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

    1989-04-01

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

  10. Reduction of regulatory risk: a network economic approach

    OpenAIRE

    Knieps, Günter; Weiß, Hans-Jörg

    2007-01-01

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

  11. Regulatory T cells as immunotherapy

    Directory of Open Access Journals (Sweden)

    Benjamin David Singer

    2014-02-01

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

  12. Regulatory fit messages and physical activity motivation.

    Science.gov (United States)

    Pfeffer, Ines

    2013-04-01

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

  13. Genetic Redundancies Enhance Information Transfer in Noisy Regulatory Circuits

    Science.gov (United States)

    Rodrigo, Guillermo; Poyatos, Juan F.

    2016-01-01

    Cellular decision making is based on regulatory circuits that associate signal thresholds to specific physiological actions. This transmission of information is subjected to molecular noise what can decrease its fidelity. Here, we show instead how such intrinsic noise enhances information transfer in the presence of multiple circuit copies. The result is due to the contribution of noise to the generation of autonomous responses by each copy, which are altogether associated with a common decision. Moreover, factors that correlate the responses of the redundant units (extrinsic noise or regulatory cross-talk) contribute to reduce fidelity, while those that further uncouple them (heterogeneity within the copies) can lead to stronger information gain. Overall, our study emphasizes how the interplay of signal thresholding, redundancy, and noise influences the accuracy of cellular decision making. Understanding this interplay provides a basis to explain collective cell signaling mechanisms, and to engineer robust decisions with noisy genetic circuits. PMID:27741249

  14. 78 FR 70602 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2013-11-26

    ... financial asset, such as a consumer or student loan, a lease, or a secured or unsecured receivable, but...-2013-046] Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of... on November 13, 2013, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with...

  15. 77 FR 14052 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2012-03-08

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... 19b-4 thereunder,\\2\\ notice is hereby given that on February 28, 2012, Financial Industry Regulatory..., departmental information barriers, space sharing arrangements, lease and/or sub-lease agreements). Standard...

  16. 77 FR 65436 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

    Science.gov (United States)

    2012-10-26

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting... Transactions October 23, 2012. I. Introduction On August 29, 2012, the Financial Industry Regulatory Authority... apply to MBS TBA transactions ``not for good delivery'' and standard data elements will be...

  17. 77 FR 8938 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2012-02-15

    ... regulatory risks and trends, irrespective of firm size. FINRA also explained that many of the line items will... important to identify revenue sources, enable FINRA to segment firms, and identify regulatory risk and... believes that more granular detail for trading revenue is warranted because the regulatory risks...

  18. 78 FR 76973 - Regulatory Capital Rules: Regulatory Capital, Implementation of Basel III, Capital Adequacy...

    Science.gov (United States)

    2013-12-20

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

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

    Science.gov (United States)

    2010-04-06

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

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

    Science.gov (United States)

    2013-09-30

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

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

    Science.gov (United States)

    2010-06-01

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

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

    Science.gov (United States)

    2012-02-03

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

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

    Science.gov (United States)

    2013-08-01

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

  4. 75 FR 68654 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2010-11-08

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on October 27, 2010, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``SEC''...

  5. 75 FR 27606 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2010-05-17

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

  6. 78 FR 37261 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2013-06-20

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

  7. 77 FR 68181 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2012-11-15

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

  8. 75 FR 8771 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2010-02-25

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

  9. 76 FR 65307 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2011-10-20

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

  10. 76 FR 11830 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-03-03

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

  11. 77 FR 77162 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2012-12-31

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of... Rule 19b-4 thereunder,\\2\\ notice is hereby given that on December 20, 2012, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``SEC''...

  12. 77 FR 4599 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2012-01-30

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

  13. 77 FR 7218 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2012-02-10

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

  14. 75 FR 36756 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2010-06-28

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

  15. 75 FR 59300 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2010-09-27

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

  16. 75 FR 39610 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2010-07-09

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

  17. 76 FR 29808 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

    Science.gov (United States)

    2011-05-23

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

  18. 76 FR 11542 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2011-03-02

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

  19. 76 FR 68240 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2011-11-03

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

  20. 77 FR 1119 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2012-01-09

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

  1. 76 FR 77034 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-12-09

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

  2. 75 FR 56641 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

    Science.gov (United States)

    2010-09-16

    ... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting..., 2010. On June 17, 2010, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the...''); and letter from Manisha Kimmel, Executive Director, Financial Information Forum, On behalf of the...

  3. 76 FR 61773 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-10-05

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

  4. 76 FR 81551 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2011-12-28

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

  5. 76 FR 25399 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-05-04

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

  6. 75 FR 69725 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2010-11-15

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

  7. 76 FR 71404 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-11-17

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

  8. 76 FR 37384 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-06-27

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

  9. 76 FR 74105 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-11-30

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

  10. Regulatory Effects of Fisetin on Microglial Activation

    Directory of Open Access Journals (Sweden)

    Jing-Yuan Chuang

    2014-06-01

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

  11. Regulatory effects of fisetin on microglial activation.

    Science.gov (United States)

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

    2014-06-26

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

  12. 78 FR 23507 - Notice of Regulatory Review

    Science.gov (United States)

    2013-04-19

    ... individual comments. Factors that FHFA's regulatory review plan identifies as relevant to the review, and... year, applying factors enumerated in the plan. The regulatory review plan is available at the following... unduly burdensome; (2) Marketplace developments, technological evolution, and related changes that...

  13. The Political Economy of Regulatory Change

    DEFF Research Database (Denmark)

    Buch-Hansen, Hubert

    2012-01-01

    This article aims to explain the broader evolution of British merger control. To this end it outlines a novel critical political economy perspective on regulation and regulatory change which differs from established political economy approaches, such as the regulatory capitalism/state perspectives...

  14. 5 CFR 880.102 - Regulatory structure.

    Science.gov (United States)

    2010-01-01

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

  15. 5 CFR 847.102 - Regulatory structure.

    Science.gov (United States)

    2010-01-01

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

  16. 5 CFR 838.102 - Regulatory structure.

    Science.gov (United States)

    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)...

  17. Meditation and its regulatory role on sleep

    Directory of Open Access Journals (Sweden)

    Ravindra P. Nagendra

    2012-04-01

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

  18. Meditation and its regulatory role on sleep.

    Science.gov (United States)

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

    2012-01-01

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

  19. Genomics in the land of regulatory science.

    Science.gov (United States)

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

    2015-06-01

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

  20. 76 FR 40208 - Regulatory Flexibility Agenda

    Science.gov (United States)

    2011-07-07

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

  1. Collective action : a regulatory focus perspective

    NARCIS (Netherlands)

    Zaal, Maarten Pieter

    2012-01-01

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

  2. Meditation and Its Regulatory Role on Sleep

    OpenAIRE

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

    2012-01-01

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

  3. 21 CFR 26.18 - Regulatory collaboration.

    Science.gov (United States)

    2010-04-01

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

  4. Regulatory Reform: Low Risk, High Promise.

    Science.gov (United States)

    Tanenbaum, Morris

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

  5. Department of Agriculture Semiannual Regulatory Agenda

    Science.gov (United States)

    2010-04-26

    ... Part III Department of Agriculture Semiannual Regulatory Agenda ] DEPARTMENT OF AGRICULTURE (USDA) DEPARTMENT OF AGRICULTURE Office of the Secretary 7 CFR Subtitle A, Chs. I-VII, IX-XII, XIV-XVIII, XXI, XXIV.... Department of Agriculture (USDA) in conformance with Executive Order 12866 ``Regulatory Planning and...

  6. 49 CFR 355.21 - Regulatory review.

    Science.gov (United States)

    2010-10-01

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

  7. Adaptive Dynamics of Regulatory Networks: Size Matters

    Directory of Open Access Journals (Sweden)

    Martinetz Thomas

    2009-01-01

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

  8. Adaptive Dynamics of Regulatory Networks: Size Matters

    Directory of Open Access Journals (Sweden)

    2009-03-01

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

  9. Sociotechnical systems as a framework for regulatory system design and evaluation: Using Work Domain Analysis to examine a new regulatory system.

    Science.gov (United States)

    Carden, Tony; Goode, Natassia; Read, Gemma J M; Salmon, Paul M

    2017-03-15

    Like most work systems, the domain of adventure activities has seen a series of serious incidents and subsequent calls to improve regulation. Safety regulation systems aim to promote safety and reduce accidents. However, there is scant evidence they have led to improved safety outcomes. In fact there is some evidence that the poor integration of regulatory system components has led to adverse safety outcomes in some contexts. Despite this, there is an absence of methods for evaluating regulatory and compliance systems. This article argues that sociotechnical systems theory and methods provide a suitable framework for evaluating regulatory systems. This is demonstrated through an analysis of a recently introduced set of adventure activity regulations. Work Domain Analysis (WDA) was used to describe the regulatory system in terms of its functional purposes, values and priority measures, purpose-related functions, object-related processes and cognitive objects. This allowed judgement to be made on the nature of the new regulatory system and on the constraints that may impact its efficacy following implementation. Importantly, the analysis suggests that the new system's functional purpose of ensuring safe activities is not fully supported in terms of the functions and objects available to fulfil them. Potential improvements to the design of the system are discussed along with the implications for regulatory system design and evaluation across the safety critical domains generally.

  10. Developing a Small Business Regulatory System

    Directory of Open Access Journals (Sweden)

    Geoff Miller

    2014-09-01

    Full Text Available IntroductionThank you for inviting me to share my thoughts on what the government is doing to reduce the burden on small business. I also look forward to hearing the other speakers talk about how to make the regulatory system more responsive and relevant to business needs.It is more than a year since the fall of Lehman Brothers and the beginning of the Australian Government’s response to the global financial crisis.Today, the Australian economy is showing encouraging signs of recovery. The Government’s policy responses have been largely responsible for placing Australia in a better position than most countries around the world.The Mid-Year Economic and Fiscal Outlook (MYEFO (released earlier this month showed that the economy is performing much better than was forecast in the last Budget — MYEFO shows that Australia is the only advanced economy to have recorded positive growth through the year to June 2009. MYEFO also upgraded the growth forecasts for the following two years with consequental falls in the expected peak unemployment rate.Although this is good news, the GFC has clearly affected, and is continuing to impact on, small business.A number of Australian Chamber of Commerce and Industry surveys have reported large falls in small business confidence and conditions throughout 2008 and early 2009. However, the August ACCI Small Business Survey reports that, while conditions for small business are expected to remain challenging, conditions are stabilising.This good news is supported by the most recent Commonwealth Bank – ACCI Business Expectations Survey, which shows that small, medium and large businesses are expecting business conditions to improve significantly during this quarter.It is true that small businesses succeed or fail on the creativity, ingenuity, innovation and imagination of their owners and staff. It is also true that small businesses are notoriously time poor. When considering ways to improve the regulatory

  11. 75 FR 79449 - Introduction to The Regulatory Plan and the Unified Agenda of Federal Regulatory and Deregulatory...

    Science.gov (United States)

    2010-12-20

    ... proposed or final form during the upcoming fiscal year. The Regulatory Plan (Plan) and the Unified Agenda... Information Service Center Introduction to The Regulatory Plan and the Unified Agenda of Federal Regulatory... Unified Agenda of Federal Regulatory and Deregulatory Actions AGENCY: Regulatory Information...

  12. Running away from stress: How regulatory modes prospectively affect athletes' stress through passion.

    Science.gov (United States)

    Lucidi, F; Pica, G; Mallia, L; Castrucci, E; Manganelli, S; Bélanger, J J; Pierro, A

    2016-06-01

    A prospective field study conducted with runners training for an upcoming marathon (Marathon of Rome 2013) examined the relation between regulatory modes, locomotion and assessment, and stress. Integrating regulatory mode theory and the dualistic model of passion, we hypothesized that the relation between regulatory modes (evaluated 3 months before the race) and the experience of stress approaching the marathon, is mediated by the type of passion (harmonious vs obsessive) athletes experience with regard to marathoning. Results revealed that (a) locomotion positively predicted harmonious passion, which in turn reduced athletes' experience of stress; and (b) assessment positively predicted obsessive passion, which in turn enhanced athletes' experience of stress. Overall, the present results suggest that proximal psychological mechanisms such as basic regulatory mode orientations can predict distal outcomes such as stress indirectly through their relation with motivational phenomena such as passion.

  13. CCS: Legal and Regulatory Review

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2010-07-01

    The International Energy Agency (IEA) considers carbon capture and storage (CCS) a crucial part of worldwide efforts to limit global warming by reducing greenhouse-gas emissions. The IEA has estimated that the broad deployment of low-carbon energy technologies could reduce projected 2050 emissions to half 2005 levels -- and that CCS could contribute about one-fifth of those reductions. Reaching that goal, however, would require around 100 CCS projects to be implemented by 2020 and over 3 000 by 2050.

  14. Orphan drugs: the regulatory environment.

    Science.gov (United States)

    Franco, Pedro

    2013-02-01

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

  15. 77 FR 59702 - Promoting U.S. EC Regulatory Compatibility

    Science.gov (United States)

    2012-09-28

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

  16. Regulatory focus and the assignment of punishment

    Directory of Open Access Journals (Sweden)

    Chloe Carmichael

    2007-06-01

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

  17. Regulatory analysis technical evaluation handbook. Final report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-01-01

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

  18. Modeling of hysteresis in gene regulatory networks.

    Science.gov (United States)

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

    2012-08-01

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

  19. Analysis of technologies and experiences for reducing occupational radiation dose and study for applying to regulations

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Joo Hyun; Park, Moon Soo; Lee, Un Jang; Song, Jae Hyuk; Kim, Byeong Soo; Kim, Chong Uk [Seoul National Univ., Seoul (Korea, Republic of)

    2003-01-15

    To reduce Occupational Radiation Dose (ORD) effectively and enhance the radiological safety, the comprehensive assessment of the experiences to reduce ORD should be made by regulatory body as well as utilities. Hence, the objective of this study is to assess the experiences for reducing ORD from the regulatory viewpoint. With the research objective, the followings are performed in this research; analysis of occupational dose trends at domestic and foreign NPPs, identification of the effective technologies for reducing ORD, examination of the effects of the technologies for reducing ORD, derivation of the regulatory means for implementing he research results. From this study, the regulatory means for effective reduction of ORD are derived. Hence, the results can be utilized as a basic materials for ALARA requirements.

  20. Regulatory bioinformatics for food and drug safety.

    Science.gov (United States)

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

    2016-10-01

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

  1. Inference of Gene Regulatory Network Based on Local Bayesian Networks.

    Science.gov (United States)

    Liu, Fei; Zhang, Shao-Wu; Guo, Wei-Feng; Wei, Ze-Gang; Chen, Luonan

    2016-08-01

    The inference of gene regulatory networks (GRNs) from expression data can mine the direct regulations among genes and gain deep insights into biological processes at a network level. During past decades, numerous computational approaches have been introduced for inferring the GRNs. However, many of them still suffer from various problems, e.g., Bayesian network (BN) methods cannot handle large-scale networks due to their high computational complexity, while information theory-based methods cannot identify the directions of regulatory interactions and also suffer from false positive/negative problems. To overcome the limitations, in this work we present a novel algorithm, namely local Bayesian network (LBN), to infer GRNs from gene expression data by using the network decomposition strategy and false-positive edge elimination scheme. Specifically, LBN algorithm first uses conditional mutual information (CMI) to construct an initial network or GRN, which is decomposed into a number of local networks or GRNs. Then, BN method is employed to generate a series of local BNs by selecting the k-nearest neighbors of each gene as its candidate regulatory genes, which significantly reduces the exponential search space from all possible GRN structures. Integrating these local BNs forms a tentative network or GRN by performing CMI, which reduces redundant regulations in the GRN and thus alleviates the false positive problem. The final network or GRN can be obtained by iteratively performing CMI and local BN on the tentative network. In the iterative process, the false or redundant regulations are gradually removed. When tested on the benchmark GRN datasets from DREAM challenge as well as the SOS DNA repair network in E.coli, our results suggest that LBN outperforms other state-of-the-art methods (ARACNE, GENIE3 and NARROMI) significantly, with more accurate and robust performance. In particular, the decomposition strategy with local Bayesian networks not only effectively reduce

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

    NARCIS (Netherlands)

    K. Irion; R. Radu

    2014-01-01

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

  3. Modernizing the Regulatory System for Biotechnology Products

    Science.gov (United States)

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

  4. Electricity distribution networks: Changing regulatory approaches

    Science.gov (United States)

    Cambini, Carlo

    2016-09-01

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

  5. A study of bacterial gene regulatory mechanisms

    DEFF Research Database (Denmark)

    Hansen, Sabine

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

  6. Safety & Regulatory Strategy : Food Safety and Innovation

    NARCIS (Netherlands)

    Kalk, C.

    2013-01-01

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

  7. 78 FR 44331 - Semiannual Regulatory Agenda

    Science.gov (United States)

    2013-07-23

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

  8. Systemic Risk and Optimal Regulatory Architecture

    NARCIS (Netherlands)

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

    2011-01-01

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

  9. Mobile Source Emissions Regulatory Compliance Data Inventory

    Data.gov (United States)

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

  10. Regulatory and Non-Regulatory Barriers which Limit the Entry of International Telecommunication Service Companies into Asian Markets

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    This paper compares the development of telecom regulation andderegulation between some typical Asian countries, and analyzes the telecom regulatory systems and industrial organizations of China. This paper also investigates the approaches and strategies of Asian countries to reduce the regulation, reinforce the competition and establish efficient telecom industries. Having examined the Asian telecommunication markets, the paper attempts to apply the lessons learned from the opening of the telecoms markets of the developed economies. Finally the paper contends that if Asian economies wish to have nationally based companies, state or private enterprises, in a competitive postion, the format of the implementation of the WTO/GATS basic telecoms agreement should be carefully examined.

  11. ATMPs for Cancer Immunotherapy: A Regulatory Overview.

    Science.gov (United States)

    Galli, Maria Cristina

    2016-01-01

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

  12. Measuring Regulatory Restrictions in Logistics Services

    OpenAIRE

    Claire HOLLWEG; Marn-Heong WONG

    2009-01-01

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

  13. IPTV Market Development and Regulatory Aspects

    DEFF Research Database (Denmark)

    Tadayoni, Reza; Sigurdsson, Halldór Matthias

    2006-01-01

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

  14. Cis-regulatory mutations in human disease.

    Science.gov (United States)

    Epstein, Douglas J

    2009-07-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Jennings, S.D.

    1990-04-01

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

  16. Combination of Neuro-Fuzzy Network Models with Biological Knowledge for Reconstructing Gene Regulatory Networks

    Institute of Scientific and Technical Information of China (English)

    Guixia Liu; Lei Liu; Chunyu Liu; Ming Zheng; Lanying Su; Chunguang Zhou

    2011-01-01

    Inferring gene regulatory networks from large-scale expression data is an important topic in both cellular systems and computational biology. The inference of regulators might be the core factor for understanding actual regulatory conditions in gene regulatory networks, especially when strong regulators do work significantly, in this paper, we propose a novel approach based on combining neuro-fuzzy network models with biological knowledge to infer strong regulators and interrelated fuzzy rules. The hybrid neuro-fuzzy architecture can not only infer the fuzzy rules, which are suitable for describing the regulatory conditions in regulatory networks, but also explain the meaning of nodes and weight value in the neural network. It can get useful rules automatically without factitious judgments. At the same time, it does not add recursive layers to the model, and the model can also strengthen the relationships among genes and reduce calculation. We use the proposed approach to reconstruct a partial gene regulatory network of yeast. The results show that this approach can work effectively.

  17. Application of omics data in regulatory toxicology: report of an international BfR expert workshop.

    Science.gov (United States)

    Marx-Stoelting, P; Braeuning, A; Buhrke, T; Lampen, A; Niemann, L; Oelgeschlaeger, M; Rieke, S; Schmidt, F; Heise, T; Pfeil, R; Solecki, R

    2015-11-01

    Advances in omics techniques and molecular toxicology are necessary to provide new perspectives for regulatory toxicology. By the application of modern molecular techniques, more mechanistic information should be gained to support standard toxicity studies and to contribute to a reduction and refinement of animal experiments required for certain regulatory purposes. The relevance and applicability of data obtained by omics methods to regulatory purposes such as grouping of chemicals, mode of action analysis or classification and labelling needs further improvement, defined validation and cautious expert judgment. Based on the results of an international expert workshop organized 2014 by the Federal Institute for Risk Assessment in Berlin, this paper is aimed to provide a critical overview of the regulatory relevance and reliability of omics methods, basic requirements on data quality and validation, as well as regulatory criteria to decide which effects observed by omics methods should be considered adverse or non-adverse. As a way forward, it was concluded that the inclusion of omics data can facilitate a more flexible approach for regulatory risk assessment and may help to reduce or refine animal testing.

  18. 75 FR 20868 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2010-04-21

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

  19. 12 CFR 914.1 - Regulatory Report defined.

    Science.gov (United States)

    2010-01-01

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

  20. Cross-border infrastructure constraints, regulatory measures and economic integration of the Dutch - German gas market

    NARCIS (Netherlands)

    Kuper, G.H.; Mulder, M.

    2013-01-01

    We estimate to which extent regulatory measures in the Dutch market have reduced the vulnerability of this market to constraints in the cross-border infrastructure with Germany, which is the largest Dutch neighbouring market. We measure this vulnerability by the degree the markets are integrated, i.

  1. Bank Risk Taking and Liquidity Creation Following Regulatory Interventions and Capital Support

    NARCIS (Netherlands)

    Berger, A.N.; Bouwman, C.H.S.; Kick, T.; Schaeck, K.

    2011-01-01

    During times of bank distress, authorities often engage in regulatory interventions and provide capital support to reduce bank risk taking. An unintended effect of such actions may be a reduction in bank liquidity creation, with possible adverse consequences for the economy as a whole. This paper te

  2. Bank risk taking and liquidity creation following regulatory interventions and capital support

    NARCIS (Netherlands)

    Berger, A.N.; Bouwman, C.H.S.; Kick, T.; Schaeck, K.

    2011-01-01

    During times of bank distress, authorities often engage in regulatory interventions and provide capital support to reduce bank risk taking. An unintended effect of such actions may be a reduction in bank liquidity creation, with possible adverse consequences for the economy as a whole. This paper te

  3. Childhood poverty and recruitment of adult emotion regulatory neurocircuitry.

    Science.gov (United States)

    Liberzon, Israel; Ma, Sean T; Okada, Go; Ho, S Shaun; Swain, James E; Evans, Gary W

    2015-11-01

    One in five American children grows up in poverty. Childhood poverty has far-reaching adverse impacts on cognitive, social and emotional development. Altered development of neurocircuits, subserving emotion regulation, is one possible pathway for childhood poverty's ill effects. Children exposed to poverty were followed into young adulthood and then studied using functional brain imaging with an implicit emotion regulation task focused. Implicit emotion regulation involved attention shifting and appraisal components. Early poverty reduced left dorsolateral prefrontal cortex recruitment in the context of emotional regulation. Furthermore, this emotion regulation associated brain activation mediated the effects of poverty on adult task performance. Moreover, childhood poverty also predicted enhanced insula and reduced hippocampal activation, following exposure to acute stress. These results demonstrate that childhood poverty can alter adult emotion regulation neurocircuitry, revealing specific brain mechanisms that may underlie long-term effects of social inequalities on health. The role of poverty-related emotion regulatory neurocircuitry appears to be particularly salient during stressful conditions.

  4. Regulatory networks in pollen development under cold stress

    Directory of Open Access Journals (Sweden)

    Kamal Dev Sharma

    2016-03-01

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

  5. Reduced Rank Regression

    DEFF Research Database (Denmark)

    Johansen, Søren

    2008-01-01

    The reduced rank regression model is a multivariate regression model with a coefficient matrix with reduced rank. The reduced rank regression algorithm is an estimation procedure, which estimates the reduced rank regression model. It is related to canonical correlations and involves calculating e...... eigenvalues and eigenvectors. We give a number of different applications to regression and time series analysis, and show how the reduced rank regression estimator can be derived as a Gaussian maximum likelihood estimator. We briefly mention asymptotic results...

  6. 77 FR 8034 - Semiannual Regulatory Agenda and Fiscal Year 2011 Regulatory Plan

    Science.gov (United States)

    2012-02-13

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

  7. 76 FR 64419 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-10-18

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

  8. 78 FR 40776 - Issuance of Regulatory Guide 1.124 and Regulatory Guide 1.130

    Science.gov (United States)

    2013-07-08

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

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

    Science.gov (United States)

    2013-10-22

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

  10. 75 FR 52380 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2010-08-25

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

  11. 75 FR 53362 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2010-08-31

    ..., director, partner or employee of another business organization or owning any stock or having any direct or... controlling, controlled by or under common control with a member or member organization shall have associated... COMMISSION Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

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

    Science.gov (United States)

    2013-06-20

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

  13. 77 FR 34379 - Notice of Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory...

    Science.gov (United States)

    2012-06-11

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

  14. Regulatory focus affects physician risk tolerance.

    Science.gov (United States)

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

    2014-01-01

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

  15. Functional characterization of variations on regulatory motifs.

    Directory of Open Access Journals (Sweden)

    Michal Lapidot

    2008-03-01

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

  16. Phylogeny based discovery of regulatory elements

    Directory of Open Access Journals (Sweden)

    Cohen Barak A

    2006-05-01

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

  17. Coded MapReduce

    OpenAIRE

    Li, Songze; Maddah-Ali, Mohammad Ali; Avestimehr, A. Salman

    2015-01-01

    MapReduce is a commonly used framework for executing data-intensive jobs on distributed server clusters. We introduce a variant implementation of MapReduce, namely "Coded MapReduce", to substantially reduce the inter-server communication load for the shuffling phase of MapReduce, and thus accelerating its execution. The proposed Coded MapReduce exploits the repetitive mapping of data blocks at different servers to create coding opportunities in the shuffling phase to exchange (key,value) pair...

  18. CD4-regulatory cells in COPD patients

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  19. Transcription regulatory networks analysis using CAGE

    KAUST Repository

    Tegnér, Jesper N.

    2009-10-01

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

  20. Current status of developmental neurotoxicity: regulatory view

    DEFF Research Database (Denmark)

    Hass, Ulla

    2003-01-01

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

  1. Targeting regulatory T cells in cancer.

    LENUS (Irish Health Repository)

    Byrne, William L

    2012-01-31

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

  2. Current approaches to gene regulatory network modelling

    Directory of Open Access Journals (Sweden)

    Brazma Alvis

    2007-09-01

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

  3. Phenotypic and functional markers for 1alpha,25-dihydroxyvitamin D(3)-modified regulatory dendritic cells

    DEFF Research Database (Denmark)

    Pedersen, A W; Holmstrøm, K; Jensen, S S;

    2009-01-01

    The clinical use of dendritic cells (DCs) to induce antigen-specific immune tolerance has been hampered by the lack of a widely acknowledged method for generating human regulatory DCs but even more so by the non-existence of reliable markers. Thus, we set out to find reliable markers that can...... CD14 and reduced CD1a on the cell surface. These VD3-treated DCs exert a long-lasting inefficient T cell stimulation and induce T cell hyporesponsiveness with regulatory potential. Importantly, such VD3-treated DCs were readily distinguishable from untreated DCs by low levels of interleukin-23...

  4. Reduce HIV Risk

    Science.gov (United States)

    ... Our research has demonstrated remarkable success in reducing HIV risk-associated sexual behaviors among African American adolescents and adults." Read More "Nursing Research" Articles Nursing Research / Improve Hospital-to-Home Transitions / Reduce ...

  5. Regulatory affairs for biomaterials and medical devices

    CERN Document Server

    Amato, Stephen F; Amato, B

    2015-01-01

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

  6. Regulatory Competition in Global Financial Markets

    DEFF Research Database (Denmark)

    Ringe, Georg

    2015-01-01

    The decades-long discussion on the merits of regulatory competition appears in a new light on the global financial market. There are a number of strategies that market participants use to avoid the reach of regulation, in particular by virtue of shifting trading abroad or else relocating activities...... competition are a reality in today’s global financial market, and the financial sector is different from their traditional fields of application: the ease of arbitrage, the fragility of banking and the risks involved are exceptional. Most importantly, regulatory arbitrage does not or only rarely occurs...

  7. Theory of Regulatory Compliance for Requirements Engineering

    CERN Document Server

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

    2010-01-01

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

  8. Regulatory issues in accreditation of toxicology laboratories.

    Science.gov (United States)

    Bissell, Michael G

    2012-09-01

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

  9. Modular arrangement of regulatory RNA elements

    Science.gov (United States)

    Roßmanith, Johanna; Narberhaus, Franz

    2017-01-01

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

  10. Excessive crying in infants with regulatory disorders.

    Science.gov (United States)

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

    1996-01-01

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

  11. Bridging the gap between academic research and regulatory health risk assessment of Endocrine Disrupting Chemicals.

    Science.gov (United States)

    Beronius, Anna; Hanberg, Annika; Zilliacus, Johanna; Rudén, Christina

    2014-12-01

    Regulatory risk assessment is traditionally based primarily on toxicity studies conducted according to standardized and internationally validated test guidelines. However, health risk assessment of endocrine disrupting chemicals (EDCs) is argued to rely on the efficient integration of findings from academic research. The aim of this review was to provide an overview of current developments to facilitate the use of academic research in regulatory risk assessment of chemicals and how certain aspects of study design and reporting are particularly important for the risk assessment process. By bridging the gap between academic research and regulatory health risk assessment of EDCs, scientific uncertainty in risk assessment conclusions can be reduced, allowing for better targeted policy decisions for chemical risk reduction.

  12. The impact of measurement errors in the identification of regulatory networks

    Directory of Open Access Journals (Sweden)

    Sato João R

    2009-12-01

    Full Text Available Abstract Background There are several studies in the literature depicting measurement error in gene expression data and also, several others about regulatory network models. However, only a little fraction describes a combination of measurement error in mathematical regulatory networks and shows how to identify these networks under different rates of noise. Results This article investigates the effects of measurement error on the estimation of the parameters in regulatory networks. Simulation studies indicate that, in both time series (dependent and non-time series (independent data, the measurement error strongly affects the estimated parameters of the regulatory network models, biasing them as predicted by the theory. Moreover, when testing the parameters of the regulatory network models, p-values computed by ignoring the measurement error are not reliable, since the rate of false positives are not controlled under the null hypothesis. In order to overcome these problems, we present an improved version of the Ordinary Least Square estimator in independent (regression models and dependent (autoregressive models data when the variables are subject to noises. Moreover, measurement error estimation procedures for microarrays are also described. Simulation results also show that both corrected methods perform better than the standard ones (i.e., ignoring measurement error. The proposed methodologies are illustrated using microarray data from lung cancer patients and mouse liver time series data. Conclusions Measurement error dangerously affects the identification of regulatory network models, thus, they must be reduced or taken into account in order to avoid erroneous conclusions. This could be one of the reasons for high biological false positive rates identified in actual regulatory network models.

  13. 76 FR 18467 - Pennsylvania Regulatory Program

    Science.gov (United States)

    2011-04-04

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

  14. Department of Commerce Semiannual Regulatory Agenda

    Science.gov (United States)

    2010-04-26

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

  15. Inferring latent gene regulatory network kinetics

    NARCIS (Netherlands)

    González, Javier; Vujačić, Ivan; Wit, Ernst

    2013-01-01

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

  16. 78 FR 42893 - Statement on Regulatory Burden

    Science.gov (United States)

    2013-07-18

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

  17. Regulatory capital requirements and bail in mechanisms

    NARCIS (Netherlands)

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

    2015-01-01

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

  18. Regulatory Challenges for Cartilage Repair Technologies.

    Science.gov (United States)

    McGowan, Kevin B; Stiegman, Glenn

    2013-01-01

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

  19. 78 FR 1646 - Semiannual Regulatory Agenda

    Science.gov (United States)

    2013-01-08

    ... provides flexibility for agencies to conduct the privacy training or require the contractor to conduct the...; Organizational Conflicts of Interest. 416 FAR Case 2010-013, Privacy 9000-AM02 Training. 417 Federal Acquisition...: Action Date FR Cite NPRM 12/00/12 Regulatory Flexibility Analysis Required: Yes. Agency Contact:...

  20. Regulatory Promotion of Emergent CCS Technology

    Energy Technology Data Exchange (ETDEWEB)

    Davies, Lincoln; Uchitel, Kirsten; Johnson, David

    2014-01-01

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

  1. Mutational robustness of gene regulatory networks.

    Directory of Open Access Journals (Sweden)

    Aalt D J van Dijk

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

  2. Deferred Tax Assests and Bank Regulatory Capital

    NARCIS (Netherlands)

    Gallemore, J.

    2012-01-01

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

  3. Regulatory Proteolysis in Arabidopsis-Pathogen Interactions

    OpenAIRE

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

    2015-01-01

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

  4. Department of Agriculture Semiannual Regulatory Agenda

    Science.gov (United States)

    2010-12-20

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

  5. Shaping Formal Networks throug the Regulatory Process

    NARCIS (Netherlands)

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

    2004-01-01

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

  6. HIDEN: Hierarchical decomposition of regulatory networks

    Directory of Open Access Journals (Sweden)

    Gülsoy Günhan

    2012-09-01

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

  7. Regulatory T-cells and autoimmunity.

    LENUS (Irish Health Repository)

    Ni Choileain, Niamh

    2012-02-03

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

  8. Independent regulatory authorities in European electricity market

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  9. 75 FR 79929 - Semiannual Regulatory Agenda

    Science.gov (United States)

    2010-12-20

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

  10. 76 FR 37996 - West Virginia Regulatory Program

    Science.gov (United States)

    2011-06-29

    ... surface coal mining and reclamation operations on non- Federal and non-Indian lands within its borders by... of approval of the West Virginia program in the January 21, 1981, Federal Register (46 FR 5915). You... actual language of State regulatory programs and program amendments because each program is drafted...

  11. Pre-commercial procurement : regulatory effectiveness?

    NARCIS (Netherlands)

    Apostol, Anca Ramona

    2014-01-01

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

  12. 76 FR 76111 - Montana Regulatory Program

    Science.gov (United States)

    2011-12-06

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

  13. RSAT 2015: Regulatory Sequence Analysis Tools.

    Science.gov (United States)

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

    2015-07-01

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

  14. Regulatory pathways in the European Union.

    Science.gov (United States)

    Kohler, Manuela

    2011-01-01

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

  15. Regulatory guidelines for biosimilars in Malaysia.

    Science.gov (United States)

    Abas, Arpah

    2011-09-01

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

  16. 76 FR 13526 - Reducing Regulatory Burden; Retrospective Review Under Executive Order 13563

    Science.gov (United States)

    2011-03-14

    ... individual listed in the FOR FURTHER INFORMATION CONTACT section. Docket: For access to the docket to read... repealed? (2) What factors should the agency consider in selecting and prioritizing rules for review? (3... efficient ways? (8) Are there rules that have been overtaken by technological developments? Can...

  17. 76 FR 13532 - Reducing Regulatory Burden; Retrospective Review Under Executive Order 13563

    Science.gov (United States)

    2011-03-14

    ... Executive Order 13563. SBA is also interested in comments about factors that we should consider in setting... regulations; (9) revise regulations to address changes in technology, economic conditions, or other factors... individual, personal or corporate benefit. Where feasible, comments should reference a specific...

  18. 78 FR 44056 - Premium Rates; Payment of Premiums; Reducing Regulatory Burden

    Science.gov (United States)

    2013-07-23

    ... benefits (UVBs)--the excess of its premium funding target over its assets. The premium funding target and... would small plans enjoy the convenience of a convergence between the premium and Form 5500 due...

  19. 76 FR 39343 - Reducing Regulatory Burden; Retrospective Review Under E.O. 13563

    Science.gov (United States)

    2011-07-06

    ... changes in net benefits, cost- effectiveness ratios, or other financial metrics? With respect specifically... this section. To view Executive Order 13563 go to: http://www.gpo.gov/fdsys/pkg/FR-2011-01-21/pdf/2011... on January 21, 2011 (76 FR 3821)), which directs agencies to conduct a retrospective analysis...

  20. 76 FR 11395 - Reducing Regulatory Burden; Retrospective Review Under E.O. 13563

    Science.gov (United States)

    2011-03-02

    .... weekdays at the above address. Due to security measures at the HUD Headquarters building, an advance... initiatives help create suitable living environments, and help to ensure that all citizens have access to.... The Executive Order also emphasizes the importance of meaningful public participation in...

  1. EUREST PLUS - European Regulatory Science on Tobacco: Policy implementation to reduce lung diseases - Proposal (Horizon2020

    Directory of Open Access Journals (Sweden)

    Constantine Vardavas

    2016-03-01

    Full Text Available EUREST-PLUS, a thirteen –partner EU joint proposal, coordinated by ENSP (Coordinator: Constantine Vardavas, aims to monitor and evaluate the impact of the TPD at an EU level. The specific objectives of the proposal are: 1. To evaluate the psychosocial and behavioural impact of TPD implementation and FCTC implementation, through the creation of a longitudinal cohort of adult smokers in 6 EU MS (Germany, Greece, Hungary, Poland, Romania, Spain in a pre- vs. post- study design. 2. To assess support for TPD implementation through secondary dataset analyses of the 2015 Special Eurobarometer on Tobacco Survey (SETS, and through trend analyses on the merged datasets of the 2009, 2012 and2015 SETS datasets. 3. To document changes in e-cigarette product parameters (technical design, labelling, packaging and chemical composition following implementation of Article 20 of the TPD. 4. To enhance innovative joint research collaborations, through the pooling and comparisons across both other EU countries of the International Tobacco Control (ITC Project, and other non-EU countries.

  2. 76 FR 26651 - Reducing Regulatory Burden; Retrospective Review Under E.O. 13563

    Science.gov (United States)

    2011-05-09

    ... heavily in the use of social media tools, such as Facebook , Twitter , blogs, and wikis for internal.... This is extremely burdensome for applicants who may not have a computer, access to a computer,...

  3. 76 FR 16700 - Reducing Regulatory Burden; Retrospective Review Under E.O. 13563

    Science.gov (United States)

    2011-03-25

    ...: Robert Cushing, Jr., 703-696-5282. SUPPLEMENTARY INFORMATION: DoD regulations may be viewed by going to... 2, 5, 32, 33, 36, 40, and/or 48. Dated: March 21, 2011. Morgan F. Park, Alternate OSD Federal Register Liaison Officer, Department of Defense. BILLING CODE 5001-06-P...

  4. 76 FR 10526 - Reducing Regulatory Burden; Retrospective Review Under E.O. 13563

    Science.gov (United States)

    2011-02-25

    ..., Department of the Interior, Room 7311, 1849 C Street, NW., Washington, DC 20240. E-mail: RegsReview@ios.doi...@ios.doi.gov . SUPPLEMENTARY INFORMATION: President Obama issued Executive Order 13563, ``Improving... links to the Department's regulations and a link to an e-mail in-box at RegsReview@ios.doi.gov...

  5. 76 FR 40645 - Reducing Regulatory Burden; Retrospective Review Under E.O. 13563

    Science.gov (United States)

    2011-07-11

    ... FURTHER INFORMATION CONTACT: Mark Lawyer, Office of the Secretary, 202-208-3181, Mark_Lawyer@ios.doi.gov... links to the plan, the Department's regulations, and an e-mail in-box at RegsReview@ios.doi.gov...

  6. Problems in the regulatory policy of the drug market

    Directory of Open Access Journals (Sweden)

    Nathália Molleis Miziara

    2015-01-01

    Full Text Available OBJECTIVE Analyze the implementation of drug price regulation policy by the Drug Market Regulation Chamber. METHODS This is an interview-based study, which was undertaken in 2012, using semi-structured questionnaires with social actors from the pharmaceutical market, the pharmaceuticals industry, consumers and the regulatory agency. In addition, drug prices were compiled based on surveys conducted in the state of Sao Paulo, at the point of sale, between February 2009 and May 2012. RESULTS The mean drug prices charged at the point of sale (pharmacies were well below the maximum price to the consumer, compared with many drugs sold in Brazil. Between 2009 and 2012, 44 of the 129 prices, corresponding to 99 drugs listed in the database of compiled prices, showed a variation of more than 20.0% in the mean prices at the point of sale and the maximum price to the consumer. In addition, many laboratories have refused to apply the price adequacy coefficient in their sales to government agencies. CONCLUSIONS The regulation implemented by the pharmaceutical market regulator was unable to significantly control prices of marketed drugs, without succeeding to push them to levels lower than those determined by the pharmaceutical industry and failing, therefore, in its objective to promote pharmaceutical support for the public. It is necessary reconstruct the regulatory law to allow market prices to be reduced by the regulator as well as institutional strengthen this government body.

  7. Tyrosol exhibits negative regulatory effects on LPS response and endotoxemia.

    Science.gov (United States)

    Lu, Jing; Huang, Guoren; Wang, Zhenning; Zhuang, Shuang; Xu, Linli; Song, Bocui; Xiong, Ying; Guan, Shuang

    2013-12-01

    Tyrosol, a phenolic compound, was isolated from wine, olive oil and other plant-derived products. In the present study, we first investigated the negative regulatory effects of tyrosol on cytokine production by lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages in vitro, and the results showed that tyrosol reduced tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) secretion. This inspired us to further study the effects of tyrosol in vivo. Tyrosol significantly attenuated TNF-α, IL-1β and IL-6 production in serum from mice challenged with LPS, and consistent with the results in vitro. In the murine model of endotoxemia, mice were treated with tyrosol prior to or after LPS challenge. The results showed that tyrosol significantly increased mice survival. We further investigated signal transduction ways to determine how tyrosol works. The data revealed that tyrosol shocked LPS-induced mitogen activated protein kinases (MAPKs) and nuclear transcription factor-κB (NF-κB) signal transduction pathways in RAW 264.7 macrophages. These observations indicated that tyrosol exerted negative regulatory effects on LPS response in vitro and in vivo through suppressing NF-κB and p38/ERK MAPK signaling pathways.

  8. Regulatory focus and burnout in nurses: The mediating effect of perception of transformational leadership.

    Science.gov (United States)

    Shi, Rui; Zhang, Shilei; Xu, Hang; Liu, Xufeng; Miao, Danmin

    2015-12-01

    This correlation study investigated the relationship between nurses' regulatory focus and burnout, as mediated by their perceptions of transformational leadership, using a cross-sectional research design with anonymous questionnaires. In July-August 2012, data were collected from 378 nurses from three hospitals in Shaanxi Province, China, using self-report questionnaires for measuring the nurses' regulatory focus, their level of burnout and their perception of whether the leadership of their supervisor was transformational. Structural equation modelling and bootstrapping procedures were used to identify the mediating effect of their perceptions of transformational leadership. The results supported our hypothesized model. The type of regulatory focus emerged as a significant predictor of burnout. Having a perception of transformational leadership partially mediated the relationship between regulatory focus and burnout. Having a promotion focus reduced burnout when the participants perceived transformational leadership, whereas having a prevention focus exhibited the opposite pattern. The mediating effect of the perception of transformational leadership suggests that a promotion focus may help diminish burnout, directly and indirectly. Nurse managers must be aware of the role of a regulatory focus and cultivate promotion focus in their followers.

  9. Global regulatory framework for production and marketing of crops biofortified with vitamins and minerals.

    Science.gov (United States)

    Mejia, Luis A; Dary, Omar; Boukerdenna, Hala

    2017-02-01

    Biofortification of crops is being introduced in several countries as a strategy to reduce micronutrient deficiencies. Biofortified products, with increased contents of micronutrients, are currently produced by conventional plant breeding, genetic modification, or nutrient-enhanced fertilization. Corn, rice, wheat, beans, pearl millet, sweet potato, and cassava have been biofortified with increased contents of provitamin A carotenoids, iron, or zinc. However, regulatory considerations are rare or nonexistent. The objective of this paper is to review the regulatory framework for production and marketing of biofortified crops in countries that have adopted this strategy. The information was identified using Internet search engines and websites of health and nutrition organizations and nongovernmental organizations and by consulting scientists and government authorities. Thus far, biofortified products introduced in Latin America, Africa, and Asia have been produced only by conventional breeding. Cultivars using other techniques are still under testing. The production and marketing of these products have been conducted without regulatory framework and under limited government control or regulatory guidance. Nevertheless, some countries have integrated biofortified crops into their nutrition agendas. Although improvements by conventional breeding have not been subject to regulations, when biofortification becomes expanded by including other techniques, an appropriate regulatory framework will be necessary.

  10. An Analysis of Regulatory Strategies for Recycling and Re-Use of Metals in Australia

    Directory of Open Access Journals (Sweden)

    Wayne Gumley

    2014-04-01

    Full Text Available This article considers regulatory strategies that promote more efficient use of material inputs within the Australian economy, with particular focus on recycling and recovery of metals, drawing upon the concept of a “circular economy”. It briefly reviews the nature of regulation and trends in regulatory strategies within changing policy contexts, and then examines the regulatory framework applicable to the various phases in the life cycle of metals, ranging from extraction of minerals to processing and assimilation of metals into finished products, through to eventual disposal of products as waste. Discussion focuses upon the regulatory strategies applied in each phase and the changing roles of government and business operators within global distribution networks. It is concluded that the prevailing political agenda favoring deregulation and reduced taxation may be a major barrier to development of new styles of regulation and more effective use of taxation powers that is needed to support a more circular economy in metals. The implication for future research is the need to substantiate the outcomes of reflexive regulatory strategies with well-designed empirical studies.

  11. Regulatory network operations in the Pathway Tools software

    Directory of Open Access Journals (Sweden)

    Paley Suzanne M

    2012-09-01

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

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

    Institute of Scientific and Technical Information of China (English)

    PU Jilong; LI Xiaoyan

    2007-01-01

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

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

    OpenAIRE

    Giresi, Paul G.; Lieb, Jason D.

    2009-01-01

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

  14. Optimal Constrained Stationary Intervention in Gene Regulatory Networks

    Directory of Open Access Journals (Sweden)

    Golnaz Vahedi

    2008-05-01

    Full Text Available A key objective of gene network modeling is to develop intervention strategies to alter regulatory dynamics in such a way as to reduce the likelihood of undesirable phenotypes. Optimal stationary intervention policies have been developed for gene regulation in the framework of probabilistic Boolean networks in a number of settings. To mitigate the possibility of detrimental side effects, for instance, in the treatment of cancer, it may be desirable to limit the expected number of treatments beneath some bound. This paper formulates a general constraint approach for optimal therapeutic intervention by suitably adapting the reward function and then applies this formulation to bound the expected number of treatments. A mutated mammalian cell cycle is considered as a case study.

  15. Optimal Constrained Stationary Intervention in Gene Regulatory Networks

    Directory of Open Access Journals (Sweden)

    Faryabi Babak

    2008-01-01

    Full Text Available A key objective of gene network modeling is to develop intervention strategies to alter regulatory dynamics in such a way as to reduce the likelihood of undesirable phenotypes. Optimal stationary intervention policies have been developed for gene regulation in the framework of probabilistic Boolean networks in a number of settings. To mitigate the possibility of detrimental side effects, for instance, in the treatment of cancer, it may be desirable to limit the expected number of treatments beneath some bound. This paper formulates a general constraint approach for optimal therapeutic intervention by suitably adapting the reward function and then applies this formulation to bound the expected number of treatments. A mutated mammalian cell cycle is considered as a case study.

  16. Modeling gene regulatory networks: A network simplification algorithm

    Science.gov (United States)

    Ferreira, Luiz Henrique O.; de Castro, Maria Clicia S.; da Silva, Fabricio A. B.

    2016-12-01

    Boolean networks have been used for some time to model Gene Regulatory Networks (GRNs), which describe cell functions. Those models can help biologists to make predictions, prognosis and even specialized treatment when some disturb on the GRN lead to a sick condition. However, the amount of information related to a GRN can be huge, making the task of inferring its boolean network representation quite a challenge. The method shown here takes into account information about the interactome to build a network, where each node represents a protein, and uses the entropy of each node as a key to reduce the size of the network, allowing the further inferring process to focus only on the main protein hubs, the ones with most potential to interfere in overall network behavior.

  17. NCCN Biosimilars White Paper: regulatory, scientific, and patient safety perspectives.

    Science.gov (United States)

    Zelenetz, Andrew D; Ahmed, Islah; Braud, Edward Louis; Cross, James D; Davenport-Ennis, Nancy; Dickinson, Barry D; Goldberg, Steven E; Gottlieb, Scott; Johnson, Philip E; Lyman, Gary H; Markus, Richard; Matulonis, Ursula A; Reinke, Denise; Li, Edward C; DeMartino, Jessica; Larsen, Jonathan K; Hoffman, James M

    2011-09-01

    Biologics are essential to oncology care. As patents for older biologics begin to expire, the United States is developing an abbreviated regulatory process for the approval of similar biologics (biosimilars), which raises important considerations for the safe and appropriate incorporation of biosimilars into clinical practice for patients with cancer. The potential for biosimilars to reduce the cost of biologics, which are often high-cost components of oncology care, was the impetus behind the Biologics Price Competition and Innovation Act of 2009, a part of the 2010 Affordable Care Act. In March 2011, NCCN assembled a work group consisting of thought leaders from NCCN Member Institutions and other organizations, to provide guidance regarding the challenges health care providers and other key stakeholders face in incorporating biosimilars in health care practice. The work group identified challenges surrounding biosimilars, including health care provider knowledge, substitution practices, pharmacovigilance, naming and product tracking, coverage and reimbursement, use in off-label settings, and data requirements for approval.

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

    Science.gov (United States)

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

  19. Legal principles of regulatory administration and nuclear safety regulation

    Energy Technology Data Exchange (ETDEWEB)

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

    2000-12-15

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

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

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

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

  1. Logical knowledge representation of regulatory relations in biomedical pathways

    DEFF Research Database (Denmark)

    Zambach, Sine; Hansen, Jens Ulrik

    2010-01-01

    Knowledge on regulatory relations, in for example regulatory pathways in biology, is used widely in experiment design by biomedical researchers and in systems biology. The knowledge has typically either been represented through simple graphs or through very expressive differential equation...

  2. Regulatory reform of Finnish environmental policy

    Energy Technology Data Exchange (ETDEWEB)

    Sairinen, R.

    2000-07-01

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

  3. Reducible oxide based catalysts

    Science.gov (United States)

    Thompson, Levi T.; Kim, Chang Hwan; Bej, Shyamal K.

    2010-04-06

    A catalyst is disclosed herein. The catalyst includes a reducible oxide support and at least one noble metal fixed on the reducible oxide support. The noble metal(s) is loaded on the support at a substantially constant temperature and pH.

  4. 76 FR 59066 - Notice of Regulatory Review Plan

    Science.gov (United States)

    2011-09-23

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

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

    Lifescience Database Archive (English)

    Full Text Available 17967718 Regulatory pathways in inflammation. Mantovani A, Garlanda C, Locati M, Ro....html) (.csml) Show Regulatory pathways in inflammation. PubmedID 17967718 Title Regulatory pathways in infl... B, Vecchi A. Publication Autoimmun Rev. 2007 Nov;7(1):8-11. Epub 2007 Mar 26. Pathway - PNG File (.png) SVG

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

    Science.gov (United States)

    Narberhaus, Franz; Vogel, Jörg

    2009-10-01

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

  7. Roadmapping as a Tool for Renewing Regulatory Practices

    DEFF Research Database (Denmark)

    Borch, Kristian; Norus, Jesper

    2004-01-01

    in this emerging and discontinuedtechnology can provide critical policy information. This type of policy intelligence canbe used to rethink the regulatory practices away from today's framework basedregulation of the emerging technologies towards a regulatory policy based on how todevelop regulatory practices based...

  8. 40 CFR 73.86 - State regulatory autonomy.

    Science.gov (United States)

    2010-07-01

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

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

    NARCIS (Netherlands)

    Kasiyanto, Safari; Gabriella, Gimigliano

    2016-01-01

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

  10. 18 CFR 367.2540 - Account 254, Other regulatory liabilities.

    Science.gov (United States)

    2010-04-01

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

  11. Regulatory Acceptance of Alternative Methods in the Development and Approval of Pharmaceuticals.

    Science.gov (United States)

    Beken, Sonja; Kasper, Peter; van der Laan, Jan-Willem

    Animal studies may be carried out to support first administration of a new medicinal product to either humans or the target animal species, or before performing clinical trials in even larger populations, or before marketing authorisation, or to control quality during production. Ethical and animal welfare considerations require that animal use is limited as much as possible. Directive 2010/63/EU on the protection of animals used for scientific purposes unambiguously fosters the application of the principle of the 3Rs when considering the choice of methods to be used.As such, today, the 3Rs are embedded in the relevant regulatory guidance both at the European (European Medicines Agency (EMA)) and (Veterinary) International Conference on Harmonization ((V)ICH) levels. With respect to non-clinical testing requirements for human medicinal products, reduction and replacement of animal testing has been achieved by the regulatory acceptance of new in vitro methods, either as pivotal, supportive or exploratory mechanistic studies. Whilst replacement of animal studies remains the ultimate goal, approaches aimed at reducing or refining animal studies have also been routinely implemented in regulatory guidelines, where applicable. The chapter provides an overview of the implementation of 3Rs in the drafting of non-clinical testing guidelines for human medicinal products at the level of the ICH. In addition, the revision of the ICH S2 guideline on genotoxicity testing and data interpretation for pharmaceuticals intended for human use is discussed as a case study.In October 2010, the EMA established a Joint ad hoc Expert Group (JEG 3Rs) with the mandate to improve and foster the application of 3Rs principles to the regulatory testing of medicinal products throughout their lifecycle. As such, a Guideline on regulatory acceptance of 3R testing approaches was drafted that defines regulatory acceptance and provides guidance on the scientific and technical criteria for regulatory

  12. Attribute Exploration of Gene Regulatory Processes

    CERN Document Server

    Wollbold, Johannes

    2012-01-01

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

  13. Regulatory Competition in Global Financial Markets

    DEFF Research Database (Denmark)

    Ringe, Georg

    2016-01-01

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

  14. Regulatory research / Pesquisa regulatória

    Directory of Open Access Journals (Sweden)

    Altair Souza de Assis

    2013-05-01

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

  15. Regulatory mechanisms link phenotypic plasticity to evolvability.

    Science.gov (United States)

    van Gestel, Jordi; Weissing, Franz J

    2016-04-18

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

  16. Papers on the nuclear regulatory dilemma

    Energy Technology Data Exchange (ETDEWEB)

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

    1985-10-01

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

  17. The regulatory niche of intestinal stem cells.

    Science.gov (United States)

    Sailaja, Badi Sri; He, Xi C; Li, Linheng

    2016-09-01

    The niche constitutes a unique category of cells that support the microenvironment for the maintenance and self-renewal of stem cells. Intestinal stem cells reside at the base of the crypt, which contains adjacent epithelial cells, stromal cells and smooth muscle cells, and soluble and cell-associated growth and differentiation factors. We summarize here recent advances in our understanding of the crucial role of the niche in regulating stem cells. The stem cell niche maintains a balance among quiescence, proliferation and regeneration of intestinal stem cells after injury. Mesenchymal cells, Paneth cells, immune cells, endothelial cells and neural cells are important regulatory components that secrete niche ligands, growth factors and cytokines. Intestinal homeostasis is regulated by niche signalling pathways, specifically Wnt, bone morphogenetic protein, Notch and epidermal growth factor. These insights into the regulatory stem cell niche during homeostasis and post-injury regeneration offer the potential to accelerate development of therapies for intestine-related disorders.

  18. Regulatory norm”: myth or reality?

    Directory of Open Access Journals (Sweden)

    Hugo Alberto Marín Hernández

    2010-06-01

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

  19. Modeling Emergence in Neuroprotective Regulatory Networks

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-01-05

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

  20. Genomic regulatory landscapes and chromosomal rearrangements

    DEFF Research Database (Denmark)

    Ladegaard, Elisabete L Engenheiro

    2008-01-01

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

  1. Medical research misconduct need regulatory reforms.

    Science.gov (United States)

    Bedi, Neeraj

    2014-10-01

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

  2. Medical research misconduct need regulatory reforms

    Directory of Open Access Journals (Sweden)

    Neeraj Bedi

    2014-01-01

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

  3. Autophagy gets in on the regulatory act

    Institute of Scientific and Technical Information of China (English)

    Steven K. Backues; Daniel J. Klionsky

    2011-01-01

    Autophagy down-regulates the Wnt signal transduction pathway via targeted degradation of a key signaling protein. This may provide an explanation for autophagy's role in tumor suppression.%@@ The eukaryotic cell has at its disposal two primary methods for getting rid of unwanted proteins: the proteasome and autophagy.The proteasome is a large protein complex comprising regulatory and proteolytic subunits whose core function is the degradation of damaged or misfolded proteins.

  4. Responding to the changing regulatory scene

    Energy Technology Data Exchange (ETDEWEB)

    Wise, P.

    1995-12-31

    The regulatory approach of the Illinois Environmental Protection Agency (EPA) is discussed in this paper. Three areas receive emphasis: (1) the changing relations between the US EPA and the states, (2) the new emphasis on pollution prevention techniques, and (3) a new environmental amnesty project. Budgetary considerations, performance partnerships, and nonregulatory compliance assistance are briefly outlined in relation to these topics. Results of the environmental amnesty program for small business, called Clean Break, are briefly reported.

  5. Evolution of evolvability in gene regulatory networks.

    Directory of Open Access Journals (Sweden)

    Anton Crombach

    Full Text Available Gene regulatory networks are perhaps the most important organizational level in the cell where signals from the cell state and the outside environment are integrated in terms of activation and inhibition of genes. For the last decade, the study of such networks has been fueled by large-scale experiments and renewed attention from the theoretical field. Different models have been proposed to, for instance, investigate expression dynamics, explain the network topology we observe in bacteria and yeast, and for the analysis of evolvability and robustness of such networks. Yet how these gene regulatory networks evolve and become evolvable remains an open question. An individual-oriented evolutionary model is used to shed light on this matter. Each individual has a genome from which its gene regulatory network is derived. Mutations, such as gene duplications and deletions, alter the genome, while the resulting network determines the gene expression pattern and hence fitness. With this protocol we let a population of individuals evolve under Darwinian selection in an environment that changes through time. Our work demonstrates that long-term evolution of complex gene regulatory networks in a changing environment can lead to a striking increase in the efficiency of generating beneficial mutations. We show that the population evolves towards genotype-phenotype mappings that allow for an orchestrated network-wide change in the gene expression pattern, requiring only a few specific gene indels. The genes involved are hubs of the networks, or directly influencing the hubs. Moreover, throughout the evolutionary trajectory the networks maintain their mutational robustness. In other words, evolution in an alternating environment leads to a network that is sensitive to a small class of beneficial mutations, while the majority of mutations remain neutral: an example of evolution of evolvability.

  6. Adaptation by Plasticity of Genetic Regulatory Networks

    Science.gov (United States)

    Brenner, Naama

    2007-03-01

    Genetic regulatory networks have an essential role in adaptation and evolution of cell populations. This role is strongly related to their dynamic properties over intermediate-to-long time scales. We have used the budding yeast as a model Eukaryote to study the long-term dynamics of the genetic regulatory system and its significance in evolution. A continuous cell growth technique (chemostat) allows us to monitor these systems over long times under controlled condition, enabling a quantitative characterization of dynamics: steady states and their stability, transients and relaxation. First, we have demonstrated adaptive dynamics in the GAL system, a classic model for a Eukaryotic genetic switch, induced and repressed by different carbon sources in the environment. We found that both induction and repression are only transient responses; over several generations, the system converges to a single robust steady state, independent of external conditions. Second, we explored the functional significance of such plasticity of the genetic regulatory network in evolution. We used genetic engineering to mimic the natural process of gene recruitment, placing the gene HIS3 under the regulation of the GAL system. Such genetic rewiring events are important in the evolution of gene regulation, but little is known about the physiological processes supporting them and the dynamics of their assimilation in a cell population. We have shown that cells carrying the rewired genome adapted to a demanding change of environment and stabilized a population, maintaining the adaptive state for hundreds of generations. Using genome-wide expression arrays we showed that underlying the observed adaptation is a global transcriptional programming that allowed tuning expression of the recruited gene to demands. Our results suggest that non-specific properties reflecting the natural plasticity of the regulatory network support adaptation of cells to novel challenges and enhance their evolvability.

  7. XcisClique: analysis of regulatory bicliques

    Directory of Open Access Journals (Sweden)

    Grene Ruth

    2006-04-01

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

  8. Population Dynamics of Genetic Regulatory Networks

    Science.gov (United States)

    Braun, Erez

    2005-03-01

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

  9. Small regulatory RNA and Legionella pneumophila

    Directory of Open Access Journals (Sweden)

    Sebastien P Faucher

    2011-05-01

    Full Text Available Legionella pneumophila is a gram-negative bacterial species that is ubiquitous in almost any aqueous environment. It is the agent of Legionnaires’ disease, an acute and often under-reported form of pneumonia. In mammals, L. pneumophila replicates inside macrophages within a modified vacuole. Many protein regulators have been identified that control virulence-related properties, including RpoS, LetA/LetS and PmrA/PmrB. In the past few years, the importance of regulation of virulence factors by small regulatory RNA has been increasingly appreciated. This is also the case in L. pneumophila where three sRNAs (RsmY, RsmZ and 6S RNA were recently shown to be important determinants of virulence regulation and 79 actively transcribed sRNAs were identified. In this review we describe current knowledge about sRNAs and their regulatory properties and how this relates to the known regulatory systems of L. pneumophila. We also provide a model for sRNA-mediated control of gene expression that serves as a framework for understanding the regulation of virulence-related properties of L. pneumophila.

  10. The role of veterinary medicine regulatory agencies.

    Science.gov (United States)

    Smith, M V

    2013-08-01

    An effective animal medicine regulatory programme includes a systematic, evidence-based means of documenting the safety and effectiveness of products before they are produced, marketed or used in a particular country or region. The programme must also include adequate monitoring and controls over the use of these substances. It is clearthat such programmes provide veterinarians, farmers and other animal medicine users with greater assurance that veterinary drugs and biologicals will be safe and effective in preventing and mitigating disease. It is important that these regulatory controls include programmes to ensure that human food obtained from treated animals is safe and that all potential toxicological and microbiological hazards that may be associated with the use of veterinary medicines have been adequately evaluated. There is a great need worldwide for veterinary medicines that provide needed therapies for vast numbers of animals and animal species and, in the case of food-producing animals, for medicinal products that enhance the productivity and efficiency of food production and ensure food safety when they are used in accordance with their approval specifications. The public health mission of regulatory agencies succeeds when they are able to put into the hands of the user an approved, safe and effective, well-manufactured and appropriately labelled medicine, and when there are adequate controls in place to assure proper compliance.

  11. Regulatory T cells in viral hepatitis

    Institute of Scientific and Technical Information of China (English)

    Eva Billerbeck; Tobias B(o)ttler; Robert Thimme

    2007-01-01

    The pathogenesis and outcome of viral infections are significantly influenced by the host immune response.The immune system is able to eliminate many viruses in the acute phase of infection. However, some viruses,like hepatitis C virus (HCV) and hepatitis B virus (HBV),can evade the host immune responses and establish a persistent infection. HCV and HBV persistence is caused by various mechanisms, like subversion of innate immune responses by viral factors, the emergence of T cell escape mutations, or T cell dysfunction and suppression.Recently, it has become evident that regulatory T cells may contribute to the pathogenesis and outcome of viral infections by suppressing antiviral immune responses.Indeed, the control of HCV and HBV specific immune responses mediated by regulatory T cells may be one mechanism that favors viral persistence, but it may also prevent the host from overwhelming T cell activity and liver damage. This review will focus on the role of regulatory T cells in viral hepatitis.

  12. Reducing Childhood Obesity

    Science.gov (United States)

    ... the NHLBI Obesity Education Initiative. (See accompanying article, " Obesity Research: A New Approach. ") We Can! focuses on three important behaviors: improved food choices, increased physical activity, and reduced recreational screen time. ...

  13. Reduced shear power spectrum

    Energy Technology Data Exchange (ETDEWEB)

    Dodelson, Scott; /Fermilab /Chicago U., Astron. Astrophys. Ctr. /Northwestern U.; Shapiro, Charles; /Chicago U. /KICP, Chicago; White, Martin J.; /UC, Berkeley, Astron.

    2005-08-01

    Measurements of ellipticities of background galaxies are sensitive to the reduced shear, the cosmic shear divided by (1-{kappa}) where {kappa} is the projected density field. They compute the difference between shear and reduced shear both analytically and with simulations. The difference becomes more important an smaller scales, and will impact cosmological parameter estimation from upcoming experiments. A simple recipe is presented to carry out the required correction.

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

    Directory of Open Access Journals (Sweden)

    Jinki Kim

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

  15. Regulatory strategies for selected Member States (Denmark, Germany, Netherlands, Spain, the UK)

    Energy Technology Data Exchange (ETDEWEB)

    Nieuwenhout, F.D.J.; Jansen, J.C.; Van der Welle, A.J. [ECN Policy Studies, Petten (Netherlands); Olmos, L.; Cossent, R.; Gomez, T. [Universidad Pontificia Comillas, Madrid (Spain); Poot, J.; Bongaerts, M. [Liander, Duiven (Netherlands); Trebolle, D. [Union Fenosa Distribucion, Madrid (Spain); Doersam, B. [MVV Energie, Mannheim (Germany); Bofinger, S.; Lichtner, P.; Gerhardt, N. [Fraunhofer Institute for Wind Energy and Energy System Technology, IWES, Bremerhaven (Germany); Jacobsen, H.; Ropenus, S.; Schroeder, S. [Risoe National Laboratory for Sustainable Energy, Technical University of Denmark DTU, Roskilde (Denmark); Auer, H.; Weissensteiner, L.; Prueggler, W.; Obersteiner, C.; Zach, K. [Energy Economics Group EEG, Vienna University of Technology, Vienna (Austria)

    2010-05-15

    This Work Package 6 report of the IMPROGRES project provides an overview of regulatory strategies and incentives, conducive to (1) network integration of increasing levels of distributed generation including notably intermittent renewable technology such as wind power and solar photovoltaics (PV) as well as (2) options for reducing impacts on surging network integration costs. Similar to the IMPROGRES project in general, this report focuses on European distribution networks. It includes specific country studies of Denmark, Germany, the Netherlands, Spain and the UK.

  16. Reducible chiral metamaterials

    CERN Document Server

    Ciattoni, Alessandro; Rizza, Carlo

    2016-01-01

    We introduce the concept of 3D reducible metamaterials whose constituent permittivity can be modelled by a factorized profile. The separated cartesian coordinates dependence, easily achieved in all-optical reconfigurable materials, allows to physically regard a reducible metamaterial as a superposition of three fictitious 1D generating media. We prove that, in the long-wavelength limit, the electromagnetic response of reducible metamaterials can be reconstructed from the properties of the 1D generating media whose interplay provides large freedom to control the electromagnetic chirality. Our approach introduces an unprecedented decomposition strategy in metamaterial science which allows the full ab-initio and flexible design of a complex 3D bianisotropic response by using 1D metamaterials as basic building blocks.

  17. A feasibility study on regulatory analysis in the nuclear regulatory decision making process in Korea

    Energy Technology Data Exchange (ETDEWEB)

    Lee, K. J.; Lee, B. W.; Lee, D. K.; Lim, C. Y.; Choi, Y. S.; Kim, K. K. [Korea Advanced Institute of Science and Technology, Taejon (Korea, Republic of)

    1996-12-15

    Nuclear safety regulation has different implications from economic regulation. In recent survey, it was found that Korea people want more regulatory effort than current one. This indicates that scientific method is necessary to improve the efficiency of regulation with limited resources of regulators. The main reason to conduct the regulatory analysis like cost-benefit analysis is obtaining the rationality of regulation to be implemented and persuading the licensees to comply under the quantified condition. That is, the ultimate goal is to verify the necessity and justice of regulation and to achieve the safety goal with minimum impacts. Guidelines and procedures developed in this study should help regulators to reach that goal.

  18. Tank closure reducing grout

    Energy Technology Data Exchange (ETDEWEB)

    Caldwell, T.B.

    1997-04-18

    A reducing grout has been developed for closing high level waste tanks at the Savannah River Site in Aiken, South Carolina. The grout has a low redox potential, which minimizes the mobility of Sr{sup 90}, the radionuclide with the highest dose potential after closure. The grout also has a high pH which reduces the solubility of the plutonium isotopes. The grout has a high compressive strength and low permeability, which enhances its ability to limit the migration of contaminants after closure. The grout was designed and tested by Construction Technology Laboratories, Inc. Placement methods were developed by the Savannah River Site personnel.

  19. Identification of developmental regulatory genes in Aspergillus nidulans by overexpression.

    Science.gov (United States)

    Marhoul, J F; Adams, T H

    1995-02-01

    Overexpression of several Aspergillus nidulans developmental regulatory genes has been shown to cause growth inhibition and development at inappropriate times. We set out to identify previously unknown developmental regulators by constructing a nutritionally inducible A. nidulans expression library containing small, random genomic DNA fragments inserted next to the alcA promoter [alcA(p)] in an A. nidulans transformation vector. Among 20,000 transformants containing random alcA(p) genomic DNA fusion constructs, we identified 66 distinct mutant strains in which alcA(p) induction resulted in growth inhibition as well as causing other detectable phenotypic changes. These growth inhibited mutants were divided into 52 FIG (Forced expression Inhibition of Growth) and 14 FAB (Forced expression Activation of brlA) mutants based on whether or not alcA(p) induction resulted in accumulation of mRNA for the developmental regulatory gene brlA. In four FAB mutants, alcA(p) induction not only activated brlA expression but also caused hyphae to differentiate into reduced conidiophores that produced viable spores from the tips as is observed after alcA(p)::brlA induction. Sequence analyses of the DNA fragments under alcA(p) control in three of these four sporulating strains showed that in two cases developmental activation resulted from overexpression of previously uncharacterized genes, whereas in the third strain, the alcA(p) was fused to brlA. The potential uses for this strategy in identifying genes whose overexpression results in specific phenotypic changes like developmental induction are discussed.

  20. Validation of Gene Regulatory Network Inference Based on Controllability

    Directory of Open Access Journals (Sweden)

    Edward eDougherty

    2013-12-01

    Full Text Available There are two distinct issues regarding network validation: (1 Does an inferred network provide good predictions relative to experimental data? (2 Does a network inference algorithm applied within a certain network model framework yield networks that are accurate relative to some criterion of goodness? The first issue concerns scientific validation and the second concerns algorithm validation. In this paper we consider inferential validation relative to controllability; that is, if an inference procedure is applied to synthetic data generated from a gene regulatory network and an intervention procedure is designed on the inferred network, how well does it perform on the true network? The reasoning behind such a criterion is that, if our purpose is to use gene regulatory networks to design therapeutic intervention strategies, then we are not concerned with network fidelity, per se, but only with our ability to design effective interventions based on the inferred network. We will consider the problem from the perspectives of stationary control, which involves designing a control policy to be applied over time based on the current state of the network, with the decision procedure itself being time independent. {The objective of a control policy is to optimally reduce the total steady-state probability mass of the undesirable states (phenotypes, which is equivalent to optimally increasing the total steady-state mass of the desirable states. Based on this criterion we compare several proposed network inference procedures. We will see that inference procedure psi may perform poorer than inference procedure xi relative to inferring the full network structure but perform better than xi relative to controllability. Hence, when one is aiming at a specific application, it may be wise to use an objective-based measure of inference validity.

  1. Current european regulatory perspectives on insulin analogues

    Directory of Open Access Journals (Sweden)

    Enzmann Harald G

    2011-07-01

    Full Text Available Abstract Insulin analogues are increasingly considered as an alternative to human insulin in the therapy of diabetes mellitus. Insulin analogues (IAs are chemically different from human insulin and may have different pharmacokinetic or pharmacodynamic properties. The significance of the modifications of the insulin molecule for the safety profile of IAs must be considered. This review describes the regulatory procedure and the expectations for the scientific content of European marketing authorization applications for innovative IAs submitted to the European Medicines Agency. Particular consideration is given to a potential cancer hazard. Specific regulatory guidance on how to address a possible carcinogenic or tumor promoting effect of innovative IAs in non-clinical studies is available. After marketing authorization, the factual access of patients to the new product will be determined to great extent by health technology assessment bodies, reimbursement decisions and the price. Whereas the marketing authorization is a European decision, pricing and reimbursement are national or regional responsibilities. The assessment of benefit and risk by the European Medicines Agency is expected to influence future decisions on price and reimbursement on a national or regional level. Collaborations between regulatory agencies and health technology assessment bodies have been initiated on European and national level to facilitate the use of the European Medicines Agency's benefit risk assessment as basis on which to build the subsequent health technology assessment. The option for combined or joint scientific advice procedures with regulators and health technology assessment bodies on European level or on a national level in several European Member States may help applicants to optimize their development program and dossier preparation in regard of both European marketing authorization application and reimbursement decisions.

  2. Powerplant productivity improvements and regulatory incentives

    Energy Technology Data Exchange (ETDEWEB)

    Hardy, D; Brown, D

    1980-10-27

    The purpose of this study was to examine the benefits to be gained from increased powerplant productivity and to validate and demonstrate the use of incentives within the regulatory process to promote the improvement of powerplant productivity. The system-wide costs savings to be gained from given productivity improvement scenarios are estimated in both the short and long term. Numerous reports and studies exist which indicate that productivity improvements at the powerplant level are feasible and cost effective. The efforts of this study widen this focus and relate system-wide productivity improvements with system-wide cost savings. The initial thrust of the regulatory section of this study is to validate the existence of reasonable incentive procedures which would enable regulatory agencies to better motivate electric utilities to improve productivity on both the powerplant and system levels. The voluntary incentive format developed in this study was designed to facilitate the link between profit and efficiency which is typically not clear in most regulated market environments. It is concluded that at the present time, many electric utilities in this country could significantly increase the productivity of their base load units, and the adoption of an incentive program of the general type recommended in this study would add to rate of return regulation the needed financial incentives to enable utilities to make such improvements without losing long-run profit. In light of the upcoming oil import target levels and mandatory cutbacks of oil and gas as boiler fuels for electric utilities, the use of incentive programs to encourage more efficient utilization of coal and nuclear base load capacity will become far more inviting over the next two decades.

  3. Process improvement for regulatory analyses of custom-blend fertilizers.

    Science.gov (United States)

    Wegner, Keith A

    2014-01-01

    Chemical testing of custom-blend fertilizers is essential to ensure that the products meet the formulation requirements. For purposes of proper crop nutrition and consumer protection, regulatory oversight promotes compliance and particular attention to blending and formulation specifications. Analyses of custom-blend fertilizer products must be performed and reported within a very narrow window in order to be effective. The Colorado Department of Agriculture's Biochemistry Laboratory is an ISO 17025 accredited facility and conducts analyses of custom-blend fertilizer products primarily during the spring planting season. Using the Lean Six Sigma (LSS) process, the Biochemistry Laboratory has reduced turnaround times from as much as 45 days to as little as 3 days. The LSS methodology focuses on waste reduction through identifying: non-value-added steps, unneeded process reviews, optimization of screening and confirmatory analyses, equipment utilization, nonessential reporting requirements, and inefficient personnel deployment. Eliminating these non-value-added activities helped the laboratory significantly shorten turnaround time and reduce costs. Key improvement elements discovered during the LSS process included: focused sample tracking, equipment redundancy, strategic supply stocking, batch size optimization, critical sample paths, elimination of nonessential QC reviews, and more efficient personnel deployment.

  4. Regulatory T Cells in Human Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Dong-Jun Peng

    2012-01-01

    Full Text Available Multiple layers of suppressive components including regulatory T (TReg cells, suppressive antigen-presenting cells, and inhibitory cytokines form suppressive networks in the ovarian cancer microenvironment. It has been demonstrated that as a major suppressive element, TReg cells infiltrate tumor, interact with several types of immune cells, and mediate immune suppression through different molecular and cellular mechanisms. In this paper, we focus on human ovarian cancer and will discuss the nature of TReg cells including their subsets, trafficking, expansion, and function. We will briefly review the development of manipulation of TReg cells in preclinical and clinical settings.

  5. Genetic Regulatory Networks that count to 3

    DEFF Research Database (Denmark)

    Lehmann, Martin; Sneppen, K.

    2013-01-01

    Sensing a graded input and differentiating between its different levels is at the core of many developmental decisions. Here, we want to examine how this can be realized for a simple system. We model gene regulatory circuits that reach distinct states when setting the underlying gene copy number ...... in the vertebrate neural tube in a development governed by the sonic hedgehog morphogen and the more robust design of a repressilator supplemented with a weak repressilator acting in the opposite direction. © 2013 Elsevier Ltd....

  6. Learning regulatory programs by threshold SVD regression.

    Science.gov (United States)

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

    2014-11-04

    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.

  7. Gene regulatory networks governing pancreas development.

    Science.gov (United States)

    Arda, H Efsun; Benitez, Cecil M; Kim, Seung K

    2013-04-15

    Elucidation of cellular and gene regulatory networks (GRNs) governing organ development will accelerate progress toward tissue replacement. Here, we have compiled reference GRNs underlying pancreas development from data mining that integrates multiple approaches, including mutant analysis, lineage tracing, cell purification, gene expression and enhancer analysis, and biochemical studies of gene regulation. Using established computational tools, we integrated and represented these networks in frameworks that should enhance understanding of the surging output of genomic-scale genetic and epigenetic studies of pancreas development and diseases such as diabetes and pancreatic cancer. We envision similar approaches would be useful for understanding the development of other organs.

  8. Evolutionary algorithms in genetic regulatory networks model

    CERN Document Server

    Raza, Khalid

    2012-01-01

    Genetic Regulatory Networks (GRNs) plays a vital role in the understanding of complex biological processes. Modeling GRNs is significantly important in order to reveal fundamental cellular processes, examine gene functions and understanding their complex relationships. Understanding the interactions between genes gives rise to develop better method for drug discovery and diagnosis of the disease since many diseases are characterized by abnormal behaviour of the genes. In this paper we have reviewed various evolutionary algorithms-based approach for modeling GRNs and discussed various opportunities and challenges.

  9. Summary Report Panel 2: Regulatory Issues.

    Science.gov (United States)

    Johnson, Craig; Dolman, Sarah

    2016-01-01

    The Effects of Noise on Aquatic Life 2013 Conference convened four panels to discuss specific topics related to the effects of anthropogenic noise on aquatic ecosystems. The second of these four panels, the Regulatory Issues Panel, brought together several different perspectives: representatives of agencies responsible for regulating activities that introduce anthropogenic noise into aquatic ecosystems: representatives of the regulated industries, agencies, and consultancies that advise regulators and regulated industries; and nongovernmental organizations and other stakeholders with an interest in anthropogenic noise. The goal of the panel was to help develop a more productive relationship between these groups.

  10. Regulatory peptides and control of food intake in non-mammalian vertebrates.

    Science.gov (United States)

    Jensen, J

    2001-03-01

    The current view of the control of food intake involves a central feeding system in the hypothalamus receiving input from peripheral systems. The presence of food in the gut stimulates the release of several regulatory peptides that control gut motility and secretion. Some of these peptides also act as feedback satiety signals, responsible for termination of a meal. Among the regulatory peptides suggested as peripheral satiety signals are cholecystokinin and gastrin releasing peptide. A more long-term peripheral regulation of food intake has also been postulated and leptin has been suggested as a regulator of food intake. Several regulatory peptides mediate orexigenic or anorexigenic effects in the central feeding system. Neuropeptide Y and galanin both act centrally and stimulate the intake of food, while corticotropin releasing factor reduces food intake. At present, most information about the regulation of food intake is gained from mammalian studies and these findings are used as a base for a discussion on the current knowledge of how regulatory peptides control appetite in non-mammalian vertebrates.

  11. 78 FR 40237 - Self-Regulatory Organizations; NYSE MKT LLC; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2013-07-03

    ... additional information regarding the terms of an order should reduce confusion and provide for a less...-Regulatory Organization's Statement on Burden on Competition The Exchange does not believe that the proposed rule change will impose any burden on competition that is not necessary or appropriate in...

  12. 77 FR 27255 - Self-Regulatory Organizations; ICE Clear Credit LLC; Order Approving Proposed Rule Change To...

    Science.gov (United States)

    2012-05-09

    ... This rule change permits ICC to make two modifications to its risk model for clearing credit default... COMMISSION Self-Regulatory Organizations; ICE Clear Credit LLC; Order Approving Proposed Rule Change To Reduce the Current Level of Risk Mutualization Among Clearing Participants and To Modify the...

  13. T-cell suppression mediated by regulatory T cells infiltrating hepatic tumors can be overcome by GITRL treatment

    NARCIS (Netherlands)

    A. Pedroza-Gonzalez (Alexander); J. Kwekkeboom (Jaap); D. Sprengers (Dave)

    2013-01-01

    textabstractRecently, we reported the accumulation of CD4+FOXP3+ regulatory T cells (Tregs) within the tumor mass of patients bearing liver cancer. Tumor-infiltrating Tregs (TiTreg) are active and potent suppressors of antitumor immunity. Importantly, treatment with GITR L reduced the immunosuppress

  14. 76 FR 43360 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-07-20

    ... clearing services using a margin methodology approved by FINRA as announced in a Regulatory Notice (``approved margin methodology''). The Interim Pilot Program shall automatically expire on January 17, 2012... otherwise meet such definition but for being subject to individual negotiation,] include any product that...

  15. Regulatory Reform in Mexico's Gas Industry Regulatory Reform in Mexico's Gas Industry

    Directory of Open Access Journals (Sweden)

    Juan Rosellón

    1995-03-01

    Full Text Available This paper addresses the economic considerations behind the regulatory policies that are being considered after the recent reforms to the gas legal framework in Mexico. These reforms let Pemex maintain its over production but allow private investment in transportarion and distribution. The main challenge for gas regulation is Mexico is to develop a competitive structure when i the initial condition is an upstream monopoly and ii there is a dominant competitor in transportation. The paper discusses the solutions that are being designed during the elaboration of the gas regulatory framework. The main purpose is to describe how economic policy is responding to a fast evolving phenomena and to suggest topics for future research. This paper addresses the economic considerations behind the regulatory policies that are being considered after the recent reforms to the gas legal framework in Mexico. These reforms let Pemex maintain its over production but allow private investment in transportarion and distribution. The main challenge for gas regulation is Mexico is to develop a competitive structure when i the initial condition is an upstream monopoly and ii there is a dominant competitor in transportation. The paper discusses the solutions that are being designed during the elaboration of the gas regulatory framework. The main purpose is to describe how economic policy is responding to a fast evolving phenomena and to suggest topics for future research.

  16. 77 FR 1773 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2012-01-11

    ..., II, and III below, which Items have been prepared by FINRA. The Commission is publishing this notice... the Commission's Public Reference Room. II. Self-Regulatory Organization's Statement of the Purpose of... court-certified class action or a putative class action, shall not be arbitrated, unless the...

  17. Automated Identification of Core Regulatory Genes in Human Gene Regulatory Networks.

    Directory of Open Access Journals (Sweden)

    Vipin Narang

    Full Text Available Human gene regulatory networks (GRN can be difficult to interpret due to a tangle of edges interconnecting thousands of genes. We constructed a general human GRN from extensive transcription factor and microRNA target data obtained from public databases. In a subnetwork of this GRN that is active during estrogen stimulation of MCF-7 breast cancer cells, we benchmarked automated algorithms for identifying core regulatory genes (transcription factors and microRNAs. Among these algorithms, we identified K-core decomposition, pagerank and betweenness centrality algorithms as the most effective for discovering core regulatory genes in the network evaluated based on previously known roles of these genes in MCF-7 biology as well as in their ability to explain the up or down expression status of up to 70% of the remaining genes. Finally, we validated the use of K-core algorithm for organizing the GRN in an easier to interpret layered hierarchy where more influential regulatory genes percolate towards the inner layers. The integrated human gene and miRNA network and software used in this study are provided as supplementary materials (S1 Data accompanying this manuscript.

  18. 77 FR 38866 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2012-06-29

    ...-regulatory organizations (``SROs'') to do so by submitting a single form, fingerprint card and a combined... regularly enhanced the CRD system by adding features and functionality (e.g., work queues, standard reports...). Fingerprint Fees FINRA processes fingerprints submitted by members on behalf of their associated persons...

  19. Identifying Synonymous Regulatory Elements in Vertebrate Genomes

    Energy Technology Data Exchange (ETDEWEB)

    Ovcharenko, I; Nobrega, M A

    2005-02-07

    Synonymous gene regulation, defined as driving shared temporal and/or spatial expression of groups of genes, is likely predicated on genomic elements that contain similar modules of certain transcription factor binding sites (TFBS). We have developed a method to scan vertebrate genomes for evolutionary conserved modules of TFBS in a predefined configuration, and created a tool, named SynoR that identify synonymous regulatory elements (SREs) in vertebrate genomes. SynoR performs de novo identification of SREs utilizing known patterns of TFBS in active regulatory elements (REs) as seeds for genome scans. Layers of multiple-species conservation allow the use of differential phylogenetic sequence conservation filters in the search of SREs and the results are displayed as to provide an extensive annotation of genes containing detected REs. Gene Ontology categories are utilized to further functionally classify the identified genes, and integrated GNF Expression Atlas 2 data allow the cataloging of tissue-specificities of the predicted SREs. We illustrate how this new tool can be used to establish a linkage between human diseases and noncoding genomic content. SynoR is publicly available at http://synor.dcode.org.

  20. The regulatory interplay between photorespiration and photosynthesis.

    Science.gov (United States)

    Timm, Stefan; Florian, Alexandra; Fernie, Alisdair R; Bauwe, Hermann

    2016-05-01

    The Calvin-Benson cycle and the photorespiratory pathway form the photosynthetic-photorespiratory supercycle that is responsible for nearly all biological CO2 fixation on Earth. In essence, supplementation with the photorespiratory pathway is necessary because the CO2-fixing enzyme of the Calvin-Benson cycle, ribulose 1,5-bisphosphate carboxylase (Rubisco), catalyses several side reactions including the oxygenation of ribulose 1,5-bisphosphate, which produces the noxious metabolite phosphoglycolate. The photorespiratory pathway recycles the phosphoglycolate to 3-phosphoglycerate and in this way allows the Calvin-Benson cycle to operate in the presence of molecular oxygen generated by oxygenic photosynthesis. While the carbon flow through the individual and combined subprocesses is well known, information on their regulatory interaction is very limited. Regulatory feedback from the photorespiratory pathway to the Calvin-Benson cycle can be presumed from numerous inhibitor experiments and was demonstrated in recent studies with transgenic plants. This complexity illustrates that we are not yet ready to rationally engineer photosynthesis by altering photorespiration since despite massive understanding of the core photorespiratory pathway our understanding of its interaction with other pathways and processes remains fragmentary.

  1. Compressed Adjacency Matrices: Untangling Gene Regulatory Networks.

    Science.gov (United States)

    Dinkla, K; Westenberg, M A; van Wijk, J J

    2012-12-01

    We present a novel technique-Compressed Adjacency Matrices-for visualizing gene regulatory networks. These directed networks have strong structural characteristics: out-degrees with a scale-free distribution, in-degrees bound by a low maximum, and few and small cycles. Standard visualization techniques, such as node-link diagrams and adjacency matrices, are impeded by these network characteristics. The scale-free distribution of out-degrees causes a high number of intersecting edges in node-link diagrams. Adjacency matrices become space-inefficient due to the low in-degrees and the resulting sparse network. Compressed adjacency matrices, however, exploit these structural characteristics. By cutting open and rearranging an adjacency matrix, we achieve a compact and neatly-arranged visualization. Compressed adjacency matrices allow for easy detection of subnetworks with a specific structure, so-called motifs, which provide important knowledge about gene regulatory networks to domain experts. We summarize motifs commonly referred to in the literature, and relate them to network analysis tasks common to the visualization domain. We show that a user can easily find the important motifs in compressed adjacency matrices, and that this is hard in standard adjacency matrix and node-link diagrams. We also demonstrate that interaction techniques for standard adjacency matrices can be used for our compressed variant. These techniques include rearrangement clustering, highlighting, and filtering.

  2. Major regulatory mechanisms involved in sperm motility.

    Science.gov (United States)

    Pereira, Rute; Sá, Rosália; Barros, Alberto; Sousa, Mário

    2017-01-01

    The genetic bases and molecular mechanisms involved in the assembly and function of the flagellum components as well as in the regulation of the flagellar movement are not fully understood, especially in humans. There are several causes for sperm immotility, of which some can be avoided and corrected, whereas other are related to genetic defects and deserve full investigation to give a diagnosis to patients. This review was performed after an extensive literature search on the online databases PubMed, ScienceDirect, and Web of Science. Here, we review the involvement of regulatory pathways responsible for sperm motility, indicating possible causes for sperm immotility. These included the calcium pathway, the cAMP-dependent protein kinase pathway, the importance of kinases and phosphatases, the function of reactive oxygen species, and how the regulation of cell volume and osmolarity are also fundamental components. We then discuss main gene defects associated with specific morphological abnormalities. Finally, we slightly discuss some preventive and treatments approaches to avoid development of conditions that are associated with unspecified sperm immotility. We believe that in the near future, with the development of more powerful techniques, the genetic causes of sperm immotility and the regulatory mechanisms of sperm motility will be better understand, thus enabling to perform a full diagnosis and uncover new therapies.

  3. RNA regulatory elements and polyadenylation in plants

    Directory of Open Access Journals (Sweden)

    Arthur G. Hunt

    2012-01-01

    Full Text Available Alternative poly(A site choice (also known as alternative polyadenylation, or APA has the potential to affect gene expression in qualitative and quantitative ways. Alternative polyadenylation may affect as many as 82% of all expressed genes in a plant. The consequences of APA include the generation of transcripts with differing 3’-UTRs (and thus differing potential regulatory potential and of transcripts with differing protein-coding potential. Genome-wide studies of possible APA suggest a linkage with pre-mRNA splicing, and indicate a coincidence of and perhaps cooperation between RNA regulatory elements that affect splicing efficiency and the recognition of novel intronic poly(A sites. These studies also raise the possibility of the existence of a novel class of polyadenylation-related cis elements that are distinct from the well-characterized plant polyadenylation signal. Many potential APA events, however, have not been associated with identifiable cis elements. The present state of the field reveals a broad scope of APA, and also numerous opportunities for research into mechanisms that govern both choice and regulation of poly(A sites in plants.

  4. The dynamics of the transnational food chain regulatory governance

    DEFF Research Database (Denmark)

    Chatzopoulou, Sevasti

    2015-01-01

    Purpose: The need for food safety and food quality standards is acknowledged by public regulators, private actors, and the society. The purpose of this paper is to identify the types of actors in the multilevel transnational food chain regulatory governance and how their interlinking affects...... regulatory outcomes over time. Design/methodology/approach – Food chain regulatory standards emerge within a complex process beyond the state. Based on interdisciplinary theoretical perspectives, namely regulatory governance and political economy, this paper provides a integrative framework of analysis...... by identifying the types of actors and their interactions in the food chain regulatory governance. Findings – Food chain regulatory standards setting have been mainly studied either from the public regulator or the firm self-regulating point of view. This paper demonstrates how the political and economics...

  5. Reducing conspiracy theory beliefs

    Directory of Open Access Journals (Sweden)

    Stojanov Ana

    2015-01-01

    Full Text Available This study aimed to look at possible ways to reduce beliefs in conspiracy theories and increase the intention to have a fictitious child vaccinated. One hundred and sixty participants answered an online questionnaire. Three groups were used. The control group did not read any text prior to answering whereas the two experimental groups read either only debunking information or information about the motives of the conspiracists and the fallacy in their reasoning in addition to the debunking paragraph. The second experimental manipulation was effective in reducing medical conspiracy theories beliefs, but not belief in conspiracy theories in general. Neither intervention was effective in increasing the likelihood to have a fictitious child vaccinated. Those not intending to vaccinate a fictitious child endorsed conspiracy theories to a greater degree. A positive correlation between beliefs in conspiracy theories and the experiential/intuitive information processing system was found.

  6. Reduced Multiplication Modules

    Indian Academy of Sciences (India)

    Karim Samei

    2011-05-01

    An -module is called a multiplication module if for each submodule of , = for some ideal of . As defined for a commutative ring , an -module is said to be reduced if the intersection of prime submodules of is zero. The prime spectrum and minimal prime submodules of the reduced module are studied. Essential submodules of are characterized via a topological property. It is shown that the Goldie dimension of is equal to the Souslin number of Spec (). Also a finitely generated module is a Baer module if and only if Spec () is an extremally disconnected space; if and only if it is a -module. It is proved that a prime submodule is minimal in if and only if for each $x\\in N,\\mathrm{Ann}(x)\

  7. Reducing rotor weight

    Energy Technology Data Exchange (ETDEWEB)

    Cheney, M.C. [PS Enterprises, Inc., Glastonbury, CT (United States)

    1997-12-31

    The cost of energy for renewables has gained greater significance in recent years due to the drop in price in some competing energy sources, particularly natural gas. In pursuit of lower manufacturing costs for wind turbine systems, work was conducted to explore an innovative rotor designed to reduce weight and cost over conventional rotor systems. Trade-off studies were conducted to measure the influence of number of blades, stiffness, and manufacturing method on COE. The study showed that increasing number of blades at constant solidity significantly reduced rotor weight and that manufacturing the blades using pultrusion technology produced the lowest cost per pound. Under contracts with the National Renewable Energy Laboratory and the California Energy Commission, a 400 kW (33m diameter) turbine was designed employing this technology. The project included tests of an 80 kW (15.5m diameter) dynamically scaled rotor which demonstrated the viability of the design.

  8. Reducing teenage pregnancy.

    Science.gov (United States)

    Fallon, Debbie

    2011-03-01

    The Teenage Pregnancy Independent Advisory Group (TPIAG) was established in 2000 to advise the government about reducing teenage pregnancy rates and supporting teenage parents to continue with their education. The group reached the end of its tenure in December 2010. This short article highlights some of the key issues from the final report and provides some insights into past achievements and future directions from an interview with Gill Frances, TPIAG's chair.

  9. Reducing medication errors.

    Science.gov (United States)

    Nute, Christine

    2014-11-25

    Most nurses are involved in medicines management, which is integral to promoting patient safety. Medicines management is prone to errors, which depending on the error can cause patient injury, increased hospital stay and significant legal expenses. This article describes a new approach to help minimise drug errors within healthcare settings where medications are prescribed, dispensed or administered. The acronym DRAINS, which considers all aspects of medicines management before administration, was devised to reduce medication errors on a cardiothoracic intensive care unit.

  10. Awareness Reduces Racial Bias

    OpenAIRE

    2014-01-01

    Can raising awareness of racial bias subsequently reduce that bias? We address this question by exploiting the widespread media attention highlighting racial bias among professional basketball referees that occurred in May 2007 following the release of an academic study. Using new data, we confirm that racial bias persisted in the years after the study's original sample, but prior to the media coverage. Subsequent to the media coverage though, the bias completely disappeared. We examine poten...

  11. Reducing Iatrogenic Risks

    Science.gov (United States)

    Ely, E. Wesley; Speroff, Theodore; Pun, Brenda T.; Boehm, Leanne; Dittus, Robert S.

    2010-01-01

    ICUs are experiencing an epidemic of patients with acute brain dysfunction (delirium) and weakness, both associated with increased mortality and long-term disability. These conditions are commonly acquired in the ICU and are often initiated or exacerbated by sedation and ventilation decisions and management. Despite > 10 years of evidence revealing the hazards of delirium, the quality chasm between current and ideal processes of care continues to exist. Monitoring of delirium and sedation levels remains inconsistent. In addition, sedation, ventilation, and physical therapy practices proven successful at reducing the frequency and severity of adverse outcomes are not routinely practiced. In this article, we advocate for the adoption and implementation of a standard bundle of ICU measures with great potential to reduce the burden of ICU-acquired delirium and weakness. Individual components of this bundle are evidence based and can help standardize communication, improve interdisciplinary care, reduce mortality, and improve cognitive and functional outcomes. We refer to this as the “ABCDE bundle,” for awakening and breathing coordination, delirium monitoring, and exercise/early mobility. This evidence-based bundle of practices will build a bridge across the current quality chasm from the “front end” to the “back end” of critical care and toward improved cognitive and functional outcomes for ICU survivors. PMID:21051398

  12. Gradual extinction reduces Reinstatement

    Directory of Open Access Journals (Sweden)

    Youssef eShiban

    2015-09-01

    Full Text Available The current study investigated whether gradually reducing the frequency of aversive stimuli during extinction can prevent the return of fear. Thirty-one participants of a three-stage procedure (acquisition, extinction and a reinstatement test on day two were randomly assigned to a standard extinction (SE and gradual extinction (GE procedure. The two groups differed only in the extinction procedure. While the SE group ran through a regular extinction process without any negative events, the frequency of the aversive stimuli during the extinction phase was gradually reduced for the GE group. The unconditioned stimulus was an air blast (5 bar, 10 ms. A spider and a scorpion were used as conditioned stimuli. The outcome variables were contingency ratings and physiological measures (skin conductance response and startle response. There were no differences found between the two groups for the acquisition and extinction phases concerning contingency ratings, SCR, or startle response. Gradual extinction compared to standard extinction significantly reduced the return of fear in the reinstatement test for the startle response but not for skin conductance response or contingency ratings. This study was successful in translating the findings in rodent to humans. The results suggest that the gradual extinction process is suitable for increasing the efficacy of fear extinction.

  13. Environmental regulatory update table: September/October 1994

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-11-01

    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 bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  14. Environmental regulatory update table, July/August 1994

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-09-01

    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 bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  15. Environmental regulatory update table, March--April 1994

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Bock, R.E. [Oak Ridge National Lab., TN (United States). Health Sciences Research Div.; Salk, M.S. [Oak Ridge National Lab., TN (United States). Environmental Sciences Div.

    1994-03-01

    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 bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  16. Environmental Regulatory Update Table, September/October 1993

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.; Danford, G.S.; Lewis, E.B.

    1993-11-01

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

  17. Environmental regulatory update table, September--October 1992

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Lewis, E.B.; Salk, M.S.

    1992-11-01

    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 bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  18. Environmental Regulatory Update Table, January/February 1992

    Energy Technology Data Exchange (ETDEWEB)

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

    1992-03-01

    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 bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action. This table is for January/February 1992.

  19. Environmental Regulatory Update Table, November--December 1992

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Lewis, E.B.; Salk, M.S.

    1993-01-01

    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 bi-monthly wit 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, January--February 1993

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.; Danford, G.S.; Lewis, E.B.

    1993-03-01

    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 bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  1. Environmental Regulatory Update Table, July--August 1992

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Lewis, E.B.; Salk, M.S.

    1992-09-01

    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 bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  2. PRIVATE REGULATORY LEGAL ACTS IN THE RUSSIAN FEDERATION

    OpenAIRE

    Magomedov, Ruslan

    2014-01-01

    Regulatory legal acts possess certain characteristics, the presence of which determines their qualities. Historically the development of forms of law in the world followed various tracks, which led to appearance of several legal systems. That is why the notion and the meaning of regulatory legal acts in them does not always coincide. This article presents a notion of private regulatory legal acts and an issue of their presence in the Russian legal system. In that context a notion of regulator...

  3. Environmental Regulatory Update Table, March/April 1993. Revision 1

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.; Danford, G.S.; Lewis, E.B.

    1993-05-01

    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 bimonthly 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, November--December 1993

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.; Danford, G.S.; Lewis, E.B.

    1994-01-01

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

  5. Environmental Regulatory Update Table, May--June 1994

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-07-01

    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 bimonthly 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/April 1993

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.; Danford, G.S.; Lewis, E.B.

    1993-05-01

    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 bimonthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  7. Environmental Regulatory Update Table July/August 1993

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.; Danford, G.S.; Lewis, E.B.

    1993-09-01

    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 bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  8. Environmental Regulatory Update Table, May/June 1993

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.; Danford, G.S.; Lewis, E.B.

    1993-07-01

    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 bimonthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  9. Environmental Regulatory Update Table, January--February 1994

    Energy Technology Data Exchange (ETDEWEB)

    Houlberg, L.M.; Hawkins, G.T.; Salk, M.S.; Danford, G.S.; Lewis, E.B.

    1994-03-01

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

  10. Recombinant biologic products versus nutraceuticals from plants - a regulatory choice?

    Science.gov (United States)

    Drake, Pascal M W; Szeto, Tim H; Paul, Mathew J; Teh, Audrey Y-H; Ma, Julian K-C

    2017-01-01

    Biotechnology has transformed the potential for plants to be a manufacturing source of pharmaceutical compounds. Now, with transgenic and transient expression techniques, virtually any biologic, including vaccines and therapeutics, could be manufactured in plants. However, uncertainty over the regulatory path for such new pharmaceuticals has been a deterrent. Consideration has been given to using alternative regulatory paths, including those for nutraceuticals or cosmetic agents. This review will consider these possibilities, and discuss the difficulties in establishing regulatory guidelines for new pharmaceutical manufacturing technologies.

  11. Information resources in state regulatory agencies-a California perspective

    Energy Technology Data Exchange (ETDEWEB)

    DiZio, S.M. [California Environmental Protection Agency, Sacramento (United States)

    1990-12-31

    Various state regulatory agencies have expressed a need for networking with information gatherers/researchers to produce a concise compilation of primary information so that the basis for regulatory standards can be scientifically referenced. California has instituted several programs to retrieve primary information, generate primary information through research, and generate unique regulatory standards by integrating the primary literature and the products of research. This paper describes these programs.

  12. Environmental Regulatory Update Table, March/April 1992

    Energy Technology Data Exchange (ETDEWEB)

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

    1992-05-01

    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 bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  13. Environmental regulatory update table November--December 1994

    Energy Technology Data Exchange (ETDEWEB)

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

    1995-01-01

    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 bi-monthly with information from the Federal Register and other sources, including direct contact with regulatory agencies. Each table entry provides a chronological record of the rulemaking process for that initiative with an abstract and a projection of further action.

  14. Environmental sciences division: Environmental regulatory update table July 1988

    Energy Technology Data Exchange (ETDEWEB)

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

    1988-08-01

    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.

  15. Schistosomes induce regulatory features in human and mouse CD1d(hi B cells: inhibition of allergic inflammation by IL-10 and regulatory T cells.

    Directory of Open Access Journals (Sweden)

    Luciën E P M van der Vlugt

    Full Text Available Chronic helminth infections, such as schistosomes, are negatively associated with allergic disorders. Here, using B cell IL-10-deficient mice, Schistosoma mansoni-mediated protection against experimental ovalbumin-induced allergic airway inflammation (AAI was shown to be specifically dependent on IL-10-producing B cells. To study the organs involved, we transferred B cells from lungs, mesenteric lymph nodes or spleen of OVA-infected mice to recipient OVA-sensitized mice, and showed that both lung and splenic B cells reduced AAI, but only splenic B cells in an IL-10-dependent manner. Although splenic B cell protection was accompanied by elevated levels of pulmonary FoxP3(+ regulatory T cells, in vivo ablation of FoxP3(+ T cells only moderately restored AAI, indicating an important role for the direct suppressory effect of regulatory B cells. Splenic marginal zone CD1d(+ B cells proved to be the responsible splenic B cell subset as they produced high levels of IL-10 and induced FoxP3(+ T cells in vitro. Indeed, transfer of CD1d(+ MZ-depleted splenic B cells from infected mice restored AAI. Markedly, we found a similarly elevated population of CD1d(hi B cells in peripheral blood of Schistosoma haematobium-infected Gabonese children compared to uninfected children and these cells produced elevated levels of IL-10. Importantly, the number of IL-10-producing CD1d(hi B cells was reduced after anti-schistosome treatment. This study points out that in both mice and men schistosomes have the capacity to drive the development of IL-10-producing regulatory CD1d(hi B cells and furthermore, these are instrumental in reducing experimental allergic inflammation in mice.

  16. Identifying cis-regulatory sequences by word profile similarity.

    Directory of Open Access Journals (Sweden)

    Garmay Leung

    Full Text Available BACKGROUND: Recognizing regulatory sequences in genomes is a continuing challenge, despite a wealth of available genomic data and a growing number of experimentally validated examples. METHODOLOGY/PRINCIPAL FINDINGS: We discuss here a simple approach to search for regulatory sequences based on the compositional similarity of genomic regions and known cis-regulatory sequences. This method, which is not limited to searching for predefined motifs, recovers sequences known to be under similar regulatory control. The words shared by the recovered sequences often correspond to known binding sites. Furthermore, we show that although local word profile clustering is predictive for the regulatory sequences involved in blastoderm segmentation, local dissimilarity is a more universal feature of known regulatory sequences in Drosophila. CONCLUSIONS/SIGNIFICANCE: Our method leverages sequence motifs within a known regulatory sequence to identify co-regulated sequences without explicitly defining binding sites. We also show that regulatory sequences can be distinguished from surrounding sequences by local sequence dissimilarity, a novel feature in identifying regulatory sequences across a genome. Source code for WPH-finder is available for download at http://rana.lbl.gov/downloads/wph.tar.gz.

  17. Regulatory Models and the Environment: Practice, Pitfalls, and Prospects

    Energy Technology Data Exchange (ETDEWEB)

    Holmes, K. John; Graham, Judith A.; McKone, Thomas; Whipple, Chris

    2008-06-01

    Computational models support environmental regulatory activities by providing the regulator an ability to evaluate available knowledge, assess alternative regulations, and provide a framework to assess compliance. But all models face inherent uncertainties, because human and natural systems are always more complex and heterogeneous than can be captured in a model. Here we provide a summary discussion of the activities, findings, and recommendations of the National Research Council's Committee on Regulatory Environmental Models, a committee funded by the US Environmental Protection Agency to provide guidance on the use of computational models in the regulatory process. Modeling is a difficult enterprise even outside of the potentially adversarial regulatory environment. The demands grow when the regulatory requirements for accountability, transparency, public accessibility, and technical rigor are added to the challenges. Moreover, models cannot be validated (declared true) but instead should be evaluated with regard to their suitability as tools to address a specific question. The committee concluded that these characteristics make evaluation of a regulatory model more complex than simply comparing measurement data with model results. Evaluation also must balance the need for a model to be accurate with the need for a model to be reproducible, transparent, and useful for the regulatory decision at hand. Meeting these needs requires model evaluation to be applied over the"life cycle" of a regulatory model with an approach that includes different forms of peer review, uncertainty analysis, and extrapolation methods than for non-regulatory models.

  18. Dynamics of network motifs in genetic regulatory networks

    Institute of Scientific and Technical Information of China (English)

    Li Ying; Liu Zeng-Rong; Zhang Jian-Bao

    2007-01-01

    Network motifs hold a very important status in genetic regulatory networks. This paper aims to analyse the dynamical property of the network motifs in genetic regulatory networks. The main result we obtained is that the dynamical property of a single motif is very simple with only an asymptotically stable equilibrium point, but the combination of several motifs can make more complicated dynamical properties emerge such as limit cycles. The above-mentioned result shows that network motif is a stable substructure in genetic regulatory networks while their combinations make the genetic regulatory network more complicated.

  19. 2012 Global Summit on Regulatory Science (GSRS-2012)--modernizing toxicology.

    Science.gov (United States)

    Miller, Margaret A; Tong, Weida; Fan, Xiaohui; Slikker, William

    2013-01-01

    Regulatory science encompasses the tools, models, techniques, and studies needed to assess and evaluate product safety, efficacy, quality, and performance. Several recent publications have emphasized the role of regulatory science in improving global health, supporting economic development and fostering innovation. As for other scientific disciplines, research in regulatory science is the critical element underpinning the development and advancement of regulatory science as a modern scientific discipline. As a regulatory agency in the 21st century, the Food and Drug Administration (FDA) has an international component that underpins its domestic mission; foods, drugs, and devices are developed and imported to the United States from across the world. The Global Summit on Regulatory Science, an international conference for discussing innovative technologies, approaches, and partnerships that enhance the translation of basic science into regulatory applications, is providing leadership for the advancement of regulatory sciences within the global context. Held annually, this international conference provides a platform where regulators, policy makers, and bench scientists from various countries can exchange views on how to develop, apply, and implement innovative methodologies into regulatory assessments in their respective countries, as well as developing a harmonized strategy to improve global public health through global collaboration.

  20. Regulatory relations represented in logics and biomedical texts

    DEFF Research Database (Denmark)

    Zambach, Sine

    Regulatory networks are used for simple modeling of varying complexity, for example within biology, economics and other elds that apply dynamic systems. In biomedicine, regulatory networks are widely used to model regulatory pathways, which, in short, are characterized by processes containing gene...... products and smaller molecules that regulate each other through dierent mechanisms through dierent paths. The relations between the building blocks of these networks are typically modeled either very expressively or very simply in graphs in information systems. The focus of this dissertation...... of information services on regulatory events within biomedicine....

  1. Global Regulatory Pathways in the Alphaproteobacteria

    Energy Technology Data Exchange (ETDEWEB)

    none

    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

  2. The regulatory epicenter of miRNAs

    Indian Academy of Sciences (India)

    Ashwani Jha; Mrigaya Mehra; Ravi Shankar

    2011-09-01

    miRNAs are small non-coding RNAs with average length of ∼21 bp. miRNA formation seems to be dependent upon multiple factors besides Drosha and Dicer, in a tissue/stage-specific manner, with interplay of several specific binding factors. In the present study, we have investigated transcription factor binding sites in and around the genomic sequences of precursor miRNAs and RNA-binding protein (RBP) sites in miRNA precursor sequences, analysed and tested in comprehensive manner. Here, we report that miRNA precursor regions are positionally enriched for binding of transcription factors as well as RBPs around the 3′ end of mature miRNA region in 5′ arm. The pattern and distribution of such regulatory sites appears to be a characteristic of precursor miRNA sequences when compared with non-miRNA sequences as negative dataset and tested statistically. When compared with 1 kb upstreamregions, a sudden sharp peak for binding sites arises in the enriched zone near the mature miRNA region. An expression-data-based correlation analysis was performed between such miRNAs and their corresponding transcription factors and RBPs for this region. Some specific groups of binding factors and associated miRNAs were identified. We also identified some of the overrepresented transcription factors and associated miRNAs with high expression correlation values which could be useful in cancer-related studies. The highly correlated groups were found to host experimentally validated composite regulatory modules, in which Lmo2-GATA1 appeared as the predominant one. For many of RBP–miRNAs associations, co-expression similarity was also evident among the associated miRNA common to given RBPs, supporting the Regulon model, suggesting a common role and common control of these miRNAs by the associated RBPs. Based on our findings, we propose that the observed characteristic distribution of regulatory sites in precursor miRNA sequence regions could be critical inmiRNA transcription, processing

  3. Dynamic simulation of regulatory networks using SQUAD

    Directory of Open Access Journals (Sweden)

    Xenarios Ioannis

    2007-11-01

    Full Text Available Abstract Background The ambition of most molecular biologists is the understanding of the intricate network of molecular interactions that control biological systems. As scientists uncover the components and the connectivity of these networks, it becomes possible to study their dynamical behavior as a whole and discover what is the specific role of each of their components. Since the behavior of a network is by no means intuitive, it becomes necessary to use computational models to understand its behavior and to be able to make predictions about it. Unfortunately, most current computational models describe small networks due to the scarcity of kinetic data available. To overcome this problem, we previously published a methodology to convert a signaling network into a dynamical system, even in the total absence of kinetic information. In this paper we present a software implementation of such methodology. Results We developed SQUAD, a software for the dynamic simulation of signaling networks using the standardized qualitative dynamical systems approach. SQUAD converts the network into a discrete dynamical system, and it uses a binary decision diagram algorithm to identify all the steady states of the system. Then, the software creates a continuous dynamical system and localizes its steady states which are located near the steady states of the discrete system. The software permits to make simulations on the continuous system, allowing for the modification of several parameters. Importantly, SQUAD includes a framework for perturbing networks in a manner similar to what is performed in experimental laboratory protocols, for example by activating receptors or knocking out molecular components. Using this software we have been able to successfully reproduce the behavior of the regulatory network implicated in T-helper cell differentiation. Conclusion The simulation of regulatory networks aims at predicting the behavior of a whole system when subject

  4. Risk-informed assessment of regulatory and design requirements for future nuclear power plants. Annual report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-08-01

    OAK B188 Risk-informed assessment of regulatory and design requirements for future nuclear power plants. Annual report. The overall goal of this research project is to support innovation in new nuclear power plant designs. This project is examining the implications, for future reactors and future safety regulation, of utilizing a new risk-informed regulatory system as a replacement for the current system. This innovation will be made possible through development of a scientific, highly risk-formed approach for the design and regulation of nuclear power plants. This approach will include the development and/or confirmation of corresponding regulatory requirements and industry standards. The major impediment to long term competitiveness of new nuclear plants in the U.S. is the capital cost component--which may need to be reduced on the order of 35% to 40% for Advanced Light Water Reactors (ALWRS) such as System 80+ and Advanced Boiling Water Reactor (ABWR). The required cost reduction for an ALWR such as AP600 or AP1000 would be expected to be less. Such reductions in capital cost will require a fundamental reevaluation of the industry standards and regulatory bases under which nuclear plants are designed and licensed. Fortunately, there is now an increasing awareness that many of the existing regulatory requirements and industry standards are not significantly contributing to safety and reliability and, therefore, are unnecessarily adding to nuclear plant costs. Not only does this degrade the economic competitiveness of nuclear energy, it results in unnecessary costs to the American electricity consumer. While addressing these concerns, this research project will be coordinated with current efforts of industry and NRC to develop risk-informed, performance-based regulations that affect the operation of the existing nuclear plants; however, this project will go further by focusing on the design of new plants.

  5. Daily subcutaneous injections of peptide induce CD4+ CD25+ T regulatory cells.

    Science.gov (United States)

    Dahlberg, P E; Schartner, J M; Timmel, A; Seroogy, C M

    2007-08-01

    Peptide immunotherapy is being explored to modulate varied disease states; however, the mechanism of action remains poorly understood. In this study, we investigated the ability of a subcutaneous peptide immunization schedule to induce of CD4(+) CD25(+) T regulatory cells. DO11.10 T cell receptor (TCR) transgenic mice on a Rag 2(-/-) background were injected subcutaneously with varied doses of purified ovalbumin (OVA(323-339)) peptide daily for 16 days. While these mice have no CD4(+) CD25(+) T regulatory cells, following this injection schedule up to 30% of the CD4(+) cells were found to express CD25. Real-time quantitative polymerase chain reaction (QPCR) analysis of the induced CD4(+) CD25(+) T cells revealed increased expression of forkhead box P3 (FoxP3), suggesting that these cells may have a regulatory function. Proliferation and suppression assays in vitro utilizing the induced CD4(+) CD25(+) T cells revealed a profound anergic phenotype in addition to potent suppressive capability. Importantly, co-injection of the induced CD4(+) CD25(+) T cells with 5,6-carboxy-succinimidyl-fluorescence-ester (CFSE)-labelled naive CD4(+) T cells (responder cells) into BALB/c recipient mice reduced proliferation and differentiation of the responder cells in response to challenge with OVA(323-339) peptide plus adjuvant. We conclude that repeated subcutaneous exposure to low-dose peptide leads to de novo induction of CD4(+) CD25(+) FoxP3(+) T regulatory cells with potent in vitro and in vivo suppressive capability, thereby suggesting that one mechanism of peptide immunotherapy appears to be induction of CD4(+) CD25(+) Foxp3(+) T regulatory cells.

  6. Manipulation of Regulatory Cells’ Responses to Treatments for Chronic Hepatitis B Virus Infection

    Science.gov (United States)

    Tavakolpour, Soheil; Alavian, Seyed Moayed; Sali, Shahnaz

    2016-01-01

    Background Identification of effective treatments in hepatitis B virus (HBV) infection remains a controversial topic. Although the currently approved drugs for HBV control the disease’s progression and also limit associated outcomes, these drugs may not fully eradicate HBV infection. In addition to better managing patients with chronic hepatitis B (CHB) infection, the induction of seroclearance by these drugs has been a commonly discussed topic in recent years. Objectives In this study, we focused on treating CHB infection via the manipulation of T cells’ responses to identify possible approaches to cure CHB. Materials and Methods All studies relevant to the role of cellular and humoral responses in HBV infection (especially regulatory cells) were investigated via a systematic search of different databases, including PubMed, Scopus, and Google Scholar. Considering extracted data and also our unpublished data regarding the association between regulatory cytokines and CHB, we introduced a novel approach for the induction of seroclearance. Results Considering the increased levels of regulatory cytokines and also regulatory T cells (Tregs) during CHB, it seems that these cells are deeply involved in CHB infection. The inhibition of regulatory T cells may reverse the dysfunction of effector T cells in patients with CHB infection. In order to inhibit Tregs’ responses, different types of approaches could be employed to restore the impaired function of effector T cells. The blockade of IL-10, IL-35, CTLA-4, PD-1, and TIM-3 were discussed throughout this study. Regardless of the efficacy of these methods, CHB patients may experience serious liver injuries due to the cytotoxic action of CD8+ T cells. Antiviral therapy and a decrease in HBV DNA to undetectable levels could also significantly reduce the risk of the hepatitis B flare. Conclusions The inhibition of Tregs is a novel therapeutic approach to cure chronically HBV infected patients. However, further studies are

  7. Prebiotics and the health benefits of fiber: current regulatory status, future research, and goals.

    Science.gov (United States)

    Brownawell, Amy M; Caers, Wim; Gibson, Glenn R; Kendall, Cyril W C; Lewis, Kara D; Ringel, Yehuda; Slavin, Joanne L

    2012-05-01

    First defined in the mid-1990s, prebiotics, which alter the composition and activity of gastrointestinal (GI) microbiota to improve health and well-being, have generated scientific and consumer interest and regulatory debate. The Life Sciences Research Organization, Inc. (LSRO) held a workshop, Prebiotics and the Health Benefits of Fiber: Future Research and Goals, in February 2011 to assess the current state of the science and the international regulatory environment for prebiotics, identify research gaps, and create a strategy for future research. A developing body of evidence supports a role for prebiotics in reducing the risk and severity of GI infection and inflammation, including diarrhea, inflammatory bowel disease, and ulcerative colitis as well as bowel function disorders, including irritable bowel syndrome. Prebiotics also increase the bioavailability and uptake of minerals and data suggest that they reduce the risk of obesity by promoting satiety and weight loss. Additional research is needed to define the relationship between the consumption of different prebiotics and improvement of human health. New information derived from the characterization of the composition and function of different prebiotics as well as the interactions among and between gut microbiota and the human host would improve our understanding of the effects of prebiotics on health and disease and could assist in surmounting regulatory issues related to prebiotic use.

  8. Adenylyl cyclase plays a regulatory role in development, stress resistance and secondary metabolism in Fusarium fujikuroi.

    Directory of Open Access Journals (Sweden)

    Jorge García-Martínez

    Full Text Available The ascomycete fungus Fusarium fujikuroi (Gibberella fujikuroi MP-C produces secondary metabolites of biotechnological interest, such as gibberellins, bikaverin, and carotenoids. Production of these metabolites is regulated by nitrogen availability and, in a specific manner, by other environmental signals, such as light in the case of the carotenoid pathway. A complex regulatory network controlling these processes is recently emerging from the alterations of metabolite production found through the mutation of different regulatory genes. Here we show the effect of the targeted mutation of the acyA gene of F. fujikuroi, coding for adenylyl cyclase. Mutants lacking the catalytic domain of the AcyA protein showed different phenotypic alterations, including reduced growth, enhanced production of unidentified red pigments, reduced production of gibberellins and partially derepressed carotenoid biosynthesis in the dark. The phenotype differs in some aspects from that of similar mutants of the close relatives F. proliferatum and F. verticillioides: contrary to what was observed in these species, ΔacyA mutants of F. fujikuroi showed enhanced sensitivity to oxidative stress (H(2O(2, but no change in heavy metal resistance or in the ability to colonize tomato tissue, indicating a high versatility in the regulatory roles played by cAMP in this fungal group.

  9. Reduced Google matrix

    CERN Document Server

    Frahm, K M

    2016-01-01

    Using parallels with the quantum scattering theory, developed for processes in nuclear and mesoscopic physics and quantum chaos, we construct a reduced Google matrix $G_R$ which describes the properties and interactions of a certain subset of selected nodes belonging to a much larger directed network. The matrix $G_R$ takes into account effective interactions between subset nodes by all their indirect links via the whole network. We argue that this approach gives new possibilities to analyze effective interactions in a group of nodes embedded in a large directed networks. Possible efficient numerical methods for the practical computation of $G_R$ are also described.

  10. Modelling reduced sparse data

    Science.gov (United States)

    Kozera, Ryszard; Noakes, Lyle

    2016-09-01

    In this paper we discuss the problem of fitting to an ordered collection of points in arbitary Euclidean space called reduced data. We are not given here the corresponding interpolation knots. Instead, these are estimated by new knots upon minimizing a relevant highly nonlinear optimization scheme based on natural spline interpolation. The existence of a global minimizer (i.e. the collection of interpolation knots in ascending order) is also addressed in this paper. Finally, Leap-Frog optimization tool is used to compute these knots approximating the unknown interpolation knots. This numerical scheme is subsequently compared with the Secant Method. Two illustrative examples are given.

  11. Nonlinearity-reduced interferometer

    Science.gov (United States)

    Wu, Chien-ming

    2007-12-01

    Periodic nonlinearity is a systematic error limiting the accuracy of displacement measurements at the nanometer level. It results from many causes such as the frequency mixing, polarization mixing, polarization-frequency mixing, and the ghost reflections. An interferometer having accuracy in displacement measurement of less than one-nanometer is necessary in nanometrology. To meet the requirement, the periodic nonlinearity should be less than deep sub-nanometer. In this paper, a nonlinearity-reduced interferometry has been proposed. Both the linear- and straightness-interferometer were tested. The developed interferometer demonstrated of a residual nonlinearity less than 25 pm.

  12. Advances in ambulatory monitoring: regulatory considerations.

    Science.gov (United States)

    Buckles, David; Aguel, Felipe; Brockman, Randall; Cheng, James; Demian, Cindy; Ho, Charles; Jensen, Donald; Mallis, Elias

    2004-01-01

    Conventional ambulatory electrocardiogram (ECG) (Holter) monitoring involves 2 or 3 surface leads recorded with electrode positions and signal characteristics that are different from diagnostic quality 12-lead ECGs due to the limitations imposed by technology on the ambulatory recorders. The rapid pace of technological development for medical devices, particularly electrocardiography, has now enabled the recording of diagnostic quality 12-lead ECG waveforms for extended time periods. This capability allows Holter recording to become another source for diagnostic 12-lead ECG records on a par with other modalities such as resting ECG and exercise stress testing. Additionally, other diagnostic techniques such as S-T segment analysis and Q-T interval analysis that rely on diagnostic quality waveforms can now be applied. All of these enhancements to the traditional Holter modality have altered the regulatory perspective of these devices, since the enhancements may represent a new intended use for the device.

  13. Modeling genomic regulatory networks with big data.

    Science.gov (United States)

    Bolouri, Hamid

    2014-05-01

    High-throughput sequencing, large-scale data generation projects, and web-based cloud computing are changing how computational biology is performed, who performs it, and what biological insights it can deliver. I review here the latest developments in available data, methods, and software, focusing on the modeling and analysis of the gene regulatory interactions in cells. Three key findings are: (i) although sophisticated computational resources are increasingly available to bench biologists, tailored ongoing education is necessary to avoid the erroneous use of these resources. (ii) Current models of the regulation of gene expression are far too simplistic and need updating. (iii) Integrative computational analysis of large-scale datasets is becoming a fundamental component of molecular biology. I discuss current and near-term opportunities and challenges related to these three points.

  14. Regulatory environment and claims - limits and opportunities.

    Science.gov (United States)

    Martin, Ambroise

    2010-01-01

    During the past decade, the use of claims became more and more important in many countries in relation to the increased awareness of consumer about the link between foods and health, offering to industry a valuable opportunity to differentiate and valorize their products and to promote innovation. However, more and more stringent regulations are developed, all based on the general principles adopted by the Codex Alimentarius Commission. In addition to the different regulatory processes and administrative requirements according to the country, the high level (and cost) of scientific substantiation of claims, the constraints introduced by nutrient profiles and the poor knowledge of the impact on consumer depending on the cultural contexts may limit these opportunities or, at least complicate their use. All these issues are briefly analyzed, highlighting some striking convergences and differences between countries.

  15. REGULATORY T–CELLS: ORIGIN AND FUNCTION

    Directory of Open Access Journals (Sweden)

    I. S. Freidlin

    2005-01-01

    Full Text Available Abstract. Over the past decade a population of so–called “regulatory T cells” (Treg cells has been linked to the prevention of autoimmunity. In this review we discuss the molecular mechanisms of Treg cells development and function including the identification of the unique molecular marker of Treg cells – the transcription factor Foxp3. We discuss also the mechanisms of suppression, which include the direct cell contact through binding of cell surface molecules CTLA–4 on Treg cells to CD80/CD86 molecules of effector T cells and the local secretion of cytokines (IL–10, TGFβ. Deficiency in or dysfunction of these cells can be a cause of autoimmune disease. These cells are a good target for designing ways to induce or abrogate immunological tolerance to self and non–self antigens. (Med. Immunol., 2005, vol.7, № 4, pp. 347–354

  16. Uterus transplantation: ethical and regulatory challenges.

    Science.gov (United States)

    Arora, Kavita Shah; Blake, Valarie

    2014-06-01

    Moving forward rapidly in the clinical research phase, uterus transplantation may be a future treatment option for women with uterine factor infertility, which accounts for three per cent of all infertility in women. This new method of treatment would allow women, who currently rely on gestational surrogacy or adoption, to gestate and birth their own genetic offspring. Since uterus transplantation carries significant risk when compared with surrogacy and adoption as well as when compared with other organ transplants, it requires greater justification because its goals are quality of life, not life-saving, in their scope. It is important to address questions regarding the physical, psychosocial and ethical risks and benefits of uterus transplantation for all three parties involved--the patient, the donor and the potential child--as well as discuss the regulatory implications as research on uterus transplantations moves forward.

  17. Regulatory and Economic Considerations of Retinal Drugs.

    Science.gov (United States)

    Shah, Ankoor R; Williams, George A

    2016-01-01

    The advent of anti-VEGF therapy for neovascular age-related macular degeneration and macular edema secondary to retinal vein occlusion and diabetes mellitus has prevented blindness in tens of thousands of people. However, the costs of these drugs are without precedent in ophthalmic drug therapeutics. An analysis of the financial implications of retinal drugs and the impact of the Food and Drug Administration on treatment of retinal disease must include not only an evaluation of the direct costs of the drugs and the costs associated with their administration, but also the cost savings which accrue from their clinical benefit. This chapter will discuss the financial and regulatory issues associated with retinal drugs.

  18. Vaccines in Argentina: a regulatory view.

    Science.gov (United States)

    Pérez, A C; Diez, R A

    2003-07-28

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

  19. Ethical and regulatory aspects of genome editing.

    Science.gov (United States)

    Kohn, Donald B; Porteus, Matthew H; Scharenberg, Andrew M

    2016-05-26

    Gene editing is a rapidly developing area of biotechnology in which the nucleotide sequence of the genome of living cells is precisely changed. The use of genome-editing technologies to modify various types of blood cells, including hematopoietic stem cells, has emerged as an important field of therapeutic development for hematopoietic disease. Although these technologies offer the potential for generation of transformative therapies for patients suffering from myriad disorders of hematopoiesis, their application for therapeutic modification of primary human cells is still in its infancy. Consequently, development of ethical and regulatory frameworks that ensure their safe and effective use is an increasingly important consideration. Here, we review a number of issues that have the potential to impact the clinical implementation of genome-editing technologies, and suggest paths forward for resolving them such that new therapies can be safely and rapidly translated to the clinic.

  20. Multiphoton imaging of renal regulatory mechanisms.

    Science.gov (United States)

    Peti-Peterdi, János; Toma, Ildikó; Sipos, Arnold; Vargas, Sarah L

    2009-04-01

    Most physiological functions of the kidneys, including the clearance of metabolic waste products, maintenance of body fluid, electrolyte homeostasis, and blood pressure, are achieved by complex interactions between multiple renal cell types and previously inaccessible structures in many organ parts that have been difficult to study. Multiphoton fluorescence microscopy offers a state-of-the-art imaging technique for deep optical sectioning of living tissues and organs with minimal deleterious effects. Dynamic regulatory processes and multiple functions in the intact kidney can be quantitatively visualized in real time, noninvasively, and with submicron resolution. This article reviews innovative multiphoton imaging technologies and their applications that provided the most complex, immediate, and dynamic portrayal of renal function-clearly depicting as well as analyzing the components and mechanisms involved in renal (patho)physiology.

  1. Will The SEC Survive Financial Regulatory Reform?

    Directory of Open Access Journals (Sweden)

    Renee M. Jones

    2009-04-01

    Full Text Available The Securities and Exchange Commission’s (“SEC” conspicuous failures during the financial crisis of 2008 have led many to question the agency’s relevance in the modern financial era. Some commentators have called for the creation of new super-agencies to assume a substantial portion of the SEC’s duties. Others highlight enforcement failures and question the agency’s commitment to its investor protection mission. Despite its recent missteps and persistent calls for regulatory overhaul, the SEC’s future seems secure for now as President Obama’s reform proposals (the “Obama Plan” as currently conceived preserve the agency’s independence.

  2. Mechanisms of T regulatory cell function.

    Science.gov (United States)

    Askenasy, Nadir; Kaminitz, Ayelet; Yarkoni, Shai

    2008-05-01

    Regulatory T cells (Treg) play a pivotal role in tolerance to self-antigens and tissue grafts, and suppression of autoimmune reactions. These cells modulate the intensity and quality of immune reactions through attenuation of the cytolytic activities of reactive immune cells. Treg cells operate primarily at the site of inflammation where they modulate the immune reaction through three major mechanisms: a) direct killing of cytotoxic cells through cell-to-cell contact, b) inhibition of cytokine production by cytotoxic cells, in particular interleukin-2, c) direct secretion of immunomodulatory cytokines, in particular TGF-beta and interleukin-10. In addition to differential contributions of these mechanisms under variable inflammatory conditions, mechanistic complexity and diversity evolves from the diverse tasks performed by various Treg cell subsets in different stages of the immune reaction. Here we attempt to integrate the current experimental evidence to delineate the major suppressive pathways of Treg cells.

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

    Directory of Open Access Journals (Sweden)

    Ping-Lung Chan

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

  4. Information capacity of genetic regulatory elements

    Science.gov (United States)

    Tkačik, Gašper; Callan, Curtis G., Jr.; Bialek, William

    2008-07-01

    Changes in a cell’s external or internal conditions are usually reflected in the concentrations of the relevant transcription factors. These proteins in turn modulate the expression levels of the genes under their control and sometimes need to perform nontrivial computations that integrate several inputs and affect multiple genes. At the same time, the activities of the regulated genes would fluctuate even if the inputs were held fixed, as a consequence of the intrinsic noise in the system, and such noise must fundamentally limit the reliability of any genetic computation. Here we use information theory to formalize the notion of information transmission in simple genetic regulatory elements in the presence of physically realistic noise sources. The dependence of this “channel capacity” on noise parameters, cooperativity and cost of making signaling molecules is explored systematically. We find that, in the range of parameters probed by recent in vivo measurements, capacities higher than one bit should be achievable. It is of course generally accepted that gene regulatory elements must, in order to function properly, have a capacity of at least one bit. The central point of our analysis is the demonstration that simple physical models of noisy gene transcription, with realistic parameters, can indeed achieve this capacity: it was not self-evident that this should be so. We also demonstrate that capacities significantly greater than one bit are possible, so that transcriptional regulation need not be limited to simple “on-off” components. The question whether real systems actually exploit this richer possibility is beyond the scope of this investigation.

  5. Regulatory criteria: Legal or ecological thresholds?

    Energy Technology Data Exchange (ETDEWEB)

    Cook, J.M.; Skorupa, J.P.; Schwarzbach, S.E. [Fish and Wildlife Service, Sacramento, CA (United States)

    1994-12-31

    Selenium-laden irrigation drainwater has been identified as a significant threat to breeding waterfowl and shorebirds in terminal sink environments throughout the western United States. Due to historic wetland habitat losses, irrigation drainwater disposal ponds represent virtually all the available breeding habitat for waterbirds in the southern San Joaquin Valley of California. Egg selenium residues from birds breeding at these ponds have been monitored by the US Fish and Wildlife Service since 1987, and physiological risk thresholds for individual and population-level hatchability and teratogenesis have been determined from these studies. For Blacknecked stilt populations, egg selenium below 3 ppm may be considered a safe level, hatchability is significantly depressed at mean egg selenium concentrations above 8 ppm, and induction of teratogenesis is virtually certain at egg selenium levels above 18 ppm (p < 0.05). Egg samples collected in 1993 from these ponds showed concentrations as high as 160 ppm. Despite the high degree of statistical confidence in these effects thresholds, and the incidence of selenium-induced bird death and deformity at these ponds, regulation of evaporation ponds has been problematic. Existing civil statutes regarding water quality are dependent on risk-based criteria, but irrigation drainwater is exempted from these regulations. The only applicable law is the Migratory Bird Treaty Act, a criminal statute with no risk-based guidelines, and consequently no wildlife safety factors. The authors present data from the San Joaquin Valley in the context of these regulatory and legal limitations. Evaluation of acute and chronic models for ambient water quality indicate that this approach may not provide adequate protection for breeding birds. Based on the inadequacy of these models, the authors consider the development of regulatory criteria for egg selenium, a standard which is ecologically relevant.

  6. Approach of Czech regulatory body to LBB

    Energy Technology Data Exchange (ETDEWEB)

    Tendera, P.

    1997-04-01

    At present there are two NPPs equipped with PWR units in Czech Republic. The Dukovany, NPP is about ten years in operation (four units 440 MW - WWBFL model 213) and Tomelin NPP is under construction (two units 1000 MW - WWER model 320). Both NPPs were built to Soviet design and according to Soviet regulations and standards but most of equipment for primary circuits was supplied by home manufacturers. The objective of the Czech LBB program is to prove the LBB status of the primary piping systems of there NPPs and the LBB concept is a part of strategy to meet western style safety standards. The reason for the Czech LBB project is a lack of some standard safety Facilities too. For both Dukovany and Tomelin NPPs a full LBB analysis should be carried out. The application of LBB to the piping system should be also a cost effective means to avoid installations of pipe whip restraints and jet shields. The Czech regulatory body issued non-mandatory requirement, {open_quotes}Leak Before Break{close_quotes} which is in compliance with national legal documents and which is based on the US NRC Regulatory Procedures and US standards (ASMF CODE, ANSI). The requirement has been published in the document {open_quotes}Safety of Nuclear Facilities{close_quotes} No 1/1991 as {open_quotes}Requirements on the Content and Format of Safety Reports and their Supplements{close_quote} and consist of two parts (1) procedure for obtaining proof of evidence {open_quotes}Leak Before Break{close_quotes} (2) leak detection systems for the pressurized reactor primary circuit. At present some changes concerning both parts of the above document will be introduced. The reasons for this modifications will be presented.

  7. Approach for Czech regulatory body to LBB

    Energy Technology Data Exchange (ETDEWEB)

    Tendera, P. [State Office for Nuclear Safety (SONS), Prague (Czech Republic)

    1997-04-01

    At present there are two NPPs equipped with PWR units in Czech Republic. The Dukovany NPP is about ten years in operation (four units 440 MW - WWER model 213) and Temelin NPP is under construction (two units 1000 MW-WWER model 320). Both NPPs were built to Soviet design and according to Soviet regulations and standards but most of equipment for primary circuits was supplied by home manufactures. The objective for the Czech LBB programme is to prove the LBB status of the primary piping systems of these NPPs and the LBB concept is a part of strategy to meet western style safety standards. The reason for the Czech LBB project is a lack of some standard safety facilities, too. For both Dukovany and Temolin NPPs a full LBB analysis should be carried out. The application of LBB to the piping system should be also a cost effective means to avoid installations of pipe whip restraints and jet shields. The Czech regulatory body issued non-mandatory requirement {open_quotes}Leak Before Break{close_quotes} which is in compliance with national legal documents and which is based on the US NRC Regulatory Procedures and US standards (ASME, CODE, ANSI). The requirement has been published in the document {open_quotes}Safety of Nuclear Facilities{close_quotes} No. 1/1991 as {open_quotes}Requirements on the Content and Format of Safety Reports and their Supplements{close_quotes} and consists of two parts (1) procedure for obtaining proof of evidence {open_quotes}Leak Before Break{close_quotes} (2) leak detection systems for the pressurized reactor primary circuit. At present some changes concerning both parts of the above document will be introduced. The reasons for this modifications will be presented.

  8. Regulatory guidance on soil cover systems

    Energy Technology Data Exchange (ETDEWEB)

    Kane, J.D. [Nuclear Regulatory Commission, Washington, DC (United States)

    1991-12-31

    The US Nuclear Regulatory Commission (NRC) in September 1991, completed revisions to 14 sections of the Standard Review Plan (SRP) for the Review of a License Application for a Low-Level Radioactive Waste Disposal Facility. The major purposes of the SRP are to ensure the quality and uniformity of the NRC staff`s safety reviews, and to present a well-defined base from which to evaluate the acceptability of information and data provided in the Safety Analysis Report (SAR) portion of the license application. SRP 3.2, entitled, Design Considerations for Normal and Abnormal/Accident Conditions, was one of the sections that was revised by the NRC staff. This revision was completed to provide additional regulatory guidance on the important considerations that need to be addressed for the proper design and construction of soil cover systems that are to be placed over the LLW. The cover system over the waste is acknowledged to be one of the most important engineered barriers for the long-term stable performance of the disposal facility. The guidance in revised SRP 3.2 summarizes the previous efforts and recommendations of the US Army Corps of Engineers (COE), and a peer review panel on the placement of soil cover systems. NRC published these efforts in NUREG/CR-5432. The discussions in this paper highlight selected recommendations on soil cover issues that the NRC staff considers important for ensuring the safe, long-term performance of the soil cover systems. The development phases to be discussed include: (1) cover design; (2) cover material selection; (3) laboratory and field testing; (4) field placement control and acceptance; and (5) penetrations through the constructed covers.

  9. Genotoxicity assessment of 4-methylimidazole: regulatory perspectives.

    Science.gov (United States)

    Morita, Takeshi; Uneyama, Chikako

    2016-01-01

    4-Methylimidazole (4-MI) is formed as a result of the Maillard reaction process, and therefore is found in many foods and beverages. It is also found in soft drinks (i.e., cola) as a by-product in the production of some caramel colors. NTP bioassays revealed clear evidence of lung carcinogenicity of 4-MI in male and female mice, but not in rats and then IARC classified 4-MI as group 2B carcinogen. Genotoxicity studies with 4-MI were negative in the Ames tests and in the erythrocyte micronucleus tests with mice or rats. US California EPA (CEPA) evaluated the testing has not been adequately comprehensive to rule out a genotoxic mode of action; as target tissue of the carcinogenicity of 4-MI was lung, the lung should be used as a source tissue for in vitro metabolic activation system. Thus, CEPA defined the No Significant Risk Level (NSRL) for 10(-5) lifetime risk level of cancer by 4-MI as 29 μg/day based on the non-threshold approach. As higher levels of 4-MI than the NSRL were identified in some kinds of cola, health concerns of 4-MI were drawn the attention. On the other hand, other regulatory bodies (e.g., European Food Safety Authority, EFSA) showed no concerns of 4-MI from the use of caramel colors in food. EFSA evaluated 4-MI is not genotoxic, so, non-observed adverse effect level of 4-MI was considered to be 80 mg/kg/day. In this paper, genotoxic assessments of 4-MI in different regulatory bodies are presented and the risk evaluation of 4-MI is discussed based on new genotoxicity data.

  10. The Role of cis Regulatory Evolution in Maize Domestication

    Science.gov (United States)

    Lemmon, Zachary H.; Bukowski, Robert; Sun, Qi; Doebley, John F.

    2014-01-01

    Gene expression differences between divergent lineages caused by modification of cis regulatory elements are thought to be important in evolution. We assayed genome-wide cis and trans regulatory differences between maize and its wild progenitor, teosinte, using deep RNA sequencing in F1 hybrid and parent inbred lines for three tissue types (ear, leaf and stem). Pervasive regulatory variation was observed with approximately 70% of ∼17,000 genes showing evidence of regulatory divergence between maize and teosinte. However, many fewer genes (1,079 genes) show consistent cis differences with all sampled maize and teosinte lines. For ∼70% of these 1,079 genes, the cis differences are specific to a single tissue. The number of genes with cis regulatory differences is greatest for ear tissue, which underwent a drastic transformation in form during domestication. As expected from the domestication bottleneck, maize possesses less cis regulatory variation than teosinte with this deficit greatest for genes showing maize-teosinte cis regulatory divergence, suggesting selection on cis regulatory differences during domestication. Consistent with selection on cis regulatory elements, genes with cis effects correlated strongly with genes under positive selection during maize domestication and improvement, while genes with trans regulatory effects did not. We observed a directional bias such that genes with cis differences showed higher expression of the maize allele more often than the teosinte allele, suggesting domestication favored up-regulation of gene expression. Finally, this work documents the cis and trans regulatory changes between maize and teosinte in over 17,000 genes for three tissues. PMID:25375861

  11. The role of cis regulatory evolution in maize domestication.

    Directory of Open Access Journals (Sweden)

    Zachary H Lemmon

    2014-11-01

    Full Text Available Gene expression differences between divergent lineages caused by modification of cis regulatory elements are thought to be important in evolution. We assayed genome-wide cis and trans regulatory differences between maize and its wild progenitor, teosinte, using deep RNA sequencing in F1 hybrid and parent inbred lines for three tissue types (ear, leaf and stem. Pervasive regulatory variation was observed with approximately 70% of ∼17,000 genes showing evidence of regulatory divergence between maize and teosinte. However, many fewer genes (1,079 genes show consistent cis differences with all sampled maize and teosinte lines. For ∼70% of these 1,079 genes, the cis differences are specific to a single tissue. The number of genes with cis regulatory differences is greatest for ear tissue, which underwent a drastic transformation in form during domestication. As expected from the domestication bottleneck, maize possesses less cis regulatory variation than teosinte with this deficit greatest for genes showing maize-teosinte cis regulatory divergence, suggesting selection on cis regulatory differences during domestication. Consistent with selection on cis regulatory elements, genes with cis effects correlated strongly with genes under positive selection during maize domestication and improvement, while genes with trans regulatory effects did not. We observed a directional bias such that genes with cis differences showed higher expression of the maize allele more often than the teosinte allele, suggesting domestication favored up-regulation of gene expression. Finally, this work documents the cis and trans regulatory changes between maize and teosinte in over 17,000 genes for three tissues.

  12. The role of cis regulatory evolution in maize domestication.

    Science.gov (United States)

    Lemmon, Zachary H; Bukowski, Robert; Sun, Qi; Doebley, John F

    2014-11-01

    Gene expression differences between divergent lineages caused by modification of cis regulatory elements are thought to be important in evolution. We assayed genome-wide cis and trans regulatory differences between maize and its wild progenitor, teosinte, using deep RNA sequencing in F1 hybrid and parent inbred lines for three tissue types (ear, leaf and stem). Pervasive regulatory variation was observed with approximately 70% of ∼17,000 genes showing evidence of regulatory divergence between maize and teosinte. However, many fewer genes (1,079 genes) show consistent cis differences with all sampled maize and teosinte lines. For ∼70% of these 1,079 genes, the cis differences are specific to a single tissue. The number of genes with cis regulatory differences is greatest for ear tissue, which underwent a drastic transformation in form during domestication. As expected from the domestication bottleneck, maize possesses less cis regulatory variation than teosinte with this deficit greatest for genes showing maize-teosinte cis regulatory divergence, suggesting selection on cis regulatory differences during domestication. Consistent with selection on cis regulatory elements, genes with cis effects correlated strongly with genes under positive selection during maize domestication and improvement, while genes with trans regulatory effects did not. We observed a directional bias such that genes with cis differences showed higher expression of the maize allele more often than the teosinte allele, suggesting domestication favored up-regulation of gene expression. Finally, this work documents the cis and trans regulatory changes between maize and teosinte in over 17,000 genes for three tissues.

  13. Analysis of Necessity of Transforming Electrical Grid Access Training and Examination Regulatory Agency Mode

    Institute of Scientific and Technical Information of China (English)

    JI Tuo; SUN Qi; ZHOU Wan-lan

    2016-01-01

    There are numerous electricians, but only a few of them have obtained certificate. Training and examination agencies provide services relating to training, examination, and certificate application and so on. Thus, training resources are not rationally utilized, and the increased training demand cannot be fully satisfied. Under such circumstances, it is recommended to transform the regulatory agency mode by establishing a scientific management process, and put forward a new mode of electrical grid access training and examination to better meet related demands. Under the coordination of examination center regulatory agency, uniform training program, training materials, charging standard, examination and certificate can be guaranteed. This project is carried out as an effort to improve the quality of electronic-engineering training and examination, so that electricity accident rate can be reduced, and the security of electrical grid operation can be guaranteed to boost the rapidly developing economy.

  14. Protein phosphatase 2A regulatory subunit B56α limits phosphatase activity in the heart.

    Science.gov (United States)

    Little, Sean C; Curran, Jerry; Makara, Michael A; Kline, Crystal F; Ho, Hsiang-Ting; Xu, Zhaobin; Wu, Xiangqiong; Polina, Iuliia; Musa, Hassan; Meadows, Allison M; Carnes, Cynthia A; Biesiadecki, Brandon J; Davis, Jonathan P; Weisleder, Noah; Györke, Sandor; Wehrens, Xander H; Hund, Thomas J; Mohler, Peter J

    2015-07-21

    Protein phosphatase 2A (PP2A) is a serine/threonine-selective holoenzyme composed of a catalytic, scaffolding, and regulatory subunit. In the heart, PP2A activity is requisite for cardiac excitation-contraction coupling and central in adrenergic signaling. We found that mice deficient in the PP2A regulatory subunit B56α (1 of 13 regulatory subunits) had altered PP2A signaling in the heart that was associated with changes in cardiac physiology, suggesting that the B56α regulatory subunit had an autoinhibitory role that suppressed excess PP2A activity. The increase in PP2A activity in the mice with reduced B56α expression resulted in slower heart rates and increased heart rate variability, conduction defects, and increased sensitivity of heart rate to parasympathetic agonists. Increased PP2A activity in B56α(+/-) myocytes resulted in reduced Ca(2+) waves and sparks, which was associated with decreased phosphorylation (and thus decreased activation) of the ryanodine receptor RyR2, an ion channel on intracellular membranes that is involved in Ca(2+) regulation in cardiomyocytes. In line with an autoinhibitory role for B56α, in vivo expression of B56α in the absence of altered abundance of other PP2A subunits decreased basal phosphatase activity. Consequently, in vivo expression of B56α suppressed parasympathetic regulation of heart rate and increased RyR2 phosphorylation in cardiomyocytes. These data show that an integral component of the PP2A holoenzyme has an important inhibitory role in controlling PP2A enzyme activity in the heart.

  15. Re-evaluation of Non-regulatory Asbestos Group Minerals for Regulatory Agencies

    Science.gov (United States)

    Dogan, M.; Dogan, A.

    2013-05-01

    There are established rules and regulations for some asbestos group minerals - amphibole group minerals of actinolite, amosite, anthophyllite, crocidolite, tremolite; and serpentine group minerals of chrysotile- called "regulatory". There are also "non-regulatory" naturally occurring asbestos (NOA) group minerals as constituent of rocks and soil, including richterite, winchite, fluoro-edenite, balangeroite, carlosturanite, gageite, arfvedsonite, and magnesio-arfvedsonite. Strong evidences for carcinogenicity of these NOA minerals in later cohorts of cancer patients demonstrated the risks associated with these minerals. In addition, although the chrysotile asbestos regulated by some organizations such as WHO, World Trade Organization, United Nations, US EPA, International Labour Organization, and EU Countries; however, controversies still continue surrounding the use of chrysotile. Determinations of polymineralic fibrous veins, mixed particles, amphibole cleavage fragments, and genetic predisposition are also important issues (i.e. Dogan et al., 2006).Therefore, accurate characterizations of chemical composition, morphology, structure, and defects are necessary in order to find out mechanism(s) of carcinogenicity of all asbestos group minerals. Calculation methods of chemical composition are still under debate because of assumption of no vacancies at any sites and intergrowth of minerals. Substitution(s) may cause deviations from the ideal chemical formula and wide variations in chemical compositions. Detail morphological and chemical quantification of individual asbestos group minerals in micro- and nano-scale may help to evaluate its true carcinogenetic mechanism(s), and consequently prevention and possibly treatment of related diseases. we propose that nonregulatory asbestos minerals and the chrysotile should be re-evaluated. The amount of fibers inhaled, in terms of weight percent and number, need also be re-evaluated by mineralogists. Finally, Regulatory

  16. Reducing Outdoor Advertising

    Directory of Open Access Journals (Sweden)

    Patrice de Rendinger

    2006-05-01

    Full Text Available The fundamental concept is that public space is not a private property. So, a facade (the outer skin, the last millimeter belongs to the town, not to the owner of the building. Changing the rendering, a window, adding or removing anything from a facade requires a permission delivered by the town's authority.In places like Paris, Bordeaux, Marseilles, Lyon, Strasbourg… everywhere one can find a registrated building such as a cathedral, a castle, or a group of ancient buildings, a national administration is controlling this permission. This administration is called «historical monuments administration» and is locally lead by a specialized architect.In the late seventies, French government decided to reduce advertising on the roads and on the city walls. Advertising on the road was leading to a confusion reducing the efficacy of the roadsigns and direction signs, which is dangerous. The reduction was under control of a national administration: the ministry of equipment in charge of the roads design. Advertising on the walls with publicity boards was under control of the cities. Every city has a townplanning regulation. Many cities included forbidding advertisement boards on the walls in this regulation.A couple of firms, but mainly once (Decaux found clever to give a hand to the cities to control advertising. Decaux developed a line of bus stop shelters including advertisements and advertising panels and paid the cities the right to put rather smaller publicities on the public domain.Now Decaux is no more alone on this market and the cities are comparing offers.Marseille turned to a foreign advertising firm who pays three times the price Decaux paid… for half of the advertising surface. Freiburg erased totally the public domain advertisements, selling the tramways and bus coachwork as advertising spaces. Paris is reopening the advertising market before the end of Deacaux's contract and will pay Deacaux a huge amount

  17. Reducing GWAS Complexity

    Science.gov (United States)

    Hazelett, Dennis J.; Conti, David V.; Han, Ying; Al Olama, Ali Amin; Easton, Doug; Eeles, Rosalind A.; Kote-Jarai, Zsofia; Haiman, Christopher A.; Coetzee, Gerhard A.

    2016-01-01

    ABSTRACT Genome-wide association studies (GWAS) have revealed numerous genomic 'hits' associated with complex phenotypes. In most cases these hits, along with surrogate genetic variation as measure by numerous single nucleotide polymorphisms (SNPs) that are in linkage disequilibrium, are not in coding genes making assignment of functionality or causality intractable. Here we propose that fine-mapping along with the matching of risk SNPs at chromatin biofeatures lessen this complexity by reducing the number of candidate functional/causal SNPs. For example, we show here that only on average 2 SNPs per prostate cancer risk locus are likely candidates for functionality/causality; we further propose that this manageable number should be taken forward in mechanistic studies. The candidate SNPs can be looked up for each prostate cancer risk region in 2 recent publications in 20151,2 from our groups. PMID:26771711

  18. Reduced Order Podolsky Model

    CERN Document Server

    Thibes, Ronaldo

    2016-01-01

    We perform the canonical and path integral quantizations of a lower-order derivatives model describing Podolsky's generalized electrodynamics. The physical content of the model shows an auxiliary massive vector field coupled to the usual electromagnetic field. The equivalence with Podolsky's original model is studied at classical and quantum levels. Concerning the dynamical time evolution we obtain a theory with two first-class and two second-class constraints in phase space. We calculate explicitly the corresponding Dirac brackets involving both vector fields. We use the Senjanovic procedure to implement the second-class constraints and the Batalin-Fradkin-Vilkovisky path integral quantization scheme to deal with the symmetries generated by the first-class constraints. The physical interpretation of the results turns out to be simpler due to the reduced derivatives order permeating the equations of motion, Dirac brackets and effective action.

  19. Reducing violent injuries: priorities for pediatrician advocacy.

    Science.gov (United States)

    Dolins, J C; Christoffel, K K

    1994-10-01

    A basic framework for developing an advocacy plan must systematically break down the large task of policy development implementation into manageable components. The basic framework described in detail in this paper includes three steps: Setting policy objectives by narrowing the scope of policy, by reviewing policy options, and by examining options against selected criteria. Developing strategies for educating the public and for approaching legislative/regulatory bodies. Evaluating the effectiveness of the advocacy action plan as a process and as an agent for change. To illustrate the variety of ways in which pediatricians can be involved in the policy process to reduce violent injuries among children and adolescents, we apply this systematic approach to three priority areas. Prohibiting the use of corporal punishment in schools is intended to curb the institutionalized legitimacy of violence that has been associated with future use of violence. Efforts to remove handguns from the environments of children and adolescents are aimed at reducing the numbers of firearm injuries inflicted upon and by minors. Comprehensive treatment of adolescent victims of assault is intended to decrease the reoccurrence of violent injuries.

  20. Regulatory and Non-regulatory Responses to Hydraulic Fracturing in Local Communities

    Science.gov (United States)

    Phartiyal, P.

    2015-12-01

    The practice of extracting oil and gas from tight rock formations using advances in technology, such as hydraulic fracturing and directional drilling, has expanded exponentially in states and localities across the country. As the scientific data collection and analysis catches up on the many potential impacts of this unconventional oil and gas development, communities are turning to their local officials to make decisions on whether and how fracking should proceed. While most regulatory authority on the issue rests with the state agencies, local officials have experimented with a wide range of regulatory, non-regulatory, and fiscal tools to manage the impacts of fracking. These impacts can occur on the local air, water, seismicity, soil, roads, schools, and affect residents, on-site workers, emergency and social services. Local officials' approaches are often influenced by their prior experience with minerals extraction in their localities. The speaker will present examples of the kinds of information sources, tools and approaches communities across the country are using, from noise barriers to setback requirements to information sharing in order to be able to balance the promise and perils of oil and gas development in their jurisdictions.

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

    Science.gov (United States)

    Giresi, Paul G; Lieb, Jason D

    2009-07-01

    The binding of sequence-specific regulatory factors and the recruitment of chromatin remodeling activities cause nucleosomes to be evicted from chromatin in eukaryotic cells. Traditionally, these active sites have been identified experimentally through their sensitivity to nucleases. Here we describe the details of a simple procedure for the genome-wide isolation of nucleosome-depleted DNA from human chromatin, termed FAIRE (Formaldehyde Assisted Isolation of Regulatory Elements). We also provide protocols for different methods of detecting FAIRE-enriched DNA, including use of PCR, DNA microarrays, and next-generation sequencing. FAIRE works on all eukaryotic chromatin tested to date. To perform FAIRE, chromatin is crosslinked with formaldehyde, sheared by sonication, and phenol-chloroform extracted. Most genomic DNA is crosslinked to nucleosomes and is sequestered to the interphase, whereas DNA recovered in the aqueous phase corresponds to nucleosome-depleted regions of the genome. The isolated regions are largely coincident with the location of DNaseI hypersensitive sites, transcriptional start sites, enhancers, insulators, and active promoters. Given its speed and simplicity, FAIRE has utility in establishing chromatin profiles of diverse cell types in health and disease, isolating DNA regulatory elements en masse for further characterization, and as a screening assay for the effects of small molecules on chromatin organization.

  2. MicroRNA 10a marks regulatory T cells

    DEFF Research Database (Denmark)

    Jeker, Lukas T; Zhou, Xuyu; Gershberg, Kseniya

    2012-01-01

    MicroRNAs (miRNAs) are crucial for regulatory T cell (Treg) stability and function. We report that microRNA-10a (miR-10a) is expressed in Tregs but not in other T cells including individual thymocyte subsets. Expression profiling in inbred mouse strains demonstrated that non-obese diabetic (NOD......) mice with a genetic susceptibility for autoimmune diabetes have lower Treg-specific miR-10a expression than C57BL/6J autoimmune resistant mice. Inhibition of miR-10a expression in vitro leads to reduced FoxP3 expression levels and miR-10a expression is lower in unstable "exFoxP3" T cells. Unstable...... and phenotype of natural Treg nor the capacity of conventional T cells to induce FoxP3 in response to TGFβ, RA, or a combination of the two. Thus, miR-10a is selectively expressed in Treg but inhibition by antagomiRs or genetic ablation resulted in discordant effects on FoxP3....

  3. Deconstructing the Emotion Regulatory Properties of Mindfulness: An Electrophysiological Investigation

    Science.gov (United States)

    Lin, Yanli; Fisher, Megan E.; Roberts, Sean M. M.; Moser, Jason S.

    2016-01-01

    The present study sought to uncover the emotion regulatory properties of mindfulness by examining its effects—differentiated as a meditative practice, state of mind and dispositional trait—on the late positive potential (LPP), an event-related potentials (ERPs) indexing emotional processing. Results revealed that mindfulness as a meditative practice produced a reduction in the difference between the LPP response to negative high arousing and neutral stimuli across time. In contrast, a state mindfulness induction (i.e., instructions to attend to the stimuli mindfully) failed to modulate the LPP. Dispositional mindfulness, however, was related to modulation of the LPP as a function of meditation practice. Dispositional mindfulness was associated with a reduction of the LPP response to negative high arousal stimuli and the difference between negative high arousal and neutral stimuli in participants who listened to a control audio recording but not for those who engaged in the guided meditation practice. Together, these findings provide experimental evidence demonstrating that brief mindfulness meditation, but not deliberate engagement in state mindfulness, produces demonstrable changes in emotional processing indicative of reduced emotional reactivity. Importantly, these effects are akin to those observed in individuals with naturally high dispositional mindfulness, suggesting that the benefits of mindfulness can be cultivated through practice. PMID:27656139

  4. Cosmetic Surgery: Regulatory Challenges in a Global Beauty Market.

    Science.gov (United States)

    Griffiths, Danielle; Mullock, Alex

    2017-02-28

    The market for cosmetic surgery tourism is growing with an increase in people travelling abroad for cosmetic surgery. While the reasons for seeking cosmetic surgery abroad may vary the most common reason is financial, but does cheaper surgery abroad carry greater risks? We explore the risks of poorly regulated cosmetic surgery to society generally before discussing how harm might be magnified in the context of cosmetic tourism, where the demand for cheaper surgery drives the market and makes surgery accessible for increasing numbers of people. This contributes to the normalisation of surgical enhancement, creating unhealthy cultural pressure to undergo invasive and risky procedures in the name of beauty. In addressing the harms of poorly regulated surgery, a number of organisations purport to provide a register of safe and ethical plastic surgeons, yet this arguably achieves little and in the absence of improved regulation the risks are likely to grow as the global market expands to meet demand. While the evidence suggests that global regulation is needed, the paper concludes that since a global regulatory response is unlikely, more robust domestic regulation may be the best approach. While domestic regulation may increase the drive towards foreign providers it may also have a symbolic effect which will reduce this drive by making people more aware of the dangers of surgery, both to society and individual physical wellbeing.

  5. Epigenetically Mediated Pathogenic Effects of Phenanthrene on Regulatory T Cells

    Directory of Open Access Journals (Sweden)

    Jing Liu

    2013-01-01

    Full Text Available Phenanthrene (Phe, a polycyclic aromatic hydrocarbon (PAH, is a major constituent of urban air pollution. There have been conflicting results regarding the role of other AhR ligands 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD and 6-formylindolo [3,2-b]carbazole (FICZ in modifying regulatory T cell populations (Treg or T helper (Th17 differentiation, and the effects of Phe have been understudied. We hypothesized that different chemical entities of PAH induce Treg to become either Th2 or Th17 effector T cells through epigenetic modification of FOXP3. To determine specific effects on T cell populations by phenanthrene, primary human Treg were treated with Phe, TCDD, or FICZ and assessed for function, gene expression, and phenotype. Methylation of CpG sites within the FOXP3 locus reduced FOXP3 expression, leading to impaired Treg function and conversion of Treg into a CD4+CD25lo Th2 phenotype in Phe-treated cells. Conversely, TCDD treatment led to epigenetic modification of IL-17A and conversion of Treg to Th17 T cells. These findings present a mechanism by which exposure to AhR-ligands mediates human T cell responses and begins to elucidate the relationship between environmental exposures, immune modulation, and initiation of human disease.

  6. Data Integration for Microarrays: Enhanced Inference for Gene Regulatory Networks

    Directory of Open Access Journals (Sweden)

    Alina Sîrbu

    2015-05-01

    Full Text Available Microarray technologies have been the basis of numerous important findings regarding gene expression in the few last decades. Studies have generated large amounts of data describing various processes, which, due to the existence of public databases, are widely available for further analysis. Given their lower cost and higher maturity compared to newer sequencing technologies, these data continue to be produced, even though data quality has been the subject of some debate. However, given the large volume of data generated, integration can help overcome some issues related, e.g., to noise or reduced time resolution, while providing additional insight on features not directly addressed by sequencing methods. Here, we present an integration test case based on public Drosophila melanogaster datasets (gene expression, binding site affinities, known interactions. Using an evolutionary computation framework, we show how integration can enhance the ability to recover transcriptional gene regulatory networks from these data, as well as indicating which data types are more important for quantitative and qualitative network inference. Our results show a clear improvement in performance when multiple datasets are integrated, indicating that microarray data will remain a valuable and viable resource for some time to come.

  7. Deconstructing the emotion regulatory properties of mindfulness: An electrophysiological investigation

    Directory of Open Access Journals (Sweden)

    Yanli Lin

    2016-09-01

    Full Text Available The present study sought to uncover the emotion regulatory properties of mindfulness by examining its effects—differentiated as a meditative practice, state of mind, and dispositional trait—on the late positive potential (LPP, an event-related potential indexing emotional processing. Results revealed that mindfulness as a meditative practice produced a reduction in the difference between the LPP response to negative high arousing and neutral stimuli across time. In contrast, a state mindfulness induction (i.e., instructions to attend to the stimuli mindfully failed to modulate the LPP. Dispositional mindfulness, however, was related to modulation of the LPP as a function of meditation practice. Dispositional mindfulness was associated with a reduction of the LPP response to negative high arousal stimuli and the difference between negative high arousal and neutral stimuli in participants who listened to a control audio recording but not for those who engaged in the guided meditation practice. Together, these findings provide experimental evidence demonstrating that brief mindfulness meditation, but not deliberate engagement in state mindfulness, produces demonstrable changes in emotional processing indicative of reduced emotional reactivity. Importantly, these effects are akin to those observed in individuals with naturally high dispositional mindfulness, suggesting that the benefits of mindfulness can be cultivated through practice.

  8. Oncogenes Activate an Autonomous Transcriptional Regulatory Circuit That Drives Glioblastoma

    Directory of Open Access Journals (Sweden)

    Dinesh K. Singh

    2017-01-01

    Full Text Available Efforts to identify and target glioblastoma (GBM drivers have primarily focused on receptor tyrosine kinases (RTKs. Clinical benefits, however, have been elusive. Here, we identify an SRY-related box 2 (SOX2 transcriptional regulatory network that is independent of upstream RTKs and capable of driving glioma-initiating cells. We identified oligodendrocyte lineage transcription factor 2 (OLIG2 and zinc-finger E-box binding homeobox 1 (ZEB1, which are frequently co-expressed irrespective of driver mutations, as potential SOX2 targets. In murine glioma models, we show that different combinations of tumor suppressor and oncogene mutations can activate Sox2, Olig2, and Zeb1 expression. We demonstrate that ectopic co-expression of the three transcription factors can transform tumor-suppressor-deficient astrocytes into glioma-initiating cells in the absence of an upstream RTK oncogene. Finally, we demonstrate that the transcriptional inhibitor mithramycin downregulates SOX2 and its target genes, resulting in markedly reduced proliferation of GBM cells in vivo.

  9. Oncogenes Activate an Autonomous Transcriptional Regulatory Circuit That Drives Glioblastoma.

    Science.gov (United States)

    Singh, Dinesh K; Kollipara, Rahul K; Vemireddy, Vamsidara; Yang, Xiao-Li; Sun, Yuxiao; Regmi, Nanda; Klingler, Stefan; Hatanpaa, Kimmo J; Raisanen, Jack; Cho, Steve K; Sirasanagandla, Shyam; Nannepaga, Suraj; Piccirillo, Sara; Mashimo, Tomoyuki; Wang, Shan; Humphries, Caroline G; Mickey, Bruce; Maher, Elizabeth A; Zheng, Hongwu; Kim, Ryung S; Kittler, Ralf; Bachoo, Robert M

    2017-01-24

    Efforts to identify and target glioblastoma (GBM) drivers have primarily focused on receptor tyrosine kinases (RTKs). Clinical benefits, however, have been elusive. Here, we identify an SRY-related box 2 (SOX2) transcriptional regulatory network that is independent of upstream RTKs and capable of driving glioma-initiating cells. We identified oligodendrocyte lineage transcription factor 2 (OLIG2) and zinc-finger E-box binding homeobox 1 (ZEB1), which are frequently co-expressed irrespective of driver mutations, as potential SOX2 targets. In murine glioma models, we show that different combinations of tumor suppressor and oncogene mutations can activate Sox2, Olig2, and Zeb1 expression. We demonstrate that ectopic co-expression of the three transcription factors can transform tumor-suppressor-deficient astrocytes into glioma-initiating cells in the absence of an upstream RTK oncogene. Finally, we demonstrate that the transcriptional inhibitor mithramycin downregulates SOX2 and its target genes, resulting in markedly reduced proliferation of GBM cells in vivo.

  10. 21 CFR 26.74 - Preservation of regulatory authority.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Preservation of regulatory authority. 26.74 Section 26.74 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL... COMMUNITY âFrameworkâ Provisions § 26.74 Preservation of regulatory authority. (a) Nothing in this...

  11. Boundaries of regulatory fit: Is it the thought that counts?

    DEFF Research Database (Denmark)

    Leikas, S.; Lindeman, M.; Roininen, K.

    2009-01-01

    The feeling of regulatory fit is thought to arise from the right kind of goal pursuit, but some studies imply that it may be evoked even by lesser involvement in the right kind of strategies. The present experiment explored the minimum of involvement necessary to evoke regulatory fit. Participant...

  12. 76 FR 24836 - Regulatory Approach for Commercial Orbital Human Spaceflight

    Science.gov (United States)

    2011-05-03

    ... Federal Aviation Administration 14 CFR Part 460 Regulatory Approach for Commercial Orbital Human... regulatory approach to commercial orbital human spaceflight by the FAA. This public meeting is intended to... 1200 New Jersey Avenue, SE., Washington, DC, between 9 a.m. and 5 p.m., Monday through Friday,...

  13. Non-transcriptional regulatory processes shape transcriptional network dynamics

    OpenAIRE

    Ray, J. Christian J; Tabor, Jeffrey J.; Igoshin, Oleg A.

    2011-01-01

    Information about the extra- or intracellular environment is often captured as biochemical signals propagating through regulatory networks. These signals eventually drive phenotypic changes, typically by altering gene expression programs in the cell. Reconstruction of transcriptional regulatory networks has given a compelling picture of bacterial physiology, but transcriptional network maps alone often fail to describe phenotypes. In many cases, the dynamical performance of transcriptional re...

  14. Evolutionary dynamics and functional roles of regulatory systems in plants

    NARCIS (Netherlands)

    Berke, L.

    2015-01-01

    Transcription, the process of generating RNA copies of the genetic information stored in the DNA, is crucial for every organism. As with other essential processes in life, correct activation and repression of transcription is governed by complex regulatory mechanisms. These regulatory mechanisms ope

  15. Regulatory considerations for translating gene therapy: a European Union perspective.

    Science.gov (United States)

    Galli, Maria Cristina

    2009-11-11

    A preclinical study on a gene therapy approach for treatment of the severe muscle weakness associated with a variety of neuromuscular disorders provides a forum to discuss the translational challenges of gene therapy from a regulatory point of view. In this Perspective, the findings are considered from the view of European regulatory requirements for first clinical use.

  16. Inferring slowly-changing dynamic gene-regulatory networks

    NARCIS (Netherlands)

    Wit, Ernst C.; Abbruzzo, Antonino

    2015-01-01

    Dynamic gene-regulatory networks are complex since the interaction patterns between their components mean that it is impossible to study parts of the network in separation. This holistic character of gene-regulatory networks poses a real challenge to any type of modelling. Graphical models are a cla

  17. Multivariate Hawkes process models of the occurrence of regulatory elements

    DEFF Research Database (Denmark)

    Carstensen, L; Sandelin, A; Winther, Ole

    2010-01-01

    BACKGROUND: A central question in molecular biology is how transcriptional regulatory elements (TREs) act in combination. Recent high-throughput data provide us with the location of multiple regulatory regions for multiple regulators, and thus with the possibility of analyzing the multivariate di...

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

    NARCIS (Netherlands)

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

    2014-01-01

    Medicines of uncertain quality, safety and efficacy can be worse than no treatment at all. It is the responsibility of national medicines regulatory authorities to protect patients from harm. Yet, there are great disparities in regulatory capacity globally, preventing large populations from accessin

  19. 76 FR 2726 - Withdrawal of Regulatory Guide 1.154

    Science.gov (United States)

    2011-01-14

    ... Regulatory Guide 1.154, ``Format and Content of Plant-Specific Pressurized Thermal Shock Safety Analysis... Regulatory Guide (RG) 1.154, ``Format and Content of Plant-Specific Pressurized Thermal Shock Safety Analysis... format and content acceptable to the NRC staff for plant-specific pressurized thermal shock (PTS)...

  20. Overall Effects of China's Recent Macroeconomic Regulatory Policies

    Institute of Scientific and Technical Information of China (English)

    LiJianwei,; ZhuShida; DavidKelly

    2004-01-01

    China's economic regulatory policies in the last few years have played an important role in curbing the slide of its consistent growth drive. In terms of overall effects, the macroeconomic regulatory policies of each fiscal year have attained their targets. In some years, however,