WorldWideScience

Sample records for opposing regulatory roles

  1. Opposing roles for interferon regulatory factor-3 (IRF-3 and type I interferon signaling during plague.

    Directory of Open Access Journals (Sweden)

    Ami A Patel

    Full Text Available Type I interferons (IFN-I broadly control innate immunity and are typically transcriptionally induced by Interferon Regulatory Factors (IRFs following stimulation of pattern recognition receptors within the cytosol of host cells. For bacterial infection, IFN-I signaling can result in widely variant responses, in some cases contributing to the pathogenesis of disease while in others contributing to host defense. In this work, we addressed the role of type I IFN during Yersinia pestis infection in a murine model of septicemic plague. Transcription of IFN-β was induced in vitro and in vivo and contributed to pathogenesis. Mice lacking the IFN-I receptor, Ifnar, were less sensitive to disease and harbored more neutrophils in the later stage of infection which correlated with protection from lethality. In contrast, IRF-3, a transcription factor commonly involved in inducing IFN-β following bacterial infection, was not necessary for IFN production but instead contributed to host defense. In vitro, phagocytosis of Y. pestis by macrophages and neutrophils was more effective in the presence of IRF-3 and was not affected by IFN-β signaling. This activity correlated with limited bacterial growth in vivo in the presence of IRF-3. Together the data demonstrate that IRF-3 is able to activate pathways of innate immunity against bacterial infection that extend beyond regulation of IFN-β production.

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

    Science.gov (United States)

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

    2010-07-01

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

  3. Opposing roles of PGD2 in GBM.

    Science.gov (United States)

    Ferreira, Matthew Thomas; Gomes, Renata Nascimento; Panagopoulos, Alexandros Theodoros; de Almeida, Fernando Gonçalves; Veiga, José Carlos Esteves; Colquhoun, Alison

    2018-01-01

    The World Health Organization classifies glioblastoma (GBM) as a grade IV astrocytoma. Despite the advances in chemotherapy, surgery, and radiation treatments that improve a patient's length of survival, the overall trajectory of the disease remains unchanged. GBM cells produce significant levels of various types of bioactive lipids. Prostaglandin D 2 (PGD 2 ) influences both pro- and anti-tumorigenic activities in the cell; however, its role in GBM is unclear. Therefore, this study aimed to identify the impact of PGD 2 on GBM cell activities in vitro. First we looked to identify the presence of the PGD 2 synthesis pathway through RT-PCR, immunohistochemistry, and HPLC-MS/MS in three GBM cell lines. Then, to observe PGD 2 's effects on cell count and apoptosis/mitosis (Hoechst 33342 stain), and migration (Transwell Assay), the cells were treated in vitro with physiological (1μM) concentrations of PGD 2 over 72h. HPLC-MS/MS was used to identify the lipid composition of patients with either Grade II/III gliomas or GBM. We identified the presence of endogenous PGD 2 with its corresponding enzymes and receptors. Exogenous PGD 2 both increased cell count (GBM. Our study demonstrates that prostaglandin D 2 possesses a dynamic, concentration-dependent effect in GBM cell activities. The increase of PGD 2 production in GBM patients suggests a pro-tumorigenic role of PGD 2 in glioma growth and invasion. Therefore, prostaglandin signaling in GBM requires further investigation to identify new targets for more effective therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Growth and remodeling play opposing roles during postnatal human heart valve development.

    Science.gov (United States)

    Oomen, Pim J A; Holland, Maria A; Bouten, Carlijn V C; Kuhl, Ellen; Loerakker, Sandra

    2018-01-19

    Tissue growth and remodeling are known to govern mechanical homeostasis in biological tissue, but their relative contributions to homeostasis remain unclear. Here, we use mechanical models, fueled by experimental findings, to demonstrate that growth and remodeling have different effects on heart valve stretch homeostasis during physiological postnatal development. Two developmental stages were considered: early-stage (from infant to adolescent) and late-stage (from adolescent to adult) development. Our models indicated that growth and remodeling play opposing roles in preserving tissue stretch and with time. During early-stage development, excessive tissue stretch was decreased by tissue growth and increased by remodeling. In contrast, during late-stage development tissue stretch was decreased by remodeling and increased by growth. Our findings contribute to an improved understanding of native heart valve adaptation throughout life, and are highly relevant for the development of tissue-engineered heart valves.

  5. Opposing roles of STAT4 and Dnmt3a in Th1 gene regulation

    Science.gov (United States)

    Pham, Duy; Yu, Qing; Walline, Crystal C.; Muthukrishnan, Rajarajeswari; Blum, Janice S.; Kaplan, Mark H.

    2013-01-01

    The Signal Transducer and Activator of Transcription factor STAT4 is a critical regulator of Th1 differentiation and inflammatory disease. Yet, how STAT4 regulates gene expression is still unclear. In this report, we define a STAT4-dependent sequence of events including H3K4 methylation, Jmjd3 association with STAT4 target loci, and a Jmjd3-dependent decrease in H3K27 trimethylation and DNA methyltransferase (Dnmt) 3a association with STAT4 target loci. Dnmt3a has an obligate role in repressing Th1 gene expression, and in Th1 cultures deficient in both STAT4 and Dnmt3a, there is recovery in the expression of a subset of Th1 genes that is sufficient to increase IFNγ production. Moreover, although STAT4-deficient mice are protected from the development of EAE, mice deficient in STAT4 and conditionally-deficient in Dnmt3a in T cells develop paralysis. Th1 genes that are de-repressed in the absence of Dnmt3a have greater induction following the ectopic expression of the Th1-associated transcription factors T-bet and Hlx1. Together, these data demonstrate that STAT4 and Dnmt3a play opposing roles in regulating Th1 gene expression, and that one mechanism for STAT4-dependent gene programming is in establishing a de-repressed genetic state susceptible to transactivation by additional fate-determining transcription factors. PMID:23772023

  6. Opposing Roles of Leptin and Ghrelin in the Equine Corpus Luteum Regulation: An In Vitro Study

    Directory of Open Access Journals (Sweden)

    António Galvão

    2014-01-01

    Full Text Available Metabolic hormones have been associated with reproductive function modulation. Thus, the aim of this study was: (i to characterize the immunolocalization, mRNA and protein levels of leptin (LEP, Ghrelin (GHR and respective receptors LEPR and Ghr-R1A, throughout luteal phase; and (ii to evaluate the role of LEP and GHR on progesterone (P4, prostaglandin (PG E2 and PGF2α, nitric oxide (nitrite, tumor necrosis factor-α (TNF; macrophage migration inhibitory factor (MIF secretion, and on angiogenic activity (BAEC proliferation, in equine corpus luteum (CL from early and mid-luteal stages. LEPR expression was decreased in late CL, while GHR/Ghr-R1A system was increased in the same stage. Regarding secretory activity, GHR decreased P4 in early CL, but increased PGF2α, nitrite and TNF in mid CL. Conversely, LEP increased P4, PGE2, angiogenic activity, MIF, TNF and nitrite during early CL, in a dose-dependent manner. The in vitro effect of LEP on secretory activity was reverted by GHR, when both factors acted together. The present results evidence the presence of LEP and GHR systems in the equine CL. Moreover, we suggest that LEP and GHR play opposing roles in equine CL regulation, with LEP supporting luteal establishment and GHR promoting luteal regression. Finally, a dose-dependent luteotrophic effect of LEP was demonstrated.

  7. On the role of radiation and dimensionality in predicting flow opposed flame spread over thin fuels

    Science.gov (United States)

    Kumar, Chenthil; Kumar, Amit

    2012-06-01

    In this work a flame-spread model is formulated in three dimensions to simulate opposed flow flame spread over thin solid fuels. The flame-spread model is coupled to a three-dimensional gas radiation model. The experiments [1] on downward spread and zero gravity quiescent spread over finite width thin fuel are simulated by flame-spread models in both two and three dimensions to assess the role of radiation and effect of dimensionality on the prediction of the flame-spread phenomena. It is observed that while radiation plays only a minor role in normal gravity downward spread, in zero gravity quiescent spread surface radiation loss holds the key to correct prediction of low oxygen flame spread rate and quenching limit. The present three-dimensional simulations show that even in zero gravity gas radiation affects flame spread rate only moderately (as much as 20% at 100% oxygen) as the heat feedback effect exceeds the radiation loss effect only moderately. However, the two-dimensional model with the gas radiation model badly over-predicts the zero gravity flame spread rate due to under estimation of gas radiation loss to the ambient surrounding. The two-dimensional model was also found to be inadequate for predicting the zero gravity flame attributes, like the flame length and the flame width, correctly. The need for a three-dimensional model was found to be indispensable for consistently describing the zero gravity flame-spread experiments [1] (including flame spread rate and flame size) especially at high oxygen levels (>30%). On the other hand it was observed that for the normal gravity downward flame spread for oxygen levels up to 60%, the two-dimensional model was sufficient to predict flame spread rate and flame size reasonably well. Gas radiation is seen to increase the three-dimensional effect especially at elevated oxygen levels (>30% for zero gravity and >60% for normal gravity flames).

  8. Role of regulatory body related to siting

    International Nuclear Information System (INIS)

    Asmis, G.J.K.

    1981-11-01

    The role of a regulatory body, the Atomic Energy Control Board of Canada, in the siting process is discussed. A description of the Board's legal structure and safety criteria is followed by an example of the implementation of these criteria in relation to the siting of the Darlington nuclear power plant, with particular reference to external hazards such as tornadoes, earthquakes and explosions

  9. Opposing Roles of Calcium and Intracellular ATP on Gating of the Purinergic P2X2 Receptor Channel

    Directory of Open Access Journals (Sweden)

    Milos B. Rokic

    2018-04-01

    Full Text Available P2X2 receptors (P2X2R exhibit a slow desensitization during the initial ATP application and a progressive, calcium-dependent increase in rates of desensitization during repetitive stimulation. This pattern is observed in whole-cell recordings from cells expressing recombinant and native P2X2R. However, desensitization is not observed in perforated-patched cells and in two-electrode voltage clamped oocytes. Addition of ATP, but not ATPγS or GTP, in the pipette solution also abolishes progressive desensitization, whereas intracellular injection of apyrase facilitates receptor desensitization. Experiments with injection of alkaline phosphatase or addition of staurosporine and ATP in the intracellular solution suggest a role for a phosphorylation-dephosphorylation in receptor desensitization. Mutation of residues that are potential phosphorylation sites identified a critical role of the S363 residue in the intracellular ATP action. These findings indicate that intracellular calcium and ATP have opposing effects on P2X2R gating: calcium allosterically facilitates receptor desensitization and ATP covalently prevents the action of calcium. Single cell measurements further revealed that intracellular calcium stays elevated after washout in P2X2R-expressing cells and the blockade of mitochondrial sodium/calcium exchanger lowers calcium concentrations during washout periods to basal levels, suggesting a role of mitochondria in this process. Therefore, the metabolic state of the cell can influence P2X2R gating.

  10. Opposing roles of Toll-like receptor and cytosolic DNA-STING signaling pathways for Staphylococcus aureus cutaneous host defense.

    Directory of Open Access Journals (Sweden)

    Philip O Scumpia

    2017-07-01

    Full Text Available Successful host defense against pathogens requires innate immune recognition of the correct pathogen associated molecular patterns (PAMPs by pathogen recognition receptors (PRRs to trigger the appropriate gene program tailored to the pathogen. While many PRR pathways contribute to the innate immune response to specific pathogens, the relative importance of each pathway for the complete transcriptional program elicited has not been examined in detail. Herein, we used RNA-sequencing with wildtype and mutant macrophages to delineate the innate immune pathways contributing to the early transcriptional response to Staphylococcus aureus, a ubiquitous microorganism that can activate a wide variety of PRRs. Unexpectedly, two PRR pathways-the Toll-like receptor (TLR and Stimulator of Interferon Gene (STING pathways-were identified as dominant regulators of approximately 95% of the genes that were potently induced within the first four hours of macrophage infection with live S. aureus. TLR signaling predominantly activated a pro-inflammatory program while STING signaling activated an antiviral/type I interferon response with live but not killed S. aureus. This STING response was largely dependent on the cytosolic DNA sensor cyclic guanosine-adenosine synthase (cGAS. Using a cutaneous infection model, we found that the TLR and STING pathways played opposite roles in host defense to S. aureus. TLR signaling was required for host defense, with its absence reducing interleukin (IL-1β production and neutrophil recruitment, resulting in increased bacterial growth. In contrast, absence of STING signaling had the opposite effect, enhancing the ability to restrict the infection. These results provide novel insights into the complex interplay of innate immune signaling pathways triggered by S. aureus and uncover opposing roles of TLR and STING in cutaneous host defense to S. aureus.

  11. TGF-β1 exerts opposing effects on grass carp leukocytes: implication in teleost immunity, receptor signaling and potential self-regulatory mechanisms.

    Directory of Open Access Journals (Sweden)

    Mu Yang

    Full Text Available In fish immunity, the regulatory role of transforming growth factor-β1 (TGF-β1 has not been fully characterized. Here we examined the immunoregulatory effects of TGF-β1 in grass carp peripheral blood leukocytes (PBL and head kidney leukocytes (HKL. It is interesting that TGF-β1 consistently stimulated the cell viability and the mRNA levels of pro-inflammatory cytokines (Tnfα and Ifnγ and T/B cell markers [Cd4-like (Cd4l, Cd8α, Cd8β and Igμ] in PBL, which contrasted with its inhibitory tone in HKL. Further studies showed that grass carp TGF-β1 type I receptor, activin receptor-like kinase 5 (ALK5, was indispensable for the immunoregulatory effects of TGF-β1 in PBL and HKL. Notably, TGF-β1 persistently attenuated ALK5 expression, whereas immunoneutralization of endogenous grass carp TGF-β1 could increase ALK5 mRNA and protein levels. It is consistent with the observation that TGF-β1 decreased the number of ALK5(+ leukocytes in PBL and HKL, revealing a negative regulation of TGF-β1 signaling at the receptor level. Moreover, transient treatment with TGF-β1 for 24 h was sufficient to induce similar cellular responses compared with the continuous treatment. This indicated a possible mechanism by which TGF-β1 triggered the down-regulation of ALK5 mRNA and protein, leading to the desensitization of grass carp leukocytes toward TGF-β1. Accordingly, our data revealed a dual role of TGF-β1 in teleost immunity in which it can serve as a positive or negative control device and provided additional mechanistic insights as to how TGF-β1 controls its signaling in vertebrate leukocytes.

  12. The Role of Regulatory and Customary Institutions to Access ...

    African Journals Online (AJOL)

    Remember me ... The findings of the study show a somewhat 'pessimistic' picture to shed light on the hitherto neglected role of informal institutions to support the ... Key words: Rural youth, Access to land, Customary/regulatory institutions,

  13. Opposing Roles of the Staphylococcus aureus Virulence Regulators, Agr and Sar, in Triton X-100- and Penicillin-Induced Autolysis

    OpenAIRE

    Fujimoto, David F.; Bayles, Kenneth W.

    1998-01-01

    The regulation of murein hydrolases is a critical aspect of peptidoglycan growth and metabolism. In the present study, we demonstrate that mutations within the Staphylococcus aureus virulence factor regulatory genes, agr and sar, affect autolysis, resulting in decreased and increased autolysis rates, respectively. Zymographic analyses of these mutant strains suggest that agr and sar exert their effects on autolysis, in part, by modulating murein hydrolase expression and/or activity.

  14. Opposing roles of RNF8/RNF168 and deubiquitinating enzymes in ubiquitination-dependent DNA double-strand break response signaling and DNA-repair pathway choice

    International Nuclear Information System (INIS)

    Nakada, Shinichiro

    2016-01-01

    The E3 ubiquitin ligases ring finger protein (RNF) 8 and RNF168 transduce the DNA double-strand break (DSB) response (DDR) signal by ubiquitinating DSB sites. The depletion of RNF8 or RNF168 suppresses the accumulation of DNA-repair regulating factors such as 53BP1 and RAP80 at DSB sites, suggesting roles for RNF8- and RNF168-mediated ubiquitination in DSB repair. This mini-review provides a brief overview of the RNF8- and RNF168-dependent DDR-signaling and DNA-repair pathways. The choice of DNA-repair pathway when RNF8- and RNF168-mediated ubiquitination-dependent DDR signaling is negatively regulated by deubiquitinating enzymes (DUBs) is reviewed to clarify how the opposing roles of RNF8/RNF168 and DUBs regulate ubiquitination-dependent DDR signaling and the choice of DNA-repair pathway

  15. Regulatory Role of Circular RNAs and Neurological Disorders.

    Science.gov (United States)

    Floris, Gabriele; Zhang, Longbin; Follesa, Paolo; Sun, Tao

    2017-09-01

    Circular RNAs (circRNAs) are a class of long noncoding RNAs that are characterized by the presence of covalently linked ends and have been found in all life kingdoms. Exciting studies in regulatory roles of circRNAs are emerging. Here, we summarize classification, characteristics, biogenesis, and regulatory functions of circRNAs. CircRNAs are found to be preferentially expressed along neural genes and in neural tissues. We thus highlight the association of circRNA dysregulation with neurodegenerative diseases such as Alzheimer's disease. Investigation of regulatory role of circRNAs will shed novel light in gene expression mechanisms during development and under disease conditions and may identify circRNAs as new biomarkers for aging and neurodegenerative disorders.

  16. Associations of collectivism with relationship commitment, passion, and mate preferences: opposing roles of parental influence and family allocentrism.

    Science.gov (United States)

    Bejanyan, Kathrine; Marshall, Tara C; Ferenczi, Nelli

    2015-01-01

    In collectivist cultures, families tend to be characterized by respect for parental authority and strong, interdependent ties. Do these aspects of collectivism exert countervailing pressures on mate choices and relationship quality? In the present research, we found that collectivism was associated with greater acceptance of parental influence over mate choice, thereby driving relationship commitment down (Studies 1 and 2), but collectivism was also associated with stronger family ties (referred to as family allocentrism), which drove commitment up (Study 2). Along similar lines, Study 1 found that collectivists' greater acceptance of parental influence on mate choice contributed to their reduced relationship passion, whereas Study 2 found that their greater family allocentrism may have enhanced their passion. Study 2 also revealed that collectivists may have reported a smaller discrepancy between their own preferences for mates high in warmth and trustworthiness and their perception of their parents' preferences for these qualities because of their stronger family allocentrism. However, their higher tolerance of parental influence may have also contributed to a smaller discrepancy in their mate preferences versus their perceptions of their parents' preferences for qualities signifying status and resources. Implications for the roles of collectivism, parental influence, and family allocentrism in relationship quality and mate selection will be discussed.

  17. Associations of Collectivism with Relationship Commitment, Passion, and Mate Preferences: Opposing Roles of Parental Influence and Family Allocentrism

    Science.gov (United States)

    Bejanyan, Kathrine; Marshall, Tara C.; Ferenczi, Nelli

    2015-01-01

    In collectivist cultures, families tend to be characterized by respect for parental authority and strong, interdependent ties. Do these aspects of collectivism exert countervailing pressures on mate choices and relationship quality? In the present research, we found that collectivism was associated with greater acceptance of parental influence over mate choice, thereby driving relationship commitment down (Studies 1 and 2), but collectivism was also associated with stronger family ties (referred to as family allocentrism), which drove commitment up (Study 2). Along similar lines, Study 1 found that collectivists’ greater acceptance of parental influence on mate choice contributed to their reduced relationship passion, whereas Study 2 found that their greater family allocentrism may have enhanced their passion. Study 2 also revealed that collectivists may have reported a smaller discrepancy between their own preferences for mates high in warmth and trustworthiness and their perception of their parents’ preferences for these qualities because of their stronger family allocentrism. However, their higher tolerance of parental influence may have also contributed to a smaller discrepancy in their mate preferences versus their perceptions of their parents’ preferences for qualities signifying status and resources. Implications for the roles of collectivism, parental influence, and family allocentrism in relationship quality and mate selection will be discussed. PMID:25719563

  18. The regulatory roles of B cell subsets in transplantation.

    Science.gov (United States)

    Chu, Zhulang; Zou, Weilong; Xu, Yanan; Sun, Qiquan; Zhao, Yong

    2018-02-01

    B cells mediate allograft rejection through antigen presentation, and production of cytokines and antibodies. More and more immunosuppressive agents specifically targeting B cells and plasma cells have been applied in clinical transplantation. However, recent studies have indicated the regulatory roles of B cells. Therefore, it is vital to clarify the different effects of B cell subsets in organ transplantation so that we can completely understand the diverse functions of B cells in transplantation. Areas covered: This review focuses on the regulatory roles of B cells in transplantation. B cell subsets with immune modulation and factors mediating immunosuppressive functions of regulatory B (Breg) cells were analyzed. Therapies targeting B cells and the application of B cells for transplant tolerance induction were discussed. Expert commentary: Besides involving rejection, B cells could also play regulatory roles in transplantation. Breg cells and the related markers may be used to predict the immune tolerant state in transplant recipients. New therapeutic strategies targeting B cells should be explored to promote tolerance induction with less impact on the host's protective immunity in organ transplanted patients.

  19. Opposing incentives for collaboration

    DEFF Research Database (Denmark)

    Dorch, Bertil F.; Wien, Charlotte; Larsen, Asger Væring

    , and gives a bonus for publications done through inter-institutionary collaboration. Credits given to universities are fractionalized between the participating universities. So far credits are not assigned to the individual authors but only to their institutions. However, it turns out that research...... collaboration is associated with a higher number of citations than single authorship which may present the author with two opposing incentives for research collaboration....

  20. Opposing roles of miR-21 and miR-29 in the progression of fibrosis in Duchenne muscular dystrophy.

    Science.gov (United States)

    Zanotti, Simona; Gibertini, Sara; Curcio, Maurizio; Savadori, Paolo; Pasanisi, Barbara; Morandi, Lucia; Cornelio, Ferdinando; Mantegazza, Renato; Mora, Marina

    2015-07-01

    Excessive extracellular matrix deposition progressively replacing muscle fibres is the endpoint of most severe muscle diseases. Recent data indicate major involvement of microRNAs in regulating pro- and anti-fibrotic genes. To investigate the roles of miR-21 and miR-29 in muscle fibrosis in Duchenne muscle dystrophy, we evaluated their expression in muscle biopsies from 14 patients, and in muscle-derived fibroblasts and myoblasts. In Duchenne muscle biopsies, miR-21 expression was significantly increased, and correlated directly with COL1A1 and COL6A1 transcript levels. MiR-21 expression was also significantly increased in Duchenne fibroblasts, more so after TGF-β1 treatment. In Duchenne fibroblasts the expression of miR-21 target transcripts PTEN (phosphatase and tensin homolog deleted on chromosome 10) and SPRY-1 (Sprouty homolog 1) was significantly reduced; while collagen I and VI transcript levels and soluble collagen production were significantly increased. MiR-29a and miR-29c were significantly reduced in Duchenne muscle and myoblasts, and miR-29 target transcripts, COL3A1, FBN1 and YY1, significantly increased. MiR-21 silencing in mdx mice reduced fibrosis in the diaphragm muscle and in both Duchenne fibroblasts and mdx mice restored PTEN and SPRY-1 expression, and significantly reduced collagen I and VI expression; while miR-29 mimicking in Duchenne myoblasts significantly decreased miR-29 target transcripts. These findings indicate that miR-21 and miR-29 play opposing roles in Duchenne muscle fibrosis and suggest that pharmacological modulation of their expression has therapeutic potential for reducing fibrosis in this condition. Copyright © 2015. Published by Elsevier B.V.

  1. The Role of Advisory Committees on Regulatory functions: Argentine Experience

    International Nuclear Information System (INIS)

    Larcher, A. M.; Arias, C.; Kunst, J. J.; Perez, R. M.; Rudelli, M.

    2004-01-01

    The Argentine Nuclear Regulatory Authority (NRA) has appointed a consultants body that advises its Board of Directors on aspects related to authorization's granting to individuals for the use of radioisotopes and ionizing radiation in medicine, research and industry. Such committee, whose existence goes back to the year 1958, is integrated by prominent professionals knowledgeable about ionizing radiation and radioisotopes applications in the medical, biomedical and industrial fields, representing important professional associations or institutions related to the practices in question. Originally, the committee was conceived as a consultation body to fulfil two important functions: To produce, in a regular way, authorized opinions at experts level to settle down questions relative to the regulation of practices, new at that time in the country, and To submit to a peer review applications for individual authorization for different uses of ionizing radiation previously it's granting by the Regulatory Authority. In this paper the role of the advisory council is analyzed from a historical perspective trying to emphasize an outstanding aspect not sufficiently analyzed linked to the capability that advisory bodies, with representative users' presence, can reach in the interpretation of regulatory standards based on a performance philosophy. Such approach outlines the permanent dilemma about the performance level of the licensee that should satisfy the Regulatory Authority. Once the broad objectives of radiation protection has been defined professional criteria is required for applying them to different practices. Balance between flexibility and avoidance of excessive uncertainty is desirable. In the authors' opinion the inclusion, inside the regulator's structure of consultants bodies giving direct participation to qualified stakeholders, far from harming the necessary independence that should characterize the regulator, on the contrary, allows to have an excellent social

  2. Nuclear Regulatory Commission and its role in environmental standards

    International Nuclear Information System (INIS)

    Mattson, R.J.

    1976-01-01

    The NRC and its predecessors in the Atomic Energy Commission represent considerable experience in environmental standards setting. The Atomic Energy Act of 1954, the 1970 Supreme Court decision on Federal pre-emption of radiation standards, the Calvert Cliffs decision of 1971, the Energy Reorganization Act of 1974, and the Appendix I ''as low as reasonably achievable'' decision of 1975, to name a few of our landmarks, are representative of the scars and the achievements of being in a role of national leadership in radiation protection. The NRC, through a variety of legislative authorities, administrative regulations, regulatory guides, and national consensus standards regulates the commercial applications of nuclear energy. The purposes of regulation are the protection of the environment, public health and safety, and national security. To understand NRC's responsibilities relative to those of other Federal and state agencies concerned with environmental protection, we will briefly review the legislative authorities which underlie our regulatory program. Then we will examine the intent or the spirit of that program as embodied in our system of regulations, guides, and standards. Finally we will speak to what's happening today and what we see in the future for environmental standards

  3. Institutions, regulatory role and economic growth of national economies

    Directory of Open Access Journals (Sweden)

    Mladen Vedriš

    2008-12-01

    Full Text Available In the present time, characterized by the rapid disturbances in all time more connected global economy, territorially as well as structurally, the role of the state’s influence and responsibility with the adequate institutional addresses and procedures, defined in larger context, becomes the essential point not only of the further growth but also of the existing relations viability. It is simply because the encirclement does not function on the principle of status quo situation any more. Therefore, the role and significance of institutions, adequate regulatory role of these addresses, in the context of demand of permanent and stable economic growth, are of particular interest in the creation of this model. This analysis gains in importance studying the realized accelerated economic growth of states from some parts of the world, notably in the period after WW II. This question turned out to be exceptionally essential during the analysis of national strategies of accelerated economic growth (catch up strategy. On the other side of analysis are the transition period and the processes realized on the territory of the East and Central European states up to 1990 that were under the strong influence of the USSR. The attempts and mistakes in the quest for adequate balance of the market role were initially indoctrinated and led by the predominant conviction that the principles of Washington consensus will lead up to accelerated and efficient change of the entire structure of national economies and new frames for future behaviour. The problems that appeared very soon led to the establishment of significantly more balanced first the understanding and then to establishing significantly, more appropriate concept of balance and complementarity of market development with the permanently present role and responsibility of the state in this process and on this road.

  4. Regulatory focus and the family-work interface : the role of regulatory fit between cohabiting partners

    NARCIS (Netherlands)

    Demerouti, E.; Bakker, A.B.; Tetrick, L.

    2014-01-01

    The aim of the present study was to examine the impact of regulatory focus in goal pursuit and regulatory fit between marital partners on family conditions and the family–work interface. We hypothesized that when both partners are high on promotion focus (fit) they experience higher developmental

  5. The role of effective communications in Nuclear Regulatory Commission licensing

    International Nuclear Information System (INIS)

    Counsil, W.G.

    1991-01-01

    Communications are essential to the licensing and general regulatory program of the Nuclear Regulatory Commission. This paper attempts to identify and address certain aspects of, and approaches to, maintaining effective and efficient communications. It considers, from the perspective of the high-level radioactive waste repository program, both internal communication within the DOE itself and external communication with the Nuclear Regulatory Commission and interested parties. Many of the points presented are based on lessons learned from electric utility experience with nuclear plants

  6. The Tumorigenic Roles of the Cellular REDOX Regulatory Systems

    Directory of Open Access Journals (Sweden)

    Stéphanie Anaís Castaldo

    2016-01-01

    Full Text Available The cellular REDOX regulatory systems play a central role in maintaining REDOX homeostasis that is crucial for cell integrity, survival, and proliferation. To date, a substantial amount of data has demonstrated that cancer cells typically undergo increasing oxidative stress as the tumor develops, upregulating these important antioxidant systems in order to survive, proliferate, and metastasize under these extreme oxidative stress conditions. Since a large number of chemotherapeutic agents currently used in the clinic rely on the induction of ROS overload or change of ROS quality to kill the tumor, the cancer cell REDOX adaptation represents a significant obstacle to conventional chemotherapy. In this review we will first examine the different factors that contribute to the enhanced oxidative stress generally observed within the tumor microenvironment. We will then make a comprehensive assessment of the current literature regarding the main antioxidant proteins and systems that have been shown to be positively associated with tumor progression and chemoresistance. Finally we will make an analysis of commonly used chemotherapeutic drugs that induce ROS. The current knowledge of cancer cell REDOX adaptation raises the issue of developing novel and more effective therapies for these tumors that are usually resistant to conventional ROS inducing chemotherapy.

  7. Regulatory focus at work : the moderating role of regulatory focus in the job demands-resources model

    NARCIS (Netherlands)

    Brenninkmeijer, V.; Demerouti, E.; Blanc, Le P.M.; Emmerik, van I.J.H.

    2010-01-01

    Purpose – The purpose of this study is to examine the moderating role of regulatory focus in the job demands-resources model. Design/methodology/approach – A questionnaire survey was conducted among 146 teachers in secondary education. It was expected that detrimental effects of job demands (i.e.

  8. Causality analysis detects the regulatory role of maternal effect genes in the early Drosophila embryo

    Directory of Open Access Journals (Sweden)

    Zara Ghodsi

    2017-03-01

    Full Text Available In developmental studies, inferring regulatory interactions of segmentation genetic network play a vital role in unveiling the mechanism of pattern formation. As such, there exists an opportune demand for theoretical developments and new mathematical models which can result in a more accurate illustration of this genetic network. Accordingly, this paper seeks to extract the meaningful regulatory role of the maternal effect genes using a variety of causality detection techniques and to explore whether these methods can suggest a new analytical view to the gene regulatory networks. We evaluate the use of three different powerful and widely-used models representing time and frequency domain Granger causality and convergent cross mapping technique with the results being thoroughly evaluated for statistical significance. Our findings show that the regulatory role of maternal effect genes is detectable in different time classes and thereby the method is applicable to infer the possible regulatory interactions present among the other genes of this network.

  9. Deciphering Fur transcriptional regulatory network highlights its complex role beyond iron metabolism in Escherichia coli

    DEFF Research Database (Denmark)

    Seo, Sang Woo; Kim, Donghyuk; Latif, Haythem

    2014-01-01

    The ferric uptake regulator (Fur) plays a critical role in the transcriptional regulation of iron metabolism. However, the full regulatory potential of Fur remains undefined. Here we comprehensively reconstruct the Fur transcriptional regulatory network in Escherichia coli K-12 MG1655 in response...

  10. Interpersonal goal support in achieving ideals and oughts: The role of dispositional regulatory focus

    NARCIS (Netherlands)

    Righetti, F.; Kumashiro, M.

    2012-01-01

    The present work examines the role of each partner's regulatory focus in the phenomenon of interpersonal goal support in close relationships. We examined the impact of regulatory orientation for interpersonal support of both ideal and ought self goals. Consistent with expectations, two studies

  11. Adolescent threat-related interpretive bias and its modification: the moderating role of regulatory control

    NARCIS (Netherlands)

    Salemink, E.; Wiers, R.W.

    2012-01-01

    Dual process models describe psychopathology as the consequence of an imbalance between a fast, impulsive system and a regulatory control system and have recently been applied to anxiety disorders. The aim of the current study was to specifically examine the role of a regulatory control system in

  12. Sales Growth of New Pharmaceuticals Across the Globe: The Role of Regulatory Regimes

    NARCIS (Netherlands)

    S. Stremersch (Stefan); A. Lemmens (Aurélie)

    2008-01-01

    textabstractPrior marketing literature has overlooked the role of regulatory regimes in explaining international sales growth of new products. This paper addresses this gap in the context of new pharmaceuticals (15 new molecules in 34 countries) and sheds light on the effect regulatory regimes have

  13. Competitive mindsets, creativity, and the role of regulatory focus

    NARCIS (Netherlands)

    Bittner, Jenny; Heidemeier, Heike

    2013-01-01

    We examined how regulatory focus and intentions to compete rather than cooperate with group members relate to creativity. Study 1 showed that a promotion focus (i.e., a focus on ideals) activated a cooperative mindset, whereas a prevention focus (i.e., a focus on responsibilities) activated a

  14. Role of cooperation activities for capacity building of Romanian Regulatory Authority (CNCAN)

    International Nuclear Information System (INIS)

    Biro, L.; Ciurea-Ercau, C.

    2010-01-01

    With a slow but active nuclear development program of sector since 1980, Romanian regulatory authority had to permanently adapt to the changes in national and international environment in order ensure continuously increase of capacity building and effectiveness, commensurate with the growing nuclear sector. Limited human resources available at the national level put the Romanian Regulatory Authority in the position of building the Technical Support Organization as part of its on organization. International cooperation played an important role in capacity building of Romanian regulatory body and providing necessary assistance in performing regulatory activities or support in development of regulatory framework. Fellowships and technical visits, workshops and training courses provided through IAEA TC at national or regional level, technical assistance provided by European Commission (EC) through PHARE Projects, all provided valuable contribution in assuring training of regulatory staff and development of proper regulatory framework in Romania. Therefore, Romanian Regulatory Authority is putting a strong accent on strengthening and promoting international cooperation through IAEA Technical Cooperation Programme, Molls between regulatory bodies, as one of the key elements in supporting capacity building of regulatory authorities in countries having small or embarking on nuclear power program. Building networks between training centers and research facilities and establishments of regional training centers represent one of the future viable options in preserving knowledge in nuclear field. (author)

  15. Interracial America. Opposing Viewpoints Series.

    Science.gov (United States)

    Szumski, Bonnie, Ed.

    Books in the Opposing Viewpoints Series present debates about current issues that can be used to teach critical reading and thinking skills. The varied opinions in each book examine different aspects of a single issue. The topics covered in this volume explore the racial and ethnic tensions that concern many Americans today. The racial divide…

  16. The role of T regulatory cells in kidney transplantation

    OpenAIRE

    Urbanová, Anna

    2011-01-01

    T regulatory lymphocytes (Treg) belong to the CD4+ cell group. They are an essential part of the immunity system. Treg cells prevent from excessive activation of effector T cells and they keep the tolerance to the tissues of the body. They have high expression of CD25 and the transcription factor Foxp3. We distinguish two basic populations of Treg cells: natural Treg cells (nTreg) created in the thym and representing 5-10 % of all CD4+ cells, and induced Treg cells (iTreg), created from naive...

  17. Religious coalition opposes gene patents.

    Science.gov (United States)

    James, J S

    1995-05-19

    The biotechnology industry is concerned about a coalition of mainstream religious leaders, working with Jeremy Rifkin of the Foundation of Economic Trends, who oppose the patenting of human and animal life forms, body parts, and genes. The coalition called a press conference on May 18 to ask the government to prohibit the current patenting practices for genetic engineering. The biotechnology industry argues that patents indicate that a company's research tool has significant value, and encourages capitalists to invest their dollars in the development of new treatments for diseases. They also argue that the 29 biotech drugs that are on the market have been developed as a result of patents on genes. Although most business leaders are united in opposing restrictions, many scientists are divided, citing both religious and scientific reasons.

  18. Opposing roles of C/EBPbeta and AP-1 in the control of fibroblast proliferation and growth arrest-specific gene expression

    DEFF Research Database (Denmark)

    Gagliardi, Mark; Maynard, Scott; Miyake, Tetsuaki

    2003-01-01

    in the levels of AP-1 proteins. Therefore, C/EBPbeta is a negative regulator of AP-1 expression and activity in CEF. The expression of cyclin D1 and cell proliferation were stimulated by the dominant negative mutant of C/EBPbeta but not in the presence of TAM67, a dominant negative mutant of c-Jun and AP-1. CEF......Chicken embryo fibroblasts (CEF) express several growth arrest-specific (GAS) gene products in G0. In contact-inhibited cells, the expression of the most abundant of these proteins, the p20K lipocalin, is activated at the transcriptional level by C/EBPbeta. In this report, we describe the role of C....../EBPbeta in CEF proliferation. We show that the expression of a dominant negative mutant of C/EBPbeta (designated Delta184-C/EBPbeta) completely inhibited p20K expression at confluence and stimulated the proliferation of CEF without inducing transformation. Mouse embryo fibroblasts nullizygous for C/EBPbeta had...

  19. Role of the Regulatory Body in Implementing Defence in Depth in Nuclear Installations - Regulatory Oversight in Egypt

    Energy Technology Data Exchange (ETDEWEB)

    El-Sheikh, B. M., E-mail: badawymel@yahoo.com [Egyptian Nuclear and Radiological Regulatory Authority Cairo (Egypt)

    2014-10-15

    The fundamental objective of all nuclear safety regulatory bodies is to ensure that nuclear facilities are operated at all times in an acceptably safe manner including the safe conduct of decommissioning activities. Defence in depth is recognized as one of the fundamental safety principles that underlie the safety of nuclear power plants. Defence in depth is implemented to provide a graded protection against a wide variety of transients, incidents and accidents, including equipment failures and human errors within nuclear power plants and events initiated outside plants. The Regulator Body plays an important role in implementing defence in depth in nuclear installations in the context of a clear allocation of responsibilities with an operating organization. This role starting with setting safety objectives and by its own independent review and technical assessment of the safety justifications provided by the operating organization in addition to safety culture investigating within relevant organizations. This paper briefly reviews this role in normal operation and post accidents, and its effects on overall nuclear safety in nuclear installations with reference to Egyptian regulatory oversight. (author)

  20. Foxo1 and Foxp1 play opposing roles in regulating the differentiation and antitumor activity of TH9 cells programmed by IL-7

    Science.gov (United States)

    Bi, Enguang; Ma, Xingzhe; Lu, Yong; Yang, Maojie; Wang, Qiang; Xue, Gang; Qian, Jianfei; Wang, Siqing; Yi, Qing

    2018-01-01

    Tumor-specific CD4+ T helper 9 (TH9) cells, so-called because of their production of the cytokine interleukin-9 (IL-9), are a powerful effector T cell subset for cancer immunotherapy. We found that pretreatment of naïve CD4+ T cells with IL-7 further enhanced their differentiation into TH9 cells and augmented their antitumor activity. IL-7 markedly increased the abundance of the histone acetyltransferase p300 by activating the STAT5 and PI3K-AKT-mTOR signaling pathways and promoting the acetylation of histones at the Il9 promoter. As a result, the transcriptional regulator Foxo1 was dephosphorylated and translocated to the nucleus, bound to the Il9 promoter, and induced the production of IL-9 protein. In contrast, Foxp1, which bound to the Il9 promoter in naïve CD4+ T cells and inhibited Il9 expression, was outcompeted for binding to the Il9 promoter by Foxo1 and translocated to the cytoplasm. Furthermore, forced expression of Foxo1 or a deficiency in Foxp1 in CD4+ T cells markedly increased the production of IL-9, whereas a deficiency in Foxo1 inhibited the ability of IL-7 to enhance the differentiation and antitumor activity of TH9 cells. Thus, we identified the roles of Foxo1 as a positive regulator and Foxp1 as a negative regulator of TH9 cell differentiation and antitumor activity, which may provide potential targets for cancer immunotherapy. PMID:29018172

  1. The role of women in nuclear - attracting public participation in regulatory decision-making process

    Science.gov (United States)

    Mohamad Jais, Azlina; Hassan, Najwa

    2018-01-01

    Public participation is vital in demonstrating transparency and enhancing effectiveness of a nuclear regulatory process. As such, it is necessary for nuclear practitioners to involve the public in key nuclear delivery milestones. This paper specifically discusses challenges faced in attracting public participation throughout the nuclear regulatory decision-making process, and highlights the roles of women in nuclear (WiN) in initiating the said public discourse.

  2. The role of risk assessment in the nuclear regulatory process

    International Nuclear Information System (INIS)

    Levine, S.

    1979-01-01

    Since the publication of the Reactor Safety Study in the USA, the basic tasks of which are summarised, the use of quantitative risk-assessment techniques for the safety of nuclear power plants has increased considerably. Some of the viewpoints expressed on the use of these techniques are examined, and their limitations are discussed. Areas where risk-assessment techniques are applied by the NRC are listed and some recent examples are discussed. Risk assessment has also been used as a criteria for deciding the topics for the NRC's recommendations for research programs. It is concluded that the major contribution of risk assessment techniques should be in the form of background analyses that will aid decision making and could also significantly affect the scope and content of regulatory reviews. (UK)

  3. Role of human neurobehavioural tests in regulatory activity on chemicals

    Science.gov (United States)

    Stephens, R.; Barker, P.

    1998-01-01

    Psychological performance tests have been used since the mid-1960s in occupational and environmental health toxicology. The interpretation of significantly different test scores in neurobehavioural studies is not straightforward in the regulation of chemicals. This paper sets out some issues which emerged from discussions at an international workshop, organised by the United Kingdom Health and Safety Executive (HSE), to discuss differences in interpretation of human neurobehavioural test data in regulatory risk assessments. The difficulties encountered by regulators confronted with neurobehavioural studies seem to be twofold; some studies lack scientific rigor; other studies, although scientifically sound, are problematic because it is not clear what interpretation to place on the results. Issues relating to each of these points are discussed. Next, scenarios within which to consider the outcomes of neurobehavioural studies are presented. Finally, conclusions and recommendations for further work are put forward.   PMID:9624273

  4. Inferring the role of transcription factors in regulatory networks

    Directory of Open Access Journals (Sweden)

    Le Borgne Michel

    2008-05-01

    Full Text Available Abstract Background Expression profiles obtained from multiple perturbation experiments are increasingly used to reconstruct transcriptional regulatory networks, from well studied, simple organisms up to higher eukaryotes. Admittedly, a key ingredient in developing a reconstruction method is its ability to integrate heterogeneous sources of information, as well as to comply with practical observability issues: measurements can be scarce or noisy. In this work, we show how to combine a network of genetic regulations with a set of expression profiles, in order to infer the functional effect of the regulations, as inducer or repressor. Our approach is based on a consistency rule between a network and the signs of variation given by expression arrays. Results We evaluate our approach in several settings of increasing complexity. First, we generate artificial expression data on a transcriptional network of E. coli extracted from the literature (1529 nodes and 3802 edges, and we estimate that 30% of the regulations can be annotated with about 30 profiles. We additionally prove that at most 40.8% of the network can be inferred using our approach. Second, we use this network in order to validate the predictions obtained with a compendium of real expression profiles. We describe a filtering algorithm that generates particularly reliable predictions. Finally, we apply our inference approach to S. cerevisiae transcriptional network (2419 nodes and 4344 interactions, by combining ChIP-chip data and 15 expression profiles. We are able to detect and isolate inconsistencies between the expression profiles and a significant portion of the model (15% of all the interactions. In addition, we report predictions for 14.5% of all interactions. Conclusion Our approach does not require accurate expression levels nor times series. Nevertheless, we show on both data, real and artificial, that a relatively small number of perturbation experiments are enough to determine

  5. Role of in-house safety analysis and research activities in regulatory decision making

    International Nuclear Information System (INIS)

    Pradhan, Santosh K.; Nagrale, Dhanesh B.; Gaikwad, Avinash J.

    2015-01-01

    Achievement of an acceptable level of nuclear safety is an essential requirement for the peaceful utilization of nuclear energy. The success of Global Nuclear Safety Regime is built upon a foundation of research. Such research has been sponsored by Governments and industry and has led to improved designs, safer and more reliable plant operation, and improvements in operating plant efficiency. A key element of this research has been the nuclear safety research performed or sponsored by regulatory organizations. In part, it has been the safety research performed or sponsored by regulatory organizations that has contributed to improved safety and has laid the foundation for activities such as risk-informed regulation, plant life extension, improved plant performance (e.g. power uprates) and new plant designs. The regulatory research program is meant to improve the regulatory authority’s knowledge where uncertainty exists, where safety margins are not well-characterized, and where regulatory decisions need to be confirmed in existing or new designs and technologies. The regulatory body get research initiated either in-house or by the licensee or through technical support organizations (TSOs). Research and analysis carried out within the regulatory body is of immense value in this context. This could be in the form of analysis of safety significant events, analysis of severe accidents, review of operating experience, independent checks of critical designs and even review of operator responses under different situations towards arriving at modifications to training programmes and licensing procedures for operating personnel. A latent benefit of regulatory research carried out by the regulators themselves is that it improves their technical competence considerably which in turn leads to high quality safety reviews and improved regulation in general. The aim of the present paper is to provide an overview of role of regulatory research and the in-house regulatory safety

  6. Regulatory Role of Small Nucleolar RNAs in Human Diseases

    Directory of Open Access Journals (Sweden)

    Grigory A. Stepanov

    2015-01-01

    Full Text Available Small nucleolar RNAs (snoRNAs are appreciable players in gene expression regulation in human cells. The canonical function of box C/D and box H/ACA snoRNAs is posttranscriptional modification of ribosomal RNAs (rRNAs, namely, 2′-O-methylation and pseudouridylation, respectively. A series of independent studies demonstrated that snoRNAs, as well as other noncoding RNAs, serve as the source of various short regulatory RNAs. Some snoRNAs and their fragments can also participate in the regulation of alternative splicing and posttranscriptional modification of mRNA. Alterations in snoRNA expression in human cells can affect numerous vital cellular processes. SnoRNA level in human cells, blood serum, and plasma presents a promising target for diagnostics and treatment of human pathologies. Here we discuss the relation between snoRNAs and oncological, neurodegenerative, and viral diseases and also describe changes in snoRNA level in response to artificial stress and some drugs.

  7. Leptin: regulatory role in bone metabolism and in flogosis

    Directory of Open Access Journals (Sweden)

    G.D. Ferraccioli

    2011-09-01

    Full Text Available Leptin is a peptidic molecule synthesized almost exclusively by adipocytes, that regulates appetite and energy expenditure at the hypothalamic level. In the last few years, further actions have been attributed to this molecule, as modulating the immune response and affecting the bone metabolism. We have reviewed if leptin contributes to the metabolic changes leading to cachexia and to the regulation of flogosis, paying attention to the pathogenetic mechanisms of cronic arthritis. Besides, considering the relationship between body mass index (BMI e bone mineral density (BMD and the protective role of the obesity towards osteoporosis, we have analysed the role of leptin on the bone metabolism

  8. Opposed slant tube diabatic sorber

    Science.gov (United States)

    Erickson, Donald C.

    2004-01-20

    A sorber comprised of at least three concentric coils of tubing contained in a shell with a flow path for liquid sorbent in one direction, a flow path for heat transfer fluid which is in counter-current heat exchange relationship with sorbent flow, a sorbate vapor port in communication with at least one of sorbent inlet or exit ports, wherein each coil is coiled in opposite direction to those coils adjoining it, whereby the opposed slant tube configuration is achieved, with structure for flow modification in the core space inside the innermost coil.

  9. Cholesterol: a novel regulatory role in myelin formation.

    Science.gov (United States)

    Saher, Gesine; Quintes, Susanne; Nave, Klaus-Armin

    2011-02-01

    Myelin consists of tightly compacted membranes that form an insulating sheath around axons. The function of myelin for rapid saltatory nerve conduction is dependent on its unique composition, highly enriched in glycosphingolipids and cholesterol. Cholesterol emerged as the only integral myelin component that is essential and rate limiting for the development of CNS and PNS myelin. Experiments with conditional mouse mutants that lack cholesterol biosynthesis in oligodendrocytes revealed that only minimal changes of the CNS myelin lipid composition are tolerated. In Schwann cells of the PNS, protein trafficking and myelin compaction depend on cholesterol. In this review, the authors summarize the role of cholesterol in myelin biogenesis and myelin disease.

  10. Beyond toxicity: a regulatory role for mitochondrial cyanide.

    Science.gov (United States)

    García, Irene; Gotor, Cecilia; Romero, Luis C

    2014-01-01

    In non-cyanogenic plants, cyanide is a co-product of ethylene and camalexin biosynthesis. To maintain cyanide at non-toxic levels, Arabidopsis plants express the mitochondrial β-cyanoalanine synthase CYS-C1. CYS-C1 knockout leads to an increased level of cyanide in the roots and leaves and a severe defect in root hair morphogenesis, suggesting that cyanide acts as a signaling factor in root development. During compatible and incompatible plant-bacteria interactions, cyanide accumulation and CYS-C1 gene expression are negatively correlated. Moreover, CYS-C1 mutation increases both plant tolerance to biotrophic pathogens and their susceptibility to necrotrophic fungi, indicating that cyanide could stimulate the salicylic acid-dependent signaling pathway of the plant immune system. We hypothesize that CYS-C1 is essential for maintaining non-toxic concentrations of cyanide in the mitochondria to facilitate cyanide's role in signaling.

  11. THE ROLE OF SELF-REGULATORY AUDITING ASSOCIATIONS IN ARRANGEMENT OF AUDIT ACTIVITIES QUALITY CONTROL

    Directory of Open Access Journals (Sweden)

    Zinaida P. Arharova

    2013-01-01

    Full Text Available The role of self-regulatory organizations in audit activities quality control is revealed in this article. Creation of a united audit association is the basis of certain regulating and auditing functions transfer from the government to the public sector.

  12. Safeguards decision making in the public and regulatory environment, and the potential role of quantitative approaches

    International Nuclear Information System (INIS)

    Sherr, T.S.

    1981-01-01

    This paper briefly examines the nature of the safeguards program's objectives and constraints, and the inherent limitations on comprehensive quantification. It discusses the nature of the public and regulatory processes employed in safeguards decision making, and examines their implications regarding the potential role of quantitative approaches to safeguards policy and operational decision making

  13. The U.S. Nuclear Regulatory Commission's role in the management of radioactive wastes

    International Nuclear Information System (INIS)

    Bernero, R.M.; Kalman, K.L.

    1991-01-01

    This paper discusses the U.S. Nuclear Regulatory Commission's (NRC's) role in the management of radioactive waste. It provides an overview of the NRC's programs for the management of High-Level and Low-Level radioctive wastes and uranium mill tailings. (author) 7 refs

  14. The intrinsic roles of regulatory instruments in mining operations

    Directory of Open Access Journals (Sweden)

    Kola O. Odeku

    2015-05-01

    Full Text Available Prospecting and exploiting natural mineral resources for economic growth and development could be beneficial if done in sustainable ways and manners. However, if the operation is done in such a way that cause harm to the environment and people, this will amount to unsustainable mining activity and anti-sustainable development. Therefore, there is need to ensure that appropriate and adequate plans and programmes are put in place in order to mitigate, minimise and avoid negative environmental impacts. Against the backdrop of these concerns and the need to ensure that the environment is not degraded and destroyed, South Africa, as part of the countries that promotes sustainable prospecting and mining has put in place and currently implementing tools known as environmental management plan and programme to regulate and control all prospecting and mining activities. These tools contain a bundle of remedial actions in the forms of compensation, rehabilitation and restoration of any harm done to the environment during the course of mining activities. They also contain information on mitigation, ingredients for good practice approach on how to conduct sustainable prospecting and mining. This article looks at the intrinsic roles of these tools and accentuates the importance and operations of their use in the decision making processe

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

    Lifescience Database Archive (English)

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

  16. Role of technical and scientific support organization In Indonesian regulatory body

    International Nuclear Information System (INIS)

    Yusri Heni, N.A.; Zarkasih, A.S.; Liliana, Y.P.; Salman, S.

    2007-01-01

    Indonesian Nuclear Energy Regulatory Agency (BAPETEN) has the function in controlling the utility of nuclear energy through regulation, licensing and inspection, with the aim, interalia, to ensure the welfare, the security and the peace of people, to assure the safety and the health of workers and public, and the environmental protection, and to prevent diversion of purpose of the nuclear material utilization (Article 14 and 15 of Act no 10, 1997 on Nuclear Energy). The role and quality of technical and scientific expertise in supporting regulatory systems are importance increase the effectiveness and public confidence. The Center for Regulatory Assessment of Nuclear Installation and Nuclear Material and Center for Regulatory Assessment of Radiation Facilities and Radioactive Sources as part of BAPETEN organization has a function as technical and scientific support for regulatory systems. The purpose of this function is to provide technical and scientific basis for decisions and activities regarding nuclear and radiation safety during regulatory processes, such as in the developing and establishing regulation, technical verification for licensing, assessment of inspection funding and enforcement. In order to meet the quality and effectiveness of technical and scientific result activity, those two centers for regulatory assesment used internal and external technical experts and joint cooperation with universities, research institutes or laboratories. The development of technical and scientific strategic planning in enhancing nuclear and radiation safety is done by the following increasing of : Human resources and expertise by internal and external training or on the job training; number for computer code to perform safety analysis, capability and quality for review and assessment, national and international cooperation, etc. (author)

  17. The role of self-regulatory efficacy, moral disengagement and guilt on doping likelihood: A social cognitive theory perspective.

    Science.gov (United States)

    Ring, Christopher; Kavussanu, Maria

    2018-03-01

    Given the concern over doping in sport, researchers have begun to explore the role played by self-regulatory processes in the decision whether to use banned performance-enhancing substances. Grounded on Bandura's (1991) theory of moral thought and action, this study examined the role of self-regulatory efficacy, moral disengagement and anticipated guilt on the likelihood to use a banned substance among college athletes. Doping self-regulatory efficacy was associated with doping likelihood both directly (b = -.16, P self-regulatory efficacy influences the likelihood to use banned performance-enhancing substances both directly and indirectly via moral disengagement.

  18. WTO+ commitments on services in Asian PTAs: The role of regulatory homogeneity and goods trade complementarity

    OpenAIRE

    Shingal, Anirudh; Ro, Martin; Sauvé, Pierre

    2018-01-01

    This paper looks at the role of applied services regulations in accounting for WTO+ commitments on trade in services in preferential trade agreements (PTAs) among Asian economies. The empirical findings suggest that Asian trading dyads with regulatory frameworks that are more similar and more trade-restrictive tend to undertake higher levels of WTO+ commitments on services in their PTAs. There is also evidence in the results for such WTO+ commitments being driven by goods trade complementarit...

  19. Security of handling radioactive sources and the role of the regulatory body in Egypt

    International Nuclear Information System (INIS)

    Salama, M.

    1998-01-01

    The motivation of the present paper was undertaken to discuss the system adopted by the National Centre for Nuclear Safety and Radiation Control (NCNSRC) in handling the radioactive sources inside the country. The system concentrates mainly on the role of the centre concerning three main categories namely regulations, licensing and training. The mutual co-operation between the regulatory body and the other agencies concerning this matter is going to be presented. (author)

  20. Role of the regulatory authority in preparation of the NPP self assessment of safety culture

    Energy Technology Data Exchange (ETDEWEB)

    Gantchev, T [Committee on the Use of Atomic Energy for Peaceful Purposes, Sofia (Bulgaria)

    1997-12-31

    We believe that with the assistance of the IAEA(ASSET Training Mission) the plant personnel will be able to prepare high quality Self Assessment Report. The main role of the Regulatory Body is to ensure correspondence with the IAEA requirements and to provide clear guidance for the most important items of the Plant Self Assessment Report. The involvement of the Operating Organization is also desirable in order to ensure the necessary resources for the implementation of the action plan. Figs.

  1. Role of the regulatory authority in preparation of the NPP self assessment of safety culture

    International Nuclear Information System (INIS)

    Gantchev, T.

    1996-01-01

    We believe that with the assistance of the IAEA(ASSET Training Mission) the plant personnel will be able to prepare high quality Self Assessment Report. The main role of the Regulatory Body is to ensure correspondence with the IAEA requirements and to provide clear guidance for the most important items of the Plant Self Assessment Report. The involvement of the Operating Organization is also desirable in order to ensure the necessary resources for the implementation of the action plan. Figs

  2. Role of Resistive Self-Regulatory Efficacy and Moral Disengagement in the Relationship between Values and Aggressiveness in Athletes

    OpenAIRE

    Albouza Y; d'Arripe-Longueville F; Corrion K

    2017-01-01

    This study examined whether athletes’ values are related to aggressiveness through self-regulatory mechanisms. Athletes (N=225) completed four questionnaires to assess their values, resistive self-regulatory efficacy, moral disengagement and aggressiveness. The results of structural equation modeling showed a good fit to the data and illustrated that: (a) The status and moral values were indirectly associated with aggressiveness through the mediating roles of resistive self-regulatory efficac...

  3. Current role of the USNRC safety research program in support of the regulatory process

    International Nuclear Information System (INIS)

    Levine, S.

    1979-01-01

    The current role of the USNRC's safety research program is shown. Some aspects of this role in the wake of the TMI accident are discused as well as some historical perspective on the development of USNRC's program, its relationship with the NRC mission, an overview of the program activities and some recent research results, and finally the impact of the TMI accident in clarifiying needs for expedited and new research activities, including the need for a greatly enhanced use of probabilistic analysis techniques to improve the coherence of its regulatory process. (author)

  4. Regulatory Roles for Long ncRNA and mRNA

    Energy Technology Data Exchange (ETDEWEB)

    Karapetyan, Armen R.; Buiting, Coen; Kuiper, Renske A.; Coolen, Marcel W., E-mail: M.Coolen@gen.umcn.nl [Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences (NCMLS), Radboud University Nijmegen Medical Centre, P.O. Box 9101, Nijmegen 6500 HB (Netherlands)

    2013-04-26

    Recent advances in high-throughput sequencing technology have identified the transcription of a much larger portion of the genome than previously anticipated. Especially in the context of cancer it has become clear that aberrant transcription of both protein-coding and long non-coding RNAs (lncRNAs) are frequent events. The current dogma of RNA function describes mRNA to be responsible for the synthesis of proteins, whereas non-coding RNA can have regulatory or epigenetic functions. However, this distinction between protein coding and regulatory ability of transcripts may not be that strict. Here, we review the increasing body of evidence for the existence of multifunctional RNAs that have both protein-coding and trans-regulatory roles. Moreover, we demonstrate that coding transcripts bind to components of the Polycomb Repressor Complex 2 (PRC2) with similar affinities as non-coding transcripts, revealing potential epigenetic regulation by mRNAs. We hypothesize that studies on the regulatory ability of disease-associated mRNAs will form an important new field of research.

  5. Regulatory Roles for Long ncRNA and mRNA

    International Nuclear Information System (INIS)

    Karapetyan, Armen R.; Buiting, Coen; Kuiper, Renske A.; Coolen, Marcel W.

    2013-01-01

    Recent advances in high-throughput sequencing technology have identified the transcription of a much larger portion of the genome than previously anticipated. Especially in the context of cancer it has become clear that aberrant transcription of both protein-coding and long non-coding RNAs (lncRNAs) are frequent events. The current dogma of RNA function describes mRNA to be responsible for the synthesis of proteins, whereas non-coding RNA can have regulatory or epigenetic functions. However, this distinction between protein coding and regulatory ability of transcripts may not be that strict. Here, we review the increasing body of evidence for the existence of multifunctional RNAs that have both protein-coding and trans-regulatory roles. Moreover, we demonstrate that coding transcripts bind to components of the Polycomb Repressor Complex 2 (PRC2) with similar affinities as non-coding transcripts, revealing potential epigenetic regulation by mRNAs. We hypothesize that studies on the regulatory ability of disease-associated mRNAs will form an important new field of research

  6. Regulatory Roles for Long ncRNA and mRNA

    Directory of Open Access Journals (Sweden)

    Marcel W. Coolen

    2013-04-01

    Full Text Available Recent advances in high-throughput sequencing technology have identified the transcription of a much larger portion of the genome than previously anticipated. Especially in the context of cancer it has become clear that aberrant transcription of both protein-coding and long non-coding RNAs (lncRNAs are frequent events. The current dogma of RNA function describes mRNA to be responsible for the synthesis of proteins, whereas non-coding RNA can have regulatory or epigenetic functions. However, this distinction between protein coding and regulatory ability of transcripts may not be that strict. Here, we review the increasing body of evidence for the existence of multifunctional RNAs that have both protein-coding and trans-regulatory roles. Moreover, we demonstrate that coding transcripts bind to components of the Polycomb Repressor Complex 2 (PRC2 with similar affinities as non-coding transcripts, revealing potential epigenetic regulation by mRNAs. We hypothesize that studies on the regulatory ability of disease-associated mRNAs will form an important new field of research.

  7. Moving through the stressed genome: Emerging regulatory roles for transposons in plant stress tolerance

    Directory of Open Access Journals (Sweden)

    Negi Pooja

    2016-10-01

    Full Text Available The recognition of a positive correlation between organism genome size with its transposable element (TE content, represents a key discovery of the field of genome biology. Considerable evidence accumulated since then suggests the involvement of TEs in genome structure, evolution and function. The global genome reorganization brought about by transposon activity might play an adaptive/regulatory role in the host response to environmental challenges, reminiscent of McClintock’s original ’Controlling Element’ hypothesis. This regulatory aspect of TEs is also garnering support in light of the recent evidences which project TEs as distributed genomic control modules. According to this view, TEs are capable of actively reprogramming host genes circuits and ultimately fine-tuning the host response to specific environmental stimuli. Moreover, the stress-induced changes in epigenetic status of TE activity may allow TEs to propagate their stress responsive elements to host genes; the resulting genome fluidity can permit phenotypic plasticity and adaptation to stress. Given their predominating presence in the plant genomes, nested organization in the genic regions and potential regulatory role in stress response, TEs hold unexplored potential for crop improvement programs. This review intends to present the current information about the roles played by TEs in plant genome organization, evolution and function, and highlight the regulatory mechanisms in plant stress responses. We will also briefly discuss the connection between TE activity, host epigenetic response and phenotypic plasticity as a critical link for traversing the translational bridge from a purely basic study of TEs, to the applied field of stress adaptation and crop improvement.

  8. Moving through the Stressed Genome: Emerging Regulatory Roles for Transposons in Plant Stress Response.

    Science.gov (United States)

    Negi, Pooja; Rai, Archana N; Suprasanna, Penna

    2016-01-01

    The recognition of a positive correlation between organism genome size with its transposable element (TE) content, represents a key discovery of the field of genome biology. Considerable evidence accumulated since then suggests the involvement of TEs in genome structure, evolution and function. The global genome reorganization brought about by transposon activity might play an adaptive/regulatory role in the host response to environmental challenges, reminiscent of McClintock's original 'Controlling Element' hypothesis. This regulatory aspect of TEs is also garnering support in light of the recent evidences, which project TEs as "distributed genomic control modules." According to this view, TEs are capable of actively reprogramming host genes circuits and ultimately fine-tuning the host response to specific environmental stimuli. Moreover, the stress-induced changes in epigenetic status of TE activity may allow TEs to propagate their stress responsive elements to host genes; the resulting genome fluidity can permit phenotypic plasticity and adaptation to stress. Given their predominating presence in the plant genomes, nested organization in the genic regions and potential regulatory role in stress response, TEs hold unexplored potential for crop improvement programs. This review intends to present the current information about the roles played by TEs in plant genome organization, evolution, and function and highlight the regulatory mechanisms in plant stress responses. We will also briefly discuss the connection between TE activity, host epigenetic response and phenotypic plasticity as a critical link for traversing the translational bridge from a purely basic study of TEs, to the applied field of stress adaptation and crop improvement.

  9. Moving through the Stressed Genome: Emerging Regulatory Roles for Transposons in Plant Stress Response

    Science.gov (United States)

    Negi, Pooja; Rai, Archana N.; Suprasanna, Penna

    2016-01-01

    The recognition of a positive correlation between organism genome size with its transposable element (TE) content, represents a key discovery of the field of genome biology. Considerable evidence accumulated since then suggests the involvement of TEs in genome structure, evolution and function. The global genome reorganization brought about by transposon activity might play an adaptive/regulatory role in the host response to environmental challenges, reminiscent of McClintock's original ‘Controlling Element’ hypothesis. This regulatory aspect of TEs is also garnering support in light of the recent evidences, which project TEs as “distributed genomic control modules.” According to this view, TEs are capable of actively reprogramming host genes circuits and ultimately fine-tuning the host response to specific environmental stimuli. Moreover, the stress-induced changes in epigenetic status of TE activity may allow TEs to propagate their stress responsive elements to host genes; the resulting genome fluidity can permit phenotypic plasticity and adaptation to stress. Given their predominating presence in the plant genomes, nested organization in the genic regions and potential regulatory role in stress response, TEs hold unexplored potential for crop improvement programs. This review intends to present the current information about the roles played by TEs in plant genome organization, evolution, and function and highlight the regulatory mechanisms in plant stress responses. We will also briefly discuss the connection between TE activity, host epigenetic response and phenotypic plasticity as a critical link for traversing the translational bridge from a purely basic study of TEs, to the applied field of stress adaptation and crop improvement. PMID:27777577

  10. The role of the Nuclear Regulatory Commission in the management of nuclear waste

    International Nuclear Information System (INIS)

    Thompson, H.L. Jr.

    1988-01-01

    In general, the US Nuclear Regulatory Commission (NRC) is responsible for reviewing and making licensing decisions to ensure that the US Department of Energy's (DOE's) high-level waste repository is designed, constructed, and operated without unreasonable risk to public health and safety. In implementing this responsibility, however, the commission's guidance to the staff is that, in the absence of unresolved safety concerns, the NRC regulatory program will not delay the executive branch's program as set forth in the DOE project decision schedule. The NRC role for the next several years will be to develop its licensing framework and to consult with DOE on its plans. An essential ingredient in the success of both NRC's and DOE's respective missions is the need for free and open exchange of information, which will assure us that the concerns of all parties are addressed. With regard to low-level radioactive waste, the states have the lead responsibility for disposal. The NRC also provides assistance to the states and compacts on such items as regulatory programs, site characterization, and mixed waste disposal. Another of the NRC's roles is in the management of uranium mill tailings. Currently, most of the NRC's attention is focused on ensuring adequate long-term stabilization of tailings

  11. The role of learning environment on high school chemistry students' motivation and self-regulatory processes

    Science.gov (United States)

    Judd, Jeffrey S.

    Changes to the global workforce and technological advancements require graduating high school students to be more autonomous, self-directed, and critical in their thinking. To reflect societal changes, current educational reform has focused on developing more problem-based, collaborative, and student-centered classrooms to promote effective self-regulatory learning strategies, with the goal of helping students adapt to future learning situations and become life-long learners. This study identifies key features that may characterize these "powerful learning environments", which I term "high self-regulating learning environments" for ease of discussion, and examine the environment's role on students' motivation and self-regulatory processes. Using direct observation, surveys, and formal and informal interviews, I identified perceptions, motivations, and self-regulatory strategies of 67 students in my high school chemistry classes as they completed academic tasks in both high and low self-regulating learning environments. With social cognitive theory as a theoretical framework, I then examined how students' beliefs and processes changed after they moved from low to a high self-regulating learning environment. Analyses revealed that key features such as task meaning, utility, complexity, and control appeared to play a role in promoting positive changes in students' motivation and self-regulation. As embedded cases, I also included four students identified as high self-regulating, and four students identified as low self-regulating to examine whether the key features of high and low self-regulating learning environments played a similar role in both groups. Analysis of findings indicates that key features did play a significant role in promoting positive changes in both groups, with high self-regulating students' motivation and self-regulatory strategies generally remaining higher than the low self-regulating students; this was the case in both environments. Findings

  12. 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.

  13. Hematopoietic chimerism and transplantation tolerance: a role for regulatory T cells

    Directory of Open Access Journals (Sweden)

    Lise ePasquet

    2011-12-01

    Full Text Available The major obstacle in transplantation medicine is rejection of donor tissues by the host’s immune system. Immunosuppressive drugs can delay but not prevent loss of transplants, and their efficiency is strongly impacted by inter-individual pharmacokinetic differences. Moreover, due to the global immunosuppression induced and to the broad distribution of their targets amongst human tissues, these drugs have severe side effects. Induction of donor-specific non-responsiveness (i.e. immunological tolerance to transplants would solve these problems and would substantially ameliorate patients’ quality of life. It is widely believed that bone marrow or hematopoietic stem cell transplantation, and resulting (mixed hematopoietic chimerism, invariably leads to immunological tolerance to organs of the same donor. A careful analysis of the literature, reviewed here, indeed shows that chimerism consistently prolongs allograft survival. However, in absence of additional conditioning leading to the development of active regulatory mechanisms, it does not prevent chronic rejection. A central role for active tolerance in transplantation-tolerance is also supported by recent data showing that genuine immunological tolerance to organ allografts can be achieved by combining induction of hematopoietic chimerism with infusion of regulatory T lymphocytes. Therefore, conditioning regimens that lead to the establishment of hematopoietic chimerism plus active regulatory mechanisms appear required for induction of genuine tolerance to allogeneic grafts.

  14. TSO Role in Supporting the Regulatory Authority in View of Safety Culture

    International Nuclear Information System (INIS)

    Khamaza, A.; Vasilishin, A.

    2016-01-01

    Human and organizational factors are always of paramount importance at nuclear and radiation safety as well as in the safety regulation provision. Major NPP accidents occurred merely reaffirm this fact. The role of an authority that regulates nuclear safety increases each time in the aftermath of accidents perceived as a shock together with the importance of scientific and technical support. SEC NRS was established in 1987, the next year after the Chernobyl NPP accident aiming to strengthen supervision over works carried out at the nuclear industry enterprises. Currently SEC NRS provides comprehensive scientific and technical support to Rostechnadzor including safety review and regulatory legal documents development to regulate safety along with safety culture.

  15. The role of regulatory uncertainty in certificate markets: A case study of the Swedish/Norwegian market

    International Nuclear Information System (INIS)

    Fagiani, Riccardo; Hakvoort, Rudi

    2014-01-01

    Price volatility in green certificate markets reflects uncertainty over future prices, representing a major source of risk for renewable energy generators. Price risk is considered the principal deficiency of this market-based policy since it causes investors to require higher returns. Moreover, investors are exposed to regulatory risk; namely, the risk that a change in the regulation will materially impact the certificate price. Regulatory uncertainty is reflected in market volatility exacerbating certificate price risk. Using an econometric approach, we investigate the role of regulatory changes on price volatility in the Swedish certificate market. The results of our analysis indicate that regulatory changes strongly affect certificate markets, resulting in periods of higher volatility. Moreover, we analyze whether certificate price volatility has changed after creating a joint Swedish/Norwegian market. Results indicate that the ambivalence surrounding the creation of this bigger market led to a period of increased price volatility between 2010 and 2011. Overall, this article brings a better understanding of the role of regulatory uncertainty on certificate markets, and gives evidence for its negative impact in terms of increased price volatility. - Highlights: • Paper analyzes the impact of regulatory changes on certificate price volatility. • Regulatory changes affect market volatility and price risk. • Regulatory uncertainty harms certificate markets. • The bigger Swedish/Norwegian market has not resulted in lower volatility yet

  16. The Role of Level-3 PSA in the Regulatory Structure for the Licensing of Future NPPs

    International Nuclear Information System (INIS)

    Jeong, Jong Tae; Han, Sang Hoon

    2008-01-01

    The probabilistic safety assessment (PSA) provides a systematic analysis to identify and quantify all risks that the plant imposed to the operators, general public and the environment and thus demonstrates compliance to regulatory risk criteria. Therefore, the PSA has been being played an important role in the development of safety requirements for the existing plants, mainly reactors using light water technology. However, the existing safety requirements may not be fully applicable to the future reactors due to the advances in technology, new safety options, and new strategies for managing abnormal plant conditions. Therefore, a comprehensive set of technology-neutral safety requirements are being developed by the IAEA and USNRC. Especially, USNRC is developing a basis for a regulatory structure that is applicable to all types of reactor designs, including gas-cooled, liquid metal, and heavy and light water-moderated reactors because metrics such as core damage and large early release may not be applicable to some advanced reactor designs. They are developing this kind of basis for a regulatory structure in order to provide a technology neutral safety approach that will guide the design, construction and operation, as well as safety assessment, of innovative reactors. They are using the quantitative safety goals expressed by means of a frequency-consequence diagram. Within this approach, the scope of the PSA needs to encompass a whole spectrum of off-normal events including frequent, infrequent, and rare initiating events and event sequences. These events include a spectrum of releases from minor to major, and sequences that address conditions less than the core damage sequences. It also needs to address the dose consequences of these event sequences as measured at the exclusion area boundary (EAB). In order to obtain dose consequences for the whole spectrum of off-normal events, the dose evaluation by using the deterministic and probabilistic approaches has to be

  17. [Regulatory role of NKT cells in the prevention of type 1 diabetes].

    Science.gov (United States)

    Ghazarian, Liana; Simoni, Yannick; Pingris, Karine; Beaudoin, Lucie; Lehuen, Agnès

    2013-01-01

    Type 1 diabetes is an autoimmune disease resulting from the destruction of pancreatic β cells by the immune system. NKT cells are innate-like T cells that can exert potent immuno-regulatory functions. The regulatory role of NKT cells was initially proposed after the observed decreased frequency of this subset in mouse models of type 1 diabetes, as well as in patients developing various autoimmune pathologies. Increasing NKT cell frequency and function prevent the development of type 1 diabetes in mouse models. Several mechanisms including IL-4 and IL-10 production by NKT cells and the accumulation of tolerogenic dendritic cells are critical for the dampening of pathogenic anti-islet T cell responses by NKT cells. Importantly, these cells can at the same time prevent diabetes and promote efficient immune responses against infectious agents. These results strengthen the potential role of NKT cells as a key target for the development of therapeutic strategies against type 1 diabetes. © 2013 médecine/sciences – Inserm.

  18. Negative emotions and behaviour: The role of regulatory emotional self-efficacy.

    Science.gov (United States)

    Mesurado, Belén; Vidal, Elisabeth Malonda; Mestre, Anna Llorca

    2018-04-01

    The objective of this study is to test a longitudinal model that analyses the direct effect of negative emotions (anger, depression and anxiety, wave 1) on prosocial and aggressive behaviour (wave 2) in adolescents. And the indirect effect of negative emotions (wave 1) on prosocial and aggressive behaviour (wave 2) through regulatory emotional self-efficacy. Data was obtained from 417 adolescents in a two-wave longitudinal study (225 girls, M age = 14.70 years) from schools located in Valencia, Spain. SEM was employed to explore longitudinal models. The results showed that anger had a direct relationship with prosocial behaviour and aggression, measured two years later. However, the depression and anxiety states did not predict prosociality and aggressiveness. The mediation role of regulatory emotional self-efficacy between negative emotion and behaviours was only partially confirmed. Finally, only the perception of self-efficacy in expressing positive affect is related to prosociality and aggressiveness. Copyright © 2018 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  19. Wind wave source functions in opposing seas

    KAUST Repository

    Langodan, Sabique

    2015-08-26

    The Red Sea is a challenge for wave modeling because of its unique two opposed wave systems, forced by opposite winds and converging at its center. We investigate the different physical aspects of wave evolution and propagation in the convergence zone. The two opposing wave systems have similar amplitude and frequency, each driven by the action of its own wind. Wave patterns at the centre of the Red Sea, as derived from extensive tests and intercomparison between model and measured data, suggest that the currently available wave model source functions may not properly represent the evolution of the local fields that appear to be characterized by a less effective wind input and an enhanced white-capping. We propose and test a possible simple solution to improve the wave-model simulation under opposing winds and waves condition. This article is protected by copyright. All rights reserved.

  20. The Spot 42 RNA: A regulatory small RNA with roles in the central metabolism

    Science.gov (United States)

    Bækkedal, Cecilie; Haugen, Peik

    2015-01-01

    The Spot 42 RNA is a 109 nucleotide long (in Escherichia coli) noncoding small regulatory RNA (sRNA) encoded by the spf (spot fourty-two) gene. spf is found in gamma-proteobacteria and the majority of experimental work on Spot 42 RNA has been performed using E. coli, and recently Aliivibrio salmonicida. In the cell Spot 42 RNA plays essential roles as a regulator in carbohydrate metabolism and uptake, and its expression is activated by glucose, and inhibited by the cAMP-CRP complex. Here we summarize the current knowledge on Spot 42, and present the natural distribution of spf, show family-specific secondary structural features of Spot 42, and link highly conserved structural regions to mRNA target binding. PMID:26327359

  1. Regulatory T cells (Treg and Their Roles in Immune System with Respect to Immunopathological Disorders

    Directory of Open Access Journals (Sweden)

    Kateřina Kondělková

    2010-01-01

    Full Text Available Regulatory T cells (Tregs are a specialized subpopulation of T cells that act to suppress immune response, thereby maintaining homeostasis and self-tolerance. It has been shown that Tregs are able to inhibit T cell proliferation and cytokine production and play a critical role in preventing autoimmunity. Different subsets with various functions of Treg cells exist. Tregs can be usually identified by flow cytometry. The most specific marker for these cells is FoxP3, which is localized intracellulary. Selected surface markers such as CD25high (high molecular density and CD127low (low molecular density could serve as surrogate markers to detect Tregs in a routine clinical practice. Dysregulation in Treg cell frequency or functions may lead to the development of autoimmune disease. Therapeutical Treg modulation is considered to be a promising therapeutical approach to treat some selected disorders, such as allergies, and to prevent allograft rejection.

  2. The Spot 42 RNA: A regulatory small RNA with roles in the central metabolism.

    Science.gov (United States)

    Bækkedal, Cecilie; Haugen, Peik

    2015-01-01

    The Spot 42 RNA is a 109 nucleotide long (in Escherichia coli) noncoding small regulatory RNA (sRNA) encoded by the spf (spot fourty-two) gene. spf is found in gamma-proteobacteria and the majority of experimental work on Spot 42 RNA has been performed using E. coli, and recently Aliivibrio salmonicida. In the cell Spot 42 RNA plays essential roles as a regulator in carbohydrate metabolism and uptake, and its expression is activated by glucose, and inhibited by the cAMP-CRP complex. Here we summarize the current knowledge on Spot 42, and present the natural distribution of spf, show family-specific secondary structural features of Spot 42, and link highly conserved structural regions to mRNA target binding.

  3. Regulatory role of prolactin in paternal behavior in male parents: A narrative review

    Directory of Open Access Journals (Sweden)

    F Hashemian

    2016-01-01

    Full Text Available In all mammalian species, a combination of neuroendocrine and experiential factors contributes to the emergence of remarkable behavioral changes observed in parental behavior. Yet, our understanding of neuroendocrine bases of paternal behavior in humans is still preliminary and more research is needed in this area. In the present review, the authors summarized hormonal bases of paternal behavior in both human and nonhuman mammalian species and focused on studies on the regulatory role of prolactin in occurrence of paternal behavior. All peer-reviewed journal articles published before 2015 for each area discussed (parental brain, hormonal bases of maternal behavior, hormonal bases of paternal behavior and the role of prolactin in regulation of paternal behavior in nonhuman mammalian species, hormonal bases of paternal behavior and the role of prolactin in regulation of paternal behavior in humans were searched by PubMed, Medline, and Scopus for original research and review articles. Publications between 1973 and 2015 were included. Similar to female parents, elevated prolactin levels in new fathers most probably contribute to child-caring behavior and facilitate behavioral and emotional states attributed to child care. Moreover, elevated parental prolactin levels after childbirth decrease the parents′ libidos so that they invest more in parental care than in fertility behavior. According to the available clinical studies, elevation in the amounts of prolactin levels after childbirth in male parents are probably associated with paternal behavior observed in humans.

  4. Induction of regulatory T cells: A role for probiotics and prebiotics to suppress autoimmunity.

    Science.gov (United States)

    Dwivedi, Mitesh; Kumar, Prasant; Laddha, Naresh C; Kemp, E Helen

    2016-04-01

    Regulatory T cells (Tregs) are comprised of a heterogeneous population of cells that play a vital role in suppressing inflammation and maintaining immune tolerance. Given the crucial role of Tregs in maintaining immune homeostasis, it is probably not surprising that many microbial species and their metabolites have the potential to induce Tregs. There is now great interest in the therapeutic potential of probiotics and prebiotics based strategies for a range of autoimmune disorders. This review will summarise recent findings concerning the role of probiotics and prebiotics in induction of Tregs to ameliorate the autoimmune conditions. In addition, the article is focused to explain the different mechanisms of Treg induction and function by these probiotics and prebiotics, based on the available studies till date. The article further proposes that induction of Tregs by probiotics and prebiotics could lead to the development of new therapeutic approach towards curbing the autoimmune response and as an alternative to detrimental immunosuppressive drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. The potential regulatory roles of NAD(+) and its metabolism in autophagy.

    Science.gov (United States)

    Zhang, Dong-Xia; Zhang, Jia-Ping; Hu, Jiong-Yu; Huang, Yue-Sheng

    2016-04-01

    (Macro)autophagy mediates the bulk degradation of defective organelles, long-lived proteins and protein aggregates in lysosomes and plays a critical role in cellular and tissue homeostasis. Defective autophagy processes have been found to contribute to a variety of metabolic diseases. However, the regulatory mechanisms of autophagy are not fully understood. Increasing data indicate that nicotinamide adenine nucleotide (NAD(+)) homeostasis correlates intimately with autophagy. NAD(+) is a ubiquitous coenzyme that functions primarily as an electron carrier of oxidoreductase in multiple redox reactions. Both NAD(+) homeostasis and its metabolism are thought to play critical roles in regulating autophagy. In this review, we discuss how the regulation of NAD(+) and its metabolism can influence autophagy. We focus on the regulation of NAD(+)/NADH homeostasis and the effects of NAD(+) consumption by poly(ADP-ribose) (PAR) polymerase-1 (PARP-1), NAD(+)-dependent deacetylation by sirtuins and NAD(+) metabolites on autophagy processes and the underlying mechanisms. Future studies should provide more direct evidence for the regulation of autophagy processes by NAD(+). A better understanding of the critical roles of NAD(+) and its metabolites on autophagy will shed light on the complexity of autophagy regulation, which is essential for the discovery of new therapeutic tools for autophagy-related diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. The Regulatory Roles of MicroRNAs in Bone Remodeling and Perspectives as Biomarkers in Osteoporosis

    Directory of Open Access Journals (Sweden)

    Mengge Sun

    2016-01-01

    Full Text Available MicroRNAs are involved in many cellular and molecular activities and played important roles in many biological and pathological processes, such as tissue formation, cancer development, diabetes, neurodegenerative diseases, and cardiovascular diseases. Recently, it has been reported that microRNAs can modulate the differentiation and activities of osteoblasts and osteoclasts, the key cells that are involved in bone remodeling process. Meanwhile, the results from our and other research groups showed that the expression profiles of microRNAs in the serum and bone tissues are significantly different in postmenopausal women with or without fractures compared to the control. Therefore, it can be postulated that microRNAs might play important roles in bone remodeling and that they are very likely to be involved in the pathological process of postmenopausal osteoporosis. In this review, we will present the updated research on the regulatory roles of microRNAs in osteoblasts and osteoclasts and the expression profiles of microRNAs in osteoporosis and osteoporotic fracture patients. The perspective of serum microRNAs as novel biomarkers in bone loss disorders such as osteoporosis has also been discussed.

  7. Information to Improve Public Perceptions of the Food and Drug Administration (FDA’s Tobacco Regulatory Role

    Directory of Open Access Journals (Sweden)

    Amira Osman

    2018-04-01

    Full Text Available While the Food and Drug Administration (FDA has had regulatory authority over tobacco products since 2009, public awareness of this authority remains limited. This research examines several broad types of information about FDA tobacco regulatory mission that may improve the perceptions of FDA as a tobacco regulator. Using Amazon Mechanical Turk, 1766 adults, smokers and non-smokers, were randomly assigned to view a statement about FDA regulatory authority that varied three information types in a 2 × 2 × 2 between subjects experimental design: (1 FDA’s roles in regulating tobacco (yes/no; (2 The scientific basis of regulations (yes/no; and (3 A potential protective function of regulations (yes/no. Using factorial ANOVA, we estimated the main and interactive effects of all three types of information and of smoking status on the perceptions of FDA. Participants that were exposed to information on FDA roles reported higher FDA credibility and a greater perceived knowledge of FDA than those who did not. Exposure to information about the scientific basis of regulations led to more negative views of the tobacco industry. Participants who learned of the FDA’s commitment to protecting the public reported higher FDA credibility and more positive attitudes toward regulations than those who did not learn of this commitment. We observed no significant interaction effects. The findings suggest that providing information about the regulatory roles and protective characterization of the FDA’s tobacco regulatory mission positively influence public perceptions of FDA and tobacco regulations.

  8. Uncovering a Dual Regulatory Role for Caspases During Endoplasmic Reticulum Stress-induced Cell Death.

    Science.gov (United States)

    Anania, Veronica G; Yu, Kebing; Gnad, Florian; Pferdehirt, Rebecca R; Li, Han; Ma, Taylur P; Jeon, Diana; Fortelny, Nikolaus; Forrest, William; Ashkenazi, Avi; Overall, Christopher M; Lill, Jennie R

    2016-07-01

    Many diseases are associated with endoplasmic reticulum (ER) stress, which results from an accumulation of misfolded proteins. This triggers an adaptive response called the "unfolded protein response" (UPR), and prolonged exposure to ER stress leads to cell death. Caspases are reported to play a critical role in ER stress-induced cell death but the underlying mechanisms by which they exert their effect continue to remain elusive. To understand the role caspases play during ER stress, a systems level approach integrating analysis of the transcriptome, proteome, and proteolytic substrate profile was employed. This quantitative analysis revealed transcriptional profiles for most human genes, provided information on protein abundance for 4476 proteins, and identified 445 caspase substrates. Based on these data sets many caspase substrates were shown to be downregulated at the protein level during ER stress suggesting caspase activity inhibits their cellular function. Additionally, RNA sequencing revealed a role for caspases in regulation of ER stress-induced transcriptional pathways and gene set enrichment analysis showed expression of multiple gene targets of essential transcription factors to be upregulated during ER stress upon inhibition of caspases. Furthermore, these transcription factors were degraded in a caspase-dependent manner during ER stress. These results indicate that caspases play a dual role in regulating the cellular response to ER stress through both post-translational and transcriptional regulatory mechanisms. Moreover, this study provides unique insight into progression of the unfolded protein response into cell death, which may help identify therapeutic strategies to treat ER stress-related diseases. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Interferon Regulatory Factor 6 Has a Protective Role in the Host Response to Endotoxic Shock.

    Directory of Open Access Journals (Sweden)

    Sophie Joly

    Full Text Available Interferon Regulatory Factor (IRF 6, a member of the IRF family, is essential for epidermal and orofacial embryonic development. Irf6 is strongly expressed in keratinocytes, in which it regulates epidermal proliferation, differentiation, and migration. A recent role for Irf6 in Toll-like receptor 2-dependent chemokine gene expression was also reported in an epithelial cell line. However, a function for Irf6 in innate immune cells was not previously reported. In the present study, we investigated the expression and function of Irf6 in bone marrow-derived neutrophils and macrophages. We show here, using a conditional knockout of Irf6 in lysosymeM expressing cells, that Irf6 is required for resistance to LPS-induced endotoxic shock. In addition, Irf6-deficient bone marrow-derived neutrophils exhibited increased chemotactic index and velocity compared with wild-type cells in vitro. TLR4-specific KC and IL6 secretions were upregulated in Irf6-deficient bone marrow-derived macrophages in vitro. These cells also exhibited an increased level of phosphorylated IkBa. Collectively, our findings suggest a role for Irf6 in the resistance to endotoxic shock due to NFk-B-mediated alteration of cytokine production.

  10. The roles of antitrust law and regulatory oversight in the restructured electricity industry

    Energy Technology Data Exchange (ETDEWEB)

    Glazer, C.A.; Little, M.B.

    1999-05-01

    The introduction of retail wheeling is changing the roles of regulators and the courts. When states unbundle the vertically integrated investor-owned utility (IOU) into generation companies, transmission companies, and distribution companies, antitrust enforcement and policy setting by the state public utility/service commissions (PUCs) will be paramount. As was seen in the deregulation of the airline industry, vigorous enforcement of antitrust laws by the courts and proper policy setting by the regulators are the keys to a successful competitive market. Many of the problems raised in the airline deregulation movement came about due to laxity in correcting clear antitrust violations and anti-competitive conditions before they caused damage to the market. As retail wheeling rolls out, it is critical for state PUCs to become attuned to these issues and, most of all, to have staff trained in these disciplines. The advent of retail wheeling changes the application of the State Action Doctrine and, in turn, may dramatically alter the role of the state PUC--meaning antitrust law and regulatory oversight must step in to protect competitors and consumers from monopolistic abuse.

  11. Circular RNA Profiling and Bioinformatic Modeling Identify Its Regulatory Role in Hepatic Steatosis.

    Science.gov (United States)

    Guo, Xing-Ya; He, Chong-Xin; Wang, Yu-Qin; Sun, Chao; Li, Guang-Ming; Su, Qing; Pan, Qin; Fan, Jian-Gao

    2017-01-01

    Circular RNAs (circRNAs) exhibit a wide range of physiological and pathological activities. To uncover their role in hepatic steatosis, we investigated the expression profile of circRNAs in HepG2-based hepatic steatosis induced by high-fat stimulation. Differentially expressed circRNAs were subjected to validation using QPCR and functional analyses using principal component analysis, hierarchical clustering, target prediction, gene ontology (GO), and pathway annotation, respectively. Bioinformatic integration established the circRNA-miRNA-mRNA regulatory network so as to identify the mechanisms underlying circRNAs' metabolic effect. Here we reported that hepatic steatosis was associated with a total of 357 circRNAs. Enrichment of transcription-related GOs, especially GO: 0006355, GO: 004589, GO: 0045944, GO: 0045892, and GO: 0000122, demonstrated their specific actions in transcriptional regulation. Lipin 1 (LPIN1) was recognized to mediate the transcriptional regulatory effect of circRNAs on metabolic pathways. circRNA-miRNA-mRNA network further identified the signaling cascade of circRNA_021412/miR-1972/LPIN1, which was characterized by decreased level of circRNA_021412 and miR-1972-based inhibition of LPIN1. LPIN1-induced downregulation of long chain acyl-CoA synthetases (ACSLs) expression finally resulted in the hepatosteatosis. These findings identify circRNAs to be important regulators of hepatic steatosis. Transcription-dependent modulation of metabolic pathways may underlie their effects, partially by the circRNA_021412/miR-1972/LPIN1 signaling.

  12. Reconstruction of the yeast Snf1 kinase regulatory network reveals its role as a global energy regulator

    DEFF Research Database (Denmark)

    Usaite, Renata; Jewett, Michael Christopher; Soberano de Oliveira, Ana Paula

    2009-01-01

    Highly conserved among eukaryotic cells, the AMP-activated kinase (AMPK) is a central regulator of carbon metabolism. To map the complete network of interactions around AMPK in yeast (Snf1) and to evaluate the role of its regulatory subunit Snf4, we measured global mRNA, protein and metabolite...

  13. Possible regulatory role of phenylalanine ammonia-lyase in the production of anthocyanins in asparagus (Asparagus officinalis L)

    NARCIS (Netherlands)

    Flores, F.B.; Oosterhaven, J.; Martinez-Madrid, M.C.; Romojaro, F.

    2005-01-01

    The regulatory role of phenylalanine ammonia-lyase (PAL) in the light-induced accumulation of anthocyanins in the epidermis of asparagus spears has been analysed. A correlation between the stimulation of PAL activity and the rise in total anthocyanin content has been observed. Light radiation

  14. RNA SURVEILLANCE– AN EMERGING ROLE FOR RNA REGULATORY NETWORKS IN AGING

    OpenAIRE

    Montano, Monty; Long, Kimberly

    2010-01-01

    In this review, we describe recent advances in the field of RNA regulatory biology and relate these advances to aging science. We introduce a new term, RNA surveillance, an RNA regulatory process that is conserved in metazoans, and describe how RNA surveillance represents molecular cross-talk between two emerging RNA regulatory systems – RNA interference and RNA editing. We discuss how RNA surveillance mechanisms influence mRNA and microRNA expression and activity during lifespan. Additionall...

  15. Consecutive opposed interactions of light waves

    International Nuclear Information System (INIS)

    Volkov, V V; Chirkin, Anatolii S

    1999-01-01

    The conditions were determined for the occurrence of the opposed interaction of waves having multiple frequencies in two consecutive three-frequency processes in periodically inhomogeneous nonlinear optical crystals. The necessary nonlinear susceptibility modulation period was calculated for an MgO:LiNbO 3 crystal. The characteristic features of the energy exchange between counterpropagating waves with parametric amplification in a low-frequency pump field were investigated. (nonlinear optical phenomena)

  16. The regulatory role of the Hungarian Geological Survey in the closure of Mecsek uranium mine

    International Nuclear Information System (INIS)

    Hamor, T.; Gombor, L.

    2001-01-01

    Under Mining Act XLIII established in 1993, the Hungarian Geological Survey was given a wide range of authority related to the environment, mining, nuclear and general constructions. In implementing these task the Survey will be supported by the well established Geological Institute of Hungary and the Eoetvoes Lorand Geophysical Institute. The Survey's role in the nuclear field includes the licensing of plans and reports on geologically related research to any nuclear facilities. The Hungarian Geological Survey is also co-authority on matters related to the establishment, construction, modification and closure, environmental protection of nuclear facilities in general and all matter related to uranium mining. The Survey's regulatory activity in radioactive waste management follows the Decree of the Minister of Industry and Tourism 62/1997 which is based on the Atomic Energy Act CXVI of 1966. These regulations were prepared in harmony with the OECD Nuclear Energy Agency and the International Atomic Energy Agency conventions, standards and guides and those of other countries. Case histories on the applications of these regulations to the closure of Mecsek uranium mine and the operation of the research laboratory tunnel for long-lived, high level radioactive waste are presented here. (author)

  17. Regulatory T cells as suppressors of anti-tumor immunity: Role of metabolism.

    Science.gov (United States)

    De Rosa, Veronica; Di Rella, Francesca; Di Giacomo, Antonio; Matarese, Giuseppe

    2017-06-01

    Novel concepts in immunometabolism support the hypothesis that glucose consumption is also used to modulate anti-tumor immune responses, favoring growth and expansion of specific cellular subsets defined in the past as suppressor T cells and currently reborn as regulatory T (Treg) cells. During the 1920s, Otto Warburg and colleagues observed that tumors consumed high amounts of glucose compared to normal tissues, even in the presence of oxygen and completely functioning mitochondria. However, the role of the Warburg Effect is still not completely understood, particularly in the context of an ongoing anti-tumor immune response. Current experimental evidence suggests that tumor-derived metabolic restrictions can drive T cell hyporesponsiveness and immune tolerance. For example, several glycolytic enzymes, deregulated in cancer, contribute to tumor progression independently from their canonical metabolic activity. Indeed, they can control apoptosis, gene expression and activation of specific intracellular pathways, thus suggesting a direct link between metabolic switches and pro-tumorigenic transcriptional programs. Focus of this review is to define the specific metabolic pathways controlling Treg cell immunobiology in the context of anti-tumor immunity and tumor progression. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Regulatory role for the memory B cell as suppressor-inducer of feedback control

    International Nuclear Information System (INIS)

    Kennedy, M.W.; Thomas, D.B.

    1983-01-01

    A regulatory role is proposed for the antigen-responsive B cell, as suppressor-inducer of feedback control during the secondary response in vivo. In a double adoptive transfer of memory cells primed to a thymus-dependent antigen from one irradiated host to another, antigen-specific suppressors are generated after a critical time in the primary recipient, able to entirely ablate a secondary anti-hapten response. Positive cell selection in the fluorescence-activated cell sorter confirmed that suppression was mediated by an Lyt-2+ T cell; however, positively selected B cells were also inhibitory and able to induce suppressors in a carrier-specific manner: B hapten induced suppressors in a carrier-primed population, and B carrier induced suppressors in a hapten-carrier population. At the peak of the antibody response in the primary host, memory B cells and their progeny were unable to differentiate further to plasma cells due to their intrinsic suppressor-inducer activity, but this autoregulatory circuit could be severed by adoptive transfer to carrier-primed, X-irradiated recipients

  19. Exploring the regulatory role of isocitrate dehydrogenase mutant protein on glioma stem cell proliferation.

    Science.gov (United States)

    Lu, H-C; Ma, J; Zhuang, Z; Qiu, F; Cheng, H-L; Shi, J-X

    2016-08-01

    Glioma is the most lethal form of cancer that originates mostly from the brain and less frequently from the spine. Glioma is characterized by abnormal regulation of glial cell differentiation. The severity of the glioma was found to be relaxed in isocitrate dehydrogenase 1 (IDH1) mutant. The present study focused on histological discrimination and regulation of cancer stem cell between IDH1 mutant and in non-IDH1 mutant glioma tissue. Histology, immunohistochemistry and Western blotting techniques are used to analyze the glioma nature and variation in glioma stem cells that differ between IDH1 mutant and in non-IDH1 mutant glioma tissue. The aggressive form of non-IDH1 mutant glioma shows abnormal cellular histological variation with prominent larger nucleus along with abnormal clustering of cells. The longer survival form of IDH1 mutant glioma has a control over glioma stem cell proliferation. Immunohistochemistry with stem cell markers, CD133 and EGFRvIII are used to demonstrate that the IDH1 mutant glioma shows limited dependence on cancer stem cells and it shows marked apoptotic signals in TUNEL assay to regulate abnormal cells. The non-IDH1 mutant glioma failed to regulate misbehaving cells and it promotes cancer stem cell proliferation. Our finding supports that the IDH1 mutant glioma has a regulatory role in glioma stem cells and their survival.

  20. Evidence for roles of the Escherichia coli Hda protein beyond regulatory inactivation of DnaA.

    Science.gov (United States)

    Baxter, Jamie C; Sutton, Mark D

    2012-08-01

    The ATP-bound form of the Escherichia coli DnaA protein binds 'DnaA boxes' present in the origin of replication (oriC) and operator sites of several genes, including dnaA, to co-ordinate their transcription with initiation of replication. The Hda protein, together with the β sliding clamp, stimulates the ATPase activity of DnaA via a process termed regulatory inactivation of DnaA (RIDA), to regulate the activity of DnaA in DNA replication. Here, we used the mutant dnaN159 strain, which expresses the β159 clamp protein, to gain insight into how the actions of Hda are co-ordinated with replication. Elevated expression of Hda impeded growth of the dnaN159 strain in a Pol II- and Pol IV-dependent manner, suggesting a role for Hda managing the actions of these Pols. In a wild-type strain, elevated levels of Hda conferred sensitivity to nitrofurazone, and suppressed the frequency of -1 frameshift mutations characteristic of Pol IV, while loss of hda conferred cold sensitivity. Using the dnaN159 strain, we identified 24 novel hda alleles, four of which supported E. coli viability despite their RIDA defect. Taken together, these findings suggest that although one or more Hda functions are essential for cell viability, RIDA may be dispensable. © 2012 Blackwell Publishing Ltd.

  1. The Regulatory Role of MicroRNAs in EMT and Cancer

    Directory of Open Access Journals (Sweden)

    Apostolos Zaravinos

    2015-01-01

    Full Text Available The epithelial to mesenchymal transition (EMT is a powerful process in tumor invasion, metastasis, and tumorigenesis and describes the molecular reprogramming and phenotypic changes that are characterized by a transition from polarized immotile epithelial cells to motile mesenchymal cells. It is now well known that miRNAs are important regulators of malignant transformation and metastasis. The aberrant expression of the miR-200 family in cancer and its involvement in the initiation and progression of malignant transformation has been well demonstrated. The metastasis suppressive role of the miR-200 members is strongly associated with a pathologic EMT. This review describes the most recent advances regarding the influence of miRNAs in EMT and the control they exert in major signaling pathways in various cancers. The ability of the autocrine TGF-β/ZEB/miR-200 signaling regulatory network to control cell plasticity between the epithelial and mesenchymal state is further discussed. Various miRNAs are reported to directly target EMT transcription factors and components of the cell architecture, as well as miRNAs that are able to reverse the EMT process by targeting the Notch and Wnt signaling pathways. The link between cancer stem cells and EMT is also reported and the most recent developments regarding clinical trials that are currently using anti-miRNA constructs are further discussed.

  2. Role of the Nuclear Regulatory Authority in the final disposal of radioactive wastes in Argentina

    International Nuclear Information System (INIS)

    Petraitis, E.J.; Siraky, G.; Novo, R.G.

    1998-01-01

    This paper describes briefly the legislative and regulatory framework in which the final disposal of radioactive wastes is carried out in Argentina. The activities of the Nuclear Regulatory Authority (ARN) and the applied approaches in relation to inspection of facilities, safety assessments of associated systems and collaboration in the matter with international agencies are also exposed. (author) [es

  3. Constitutive GITR Activation Reduces Atherosclerosis by Promoting Regulatory CD4+ T-Cell Responses-Brief Report

    NARCIS (Netherlands)

    Meiler, Svenja; Smeets, Esther; Winkels, Holger; Shami, Annelie; Pascutti, Maria Fernanda; Nolte, Martijn A.; Beckers, Linda; Weber, Christian; Gerdes, Norbert; Lutgens, Esther

    2016-01-01

    Glucocorticoid-induced tumor necrosis factor receptor family-related protein (GITR) is expressed on CD4(+) effector memory T cells and regulatory T cells; however, its role on these functionally opposing cell types in atherosclerosis is not fully understood. Low-density lipoprotein

  4. Broadening the cancer and cognition landscape: the role of self-regulatory challenges.

    Science.gov (United States)

    Arndt, Jamie; Das, Enny; Schagen, Sanne B; Reid-Arndt, Stephanie A; Cameron, Linda D; Ahles, Tim A

    2014-01-01

    The potentially detrimental effects of cancer and related treatments on cognitive functioning have emerged as one of the key foci of cancer survivorship research, but little is known about how psychological variables other than depression influence these relationships. To illustrate the potential of social psychological perspectives, we examine how a self-regulatory analysis and specific self-regulatory challenges of contending with cancer-related expectancies and stereotypes provide conceptual frameworks for understanding some of the potential causes and consequences of cancer-related cognitive deficits. Literatures on cancer-related cognitive deficits, self-regulatory ego depletion, expectancy stereotypes, and their points of convergence are briefly reviewed. A review and conceptual integration of relevant literatures suggest that coping with cancer can impair self-regulatory capacity. There is an overlap between cognitive deficits associated with self-regulatory challenge and with cancer and its treatment, and restoring self-regulatory resources can attenuate cancer-related cognitive deficits. Examination of specific regulatory challenges of contending with expectancies and stereotypes related to treatment suggests insights that can inform when and among whom cognitive deficits may most likely emerge. Integrating social psychological ideas with a substantial knowledge base can illustrate novel research trajectories that can deepen our understanding of cancer-related cognitive deficits and their impact on psychosocial well-being. Copyright © 2013 John Wiley & Sons, Ltd.

  5. The costly benefits of opposing agricultural biotechnology.

    Science.gov (United States)

    Apel, Andrew

    2010-11-30

    Rigorous application of a simple definition of what constitutes opposition to agricultural biotechnology readily encompasses a wide array of key players in national and international systems of food production, distribution and governance. Even though the sum of political and financial benefits of opposing agricultural biotechnology appears vastly to outweigh the benefits which accrue to providers of agricultural biotechnology, technology providers actually benefit from this opposition. If these barriers to biotechnology were removed, subsistence farmers still would not represent a lucrative market for improved seed. The sum of all interests involved ensures that subsistence farmers are systematically denied access to agricultural biotechnology. Copyright © 2010 Elsevier B.V. All rights reserved.

  6. The role of Foxp3+ regulatory T cells in liver transplant tolerance.

    Science.gov (United States)

    Li, W; Carper, K; Zheng, X X; Kuhr, C S; Reyes, J D; Liang, Y; Perkins, D L; Thomson, A W; Perkins, J D

    2006-12-01

    The liver has long been considered a tolerogenic organ that favors the induction of peripheral tolerance. The mechanisms underlying liver tolerogenicity remain largely undefined. In this study, we characterized Foxp3-expressing CD4+ CD25+ regulatory T cells (Treg) in liver allograft recipients and examined the role of Treg in inherent liver tolerogenicity by employing the mouse spontaneous liver transplant tolerance model. Orthotopic liver transplantation was performed from C57BL/10 (H2b) to C3H/HeJ (H2k) mice. The percentage of CD4+ CD25+ Treg was expanded in the liver grafts and recipient spleens from day 5 up to day 100 posttransplantation, associated with high intracellular Foxp3 and CTLA4 expression. Immunohistochemistry further demonstrated significant numbers of Foxp3+ cells in the liver grafts and recipient spleens and increased transforming growth factor beta expression in the recipient spleens throughout the time courses. Adoptive transfer of spleen cells from the long-term liver allograft survivors significantly prolonged donor heart graft survival. Depletion of recipient CD4+ CD25+ Treg using anti-CD25 monoclonal antibody (250 microg/d) induced acute liver allograft rejection, associated with elevated anti-donor T-cell proliferative responses, CTL and natural killer activities, enhanced interleukin (IL)-2, interferon-gamma, IL-10, and decreased IL-4 production, and decreased T-cell apoptotic activity in anti-CD25-treated recipients. Moreover, CTLA4 blockade by anti-CTLA4 monoclonal antibody administration exacerbated liver graft rejection when combined with anti-CD25 monoclonal antibody. Thus, Foxp3+ CD4+ CD25+ Treg appear to underpin spontaneous acceptance of major histocompatability complex- mismatched liver allografts in mice. CTLA4, IL-4, and apoptosis of alloreactive T cells appear to contribute to the function of Treg and regulation of graft outcome.

  7. Negative regulatory role of PI3-kinase in TNF-induced tumor necrosis.

    Science.gov (United States)

    Matschurat, Susanne; Blum, Sabine; Mitnacht-Kraus, Rita; Dijkman, Henry B P M; Kanal, Levent; De Waal, Robert M W; Clauss, Matthias

    2003-10-20

    Tissue factor is the prime initiator of blood coagulation. Expression of tissue factor in tumor endothelial cells leads to thrombus formation, occlusion of vessels and development of hemorrhagic infarctions in the tumor tissue, often followed by regression of the tumor. Tumor cells produce endogenous vascular endothelial growth factor (VEGF), which sensitizes endothelial cells for systemically administered tumor necrosis factor alpha (TNF alpha) and synergistically enhances the TNF-induced expression of tissue factor. We have analyzed the pathways involved in the induction of tissue factor in human umbilical cord vein endothelial cells (HUVECs) after combined stimulation with TNF and VEGF. By using specific low molecular weight inhibitors, we demonstrated that protein kinase C (PKC), p44/42 and p38 mitogen-activated protein (MAP) kinases, and stress-activated protein kinase (JNK) are essentially involved in the induction of tissue factor. In contrast, the application of wortmannin, an inhibitor of phosphatidylinositol 3 (PI3)-kinase, led to strongly enhanced expression of tissue factor in TNF- and VEGF-treated cells, implicating a negative regulatory role for PI3-kinase. In vivo, the application of wortmannin promoted the formation of TNF-induced hemorrhages and intratumoral necroses in murine meth A tumors. The co-injection of wortmannin lowered the effective dose of applied TNF. Therefore, it is conceivable that the treatment of TNF-sensitive tumors with a combination of TNF and wortmannin will ensure the selective damage of the tumor endothelium and minimize the risk of systemic toxicity of TNF. TNF-treatment in combination with specific inhibition of PI3-kinase is a novel concept in anti-cancer therapy. Copyright 2003 Wiley-Liss, Inc.

  8. Assessing the role of regulatory bodies in managing health professional issues and errors in Europe.

    Science.gov (United States)

    Risso-Gill, Isabelle; Legido-Quigley, H; Panteli, D; Mckee, M

    2014-08-01

    This paper explores how medical regulatory bodies in nine European countries manage professional issues involving quality and patient safety, to build on limited existing information on procedures for regulating medical professionals in Europe. Twelve vignettes describing scenarios of concerns about standards of physicians were developed, covering clinical, criminal and administrative matters. Medical regulatory bodies in nine European countries were asked what action they would normally take in each situation. Their responses were related to their regulatory mandate. Responses varied greatly across participating countries. Regulators are always involved where patients are at risk or where a criminal offence is committed within the clinical setting. Non-criminal medical issues were generally handled by the employer, if any, at their discretion. Countries varied in the use of punitive measures, the extent to which they took an interest in issues arising outside professional activities, and whether they dealt with issues themselves or referred cases to another regulatory authority or took no action at all. There is little consistency across Europe on the regulation of medical professionals. There is considerable diversity in the range of topics that regulatory bodies oversee, with almost all covering health care quality and safety and others encompassing issues related to reputation, respect and trust. These inconsistencies have significant implications for professional mobility, patient safety and quality of care. © The Author 2014. Published by Oxford University Press in association with the International Society for Quality in Health Care; all rights reserved.

  9. The role of regulatory council in the energy sector from the aspect of consumers' protection

    International Nuclear Information System (INIS)

    Banovac, E.; Pavlovic, D.; Boljesic, K.

    2003-01-01

    The consumers' protection legal base, with few factors of new legislative consumers' protection legislation in European Union, in the Law on Consumers' Protection, and in the set of the Croatian Energy Laws is shown in this paper. Special attention in this paper is paid on five factors of regulatory body's orientation to the consumers' protection field, which energy regulatory body's policy should be included. The model of consumers' protection in the energy sector is shown, with the scheme of Three-component interactive subsystems: basic legislation which is determined consumers' protection policy, planning activities for consumers' protection (short and long time plans), and performing activities for consumers' protection. Furthermore, the approach of consumers' protection in the energy sectors in European Union are described. The paper gives the model of consumers' protection in the Croatian energy sector, and Croatian Energy Regulatory Council' approach to this issue. The table, with the data of specific consumers' protection problems in practice, those the Croatian Energy Regulatory Council as a regulatory body have been settled, is shown.(author)

  10. Targeted resequencing of regulatory regions at schizophrenia risk loci: Role of rare functional variants at chromatin repressive states.

    Science.gov (United States)

    González-Peñas, Javier; Amigo, Jorge; Santomé, Luis; Sobrino, Beatriz; Brenlla, Julio; Agra, Santiago; Paz, Eduardo; Páramo, Mario; Carracedo, Ángel; Arrojo, Manuel; Costas, Javier

    2016-07-01

    There is mounting evidence that regulatory variation plays an important role in genetic risk for schizophrenia. Here, we specifically search for regulatory variants at risk by sequencing promoter regions of twenty-three genes implied in schizophrenia by copy number variant or genome-wide association studies. After strict quality control, a total of 55,206bp per sample were analyzed in 526 schizophrenia cases and 516 controls from Galicia, NW Spain, using the Applied Biosystems SOLiD System. Variants were filtered based on frequency from public databases, chromatin states from the RoadMap Epigenomics Consortium at tissues relevant for schizophrenia, such as fetal brain, mid-frontal lobe, and angular gyrus, and prediction of functionality from RegulomeDB. The proportion of rare variants at polycomb repressive chromatin state at relevant tissues was higher in cases than in controls. The proportion of rare variants with predicted regulatory role was significantly higher in cases than in controls (P=0.0028, OR=1.93, 95% C.I.=1.23-3.04). Combination of information from both sources led to the identification of an excess of carriers of rare variants with predicted regulatory role located at polycomb repressive chromatin state at relevant tissues in cases versus controls (P=0.0016, OR=19.34, 95% C.I.=2.45-2495.26). The variants are located at two genes affected by the 17q12 copy number variant, LHX1 and HNF1B. These data strongly suggest that a specific epigenetic mechanism, chromatin remodeling by histone modification during early development, may be impaired in a subset of schizophrenia patients, in agreement with previous data. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. NKT Cell Subsets Can Exert Opposing Effects in Autoimmunity, Tumor Surveillance and Inflammation

    Science.gov (United States)

    Viale, Rachael; Ware, Randle; Maricic, Igor; Chaturvedi, Varun; Kumar, Vipin

    2014-01-01

    The innate-like natural killer T (NKT) cells are essential regulators of immunity. These cells comprise at least two distinct subsets and recognize different lipid antigens presented by the MHC class I like molecules CD1d. The CD1d-dependent recognition pathway of NKT cells is highly conserved from mouse to humans. While most type I NKT cells can recognize αGalCer and express a semi-invariant T cell receptor (TCR), a major population of type II NKT cells reactive to sulfatide utilizes an oligoclonal TCR. Furthermore TCR recognition features of NKT subsets are also distinctive with almost parallel as opposed to perpendicular footprints on the CD1d molecules for the type I and type II NKT cells respectively. Here we present a view based upon the recent studies in different clinical and experimental settings that while type I NKT cells are more often pathogenic, they may also be regulatory. On the other hand, sulfatide-reactive type II NKT cells mostly play an inhibitory role in the control of autoimmune and inflammatory diseases. Since the activity and cytokine secretion profiles of NKT cell subsets can be modulated differently by lipid ligands or their analogs, novel immunotherapeutic strategies are being developed for their differential activation for potential intervention in inflammatory diseases. PMID:25288922

  12. Opposing actions of dibutyryl cyclic AMP and GMP on temperature in conscious guinea-pigs

    Science.gov (United States)

    Kandasamy, S. B.; Williaes, B. A.

    1983-01-01

    It is shown that the intracerebroventricular administration of dibutyryl cyclic AMP (Db-cAMP) induced hyperthermia in guinea pigs which was not mediated through prostaglandins or norepinephrine since a prostaglandin synthesis inhibitor and an alpha-adrenergic receptor blocking agent did not antagonize the hyperthermia. However, the hyperthermic response to Db-cAMP was attenuated by the central administration of a beta-adrenergic receptor antagonist, which indicates that cAMP may be involved, through beta-adrenergic receptors, in the central regulation of heat production and conservation. The central administration of Db-cGMP produced hypothermia which was not mediated via histamine H1 or H2 receptors and serotonin. The antagonism of hypothermia induced by Db-cGMP and acetylcholine + physostigmine by central administration of a cholinergic muscarine receptor antagonist and not by a cholinergic nicotinic receptor antagonist suggests that cholinoceptive neurons and endogenous cGMP may regulate heat loss through cholinergic muscarine receptors. It is concluded that these results indicate a regulatory role in thermoregulation provided by a balance between opposing actions of cAMP and cGMP in guinea pigs.

  13. Regulation and regulatory role of WNT signaling in potentiating FSH action during bovine dominant follicle selection.

    Directory of Open Access Journals (Sweden)

    P S P Gupta

    Full Text Available Follicular development occurs in wave like patterns in monotocous species such as cattle and humans and is regulated by a complex interaction of gonadotropins with local intrafollicular regulatory molecules. To further elucidate potential mechanisms controlling dominant follicle selection, granulosa cell RNA harvested from F1 (largest and F2 (second largest follicles isolated at predeviation (PD and onset of diameter deviation (OD stages of the first follicular wave was subjected to preliminary RNA transcriptome analysis. Expression of numerous WNT system components was observed. Hence experiments were performed to test the hypothesis that WNT signaling modulates FSH action on granulosa cells during follicular waves. Abundance of mRNA for WNT pathway members was evaluated in granulosa cells harvested from follicles at emergence (EM, PD, OD and early dominance (ED stages of the first follicular wave. In F1 follicles, abundance of CTNNB1 and DVL1 mRNAs was higher and AXIN2 mRNA was lower at ED versus EM stages and DVL1 and FZD6 mRNAs were higher and AXIN2 mRNA was lower in F1 versus F2 follicle at the ED stage. Bovine granulosa cells were treated in vitro with increasing doses of the WNT inhibitor IWR-1+/- maximal stimulatory dose of FSH. IWR-1 treatment blocked the FSH-induced increase in granulosa cell numbers and reduced the FSH-induced increase in estradiol. Granulosa cells were also cultured in the presence or absence of FSH +/- IWR-1 and hormonal regulation of mRNA for WNT pathway members and known FSH targets determined. FSH treatment increased CYP19A1, CCND2, CTNNB1, AXIN2 and FZD6 mRNAs and the stimulatory effect on CYP19A1 mRNA was reduced by IWR-1. In contrast, FSH reduced CARTPT mRNA and IWR-1 partially reversed the inhibitory effect of FSH. Results support temporal and hormonal regulation and a potential role for WNT signaling in potentiating FSH action during dominant follicle selection.

  14. The pleasures and pains of distinct self-construals: the role of interdependence in regulatory focus.

    Science.gov (United States)

    Lee, A Y; Aaker, J L; Gardner, W L

    2000-06-01

    Regulatory focus theory distinguishes between self-regulatory processes that focus on promotion and prevention strategies for goal pursuit. Five studies provide support for the hypothesis that these strategies differ for individuals with distinct self-construals. Specifically, individuals with a dominant independent self-construal were predicted to place more emphasis on promotion-focused information, and those with a dominant interdependent self-construal on prevention-focused information. Support for this hypothesis was obtained for participants who scored high versus low on the Self-Construal Scale, participants who were presented with an independent versus interdependent situation, and participants from a Western versus Eastern culture. The influence of interdependence on regulatory focus was observed in both importance ratings of information and affective responses consistent with promotion or prevention focus.

  15. Quality and safety of nuclear installations: the role of administration, and, nuclear safety and regulatory procedures

    International Nuclear Information System (INIS)

    Queniart, D.

    1979-12-01

    In the first paper the author defines the concepts of safety and quality and describes the means of intervention by the Public Authorities in safety matters of nuclear installations. These include individual authorisations, definition and application of technical rules and surveillance of installations. In the second paper he defines the distinction between radiation protection and safety and presents the legislative and regulatory plan for nuclear safety in France. A central safety service for nuclear installations was created in March 1973 within the Ministry of Industrial and Scientific Development, where, amongst other tasks, it draws up regulatory procedures and organizes inspections of the installations. The main American regulations for light water reactors are outlined and the French regulatory system for different types of reactors discussed

  16. The role of the US regulatory process in public acceptance of nuclear power

    International Nuclear Information System (INIS)

    Rowden, M.A.

    1977-01-01

    This paper focuses, on NRC's regulatory responsibilities in relation to public acceptance of nuclear power. Since public attitudes in the United States may influence reaction to nuclear power in other nations, it is fair to say that the credibility of our regulatory program has international significance. Stated simply, unless the public is convinced that the regulatory process is effective in assuring safety, safeguarding nuclear facilities and materials, and protecting the environment, the use of nuclear power could be curtailed or even brought to a halt. Not only must the regulatory process be effective, it must at the same time be recognized by the public as being effective. Opinion polls in the United States have shown consistently that a majority of Americans believe it is important to develop nuclear power to help meet our future energy needs. The direction of public concern has shifted from year to year. Most recently, public apprehension has been expressed about the potential hazards of long-term storage of the high-level wastes from spent fuel reprocessing, and about the risks that nuclear materials and facilities may be subject to theft or diversion or sabotage. Uppermost in the public mind is the question whether the regulatory process can cope with these potential threats to public health and safety. The licensing process of the NRC is conducted in full public view. Issues of a generic nature are aired in rulemaking hearings, while each proposal to construct and operate a nuclear power plant or a facility such as fuel reprocessing plant is the subject of public hearings, which are held near the site of the proposed plant. During the last two years, we have noted that some persons who object to nuclear power plants have indicated that they believe that decisions to permit construction of such plants should be made at the State government level, rather than by a Federal agency. As a result, there now are movements to enact State laws and to set up State

  17. Probabilistic risk analysis and its role in regulatory activity in a developing country

    International Nuclear Information System (INIS)

    Arredondo-Sanchez, C.

    1985-01-01

    The author discusses the criterion adopted for regulatory activity in a developing country with a nuclear power plant. He describes the problems that have to be overcome as a result of changes in the regulations during construction of the plant. There is discussion of the action taken by the regulatory body when introducing the method of probabilistic risk analysis. The part played by this form of analysis in quantifying the safety objectives proposed in the USA together with its limitations and the problems involved in this methodology are examined. Lastly, the author gives an opinion on the use that probabilistic risk analysis should be put to in developing countries such as Mexico. (author)

  18. Regulatory role of melatonin and BMP-4 in prolactin production by rat pituitary lactotrope GH3 cells.

    Science.gov (United States)

    Ogura-Ochi, Kanako; Fujisawa, Satoshi; Iwata, Nahoko; Komatsubara, Motoshi; Nishiyama, Yuki; Tsukamoto-Yamauchi, Naoko; Inagaki, Kenichi; Wada, Jun; Otsuka, Fumio

    2017-08-01

    The effects of melatonin on prolactin production and its regulatory mechanism remain uncertain. We investigated the regulatory role of melatonin in prolactin production using rat pituitary lactotrope GH3 cells by focusing on the bone morphogenetic protein (BMP) system. Melatonin receptor activation, induced by melatonin and its receptor agonist ramelteon, significantly suppressed basal and forskolin-induced prolactin secretion and prolactin mRNA expression in GH3 cells. The melatonin MT2 receptor was predominantly expressed in GH3 cells, and the inhibitory effects of melatonin on prolactin production were reversed by treatment with the receptor antagonist luzindole, suggesting functional involvement of MT2 action in the suppression of prolactin release. Melatonin receptor activation also suppressed BMP-4-induced prolactin expression by inhibiting phosphorylation of Smad and transcription of the BMP-target gene Id-1, while BMP-4 treatment upregulated MT2 expression. Melatonin receptor activation suppressed basal, BMP-4-induced and forskolin-induced cAMP synthesis; however, BtcAMP-induced prolactin mRNA expression was not affected by melatonin or ramelteon, suggesting that MT2 activation leads to inhibition of prolactin production through the suppression of Smad signaling and cAMP synthesis. Experiments using intracellular signal inhibitors revealed that the ERK pathway is, at least in part, involved in prolactin induction by GH3 cells. Thus, a new regulatory role of melatonin involving BMP-4 in prolactin secretion was uncovered in lactotrope GH3 cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. On the role of sparseness in the evolution of modularity in gene regulatory networks.

    Science.gov (United States)

    Espinosa-Soto, Carlos

    2018-05-01

    Modularity is a widespread property in biological systems. It implies that interactions occur mainly within groups of system elements. A modular arrangement facilitates adjustment of one module without perturbing the rest of the system. Therefore, modularity of developmental mechanisms is a major factor for evolvability, the potential to produce beneficial variation from random genetic change. Understanding how modularity evolves in gene regulatory networks, that create the distinct gene activity patterns that characterize different parts of an organism, is key to developmental and evolutionary biology. One hypothesis for the evolution of modules suggests that interactions between some sets of genes become maladaptive when selection favours additional gene activity patterns. The removal of such interactions by selection would result in the formation of modules. A second hypothesis suggests that modularity evolves in response to sparseness, the scarcity of interactions within a system. Here I simulate the evolution of gene regulatory networks and analyse diverse experimentally sustained networks to study the relationship between sparseness and modularity. My results suggest that sparseness alone is neither sufficient nor necessary to explain modularity in gene regulatory networks. However, sparseness amplifies the effects of forms of selection that, like selection for additional gene activity patterns, already produce an increase in modularity. That evolution of new gene activity patterns is frequent across evolution also supports that it is a major factor in the evolution of modularity. That sparseness is widespread across gene regulatory networks indicates that it may have facilitated the evolution of modules in a wide variety of cases.

  20. 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…

  1. Development of safety culture at Kozloduy NPP: The role of the regulatory body

    International Nuclear Information System (INIS)

    Miliovsky, Ventzislav

    2002-01-01

    An evolution is made upon external factor that accompany the development of safety culture at Kozloduy NPP (KNPP). The two basic stages and the major results achieved independently and with external assistance were considered in the process of development of safety culture. The areas in which the regulatory body insists on having active participation were defined. (author)

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  3. The Role of Regulatory Pressure in Banks’ Capital and Risk Decisions

    Directory of Open Access Journals (Sweden)

    Alessandra Tanda

    2015-06-01

    Full Text Available Capital regulation represents the core of prudential regulation in banking. Despite the aim of the regulators to have a safer and more robust banking industry, the effects of capital regulation on banks’ capital and risk decisions appear ambiguous. The paper analyses the relationship between capital and risk changes and the impact of regulatory pressure for a sample of European banks during the period 2006–2010, which encompasses the start of the latest financial crisis. Results highlight that banks tend to adopt a different behaviour depending on the capital ratio considered, supporting the so-called ‘gamble for resurrection’ hypothesis. Evidence supports the rethinking of the regulatory framework, especially with reference to higher and stricter capital requirements.

  4. Role of Sodium Bicarbonate Cotransporters in Intracellular pH Regulation and Their Regulatory Mechanisms in Human Submandibular Glands.

    Science.gov (United States)

    Namkoong, Eun; Shin, Yong-Hwan; Bae, Jun-Seok; Choi, Seulki; Kim, Minkyoung; Kim, Nahyun; Hwang, Sung-Min; Park, Kyungpyo

    2015-01-01

    Sodium bicarbonate cotransporters (NBCs) are involved in the pH regulation of salivary glands. However, the roles and regulatory mechanisms among different NBC isotypes have not been rigorously evaluated. We investigated the roles of two different types of NBCs, electroneutral (NBCn1) and electrogenic NBC (NBCe1), with respect to pH regulation and regulatory mechanisms using human submandibular glands (hSMGs) and HSG cells. Intracellular pH (pHi) was measured and the pHi recovery rate from cell acidification induced by an NH4Cl pulse was recorded. Subcellular localization and protein phosphorylation were determined using immunohistochemistry and co-immunoprecipitation techniques. We determined that NBCn1 is expressed on the basolateral side of acinar cells and the apical side of duct cells, while NBCe1 is exclusively expressed on the apical membrane of duct cells. The pHi recovery rate in hSMG acinar cells, which only express NBCn1, was not affected by pre-incubation with 5 μM PP2, an Src tyrosine kinase inhibitor. However, in HSG cells, which express both NBCe1 and NBCn1, the pHi recovery rate was inhibited by PP2. The apparent difference in regulatory mechanisms for NBCn1 and NBCe1 was evaluated by artificial overexpression of NBCn1 or NBCe1 in HSG cells, which revealed that the pHi recovery rate was only inhibited by PP2 in cells overexpressing NBCe1. Furthermore, only NBCe1 was significantly phosphorylated and translocated by NH4Cl, which was inhibited by PP2. Our results suggest that both NBCn1 and NBCe1 play a role in pHi regulation in hSMG acinar cells, and also that Src kinase does not regulate the activity of NBCn1.

  5. Role of Sodium Bicarbonate Cotransporters in Intracellular pH Regulation and Their Regulatory Mechanisms in Human Submandibular Glands.

    Directory of Open Access Journals (Sweden)

    Eun Namkoong

    Full Text Available Sodium bicarbonate cotransporters (NBCs are involved in the pH regulation of salivary glands. However, the roles and regulatory mechanisms among different NBC isotypes have not been rigorously evaluated. We investigated the roles of two different types of NBCs, electroneutral (NBCn1 and electrogenic NBC (NBCe1, with respect to pH regulation and regulatory mechanisms using human submandibular glands (hSMGs and HSG cells. Intracellular pH (pHi was measured and the pHi recovery rate from cell acidification induced by an NH4Cl pulse was recorded. Subcellular localization and protein phosphorylation were determined using immunohistochemistry and co-immunoprecipitation techniques. We determined that NBCn1 is expressed on the basolateral side of acinar cells and the apical side of duct cells, while NBCe1 is exclusively expressed on the apical membrane of duct cells. The pHi recovery rate in hSMG acinar cells, which only express NBCn1, was not affected by pre-incubation with 5 μM PP2, an Src tyrosine kinase inhibitor. However, in HSG cells, which express both NBCe1 and NBCn1, the pHi recovery rate was inhibited by PP2. The apparent difference in regulatory mechanisms for NBCn1 and NBCe1 was evaluated by artificial overexpression of NBCn1 or NBCe1 in HSG cells, which revealed that the pHi recovery rate was only inhibited by PP2 in cells overexpressing NBCe1. Furthermore, only NBCe1 was significantly phosphorylated and translocated by NH4Cl, which was inhibited by PP2. Our results suggest that both NBCn1 and NBCe1 play a role in pHi regulation in hSMG acinar cells, and also that Src kinase does not regulate the activity of NBCn1.

  6. An essential regulatory role of downstream of kinase-1 in the ovalbumin-induced murine model of asthma.

    Directory of Open Access Journals (Sweden)

    Chang-Min Lee

    Full Text Available The downstream of kinase (DOK-1 is involved in the protein tyrosine kinase (PTK pathway in mast cells, but the role of DOK-1 in the pathogenesis of asthma has not been defined. In this study, we have demonstrated a novel regulatory role of DOK-1 in airway inflammation and physiologic responses in a murine model of asthma using lentiviral vector containing DOK-1 cDNA or DOK-1-specific ShRNA. The OVA-induced inflammatory cells, airway hyperresponsiveness, Th2 cytokine expression, and mucus response were significantly reduced in DOK-1 overexpressing mice compared to OVA-challenged control mice. The transgenic introduction of DOK-1 significantly stimulated the activation and expression of STAT-4 and T-bet, while impressively inhibiting the activation and expression of STAT-6 and GATA-3 in airway epithelial cells. On the other hand, DOK-1 knockdown mice enhanced STAT-6 expression and its nuclear translocation compared to OVA-challenged control mice. When viewed in combination, our studies demonstrate DOK-1 regulates allergen-induced Th2 immune responses by selective stimulation and inhibition of STAT-4 and STAT-6 signaling pathways, respectively. These studies provide a novel insight on the regulatory role of DOK-1 in allergen-induced Th2 inflammation and airway responses, which has therapeutic potential for asthma and other allergic diseases.

  7. Role of plant MicroRNA in cross-species regulatory networks of humans.

    Science.gov (United States)

    Zhang, Hao; Li, Yanpu; Liu, Yuanning; Liu, Haiming; Wang, Hongyu; Jin, Wen; Zhang, Yanmei; Zhang, Chao; Xu, Dong

    2016-08-08

    It has been found that microRNAs (miRNAs) can function as a regulatory factor across species. For example, food-derived plant miRNAs may pass through the gastrointestinal (GI) tract, enter into the plasma and serum of mammals, and interact with endogenous RNAs to regulate their expression. Although this new type of regulatory mechanism is not well understood, it provides a fresh look at the relationship between food consumption and physiology. To investigate this new type of mechanism, we conducted a systematic computational study to analyze the potential functions of these dietary miRNAs in the human body. In this paper, we predicted human and plant target genes using RNAhybrid and set some criteria to further filter them. Then we built the cross-species regulatory network according to the filtered targets, extracted central nodes by PageRank algorithm and built core modules. We summarized the functions of these modules to three major categories: ion transport, metabolic process and stress response, and especially some target genes are highly related to ion transport, polysaccharides and the lipid metabolic process. Through functional analysis, we found that human and plants have similar functions such as ion transport and stress response, so our study also indicates the existence of a close link between exogenous plant miRNA targets and digestive/urinary organs. According to our analysis results, we suggest that the ingestion of these plant miRNAs may have a functional impact on consuming organisms in a cross-kingdom way, and the dietary habit may affect the physiological condition at a genetic level. Our findings may be useful for discovering cross-species regulatory mechanism in further study.

  8. The impact of the new regulatory paradigm on the role of banks in financing the economy

    OpenAIRE

    Barut, M.-L.; Rouillé, N.; Sanchez, M.

    2015-01-01

    The financial crisis exposed the weaknesses and excesses of the banking system, notably its growing reliance on short-term market financing, excessive levels of leverage, and the fact that many banks were conducting high-risk market activities alongside retail banking activities. In 2009, in reaction to the crisis, regulatory authorities embarked on an ambitious agenda of reforms to financial regulations, aimed at cleaning up and reinforcing the banking system and ensuring it can meet the cre...

  9. Childhood cumulative risk and obesity: the mediating role of self-regulatory ability.

    Science.gov (United States)

    Evans, Gary W; Fuller-Rowell, Thomas E; Doan, Stacey N

    2012-01-01

    We tested whether early childhood risk exposures are related to weight gain in adolescence and evaluate an underlying mechanism, self-regulatory behavior, for the risk-obesity link. Cumulative risk exposure to 9 sociodemographic (eg, poverty), physical (eg, substandard housing), and psychosocial (eg, family turmoil) stressors was assessed in 244 nine-year-old children. BMI was calculated at age 9 and then 4 years later. At age 9, children's ability to delay gratification as an index of self-regulatory behavior was assessed. Path analyses were then estimated to evaluate our mediational model (Cumulative risk → Self-regulation → BMI) over a 4-year period in a prospective, longitudinal design. Nine-year-old children exposed to a greater accumulation of multiple risk factors show larger gains in adiposity over the next four year period, net of their initial BMI. These gains in BMI during early adolescence are largely accounted for by deteriorated self-regulatory abilities among children facing more cumulative risks. Early childhood risk exposure leads to larger gains in BMI in adolescence. Given the importance of childhood adiposity to the development of obesity later in life, understanding the underlying mechanisms that link early experience to weight gain is an essential task. Deficiencies in self-regulation in response to chronic stress appears to be an important agent in the obesity epidemic.

  10. The mass media role in acceptance activities of Slovak Republic's Nuclear Regulatory Authority

    International Nuclear Information System (INIS)

    Seliga, Mojmir

    1998-01-01

    Communication is the vital link between Nuclear Regulatory Authority and the public. If people do not know and understand the facts on which optimal a safety energy choice decisions should be based they cannot make informed decisions on how their own objectives can be met. The following ten commandments of communications are pointed out: be yourself; be comfortable and confident; be honest; be brief; be human; be personal; be positive and consistent; be attentive; be energetic; be committed and sincere. The important aspect is to test whether the nuclear energy in the Slovak Republic is acceptable according to mandatory rules and if its operation is regulated by the state through the independent institution - the Nuclear Regulatory Authority of the Slovak Republic (UJD). The media in Slovakia has on important power. Many organizations are therefore apprehensive when dealing with the press, radio and television. Many people would simply prefer not to get panicked when the dreaded microphones and cameras do appear. UJD considers the whole area of public relations as an essential component of its activity. UJD intends to offer the public true, systematic, qualified, understandable and independent information, regarding the safety of nuclear power plants, as well as regarding the methods and results of UJD work. Generally, public information is considered a significant contribution to the creation of confidence into the regulatory work. The paper presents the UJD communication program and relations with media as well as the preparedness of public information in case of emergency

  11. Collective statement on the role of research in a nuclear regulatory context

    International Nuclear Information System (INIS)

    2001-01-01

    In the present context of deregulation and privatisation of the nuclear industry, maintaining an adequate level of nuclear safety research is a primary concern for nuclear regulators, researchers and nuclear power plant licensees, as well as for government officials and the public. While these different stakeholders may have common concerns and interests, there may also be differences. At the international level, it is important to understand that divisions exist both within and among countries, not only in national cultures but also in the way regulators, researchers and licensees view the rote of research. An international gathering under the auspices of the OECD Nuclear Energy Agency (NEA) took place in June 2001, bringing together heads of nuclear regulatory bodies of NEA Member countries, senior regulators, senior executives of research organisations and leaders from the nuclear industry to discuss their perceptions of the rote of research in a nuclear regulatory context. This collective statement represents an international consensus on a rationale for regulatory research for currently operating nuclear reactors and for future reactors, and sets forth specific recommendations to NEA standing technical committees and Member countries. The intended audience is primarily nuclear safety regulators, senior researchers and industry leaders. Government authorities, nuclear power plant operators and the general public may also be interested. (author)

  12. Dual Role of GM-CSF as a Pro-Inflammatory and a Regulatory Cytokine: Implications for Immune Therapy

    Science.gov (United States)

    Bhattacharya, Palash; Budnick, Isadore; Singh, Medha; Thiruppathi, Muthusamy; Alharshawi, Khaled; Elshabrawy, Hatem; Holterman, Mark J.

    2015-01-01

    Granulocyte macrophage colony stimulating factor (GM-CSF) is generally recognized as an inflammatory cytokine. Its inflammatory activity is primarily due its role as a growth and differentiation factor for granulocyte and macrophage populations. In this capacity, among other clinical applications, it has been used to bolster anti-tumor immune responses. GM-CSF-mediated inflammation has also been implicated in certain types of autoimmune diseases, including rheumatoid arthritis and multiple sclerosis. Thus, agents that can block GM-CSF or its receptor have been used as anti-inflammatory therapies. However, a review of literature reveals that in many situations GM-CSF can act as an anti-inflammatory/regulatory cytokine. We and others have shown that GM-CSF can modulate dendritic cell differentiation to render them “tolerogenic,” which, in turn, can increase regulatory T-cell numbers and function. Therefore, the pro-inflammatory and regulatory effects of GM-CSF appear to depend on the dose and the presence of other relevant cytokines in the context of an immune response. A thorough understanding of the various immunomodulatory effects of GM-CSF will facilitate more appropriate use and thus further enhance its clinical utility. PMID:25803788

  13. Regulatory role of XynR (YagI) in catabolism of xylonate in Escherichia coli K-12.

    Science.gov (United States)

    Shimada, Tomohiro; Momiyama, Eri; Yamanaka, Yuki; Watanabe, Hiroki; Yamamoto, Kaneyoshi; Ishihama, Akira

    2017-12-01

    The genome of Escherichia coli K-12 contains ten cryptic phages, altogether constituting about 3.6% of the genome in sequence. Among more than 200 predicted genes in these cryptic phages, 14 putative transcription factor (TF) genes exist, but their regulatory functions remain unidentified. As an initial attempt to make a breakthrough for understanding the regulatory roles of cryptic phage-encoded TFs, we tried to identify the regulatory function of CP4-6 cryptic prophage-encoded YagI with unknown function. After SELEX screening, YagI was found to bind mainly at a single site within the spacer of bidirectional transcription units, yagA (encoding another uncharacterized TF) and yagEF (encoding 2-keto-3-deoxy gluconate aldolase, and dehydratase, respectively) within this prophage region. YagEF enzymes are involved in the catabolism of xylose downstream from xylonate. We then designated YagI as XynR (regulator of xylonate catabolism), one of the rare single-target TFs. In agreement with this predicted regulatory function, the activity of XynR was suggested to be controlled by xylonate. Even though low-affinity binding sites of XynR were identified in the E. coli K-12 genome, they all were inside open reading frames, implying that the regulation network of XynR is still fixed within the CR4-6 prophage without significant influence over the host E. coli K-12. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. CD4 T cells mediate both positive and negative regulation of the immune response to HIV infection: complex role of T follicular helper cells and Regulatory T cells in pathogenesis

    Directory of Open Access Journals (Sweden)

    Chansavath ePhetsouphanh

    2015-01-01

    Full Text Available HIV-1 infection results in chronic activation of cells in lymphoid tissue, including T cells, B cells and myeloid lineage cells. The resulting characteristic hyperplasia is an amalgam of proliferating host immune cells in the adaptive response, increased concentrations of innate response mediators due to viral and bacterial products, and homeostatic responses to inflammation. While it is generally thought that CD4 T cells are greatly depleted, in fact, two types of CD4 T cells appear to be increased, namely regulatory T cells (Tregs and T follicular helper cells (Tfh. These cells have opposing roles, but may both be important in the pathogenic process. Whether Tregs are failing in their role to limit lymphocyte activation is unclear, but there is no doubt now that Tfh are associated with B cell hyperplasia and increased germinal centre activity. Antiretroviral therapy (ART may reduce the lymphocyte activation, but not completely, and therefore there is a need for interventions that selectively enhance normal CD4 function without exacerbating Tfh, B cell or Treg dysfunction.

  15. Reflections on the role of the pharmacy regulatory authority in enhancing quality related event reporting in community pharmacies.

    Science.gov (United States)

    Boyle, Todd A; Bishop, Andrea C; Mahaffey, Thomas; Mackinnon, Neil J; Ashcroft, Darren M; Zwicker, Bev; Reid, Carolyn

    2014-01-01

    Given the demanding nature of providing pharmacy services, coupled with the expanded scope of practice of the professions in jurisdictions around the world, greater commitment to continuous quality improvement through adoption of quality-related event (QRE) reporting is necessary to ensure patient safety. Pharmacy regulatory authorities (PRAs) are in a unique position to enhance QRE reporting and learning through the standardization of expected practice. This study was aimed to gain a better understanding of the perceived roles of PRAs in enhancing QRE reporting and learning in community pharmacies, and identifying regulatory best practices to execute such roles. A purposive case sampling approach was used to identify PRA staff members from two groups (Deputy registrars and pharmacy inspectors) in 10 Canadian jurisdictions to participate in focus groups in the fall of 2011. Focus groups were used to explore perceptions of the role of PRAs in enhancing and promoting QRE reporting and learning, and perceived barriers to effective implementation in practice. Thematic analysis was used to analyze the qualitative data. Two focus groups were conducted, one with seven Deputy registrars/Practice managers, and one with nine pharmacy inspectors. Five themes were identified, including (1) defining QRE reporting and compliance, (2) navigating role conflict, (3) educating for enhanced QRE reporting and learning, (4) promoting the positive/removing the fear of QREs, and (5) tailoring QRE reporting and learning consistency. Overall, participants perceived a strong role for PRAs in enhancing QRE reporting and learning and providing education for pharmacies to support their compliance with reporting standards. However, PRAs must navigate the conflict inherent in both educating and promoting a process for achieving a standard while simultaneously inspecting compliance to that standard. Ensuring pharmacies have autonomy in operationalizing standards may help to mitigate this conflict

  16. REFLECTIONS ON THE ROLE OF THE PHARMACY REGULATORY AUTHORITY IN ENHANCING QUALITY RELATED EVENT REPORTING IN COMMUNITY PHARMACIESi

    Science.gov (United States)

    Boyle, Todd A.; Bishop, Andrea C.; Mahaffey, Thomas; MacKinnon, Neil J.; Ashcroft, Darren; Zwicker, Bev; Reid, Carolyn

    2016-01-01

    Background Given the demanding nature of providing pharmacy services, coupled with the expanded scope of practice of the professions in jurisdictions around the world, greater commitment to continuous quality improvement through adoption of quality related event (QRE) reporting is necessary to ensure patient safety. Pharmacy regulatory authorities (PRAs) are in a unique position to enhance QRE reporting and learning through the standardization of expected practice Objective This study aims to better understand the perceived roles of PRAs in enhancing QRE reporting and learning in community pharmacies and identifying regulatory best practices to execute such roles. Methods A purposive case sampling approach was used to identify PRA staff members from two groups (deputy registrars and pharmacy inspectors) in 10 Canadian jurisdictions to participate in focus groups in the fall of 2011. Focus groups were used to explore perceptions of the role of PRAs in enhancing and promoting QRE reporting and learning, and perceived barriers to effective implementation in practice. Thematic analysis was used to analyze the qualitative data. Results Two focus groups were conducted, one with seven deputy registrars/practice managers and one with nine pharmacy inspectors. Five themes were identified, including (1) defining QRE reporting and compliance, (2) navigating role conflict, (3) educating for enhanced QRE reporting and learning, (4) promoting the positive/removing the fear of QREs, and (5) tailoring QRE reporting and learning consistency. Conclusions Overall, participants perceived a strong role for PRAs in enhancing QRE reporting and learning and providing education for pharmacies to support their compliance with reporting standards. However, PRAs must navigate the conflict inherent in both educating and promoting a process for achieving a standard while simultaneously inspecting compliance to that standard. Ensuring pharmacies have autonomy in operationalizing standards may

  17. [Regulatory Mechanisms of PD-L1 Expression and Its Role in Immune Evasion].

    Science.gov (United States)

    Kataoka, Keisuke

    2017-11-01

    Immune checkpoint blockade therapy using anti-PD-1 or anti-PD-L1 antibodies can unleash anti-tumor immunity and induce durable remission in a variety ofhuman cancers. However, the regulatory mechanisms of PD-L1 expression mediating immune evasion ofcancer cells have not been fully elucidated, including the genetic alterations causing PD-L1 overexpression. Recently, we have reported a novel genetic mechanism ofimmune evasion associated with structural variations(SVs)disrupting the 3'-untranslated region(UTR)ofthe PD-L1 gene in various malignancies, such as aggressive lymphomas and gastrointestinal cancers. Despite a heterogenous nature ofthese SVs, they are closely associated with a marked upregulation of PD-L1 expression, which augments tumor growth and escape from anti-tumor immunity. Here we present an overview of the regulatory mechanisms of PD-L1 expression in cancer cells, highlighting the genetic mechanisms of PD-L1 constitutive activation, with specific focus on PD-L1 3'-UTR disruption.

  18. Regulatory Mode and Risk-Taking: The Mediating Role of Anticipated Regret.

    Science.gov (United States)

    Panno, Angelo; Lauriola, Marco; Pierro, Antonio

    2015-01-01

    We propose that decision maker's regulatory mode affects risk-taking through anticipated regret. In the Study 1 either a locomotion or an assessment orientation were experimentally induced, and in the Studies 2 and 3 these different orientations were assessed as chronic individual differences. To assess risk-taking we used two behavioral measures of risk: BART and hot-CCT. The results show that experimentally induced assessment orientation--compared to locomotion--leads to decreased risk-taking through increased anticipated regret (Study 1). People chronically predisposed to be in the assessment state take less risk through increased anticipated regret (Study 2 and Study 3). Study 2 results also show a marginally non-significant indirect effect of chronic locomotion mode on BART through anticipated regret. Differently, Study 3 shows that people chronically predisposed to be in the locomotion state take greater risk through decreased anticipated regret, when play a dynamic risk task triggering stronger emotional arousal. Through all three studies, the average effect size for the relationship of assessment with anticipated regret was in the moderate-large range, whereas for risk-taking was in the moderate range. The average effect size for the relationship of locomotion with anticipated regret was in the moderate range, whereas for risk-taking was in the small-moderate range. These results increase our understanding of human behavior under conditions of risk obtaining novel insights into regulatory mode theory and decision science.

  19. Role of partnership in enhancing the performance of radiation regulatory authority in Zambia

    International Nuclear Information System (INIS)

    Banda, S.C.

    2003-01-01

    The National Radiation Infrastructure includes legislation, human resource, technical capacity to execute responsibilities of the regulatory (1). In cases of developing countries like Zambia, special challenges arise in view of the constraints both in terms of human resource and funding. This paper will highlight same measures that may be undertaken to improve the operations of nation radiation protection infrastructure. The measures include collaboration with Science and Technology organisations that have technical capacity, delegation of responsible to key institutions that may have competence and generation of funds through training and provision of reliable quality service. (2). In Zambia, some achievements in this line have been registered by Radiation Protection Board working with the University of Zambia and National Institute for Scientific and Industrial Research (3). Some measures of generation of funds have been done though utilization of the generated remains to be the limiting factor to exploit fully benefits that may arise from the use of the monies generated from services. Partnerships with private sector may be used as regulatory authorities for support to its programme in particular the public awareness campaign. Sponsorship by a Private Cellar Phone Company (Telecel Zambia) and Rotary Club of Lusaka for Radiation Week to Radiation Protection Service under Theme 'Safe Radiation Use' is one such an example. The other opportunity is the technical cooperation with regional and international organisations such as SADC, IAEA, WHO, Interpol, EU and WCO for technical capacity building, human resource development and information access. (author)

  20. Understanding the relative roles of pharmacogenetics and ontogeny in pediatric drug development and regulatory science.

    Science.gov (United States)

    Leeder, J Steven; Kearns, Gregory L; Spielberg, Stephen P; van den Anker, John

    2010-12-01

    Understanding the dose-exposure-response relationship across the pediatric age spectrum from preterm and term newborns to infants, children, adolescents, and adults is a major challenge for clinicians, pharmaceutical companies, and regulatory agencies. Over the past 3 decades, clinical investigations of many drugs commonly used in pediatric therapeutics have provided valuable insights into age-associated differences in drug disposition and action. However, our understanding of the contribution of genetic variation to variability in drug disposition and response in children generally has lagged behind that of adults. This article proposes a systematic approach that can be used to assess the relative contributions of ontogeny and genetic variation for a given compound. Application of the strategy is illustrated using the current regulatory dilemma posed by the safety and effectiveness of over-the-counter cough and cold remedies as an example. The results of the analysis can be used to aid in the design of studies to yield maximally informative data in pediatric populations of different ages and developmental stages and thereby improve the efficiency of study design.

  1. Role of In Vitro Release Methods in Liposomal Formulation Development: Challenges and Regulatory Perspective.

    Science.gov (United States)

    Solomon, Deepak; Gupta, Nilesh; Mulla, Nihal S; Shukla, Snehal; Guerrero, Yadir A; Gupta, Vivek

    2017-11-01

    In the past few years, measurement of drug release from pharmaceutical dosage forms has been a focus of extensive research because the release profile obtained in vitro can give an indication of the drug's performance in vivo. Currently, there are no compendial in vitro release methods designed for liposomes owing to a range of experimental challenges, which has created a major hurdle for both development and regulatory acceptance of liposome-based drug products. In this paper, we review the current techniques that are most often used to assess in vitro drug release from liposomal products; these include the membrane diffusion techniques (dialysis, reverse dialysis, fractional dialysis, and microdialysis), the sample-and-separate approach, the in situ method, the continuous flow, and the modified United States Pharmacopeia methods (USP I and USP IV). We discuss the principles behind each of the methods and the criteria that assist in choosing the most appropriate method for studying drug release from a liposomal formulation. Also, we have included information concerning the current regulatory requirements for liposomal drug products in the United States and in Europe. In light of increasing costs of preclinical and clinical trials, applying a reliable in vitro release method could serve as a proxy to expensive in vivo bioavailability studies. Graphical Abstract Appropriate in-vitro drug release test from liposomal products is important to predict the in-vivo performance.

  2. Multiple regulatory roles of the mouse transmembrane adaptor protein NTAL in gene transcription and mast cell physiology.

    Directory of Open Access Journals (Sweden)

    Iva Polakovicova

    Full Text Available Non-T cell activation linker (NTAL; also called LAB or LAT2 is a transmembrane adaptor protein that is expressed in a subset of hematopoietic cells, including mast cells. There are conflicting reports on the role of NTAL in the high affinity immunoglobulin E receptor (FcεRI signaling. Studies carried out on mast cells derived from mice with NTAL knock out (KO and wild type mice suggested that NTAL is a negative regulator of FcεRI signaling, while experiments with RNAi-mediated NTAL knockdown (KD in human mast cells and rat basophilic leukemia cells suggested its positive regulatory role. To determine whether different methodologies of NTAL ablation (KO vs KD have different physiological consequences, we compared under well defined conditions FcεRI-mediated signaling events in mouse bone marrow-derived mast cells (BMMCs with NTAL KO or KD. BMMCs with both NTAL KO and KD exhibited enhanced degranulation, calcium mobilization, chemotaxis, tyrosine phosphorylation of LAT and ERK, and depolymerization of filamentous actin. These data provide clear evidence that NTAL is a negative regulator of FcεRI activation events in murine BMMCs, independently of possible compensatory developmental alterations. To gain further insight into the role of NTAL in mast cells, we examined the transcriptome profiles of resting and antigen-activated NTAL KO, NTAL KD, and corresponding control BMMCs. Through this analysis we identified several genes that were differentially regulated in nonactivated and antigen-activated NTAL-deficient cells, when compared to the corresponding control cells. Some of the genes seem to be involved in regulation of cholesterol-dependent events in antigen-mediated chemotaxis. The combined data indicate multiple regulatory roles of NTAL in gene expression and mast cell physiology.

  3. Regulatory aspects of teratology: role of the Food and Drug Administration

    International Nuclear Information System (INIS)

    Kelsey, F.O.

    1982-01-01

    The Food and Drug Administration is a scientific regulatory agency whose consumer protection activities cover a wide range of products including foods and additives, and pesticide residues on foods; drugs; cosmetics; medical devices; and radiation-emitting electronic products. Amongst its concerns is the possible teratogen effects of regulated products to which the pregnant woman is exposed. The policies and programs of the agency directed toward reducing such risks to the unborn are reviewed. These measures include guidelines for animal reproduction studies and for clinical trials involving women to childbearing potential; labeling of products to disclose known or possible harm to the fetus or embryo; surveillance procedures designed to detect previously unsuspected adverse effects of marketed products; research activities designed to develop better understanding of developmental toxicology and improved techniques for detecting embryocidal and embryotoxic effects; and educational efforts directed both to professionals and the public regarding hazards to the unborn of agency-regulated products

  4. Pathogenesis and pharmacologic treatment of obesity: the role of energy regulatory mechanism.

    Science.gov (United States)

    Manulu, Mangatas S M; Sutanegara, I N Dwi

    2006-01-01

    Obesity has become a worldwide public health problem affecting millions of people. This is a chronic, stigmatized, and costly disease, rarely curable and is increasing in prevalence to a point today where we define obesity as an epidemic disease that not only in developed but also on developing countries. The pathogenesis of obesity is largely unknown, especially about energy regulatory mechanism that involved wide area of neuroendocrinology that is very interesting but very complex and makes internists "refuse" to learn. Obesity occurs through a longstanding imbalance between energy intake and energy expenditure, influenced by a complex biologic system that regulates appetite and adiposity. Obesity influences the pathogenesis of hypertension, type 2 diabetes, dyslipidemia, kidney, heart, and cerebrovascular disease. It is very wise for every internist to learn the pathogenesis and treatment of this worldwide diseases. Until now, the available treatments, including drugs, are palliative and are effective only while the treatment is being actively used; and besides so many side effects reported.

  5. Regulatory role and approach of BARC Safety Council in safety and occupational health in BARC facilities

    International Nuclear Information System (INIS)

    Rajdeep; Jayarajan, K.; Taly, Y.K.

    2016-01-01

    Bhabha Atomic Research Centre is involved in multidisciplinary research and developmental activities, related to peaceful use of nuclear energy and its societal benefits. In order to achieve high level of performance of these facilities, the best efforts are made to maintain good health of the plant personnel and good working conditions. BARC Safety Council (BSC), which is the regulatory body for BARC facilities, regulates radiation safety, industrial safety and surveillance of occupational health, by implementing various rules and guidelines in BARC facilities. BARC Safety framework consists of various committees in a 3-tier system. The first tier is BSC, which is the apex body authorized for issuing directives, permissions, consents and authorizations. It is having responsibility of ensuring protection and safety of public, environment, personnel and facilities of BARC through enforcement of radiation protection and industrial safety programmes. Besides the 18 committees in 2"n"d tier, there are 6 other expert committees which assist in functioning of BSC. (author)

  6. The dual effects of leading for safety: The mediating role of employee regulatory focus.

    Science.gov (United States)

    Kark, Ronit; Katz-Navon, Tal; Delegach, Marianna

    2015-09-01

    This study examined the underlying mechanisms through which transformational and transactional leadership influence employee safety behaviors. Linking leadership theory with self-regulatory focus (SRF) theory, we examined a model of dual effects of leadership on safety initiative and safety compliance behaviors as mediated by promotion and prevention self-regulations. We conducted an experimental study (N = 107), an online study (N = 99) and a field study (N = 798 employees and 49 managers). Results demonstrated that followers' situational promotion focus mediated the positive relationship between transformational leadership and safety initiative behaviors. Through all 3 studies, transactional active leadership was positively associated with followers' situational prevention focus, however, the association between followers' prevention focus and safety compliance behaviors was inconsistent, showing the expected mediation relationships in the experimental setting, but not in the online and field studies. We discuss theoretical and practical implications of the findings. (c) 2015 APA, all rights reserved).

  7. Role of bundle helices in a regulatory crosstalk in the trimeric betaine transporter BetP.

    Science.gov (United States)

    Gärtner, Rebecca M; Perez, Camilo; Koshy, Caroline; Ziegler, Christine

    2011-12-02

    The Na(+)-coupled betaine symporter BetP regulates transport activity in response to hyperosmotic stress only in its trimeric state, suggesting a regulatory crosstalk between individual protomers. BetP shares the overall fold of two inverted structurally related five-transmembrane (TM) helix repeats with the sequence-unrelated Na(+)-coupled symporters LeuT, vSGLT, and Mhp1, which are neither trimeric nor regulated in transport activity. Conformational changes characteristic for this transporter fold involve the two first helices of each repeat, which form a four-TM-helix bundle. Here, we identify two ionic networks in BetP located on both sides of the membrane that might be responsible for BetP's unique regulatory behavior by restricting the conformational flexibility of the four-TM-helix bundle. The cytoplasmic ionic interaction network links both first helices of each repeat in one protomer to the osmosensing C-terminal domain of the adjacent protomer. Moreover, the periplasmic ionic interaction network conformationally locks the four-TM-helix bundle between the same neighbor protomers. By a combination of site-directed mutagenesis, cross-linking, and betaine uptake measurements, we demonstrate how conformational changes in individual bundle helices are transduced to the entire bundle by specific inter-helical interactions. We suggest that one purpose of bundle networking is to assist crosstalk between protomers during transport regulation by specifically modulating the transition from outward-facing to inward-facing state. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. France's Efforts to Promote NPP Exports and the Implications on the Role of Nuclear Regulatory Body

    International Nuclear Information System (INIS)

    Oh, Chae-Woon; Chang, Hyun-Sop; Choi, Young-Sung

    2008-01-01

    The global society facing sky-rocketing oil prices, global warming effects, and increased demand for electricity recognizes the comparative advantages of nuclear energy in terms of environmental impact and economic efficiency over the other energy sources of current use. Approximately 300 nuclear power plants (NPPs) expect to be constructed until 2030 worldwide. Accordingly, the global market size of nuclear power industry becomes scaled up to the extent of U$75 billion on the assumption that the construction of one reactor costs around U$2.5 billion. The nations in possession of advanced nuclear technology such as the U.S., France, Japan, etc not only recognized an abounding profitability in nuclear industry and anticipated nuclear renaissance but also prepared long before whatever necessary to expand their nuclear programs beyond their domestic boundaries. Amongst those nations, it seems to be France that has unfolded a remarkable array of government-led activities to export Evolutionary Pressurized Reactors (EPRs) under the cooperation of President, relevant government administration, utilities even a regulatory body. The omni-directional activities of France and its implications are presented in this paper

  9. A regulatory perspective of the role of construction in revitalizing the United States nuclear industry

    International Nuclear Information System (INIS)

    Stello, V. Jr.

    1983-01-01

    Technical and managerial experience in nuclear power plant construction is presented from the perspective of the United States Nuclear Regulatory Commission (NRC). In the context of actions that would contribute to revitalizing the nuclear industry in the United States of America, greater effectiveness of utility management during construction is proposed. The reasons why management effectiveness is so important are developed beginning with summaries of defects that were built into several US plants under construction. The root causes of these significant defects were management failures. In terms of benefits, effective management is important because of its effects on nuclear safety, project construction costs, and future reliability of the plant after commissioning. Actions that would enhance good management include emphasizing the inseparable nature of production and quality, that quality cannot be inspected into a plant, and that a strong construction management staff and exchanges of experience and information are essential. Techniques that have been used successfully in construction management are discussed. NRC and industry initiatives are in progress to improve management responsibility and learning from experience. Projects include Owner's Certification, assessments of licensee performance, fostering good practices across the industry, and improving the NRC inspection programme. Revitalization will not be easy, but it is achievable. (author)

  10. Apoptosis following interleukin-2 withdrawal from T cells: evidence for a regulatory role of CD18 (beta 2-integrin) molecules

    DEFF Research Database (Denmark)

    Röpke, C; Gladstone, P; Nielsen, M

    1996-01-01

    , these findings suggest that CD18 molecules (beta 2-integrins) play a regulatory role in the apoptotic response following cytokine withdrawal, and that the regulation is mediated, at least partly, through T-T cell interactions. Thus, apoptotic death following IL-2 deprivation appears to be under "social" control...... activated T cells. Thus, removal of IL-2 from proliferating T cells not only induces growth arrest, but triggers a massive cell death due to apoptosis. While the apoptotic response involves a series of well-described events, it remains less clear how apoptosis is regulated following IL-2 withdrawal. Here...... molecules (CD28, CD29, CD49d, CD80, CD86) did not. Secondly, IL-2 withdrawal resulted in a retarded apoptotic response in LFA-1 (CD11a/CD18) negative T cells obtained from a leukocyte adhesion deficiency (LAD) patient, as compared to LFA-1 positive T cell lines. Thirdly, co-culture of LFA-1 positive...

  11. Reconstruction of the yeast Snf1 kinase regulatory network reveals its role as a global energy regulator

    Science.gov (United States)

    Usaite, Renata; Jewett, Michael C; Oliveira, Ana Paula; Yates, John R; Olsson, Lisbeth; Nielsen, Jens

    2009-01-01

    Highly conserved among eukaryotic cells, the AMP-activated kinase (AMPK) is a central regulator of carbon metabolism. To map the complete network of interactions around AMPK in yeast (Snf1) and to evaluate the role of its regulatory subunit Snf4, we measured global mRNA, protein and metabolite levels in wild type, Δsnf1, Δsnf4, and Δsnf1Δsnf4 knockout strains. Using four newly developed computational tools, including novel DOGMA sub-network analysis, we showed the benefits of three-level ome-data integration to uncover the global Snf1 kinase role in yeast. We for the first time identified Snf1's global regulation on gene and protein expression levels, and showed that yeast Snf1 has a far more extensive function in controlling energy metabolism than reported earlier. Additionally, we identified complementary roles of Snf1 and Snf4. Similar to the function of AMPK in humans, our findings showed that Snf1 is a low-energy checkpoint and that yeast can be used more extensively as a model system for studying the molecular mechanisms underlying the global regulation of AMPK in mammals, failure of which leads to metabolic diseases. PMID:19888214

  12. Deep transcriptome profiling of mammalian stem cells supports a regulatory role for retrotransposons in pluripotency maintenance

    DEFF Research Database (Denmark)

    Fort, Alexandre; Hashimoto, Kosuke; Yamada, Daisuke

    2014-01-01

    The importance of microRNAs and long noncoding RNAs in the regulation of pluripotency has been documented; however, the noncoding components of stem cell gene networks remain largely unknown. Here we investigate the role of noncoding RNAs in the pluripotent state, with particular emphasis on nucl...

  13. Role of regulatory T cells in acute myeloid leukemia patients undergoing relapse-preventive immunotherapy.

    Science.gov (United States)

    Sander, Frida Ewald; Nilsson, Malin; Rydström, Anna; Aurelius, Johan; Riise, Rebecca E; Movitz, Charlotta; Bernson, Elin; Kiffin, Roberta; Ståhlberg, Anders; Brune, Mats; Foà, Robin; Hellstrand, Kristoffer; Thorén, Fredrik B; Martner, Anna

    2017-11-01

    Regulatory T cells (T regs ) have been proposed to dampen functions of anti-neoplastic immune cells and thus promote cancer progression. In a phase IV trial (Re:Mission Trial, NCT01347996, http://www.clinicaltrials.gov ) 84 patients (age 18-79) with acute myeloid leukemia (AML) in first complete remission (CR) received ten consecutive 3-week cycles of immunotherapy with histamine dihydrochloride (HDC) and low-dose interleukin-2 (IL-2) to prevent relapse of leukemia in the post-consolidation phase. This study aimed at defining the features, function and dynamics of Foxp3 + CD25 high CD4 + T regs during immunotherapy and to determine the potential impact of T regs on relapse risk and survival. We observed a pronounced increase in T reg counts in peripheral blood during initial cycles of HDC/IL-2. The accumulating T regs resembled thymic-derived natural T regs (nT regs ), showed augmented expression of CTLA-4 and suppressed the cell cycle proliferation of conventional T cells ex vivo. Relapse of AML was not prognosticated by T reg counts at onset of treatment or after the first cycle of immunotherapy. However, the magnitude of T reg induction was diminished in subsequent treatment cycles. Exploratory analyses implied that a reduced expansion of T regs in later treatment cycles and a short T reg telomere length were significantly associated with a favorable clinical outcome. Our results suggest that immunotherapy with HDC/IL-2 in AML entails induction of immunosuppressive T regs that may be targeted for improved anti-leukemic efficiency.

  14. Overeruption of teeth opposing removable partial dentures: a preliminary study.

    Science.gov (United States)

    Matsuda, Ken-Ichi; Miyashita, Yuji; Ikebe, Kazunori; Enoki, Kaori; Kurushima, Yuko; Mihara, Yusuke; Maeda, Yoshinobu

    2014-01-01

    One of the purposes of prosthodontic treatment is to prevent overeruption of opposing teeth, but there is currently minimal literature describing the efficacy of removable partial dentures (RPDs) in performing this function. This study investigated overeruption following RPD treatment. The study participants were 33 patients treated with RPDs, and overeruption was evaluated by comparing the surface computeraided design data of dental casts made at two different time points-before and after RPD treatment. Overeruption was observed in 38.1% of teeth opposed by the RPD, which was much less than the proportion of teeth that overerupted when not opposed by the RPD.

  15. The regulatory role of heparin on c-Met signaling in hepatocellular carcinoma cells.

    Science.gov (United States)

    İşcan, Evin; Güneş, Aysim; Korhan, Peyda; Yılmaz, Yeliz; Erdal, Esra; Atabey, Neşe

    2017-06-01

    The role of heparin as an anticoagulant is well defined; however, its role in tumorigenesis and tumor progression is not clear yet. Some studies have shown that anticoagulant treatment in cancer patients improve overall survival, however, recent clinical trials have not shown a survival benefit in cancer patients receiving heparin treatment. In our previous studies we have shown the inhibitory effects of heparin on Hepatocyte Growth Factor (HGF)-induced invasion and migration in hepatocellular carcinoma (HCC) cells. In this study, we showed the differential effects of heparin on the behaviors of HCC cells based on the presence or absence of HGF. In the absence of HGF, heparin activated HGF/c-Met signaling and promoted motility and invasion in HCC cells. Heparin treatment led to c-Met receptor dimerization and activated c-Met signaling in an HGF independent manner. Heparin-induced c-Met activation increased migration and invasion through ERK1/2, early growth response factor 1 (EGR1) and Matrix Metalloproteinases (MMP) axis. Interestingly, heparin modestly decreased the proliferation of HCC cells by inhibiting activatory phosphorylation of Akt. The inhibition of c-Met signaling reversed heparin-induced increase in motility and invasion and, proliferation inhibition. Our study provides a new perspective into the role of heparin on c-Met signaling in HCC.

  16. Protein Kinase A Regulatory Subunit Isoforms Regulate Growth and Differentiation in Mucor circinelloides: Essential Role of PKAR4

    Science.gov (United States)

    Ocampo, J.; McCormack, B.; Navarro, E.; Moreno, S.; Garre, V.

    2012-01-01

    The protein kinase A (PKA) signaling pathway plays a role in regulating growth and differentiation in the dimorphic fungus Mucor circinelloides. PKA holoenzyme is comprised of two catalytic (C) and two regulatory (R) subunits. In M. circinelloides, four genes encode the PKAR1, PKAR2, PKAR3, and PKAR4 isoforms of R subunits. We have constructed null mutants and demonstrate that each isoform has a different role in growth and differentiation. The most striking finding is that pkaR4 is an essential gene, because only heterokaryons were obtained in knockout experiments. Heterokaryons with low levels of wild-type nuclei showed an impediment in the emission of the germ tube, suggesting a pivotal role of this gene in germ tube emergence. The remaining null strains showed different alterations in germ tube emergence, sporulation, and volume of the mother cell. The pkaR2 null mutant showed an accelerated germ tube emission and was the only mutant that germinated under anaerobic conditions when glycine was used as a nitrogen source, suggesting that pkaR2 participates in germ tube emergence by repressing it. From the measurement of the mRNA and protein levels of each isoform in the wild-type and knockout strains, it can be concluded that the expression of each subunit has its own mechanism of differential regulation. The PKAR1 and PKAR2 isoforms are posttranslationally modified by ubiquitylation, suggesting another regulation point in the specificity of the signal transduction. The results indicate that each R isoform has a different role in M. circinelloides physiology, controlling the dimorphism and contributing to the specificity of cyclic AMP (cAMP)-PKA pathway. PMID:22635921

  17. Regulatory roles and therapeutic potential of microRNA in sarcoma.

    Science.gov (United States)

    Lim, Hui Jun; Yang, Jia-Lin

    2016-01-01

    MicroRNAs (miRNAs) are single-stranded noncoding RNAs involved in various biological processes, including cell differentiation and development. They play multiple key roles as tumour suppressors, oncogenes or both in particular cases. This review aims to summarise current findings of the expression of miRNAs and their role in clinical oncology. Current knowledge regarding the involvement of miRNAs in different sarcoma subtypes will be assessed, in conjunction with their potential application as therapeutic targets. Relevant articles in scientific databases were identified using a combination of search terms, including "microRNA," "deregulation," "sarcoma," and "targeted therapy". These databases included Medline, Embase, Cochrane Review, Pubmed and Scopus. Aberrant miRNA expression patterns have been identified in a range of sarcoma subtypes, and differences in miRNA expression profiles between malignant cells and their normal counterparts suggests that miRNAs play key roles in sarcoma development. The identification of unique miRNA patterns in individual tumour types could possibly be used as a diagnostic tool in sarcoma. Moreover, identification of these miRNAs provides novel targets for the development of therapeutic strategies in distinct sarcoma subtypes. miRNAs hold significant potential as diagnostic biomarkers, as well as therapeutic targets in sarcoma. Possible future clinical applications include the use of miRNA pathways as therapeutic targets or miRNA expression profiling as a means of patient selection. The involvement miRNAs will undoubtedly contribute to the advancement of future targeted therapeutic interventions in sarcoma, and further establishment of appropriate delivery systems is vital for their use in clinical settings. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. A Novel Gibberellin-Induced Gene from Rice and Its Potential Regulatory Role in Stem Growth1

    Science.gov (United States)

    van der Knaap, Esther; Kim, Jeong Hoe; Kende, Hans

    2000-01-01

    Os-GRF1 (Oryza sativa-GROWTH-REGULATING FACTOR1) was identified in a search for genes that are differentially expressed in the intercalary meristem of deepwater rice (Oryza sativa L.) internodes in response to gibberellin (GA). Os-GRF1 displays general features of transcription factors, contains a functional nuclear localization signal, and has three regions with similarities to sequences in the database. One of these regions is similar to a protein interaction domain of SWI2/SNF2, which is a subunit of a chromatin-remodeling complex in yeast. The two other domains are novel and found only in plant proteins of unknown function. To study its role in plant growth, Os-GRF1 was expressed in Arabidopsis. Stem elongation of transformed plants was severely inhibited, and normal growth could not be recovered by the application of GA. Our results indicate that Os-GRF1 belongs to a novel class of plant proteins and may play a regulatory role in GA-induced stem elongation. PMID:10712532

  19. Drosophila Protein Kinase CK2: Genetics, Regulatory Complexity and Emerging Roles during Development

    Directory of Open Access Journals (Sweden)

    Mohna Bandyopadhyay

    2016-12-01

    Full Text Available CK2 is a Ser/Thr protein kinase that is highly conserved amongst all eukaryotes. It is a well-known oncogenic kinase that regulates vital cell autonomous functions and animal development. Genetic studies in the fruit fly Drosophila are providing unique insights into the roles of CK2 in cell signaling, embryogenesis, organogenesis, neurogenesis, and the circadian clock, and are revealing hitherto unknown complexities in CK2 functions and regulation. Here, we review Drosophila CK2 with respect to its structure, subunit diversity, potential mechanisms of regulation, developmental abnormalities linked to mutations in the gene encoding CK2 subunits, and emerging roles in multiple aspects of eye development. We examine the Drosophila CK2 “interaction map” and the eye-specific “transcriptome” databases, which raise the prospect that this protein kinase has many additional targets in the developing eye. We discuss the possibility that CK2 functions during early retinal neurogenesis in Drosophila and mammals bear greater similarity than has been recognized, and that this conservation may extend to other developmental programs. Together, these studies underscore the immense power of the Drosophila model organism to provide new insights and avenues to further investigate developmentally relevant targets of this protein kinase.

  20. Emergency planning and response - role nad responsibilities of the regulatory body

    International Nuclear Information System (INIS)

    Nizamska, M.

    1999-01-01

    The development of a emergency plan and organisation of adequate emergency preparedness in case of radiological accident in NPP cannot be effective without the appropriate preparatory work. In most countries, also in Republic of Bulgaria, several organisations are identified to have a potential role to play in a radiological emergency. For these reason is very important to have a national organisation, with a mandate to organise, inspect and co-ordinate the possibility of ministries and institution to react in case of radiological emergency, i.e. to quarantine the possibility for implementation of adequate counter measure for protection of the population and environment in case of radiological emergency in NPP. For the purposes of the emergency planning and response the NPP operator, ministries and the institutions developed an Emergency plan - NPP Emergency Plan and National Emergency Plan. The development of the emergency plans will be impossible without the good co-operation of the organisations which have a responsibilities in a radiological emergency. Once emergency plans are adopted, each individual organisation, also the NPP operator, must ensure that in can carry out its role effectively in accordance with the emergency plan and can develop the appropriate organisation for action and implementation of protection counter measures. For testing the emergency plans a regular exercise must be organised. Periodic reviews of the plan and modifications, based on actual events and exercise experience must be performed. The main aim of these report is to present the Bulgarian emergency planning organisation and response by explaining the national emergency panning and response legislation, implementation of IAEA recommendations and exercise experience

  1. The regulatory role of the state strategic management in the development of the regional entrepreneurial sphere

    Directory of Open Access Journals (Sweden)

    Yukhneva Nina

    2017-01-01

    Full Text Available The system of state strategic management (SGSO today is an Outpost of the state, exercising the functions of strategic management, development and predicates, and conducting an evaluation of the effectiveness and quality of the planned trajectories of economic development of the regions, regions and the state as a whole. It SGSW today is designed to ensure that the nationally oriented domestic policies that contribute to progressive and bold actions of the Russian Federation on the world stage. SHSU today is to create conditions for the development of science, research training, new knowledge-based economy. SHSU should form a system of state orders, which is of fundamental importance for the development of strategic projects in the field of medicine and health, agriculture, defense industry, etc. And, most importantly, SHSU needs today and support the process of re-industrialization of the country, technical re-equipment of all areas of production and management. In the new knowledge economy SHSU performs the role of the intellectual and information center regulation and strategic planning of development of the entire socio-economic sphere of the society centre to ensure the development of a database of fundamental and applied research, development, centre, guaranteeing the protection of copyright and introduction of innovative products, including new technical and technological solutions.

  2. The Regulatory Role of Signaling Crosstalk in Hypertrophy of MSCs and Human Articular Chondrocytes

    Directory of Open Access Journals (Sweden)

    Leilei Zhong

    2015-08-01

    Full Text Available Hypertrophic differentiation of chondrocytes is a main barrier in application of mesenchymal stem cells (MSCs for cartilage repair. In addition, hypertrophy occurs occasionally in osteoarthritis (OA. Here we provide a comprehensive review on recent literature describing signal pathways in the hypertrophy of MSCs-derived in vitro differentiated chondrocytes and chondrocytes, with an emphasis on the crosstalk between these pathways. Insight into the exact regulation of hypertrophy by the signaling network is necessary for the efficient application of MSCs for articular cartilage repair and for developing novel strategies for curing OA. We focus on articles describing the role of the main signaling pathways in regulating chondrocyte hypertrophy-like changes. Most studies report hypertrophic differentiation in chondrogenesis of MSCs, in both human OA and experimental OA. Chondrocyte hypertrophy is not under the strict control of a single pathway but appears to be regulated by an intricately regulated network of multiple signaling pathways, such as WNT, Bone morphogenetic protein (BMP/Transforming growth factor-β (TGFβ, Parathyroid hormone-related peptide (PTHrP, Indian hedgehog (IHH, Fibroblast growth factor (FGF, Insulin like growth factor (IGF and Hypoxia-inducible factor (HIF. This comprehensive review describes how this intricate signaling network influences tissue-engineering applications of MSCs in articular cartilage (AC repair, and improves understanding of the disease stages and cellular responses within an OA articular joint.

  3. Regulatory role of neuron-restrictive silencing factor in expression of TRPC1

    International Nuclear Information System (INIS)

    Ohba, Takayoshi; Watanabe, Hiroyuki; Takahashi, Yoichiro; Suzuki, Takashi; Miyoshi, Ichiro; Nakayama, Shinnsuke; Satoh, Eisaku; Iino, Kenji; Sasano, Hironobu; Mori, Yasuo; Kuromitsu, Sadao; Imagawa, Keiichi; Saito, Yoshihiko; Iijima, Toshihiko; Ito, Hiroshi; Murakami, Manabu

    2006-01-01

    Neuron-restrictive silencer factor (NRSF) binds its consensus element to repress the transcription of various genes. The dominant-negative form (dnNRSF) has a hypertrophic effect on cardiogenesis through an unidentified mechanism. We examined the involvement of transient receptor potential (TRP) channel proteins, using transgenic mice overexpressing dnNRSF (dnNRSF mice). Electrophoretic mobility-shift assays revealed an interaction between NRSF and a neuron-restrictive silencer element-like sequence in intron 4 of TRPC1 genomic DNA. According to RT-PCR and Western analyses, TRPC1 was up-regulated in dnNRSF mouse heart. Transient overexpression of TRPC1 in HEK 293T cells increased the activity of the nuclear factor in activated T cells (NFAT) promoter and stimulated store-operated Ca 2+ channel (SOCC)-mediated Ca 2+ entry. Transfection of TRPC1 into primary cardiomyocytes increased NFAT activity, indicating a major role for TRPC1 in NFAT activation. Our findings strongly suggest that NRSF regulates TRP1 gene expression and causes changes in the levels of calcium entry through SOCCs

  4. Regulatory mechanisms of RNA function: emerging roles of DNA repair enzymes.

    Science.gov (United States)

    Jobert, Laure; Nilsen, Hilde

    2014-07-01

    The acquisition of an appropriate set of chemical modifications is required in order to establish correct structure of RNA molecules, and essential for their function. Modification of RNA bases affects RNA maturation, RNA processing, RNA quality control, and protein translation. Some RNA modifications are directly involved in the regulation of these processes. RNA epigenetics is emerging as a mechanism to achieve dynamic regulation of RNA function. Other modifications may prevent or be a signal for degradation. All types of RNA species are subject to processing or degradation, and numerous cellular mechanisms are involved. Unexpectedly, several studies during the last decade have established a connection between DNA and RNA surveillance mechanisms in eukaryotes. Several proteins that respond to DNA damage, either to process or to signal the presence of damaged DNA, have been shown to participate in RNA quality control, turnover or processing. Some enzymes that repair DNA damage may also process modified RNA substrates. In this review, we give an overview of the DNA repair proteins that function in RNA metabolism. We also discuss the roles of two base excision repair enzymes, SMUG1 and APE1, in RNA quality control.

  5. Regulatory Role of N6 -methyladenosine (m6 A) Methylation in RNA Processing and Human Diseases.

    Science.gov (United States)

    Wei, Wenqiang; Ji, Xinying; Guo, Xiangqian; Ji, Shaoping

    2017-09-01

    N 6 -methyladenosine (m 6 A) modification is an abundant and conservative RNA modification in bacterial and eukaryotic cells. m 6 A modification mainly occurs in the 3' untranslated regions (UTRs) and near the stop codons of mRNA. Diverse strategies have been developed for identifying m 6 A sites in single nucleotide resolution. Dynamic regulation of m 6 A is found in metabolism, embryogenesis, and developmental processes, indicating a possible epigenetic regulation role along RNA processing and exerting biological functions. It has been known that m 6 A editing involves in nuclear RNA export, mRNA degradation, protein translation, and RNA splicing. Deficiency of m 6 A modification will lead to kinds of diseases, such as obesity, cancer, type 2 diabetes mellitus (T2DM), infertility, and developmental arrest. Some specific inhibitors against methyltransferase and demethylase have been developed to selectively regulate m 6 A modification, which may be advantageous for treatment of m 6 A related diseases. J. Cell. Biochem. 118: 2534-2543, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  6. Novel mitochondrial substrates of omi indicate a new regulatory role in neurodegenerative disorders.

    Directory of Open Access Journals (Sweden)

    Felicity Johnson

    Full Text Available The mitochondrial protease OMI (also known as HtrA2 has been implicated in Parkinson's Disease (PD and deletion or protease domain point mutations have shown profound neuropathologies in mice. A beneficial role by OMI, in preserving cell viability, is assumed to occur via the avoidance of dysfunctional protein turnover. However relatively few substrates for mitochondrial Omi are known. Here we report our identification of three novel mitochondrial substrates that impact metabolism and ATP production. Using a dual proteomic approach we have identified three interactors based upon ability to bind to OMI, and/or to persist in the proteome after OMI activity has been selectively inhibited. One candidate, the chaperone HSPA8, was common to each independent study. Two others (PDHB subunit and IDH3A subunit did not appear to bind to OMI, however persisted in the mito-proteome when OMI was inhibited. Pyruvate dehydrogenase (PDH and isocitrate dehydrogenase (IDH are two key Kreb's cycle enzymes that catalyse oxidative decarboxylation control points in mitochondrial respiration. We verified both PDHB and IDH3A co-immunoprecipitate with HSPA8 and after elution, were degraded by recombinant HtrA2 in vitro. Additionally our gene expression studies, using rotenone (an inhibitor of Complex I showed Omi expression was silenced when pdhb and idh3a were increased when a sub-lethal dose was applied. However higher dose treatment caused increased Omi expression and decreased levels of pdhb and idh3a transcripts. This implicates mitochondrial OMI in a novel mechanism relating to metabolism.

  7. Penatalaksanaan Repair Palatoplasty dengan Teknik Furlow Double Opposing Z Plasty

    Directory of Open Access Journals (Sweden)

    Pingky Krisna Arindra

    2015-06-01

    metode Furlow double opposing z plasty dengan kombinasi insisi lateral, dan didapatkan hasil menutupnya celah di palatum mole sampai dengan uvula. Telah dilakukan operasi repair palatoplasi dengan metode Furlow double opposing z plasty. Teknik ini dilakukan untuk menghindari insisi yang terlalu luas dikarenakan terdapatnya jaringan fibrous yang tebal pada mukosa palatum pasca operasi sebelumnya. Tujuan studi kasus adalah untuk mengetahui kemampuan teknik Furlow Double Opposing Z Plasty sebagai prosedur repair palatoplasty.   Repair Palatoplasty Management with Furlow Double Opposing Z Plasty Technique. Cases of cleft lip and palate are one of the deformity disorders that often occur. There are variety of clinical appearance ranging from incomplete to complete cases. Clinical appearance with different width requires proper surgical technique. Patients with cleft lip and palate had undergone surgical intervention, so that they needed surgical correction to repair the result or failure of the previous surgery. A Four year old boy complain there was cleft on the soft palate. The patient was diagnosed with labiognatopalatoscisis. The patient had undergone two stages of cleft lip surgery and twice of cleft palate surgery with pushback method and repair with z plasty, however the result was unsatisfactory. Further, the patient underwent repair palatoplasty surgery with Furlow double opposing z plasty method combined with lateral relaxing insicion. The result in the post surgery was the closure of cleft soft palate up to uvula. Repair palataplasty surgery has been done with Furlow double opposing z plasty method. This technique could avoid extended incision due to thick fibrous tissue on the palatum mucosa as the result of serial previous surgery. The aim of this case case study is to determine the technical capabilities of Furlow Double Opposing Z Plasty as palatoplasty repair procedure.

  8. Mutually opposing forces during locomotion can eliminate the tradeoff between maneuverability and stability

    Science.gov (United States)

    Cowan, Noah; Sefati, Shahin; Neveln, Izaak; Roth, Eatai; Mitchell, Terence; Snyder, James; Maciver, Malcolm; Fortune, Eric

    A surprising feature of animal locomotion is that organisms typically produce substantial forces in directions other than what is necessary to move the animal through its environment, such as perpendicular to, or counter to, the direction of travel. The effect of these forces has been difficult to observe because they are often mutually opposing and therefore cancel out. Using a combination of robotic physical modeling, computational modeling, and biological experiments, we discovered that these forces serve an important role: to simplify and enhance the control of locomotion. Specifically, we examined a well-suited model system, the glass knifefish Eigenmannia virescens, which produces mutually opposing forces during a hovering behavior. By systematically varying the locomotor parameters of our biomimetic robot, and measuring the resulting forces and kinematics, we demonstrated that the production and differential control of mutually opposing forces is a strategy that generates passive stabilization while simultaneously enhancing maneuverability. Mutually opposing forces during locomotion are widespread across animal taxa, and these results indicate that such forces can eliminate the tradeoff between stability and maneuverability, thereby simplifying robotic and neural control.

  9. Regulatory T-cells in B-cell chronic lymphocytic leukemia: their role in disease progression and autoimmune cytopenias.

    Science.gov (United States)

    Lad, Deepesh P; Varma, Subhash; Varma, Neelam; Sachdeva, Man Updesh Singh; Bose, Parveen; Malhotra, Pankaj

    2013-05-01

    Regulatory T-cells (Tregs) have been shown to be important for the balance of autoimmunity and oncogenesis. Tregs have a protective role in autoimmune diseases and conversely promote oncogenesis. Chronic lymphocytic leukemia (CLL) is unique in being at the cross-roads of oncogenesis and autoimmunity. We studied Tregs, defined as CD4+CD25(high)CD127(low)FOXP3+, in 32 treatment-naive patients with CLL. Our study shows that patients with CLL had a higher absolute Treg count than the control group (p < 0.001). A progressive increase of Tregs was noted in advanced stages of the disease (p < 0.001). The increase in absolute Treg count is more significant than the increase in percentage Tregs. The absolute Treg count appears to be more important in disease pathogenesis. The absolute Treg count was significantly higher in those patients having autoimmune cytopenias. There was an inverse correlation between lymphocyte doubling time and absolute Treg count (p = 0.03). The absolute Treg count may be used as a prognostic marker in CLL.

  10. APS, an adaptor molecule containing PH and SH2 domains, has a negative regulatory role in B cell proliferation

    International Nuclear Information System (INIS)

    Iseki, Masanori; Kubo-Akashi, Chiyomi; Kwon, Sang-Mo; Yamaguchi, Akiko; Takatsu, Kiyoshi; Takaki, Satoshi

    2005-01-01

    Adaptor molecule containing PH and SH2 domains (APS) is an intracellular adaptor protein that forms part of an adaptor family along with Lnk and SH2-B. APS transcripts are expressed in various tissues including brain, kidney, and muscle, as well as in splenic B cells but not in T cells. We investigated the functions of APS in B cell development and activation by generating APS-transgenic (APS-Tg) mice that overexpressed APS in lymphocytes. The number of B-1 cells in the peritoneal cavity was reduced in APS-Tg mice, as were B-2 cells in the spleen. B cell development in the bone marrow was partially impaired at the transition stage from proliferating large pre-B to small pre-B cells. B cell proliferation induced by B cell receptor (BCR) crosslinking but not by other B cell mitogens was also impaired in APS-Tg mice. APS co-localized with BCR complexes and filamentous actin in activated APS-Tg B cells. Thus, APS appears to play novel negative regulatory roles in BCR signaling, actin reorganization pathways, and control of compartment sizes of B-lineage cells

  11. Critical role for thymic CD19+CD5+CD1dhiIL-10+ regulatory B cells in immune homeostasis.

    Science.gov (United States)

    Xing, Chen; Ma, Ning; Xiao, He; Wang, Xiaoqian; Zheng, Mingke; Han, Gencheng; Chen, Guojiang; Hou, Chunmei; Shen, Beifen; Li, Yan; Wang, Renxi

    2015-03-01

    This study tested the hypothesis that besides the spleen, LNs, peripheral blood, and thymus contain a regulatory IL-10-producing CD19(+)CD5(+)CD1d(high) B cell subset that may play a critical role in the maintenance of immune homeostasis. Indeed, this population was identified in the murine thymus, and furthermore, when cocultured with CD4(+) T cells, this population of B cells supported the maintenance of CD4(+)Foxp3(+) Tregs in vitro, in part, via the CD5-CD72 interaction. Mice homozygous for Cd19(Cre) (CD19(-/-)) express B cells with impaired signaling and humoral responses. Strikingly, CD19(-/-) mice produce fewer CD4(+)Foxp3(+) Tregs and a greater percentage of CD4(+)CD8(-) and CD4(-)CD8(+) T cells. Consistent with these results, transfer of thymic CD19(+)CD5(+)CD1d(hi) B cells into CD19(-/-) mice resulted in significantly up-regulated numbers of CD4(+)Foxp3(+) Tregs with a concomitant reduction in CD4(+)CD8(-) and CD4(-)CD8(+) T cell populations in the thymus, spleen, and LNs but not in the BM of recipient mice. In addition, thymic CD19(+)CD5(+)CD1d(hi) B cells significantly suppressed autoimmune responses in lupus-like mice via up-regulation of CD4(+)Foxp3(+) Tregs and IL-10-producing Bregs. This study suggests that thymic CD19(+)CD5(+)CD1d(hi)IL-10(+) Bregs play a critical role in the maintenance of immune homeostasis. © Society for Leukocyte Biology.

  12. Role of the DmpR-mediated regulatory circuit in bacterial biodegradation properties in methylphenol-amended soils.

    Science.gov (United States)

    Sarand, I; Skärfstad, E; Forsman, M; Romantschuk, M; Shingler, V

    2001-01-01

    Pathway substrates and some structural analogues directly activate the regulatory protein DmpR to promote transcription of the dmp operon genes encoding the (methyl)phenol degradative pathway of Pseudomonas sp. strain CF600. While a wide range of phenols can activate DmpR, the location and nature of substituents on the basic phenolic ring can limit the level of activation and thus utilization of some compounds as assessed by growth on plates. Here we address the role of the aromatic effector response of DmpR in determining degradative properties in two soil matrices that provide different nutritional conditions. Using the wild-type system and an isogenic counterpart containing a DmpR mutant with enhanced ability to respond to para-substituted phenols, we demonstrate (i) that the enhanced in vitro biodegradative capacity of the regulator mutant strain is manifested in the two different soil types and (ii) that exposure of the wild-type strain to 4-methylphenol-contaminated soil led to rapid selection of a subpopulation exhibiting enhanced capacities to degrade the compound. Genetic and functional analyses of 10 of these derivatives demonstrated that all harbored a single mutation in the sensory domain of DmpR that mediated the phenotype in each case. These findings establish a dominating role for the aromatic effector response of DmpR in determining degradation properties. Moreover, the results indicate that the ability to rapidly adapt regulator properties to different profiles of polluting compounds may underlie the evolutionary success of DmpR-like regulators in controlling aromatic catabolic pathways.

  13. FOXP3: required but not sufficient. the role of GARP (LRRC32) as a safeguard of the regulatory phenotype.

    Science.gov (United States)

    Probst-Kepper, M; Balling, R; Buer, J

    2010-08-01

    FOXP3 is essential for the development and function of regulatory CD4(+)CD25(hi) T (T(reg)) cells. However, recent evidence suggests that FOXP3 alone is not sufficient to completely explain the regulatory phenotype of these key players in autoimmunity and inflammation: after being activated, conventional human CD4(+) T cells transiently up-regulate FOXP3 without acquiring a regulatory function. Researchers have recently found that glycoprotein A repetitions predominant (GARP, or LRRC32) is a T(reg)-specific receptor that binds latent TGF-beta and dominantly controls FOXP3 and the regulatory phenotype via a positive feedback loop. This finding provides a missing link in our molecular understanding of FOXP3 in T(reg) cells. This viewpoint focuses on GARP as safeguard of FOXP3 and the regulatory phenotype.

  14. Evidence for a role of regulatory T cells in mediating the atheroprotective effect of apolipoprotein B peptide vaccine.

    Science.gov (United States)

    Wigren, M; Kolbus, D; Dunér, P; Ljungcrantz, I; Söderberg, I; Björkbacka, H; Fredrikson, G N; Nilsson, J

    2011-05-01

    Autoimmune responses against oxidized low-density lipoprotein are considered to play an important pro-inflammatory role in atherosclerosis and to promote disease progression. T-regulatory cells (Tregs) are immunosuppressive cells that have an important part in maintaining self-tolerance and protection against autoimmunity. We investigated whether aBp210, a prototype atherosclerosis vaccine based on a peptide sequence derived from apolipoprotein B, inhibits atherosclerosis through the activation of Tregs. Six-week-old Apoe(-/-) mice were immunized with aBp210 and received booster immunizations 3 and 5 weeks later, as well as 1 week before being killed at 25 weeks of age. At 12 weeks, immunized mice had increased expression of the Treg marker CD25 on circulating CD4 cells, and concanavalin A (Con A)-induced interferon-γ, interleukin (IL)-4, and IL-10 release from splenocytes was markedly depressed. At 25 weeks, there was a fivefold expansion of splenic CD4+ CD25+ Foxp3 Tregs, a 65% decrease in Con A-induced splenic T-cell proliferation and a 37% reduction in the development of atherosclerosis in immunized mice. Administration of blocking antibodies against CD25 neutralized aBp210-induced Treg activation as well as the reduction of atherosclerosis. The present findings demonstrate that immunization of Apoe(-/-) mice with the apolipoprotein B peptide vaccine aBp210 is associated with activation of Tregs. Administration of antibodies against CD25 results in depletion of Tregs and blocking of the atheroprotective effect of the vaccine. Modulation in atherosclerosis-related autoimmunity by antigen-specific activation of Tregs represents a novel approach for treatment of atherosclerosis. © 2010 The Association for the Publication of the Journal of Internal Medicine.

  15. The regulatory role of endogenous iron on greenhouse gas emissions under intensive nitrogen fertilization in subtropical soils of China.

    Science.gov (United States)

    Han, Jiangpei; Shi, Liangsheng; Wang, Yakun; Chen, Zhuowei; Wu, Laosheng

    2018-05-01

    Anaerobic batch experiments were conducted to study the regulatory role of endogenous iron in greenhouse gas emissions under intensive nitrogen fertilization in subtropical soils of China. Fe 2+ , Fe 3+ , and NO 3 - -N dynamics and N 2 O, CH 4 , and CO 2 emissions, as well as the relationships between N fertilizer, endogenous iron, and greenhouse gas emissions were investigated. The emissions of N 2 O increased to different extents from all the test soils by N1 (260 mg N kg -1 ) application compared with N0. After 24 days of anaerobic incubation, the cumulative emissions of N 2 O from red soils in De'an (DR) were significantly higher than that from paddy soils in De'an (DP) and Qujialing (QP) under N1. However, N application enhanced CH 4 and CO 2 emissions from the red soils slightly but inhibited the emissions from paddy soils. The maximal CH 4 and CO 2 emission fluxes occurred in DP soil without N input. Pearson's correlation analysis showed that there were significant correlations (P greenhouse gas emissions mainly through the involvement in denitrification. The proportion of the electrons donated by Fe 2+ used for N 2 O production in denitrification in DP soil was approximately 37.53%. Moreover, positive correlations between Fe 2+ and CH 4 , CO 2 were found in both DR and QP soils, suggesting that endogenous iron might regulate the anaerobic decomposition of organic carbon to CH 4 and CO 2 in the two soils. Soil pH was also an important factor controlling greenhouse gas emissions by affecting endogenous iron availability and C and N transformation processes.

  16. A dynamic dual role of IL-2 signaling in the two-step differentiation process of adaptive regulatory T cells.

    Science.gov (United States)

    Guo, Zhiyong; Khattar, Mithun; Schroder, Paul M; Miyahara, Yoshihiro; Wang, Guohua; He, Xiaoshung; Chen, Wenhao; Stepkowski, Stanislaw M

    2013-04-01

    The molecular mechanism of the extrathymic generation of adaptive, or inducible, CD4(+)Foxp3(+) regulatory T cells (iTregs) remains incompletely defined. We show that exposure of splenic CD4(+)CD25(+)Foxp3(-) cells to IL-2, but not other common γ-chain cytokines, resulted in Stat5 phosphorylation and induced Foxp3 expression in ∼10% of the cells. Thus, IL-2/Stat5 signaling may be critical for Foxp3 induction in peripheral CD4(+)CD25(+)Foxp3(-) iTreg precursors. In this study, to further define the role of IL-2 in the formation of iTreg precursors as well as their subsequent Foxp3 expression, we designed a two-step iTreg differentiation model. During the initial "conditioning" step, CD4(+)CD25(-)Foxp3(-) naive T cells were activated by TCR stimulation. Inhibition of IL-2 signaling via Jak3-Stat5 was required during this step to generate CD4(+)CD25(+)Foxp3(-) cells containing iTreg precursors. During the subsequent Foxp3-induction step driven by cytokines, IL-2 was the most potent cytokine to induce Foxp3 expression in these iTreg precursors. This two-step method generated a large number of iTregs with relatively stable expression of Foxp3, which were able to prevent CD4(+)CD45RB(high) cell-mediated colitis in Rag1(-/-) mice. In consideration of this information, whereas initial inhibition of IL-2 signaling upon T cell priming generates iTreg precursors, subsequent activation of IL-2 signaling in these precursors induces the expression of Foxp3. These findings advance the understanding of iTreg differentiation and may facilitate the therapeutic use of iTregs in immune disorders.

  17. The influence of regulatory fit on evaluation and intentions to buy genetically modified foods: The mediating role of social identification

    NARCIS (Netherlands)

    Fransen, M.L.; Reinders, M.J.; Bartels, J.; Maassen, R.L.

    2010-01-01

    The present study examines how communicated messages could be effective in affecting consumers' attitudes and behavioural intentions regarding genetically modified (GM) foods. Based on Regulatory Focus Theory, it was hypothesized that exposure to a communication message matching a consumer's

  18. Consumers and Makers: Exploring Opposing Paradigms of Millennial College Readiness

    Science.gov (United States)

    Jackson, Matthew

    2017-01-01

    The political and technological circumstances of the past two decades have culminated in opposing epistemic paradigms of college readiness, where millennial students' conceptual understanding of "learning" is both narrowed to meet the demands of school systems bound to accountability and amplified by a rapidly evolving digital world. The…

  19. Opposing Amygdala and Ventral Striatum Connectivity during Emotion Identification

    Science.gov (United States)

    Satterthwaite, Theodore D.; Wolf, Daniel H.; Pinkham, Amy E.; Ruparel, Kosha; Elliott, Mark A.; Valdez, Jeffrey N.; Overton, Eve; Seubert, Janina; Gur, Raquel E.; Gur, Ruben C.; Loughead, James

    2011-01-01

    Lesion and electrophysiological studies in animals provide evidence of opposing functions for subcortical nuclei such as the amygdala and ventral striatum, but the implications of these findings for emotion identification in humans remain poorly described. Here we report a high-resolution fMRI study in a sample of 39 healthy subjects who performed…

  20. An enhanced computational platform for investigating the roles of regulatory RNA and for identifying functional RNA motifs

    OpenAIRE

    Chang, Tzu-Hao; Huang, Hsi-Yuan; Hsu, Justin Bo-Kai; Weng, Shun-Long; Horng, Jorng-Tzong; Huang, Hsien-Da

    2013-01-01

    Background Functional RNA molecules participate in numerous biological processes, ranging from gene regulation to protein synthesis. Analysis of functional RNA motifs and elements in RNA sequences can obtain useful information for deciphering RNA regulatory mechanisms. Our previous work, RegRNA, is widely used in the identification of regulatory motifs, and this work extends it by incorporating more comprehensive and updated data sources and analytical approaches into a new platform. Methods ...

  1. Enhancing Tissue Engineering and Regenerative Medicine Product Commercialization: The Role of Science in Regulatory Decision-Making for the TE/RM Product Development.

    Science.gov (United States)

    Bertram, Timothy A; Johnson, Peter C; Tawil, Bill J; Van Dyke, Mark; Hellman, Kiki B

    2015-10-01

    TERMIS-AM Industry Committee (TERMIS-AM/IC), in collaboration with the TERMIS-Europe (EU)/IC, conducted a symposium involving the European Medicines Agency and the U.S. Food and Drug Administration (FDA) toward building an understanding of the rational basis for regulatory decision-making and providing a framework for decisions made during the evaluation of safety and efficacy of TE/RM technologies. This symposium was held in August 2012 during the TERMIS-WC in Vienna, Austria. Emerging from this international initiative by the European Union and the United States, representatives from the respective agencies demonstrated that there are ongoing interagency efforts for developing common national practices toward harmonization of regulatory requirements for the TE/RM products. To extend a broad-based understanding of the role of science in regulatory decision-making, TERMIS-AM/IC, in cooperation with the FDA, organized a symposium at the 2014 TERMIS-AM Annual Meeting, which was held in Washington, DC. This event provided insights from leaders in the FDA and TERMIS on the current status of regulatory approaches for the approved TE/RM products, the use of science in making regulatory decisions, and TE/RM technologies that are in the development pipeline to address unmet medical needs. A far-ranging discussion with FDA representatives, industrialists, physicians, regenerative medicine biologists, and tissue engineers considered the gaps in today's scientific and regulatory understanding of TE/RM technologies. The identified gaps represent significant opportunities to advance TE/RM technologies toward commercialization.

  2. Opposing nodal and BMP signals regulate left-right asymmetry in the sea urchin larva.

    Directory of Open Access Journals (Sweden)

    Yi-Jyun Luo

    Full Text Available Nodal and BMP signals are important for establishing left-right (LR asymmetry in vertebrates. In sea urchins, Nodal signaling prevents the formation of the rudiment on the right side. However, the opposing pathway to Nodal signaling during LR axis establishment is not clear. Here, we revealed that BMP signaling is activated in the left coelomic pouch, specifically in the veg2 lineage, but not in the small micromeres. By perturbing BMP activities, we demonstrated that BMP signaling is required for activating the expression of the left-sided genes and the formation of the left-sided structures. On the other hand, Nodal signals on the right side inhibit BMP signaling and control LR asymmetric separation and apoptosis of the small micromeres. Our findings show that BMP signaling is the positive signal for left-sided development in sea urchins, suggesting that the opposing roles of Nodal and BMP signals in establishing LR asymmetry are conserved in deuterostomes.

  3. Mimicry of the regulatory role of urokinase in lamellipodia formation by introduction of a non-native interdomain disulfide bond in its receptor

    DEFF Research Database (Denmark)

    Gårdsvoll, Henrik; Kjærgaard, Magnus; Jacobsen, Benedikte

    2011-01-01

    The high-affinity interaction between the urokinase-type plasminogen activator (uPA) and its glycolipid-anchored receptor (uPAR) plays a regulatory role for both extravascular fibrinolysis and uPAR-mediated adhesion and migration on vitronectin-coated surfaces. We have recently proposed that the ......The high-affinity interaction between the urokinase-type plasminogen activator (uPA) and its glycolipid-anchored receptor (uPAR) plays a regulatory role for both extravascular fibrinolysis and uPAR-mediated adhesion and migration on vitronectin-coated surfaces. We have recently proposed...... that the adhesive function of uPAR is allosterically regulated via a "tightening" of its three-domain structure elicited by uPA binding. To challenge this proposition, we redesigned the uPAR structure to limit its inherent conformational flexibility by covalently tethering domains DI and DIII via a non...... adhering to vitronectin. In this respect, the engineered constraint in uPAR(H47C-N259C) thus bypasses the regulatory role of uPA binding, resulting in a constitutively active uPAR. In conclusion, our data argue for a biological relevance of the interdomain dynamics of the glycolipid-anchored u...

  4. In vivo FRET imaging revealed a regulatory role of RanGTP in kinetochore-microtubule attachments via Aurora B kinase.

    Directory of Open Access Journals (Sweden)

    Yoke-Peng Lee

    Full Text Available Under the fluctuating circumstances provided by the innate dynamics of microtubules and opposing tensions resulted from microtubule-associated motors, it is vital to ensure stable kinetochore-microtubule attachments for accurate segregation. However, a comprehensive understanding of how this regulation is mechanistically achieved remains elusive. Using our newly designed live cell FRET time-lapse imaging, we found that post-metaphase RanGTP is crucial in the maintenance of stable kinetochore-microtubule attachments by regulating Aurora B kinase via the NES-bearing Mst1. More importantly, our study demonstrates that by ensuring stable alignment of metaphase chromosomes prior to segregation, RanGTP is indispensible in governing the genomic integrity and the fidelity of cell cycle progression. Our findings suggest an additional role of RanGTP beyond its known function in mitotic spindle assembly during the prometaphase-metaphase transition.

  5. Trust in regulatory regimes

    NARCIS (Netherlands)

    Six, Frédérique; Verhoest, Koen

    2017-01-01

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

  6. Regulatory agencies and regulatory risk

    OpenAIRE

    Knieps, Günter; Weiß, Hans-Jörg

    2008-01-01

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

  7. Cell-intrinsic role for NF-kappa B-inducing kinase in peripheral maintenance but not thymic development of Foxp3+ regulatory T cells in mice.

    Directory of Open Access Journals (Sweden)

    Susan E Murray

    Full Text Available NF-κB inducing kinase (NIK, MAP3K14 is a key signaling molecule in non-canonical NF-κB activation, and NIK deficient mice have been instrumental in deciphering the immunologic role of this pathway. Global ablation of NIK prevents lymph node development, impairs thymic stromal development, and drastically reduces B cells. Despite altered thymic selection, T cell numbers are near normal in NIK deficient mice. The exception is CD4(+ regulatory T cells (Tregs, which are reduced in the thymus and periphery. Defects in thymic stroma are known to contribute to impaired Treg generation, but whether NIK also plays a cell intrinsic role in Tregs is unknown. Here, we compared intact mice with single and mixed BM chimeric mice to assess the intrinsic role of NIK in Treg generation and maintenance. We found that while NIK expression in stromal cells suffices for normal thymic Treg development, NIK is required cell-intrinsically to maintain peripheral Tregs. In addition, we unexpectedly discovered a cell-intrinsic role for NIK in memory phenotype conventional T cells that is masked in intact mice, but revealed in BM chimeras. These results demonstrate a novel role for NIK in peripheral regulatory and memory phenotype T cell homeostasis.

  8. Numerical and experimental study of two turbulent opposed plane jets

    Energy Technology Data Exchange (ETDEWEB)

    Besbes, Sonia; Mhiri, Hatem [Laboratoire de Mecanique des Fluides et Thermique, Ecole Nationale d' Ingenieurs de Monastir, Route de Ouardanine, Monastir (Tunisia); Le Palec, Georges; Bournot, Philippe [Institut de Mecanique de Marseille, UNIMECA, Technopole de Chateau-Gombert, 60 rue Joliot-Curie, 13453 Marseille (France)

    2003-09-01

    The turbulent interaction between two opposed plane jets separated by a distance H is experimentally studied by using a PIV (Particle Image Velocimetry) method and numerically investigated by means of a finite volume code. Two turbulence models have been tested: the standard k-{epsilon} model and a second-order model. The validation of the numerical study was performed by comparing the results with experimental data obtained for the case of two interacting opposed jets at ambient temperature (isothermal case). The effect of the angle of inclination of the jets is studied. Conclusions of the validation are then used to study the interaction between two jets, one being maintained at ambient temperature whereas the other is heated. Results show that the stagnation point moves towards the heated jet. It is shown that the heating induces a stabilizing effect on the flow. (orig.)

  9. Opposing flow in square porous annulus: Influence of Dufour effect

    International Nuclear Information System (INIS)

    Athani, Abdulgaphur; Al-Rashed, Abdullah A. A. A.; Khaleed, H. M. T.

    2016-01-01

    Heat and mass transfer in porous medium is very important area of research which is also termed as double diffusive convection or thermo-solutal convection. The buoyancy ratio which is the ratio of thermal to concentration buoyancy can have negative values thus leading to opposing flow. This article is aimed to study the influence of Dufour effect on the opposing flow in a square porous annulus. The partial differential equations that govern the heat and mass transfer behavior inside porous medium are solved using finite element method. A three node triangular element is used to divide the porous domain into smaller elements. Results are presented with respect to geometric and physical parameters such as duct diameter ratio, Rayleigh number, radiation parameter etc. It is found that the heat transfer increase with increase in Rayleigh number and radiation parameter. It is observed that Dufour coefficient has more influence on velocity profile.

  10. Opposing flow in square porous annulus: Influence of Dufour effect

    Energy Technology Data Exchange (ETDEWEB)

    Athani, Abdulgaphur, E-mail: abbu.bec@gmail.com [Dept. of Mechanical Engineering, Anjuman Institute of Technology & Management, Bhatkal (India); Al-Rashed, Abdullah A. A. A., E-mail: aa.alrashed@paaet.edu.kw [Dept. of Automotive and Marine Engineering Technology, College of Technological Studies, The Public Authority for Applied Education and Training (Kuwait); Khaleed, H. M. T., E-mail: khalid-tan@yahoo.com [Dept of Mechanical Engineering, Faculty of Engineering, Islamic University, Madinah Munawwarra (Saudi Arabia)

    2016-06-21

    Heat and mass transfer in porous medium is very important area of research which is also termed as double diffusive convection or thermo-solutal convection. The buoyancy ratio which is the ratio of thermal to concentration buoyancy can have negative values thus leading to opposing flow. This article is aimed to study the influence of Dufour effect on the opposing flow in a square porous annulus. The partial differential equations that govern the heat and mass transfer behavior inside porous medium are solved using finite element method. A three node triangular element is used to divide the porous domain into smaller elements. Results are presented with respect to geometric and physical parameters such as duct diameter ratio, Rayleigh number, radiation parameter etc. It is found that the heat transfer increase with increase in Rayleigh number and radiation parameter. It is observed that Dufour coefficient has more influence on velocity profile.

  11. Two Opposing Effects (Yin and Yang) Determine Cancer Progression.

    Science.gov (United States)

    Huang, Shujun; Kurubanjerdjit, Nilubon; Xu, Wayne

    2017-01-01

    In this review, we introduce a new vision of cancer describing opposing effects that control progression. Cancer is a paradigm of opposing of "Yin" and "Yang," with Yin being the effect to promote cancer and Yang that to maintain the normal state. This Yin Yang hypothesis has been used to select Yin and Yang genes to develop multigene signatures for determining prognosis in lung and breast cancer. Most of the Yin genes are involved in cell survival, growth, and proliferation, whereas most Yang genes are involved in cell apoptosis. Furthermore, Yin and Yang pathways have been identified in breast cancer and compounds that can inhibit the Yin pathways or activate the Yang pathways have been examined, suggesting a new promising targeting therapy for cancer. We are building a Yin Yang model to represent the dynamic change of Yin and Yang genes and pathways.

  12. Where we stand, where we are moving: Surveying computational techniques for identifying miRNA genes and uncovering their regulatory role

    KAUST Repository

    Kleftogiannis, Dimitrios A.; Korfiati, Aigli; Theofilatos, Konstantinos A.; Likothanassis, Spiridon D.; Tsakalidis, Athanasios K.; Mavroudi, Seferina P.

    2013-01-01

    Traditional biology was forced to restate some of its principles when the microRNA (miRNA) genes and their regulatory role were firstly discovered. Typically, miRNAs are small non-coding RNA molecules which have the ability to bind to the 3'untraslated region (UTR) of their mRNA target genes for cleavage or translational repression. Existing experimental techniques for their identification and the prediction of the target genes share some important limitations such as low coverage, time consuming experiments and high cost reagents. Hence, many computational methods have been proposed for these tasks to overcome these limitations. Recently, many researchers emphasized on the development of computational approaches to predict the participation of miRNA genes in regulatory networks and to analyze their transcription mechanisms. All these approaches have certain advantages and disadvantages which are going to be described in the present survey. Our work is differentiated from existing review papers by updating the methodologies list and emphasizing on the computational issues that arise from the miRNA data analysis. Furthermore, in the present survey, the various miRNA data analysis steps are treated as an integrated procedure whose aims and scope is to uncover the regulatory role and mechanisms of the miRNA genes. This integrated view of the miRNA data analysis steps may be extremely useful for all researchers even if they work on just a single step. © 2013 Elsevier Inc.

  13. Where we stand, where we are moving: Surveying computational techniques for identifying miRNA genes and uncovering their regulatory role

    KAUST Repository

    Kleftogiannis, Dimitrios A.

    2013-06-01

    Traditional biology was forced to restate some of its principles when the microRNA (miRNA) genes and their regulatory role were firstly discovered. Typically, miRNAs are small non-coding RNA molecules which have the ability to bind to the 3\\'untraslated region (UTR) of their mRNA target genes for cleavage or translational repression. Existing experimental techniques for their identification and the prediction of the target genes share some important limitations such as low coverage, time consuming experiments and high cost reagents. Hence, many computational methods have been proposed for these tasks to overcome these limitations. Recently, many researchers emphasized on the development of computational approaches to predict the participation of miRNA genes in regulatory networks and to analyze their transcription mechanisms. All these approaches have certain advantages and disadvantages which are going to be described in the present survey. Our work is differentiated from existing review papers by updating the methodologies list and emphasizing on the computational issues that arise from the miRNA data analysis. Furthermore, in the present survey, the various miRNA data analysis steps are treated as an integrated procedure whose aims and scope is to uncover the regulatory role and mechanisms of the miRNA genes. This integrated view of the miRNA data analysis steps may be extremely useful for all researchers even if they work on just a single step. © 2013 Elsevier Inc.

  14. Transport synthetic acceleration with opposing reflecting boundary conditions

    Energy Technology Data Exchange (ETDEWEB)

    Zika, M R; Adams, M L

    2000-02-01

    The transport synthetic acceleration (TSA) scheme is extended to problems with opposing reflecting boundary conditions. This synthetic method employs a simplified transport operator as its low-order approximation. A procedure is developed that allows the use of the conjugate gradient (CG) method to solve the resulting low-order system of equations. Several well-known transport iteration algorithms are cast in a linear algebraic form to show their equivalence to standard iterative techniques. Source iteration in the presence of opposing reflecting boundary conditions is shown to be equivalent to a (poorly) preconditioned stationary Richardson iteration, with the preconditioner defined by the method of iterating on the incident fluxes on the reflecting boundaries. The TSA method (and any synthetic method) amounts to a further preconditioning of the Richardson iteration. The presence of opposing reflecting boundary conditions requires special consideration when developing a procedure to realize the CG method for the proposed system of equations. The CG iteration may be applied only to symmetric positive definite matrices; this condition requires the algebraic elimination of the boundary angular corrections from the low-order equations. As a consequence of this elimination, evaluating the action of the resulting matrix on an arbitrary vector involves two transport sweeps and a transmission iteration. Results of applying the acceleration scheme to a simple test problem are presented.

  15. Physical Activity in the Transition to University: The Role of Past Behavior and Concurrent Self-Regulatory Efficacy

    Science.gov (United States)

    Crozier, Alyson J.; Gierc, Madelaine S. H.; Locke, Sean R.; Brawley, Lawrence R.

    2015-01-01

    Objective: Two studies were conducted to examine the relationship between past physical activity, concurrent self-regulatory efficacy (CSRE), and current physical activity during the transition to university. Participants: Study 1 included 110 first-year undergraduate students recruited during October/November of 2012. Study 2 involved 86…

  16. ‘Fit for charity’: the moderating role of private self-focus in the persuasiveness of regulatory fit

    NARCIS (Netherlands)

    Fransen, M.L.; Fennis, B.M.; Vohs, K.D.; Pruyn, A.T.H.

    2009-01-01

    The present research extends work on the ‘the value from fit’ principle by showing that regulatory fit effects on charitable behavior are stronger for consumers high in private self-focus. Based on previous research showing that individuals high in private self-focus are more affected by external

  17. Identification of CsrC and Characterization of Its Role in Epithelial Cell Invasion in Salmonella enterica Serovar Typhimurium

    OpenAIRE

    Fortune, Doreen R.; Suyemoto, Mitsu; Altier, Craig

    2006-01-01

    The csr regulatory system of Salmonella regulates the expression of the genes of Salmonella pathogenicity island 1 (SPI1) required for the invasion of epithelial cells. This system consists of the posttranscriptional regulator CsrA and an untranslated regulatory RNA, CsrB, that opposes the action of CsrA. Here we identify and characterize the role of a second regulatory RNA, CsrC, whose ortholog was discovered previously in Escherichia coli. We show that a mutant of csrC has only mild defects...

  18. Negative Correlation between Circulating CD4+FOXP3+CD127− Regulatory T Cells and Subsequent Antibody Responses to Infant Measles Vaccine but Not Diphtheria–Tetanus–Pertussis Vaccine Implies a Regulatory Role

    Directory of Open Access Journals (Sweden)

    Jorjoh Ndure

    2017-08-01

    Full Text Available Regulatory T cells (Tregs play a key homeostatic role by suppressing immune responses. They have been targeted in mouse and human cancer studies to improve vaccine immunogenicity and tumor clearance. A number of commercially available drugs and experimental vaccine adjuvants have been shown to target Tregs. Infants have high numbers of Tregs and often have poor responses to vaccination, yet the role Tregs play in controlling vaccine immunogenicity has not been explored in this age group. Herein, we explore the role of CD4+FOXP3+CD127− Tregs in controlling immunity in infant males and females to vaccination with diphtheria–tetanus–whole cell pertussis (DTP and/or measles vaccine (MV. We find correlative evidence that circulating Tregs at the time of vaccination suppress antibody responses to MV but not DTP; and Tregs 4 weeks after DTP vaccination may suppress vaccine-specific cellular immunity. This opens the exciting possibility that Tregs may provide a future target for improved vaccine responses in early life, including reducing the number of doses of vaccine required. Such an approach would need to be safe and the benefits outweigh the risks, thus further research in this area is required.

  19. Roles and contributions of pharmacists in regulatory affairs at the Centers for Disease Control and Prevention for public health emergency preparedness and response.

    Science.gov (United States)

    Bhavsar, Tina R; Kim, Hye-Joo; Yu, Yon

    To provide a general description of the roles and contributions of three pharmacists from the Regulatory Affairs program (RA) at the Centers for Disease Control and Prevention (CDC) who are involved in emergency preparedness and response activities, including the 2009 pandemic influenza A (H1N1) public health emergency. Atlanta, GA. RA consists of a staff of nine members, three of whom are pharmacists. The mission of RA is to support CDC's preparedness and emergency response activities and to ensure regulatory compliance for critical medical countermeasures against potential threats from natural, chemical, biological, radiological, or nuclear events. RA was well involved in the response to the H1N1 outbreak through numerous activities, such as submitting multiple Emergency Use Authorization (EUA) requests to the Food and Drug Administration, including those for medical countermeasures to be deployed from the Strategic National Stockpile, and developing the CDC EUA website (www.cdc.gov/h1n1flu/eua). RA will continue to support current and future preparedness and emergency response activities by ensuring that the appropriate regulatory mechanisms are in place for the deployment of critical medical countermeasures from the Strategic National Stockpile against threats to public health.

  20. The immunoregulatory role of type I and type II NKT cells in cancer and other diseases

    Science.gov (United States)

    Terabe, Masaki; Berzofsky, Jay A.

    2014-01-01

    NKT cells are CD1d-restricted T cells that recognize lipid antigens. They also have been shown to play critical roles in the regulation of immune responses. In the immune responses against tumors, two subsets of NKT cells, type I and type II, play opposing roles and cross-regulate each other. As members of both the innate and adaptive immune systems, which form a network of multiple components, they also interact with other immune components. Here we discuss the function of NKT cells in tumor immunity and their interaction with other regulatory cells, especially CD4+CD25+Foxp3+ regulatory T cells. PMID:24384834

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

    OpenAIRE

    Kerber, Wolfgang; Wendel, Julia

    2016-01-01

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

  2. Cleft Palate Repair Using a Double Opposing Z-Plasty.

    Science.gov (United States)

    Moores, Craig; Shah, Ajul; Steinbacher, Derek M

    2016-07-01

    Cleft palate is a common congenital defect with several described surgical repairs. The most successful treatment modality remains a controversy. The goals of repair focus on achievement of normal speech and optimizing velopharyngeal function while minimizing both fistula formation and facial growth restriction. In this video, the authors demonstrate use of the double opposing Z-plasty technique in the repair of a Veau II type cleft palate. The video demonstrates the marking, incisions, dissection, and repair of the cleft. It also examines the use of von Langenbeck-type relaxing incisions and demonstrates a specific approach to the repair of this particular cleft. The authors believe that the Furlow double opposing Z-plasty with the von Langenbeck relaxing incision can provide the best postoperative outcome by combining the benefits of each individual operation. The Z-plasty technique works to correct the aberrant muscle of the soft palate while increasing the length of the palate. The authors believe that this results in better velopharyngeal function.

  3. Disentangling opposing effects of motivational states on pain perception

    Science.gov (United States)

    Geuter, Stephan; Cunningham, Jonathan T.; Wager, Tor D.

    2016-01-01

    Abstract Introduction: Although the motivation to avoid injury and pain is central to human and animal behavior, this goal compete priority with other homeostatic goals. Animal studies have shown that competing motivational states, such as thirst, reduce pain. However, such states may also induce negative mood, which in humans has been found to increase pain. These opposing effects complicate study of the effects of motivational states in humans. Objectives: To evaluate concurrent effects of motivational state competition and mood on pain ratings. Methods: We compared a thirst challenge against a control group and measured thirst and mood as potential mediators. Pain induced through contact heat stimulation on the left forearm and was tested at 3 time points: before group randomization, after thirst induction, and after rehydration. Results: Overall, the thirst group reported more pain when thirsty compared with baseline and controls. Mediation analyses showed evidence for two opposing effects. First, the thirst challenge increased negative mood and thirstiness, which was related to increased pain. Second, the thirst challenge produced a direct, pain-reducing effect. Conclusion: Competing motivational states reduce pain but also induce concurrent mood changes that can mask motivational state-related effects. PMID:27747310

  4. Regulatory activities

    International Nuclear Information System (INIS)

    2001-01-01

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

  5. The effects of message framing and risk perceptions for HPV vaccine campaigns: focus on the role of regulatory fit.

    Science.gov (United States)

    Park, Sun-Young

    2012-01-01

    This study investigates the effects of framing and risk perception, and their interaction effects on human papillomavirus (HPV) vaccination. Based on a 2 (message frames) × 2 (perceived risk) experimental design, the interaction effects reveal the effectiveness of loss- (vs. gain-) framed messages would be maximized for high (vs. low) perceived risk condition. Based on regulatory fit principles the synergy effects are shown in terms of attitudes toward advertising and HPV vaccination, HPV vaccination intention, and ad-promoted behavioral intention. The findings indicate right message appeals should be selected for the right target audiences in the setting of HPV vaccine promotions.

  6. A PTEN-COL17A1 fusion gene and its novel regulatory role in Collagen XVII expression and GBM malignance.

    Science.gov (United States)

    Yan, Xiaoyan; Zhang, Chuanbao; Liang, Tingyu; Yang, Fan; Wang, Haoyuan; Wu, Fan; Wang, Wen; Wang, Zheng; Cheng, Wen; Xu, Jiangnan; Jiang, Tao; Chen, Jing; Ding, Yaozhong

    2017-10-17

    Collagen XVII expression has recently been demonstrated to be correlated with the tumor malignance. While Collagen XVII is known to be widely distributed in neurons of the human brain, its precise role in pathogenesis of glioblastoma multiforme (GBM) is unknown. In this study, we identified and characterized a new PTEN-COL17A1 fusion gene in GMB using transcriptome sequencing. Although fusion gene did not result in measurable fusion protein production, its presence is accompanied with high levels of COL17A1 expression, revealed a novel regulatory mechanism of Collagen XVII expression by PTEN-COL17A1 gene fusion. Knocked down Collagen XVII expression in glioma cell lines resulted in decreased tumor invasiveness, along with significant reduction of MMP9 expression, while increased Collagen XVII expression promotes invasive activities of glioma cells and associated with GBM recurrences. Together, our results uncovered a new PTEN-COL17A1 fusion gene and its novel regulatory role in Collagen XVII expression and GBM malignance, and demonstrated that COL17A1 could serve as a useful prognostic biomarker and therapeutic targets for GBM.

  7. The Role of Interferon Regulatory Factor-1 (IRF1) in Overcoming Antiestrogen Resistance in the Treatment of Breast Cancer

    International Nuclear Information System (INIS)

    Schwartz, J.L.; Shajahan, A.N.; Clarke, R.

    2011-01-01

    Resistance to endocrine therapy is common among breast cancer patients with estrogen receptor alpha-positive (ER+) tumors and limits the success of this therapeutic strategy. While the mechanisms that regulate endocrine responsiveness and cell fate are not fully understood, interferon regulatory factor-1 (IRF1) is strongly implicated as a key regulatory node in the underlying signaling network. IRF1 is a tumor suppressor that mediates cell fate by facilitating apoptosis and can do so with or without functional p53. Expression of IRF1 is down regulated in endocrine-resistant breast cancer cells, protecting these cells from IRF1-induced inhibition of proliferation and/or induction of cell death. Nonetheless, when IRF1 expression is induced following IFN treatment, antiestrogen sensitivity is restored by a process that includes the inhibition of pro survival BCL2 family members and caspase activation. These data suggest that a combination of endocrine therapy and compounds that effectively induce IRF1 expression may be useful for the treatment of many ER+ breast cancers. By understanding IRF1 signaling in the context of endocrine responsiveness, we may be able to develop novel therapeutic strategies and better predict how patients will respond to endocrine therapy

  8. How Stereotype Threat Affects Healthy Older Adults' Performance on Clinical Assessments of Cognitive Decline: The Key Role of Regulatory Fit.

    Science.gov (United States)

    Barber, Sarah J; Mather, Mara; Gatz, Margaret

    2015-11-01

    Stereotype threat can impair older adults' performance on clinical assessments for cognitive decline. We examined why this occurs. Based upon the regulatory focus account of stereotype threat, we predicted that the effects of stereotype threat should depend upon the assessments' reward structure. Stereotype threat should be associated with poor performance when the assessment emphasizes gaining correct answers, but not when it emphasizes avoiding mistakes. Healthy older adults completed a series of mental status examinations. Half of the participants completed these examinations under stereotype threat about their cognitive abilities. Monetary incentives were also manipulated. For half of the participants correct responding led to gains. For the remaining participants incorrect responding/forgetting led to losses. Consistent with the regulatory focus account, stereotype threat was associated with poor performance when the mental status examinations had a gains-based structure, but not when they had a losses-based structure. Older adults respond to stereotype threat by becoming vigilant to avoid the losses that will make them their worst. Researchers and clinicians can capitalize on this motivational change to combat stereotype threat's negative effects. By using a loss-avoidance frame, stereotype threat's negative effects can be attenuated or even eliminated. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. How Stereotype Threat Affects Healthy Older Adults’ Performance on Clinical Assessments of Cognitive Decline: The Key Role of Regulatory Fit

    Science.gov (United States)

    Mather, Mara; Gatz, Margaret

    2015-01-01

    Objectives. Stereotype threat can impair older adults’ performance on clinical assessments for cognitive decline. We examined why this occurs. Based upon the regulatory focus account of stereotype threat, we predicted that the effects of stereotype threat should depend upon the assessments’ reward structure. Stereotype threat should be associated with poor performance when the assessment emphasizes gaining correct answers, but not when it emphasizes avoiding mistakes. Method. Healthy older adults completed a series of mental status examinations. Half of the participants completed these examinations under stereotype threat about their cognitive abilities. Monetary incentives were also manipulated. For half of the participants correct responding led to gains. For the remaining participants incorrect responding/forgetting led to losses. Results. Consistent with the regulatory focus account, stereotype threat was associated with poor performance when the mental status examinations had a gains-based structure, but not when they had a losses-based structure. Discussion. Older adults respond to stereotype threat by becoming vigilant to avoid the losses that will make them their worst. Researchers and clinicians can capitalize on this motivational change to combat stereotype threat’s negative effects. By using a loss-avoidance frame, stereotype threat’s negative effects can be attenuated or even eliminated. PMID:25752896

  10. U.S. Nuclear Regulatory Commission Role and Activities Related to U.S. Department of Energy Incidental Waste Determinations

    International Nuclear Information System (INIS)

    Bradford, A.H.; Esh, D.W.; Ridge, A.C.

    2006-01-01

    Section 3116 of the Ronald W. Reagan National Defense Authorization Act for Fiscal Year 2005 (NDAA) requires the U.S. Department of Energy (DOE) to consult with the U.S. Nuclear Regulatory Commission (NRC) for certain non-high level waste (HLW) determinations. Under the NDAA, NRC performs consultative technical reviews of DOE's waste determinations and monitors DOE's disposal actions for such waste, but the NRC does not have regulatory authority over DOE's waste disposal activities. The NDAA provides the criteria that must be met to determine that waste is not HLW. The criteria require that the waste does not need to be disposed of in a geologic repository, that highly radioactive radionuclides be removed to the maximum extent practical, and that the performance objectives of 10 CFR 61, Subpart C, be met. The performance objectives contain criteria for protection of the public, protection of inadvertent intruders, protection of workers, and stability of the disposal site after closure. This paper describes NRC's approach to implementing its responsibilities under the NDAA, as well as similar activities being performed for sites not covered by the NDAA. (authors)

  11. Regulatory behavior and frontal activity: Considering the role of revised-BIS in relative right frontal asymmetry.

    Science.gov (United States)

    Gable, Philip A; Neal, Lauren B; Threadgill, A Hunter

    2018-01-01

    Essential to human behavior are three core personality systems: approach, avoidance, and a regulatory system governing the two motivational systems. Decades of research has linked approach motivation with greater relative left frontal-cortical asymmetry. Other research has linked avoidance motivation with greater relative right frontal-cortical asymmetry. However, past work linking withdrawal motivation with greater relative right frontal asymmetry has been mixed. The current article reviews evidence suggesting that activation of the regulatory system (revised Behavioral Inhibition System [r-BIS]) may be more strongly related to greater relative right frontal asymmetry than withdrawal motivation. Specifically, research suggests that greater activation of the r-BIS is associated with greater relative right frontal activity, and reduced r-BIS activation is associated with reduced right frontal activity (greater relative left frontal activity). We review evidence examining trait and state frontal activity using EEG, source localization, lesion studies, neuronal stimulation, and fMRI supporting the idea that r-BIS may be the core personality system related to greater relative right frontal activity. In addition, the current review seeks to disentangle avoidance motivation and r-BIS as substrates of relative right frontal asymmetry. © 2017 Society for Psychophysiological Research.

  12. Nonword repetition in lexical decision: support for two opposing processes.

    Science.gov (United States)

    Wagenmakers, Eric-Jan; Zeelenberg, René; Steyvers, Mark; Shiffrin, Richard; Raaijmakers, Jeroen

    2004-10-01

    We tested and confirmed the hypothesis that the prior presentation of nonwords in lexical decision is the net result of two opposing processes: (1) a relatively fast inhibitory process based on global familiarity; and (2) a relatively slow facilitatory process based on the retrieval of specific episodic information. In three studies, we manipulated speed-stress to influence the balance between the two processes. Experiment 1 showed item-specific improvement for repeated nonwords in a standard "respond-when-ready" lexical decision task. Experiment 2 used a 400-ms deadline procedure and showed performance for nonwords to be unaffected by up to four prior presentations. In Experiment 3 we used a signal-to-respond procedure with variable time intervals and found negative repetition priming for repeated nonwords. These results can be accounted for by dual-process models of lexical decision.

  13. Neural Circuit to Integrate Opposing Motions in the Visual Field.

    Science.gov (United States)

    Mauss, Alex S; Pankova, Katarina; Arenz, Alexander; Nern, Aljoscha; Rubin, Gerald M; Borst, Alexander

    2015-07-16

    When navigating in their environment, animals use visual motion cues as feedback signals that are elicited by their own motion. Such signals are provided by wide-field neurons sampling motion directions at multiple image points as the animal maneuvers. Each one of these neurons responds selectively to a specific optic flow-field representing the spatial distribution of motion vectors on the retina. Here, we describe the discovery of a group of local, inhibitory interneurons in the fruit fly Drosophila key for filtering these cues. Using anatomy, molecular characterization, activity manipulation, and physiological recordings, we demonstrate that these interneurons convey direction-selective inhibition to wide-field neurons with opposite preferred direction and provide evidence for how their connectivity enables the computation required for integrating opposing motions. Our results indicate that, rather than sharpening directional selectivity per se, these circuit elements reduce noise by eliminating non-specific responses to complex visual information. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Islam, Islamophobia and the West: Opposing Views and Social Reality

    Directory of Open Access Journals (Sweden)

    Adila Pavelić

    2015-12-01

    Full Text Available Through reviewing different and often opposing views on the relationship between Islam and the West, the paper aims to offer a better understanding of this relationship, and of Islamophobia as an old, yet increasingly actual and in many respects relevant social problem. A short historical overview of the understanding of the relationship between Islam and the West, and various definitions of Islamophobia, are followed by examination of some recent works that from different perspectives deal with the issue. Firstly, is given insight into the works written by Western theorists who describe the relationship between Islam and the West within the framework of the idea of the clash of civilizations while, at the same time, labeling Islam often as a non-modern religion and culture whose members reject Western values such as democracy, freedom and gender equality. In contrast to them are introduced the authors whose argumentation opposes stereotypical views of Islam; among them are also those that critically address Islamophobia in today’s Western society, either by presenting results of their research on Islamophobia or by documenting the dominant media image of Islam, which has been perpetuating stereotypes, especially in the aftermath of the terrorist attacks on New York in 2001. Lastly, it is concluded that, regardless of the origin of works dealing with the relationship between Islam and the West or of the type of their arguments, they more often than not interpret Islam and the West primarily as two separate, self-contained and in itself incompatible worlds. In doing so, the authors here argue, they employ an essentialist and reductionist approach not only to Islam – as it might be assumed – but also to the West, while the relationship between Islam and the West is simplified and schematized.

  15. Strength training and testosterone treatment have opposing effects on migration inhibitor factor levels in ageing men

    DEFF Research Database (Denmark)

    Glintborg, D.; Christensen, L. L.; Kvorning, T.

    2013-01-01

    Strength Training and Testosterone Treatment Have Opposing Effects on Migration Inhibitor Factor Levels in Ageing Men......Strength Training and Testosterone Treatment Have Opposing Effects on Migration Inhibitor Factor Levels in Ageing Men...

  16. Materialists on Facebook: the self-regulatory role of social comparisons and the objectification of Facebook friends.

    Science.gov (United States)

    Ozimek, Phillip; Baer, Fiona; Förster, Jens

    2017-11-01

    In this study, we examine chronic materialism as a possible motive for Facebook usage. We test an explanatory mediation model predicting that materialists use Facebook more frequently, because they compare themselves to others, they objectify and instrumentalize others, and they accumulate friends. For this, we conducted two online surveys ( N 1 = 242, N 2 = 289) assessing demographic variables, Facebook use, social comparison, materialism, objectification and instrumentalization. Results confirm the predicted mediation model. Our findings suggest that Facebook can be used as a means to an end in a way of self-regulatory processes, like satisfying of materialistic goals. The findings are the first evidence for our Social Online Self-regulation Theory (SOS-T), which contains numerous predictions that can be tested in the future.

  17. Materialists on Facebook: the self-regulatory role of social comparisons and the objectification of Facebook friends

    Directory of Open Access Journals (Sweden)

    Phillip Ozimek

    2017-11-01

    Full Text Available In this study, we examine chronic materialism as a possible motive for Facebook usage. We test an explanatory mediation model predicting that materialists use Facebook more frequently, because they compare themselves to others, they objectify and instrumentalize others, and they accumulate friends. For this, we conducted two online surveys (N1 = 242, N2 = 289 assessing demographic variables, Facebook use, social comparison, materialism, objectification and instrumentalization. Results confirm the predicted mediation model. Our findings suggest that Facebook can be used as a means to an end in a way of self-regulatory processes, like satisfying of materialistic goals. The findings are the first evidence for our Social Online Self-regulation Theory (SOS-T, which contains numerous predictions that can be tested in the future. Keywords: Psychology, Information science

  18. Rol de las células T regulatorias en esclerosis múltiple Role of T-regulatory cells in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Juan Ignacio Rojas

    2010-02-01

    Full Text Available La esclerosis múltiple (EM es una enfermedad inflamatoria autoinmune desmielinizante del sistema nervioso central (SNC. La mayoría de las enfermedades autoinmunes se originan por la activación anormal de la respuesta inflamatoria contra auto-antígenos (la mayoría de ellos desconocidos a la fecha como consecuencia de la pérdida de la tolerancia periférica. Las células T-regulatorias constituyen un grupo esencial de linfocitos T encargados del mantenimiento de la tolerancia periférica, la prevención de enfermedades autoinmunes y la limitación de enfermedades inflamatorias crónicas. Teniendo en cuenta la importancia de la tolerancia periférica, las células T-regulatorias serían componentes cruciales en el escenario fisiopatológico de los procesos autoinmunes, incluyendo la EM. El presente trabajo recopila los conocimientos actuales sobre la función de las células T-regulatorias en la EM, la enfermedad autoinmune desmielinizante del SNC más prevalente en los seres humanos.Multiple sclerosis (MS is an autoimmune inflammatory demyelinating disease of the central nervous system (CNS. Most of autoimmune diseases arise by an abnormal activation of the inflammatory response against self-antigens (most of them unknown up to date as a consequence of dysfunction in peripheral tolerance. Regulatory T-cells are essential for maintaining peripheral tolerance, preventing autoimmune diseases and limiting chronic inflammatory conditions. Based on that knowledge, T-regulatory cells have emerged as a key component of the physiopathology of autoimmune diseases including MS. This review compiles the current knowledge on the role and function of T-regulatory cells in MS, the most prevalent CNS autoimmune disease in humans.

  19. Opposing Fat Metabolism Pathways Triggered by a Single Gene

    OpenAIRE

    Gilst, Marc R. Van; Hadjivassiliou, Haralambos; Jolly, Amber; Yamamoto, Keith R

    2005-01-01

    Mammalian nuclear hormone receptors (NHRs), such as liver X receptor, farnesoid X receptor, and peroxisome proliferator-activated receptors (PPARs), precisely control energy metabolism. Consequently, these receptors are important targets for the treatment of metabolic diseases, including diabetes and obesity. A thorough understanding of NHR fat regulatory networks has been limited, however, by a lack of genetically tractable experimental systems. Here we show that deletion of the Caenorhabdit...

  20. Positive and negative affect produce opposing task-irrelevant stimulus preexposure effects.

    Science.gov (United States)

    Lazar, Josef; Kaplan, Oren; Sternberg, Terri; Lubow, R E

    2012-06-01

    In three experiments, groups were exposed to either positive or negative affect video clips, after which they were presented with a series of task-irrelevant stimuli. In the subsequent test task, subjects were required to learn an association between the previously irrelevant stimulus and a consequence, and between a new stimulus and a consequence. Induced positive affect produced a latent inhibition effect (poorer evidence of learning with the previously irrelevant stimulus than with the novel stimulus). In opposition to this, induced negative affect resulted in better evidence of learning with a previously irrelevant stimulus than with a novel stimulus. In general, the opposing effects also were present in participants scoring high on self-report questionnaires of depression (Experiments 2 and 3). These unique findings were predicted and accounted for on the basis of two principles: (a) positive affect broadens the attentional field and negative affect contracts it; and (b) task-irrelevant stimuli are processed in two successive stages, the first encodes stimulus properties, and the second encodes stimulus relationships. The opposing influences of negative and positive mood on the processing of irrelevant stimuli have implications for the role of emotion in general theories of cognition, and possibly for resolving some of the inconsistent findings in research with schizophrenia patients.

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

    Directory of Open Access Journals (Sweden)

    Jinhua Liu

    2014-10-01

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

  2. Opposed-phase MR imaging of lipid storage myopathy in a case of Chanarin-Dorfman disease

    International Nuclear Information System (INIS)

    Gaeta, Michele; Celona, Antonio; Racchiusa, Sergio; Mazziotti, Silvio; Minutoli, Fabio; Toscano, Antonio; Musumeci, Olimpia

    2008-01-01

    Chanarin-Dorfman disease (CDD) is a rare genetic disorder characterized by ichthyosis, myopathy, central nervous system disturbances, and intracellular lipid storage in muscle fibers, hepatocytes, and granulocytes. We describe skeletal muscle magnetic resonance imaging findings in a case of CDD, outlining the potential role of GE T1-weighted opposed-phase sequence (chemical shift imaging) in the evaluation of lipid storage myopathies. (orig.)

  3. Opposed-phase MR imaging of lipid storage myopathy in a case of Chanarin-Dorfman disease

    Energy Technology Data Exchange (ETDEWEB)

    Gaeta, Michele; Celona, Antonio; Racchiusa, Sergio; Mazziotti, Silvio [University of Messina, Department of Radiological Sciences, Messina (Italy); Minutoli, Fabio [University of Messina, Department of Radiological Sciences, Messina (Italy); A.O.U. ' ' Policlinico G. Martino' ' , Dipartimento di Scienze Radiologiche, Messina (Italy); Toscano, Antonio; Musumeci, Olimpia [University of Messina, Department of Neurosciences, Psychiatry and Anaesthesiology, Messina (Italy)

    2008-11-15

    Chanarin-Dorfman disease (CDD) is a rare genetic disorder characterized by ichthyosis, myopathy, central nervous system disturbances, and intracellular lipid storage in muscle fibers, hepatocytes, and granulocytes. We describe skeletal muscle magnetic resonance imaging findings in a case of CDD, outlining the potential role of GE T1-weighted opposed-phase sequence (chemical shift imaging) in the evaluation of lipid storage myopathies. (orig.)

  4. Through the regulatory hoop

    International Nuclear Information System (INIS)

    Kirner, N.P.

    1985-01-01

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

  5. Natural ventilation of buildings: opposing wind and buoyancy

    Science.gov (United States)

    Linden, Paul; Hunt, Gary

    1998-11-01

    The use of natural ventilation in buildings is an attractive way to reduce energy usage thereby reducing costs and CO2 emissions. Generally, it is necessary to remove excess heat from a building and the designer can use the buoyancy forces associated with the above ambient temperatures within the building to drive a flow - 'stack' ventilation. The most efficient mode is displacement ventilation where warm air accumulates near the top of the building and flows out through upper level vents and cooler air flows in at lower levels. Ventilation will also be driven between these lower and upper openings by the wind. We report on laboratory modeling and theory which investigates the effects of an opposing wind on stack ventilation driven by a constant source of heat within a space under displacement ventilation. We show that there is a critical wind speed, expressed in dimensionless terms as a critical Froude number, above which displacement ventilation is replaced by (less efficient) mixing ventilation with reversed flow. Below this critical speed, displacement ventilation, in which the interior has a two-layer stratification, is maintained. The criterion for the change in ventilation mode is derived from general considerations of mixing efficiencies in stratified flows. We conclude that even when wind effects might appear to be dominant, the inhibition of mixing by the stable stratification within the space ensures that stack ventilation can operate over a wide range of apparently adverse conditions.

  6. Opposing effects of humidity on rhodochrosite surface oxidation.

    Science.gov (United States)

    Na, Chongzheng; Tang, Yuanzhi; Wang, Haitao; Martin, Scot T

    2015-03-03

    Rhodochrosite (MnCO3) is a model mineral representing carbonate aerosol particles containing redox-active elements that can influence particle surface reconstruction in humid air, thereby affecting the heterogeneous transformation of important atmospheric constituents such as nitric oxides, sulfur dioxides, and organic acids. Using in situ atomic force microscopy, we show that the surface reconstruction of rhodochrosite in humid oxygen leads to the formation and growth of oxide nanostructures. The oxidative reconstruction consists of two consecutive processes with distinctive time scales, including a long waiting period corresponding to slow nucleation and a rapid expansion phase corresponding to fast growth. By varying the relative humidity from 55 to 78%, we further show that increasing humidity has opposing effects on the two processes, accelerating nucleation from 2.8(±0.2) × 10(-3) to 3.0(±0.2) × 10(-2) h(-1) but decelerating growth from 7.5(±0.3) × 10(-3) to 3.1(±0.1) × 10(-3) μm(2) h(-1). Through quantitative analysis, we propose that nanostructure nucleation is controlled by rhodochrosite surface dissolution, similar to the dissolution-precipitation mechanism proposed for carbonate mineral surface reconstruction in aqueous solution. To explain nanostructure growth in humid oxygen, a new Cabrera-Mott mechanism involving electron tunneling and solid-state diffusion is proposed.

  7. Bidirectional transport of organelles: unity and struggle of opposing motors.

    Science.gov (United States)

    Bryantseva, Sofiya A; Zhapparova, Olga N

    2012-01-01

    Bidirectional transport along microtubules is ensured by opposing motor proteins: cytoplasmic dynein that drives cargo to the minus-ends and various kinesins that generally move to the plus-ends of microtubules. Regulation of motor proteins that are simultaneously bound to the same organelle is required to maintain directional transport and prevent pausing of cargo pulled away by motors of opposite polarity. Debates of the recent decade have been focused on two possible mechanisms of such regulation: (i) coordination, which implies that only one type of motors is active at a given time, and (ii) tug-of-war, which assumes that both motors are active at the same time and that direction of transport depends on the outcome of motor's confrontation. The initial idea of coordination has been challenged by observations of simultaneous activity of plus- and minus-end-directed motors applied to the same cargo. Analysis of the available data indicates that coordination and tug-of-war theories rather complement than contradict each other: cargo interacts with two teams of active motors, the resulting direction and the winner team are determined by coordination complexes, but the activity of the loser team is never completely inhibited and remains at some background level. Such persisting activity might enhance the overall efficiency of transport by increasing processivity or helping to overcome the obstacles on microtubule track. © The Author(s) Journal compilation © 2012 Portland Press Limited

  8. The role of national regulatory authority in monitoring of radioactivity and in case of seizure of radioactive or nuclear material

    International Nuclear Information System (INIS)

    Morkunas, G.

    2002-01-01

    Full text: The Radiation Protection Centre is a regulatory authority in radiation protection in Lithuania. Its main tasks are licensing of practices, supervision, control and enforcement of radiation protection requirements, dosimetric, radiometric and spectrometric measurements, evaluation of exposure and its sources, expertise and advice on optimization of radiation protection. Its activities may be divided into two main parts -- regulatory and analytical ones. Food, drinking water, environmental, wipe and other samples are monitored, the appropriate evaluation of doses is done. The data on concentrations of artificial radionuclides in different bodies are available. The laboratory is to be accredited according to the ISO 17025 standard in the framework of Phare Twinning Project. In case of seized radioactive or nuclear material the Radiation Protection Centre has to identify the necessary radiation protection means for members of public and emergency workers, perform measurements of dose rate and radioactive contamination, and, if necessary, evaluate doses received due to the seized radioactive or nuclear material. Since the Radiation Protection Centre has its departments in the largest cities of Lithuania the above mentioned measures can be taken very urgently, especially the ones connected with primary evaluation of situation and identification of optimized radiation protection measures. The Radiation Protection Centre has its own possibilities of identification of radionuclides in the seized material. Such installations as HpGe spectrometers (Oxford and Canberra), equipment for radiochemical separation of U, Pu and actinides, alpha spectrometer, liquid scintillation spectrometer and neutron rem counter are available. There were a few cases when seized material had to be analyzed also. Different sources were found in different places of Lithuania, and it was necessary to define the activity and isotopic content of these sources. The following scheme is used in

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

    Science.gov (United States)

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

    2013-11-01

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

  10. Role of the SaeRS two-component regulatory system in Staphylococcus epidermidis autolysis and biofilm formation

    Science.gov (United States)

    2011-01-01

    Background Staphylococcus epidermidis (SE) has emerged as one of the most important causes of nosocomial infections. The SaeRS two-component signal transduction system (TCS) influences virulence and biofilm formation in Staphylococcus aureus. The deletion of saeR in S. epidermidis results in impaired anaerobic growth and decreased nitrate utilization. However, the regulatory function of SaeRS on biofilm formation and autolysis in S. epidermidis remains unclear. Results The saeRS genes of SE1457 were deleted by homologous recombination. The saeRS deletion mutant, SE1457ΔsaeRS, exhibited increased biofilm formation that was disturbed more severely (a 4-fold reduction) by DNase I treatment compared to SE1457 and the complementation strain SE1457saec. Compared to SE1457 and SE1457saec, SE1457ΔsaeRS showed increased Triton X-100-induced autolysis (approximately 3-fold) and decreased cell viability in planktonic/biofilm states; further, SE1457ΔsaeRS also released more extracellular DNA (eDNA) in the biofilms. Correlated with the increased autolysis phenotype, the transcription of autolysis-related genes, such as atlE and aae, was increased in SE1457ΔsaeRS. Whereas the expression of accumulation-associated protein was up-regulated by 1.8-fold in 1457ΔsaeRS, the expression of an N-acetylglucosaminyl transferase enzyme (encoded by icaA) critical for polysaccharide intercellular adhesin (PIA) synthesis was not affected by the deletion of saeRS. Conclusions Deletion of saeRS in S. epidermidis resulted in an increase in biofilm-forming ability, which was associated with increased eDNA release and up-regulated Aap expression. The increased eDNA release from SE1457ΔsaeRS was associated with increased bacterial autolysis and decreased bacterial cell viability in the planktonic/biofilm states. PMID:21702925

  11. Role of the SaeRS two-component regulatory system in Staphylococcus epidermidis autolysis and biofilm formation

    Directory of Open Access Journals (Sweden)

    Francois Patrice

    2011-06-01

    Full Text Available Abstract Background Staphylococcus epidermidis (SE has emerged as one of the most important causes of nosocomial infections. The SaeRS two-component signal transduction system (TCS influences virulence and biofilm formation in Staphylococcus aureus. The deletion of saeR in S. epidermidis results in impaired anaerobic growth and decreased nitrate utilization. However, the regulatory function of SaeRS on biofilm formation and autolysis in S. epidermidis remains unclear. Results The saeRS genes of SE1457 were deleted by homologous recombination. The saeRS deletion mutant, SE1457ΔsaeRS, exhibited increased biofilm formation that was disturbed more severely (a 4-fold reduction by DNase I treatment compared to SE1457 and the complementation strain SE1457saec. Compared to SE1457 and SE1457saec, SE1457ΔsaeRS showed increased Triton X-100-induced autolysis (approximately 3-fold and decreased cell viability in planktonic/biofilm states; further, SE1457ΔsaeRS also released more extracellular DNA (eDNA in the biofilms. Correlated with the increased autolysis phenotype, the transcription of autolysis-related genes, such as atlE and aae, was increased in SE1457ΔsaeRS. Whereas the expression of accumulation-associated protein was up-regulated by 1.8-fold in 1457ΔsaeRS, the expression of an N-acetylglucosaminyl transferase enzyme (encoded by icaA critical for polysaccharide intercellular adhesin (PIA synthesis was not affected by the deletion of saeRS. Conclusions Deletion of saeRS in S. epidermidis resulted in an increase in biofilm-forming ability, which was associated with increased eDNA release and up-regulated Aap expression. The increased eDNA release from SE1457ΔsaeRS was associated with increased bacterial autolysis and decreased bacterial cell viability in the planktonic/biofilm states.

  12. Circulating Regulatory T-Cells in Monoclonal Gammopathies of Uncertain Significance and Multiple Myeloma: In Search of a Role

    Directory of Open Access Journals (Sweden)

    Giovanni D’Arena

    2016-01-01

    Full Text Available The frequency and function of regulatory T-cells (Tregs in multiple myeloma (MM are still matter of debate. The percentage and absolute number of circulating Tregs (CD4+CD25+high  densityCD127-/low  density from 39 patients with untreated MM and 44 patients with monoclonal gammopathies of uncertain significance (MGUS were tested and compared with 20 healthy subjects as controls. The mean percentage number of circulating Tregs was 2.1%  ± 1.0 (range 0.75–6.1% in MM patients; 2.1%  ± 0.9 (range 0.3–4.4% in MGUS; and 1.5%  ± 0.4 (range 0.9–2.1% in controls (p ns. Mean absolute number of Tregs was 36.3/μL ± 23.7 (range 6.7–149/μL in MM; 38.8/μL ± 19.1 (range 4.3–87/μL in MGUS; and 39.4/μL ± 12.5 (range 18–63/μL in controls (p ns. After a median follow-up of 38 months, 5 MGUS and 2 smoldering MM (SMM transformed into overt MM; however Tregs number did not predict this evolution. With respect to MM patients and after a median follow-up of 33 months, Tregs did not show any significant correlation with main clinical and laboratory characteristics. Finally, from a functional point of view, Tregs displayed an effective suppressor function, irrespective of disease status. This study indicates that the number of circulating Tregs does not differ in different monoclonal gammopathies and normal subjects and do not correlate with clinical features of MM.

  13. Dominant role of antigen dose in CD4+Foxp3+ regulatory T cell induction and expansion1

    Science.gov (United States)

    Turner, Michael S.; Kane, Lawrence P.; Morel, Penelope A.

    2009-01-01

    The definitions of tolerogenic vs. immunogenic dendritic cells (DC) remain controversial. Immature DC have been shown to induce T regulatory cells (Treg) specific for foreign and allo-antigens. However, we have previously reported that mature DC (G4DC) prevented the onset of autoimmune diabetes whereas immature DC (GMDC) were therapeutically ineffective. In this study, islet-specific CD4+ T cells from BDC2.5 TCR Tg mice were stimulated, in the absence of exogenous cytokine, with GMDC or G4DC pulsed with high- or low-affinity antigenic peptides and examined for Treg induction. Both GMDC and G4DC presenting low peptide doses induced weak TCR signaling via the Akt/mTOR pathway, resulting in significant expansion of Foxp3+ Treg. Furthermore, unpulsed G4DC, but not GMDC, also induced Treg. High peptide doses induced strong Akt/mTOR signaling and favored the expansion of Foxp3neg Th cells. The inverse correlation of Foxp3 and Akt/mTOR signaling was also observed in DO11.10 and OT-II TCR-Tg T cells and was recapitulated with anti-CD3/CD28 stimulation in the absence of DC. IL-6 production in these cultures correlated positively with antigen dose and inversely with Treg expansion. Studies with T cells or DC from IL-6−/− mice revealed that IL-6 production by T cells was more important in the inhibition of Treg induction at low antigen doses. These studies indicate that strength of Akt/mTOR signaling, a critical T cell intrinsic determinant for Treg vs Th induction, can be controlled by adjusting the dose of antigenic peptide. Furthermore, this operates in a dominant fashion over DC phenotype and cytokine production. PMID:19801514

  14. Large-volume static compression using nano-polycrystalline diamond for opposed anvils in compact cells

    International Nuclear Information System (INIS)

    Okuchi, T; Sasaki, S; Ohno, Y; Osakabe, T; Odake, S; Kagi, H

    2010-01-01

    In order to extend the pressure regime of intrinsically low-sensitivity methods of measurement, such as neutron scattering and NMR, sample volume to be compressed in compact opposed-anvil cells is desired to be significantly increased. We hereby conducted a series of experiments using two types of compact cells equipped with enforced loading mechanisms. Super-hard nano-polycrystalline diamond (NPD) anvils were carefully prepared for large-volume compression in these cells. These anvils are harder, larger and stronger than single crystal diamond anvils, so that they could play an ideal role to accept the larger forces. Supported and unsupported anvil geometries were separately tested to evaluate this expectation. In spite of insufficient support to the anvils, pressures to 14 GPa were generated for the sample volume of > 0.1 mm 3 , without damaging the NPD anvils. These results demonstrate a large future potential of compact cells equipped with NPD anvils and enforced loading mechanism.

  15. HPRT deficiency coordinately dysregulates canonical Wnt and presenilin-1 signaling: a neuro-developmental regulatory role for a housekeeping gene?

    Directory of Open Access Journals (Sweden)

    Tae Hyuk Kang

    2011-01-01

    Full Text Available We have used microarray-based methods of global gene expression together with quantitative PCR and Western blot analysis to identify dysregulation of genes and aberrant cellular processes in human fibroblasts and in SH-SY5Y neuroblastoma cells made HPRT-deficient by transduction with a retrovirus stably expressing an shRNA targeted against HPRT. Analysis of the microarray expression data by Gene ontology (GO and Gene Set Enrichment Analysis (GSEA as well as significant pathway analysis by GeneSpring GX10 and Panther Classification System reveal that HPRT deficiency is accompanied by aberrations in a variety of pathways known to regulate neurogenesis or to be implicated in neurodegenerative disease, including the canonical Wnt/β-catenin and the Alzheimer's disease/presenilin signaling pathways. Dysregulation of the Wnt/β-catenin pathway is confirmed by Western blot demonstration of cytosolic sequestration of β-catenin during in vitro differentiation of the SH-SY5Y cells toward the neuronal phenotype. We also demonstrate that two key transcription factor genes known to be regulated by Wnt signaling and to be vital for the generation and function of dopaminergic neurons; i.e., Lmx1a and Engrailed 1, are down-regulated in the HPRT knockdown SH-SY5Y cells. In addition to the Wnt signaling aberration, we found that expression of presenilin-1 shows severely aberrant expression in HPRT-deficient SH-SY5Y cells, reflected by marked deficiency of the 23 kDa C-terminal fragment of presenilin-1 in knockdown cells. Western blot analysis of primary fibroblast cultures from two LND patients also shows dysregulated presenilin-1 expression, including aberrant proteolytic processing of presenilin-1. These demonstrations of dysregulated Wnt signaling and presenilin-1 expression together with impaired expression of dopaminergic transcription factors reveal broad pleitropic neuro-regulatory defects played by HPRT expression and suggest new directions for

  16. Subcomponents of psychopathy have opposing correlations with punishment judgments.

    Science.gov (United States)

    Schaich Borg, Jana; Kahn, Rachel E; Sinnott-Armstrong, Walter; Kurzban, Robert; Robinson, Paul H; Kiehl, Kent A

    2013-10-01

    Psychopathy research is plagued by an enigma: Psychopaths reliably act immorally, but they also accurately report whether an action is morally wrong. The current study revealed that cooperative suppressor effects and conflicting subsets of personality traits within the construct of psychopathy might help explain this conundrum. Among a sample of adult male offenders (N = 100) who ranked deserved punishment of crimes, Psychopathy Checklist-Revised (PCL-R) total scores were not linearly correlated with deserved punishment task performance. However, these null results masked significant opposing associations between task performance and factors of psychopathy: the PCL-R Interpersonal/Affective (i.e., manipulative and callous) factor was positively associated with task performance, while the PCL-R Social Deviance (i.e., impulsive and antisocial) factor was simultaneously negatively associated with task performance. These relationships were qualified by a significant interaction where the Interpersonal/Affective traits were positively associated with task performance when Social Deviance traits were high, but Social Deviance traits were negatively associated with task performance when Interpersonal/Affective traits were low. This interaction helped reveal a significant nonlinear relationship between PCL-R total scores and task performance such that individuals with very low or very high PCL-R total scores performed better than those with middle-range PCL-R total scores. These results may explain the enigma of why individuals with very high psychopathic traits, but not other groups of antisocial individuals, usually have normal moral judgment in laboratory settings, but still behave immorally, especially in contexts where social deviance traits have strong influence.

  17. Advancing regulatory science to bring novel medical devices for use in emergency care to market: the role of the Food and Drug Administration.

    Science.gov (United States)

    Scully, Christopher G; Forrest, Shawn; Galeotti, Loriano; Schwartz, Suzanne B; Strauss, David G

    2015-04-01

    The Food and Drug Administration (FDA) performs regulatory science to provide science-based medical product regulatory decisions. This article describes the types of scientific research the FDA's Center for Devices and Radiological Health performs and highlights specific projects related to medical devices for emergency medicine. In addition, this article discusses how results from regulatory science are used by the FDA to support the regulatory process as well as how the results are communicated to the public. Regulatory science supports the FDA's mission to assure safe, effective, and high-quality medical products are available to patients. Published by Elsevier Inc.

  18. Type I interferons have opposing effects during the emergence and recovery phases of colitis.

    Science.gov (United States)

    Rauch, Isabella; Hainzl, Eva; Rosebrock, Felix; Heider, Susanne; Schwab, Clarissa; Berry, David; Stoiber, Dagmar; Wagner, Michael; Schleper, Christa; Loy, Alexander; Urich, Tim; Müller, Mathias; Strobl, Birgit; Kenner, Lukas; Decker, Thomas

    2014-09-01

    The contribution of the innate immune system to inflammatory bowel disease (IBD) is under intensive investigation. Research in animal models has demonstrated that type I interferons (IFN-Is) protect from IBD. In contrast, studies of patients with IBD have produced conflicting results concerning the therapeutic potential of IFN-Is. Here, we present data suggesting that IFN-Is play dual roles as regulators of intestinal inflammation in dextran sodium sulfate (DSS)-treated C57BL/6 mice. Though IFN-Is reduced acute intestinal damage and the abundance of colitis-associated intestinal bacteria caused by treatment with a high dose of DSS, they also inhibited the resolution of inflammation after DSS treatment. IFN-Is played an anti-inflammatory role by suppressing the release of IL-1β from the colon MHC class II(+) cells. Consistently, IL-1 receptor blockade reduced the severity of inflammation in IFN-I receptor-deficient mice and myeloid cell-restricted ablation of the IFN-I receptor was detrimental. The proinflammatory role of IFN-Is during recovery from DSS treatment was caused by IFN-I-dependent cell apoptosis as well as an increase in chemokine production and infiltrating inflammatory monocytes and neutrophils. Thus, IFN-Is play opposing roles in specific phases of intestinal injury and inflammation, which may be important for guiding treatment strategies in patients. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Regulatory role of NKG2D+ NK cells in intestinal lamina propria by secreting double-edged Th1 cytokines in ulcerative colitis.

    Science.gov (United States)

    Wang, Fan; Peng, Pai-Lan; Lin, Xue; Chang, Ying; Liu, Jing; Zhou, Rui; Nie, Jia-Yan; Dong, Wei-Guo; Zhao, Qiu; Li, Jin

    2017-11-17

    The role of intestinal lamina propria (LP) NKG2D+ NK cells is unclear in regulating Th1/Th2 balance in ulcerative colitis (UC). In this study, we investigated the frequency of LP NKG2D+ NK cells in DSS-induced colitis model and intestinal mucosal samples of UC patients, as well as the secretion of Th1/Th2/Th17 cytokines in NK cell lines after MICA stimulation. The role of Th1 cytokines in UC was validated by bioinformatics analysis. We found that DSS-induced colitis in mice was characterized by a Th2-mediated process. In acute phrase, the frequency of LP NKG2D+ lymphocytes increased significantly and decreased in remission, while the frequency of LP NKG2D+ NK cells decreased significantly in acute phase and increased in remission. No obvious change was found in the frequency of total LP NK cells. Similarly, severe UC patients had a higher expression of mucosal NKG2D and a lower number of NKG2D+ NK cells than mild to moderate UC. In NK cell lines, the MICA stimulation could induce a predominant secretion of Th1 cytokines (TNF, IFN-γ). Furthermore, in bioinformatics analysis, mucosal Th1 cytokine of TNF, showed a double-edged role in UC when compared to the Th1-mediated disease of Crohn's colitis. In conclusion, LP NKG2D+ NK cells partially played a regulatory role in UC through secreting Th1 cytokines to regulate the Th2-predominant Th1/Th2 imbalance, despite of the concomitant pro-inflammatory effects of Th1 cytokines.

  20. The role of First Nations in oil and gas development under federal regulatory regimes: Options for change and lessons from New Zealand

    Energy Technology Data Exchange (ETDEWEB)

    Davis, T. R. [Borden, Ladner, Gervais, LLP., Ottawa, ON (Canada)

    2001-07-01

    This thesis was prepared at the University of Ottawa in partial fulfillment of the requirements for the degree of Master of Laws (LL.M.). It is included here in its entirety. It outlines the role played by First Nations under federal oil and gas regulatory regimes and makes recommendations designed to enable First Nations groups to participate in oil and gas development. A persuasive argument is made on legal and policy grounds for an active role for First Nations in oil and gas development within their traditional territories. This position is supported by a comprehensive analysis of three federal oil and gas regimes -- the Northern, Offshore and Indian Reserve regimes -- their legislative frameworks and recent developments in aboriginal jurisprudence and policy. Further support for the recommendations is adduced by comparing the Canadian situation with relevant contemporary resource management issues in New Zealand. The author recommends the immediate creation of a Consultation Model for a range of consultation processes that vary depending upon the nature of the issue. Over the longer term, development of First Nation Models is recommended. These models should be adjustable by careful monitoring of the successes and failures of First Nation oil and gas management regimes under Comprehensive Land Claim Agreements. It is suggested that internal capacity issues with respect to infrastructure and expertise must be addressed before First Nation groups can establish economically viable oil and gas models. [320 refs.].

  1. Non-coding RNAs in Mesenchymal Stem Cell-Derived Extracellular Vesicles: Deciphering Regulatory Roles in Stem Cell Potency, Inflammatory Resolve, and Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Farah Fatima

    2017-10-01

    Full Text Available Extracellular vesicles (EVs are heterogeneous populations of nano- and micro-sized vesicles secreted by various cell types. There is mounting evidence that EVs have widespread roles in transporting proteins, lipids, and nucleic acids between cells and serve as mediators of intercellular communication. EVs secreted from stem cells could function as paracrine factors, and appear to mimic and recapitulate several features of their secreting cells. EV-mediated transport of regulatory RNAs provides a novel source of trans-regulation between cells. As such, stem cells have evolved unique forms of paracrine mechanisms for recapitulating their potencies with specialized functions by transporting non-coding RNAs (ncRNAs via EVs. This includes the dissemination of stem cell-derived EV-ncRNAs and their regulatory effects elicited in differentiation, self-renewal, pluripotency, and the induction of reparative programs. Here, we summarize and discuss the therapeutic effects of mesenchymal stem cell-derived EV-ncRNAs in the induction of intrinsic regenerative programs elicited through regulating several mechanisms. Among them, most noticeable are the EV-mediated enrichment of ncRNAs at the injury sites contributing the regulation of matrix remodeling, epithelial mesenchymal transitions, and attraction of fibroblasts. Additionally, we emphasize EV-mediated transmission of anti-inflammatory RNAs from stem cells to injury site that potentially orchestrate the resolution of the inflammatory responses and immune alleviation to better facilitate healing processes. Collectively, this knowledge indicates a high value and potential of EV-mediated RNA-based therapeutic approaches in regenerative medicine.

  2. Conserved regulatory modules in the Sox9 testis-specific enhancer predict roles for SOX, TCF/LEF, Forkhead, DMRT, and GATA proteins in vertebrate sex determination.

    Science.gov (United States)

    Bagheri-Fam, Stefan; Sinclair, Andrew H; Koopman, Peter; Harley, Vincent R

    2010-03-01

    While the primary sex determining switch varies between vertebrate species, a key downstream event in testicular development, namely the male-specific up-regulation of Sox9, is conserved. To date, only two sex determining switch genes have been identified, Sry in mammals and the Dmrt1-related gene Dmy (Dmrt1bY) in the medaka fish Oryzias latipes. In mice, Sox9 expression is evidently up-regulated by SRY and maintained by SOX9 both of which directly activate the core 1.3 kb testis-specific enhancer of Sox9 (TESCO). How Sox9 expression is up-regulated and maintained in species without Sry (i.e. non-mammalian species) is not understood. In this study, we have undertaken an in-depth comparative genomics approach and show that TESCO contains an evolutionarily conserved region (ECR) of 180 bp which is present in marsupials, monotremes, birds, reptiles and amphibians. The ECR contains highly conserved modules that predict regulatory roles for SOX, TCF/LEF, Forkhead, DMRT, and GATA proteins in vertebrate sex determination/differentiation. Our data suggest that tetrapods share common aspects of Sox9 regulation in the testis, despite having different sex determining switch mechanisms. They also suggest that Sox9 autoregulation is an ancient mechanism shared by all tetrapods, raising the possibility that in mammals, SRY evolved by mimicking this regulation. The validation of ECR regulatory sequences conserved from human to frogs will provide new insights into vertebrate sex determination. Copyright 2009 Elsevier Ltd. All rights reserved.

  3. Role of AtCDC48 & the AtCDC48 Regulatory Protein Family, PUX, in Plant Cell Morphogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Bednarek, Sebastian, Y.

    2009-11-08

    The long-term objective of this work is to understand the molecular events and mechanisms involved in secretory membrane trafficking and organelle biogenesis, which are crucial for normal plant growth and development. Our studies have suggested a vital role for the cytosolic chaperone Cdc48p/p97 during cytokinesis and cell expansion which are highly dependent upon secretory membrane trafficking. Localization studies have shown that the plant Cdc48p/p97, AtCDC48, and the Arabidopsis ortholog of the ER- and Golgi-associated SNARE, syntaxin 5, (referred to as SYP31) are targeted to the division plane during cytokinesis. In addition, AtCDC48 and SYP31 were shown to interact in vitro and in vivo. To characterize further the function of AtCDC48 and SYP31 we have utilized affinity chromatography and MALDI-MS to identify several plant-specific proteins that interact with SYP31 and/or modulate the activity of AtCDC48 including two UBX (i.e. ubiquitin-like) domain containing proteins, PUX1 and PUX2 (Proteins containing UBX domain). These proteins define a plant protein family consisting of 15 uncharacterized members that we postulate interact with AtCDC48. Biochemical studies have demonstrated that PUX2 is a novel membrane adapter for AtCDC48 that mediates AtCDC48/SYP31 interaction and is likely to control AtCDC48-dependent membrane fusion. In contrast, PUX1 negatively regulates AtCDC48 by inhibiting its ATPase activity and by promoting the disassembly of the active hexamer. These findings provide the first evidence that the assembly and disassembly of the CDC48/p97complex is actually a dynamic process. This new unexpected level of regulation for CDC48/p97 was demonstrated to be critical in vivo as pux1 loss-of-function mutants grow faster than wild-type plants. These studies suggest a role for AtCDC48 in plant cell cycle progression including cytokinesis and/or cell expansion. The proposed studies are designed to: 1) characterize further the localization and function of At

  4. Final disposal of spent nuclear fuel - regulatory system and roles of different actors during the decision process

    International Nuclear Information System (INIS)

    2009-03-01

    In November 2006 Swedish Nuclear Fuels Co. applied for a license to build a plant for encapsulation of spent nuclear fuels at Oskarshamn, Sweden. The company also have plans to apply, in 2009, for a license to construct a underground repository for spent nuclear fuels. KASAM arranged a seminar in November 2006 in order to describe and discuss the licensing rules and regulations and the roles of different parties in the decision making. Another objective of the seminar was to point out possible ambiguities in this process. Another interesting question under discussion was in what ways the basic data for the decision should be produced. The seminar covered the part of the process beginning with the application for a license and ending with the government approval/rejection of the application. Most time was spent on the legal aspects of the process

  5. Final disposal of spent nuclear fuel - regulatory system and roles of different actors during the decision process

    Energy Technology Data Exchange (ETDEWEB)

    2009-03-15

    In November 2006 Swedish Nuclear Fuels Co. applied for a license to build a plant for encapsulation of spent nuclear fuels at Oskarshamn, Sweden. The company also have plans to apply, in 2009, for a license to construct a underground repository for spent nuclear fuels. KASAM arranged a seminar in November 2006 in order to describe and discuss the licensing rules and regulations and the roles of different parties in the decision making. Another objective of the seminar was to point out possible ambiguities in this process. Another interesting question under discussion was in what ways the basic data for the decision should be produced. The seminar covered the part of the process beginning with the application for a license and ending with the government approval/rejection of the application. Most time was spent on the legal aspects of the process

  6. Nicotinic Acid Adenine Dinucleotide Phosphate Plays a Critical Role in Naive and Effector Murine T Cells but Not Natural Regulatory T Cells.

    Science.gov (United States)

    Ali, Ramadan A; Camick, Christina; Wiles, Katherine; Walseth, Timothy F; Slama, James T; Bhattacharya, Sumit; Giovannucci, David R; Wall, Katherine A

    2016-02-26

    Nicotinic acid adenine dinucleotide phosphate (NAADP), the most potent Ca(2+) mobilizing second messenger discovered to date, has been implicated in Ca(2+) signaling in some lymphomas and T cell clones. In contrast, the role of NAADP in Ca(2+) signaling or the identity of the Ca(2+) stores targeted by NAADP in conventional naive T cells is less clear. In the current study, we demonstrate the importance of NAADP in the generation of Ca(2+) signals in murine naive T cells. Combining live-cell imaging methods and a pharmacological approach using the NAADP antagonist Ned-19, we addressed the involvement of NAADP in the generation of Ca(2+) signals evoked by TCR stimulation and the role of this signal in downstream physiological end points such as proliferation, cytokine production, and other responses to stimulation. We demonstrated that acidic compartments in addition to the endoplasmic reticulum were the Ca(2+) stores that were sensitive to NAADP in naive T cells. NAADP was shown to evoke functionally relevant Ca(2+) signals in both naive CD4 and naive CD8 T cells. Furthermore, we examined the role of this signal in the activation, proliferation, and secretion of effector cytokines by Th1, Th2, Th17, and CD8 effector T cells. Overall, NAADP exhibited a similar profile in mediating Ca(2+) release in effector T cells as in their counterpart naive T cells and seemed to be equally important for the function of these different subsets of effector T cells. This profile was not observed for natural T regulatory cells. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Nicotinic Acid Adenine Dinucleotide Phosphate Plays a Critical Role in Naive and Effector Murine T Cells but Not Natural Regulatory T Cells*

    Science.gov (United States)

    Ali, Ramadan A.; Camick, Christina; Wiles, Katherine; Walseth, Timothy F.; Slama, James T.; Bhattacharya, Sumit; Giovannucci, David R.; Wall, Katherine A.

    2016-01-01

    Nicotinic acid adenine dinucleotide phosphate (NAADP), the most potent Ca2+ mobilizing second messenger discovered to date, has been implicated in Ca2+ signaling in some lymphomas and T cell clones. In contrast, the role of NAADP in Ca2+ signaling or the identity of the Ca2+ stores targeted by NAADP in conventional naive T cells is less clear. In the current study, we demonstrate the importance of NAADP in the generation of Ca2+ signals in murine naive T cells. Combining live-cell imaging methods and a pharmacological approach using the NAADP antagonist Ned-19, we addressed the involvement of NAADP in the generation of Ca2+ signals evoked by TCR stimulation and the role of this signal in downstream physiological end points such as proliferation, cytokine production, and other responses to stimulation. We demonstrated that acidic compartments in addition to the endoplasmic reticulum were the Ca2+ stores that were sensitive to NAADP in naive T cells. NAADP was shown to evoke functionally relevant Ca2+ signals in both naive CD4 and naive CD8 T cells. Furthermore, we examined the role of this signal in the activation, proliferation, and secretion of effector cytokines by Th1, Th2, Th17, and CD8 effector T cells. Overall, NAADP exhibited a similar profile in mediating Ca2+ release in effector T cells as in their counterpart naive T cells and seemed to be equally important for the function of these different subsets of effector T cells. This profile was not observed for natural T regulatory cells. PMID:26728458

  8. Regulatory role of OsMADS34 in the determination of glumes fate, grain yield and quality in rice

    Directory of Open Access Journals (Sweden)

    Deyong Ren

    2016-12-01

    Full Text Available Grasses produce seeds on spikelets, a unique type of inflorescence. Despite the importance of grass crops for food, the genetic mechanisms that control spikelet development remain poorly understood. In this study, we used m34-z, a new mutant allele of the rice (Oryza sativa E-class gene OsMADS34, to examine OsMADS34 function in determining the identities of glumes (rudimentary glume and sterile lemma and grain size. In the m34-z mutant, both the rudimentary glume and sterile lemma were homeotically converted to the lemma-like organs and acquired the lemma identity, suggesting that OsMADS34 plays important roles in the development of glumes. In the m34-z mutant, most of the grains from the secondary panicle branches were decreased in size, compared with grains from wild type, but no differences were observed in the grains from the primary panicle branches. The amylose content and gel consistency, and a seed-setting rate from the secondary panicle branches were reduced in the m34-z mutant. Interesting, transcriptional activity analysis revealed that OsMADS34 protein was a transcription repressor and it may influence grain yield by suppressing the expressions of BG1, GW8, GW2 and GL7 in the m34-z mutant. These findings revealed that OsMADS34 largely affects grain yield by affecting the size of grains from the secondary branches.

  9. Roles of the adenosine receptor and CD73 in the regulatory effect of γδ T cells.

    Directory of Open Access Journals (Sweden)

    Dongchun Liang

    Full Text Available The adenosine A2A receptor (A2AR, the main functional adenosine receptor on murine T cells, plays a unique role in the attenuation of inflammation and tissue damage in vivo. Here, we showed that, of the immune cell types tested, activated γδ T cells expressed the highest levels of A2AR mRNA and that A2AR ligation inhibited αβ T cell activation, but enhanced γδ T cell activation. We also showed that the inhibitory effect of an adenosine receptor agonist on autoreactive T cells was prevented by addition of a low percentage of activated γδ T cells. Furthermore, compared to resting cells, activated γδ T cells expressed significantly lower levels of CD73, an enzyme involved in the generation of extracellular adenosine. Exogenous AMP had a significant inhibitory effect on autoreactive T cell responses, but only in the presence of CD73+ γδ T cells, and this effect was abolished by a CD73 inhibitor. Our results show that expression of increased amounts of A2AR allows γδ T cells to bind adenosine and thereby attenuate its suppressive effect, while decreased expression of CD73 results in less generation of adenosine in the inflammatory site. Together, these events allow activated γδ T cells to acquire increased proinflammatory activity, leading to augmented autoimmune responses.

  10. Opposing actions of endocannabinoids on cholangiocarcinoma growth is via the differential activation of Notch signaling

    Energy Technology Data Exchange (ETDEWEB)

    Frampton, Gabriel; Coufal, Monique [Department of Internal Medicine, Texas A and M Health Science Center College of Medicine, Temple, TX (United States); Li, Huang [Department of Internal Medicine, Texas A and M Health Science Center College of Medicine, Temple, TX (United States); Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou (China); Ramirez, Jonathan [Digestive Disease Research Center, Scott and White Hospital, Temple, TX (United States); DeMorrow, Sharon, E-mail: demorrow@medicine.tamhsc.edu [Department of Internal Medicine, Texas A and M Health Science Center College of Medicine, Temple, TX (United States); Digestive Disease Research Center, Scott and White Hospital, Temple, TX (United States)

    2010-05-15

    The endocannabinoids anandamide (AEA) and 2-arachidonylglycerol (2-AG) have opposing effects on cholangiocarcinoma growth. Implicated in cancer, Notch signaling requires the {gamma}-secretase complex for activation. The aims of this study were to determine if the opposing effects of endocannabinoids depend on the differential activation of the Notch receptors and to demonstrate that the differential activation of these receptors are due to presenilin 1 containing- and presenilin 2 containing-{gamma}-secretase complexes. Mz-ChA-1 cells were treated with AEA or 2-AG. Notch receptor expression, activation, and nuclear translocation were determined. Specific roles for Notch 1 and 2 on cannabinoid-induced effects were determined by transient transfection of Notch 1 or 2 shRNA vectors before stimulation with AEA or 2-AG. Expression of presenilin 1 and 2 was determined after AEA or 2-AG treatment, and the involvement of presenilin 1 and 2 in the cannabinoid-induced effects was demonstrated in cell lines with low presenilin 1 or 2 expression. Antiproliferative effects of AEA required increased Notch 1 mRNA, activation, and nuclear translocation, whereas the growth-promoting effects induced by 2-AG required increased Notch 2 mRNA expression, activation, and nuclear translocation. AEA increased presenilin 1 expression and recruitment into the {gamma}-secretase complex, whereas 2-AG increased expression and recruitment of presenilin 2. The development of novel therapeutic strategies aimed at modulating the endocannabinoid system or mimicking the mode of action of AEA on Notch signaling pathways would prove beneficial for cholangiocarcinoma management.

  11. Opposing actions of endocannabinoids on cholangiocarcinoma growth is via the differential activation of Notch signaling

    International Nuclear Information System (INIS)

    Frampton, Gabriel; Coufal, Monique; Li, Huang; Ramirez, Jonathan; DeMorrow, Sharon

    2010-01-01

    The endocannabinoids anandamide (AEA) and 2-arachidonylglycerol (2-AG) have opposing effects on cholangiocarcinoma growth. Implicated in cancer, Notch signaling requires the γ-secretase complex for activation. The aims of this study were to determine if the opposing effects of endocannabinoids depend on the differential activation of the Notch receptors and to demonstrate that the differential activation of these receptors are due to presenilin 1 containing- and presenilin 2 containing-γ-secretase complexes. Mz-ChA-1 cells were treated with AEA or 2-AG. Notch receptor expression, activation, and nuclear translocation were determined. Specific roles for Notch 1 and 2 on cannabinoid-induced effects were determined by transient transfection of Notch 1 or 2 shRNA vectors before stimulation with AEA or 2-AG. Expression of presenilin 1 and 2 was determined after AEA or 2-AG treatment, and the involvement of presenilin 1 and 2 in the cannabinoid-induced effects was demonstrated in cell lines with low presenilin 1 or 2 expression. Antiproliferative effects of AEA required increased Notch 1 mRNA, activation, and nuclear translocation, whereas the growth-promoting effects induced by 2-AG required increased Notch 2 mRNA expression, activation, and nuclear translocation. AEA increased presenilin 1 expression and recruitment into the γ-secretase complex, whereas 2-AG increased expression and recruitment of presenilin 2. The development of novel therapeutic strategies aimed at modulating the endocannabinoid system or mimicking the mode of action of AEA on Notch signaling pathways would prove beneficial for cholangiocarcinoma management.

  12. Studying the striving and opposing forces in newspaper journalism: the actantial model of health promotion.

    Science.gov (United States)

    Aarva, Pauliina; Tampere, Marja Pakarinen

    2006-06-01

    The cultural aspects of health promotion are important in policy development as well as in assessing effectiveness of health promotion activities. The discourses on promoting health and well-being in journalism reflect the health promotion culture in society. This article illustrates how health promotion is portrayed by 147 newspaper items from the two Finnish quality dailies during the period 2002-2004 and introduces a semiotic Actantial Model of Health Promotion (AMHP) for studying health promotion cultures. The most popular news themes on health promotion were physical and social environment, welfare services, nutrition and obesity, and mental well-being. The actants (actors, actions and abstract factor) of health promotion were identified and the AMHP with seven key actants (generator, health-object, public, tool, executor, threat and obstacle) was constructed. The model sheds light on two sides of health promotion discourses in journalism. The dominant culture of health promotion was represented by policy actions, information, education and scientific research, which were defined by health experts, decision-makers and researchers. Representations of the opposite culture--'the otherness' of health promotion included external harmful factors and unhealthy behaviours, mentalities opposed to being health-oriented, rationally uncontrolled living, disorder, disharmony and insecurity. The opposing factors were presented by people and institutions lacking the will, ability or motivation for a health-oriented life. To understand better the values of health promotion, it is necessary to assess the characteristics of the opposite side of health promotion culture, because the current dominant values can be described more clearly by the boundaries--by 'otherness'. The study argues that the AMHP can be used as a semiotic method to identify the value dimensions and the boundaries between the dominant and the opposite discourses of health promotion in various communications

  13. The regulatory mechanism of Hsp90α secretion from endothelial cells and its role in angiogenesis during wound healing

    International Nuclear Information System (INIS)

    Song, Xiaomin; Luo, Yongzhang

    2010-01-01

    Research highlights: → Growth factors such as bFGF, VEGF, PDGF and SDF-1 stimulate Hsp90α secretion from endothelial cells. → Secreted Hsp90α localizes on the leading edge of activated endothelial cells. → Secreted Hsp90α promotes angiogenesis in wound healing. -- Abstract: Heat shock protein 90α (Hsp90α) is a ubiquitously expressed molecular chaperone, which is essential for the maintenance of eukaryote homeostasis. Hsp90α can also be secreted extracellularly and is associated with several physiological and pathological processes including wound healing, cancer, infectious diseases and diabetes. Angiogenesis, defined as the sprouting of new blood vessels from pre-existing capillaries via endothelial cell proliferation and migration, commonly occurs in and contributes to the above mentioned processes. However, the secretion of Hsp90α from endothelial cells and also its function in angiogenesis are still unclear. Here we investigated the role of extracellular Hsp90α in angiogenesis using dermal endothelial cells in vitro and a wound healing model in vivo. We find that the secretion of Hsp90α but not Hsp90β is increased in activated endothelial cells with the induction of angiogenic factors and matrix proteins. Secreted Hsp90α localizes on the leading edge of endothelial cells and promotes their angiogenic activities, whereas Hsp90α neutralizing antibodies reverse the effect. Furthermore, using a mouse skin wound healing model in vivo, we demonstrate that extracellular Hsp90α localizes on blood vessels in granulation tissues of wounded skin and promotes angiogenesis during wound healing. Taken together, our study reveals that Hsp90α can be secreted by activated endothelial cells and is a positive regulator of angiogenesis, suggesting the potential application of Hsp90α as a stimulator for wound repair.

  14. The regulatory mechanism of Hsp90{alpha} secretion from endothelial cells and its role in angiogenesis during wound healing

    Energy Technology Data Exchange (ETDEWEB)

    Song, Xiaomin [National Engineering Laboratory for Anti-tumor Protein Therapeutics, Tsinghua University, Beijing 100084 (China); Beijing Key Laboratory for Protein Therapeutics, Tsinghua University, Beijing 100084 (China); Cancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing 100084 (China); Luo, Yongzhang, E-mail: yluo@tsinghua.edu.cn [National Engineering Laboratory for Anti-tumor Protein Therapeutics, Tsinghua University, Beijing 100084 (China); Beijing Key Laboratory for Protein Therapeutics, Tsinghua University, Beijing 100084 (China); Cancer Biology Laboratory, School of Life Sciences, Tsinghua University, Beijing 100084 (China)

    2010-07-16

    Research highlights: {yields} Growth factors such as bFGF, VEGF, PDGF and SDF-1 stimulate Hsp90{alpha} secretion from endothelial cells. {yields} Secreted Hsp90{alpha} localizes on the leading edge of activated endothelial cells. {yields} Secreted Hsp90{alpha} promotes angiogenesis in wound healing. -- Abstract: Heat shock protein 90{alpha} (Hsp90{alpha}) is a ubiquitously expressed molecular chaperone, which is essential for the maintenance of eukaryote homeostasis. Hsp90{alpha} can also be secreted extracellularly and is associated with several physiological and pathological processes including wound healing, cancer, infectious diseases and diabetes. Angiogenesis, defined as the sprouting of new blood vessels from pre-existing capillaries via endothelial cell proliferation and migration, commonly occurs in and contributes to the above mentioned processes. However, the secretion of Hsp90{alpha} from endothelial cells and also its function in angiogenesis are still unclear. Here we investigated the role of extracellular Hsp90{alpha} in angiogenesis using dermal endothelial cells in vitro and a wound healing model in vivo. We find that the secretion of Hsp90{alpha} but not Hsp90{beta} is increased in activated endothelial cells with the induction of angiogenic factors and matrix proteins. Secreted Hsp90{alpha} localizes on the leading edge of endothelial cells and promotes their angiogenic activities, whereas Hsp90{alpha} neutralizing antibodies reverse the effect. Furthermore, using a mouse skin wound healing model in vivo, we demonstrate that extracellular Hsp90{alpha} localizes on blood vessels in granulation tissues of wounded skin and promotes angiogenesis during wound healing. Taken together, our study reveals that Hsp90{alpha} can be secreted by activated endothelial cells and is a positive regulator of angiogenesis, suggesting the potential application of Hsp90{alpha} as a stimulator for wound repair.

  15. Perceptions of regulatory approaches

    International Nuclear Information System (INIS)

    Halin, Magnus; Leinonen, Ruusaliisa

    2012-01-01

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

  16. Regulatory role of tetR gene in a novel gene cluster of Acidovorax avenae subsp. avenae RS-1 under oxidative stress

    Directory of Open Access Journals (Sweden)

    He eLiu

    2014-10-01

    Full Text Available Acidovorax avenae subsp. avenae is the causal agent of bacterial brown stripe disease in rice. In this study, we characterized a novel horizontal transfer of a gene cluster, including tetR, on the chromosome of A. avenae subsp. avenae RS-1 by genome-wide analysis. TetR acted as a repressor in this gene cluster and the oxidative stress resistance was enhanced in tetR-deletion mutant strain. Electrophoretic mobility shift assay (EMSA demonstrated that TetR regulator bound directly to the promoter of this gene cluster. Consistently, the results of quantitative real-time PCR also showed alterations in expression of associated genes. Moreover, the proteins affected by TetR under oxidative stress were revealed by comparing proteomic profiles of wild-type and mutant strains via 1D SDS-PAGE and LC-MS/MS analyses. Taken together, our results demonstrated that tetR gene in this novel gene cluster contributed to cell survival under oxidative stress, and TetR protein played an important regulatory role in growth kinetics, biofilm-forming capability, SOD and catalase activity, and oxide detoxicating ability.

  17. Regulatory role of tetR gene in a novel gene cluster of Acidovorax avenae subsp. avenae RS-1 under oxidative stress.

    Science.gov (United States)

    Liu, He; Yang, Chun-Lan; Ge, Meng-Yu; Ibrahim, Muhammad; Li, Bin; Zhao, Wen-Jun; Chen, Gong-You; Zhu, Bo; Xie, Guan-Lin

    2014-01-01

    Acidovorax avenae subsp. avenae is the causal agent of bacterial brown stripe disease in rice. In this study, we characterized a novel horizontal transfer of a gene cluster, including tetR, on the chromosome of A. avenae subsp. avenae RS-1 by genome-wide analysis. TetR acted as a repressor in this gene cluster and the oxidative stress resistance was enhanced in tetR-deletion mutant strain. Electrophoretic mobility shift assay demonstrated that TetR regulator bound directly to the promoter of this gene cluster. Consistently, the results of quantitative real-time PCR also showed alterations in expression of associated genes. Moreover, the proteins affected by TetR under oxidative stress were revealed by comparing proteomic profiles of wild-type and mutant strains via 1D SDS-PAGE and LC-MS/MS analyses. Taken together, our results demonstrated that tetR gene in this novel gene cluster contributed to cell survival under oxidative stress, and TetR protein played an important regulatory role in growth kinetics, biofilm-forming capability, superoxide dismutase and catalase activity, and oxide detoxicating ability.

  18. The lncRNA Malat1 Is Dispensable for Mouse Development but Its Transcription Plays a cis-Regulatory Role in the Adult

    Directory of Open Access Journals (Sweden)

    Bin Zhang

    2012-07-01

    Full Text Available Genome-wide studies have identified thousands of long noncoding RNAs (lncRNAs lacking protein-coding capacity. However, most lncRNAs are expressed at a very low level, and in most cases there is no genetic evidence to support their in vivo function. Malat1 (metastasis associated lung adenocarcinoma transcript 1 is among the most abundant and highly conserved lncRNAs, and it exhibits an uncommon 3′-end processing mechanism. In addition, its specific nuclear localization, developmental regulation, and dysregulation in cancer are suggestive of it having a critical biological function. We have characterized a Malat1 loss-of-function genetic model that indicates that Malat1 is not essential for mouse pre- and postnatal development. Furthermore, depletion of Malat1 does not affect global gene expression, splicing factor level and phosphorylation status, or alternative pre-mRNA splicing. However, among a small number of genes that were dysregulated in adult Malat1 knockout mice, many were Malat1 neighboring genes, thus indicating a potential cis-regulatory role of Malat1 gene transcription.

  19. Uranium - what role

    International Nuclear Information System (INIS)

    Grey, T.; Gaul, J.; Crooks, P.; Robotham, R.

    1980-01-01

    Opposing viewpoints on the future role of uranium are presented. Topics covered include the Australian Government's uranium policy, the status of nuclear power around the world, Australia's role as a uranium exporter and problems facing the nuclear industry

  20. Homeostatic regulatory role of Pokemon in NF-κB signaling: stimulating both p65 and IκBα expression in human hepatocellular carcinoma cells.

    Science.gov (United States)

    Zhang, Nan-Nan; Sun, Qin-Sheng; Chen, Zhe; Liu, Feng; Jiang, Yu-Yang

    2013-01-01

    NF-κB consists of p50, p65 (RelA), p52, c-Rel, and RelB, and among them p65 is a representative protein to investigate the regulation and function of this signaling. NF-κB integrates inflammation and carcinogenesis and regulates the expression of a variety of genes in response to immunity, inflammation, and apoptosis. IκBα acts as an inhibitor of NF-κB through forming an inactive NF-κB/IκBα complex. Pokemon is a ubiquitous transcription factor involved in different signaling pathways, playing a pivotal role in cell proliferation, anti-apoptosis, embryonic development, and maintenance. In this study, we found that p65 and IκBα are both novel regulatory targets of Pokemon. Ectopic expression of Pokemon in immortalized liver cells HL7702 enhanced p65 and IκBα expression, whereas silencing of Pokemon in hepatocellular carcinoma cells QGY7703 reduced cellular p65 levels. ChIP assay and targeted mutagenesis revealed that Pokemon directly binds to the element of -434 to -430 bp in p65 promoter and of -453 to -448 bp in IκBα promoter and stimulates luciferase reporter gene expression. Co-transfection of Pokemon with p65 or IκBα promoter-reporter notably enhanced their promoter activity. These data suggest that Pokemon activates the expression of both p65 and IκBα by sequence-specific binding to their promoters and plays a dual role in regulating NF-κB signaling.

  1. The edentulous mandible opposing maxillary natural teeth: treatment considerations utilizing implant overdentures.

    Science.gov (United States)

    Winkler, S; Monasky, G E

    1993-01-01

    The restoration of the edentulous mandible opposing all or part of the maxillary natural dentition with implant overdentures is described. There are many situations in which the maxillary teeth opposing an edentulous mandible can and should be retained. Mandibular implant overdentures can be utilized as long as health considerations, morphologic features of the resorbed mandible, and maxillomandibular jaw relationships are satisfactory.

  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. Regulatory Governance

    DEFF Research Database (Denmark)

    Kjær, Poul F.; Vetterlein, Antje

    2018-01-01

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

  4. The role of the Staphylococcal VraTSR regulatory system on vancomycin resistance and vanA operon expression in vancomycin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Qureshi, Nadia K; Yin, Shaohui; Boyle-Vavra, Susan

    2014-01-01

    Vancomycin is often the preferred treatment for invasive methicillin-resistant Staphylococcus aureus (MRSA) infection. With the increase in incidence of MRSA infections, the use of vancomycin has increased and, as feared, isolates of vancomycin-resistant Staphylococcus aureus (VRSA) have emerged. VRSA isolates have acquired the entercoccal vanA operon contained on transposon (Tn) 1546 residing on a conjugal plasmid. VraTSR is a vancomycin and β-lactam-inducible three-component regulatory system encoded on the S. aureus chromosome that modulates the cell-wall stress response to cell-wall acting antibiotics. Mutation in vraTSR has shown to increase susceptibility to β-lactams and vancomycin in clinical VISA strains and in recombinant strain COLVA-200 which expresses a plasmid borne vanA operon. To date, the role of VraTSR in vanA operon expression in VRSA has not been demonstrated. In this study, the vraTSR operon was deleted from the first clinical VRSA strain (VRS1) by transduction with phage harvested from a USA300 vraTSR operon deletion strain. The absence of the vraTSR operon and presence of the vanA operon were confirmed in the transductant (VRS1Δvra) by PCR. Broth MIC determinations, demonstrated that the vancomycin MIC of VRS1Δvra (64 µg/ml) decreased by 16-fold compared with VRS1 (1024 µg/ml). The effect of the vraTSR operon deletion on expression of the van gene cluster (vanA, vanX and vanR) was examined by quantitative RT-PCR using relative quantification. A 2-5-fold decreased expression of the vanA operon genes occured in strain VRS1Δvra at stationary growth phase compared with the parent strain, VRS1. Both vancomycin resistance and vancomycin-induced expression of vanA and vanR were restored by complementation with a plasmid harboring the vraTSR operon. These findings demonstrate that expression in S. aureus of the horizontally acquired enterococcal vanA gene cluster is enhanced by the staphylococcal three-component cell wall stress regulatory

  5. Exploring Regulatory Mechanisms of Atrial Myocyte Hypertrophy of Mitral Regurgitation through Gene Expression Profiling Analysis: Role of NFAT in Cardiac Hypertrophy.

    Directory of Open Access Journals (Sweden)

    Tzu-Hao Chang

    Full Text Available Left atrial enlargement in mitral regurgitation (MR predicts a poor prognosis. The regulatory mechanisms of atrial myocyte hypertrophy of MR patients remain unknown.This study comprised 14 patients with MR, 7 patients with aortic valve disease (AVD, and 6 purchased samples from normal subjects (NC. We used microarrays, enrichment analysis and quantitative RT-PCR to study the gene expression profiles in the left atria. Microarray results showed that 112 genes were differentially up-regulated and 132 genes were differentially down-regulated in the left atria between MR patients and NC. Enrichment analysis of differentially expressed genes demonstrated that "NFAT in cardiac hypertrophy" pathway was not only one of the significant associated canonical pathways, but also the only one predicted with a non-zero score of 1.34 (i.e. activated through Ingenuity Pathway Analysis molecule activity predictor. Ingenuity Pathway Analysis Global Molecular Network analysis exhibited that the highest score network also showed high association with cardiac related pathways and functions. Therefore, 5 NFAT associated genes (PPP3R1, PPP3CB, CAMK1, MEF2C, PLCE1 were studies for validation. The mRNA expressions of PPP3CB and MEF2C were significantly up-regulated, and CAMK1 and PPP3R1 were significantly down-regulated in MR patients compared to NC. Moreover, MR patients had significantly increased mRNA levels of PPP3CB, MEF2C and PLCE1 compared to AVD patients. The atrial myocyte size of MR patients significantly exceeded that of the AVD patients and NC.Differentially expressed genes in the "NFAT in cardiac hypertrophy" pathway may play a critical role in the atrial myocyte hypertrophy of MR patients.

  6. Elucidation of the regulatory role of the fructose operon reveals a novel target for enhancing the NADPH supply in Corynebacterium glutamicum.

    Science.gov (United States)

    Wang, Zhihao; Chan, Siu Hung Joshua; Sudarsan, Suresh; Blank, Lars M; Jensen, Peter Ruhdal; Solem, Christian

    2016-11-01

    The performance of Corynebacterium glutamicum cell factories producing compounds which rely heavily on NADPH has been reported to depend on the sugar being metabolized. While some aspects of this phenomenon have been elucidated, there are still many unresolved questions as to how sugar metabolism is linked to redox and to the general metabolism. We here provide new insights into the regulation of the metabolism of this important platform organism by systematically characterizing mutants carrying various lesions in the fructose operon. Initially, we found that a strain where the dedicated fructose uptake system had been inactivated (KO-ptsF) was hampered in growth on sucrose minimal medium, and suppressor mutants appeared readily. Comparative genomic analysis in conjunction with enzymatic assays revealed that suppression was linked to inactivation of the pfkB gene, encoding a fructose-1-phosphate kinase. Detailed characterization of KO-ptsF, KO-pfkB and double knock-out (DKO) derivatives revealed a strong role for sugar-phosphates, especially fructose-1-phosphate (F1P), in governing sugar as well as redox metabolism due to effects on transcriptional regulation of key genes. These findings allowed us to propose a simple model explaining the correlation between sugar phosphate concentration, gene expression and ultimately the observed phenotype. To guide us in our analysis and help us identify bottlenecks in metabolism we debugged an existing genome-scale model onto which we overlaid the transcriptome data. Based on the results obtained we managed to enhance the NADPH supply and transform the wild-type strain into delivering the highest yield of lysine ever obtained on sucrose and fructose, thus providing a good example of how regulatory mechanisms can be harnessed for bioproduction. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

  7. Sequence and Expression Analysis of Interferon Regulatory Factor 10 (IRF10 in Three Diverse Teleost Fish Reveals Its Role in Antiviral Defense.

    Directory of Open Access Journals (Sweden)

    Qiaoqing Xu

    Full Text Available Interferon regulatory factor (IRF 10 was first found in birds and is present in the genome of other tetrapods (but not humans and mice, as well as in teleost fish. The functional role of IRF10 in vertebrate immunity is relatively unknown compared to IRF1-9. The target of this research was to clone and characterize the IRF10 genes in three economically important fish species that will facilitate future evaluation of this molecule in fish innate and adaptive immunity.In the present study, a single IRF10 gene was cloned in grass carp Ctenopharyngodon idella and Asian swamp eel Monopterus albus, and two, named IRF10a and IRF10b, in rainbow trout Oncorhynchus mykiss. The fish IRF10 molecules share highest identities to other vertebrate IRF10s, and have a well conserved DNA binding domain, IRF-associated domain, and an 8 exon/7 intron structure with conserved intron phase. The presence of an upstream ATG or open reading frame (ORF in the 5'-untranslated region of different fish IRF10 cDNA sequences suggests potential regulation at the translational level, and this has been verified by in vitro transcription/translation experiments of the trout IRF10a cDNA, but would still need to be validated in fish cells.Both trout IRF10 paralogues are highly expressed in thymus, blood and spleen but are relatively low in head kidney and caudal kidney. Trout IRF10b expression is significantly higher than IRF10a in integumentary tissues i.e. gills, scales, skin, intestine, adipose fin and tail fins, suggesting that IRF10b may be more important in mucosal immunity. The expression of both trout IRF10 paralogues is up-regulated by recombinant IFN-γ. The expression of the IRF10 genes is highly induced by Poly I:C in vitro and in vivo, and by viral infection, but is less responsive to peptidoglycan and bacterial infection, suggesting an important role of fish IRF10 in antiviral defense.

  8. Role of the two-component regulatory system arlRS in ica operon and aap positive but non-biofilm-forming Staphylococcus epidermidis isolates from hospitalized patients.

    Science.gov (United States)

    Wu, Yang; Liu, Jingran; Jiang, Juan; Hu, Jian; Xu, Tao; Wang, Jiaxue; Qu, Di

    2014-11-01

    The ica operon and aap gene are important factors for Staphylococcus epidermidis biofilm formation. However, we found 15 out of 101 S. epidermidis strains isolated from patients had both the ica operon and the aap gene in the genome but could not form biofilms (ica(+)aap(+)/BF(-) isolates). Compared with standard strain RP62A, the 15 ica(+)aap(+)/BF(-) isolates had similar growth curves and initial attachment abilities, but had much lower apparent transcription levels of the icaA gene and significantly less production of polysaccharide intercellular adhesion (PIA). Furthermore, the expression of accumulation-associated protein in ica(+)aap(+)/BF(-) isolates was much weaker than in RP62A. The mRNA levels of icaADBC transcription-related regulatory genes, including icaR, sarA, rsbU, srrA, arlRS and luxS, were measured in the 15 ica(+)aap(+)/BF(-) clinical isolates. The mRNA levels of arlR and rsbU in all of the ica(+)aap(+)/BF(-) isolates were lower than in RP62A at 4 h. At 10 h, 14/15 of the isolates showed lower mRNA levels of arlR and rsbU than shown by RP62A. However, expression of sarA, luxS, srrA and icaR varied in different ica(+)aap(+)/BF(-) isolates. To further investigate the role of arlRS in biofilm formation, we analyzed icaA, sarA and rsbU transcription, PIA synthesis, Aap expression and biofilm formation in an arlRS deletion mutant of S. epidermidis strain 1457 and all were much less than in the wild type strain. This is consistent with the hypothesis that ArlRS may play an important role in regulating biofilm formation by the ica(+)aap(+)/BF(-)S. epidermidis clinical isolates and operate via both ica-dependent and Aap-dependent pathways. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Developing regulatory approaches

    International Nuclear Information System (INIS)

    Axelsson, Lars

    2012-01-01

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

  10. Opposing roles for GABAA and GABAC receptors in short-term memory formation in young chicks.

    Science.gov (United States)

    Gibbs, M E; Johnston, G A R

    2005-01-01

    The inhibitory neurotransmitter GABA has both inhibitory and enhancing effects on short-term memory for a bead discrimination task in the young chick. Low doses of GABA (1-3 pmol/hemisphere) injected into the multimodal association area of the chick forebrain, inhibit strongly reinforced memory, whereas higher doses (30-100 pmol/hemisphere) enhance weakly reinforced memory. The effect of both high and low doses of GABA is clearly on short-term memory in terms of both the time of injection and in the time that the memory loss occurs. We argue on the basis of relative sensitivities to GABA and to selective GABA receptor antagonists that low doses of GABA act at GABAC receptors (EC50 approximately 1 microM) and the higher doses of GABA act via GABAA receptors (EC50 approximately 10 microM). The selective GABAA receptor antagonist bicuculline inhibited strongly reinforced memory in a dose and time dependent manner, whereas the selective GABAC receptor antagonists TPMPA and P4MPA enhanced weakly reinforced in a dose and time dependent manner. Confirmation that different levels of GABA affect different receptor subtypes was demonstrated by the shift in the GABA dose-response curves to the selective antagonists. It is clear that GABA is involved in the control of short-term memory formation and its action, enhancing or inhibiting, depends on the level of GABA released at the time of learning.

  11. Opposing roles for RhoH GTPase during T-cell migration and activation

    Science.gov (United States)

    Baker, Christina M.; Comrie, William A.; Hyun, Young-Min; Chung, Hung-Li; Fedorchuk, Christine A.; Lim, Kihong; Brakebusch, Cord; McGrath, James L.; Waugh, Richard E.; Meier-Schellersheim, Martin; Kim, Minsoo

    2012-01-01

    T cells spend the majority of their time perusing lymphoid organs in search of cognate antigen presented by antigen presenting cells (APCs) and then quickly recirculate through the bloodstream to another lymph node. Therefore, regulation of a T-cell response is dependent upon the ability of cells to arrive in the correct location following chemokine gradients (“go” signal) as well as to receive appropriate T-cell receptor (TCR) activation signals upon cognate antigen recognition (“stop” signal). However, the mechanisms by which T cells regulate these go and stop signals remain unclear. We found that overexpression of the hematopoietic-specific RhoH protein in the presence of chemokine signals resulted in decreased Rap1–GTP and LFA-1 adhesiveness to ICAM-1, thus impairing T-cell chemotaxis; while in the presence of TCR signals, there were enhanced and sustained Rap1–GTP and LFA-1 activation as well as prolonged T:APC conjugates. RT-PCR analyses of activated CD4+ T cells and live images of T-cell migration and immunological synapse (IS) formation revealed that functions of RhoH took place primarily at the levels of transcription and intracellular distribution. Thus, we conclude that RhoH expression provides a key molecular determinant that allows T cells to switch between sensing chemokine-mediated go signals and TCR-dependent stop signals. PMID:22689994

  12. The Opposing Roles of Nucleophosmin and the ARF Tumor Suppressor in Breast Cancer

    Science.gov (United States)

    2007-04-01

    3809.2006 Copyright © 2006, American Society for Microbiology . All Rights Reserved. Nucleophosmin Is Essential for Ribosomal Protein L5 Nuclear Export Yue...Gotanda, T.; Kubo, H.; Nishiyama, K.; Kawahara, M.; Nakagawa, M. Biochem. Biophys. Res. Commun., 2006, 339, 790. [71] Woods, Y.L.; Xirodimas, D.P.; Prescott

  13. Opposing roles for RhoH GTPase during T-cell migration and activation

    DEFF Research Database (Denmark)

    Baker, Christina M; Comrie, William A; Hyun, Young-Min

    2012-01-01

    T cells spend the majority of their time perusing lymphoid organs in search of cognate antigen presented by antigen presenting cells (APCs) and then quickly recirculate through the bloodstream to another lymph node. Therefore, regulation of a T-cell response is dependent upon the ability of cells...

  14. GlmS and NagB regulate amino sugar metabolism in opposing directions and affect Streptococcus mutans virulence.

    Directory of Open Access Journals (Sweden)

    Miki Kawada-Matsuo

    Full Text Available Streptococcus mutans is a cariogenic pathogen that produces an extracellular polysaccharide (glucan from dietary sugars, which allows it to establish a reproductive niche and secrete acids that degrade tooth enamel. While two enzymes (GlmS and NagB are known to be key factors affecting the entrance of amino sugars into glycolysis and cell wall synthesis in several other bacteria, their roles in S. mutans remain unclear. Therefore, we investigated the roles of GlmS and NagB in S. mutans sugar metabolism and determined whether they have an effect on virulence. NagB expression increased in the presence of GlcNAc while GlmS expression decreased, suggesting that the regulation of these enzymes, which functionally oppose one another, is dependent on the concentration of environmental GlcNAc. A glmS-inactivated mutant could not grow in the absence of GlcNAc, while nagB-inactivated mutant growth was decreased in the presence of GlcNAc. Also, nagB inactivation was found to decrease the expression of virulence factors, including cell-surface protein antigen and glucosyltransferase, and to decrease biofilm formation and saliva-induced S. mutans aggregation, while glmS inactivation had the opposite effects on virulence factor expression and bacterial aggregation. Our results suggest that GlmS and NagB function in sugar metabolism in opposing directions, increasing and decreasing S. mutans virulence, respectively.

  15. Differential effects of IL-2 and IL-21 on expansion of the CD4+ CD25+ Foxp3+ T regulatory cells with redundant roles in natural killer cell mediated antibody dependent cellular cytotoxicity in chronic lymphocytic leukemia.

    Science.gov (United States)

    Gowda, Aruna; Ramanunni, Asha; Cheney, Carolyn; Rozewski, Darlene; Kindsvogel, Wayne; Lehman, Amy; Jarjoura, David; Caligiuri, Michael; Byrd, John C; Muthusamy, Natarajan

    2010-01-01

    CD4(+) CD25(+) regulatory T cells are expanded in solid and hematological malignancies including chronic lymphocytic leukemia (CLL). Several cytokines and co-stimulatory molecules are required for generation, survival and maintenance of their suppressive effect. We and others have shown direct cytotoxic effect of the novel common gamma chain cytokine interleukin (IL)-21 on primary B cells from CLL patients. Since members of this family of cytokines are known to exhibit their effects on diverse immune cells, we have examined the effects of IL-21 on CLL patient derived regulatory T cell (Treg) induction, expansion and the inhibitory effect on natural killer cells in vitro. We demonstrate here the expression of IL-21 receptor in CD4(+)CD25(High) regulatory cells from CLL patients. In contrast to IL-2, the IL-21 cytokine failed to mediate expansion of regulatory T cells or induced expression of Foxp3 in CD4(+)CD25(Intermediate) or CD4(+)CD25(Dim/-) T cells in whole blood derived from CLL patients. Interestingly, in contrast to their differential effects on expansion of the CD4(+)CD25(+)Foxp3(+)T cells, IL-2 and IL-21 exhibited a redundant role in Treg mediated suppression of NK cell mediated antibody dependent cytotoxicity function. Given the infusion related toxicities and pro-survival effect of IL-2 in CLL, these studies provide a rationale to explore IL-21 as an alternate gamma chain cytokine in CLL therapy.

  16. Low-ω3 Fatty Acid and Soy Protein Attenuate Alcohol-Induced Fatty Liver and Injury by Regulating the Opposing Lipid Oxidation and Lipogenic Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Karina Reyes-Gordillo

    2016-01-01

    Full Text Available Chronic ethanol-induced downregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α and upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-beta (PGC1β affect hepatic lipid oxidation and lipogenesis, respectively, leading to fatty liver injury. Low-ω3 fatty acid (Low-ω3FA that primarily regulates PGC1α and soy protein (SP that seems to have its major regulatory effect on PGC1β were evaluated for their protective effects against ethanol-induced hepatosteatosis in rats fed with Lieber-deCarli control or ethanol liquid diets with high or low ω3FA fish oil and soy protein. Low-ω3FA and SP opposed the actions of chronic ethanol by reducing serum and liver lipids with concomitant decreased fatty liver. They also prevented the downregulation of hepatic Sirtuin 1 (SIRT1 and PGC1α and their target fatty acid oxidation pathway genes and attenuated the upregulation of hepatic PGC1β and sterol regulatory element-binding protein 1c (SREBP1c and their target lipogenic pathway genes via the phosphorylation of 5′ adenosine monophosphate-activated protein kinase (AMPK. Thus, these two novel modulators attenuate ethanol-induced hepatosteatosis and consequent liver injury potentially by regulating the two opposing lipid oxidation and lipogenic pathways.

  17. Regulatory Physiology

    Science.gov (United States)

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

    1999-01-01

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

  18. Regulatory Benchmarking

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    2017-01-01

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

  19. Regulatory Benchmarking

    DEFF Research Database (Denmark)

    Agrell, Per J.; Bogetoft, Peter

    2017-01-01

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

  20. Role of regulatory subunits and protein kinase inhibitor (PKI) in determining nuclear localization and activity of the catalytic subunit of protein kinase A.

    Science.gov (United States)

    Wiley, J C; Wailes, L A; Idzerda, R L; McKnight, G S

    1999-03-05

    Regulation of protein kinase A by subcellular localization may be critical to target catalytic subunits to specific substrates. We employed epitope-tagged catalytic subunit to correlate subcellular localization and gene-inducing activity in the presence of regulatory subunit or protein kinase inhibitor (PKI). Transiently expressed catalytic subunit distributed throughout the cell and induced gene expression. Co-expression of regulatory subunit or PKI blocked gene induction and prevented nuclear accumulation. A mutant PKI lacking the nuclear export signal blocked gene induction but not nuclear accumulation, demonstrating that nuclear export is not essential to inhibit gene induction. When the catalytic subunit was targeted to the nucleus with a nuclear localization signal, it was not sequestered in the cytoplasm by regulatory subunit, although its activity was completely inhibited. PKI redistributed the nuclear catalytic subunit to the cytoplasm and blocked gene induction, demonstrating that the nuclear export signal of PKI can override a strong nuclear localization signal. With increasing PKI, the export process appeared to saturate, resulting in the return of catalytic subunit to the nucleus. These results demonstrate that both the regulatory subunit and PKI are able to completely inhibit the gene-inducing activity of the catalytic subunit even when the catalytic subunit is forced to concentrate in the nuclear compartment.

  1. A Dialogic Vaccine to Bridge Opposing Cultural Viewpoints Based on Bakhtin's Views on Dialogue and Estrangement.

    Science.gov (United States)

    Tajima, Atsushi

    2017-09-01

    Today, we face global conflicts between opposing ideologies that may be described in terms of cultural viewpoints and value judgments. It is difficult for individuals to determine whether ideologies are right or wrong because each ideology has its own worldview and sense of justice. Psychologists have an urgent mission to defuse the likelihood of fatal clashes between opposing cultural perspectives (ideologies), and to propose paradigms for peaceful coexistence. This paper examines the series of papers (Oh, Integrative Psychological and Behavioral Science, 51, 2017; Sakakibara, Integrative Psychological and Behavioral Science, 51, 2017; Watanabe, Integrative Psychological & Behavioral Science, 51, 2017) contributed to this volume that investigate the effects of high school and university educational programs promoting productive dialogue aimed at bridging, or transcending, conflicting perspectives among Japanese, Chinese, and Korean students. Here, I have evaluated the capacity of these educational programs to coordinate opposing cultural ideologies using the framework of Bakhtin's theories of dialogue and estrangement. Bakhtin viewed discourse with others who had opposing viewpoints as an opportunity to learn to overcome the one-sidedness of ideology, which ensues from automatic value judgments made by each speaker according to their culture, and he affirmed the value of flexible attitudes toward opposing viewpoints. In this paper, I review Bakhtin's theories relating to communication in a context of different cultural viewpoints, assess the general values of the educational practices mentioned above, and propose new concepts for applying these methods to other educational fields in the future using Bakhtin's theoretical viewpoints.

  2. Strengthening Regulatory Competence in Pakistan

    International Nuclear Information System (INIS)

    Sadiq, M.

    2016-01-01

    Capacity building of Pakistan Nuclear Regulatory Authority is considered an essential element in pursuit of its vision to become a world class regulatory body. Since its inception in 2001, PNRA has continuously endeavoured to invest in its people, develop training infrastructure and impart sound knowledge and professional skills with the aim to improve its regulatory effectiveness. The use of nuclear and radioactive material in Pakistan has increased manifold in recent years, thus induction of more manpower was needed for regulatory oversight. PNRA adopted two pronged approach for meeting the manpower demand (a) employment of university graduates through fast track recruitment drive and (b) induction of graduates by offering fellowships for Master degree programs. Although, the newly employed staff was selected on the basis of their excellent academic qualifications in basic and applied sciences, but they required rigorous knowledge and skills in regulatory perspectives. In order to implement a structured training program, PNRA conducted Training Needs Assessment (TNA) and identified competency gaps of the regulatory staff in legal, technical, regulatory practice and behavioural domains. PNRA took several initiatives for capacity building which included establishment of a training centre for sustainability of trainings, initiation of a fellowship scheme for Master program, attachment of staff at local institutes for on-the-job training and placement at foreign regulatory bodies and organizations for technical development with the assistance of IAEA. The above strategies have been very beneficial in competence building of the PNRA staff to perform all regulatory activities indigenously for nuclear power plants, research reactors and radiation facilities. Provision of vibrant technical support to IAEA and Member States in various programs by PNRA is a landmark of these competence development efforts. This paper summarizes PNRA initiatives and the International Atomic

  3. The changing regulatory environment

    International Nuclear Information System (INIS)

    Caron, G.

    1999-01-01

    The role and value of regulation in the energy sector was discussed, demonstrating how, despite common perception, regulation is an essential part of Canada's strategy to find and develop new opportunities. The future vision of regulation for industry participants was presented with particular focus on issues related to streamlining the regulatory process. As far as pipelines are concerned, regulatory actions are necessary to facilitate capacity increases and to ensure the line's integrity, safety and environmental record. Furthermore, regulation provides economic solutions where market forces cannot provide them, as for example where business has elements of monopoly. It arbitrates interests of landowners, business, consumers, and environmental groups. It looks for ways to ensure conditions under which competition can flourish. It acts as the guardian of citizens' rights in a democratic society by providing citizens with an opportunity to be heard on the building or expansion of pipelines and associated facilities. As citizens become more and more concerned about their property and the land that surrounds them, citizen involvement in decision making about how industry activity affects their quality of life will become correspondingly more important. Regulatory agencies are committed to facilitate this engagement by flexible hearing procedures and by making use of evolving communication and information technology

  4. Regulatory aspects of radiopharmaceuticals

    International Nuclear Information System (INIS)

    Kristensen, K.

    1985-01-01

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

  5. A new method of thermal protection by opposing jet for a hypersonic aeroheating strut

    Science.gov (United States)

    Qin, Jiang; Ning, Dongpo; Feng, Yu; Zhang, Junlong; Feng, Shuo; Bao, Wen

    2017-06-01

    This paper presents the numerical investigation of thermal protection of scramjet strut by opposing jet in supersonic stream of Mach number 6 with a hydrogen fueled scramjet strut model using CFD software. Simulation results indicate that when a small amount of fuel is injected from the nose of the strut, the bow shock is pushed away from the strut, and the heat flux is reduced in the strut, especially at the leading edge. Opposing jet forms a recirculation region near the nozzle so that the strut is covered with low temperature fuel and separated from free stream. An appropriate total pressure ratio can be used to reduce not only aerodynamic heating but also the drag of strut. It is therefore concluded that thermal protection of scramjet strut by opposing jet is one of the promising ways to protect scramjet strut in high enthalpy stream.

  6. Opposing effects of 5,7-DHT infusions into the orbitofrontal cortex and amygdala on flexible responding.

    Science.gov (United States)

    Man, M S; Dalley, J W; Roberts, A C

    2010-07-01

    Central serotonin is implicated in a variety of emotional and behavioral control processes. Serotonin depletion can lead to exaggerated aversive processing and deficient response inhibition, effects that have been linked to serotonin's actions in the amygdala and orbitofrontal cortex (OFC), respectively. However, a direct comparison of serotonin manipulations within the OFC and amygdala in the same experimental context has not been undertaken. This study compared the effects of infusing the serotonin neurotoxin, 5,7-dihydroxytryptamine into the OFC and amygdala of marmosets performing an appetitive test of response inhibition. Marmosets had to learn to inhibit a prepotent response tendency to choose a box containing high-incentive food and instead choose a box containing low-incentive food, to obtain reward. OFC infusions caused long-lasting reductions in serotonin tissue levels, as revealed at postmortem, and exaggerated prepotent responses. In contrast, the significantly reduced prepotent responses following amygdala infusions occurred at a time when serotonin tissue levels had undergone considerable recovery, but there remained residual reductions in extracellular serotonin, in vivo. These opposing behavioral effects of serotonin manipulations in the same experimental context may be understood in terms of the top-down regulatory control of the amygdala by the OFC.

  7. The role of radiation regulatory agencies of the Republic of the Philippines in the education and training of workers occupationally exposed to radiation

    International Nuclear Information System (INIS)

    Perio Peralta, Agnette de

    2008-01-01

    In the Republic of the Philippines, there are two national radiation regulatory agencies. One is the Philippine Nuclear Research Institute (PNRI) which has the regulatory mandate over radioactive materials. The other one is the Bureau of Health Devices and Technology (BHDT) which has the regulatory mandate over radiation devices. Since a major requirement in regulating use of radiation sources is the appropriate qualification of the workers occupationally exposed to radiation, the paper discusses the strategies and activities of these two agencies to ensure that these workers have the necessary education and training to do their work properly. Some of these are the conduct of training courses in cooperation with the relevant professional societies, conduct of distance aided training in cooperation with the IAEA, initiation and active involvement in the establishment and continued existence of the masteral degree program in medical physics which was established with IAEA technical assistance, assistance to lawmakers in drafting pertinent legislation, and creation of joint technical working groups to ensure harmonization of standards and regulations, among others. The Philippines has adopted a national policy that users of radiation and radioactive materials have the primary responsibility for radiation safety. The PNRI and the BHDT have adopted strategies which have been very useful in the effective implementation of their regulations. (author)

  8. 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.

  9. Regulatory Expectations for Safety Culture

    International Nuclear Information System (INIS)

    Jung, Su Jin; Oh, Jang Jin; Choi, Young Sung

    2014-01-01

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

  10. POLYCYCLIC AROMATIC HYDROCARBON FORMATION IN OPPOSED FLOW DIFFUSION FLAMES OF ETHANE. (R825412)

    Science.gov (United States)

    AbstractThe effect of fuel-side carbon density on the levels of polycyclic aromatic hydrocarbon (PAH) formation in atmospheric pressure, opposed flow, ethane diffusion flames has been studied using heated micro-probe sampling and gas chromatography/mass spectrometry (...

  11. MRI of bone marrow: opposed-phase gradient-echo sequences with long repetition time

    International Nuclear Information System (INIS)

    Seiderer, M.; Staebler, A.; Wagner, H.

    1999-01-01

    Signal intensity for opposed-phase gradient-echo (GE) sequences of tissues composed of fat- and water-equivalent cells such as red bone marrow is extremely sensitive to variation of the ratio of both cell populations (fat-to-water ratio Q F/W ). Because most bone marrow pathology results in variation of Q F/W , GE sequences are characterized by high-contrast imaging of pathology. The aim of this study was to evaluate the influence of TR, TE, FA, Q F/W and histology on signal intensity. Signal intensity of opposed-phase GE sequences as a function of TR, TE, FA, and Q F/W was measured for a fat-water phantom and cadaver specimens of normal bone marrow (red and yellow) and pathological bone marrow (tumors). All specimens were correlated to histology. Opposed-phase GE imaging of red bone marrow pathology results in low-signal-intensity imaging of intact red bone marrow and high-signal-intensity positive contrast imaging of pathology associated with a change in Q F/W . In first-order approximation the signal intensity of pathology is linearly correlated to the change in Q F/W . Opposed-phase GE imaging is a sensitive imaging technique for red bone marrow pathology. Relative contrast of red bone marrow pathology is similar to fat-suppressed imaging techniques. Acquisition time is identical to T1-weighted SE sequences. (orig.)

  12. Attitudes toward hydraulic fracturing: The opposing forces of political conservatism and basic knowledge about fracking

    OpenAIRE

    Choma, BL; Hanoch, Y; Currie, S

    2016-01-01

    publisher: Elsevier articletitle: Attitudes toward hydraulic fracturing: The opposing forces of political conservatism and basic knowledge about fracking journaltitle: Global Environmental Change articlelink: http://dx.doi.org/10.1016/j.gloenvcha.2016.03.004 content_type: article copyright: © 2016 Elsevier Ltd. All rights reserved.

  13. Regulation of the expression of GARP/latent-TGF-β1 complexes on mouse T cells and their role in Regulatory T Cell and Th17 differentiation1

    OpenAIRE

    Edwards, Justin P.; Fujii, Hodaka; Zhou, Angela X.; Creemers, John; Unutmaz, Derya; Shevach, Ethan M.

    2013-01-01

    GARP/LRRC32 has previously been defined as a marker of activated human regulatory T-cells (Tregs) that is responsible for surface localization of latent TGF-β1. We find that GARP and latent TGF-β1 are also found on mouse Tregs activated via TCR stimulation, but in contrast to human Tregs, GARP is also expressed at a low level on resting Tregs. The expression of GARP can be upregulated on mouse Tregs by IL-2 or IL-4 exposure in the absence of TCR signaling. GARP is expressed at a low level on ...

  14. Steric Pressure among Membrane-Bound Polymers Opposes Lipid Phase Separation.

    Science.gov (United States)

    Imam, Zachary I; Kenyon, Laura E; Carrillo, Adelita; Espinoza, Isai; Nagib, Fatema; Stachowiak, Jeanne C

    2016-04-19

    Lipid rafts are thought to be key organizers of membrane-protein complexes in cells. Many proteins that interact with rafts have bulky polymeric components such as intrinsically disordered protein domains and polysaccharide chains. Therefore, understanding the interaction between membrane domains and membrane-bound polymers provides insights into the roles rafts play in cells. Multiple studies have demonstrated that high concentrations of membrane-bound polymeric domains create significant lateral steric pressure at membrane surfaces. Furthermore, our recent work has shown that lateral steric pressure at membrane surfaces opposes the assembly of membrane domains. Building on these findings, here we report that membrane-bound polymers are potent suppressors of membrane phase separation, which can destabilize lipid domains with substantially greater efficiency than globular domains such as membrane-bound proteins. Specifically, we created giant vesicles with a ternary lipid composition, which separated into coexisting liquid ordered and disordered phases. Lipids with saturated tails and poly(ethylene glycol) (PEG) chains conjugated to their head groups were included at increasing molar concentrations. When these lipids were sparse on the membrane surface they partitioned to the liquid ordered phase. However, as they became more concentrated, the fraction of GUVs that were phase-separated decreased dramatically, ultimately yielding a population of homogeneous membrane vesicles. Experiments and physical modeling using compositions of increasing PEG molecular weight and lipid miscibility phase transition temperature demonstrate that longer polymers are the most efficient suppressors of membrane phase separation when the energetic barrier to lipid mixing is low. In contrast, as the miscibility transition temperature increases, longer polymers are more readily driven out of domains by the increased steric pressure. Therefore, the concentration of shorter polymers required

  15. 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.

  16. The role of Personal Self-Regulation and Regulatory Teaching to predict motivational-affective variables, achievement and satisfaction: A structural model

    Directory of Open Access Journals (Sweden)

    Jesus ede la Fuente

    2015-04-01

    Full Text Available The present investigation examines how personal self-regulation (presage variable and regulatory teaching (process variable of teaching relate to learning approaches, strategies for coping with stress, and self-regulated learning (process variables of learning and, finally, how they relate to performance and satisfaction with the learning process (product variables. The objective was to clarify the associative and predictive relations between these variables, as contextualized in two different models that use the presage-process-product paradigm (the Biggs and DEDEPRO models. A total of 1101 university students participated in the study. The design was cross-sectional and retrospective with attributional (or selection variables, using correlations and structural analysis. The results provide consistent and significant empirical evidence for the relationships hypothesized, incorporating variables that are part of and influence the teaching-learning process in Higher Education. Findings confirm the importance of interactive relationships within the teaching-learning process, where personal self-regulation is assumed to take place in connection with regulatory teaching. Variables that are involved in the relationships validated here reinforce the idea that both personal factors and teaching and learning factors should be taken into consideration when dealing with a formal teaching-learning context at university.

  17. Branching of the PIF3 regulatory network in Arabidopsis: roles of PIF3-regulated MIDAs in seedling development in the dark and in response to light.

    Science.gov (United States)

    Sentandreu, Maria; Leivar, Pablo; Martín, Guiomar; Monte, Elena

    2012-04-01

    Plants need to accurately adjust their development after germination in the underground darkness to ensure survival of the seedling, both in the dark and in the light upon reaching the soil surface. Recent studies have established that the photoreceptors phytochromes and the bHLH phytochrome interacting factors PIFs regulate seedling development to adjust it to the prevailing light environment during post-germinative growth. However, complete understanding of the downstream regulatory network implementing these developmental responses is still lacking. In a recent work, published in The Plant Cell, we report a subset of PIF3-regulated genes in dark-grown seedlings that we have named MIDAs (MISREGULATED IN DARK). Analysis of their functional relevance using mutants showed that four of them present phenotypic alterations in the dark, and that each affected a particular facet of seedling development, suggesting organ-specific branching in the signal that PIF3 relays downstream. Furthermore, our results also showed an altered response to light in seedlings with an impaired PIF3/MIDA regulatory network, indicating that these factors might also be essential to initiate and optimize the developmental adjustment of the seedling to the light environment.

  18. The role of personal self-regulation and regulatory teaching to predict motivational-affective variables, achievement, and satisfaction: a structural model

    Science.gov (United States)

    De la Fuente, Jesus; Zapata, Lucía; Martínez-Vicente, Jose M.; Sander, Paul; Cardelle-Elawar, María

    2014-01-01

    The present investigation examines how personal self-regulation (presage variable) and regulatory teaching (process variable of teaching) relate to learning approaches, strategies for coping with stress, and self-regulated learning (process variables of learning) and, finally, how they relate to performance and satisfaction with the learning process (product variables). The objective was to clarify the associative and predictive relations between these variables, as contextualized in two different models that use the presage-process-product paradigm (the Biggs and DEDEPRO models). A total of 1101 university students participated in the study. The design was cross-sectional and retrospective with attributional (or selection) variables, using correlations and structural analysis. The results provide consistent and significant empirical evidence for the relationships hypothesized, incorporating variables that are part of and influence the teaching–learning process in Higher Education. Findings confirm the importance of interactive relationships within the teaching–learning process, where personal self-regulation is assumed to take place in connection with regulatory teaching. Variables that are involved in the relationships validated here reinforce the idea that both personal factors and teaching and learning factors should be taken into consideration when dealing with a formal teaching–learning context at university. PMID:25964764

  19. Inference of Low and High-Grade Glioma Gene Regulatory Networks Delineates the Role of Rnd3 in Establishing Multiple Hallmarks of Cancer.

    Directory of Open Access Journals (Sweden)

    Kim Clarke

    2015-07-01

    Full Text Available Gliomas are a highly heterogeneous group of brain tumours that are refractory to treatment, highly invasive and pro-angiogenic. Glioblastoma patients have an average survival time of less than 15 months. Understanding the molecular basis of different grades of glioma, from well differentiated, low-grade tumours to high-grade tumours, is a key step in defining new therapeutic targets. Here we use a data-driven approach to learn the structure of gene regulatory networks from observational data and use the resulting models to formulate hypothesis on the molecular determinants of glioma stage. Remarkably, integration of available knowledge with functional genomics datasets representing clinical and pre-clinical studies reveals important properties within the regulatory circuits controlling low and high-grade glioma. Our analyses first show that low and high-grade gliomas are characterised by a switch in activity of two subsets of Rho GTPases. The first one is involved in maintaining normal glial cell function, while the second is linked to the establishment of multiple hallmarks of cancer. Next, the development and application of a novel data integration methodology reveals novel functions of RND3 in controlling glioma cell migration, invasion, proliferation, angiogenesis and clinical outcome.

  20. As to achieve regulatory action, regulatory approaches

    International Nuclear Information System (INIS)

    Cid, R.; Encinas, D.

    2014-01-01

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

  1. Two group A streptococcal peptide pheromones act through opposing Rgg regulators to control biofilm development.

    Directory of Open Access Journals (Sweden)

    Jennifer C Chang

    2011-08-01

    Full Text Available Streptococcus pyogenes (Group A Streptococcus, GAS is an important human commensal that occasionally causes localized infections and less frequently causes severe invasive disease with high mortality rates. How GAS regulates expression of factors used to colonize the host and avoid immune responses remains poorly understood. Intercellular communication is an important means by which bacteria coordinate gene expression to defend against host assaults and competing bacteria, yet no conserved cell-to-cell signaling system has been elucidated in GAS. Encoded within the GAS genome are four rgg-like genes, two of which (rgg2 and rgg3 have no previously described function. We tested the hypothesis that rgg2 or rgg3 rely on extracellular peptides to control target-gene regulation. We found that Rgg2 and Rgg3 together tightly regulate two linked genes encoding new peptide pheromones. Rgg2 activates transcription of and is required for full induction of the pheromone genes, while Rgg3 plays an antagonistic role and represses pheromone expression. The active pheromone signals, termed SHP2 and SHP3, are short and hydrophobic (DI[I/L]IIVGG, and, though highly similar in sequence, their ability to disrupt Rgg3-DNA complexes were observed to be different, indicating that specificity and differential activation of promoters are characteristics of the Rgg2/3 regulatory circuit. SHP-pheromone signaling requires an intact oligopeptide permease (opp and a metalloprotease (eep, supporting the model that pro-peptides are secreted, processed to the mature form, and subsequently imported to the cytoplasm to interact directly with the Rgg receptors. At least one consequence of pheromone stimulation of the Rgg2/3 pathway is increased biogenesis of biofilms, which counteracts negative regulation of biofilms by RopB (Rgg1. These data provide the first demonstration that Rgg-dependent quorum sensing functions in GAS and substantiate the role that Rggs play as peptide

  2. The Role of Cytotoxic T-lymphocyte-associated Protein 4 (CTLA-4) Gene, Thyroid Stimulating Hormone Receptor (TSHR) Gene and Regulatory T-cells as Risk Factors for Relapse in Patients with Graves Disease.

    Science.gov (United States)

    Eliana, Fatimah; Suwondo, Pradana; Asmarinah, Asmarinah; Harahap, Alida; Djauzi, Samsuridjal; Prihartono, Joedo; Pemayun, Tjokorda Gde Dalem

    2017-07-01

    graves' disease (GD) is the most common condition of thyrotoxicosis. The management of GD is initiated with the administration of antithyroid drugs; however, it requires a long time to achieve remission. In reality more than 50% of patients who had remission may be at risk for relapse after the drug is stopped. This study aimed to evaluate the role of clinical factors such as smoking habit, degree of ophtalmopathy, degree of thyroid enlargement; genetic factors such as CTLA-4 gene on nucleotide 49 at codon 17 of exon 1, CTLA-4 gene of promotor -318, TSHR gene polymorphism rs2268458 of intron 1; and immunological factors such as regulatory T cells (Treg) and thyroid receptor antibody (TRAb); that affecting the relapse of patients with Graves' disease in Indonesia. this was a case-control study, that compared 72 subjects who had relapse and 72 subjects without relapse at 12 months after cessation of antithyroid treatment, who met the inclusion criteria. Genetic polymorphism examination was performed using PCR-RFLP. The number of regulatory T cells was counted using flow cytometry analysis and ELISA was used to measure TRAb. The logistic regression was used since the dependent variables were categorical variables. the analysis of this study demonstrated that there was a correlation between relapse of disease and family factors (p=0.008), age at diagnosis (p=0.021), 2nd degree of Graves' ophthalmopathy (p=0.001), enlarged thyroid gland, which exceeded the lateral edge of the sternocleidomastoid muscles (p=0.040), duration of remission period (p=0.029), GG genotype of CTLA-4 gene on the nucleotide 49 at codon 17 of exon 1 (p=0.016), CC genotype of TSHR gene on the rs2268458 of intron 1 (p=0.003), the number of regulatory T cells (p=0.001) and TRAb levels (p=0.002). genetic polymorphisms of CTLA-4 gene on the nucleotide 49 at codon 17 of exon 1, TSHR gene SNP rs2268458 of intron 1, number of regulatory T cells and TRAb levels play a role as risk factors for relapse in

  3. The Role of Cytotoxic T-lymphocyte-associated Protein 4 (CTLA-4 Gene, Thyroid Stimulating Hormone Receptor (TSHR Gene and Regulatory T-cells as Risk Factors for Relapse in Patients with Graves Disease

    Directory of Open Access Journals (Sweden)

    Fatimah Eliana

    2017-11-01

    Full Text Available Background: graves’ disease (GD is the most common condition of thyrotoxicosis. The management of GD is initiated with the administration of antithyroid drugs; however, it requires a long time to achieve remission. In reality more than 50% of patients who had remission may be at risk for relapse after the drug is stopped. This study aimed to evaluate the role of clinical factors such as smoking habit, degree of ophtalmopathy, degree of thyroid enlargement; genetic factors such as CTLA-4 gene on nucleotide 49 at codon 17 of exon 1, CTLA-4 gene of promotor -318, TSHR gene polymorphism rs2268458 of intron 1; and immunological factors such as regulatory T cells (Treg and thyroid receptor antibody (TRAb; that affecting the relapse of patients with Graves’ disease in Indonesia. Methods: this was a case-control study, that compared 72 subjects who had relapse and 72 subjects without relapse at 12 months after cessation of antithyroid treatment, who met the inclusion criteria. Genetic polymorphism examination was performed using PCR-RFLP. The number of regulatory T cells was counted using flow cytometry analysis and ELISA was used to measure TRAb. The logistic regression was used since the dependent variables were categorical variables. Results: the analysis of this study demonstrated that there was a correlation between relapse of disease and family factors (p=0.008, age at diagnosis (p=0.021, 2nd degree of Graves’ ophthalmopathy (p=0.001, enlarged thyroid gland, which exceeded the lateral edge of the sternocleidomastoid muscles (p=0.040, duration of remission period (p=0.029, GG genotype of CTLA-4 gene on the nucleotide 49 at codon 17 of exon 1 (p=0.016, CC genotype of TSHR gene on the rs2268458 of intron 1 (p=0.003, the number of regulatory T cells (p=0.001 and TRAb levels (p=0.002. Conclusion: genetic polymorphisms of CTLA-4 gene on the nucleotide 49 at codon 17 of exon 1, TSHR gene SNP rs2268458 of intron 1, number of regulatory T cells and

  4. Global mapping of cell type-specific open chromatin by FAIRE-seq reveals the regulatory role of the NFI family in adipocyte differentiation.

    Directory of Open Access Journals (Sweden)

    Hironori Waki

    2011-10-01

    Full Text Available Identification of regulatory elements within the genome is crucial for understanding the mechanisms that govern cell type-specific gene expression. We generated genome-wide maps of open chromatin sites in 3T3-L1 adipocytes (on day 0 and day 8 of differentiation and NIH-3T3 fibroblasts using formaldehyde-assisted isolation of regulatory elements coupled with high-throughput sequencing (FAIRE-seq. FAIRE peaks at the promoter were associated with active transcription and histone modifications of H3K4me3 and H3K27ac. Non-promoter FAIRE peaks were characterized by H3K4me1+/me3-, the signature of enhancers, and were largely located in distal regions. The non-promoter FAIRE peaks showed dynamic change during differentiation, while the promoter FAIRE peaks were relatively constant. Functionally, the adipocyte- and preadipocyte-specific non-promoter FAIRE peaks were, respectively, associated with genes up-regulated and down-regulated by differentiation. Genes highly up-regulated during differentiation were associated with multiple clustered adipocyte-specific FAIRE peaks. Among the adipocyte-specific FAIRE peaks, 45.3% and 11.7% overlapped binding sites for, respectively, PPARγ and C/EBPα, the master regulators of adipocyte differentiation. Computational motif analyses of the adipocyte-specific FAIRE peaks revealed enrichment of a binding motif for nuclear family I (NFI transcription factors. Indeed, ChIP assay showed that NFI occupy the adipocyte-specific FAIRE peaks and/or the PPARγ binding sites near PPARγ, C/EBPα, and aP2 genes. Overexpression of NFIA in 3T3-L1 cells resulted in robust induction of these genes and lipid droplet formation without differentiation stimulus. Overexpression of dominant-negative NFIA or siRNA-mediated knockdown of NFIA or NFIB significantly suppressed both induction of genes and lipid accumulation during differentiation, suggesting a physiological function of these factors in the adipogenic program. Together, our

  5. Opposing effects of cAMP and T259 phosphorylation on plasma membrane diffusion of the water channel aquaporin-5 in Madin-Darby canine kidney cells

    DEFF Research Database (Denmark)

    Koffman, Jennifer Skaarup; Christensen, Eva Arnspang; Marlar, Saw

    2015-01-01

    Aquaporin-5 (AQP5) facilitates passive water transport in glandular epithelia in response to secretory stimuli via intracellular pathways involving calcium release, cAMP and protein kinase A (PKA). In epithelial plasma membranes, AQP5 may be acutely regulated to facilitate water transport...... in the plasma membrane diffusion coefficient of AQP5. We aimed to test the short-term regulatory effects of the above pathways, by measuring lateral diffusion of AQP5 and an AQP5 phospho-mutant, T259A, using k-space Image Correlation Spectroscopy of quantum dot- and EGFP-labeled AQP5. Elevated cAMP and PKA...... inhibition significantly decreased lateral diffusion of AQP5, whereas T259A mutation showed opposing effects; slowing diffusion without stimulation and increasing diffusion to basal levels after cAMP elevation. Thus, lateral diffusion of AQP5 is significantly regulated by cAMP, PKA, and T259 phosphorylation...

  6. The role of regulatory T cells during the attenuation of graft-versus-leukemia activity following donor leukocyte infusion in mice.

    Science.gov (United States)

    Choi, Mi-Sun; Lim, Ji-Young; Cho, Byung-Sik; Kim, Yoo-Jin; Chung, Nack-Gyun; Jeong, Dae Chul; Youn, Hyewon; Lee, Chulbom; Choi, Eun Young; Min, Chang-Ki

    2011-12-01

    We investigated how the graft-versus-leukemia (GVL) effect is attenuated in the tumor microenvironment using a murine model of non-myeloablative allo-HSCT (NM-HSCT) plus delayed donor leukocyte infusion (DLI) in a haploidentical B6→F1 strain combination. In-line with aggravated leukemia growth, the proportions of effector T cells expressing IFN-γ (Teffs) in spleen were reduced and attenuated GVL activity was found to be accompanied by a rebound in CD4(+)Foxp3(+) regulatory T cells (Tregs) in tumor-draining lymph nodes and tumor tissues. DLI-derived Tregs and Teffs may be potential indicators of presence of leukemic progression after DLI in this GVL model. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. The role of research-article writing motivation and self-regulatory strategies in explaining research-article abstract writing ability.

    Science.gov (United States)

    Lin, Ming-Chia; Cheng, Yuh-Show; Lin, Sieh-Hwa; Hsieh, Pei-Jung

    2015-04-01

    The purpose of the study was to investigate the effects of research-article writing motivation and use of self-regulatory writing strategies in explaining second language (L2) research-article abstract writing ability, alongside the L2 literacy effect. Four measures were administered: a L2 literacy test, a research abstract performance assessment, and inventories of writing motivation and strategy. Participants were L2 graduate students in Taiwan (N=185; M age=25.8 yr., SD=4.5, range=22-53). Results of structural equation modeling showed a direct effect of motivation on research-article writing ability, but no direct effect of strategy or indirect effect of motivation via strategy on research-article writing ability, with L2 literacy controlled. The findings suggest research-article writing instruction should address writing motivation, besides L2 literacy.

  8. Role of calpain in eccentric contraction-induced proteolysis of Ca2+-regulatory proteins and force depression in rat fast-twitch skeletal muscle.

    Science.gov (United States)

    Kanzaki, Keita; Watanabe, Daiki; Kuratani, Mai; Yamada, Takashi; Matsunaga, Satoshi; Wada, Masanobu

    2017-02-01

    The aim of this study was to examine the in vivo effects of eccentric contraction (ECC) on calpain-dependent proteolysis of Ca 2+ -regulatory proteins and force production in fast-twitch skeletal muscles. Rat extensor digitorum longus muscles were exposed to 200 repeated ECC in situ and excised immediately [recovery 0 (REC0)] or 3 days [recovery 3 (REC3)] after cessation of ECC. Calpain inhibitor (CI)-treated rats were intraperitoneally injected with MDL-28170 before ECC and during REC3. Tetanic force was markedly reduced at REC0 and remained reduced at REC3. CI treatment ameliorated the ECC-induced force decline but only at REC3. No evidence was found for proteolysis of dihydropyridine receptor (DHPR), junctophilin (JP)1, JP2, ryanodine receptor (RyR), sarcoplasmic reticulum Ca 2+ -ATPase (SERCA)1a, or junctional face protein-45 at REC0. At REC3, ECC resulted in decreases in DHPR, JP1, JP2, RyR, and SERCA1a. CI treatment prevented the decreases in DHPR, JP1, and JP2, whereas it had little effect on RyR and SERCA1a. These findings suggest that DHPR, JP1, and JP2, but not RyR and SERCA1a, undergo calpain-dependent proteolysis in in vivo muscles subjected to ECC and that impaired function of DHPR and/or JP might cause prolonged force deficits with ECC. NEW & NOTEWORTHY Calpain-dependent proteolysis is one of the contributing factors to muscle damage that occurs with eccentric contraction (ECC). It is unclear, however, whether calpains account for proteolysis of Ca 2+ -regulatory proteins in in vivo muscles subjected to ECC. Here, we provide evidence that dihydropyridine receptor and junctophilin, but not ryanodine receptor and sarcoplasmic reticulum Ca 2+ -ATPase, undergo calpain-dependent proteolysis. Copyright © 2017 the American Physiological Society.

  9. The regulatory dynamic

    International Nuclear Information System (INIS)

    Dybwad, C.

    2001-01-01

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

  10. The Regulatory Independence of FANR

    International Nuclear Information System (INIS)

    ALNuaimi, Fatema; Choi, Kwang Shik

    2012-01-01

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

  11. The Regulatory Independence of FANR

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-05-15

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

  12. Regulatory T cell suppressive potency dictates the balance between bacterial proliferation and clearance during persistent Salmonella infection.

    Directory of Open Access Journals (Sweden)

    Tanner M Johanns

    2010-08-01

    Full Text Available The pathogenesis of persistent infection is dictated by the balance between opposing immune activation and suppression signals. Herein, virulent Salmonella was used to explore the role and potential importance of Foxp3-expressing regulatory T cells in dictating the natural progression of persistent bacterial infection. Two distinct phases of persistent Salmonella infection are identified. In the first 3-4 weeks after infection, progressively increasing bacterial burden was associated with delayed effector T cell activation. Reciprocally, at later time points after infection, reductions in bacterial burden were associated with robust effector T cell activation. Using Foxp3(GFP reporter mice for ex vivo isolation of regulatory T cells, we demonstrate that the dichotomy in infection tempo between early and late time points is directly paralleled by drastic changes in Foxp3(+ Treg suppressive potency. In complementary experiments using Foxp3(DTR mice, the significance of these shifts in Treg suppressive potency on infection outcome was verified by enumerating the relative impacts of regulatory T cell ablation on bacterial burden and effector T cell activation at early and late time points during persistent Salmonella infection. Moreover, Treg expression of CTLA-4 directly paralleled changes in suppressive potency, and the relative effects of Treg ablation could be largely recapitulated by CTLA-4 in vivo blockade. Together, these results demonstrate that dynamic regulation of Treg suppressive potency dictates the course of persistent bacterial infection.

  13. Repair of closely opposed cyclobutyl pyrimidine dimers in UV-sensitive human diploid fibroblasts

    International Nuclear Information System (INIS)

    Lam, L.H.; Reynolds, R.J.

    1986-01-01

    An enzyme-sensitive site assay has been used to examine the fate of closely opposed pyrimidine dimers in fibroblasts from individuals afflicted with various genetic disorders that confer increased cellular sensitivity to UV radiation. The disappearance of bifilar enzyme-sensitive sites was found to be normal in cells from individuals with Fanconi's anemia, Cockayne's syndrome, dyskeratosis congenita and the variant form of xeroderma pigmentosum. The rate of bifilar enzyme-sensitive site removal in XP cells assigned to complementation group C was reduced by an amount similar to that observed for the repair of isolated dimers. Our results indicate that the initiation of repair at closely opposed dimers is slow in XP-C cells but normal in all other cells examined. (Auth.)

  14. 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.

  15. Development and Experimental Investigation of a Two-Stroke Opposed-Piston Free-Piston Engine

    OpenAIRE

    Schneider, Stephan; Chiodi, Marco; Friedrich, Horst E.; Bargende, Michael

    2016-01-01

    The proposed paper deals with the development process and initial measurement results of an opposed-piston combustion engine for application in a Free-Piston Linear Generator (FPLG). The FPLG, which is being developed at the German Aerospace Center (DLR), is an innovative internal combustion engine for a fuel based electrical power supply. With its arrangement, the pistons freely oscillate between the compression chamber of the combustion unit and a gas spring with no mechanical coupling like...

  16. Research on the Common Rail Pressure Overshoot of Opposed-Piston Two-Stroke Diesel Engines

    OpenAIRE

    Yi Lu; Changlu Zhao; Zhe Zuo; Fujun Zhang; Shuanlu Zhang

    2017-01-01

    The common rail pressure has a direct influence on the working stability of Opposed-Piston Two-Stroke (OP2S) diesel engines, especially on performance indexes such as power, economy and emissions. Meanwhile, the rail pressure overshoot phenomenon occurs frequently due to the operating characteristics of OP2S diesel engines, which could lead to serious consequences. In order to solve the rail pressure overshoot problem of OP2S diesel engines, a nonlinear concerted algorithm adding a speed stat...

  17. Why do older people oppose physician-assisted dying? A qualitative study.

    Science.gov (United States)

    Malpas, Phillipa J; Wilson, Maria K R; Rae, Nicola; Johnson, Malcolm

    2014-04-01

    Physician-assisted dying at the end of life has become a significant issue of public discussion. While legally available in a number of countries and jurisdictions, it remains controversial and illegal in New Zealand. The study aimed to explore the reasons some healthy older New Zealanders oppose physician-assisted dying in order to inform current debate. Recorded interviews were transcribed and analysed by the authors after some edits had been made by respondents. In all, 11 older participants (over 65 years) who responded to advertisements placed in Grey Power magazines and a University of Auckland email list were interviewed for around 1 h and asked a number of open-ended questions. Four central themes opposing physician-assisted dying were identified from the interviews: one's personal experience with health care and dying and death, religious reasoning and beliefs, slippery slope worries and concern about potential abuses if physician-assisted dying were legalised. An important finding of the study suggests that how some older individuals think about physician-assisted dying is strongly influenced by their past experiences of dying and death. While some participants had witnessed good, well-managed dying and death experiences which confirmed for them the view that physician-assisted dying was unnecessary, those who had witnessed poor dying and death experiences opposed physician-assisted dying on the grounds that such practices could come to be abused by others.

  18. High rate reactive sputtering in an opposed cathode closed-field unbalanced magnetron sputtering system

    Science.gov (United States)

    Sproul, William D.; Rudnik, Paul J.; Graham, Michael E.; Rohde, Suzanne L.

    1990-01-01

    Attention is given to an opposed cathode sputtering system constructed with the ability to coat parts with a size up to 15 cm in diameter and 30 cm in length. Initial trials with this system revealed very low substrate bias currents. When the AlNiCo magnets in the two opposed cathodes were arranged in a mirrored configuration, the plasma density at the substrate was low, and the substrate bias current density was less than 1 mA/sq cm. If the magnets were arranged in a closed-field configuration where the field lines from one set of magnets were coupled with the other set, the substrate bias current density was as high as 5.7 mA/sq cm when NdFeB magnets were used. In the closed-field configuration, the substrate bias current density was related to the magnetic field strength between the two cathodes and to the sputtering pressure. Hard well-adhered TiN coatings were reactively sputtered in the opposed cathode system in the closed-field configuration, but the mirrored configuration produced films with poor adhesion because of etching problems and low plasma density at the substrate.

  19. Opposing Cholinergic and Serotonergic Modulation of Layer 6 in Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Daniel W. Sparks

    2018-01-01

    Full Text Available Prefrontal cortex is a hub for attention processing and receives abundant innervation from cholinergic and serotonergic afferents. A growing body of evidence suggests that acetylcholine (ACh and serotonin (5-HT have opposing influences on tasks requiring attention, but the underlying neurophysiology of their opposition is unclear. One candidate target population is medial prefrontal layer 6 pyramidal neurons, which provide feedback modulation of the thalamus, as well as feed-forward excitation of cortical interneurons. Here, we assess the response of these neurons to ACh and 5-HT using whole cell recordings in acute brain slices from mouse cortex. With application of exogenous agonists, we show that individual layer 6 pyramidal neurons are bidirectionally-modulated, with ACh and 5-HT exerting opposite effects on excitability across a number of concentrations. Next, we tested the responses of layer 6 pyramidal neurons to optogenetic release of endogenous ACh or 5-HT. These experiments were performed in brain slices from transgenic mice expressing channelrhodopsin in either ChAT-expressing cholinergic neurons or Pet1-expressing serotonergic neurons. Light-evoked endogenous neuromodulation recapitulated the effects of exogenous neurotransmitters, showing opposing modulation of layer 6 pyramidal neurons by ACh and 5-HT. Lastly, the addition of 5-HT to either endogenous or exogenous ACh significantly suppressed the excitation of pyramidal neurons in prefrontal layer 6. Taken together, this work suggests that the major corticothalamic layer of prefrontal cortex is a substrate for opposing modulatory influences on neuronal activity that could have implications for regulation of attention.

  20. Opposing Cholinergic and Serotonergic Modulation of Layer 6 in Prefrontal Cortex.

    Science.gov (United States)

    Sparks, Daniel W; Tian, Michael K; Sargin, Derya; Venkatesan, Sridevi; Intson, Katheron; Lambe, Evelyn K

    2017-01-01

    Prefrontal cortex is a hub for attention processing and receives abundant innervation from cholinergic and serotonergic afferents. A growing body of evidence suggests that acetylcholine (ACh) and serotonin (5-HT) have opposing influences on tasks requiring attention, but the underlying neurophysiology of their opposition is unclear. One candidate target population is medial prefrontal layer 6 pyramidal neurons, which provide feedback modulation of the thalamus, as well as feed-forward excitation of cortical interneurons. Here, we assess the response of these neurons to ACh and 5-HT using whole cell recordings in acute brain slices from mouse cortex. With application of exogenous agonists, we show that individual layer 6 pyramidal neurons are bidirectionally-modulated, with ACh and 5-HT exerting opposite effects on excitability across a number of concentrations. Next, we tested the responses of layer 6 pyramidal neurons to optogenetic release of endogenous ACh or 5-HT. These experiments were performed in brain slices from transgenic mice expressing channelrhodopsin in either ChAT-expressing cholinergic neurons or Pet1-expressing serotonergic neurons. Light-evoked endogenous neuromodulation recapitulated the effects of exogenous neurotransmitters, showing opposing modulation of layer 6 pyramidal neurons by ACh and 5-HT. Lastly, the addition of 5-HT to either endogenous or exogenous ACh significantly suppressed the excitation of pyramidal neurons in prefrontal layer 6. Taken together, this work suggests that the major corticothalamic layer of prefrontal cortex is a substrate for opposing modulatory influences on neuronal activity that could have implications for regulation of attention.

  1. Two different approaches for creating a prescribed opposed-flow velocity field for flame spread experiments

    Directory of Open Access Journals (Sweden)

    Carmignani Luca

    2015-01-01

    Full Text Available Opposed-flow flame spread over solid fuels is a fundamental area of research in fire science. Typically combustion wind tunnels are used to generate the opposing flow of oxidizer against which a laminar flame spread occurs along the fuel samples. The spreading flame is generally embedded in a laminar boundary layer, which interacts with the strong buoyancy-induced flow to affect the mechanism of flame spread. In this work, two different approaches for creating the opposed-flow are compared. In the first approach, a vertical combustion tunnel is used where a thin fuel sample, thin acrylic or ashless filter paper, is held vertically along the axis of the test-section with the airflow controlled by controlling the duty cycles of four fans. As the sample is ignited, a flame spreads downward in a steady manner along a developing boundary layer. In the second approach, the sample is held in a movable cart placed in an eight-meter tall vertical chamber filled with air. As the sample is ignited, the cart is moved downward (through a remote-controlled mechanism at a prescribed velocity. The results from the two approaches are compared to establish the boundary layer effect on flame spread over thin fuels.

  2. Serelaxin as a novel therapeutic opposing fibrosis and contraction in lung diseases.

    Science.gov (United States)

    Lam, Maggie; Royce, Simon G; Samuel, Chrishan S; Bourke, Jane E

    2018-07-01

    The most common therapies for asthma and other chronic lung diseases are anti-inflammatory agents and bronchodilators. While these drugs oppose disease symptoms, they do not reverse established structural changes in the airways and their therapeutic efficacy is reduced with increasing disease severity. The peptide hormone, relaxin, is a Relaxin Family Peptide Receptor 1 (RXFP1) receptor agonist with unique combined effects in the lung that differentiates it from these existing therapies. Relaxin has previously been reported to have cardioprotective effects in acute heart failure as well anti-fibrotic actions in several organs. This review focuses on recent experimental evidence of the beneficial effects of chronic relaxin treatment in animal models of airways disease demonstrating inhibition of airway hyperresponsiveness and reversal of established fibrosis, consistent with potential therapeutic benefit. Of particular interest, accumulating evidence demonstrates that relaxin can also acutely oppose contraction by reducing the release of mast cell-derived bronchoconstrictors and by directly eliciting bronchodilation. When used in combination, chronic and acute treatment with relaxin has been shown to enhance responsiveness to both glucocorticoids and β 2 -adrenoceptor agonists respectively. While the mechanisms underlying these beneficial actions remain to be fully elucidated, translation of these promising combined preclinical findings is critical in the development of relaxin as a novel alternative or adjunct therapeutic opposing multiple aspects of airway pathology in lung diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. A minimal murine Msx-1 gene promoter. Organization of its cis-regulatory motifs and their role in transcriptional activation in cells in culture and in transgenic mice.

    Science.gov (United States)

    Takahashi, T; Guron, C; Shetty, S; Matsui, H; Raghow, R

    1997-09-05

    To dissect the cis-regulatory elements of the murine Msx-1 promoter, which lacks a conventional TATA element, a putative Msx-1 promoter DNA fragment (from -1282 to +106 base pairs (bp)) or its congeners containing site-specific alterations were fused to luciferase reporter and introduced into NIH3T3 and C2C12 cells, and the expression of luciferase was assessed in transient expression assays. The functional consequences of the sequential 5' deletions of the promotor revealed that multiple positive and negative regulatory elements participate in regulating transcription of the Msx-1 gene. Surprisingly, however, the optimal expression of Msx-1 promoter in either NIH3T3 or C2C12 cells required only 165 bp of the upstream sequence to warrant detailed examination of its structure. Therefore, the functional consequences of site-specific deletions and point mutations of the cis-acting elements of the minimal Msx-1 promoter were systematically examined. Concomitantly, potential transcriptional factor(s) interacting with the cis-acting elements of the minimal promoter were also studied by gel electrophoretic mobility shift assays and DNase I footprinting. Combined analyses of the minimal promoter by DNase I footprinting, electrophoretic mobility shift assays, and super shift assays with specific antibodies revealed that 5'-flanking regions from -161 to -154 and from -26 to -13 of the Msx-1 promoter contains an authentic E box (proximal E box), capable of binding a protein immunologically related to the upstream stimulating factor 1 (USF-1) and a GC-rich sequence motif which can bind to Sp1 (proximal Sp1), respectively. Additionally, we observed that the promoter activation was seriously hampered if the proximal E box was removed or mutated, and the promoter activity was eliminated completely if the proximal Sp1 site was similarly altered. Absolute dependence of the Msx-1 minimal promoter on Sp1 could be demonstrated by transient expression assays in the Sp1-deficient

  4. Professional and Regulatory Search

    Science.gov (United States)

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

  5. Adenoviral vector-mediated GM-CSF gene transfer improves anti-mycobacterial immunity in mice - role of regulatory T cells.

    Science.gov (United States)

    Singpiel, Alena; Kramer, Julia; Maus, Regina; Stolper, Jennifer; Bittersohl, Lara Friederike; Gauldie, Jack; Kolb, Martin; Welte, Tobias; Sparwasser, Tim; Maus, Ulrich A

    2018-03-01

    Granulocyte macrophage-colony stimulating factor (GM-CSF) is a hematopoietic growth factor involved in differentiation, survival and activation of myeloid and non-myeloid cells with important implications for lung antibacterial immunity. Here we examined the effect of pulmonary adenoviral vector-mediated delivery of GM-CSF (AdGM-CSF) on anti-mycobacterial immunity in M. bovis BCG infected mice. Exposure of M. bovis BCG infected mice to AdGM-CSF either applied on 6h, or 6h and 7days post-infection substantially increased alveolar recruitment of iNOS and IL-12 expressing macrophages, and significantly increased accumulation of IFNγ pos T cells and particularly regulatory T cells (Tregs). This was accompanied by significantly reduced mycobacterial loads in the lungs of mice. Importantly, diphtheria toxin-induced depletion of Tregs did not influence mycobacterial loads, but accentuated immunopathology in AdGM-CSF-exposed mice infected with M. bovis BCG. Together, the data demonstrate that AdGM-CSF therapy improves lung protective immunity against M. bovis BCG infection in mice independent of co-recruited Tregs, which however critically contribute to limit lung immunopathology in BCG-infected mice. These data may be relevant to the development of immunomodulatory strategies to limit immunopathology-based lung injury in tuberculosis in humans. Copyright © 2017 Elsevier GmbH. All rights reserved.

  6. Identification and characterization of PhbF: a DNA binding protein with regulatory role in the PHB metabolism of Herbaspirillum seropedicae SmR1.

    Science.gov (United States)

    Kadowaki, Marco A S; Müller-Santos, Marcelo; Rego, Fabiane G M; Souza, Emanuel M; Yates, Marshall G; Monteiro, Rose A; Pedrosa, Fabio O; Chubatsu, Leda S; Steffens, Maria B R

    2011-10-14

    Herbaspirillum seropedicae SmR1 is a nitrogen fixing endophyte associated with important agricultural crops. It produces polyhydroxybutyrate (PHB) which is stored intracellularly as granules. However, PHB metabolism and regulatory control is not yet well studied in this organism. In this work we describe the characterization of the PhbF protein from H. seropedicae SmR1 which was purified and characterized after expression in E. coli. The purified PhbF protein was able to bind to eleven putative promoters of genes involved in PHB metabolism in H. seropedicae SmR1. In silico analyses indicated a probable DNA-binding sequence which was shown to be protected in DNA footprinting assays using purified PhbF. Analyses using lacZ fusions showed that PhbF can act as a repressor protein controlling the expression of PHB metabolism-related genes. Our results indicate that H. seropedicae SmR1 PhbF regulates expression of phb-related genes by acting as a transcriptional repressor. The knowledge of the PHB metabolism of this plant-associated bacterium may contribute to the understanding of the plant-colonizing process and the organism's resistance and survival in planta.

  7. Identification and characterization of PhbF: A DNA binding protein with regulatory role in the PHB metabolism of Herbaspirillum seropedicae SmR1

    Directory of Open Access Journals (Sweden)

    Pedrosa Fabio O

    2011-10-01

    Full Text Available Abstract Background Herbaspirillum seropedicae SmR1 is a nitrogen fixing endophyte associated with important agricultural crops. It produces polyhydroxybutyrate (PHB which is stored intracellularly as granules. However, PHB metabolism and regulatory control is not yet well studied in this organism. Results In this work we describe the characterization of the PhbF protein from H. seropedicae SmR1 which was purified and characterized after expression in E. coli. The purified PhbF protein was able to bind to eleven putative promoters of genes involved in PHB metabolism in H. seropedicae SmR1. In silico analyses indicated a probable DNA-binding sequence which was shown to be protected in DNA footprinting assays using purified PhbF. Analyses using lacZ fusions showed that PhbF can act as a repressor protein controlling the expression of PHB metabolism-related genes. Conclusions Our results indicate that H. seropedicae SmR1 PhbF regulates expression of phb-related genes by acting as a transcriptional repressor. The knowledge of the PHB metabolism of this plant-associated bacterium may contribute to the understanding of the plant-colonizing process and the organism's resistance and survival in planta.

  8. Re: Penetration Behavior of Opposed Rows of Staggered Secondary Air Jets Depending on Jet Penetration Coefficient and Momentum Flux Ratio

    Science.gov (United States)

    Holdeman, James D.

    2016-01-01

    The purpose of this article is to explain why the extension of the previously published C = (S/Ho)sqrt(J) scaling for opposed rows of staggered jets wasn't directly successful in the study by Choi et al. (2016). It is not surprising that staggered jets from opposite sides do not pass each other at the expected C value, because Ho/D and sqrt(J) are much larger than the maximum in previous studies. These, and large x/D's, tend to suggest development of 2-dimensional flow. Although there are distinct optima for opposed rows of in-line jets, single-side injection, and opposed rows of staggered jets based on C, opposed rows of staggered jets provide as good or better mixing performance, at any C value, than opposed rows of in-line jets or jets from single-side injection.

  9. Future nuclear regulatory challenges

    International Nuclear Information System (INIS)

    Royen, J.

    1998-01-01

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

  10. Single-base resolution maps of cultivated and wild rice methylomes and regulatory roles of DNA methylation in plant gene expression

    DEFF Research Database (Denmark)

    Li, Xin; Zhu, Jingde; Hu, Fengyi

    2012-01-01

    DNA methylation plays important biological roles in plants and animals. To examine the rice genomic methylation landscape and assess its functional significance, we generated single-base resolution DNA methylome maps for Asian cultivated rice Oryza sativa ssp. japonica, indica and their wild rela...

  11. Effects of Scavenging System Configuration on In-Cylinder Air Flow Organization of an Opposed-Piston Two-Stroke Engine

    OpenAIRE

    Fukang Ma; Changlu Zhao; Fujun Zhang; Zhenfeng Zhao; Shuanlu Zhang

    2015-01-01

    In-cylinder air flow is very important from the point of view of mixture formation and combustion. In this direction, intake chamber structure and piston crown shape play a very crucial role for in-cylinder air pattern of opposed-piston two-stroke (OP2S) engines. This study is concerned with the three-dimensional (3D) computational fluid dynamics (CFD) analysis of in-cylinder air motion coupled with the comparison of predicted results with the zero-dimensional (0D) parametric model. Three con...

  12. Regulation of the expression of GARP/latent-TGF-β1 complexes on mouse T cells and their role in Regulatory T Cell and Th17 differentiation1

    Science.gov (United States)

    Edwards, Justin P.; Fujii, Hodaka; Zhou, Angela X.; Creemers, John; Unutmaz, Derya; Shevach, Ethan M.

    2013-01-01

    GARP/LRRC32 has previously been defined as a marker of activated human regulatory T-cells (Tregs) that is responsible for surface localization of latent TGF-β1. We find that GARP and latent TGF-β1 are also found on mouse Tregs activated via TCR stimulation, but in contrast to human Tregs, GARP is also expressed at a low level on resting Tregs. The expression of GARP can be upregulated on mouse Tregs by IL-2 or IL-4 exposure in the absence of TCR signaling. GARP is expressed at a low level on Tregs within the thymus and Treg precursors from the thymus concomitantly express GARP and Foxp3 upon exposure to IL-2. The expression of GARP is independent of TGF-β1 and TGF-β1 loading into GARP and is independent of furin-mediated processing of pro-TGF-β1 to latent TGF-β1. Specific deletion of GARP in CD4+ T cells results in lack of expression of latent-TGF-β1 on activated Tregs. GARP-deficient Tregs develop normally, are present in normal numbers in peripheral tissues, and are fully competent suppressors of the activation of T conventional cells in vitro. Activated Tregs expressing GARP/latent-TGF-β1 complexes are potent inducers of Th17 differentiation in the presence of exogenous IL-6 and inducers of Treg in the presence of IL-2. Induction of both Th17 producing cells and Treg is preferentially induced by Tregs expressing the latent-TGF-β1/GARP complex on their cell surface rather than by secreted latent-TGF-β1. PMID:23645881

  13. Regulation of the expression of GARP/latent TGF-β1 complexes on mouse T cells and their role in regulatory T cell and Th17 differentiation.

    Science.gov (United States)

    Edwards, Justin P; Fujii, Hodaka; Zhou, Angela X; Creemers, John; Unutmaz, Derya; Shevach, Ethan M

    2013-06-01

    GARP/LRRC32 was defined as a marker of activated human regulatory T cells (Tregs) that is responsible for surface localization of latent TGF-β1. We find that GARP and latent TGF-β1 are also found on mouse Tregs activated via TCR stimulation; however, in contrast to human Tregs, GARP is also expressed at a low level on resting Tregs. The expression of GARP can be upregulated on mouse Tregs by IL-2 or IL-4 exposure in the absence of TCR signaling. GARP is expressed at a low level on Tregs within the thymus, and Treg precursors from the thymus concomitantly express GARP and Foxp3 upon exposure to IL-2. The expression of GARP is independent of TGF-β1 and TGF-β1 loading into GARP and is independent of furin-mediated processing of pro-TGF-β1 to latent TGF-β1. Specific deletion of GARP in CD4(+) T cells results in lack of expression of latent TGF-β1 on activated Tregs. GARP-deficient Tregs develop normally, are present in normal numbers in peripheral tissues, and are fully competent suppressors of the activation of conventional T cells in vitro. Activated Tregs expressing GARP/latent TGF-β1 complexes are potent inducers of Th17 differentiation in the presence of exogenous IL-6 and inducers of Treg in the presence of IL-2. Induction of both Th17-producing cells and Tregs is caused preferentially by Tregs expressing the latent TGF-β1/GARP complex on their cell surface rather than by secreted latent TGF-β1.

  14. The suppression of tomato defence response genes upon potato cyst nematode infection indicates a key regulatory role of miRNAs.

    Science.gov (United States)

    Święcicka, Magdalena; Skowron, Waldemar; Cieszyński, Piotr; Dąbrowska-Bronk, Joanna; Matuszkiewicz, Mateusz; Filipecki, Marcin; Koter, Marek Daniel

    2017-04-01

    Potato cyst nematode Globodera rostochiensis is an obligate parasite of solanaceous plants, triggering metabolic and morphological changes in roots which may result in substantial crop yield losses. Previously, we used the cDNA-AFLP to study the transcriptional dynamics in nematode infected tomato roots. Now, we present the rescreening of already published, upregulated transcript-derived fragment dataset using the most current tomato transcriptome sequences. Our reanalysis allowed to add 54 novel genes to 135, already found as upregulated in tomato roots upon G. rostochiensis infection (in total - 189). We also created completely new catalogue of downregulated sequences leading to the discovery of 76 novel genes. Functional classification of candidates showed that the 'wound, stress and defence response' category was enriched in the downregulated genes. We confirmed the transcriptional dynamics of six genes by qRT-PCR. To place our results in a broader context, we compared the tomato data with Arabidopsis thaliana, revealing similar proportions of upregulated and downregulated genes as well as similar enrichment of defence related transcripts in the downregulated group. Since transcript suppression is quite common in plant-nematode interactions, we assessed the possibility of miRNA-mediated inverse correlation on several tomato sequences belonging to NB-LRR and receptor-like kinase families. The qRT-PCR of miRNAs and putative target transcripts showed an opposite expression pattern in 9 cases. These results together with in silico analyses of potential miRNA targeting to the full repertoire of tomato R-genes show that miRNA mediated gene suppression may be a key regulatory mechanism during nematode parasitism. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. Promoting Implementation of Safety Culture in Nuclear Application for Industrial Facilities; an Important Role of Nuclear Energy Regulatory Agency in Indonesia

    Energy Technology Data Exchange (ETDEWEB)

    Setianingsih, Lilis Susanti [KINS-KAIST Master Degree Program, Daejeon (Korea, Republic of)

    2012-03-15

    Implementation of nuclear energy for industrial purposes has reached its highest peak. BAPETEN, as Nuclear Energy Regulatory Agency of Indonesia has published regulations regarding nuclear energy utilization. As high risk associating such utilization requires direct and thoroughly supervision in order to assure its compliance to safety and security aspect, procedures related to operational activities must by fully applied. Radiation Protection Program as one type of procedures that must be available in nuclear energy utilization operation is intended to provide operators specifically technical guidance to avoid undesired negative effects of incidents or accidents. It is the responsibility of managerial level in a company to provide the procedures and to further supervise their application in the field. Radiation workers, those are all employees working in or within radiation area must understand how to execute the procedures properly. The radiation protection program is intended to protect workers, member of community and property as well as the environment from the negative impacts of nuclear utilization operational due to its radiation exposure. Safety culture, a compound of nature derived from behavior of organization and people within the organization to pay a full attention and give main priority in radiation safety matters, is expected to be achieved by implementing the radiation protection program as safety habits at the work place. It requires a management commitment to ensure that all aspect in safety and, whenever necessary, security are accomplished within the radiation protection program in order to build a safety culture in a radiation work place. Government Regulation No. 33 2007 about Safety for Ionizing Radiation and Security for Radioactive Source and Government Regulation No. 29 2008 regarding Licensing for Utilization of Ionizing Radiation and Nuclear Material present regulation and arrangement related to radiation protection program as a basic

  16. Promoting Implementation of Safety Culture in Nuclear Application for Industrial Facilities; an Important Role of Nuclear Energy Regulatory Agency in Indonesia

    International Nuclear Information System (INIS)

    Setianingsih, Lilis Susanti

    2012-01-01

    Implementation of nuclear energy for industrial purposes has reached its highest peak. BAPETEN, as Nuclear Energy Regulatory Agency of Indonesia has published regulations regarding nuclear energy utilization. As high risk associating such utilization requires direct and thoroughly supervision in order to assure its compliance to safety and security aspect, procedures related to operational activities must by fully applied. Radiation Protection Program as one type of procedures that must be available in nuclear energy utilization operation is intended to provide operators specifically technical guidance to avoid undesired negative effects of incidents or accidents. It is the responsibility of managerial level in a company to provide the procedures and to further supervise their application in the field. Radiation workers, those are all employees working in or within radiation area must understand how to execute the procedures properly. The radiation protection program is intended to protect workers, member of community and property as well as the environment from the negative impacts of nuclear utilization operational due to its radiation exposure. Safety culture, a compound of nature derived from behavior of organization and people within the organization to pay a full attention and give main priority in radiation safety matters, is expected to be achieved by implementing the radiation protection program as safety habits at the work place. It requires a management commitment to ensure that all aspect in safety and, whenever necessary, security are accomplished within the radiation protection program in order to build a safety culture in a radiation work place. Government Regulation No. 33 2007 about Safety for Ionizing Radiation and Security for Radioactive Source and Government Regulation No. 29 2008 regarding Licensing for Utilization of Ionizing Radiation and Nuclear Material present regulation and arrangement related to radiation protection program as a basic

  17. Regulatory activities; Actividades regulatorias

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-07-01

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

  18. Patient satisfaction with maxillary 3-implant overdentures using different attachment systems opposing mandibular 2-implant overdentures.

    Science.gov (United States)

    Al-Zubeidi, Mohammed I; Alsabeeha, Nabeel H M; Thomson, W Murray; Payne, Alan G T

    2012-05-01

    Patient-based outcomes with maxillary overdentures on a minimum number of implants, opposing mandibular 2-implant overdentures are not evident in the literature. To evaluate patient's satisfaction with maxillary 3-implant overdentures, opposing mandibular 2-implant overdentures, using two different attachment systems over the first 2 years of service. Forty participants wearing mandibular 2-implant overdentures for 3 years were randomly allocated to one of two similar implant system groups to receive maxillary 3-implant overdentures. Twenty participants were allocated to splinted and unsplinted attachment system treatment groups for each system. Patient satisfaction with pre-treatment complete maxillary dentures, with maxillary 3-implant overdentures at baseline and annually for 2 years, was measured using visual analogue scale questionnaires and the oral health impact profiles. Palatal coverage of the maxillary overdentures was reduced at the first annual recall. Data showed significant improvement in pain reduction, comfort, stability, and function variables of the visual analogue scale after treatment. Analysis by prosthodontic design using visual analogue scale showed no significant difference. The total oral health impact profile-14 scores after treatment for all participants, regardless of prosthodontic design, were significantly lower (more satisfied). The overall oral health impact profile-20E score at baseline was significantly higher (more satisfied) compared with pre-treatment conventional maxillary dentures. No significant changes were observed in the first or second years compared with baseline results. Twenty-two participants (84.6%) preferred reduced palatal coverage, regardless of prosthodontic design, after 1 year. Twenty participants (76.9%) still preferred reduced palatal coverage at the end of the second year. The provision of maxillary 3-implant overdentures to oppose mandibular 2-implant overdentures significantly improve levels of patient

  19. Charging process analysis of an opposed-piston two-stroke aircraft Diesel engine

    Directory of Open Access Journals (Sweden)

    Grabowski Łukasz

    2017-01-01

    Full Text Available This paper presents the research results on a 1D model of an opposed-piston two-stroke aircraft Diesel engine. The research aimed at creating a model of the engine in question to investigate how engine performance is affected by the compressor gear ratio. The power was constant at all the operating points. The research results are presented as graphs of power consumed by the compressor, compressor efficiency and brake specific fuel consumption. The optimal range of compressor gear ratio in terms of engine efficiency was defined from the research results.

  20. Heat transfer and fluid flow in regular rod arrays with opposing flow

    International Nuclear Information System (INIS)

    Yang, J.W.

    1979-01-01

    The heat transfer and fluid flow problem of opposing flow in the fully developed laminar region has been solved analytically for regular rod arrays. The problem is governed by two parameters: the pitch-to-diameter ratio and the Grashof-to-Reynolds number ratio. The critical Gr/Re ratios for flow separation caused by the upward buoyancy force on the downward flow were evaluated for a large range of P/D ratios of the triangular array. Numerical results reveal that both the heat transfer and pressure loss are reduced by the buoyancy force. Applications to nuclear reactors are discussed

  1. Ontario regulatory update

    International Nuclear Information System (INIS)

    Thompson, P.

    1998-01-01

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

  2. The role of dietary sodium intake on the modulation of T helper 17 cells and regulatory T cells in patients with rheumatoid arthritis and systemic lupus erythematosus

    Science.gov (United States)

    Massaro, Laura; Barbati, Cristiana; Vomero, Marta; Ceccarelli, Fulvia; Spinelli, Francesca Romana; Riccieri, Valeria; Spagnoli, Alessandra; Alessandri, Cristiano; Desideri, Giovambattista; Conti, Fabrizio

    2017-01-01

    We aimed at investigating whether the frequency and function of T helper 17 (Th17) and regulatory T cells (Treg) are affected by a restriction of dietary sodium intake in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We enrolled RA and SLE patients not receiving drugs known to increase urinary sodium excretion. Patients underwent a dietary regimen starting with a restricted daily sodium intake followed by a normal-sodium daily intake. The timepoints were identified at baseline (T0), after 3 weeks of low-sodium dietary regimen (T3), after 2 weeks of normal-sodium dietary regimen (T5). On these visits, we measured the 24-hour urinary sodium excretion, the frequency and function of Th17 and Treg cells in the peripheral blood, the serum levels of cytokines. Analysis of urinary sodium excretion confirmed adherence to the dietary regimen. In RA patients, a trend toward a reduction in the frequencies of Th17 cells over the low-sodium dietary regimen followed by an increase at T5 was observed, while Treg cells exhibited the opposite trend. SLE patients showed a progressive reduction in the percentage of Th17 cells that reached a significance at T5 compared to T0 (p = 0.01) and an increase in the percentage of Treg cells following the low-sodium dietary regimen at both T1 and T3 compared to T0 (p = 0.04 and p = 0.02, respectively). No significant apoptosis or proliferation modulation was found. In RA patients, we found a reduction at T5 compared to T0 in serum levels of both TGFβ (p = 0.0016) and IL-9 (p = 0.0007); serum IL-9 levels were also reduced in SLE patients at T5 with respect to T0 (p = 0.03). This is the first study investigating the effects of dietary sodium intake on adaptive immunity. Based on the results, we hypothesize that a restricted sodium dietary intake may dampen the inflammatory response in RA and SLE patients. PMID:28877244

  3. Regulatory governance of telecommunications liberalisation in Taiwan

    International Nuclear Information System (INIS)

    Cheng, Kuo-Tai; Hebenton, Bill

    2008-01-01

    This paper examines the changing role of government and market in regulating the telecommunications sector from since 1996 in Taiwan. It contextualises the theoretical aspects of regulatory governance for institutional design and practices, and reviews the concepts and mechanisms for appraising privatisation and regulatory systems. Using a conceptual framework for researching privatisation and regulation, it describes the process and issues pertinent to telecommunications liberalisation and privatisation in Taiwan, supported by a brief presentation of theoretical points of view as well as practitioners' views. The paper presents results concerning criteria for appraising privatisation and regulatory governance and considers policy lessons that can be learned from the experiences of the Taiwanese telecommunications sector's liberalisation. (author)

  4. Nuclear Regulatory Commission: more aggressive leadership needed

    International Nuclear Information System (INIS)

    Staats, E.B.

    1980-01-01

    The Energy Reorganization Act of 1974 which established the Nuclear Regulatory Commission required GAO to evaluate the Commission's performance by January 18, 1980. This report responds to that requirement. GAO concluded that, although improvements have been made, the Commission's nuclear regulatory performance can be characterized best as slow, indecisive, cautious - in a word, complacent. This has largely resulted from a lack of aggressive leadership as evidenced by the Commissioners' failure to establish regulatory goals, control policymaking, and most importantly, clearly define their roles in nuclear regulation

  5. Functional and topological characteristics of mammalian regulatory domains

    Science.gov (United States)

    Symmons, Orsolya; Uslu, Veli Vural; Tsujimura, Taro; Ruf, Sandra; Nassari, Sonya; Schwarzer, Wibke; Ettwiller, Laurence; Spitz, François

    2014-01-01

    Long-range regulatory interactions play an important role in shaping gene-expression programs. However, the genomic features that organize these activities are still poorly characterized. We conducted a large operational analysis to chart the distribution of gene regulatory activities along the mouse genome, using hundreds of insertions of a regulatory sensor. We found that enhancers distribute their activities along broad regions and not in a gene-centric manner, defining large regulatory domains. Remarkably, these domains correlate strongly with the recently described TADs, which partition the genome into distinct self-interacting blocks. Different features, including specific repeats and CTCF-binding sites, correlate with the transition zones separating regulatory domains, and may help to further organize promiscuously distributed regulatory influences within large domains. These findings support a model of genomic organization where TADs confine regulatory activities to specific but large regulatory domains, contributing to the establishment of specific gene expression profiles. PMID:24398455

  6. Top-level regulatory criteria for the standard MHTGR

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1986-10-15

    The Licensing Plan for the Standard MHTGR (Ref. 1) describes a program to support a U.S. Nuclear Regulatory Commission (NRC) design review and approval. The Plan calls for the submittal of Top-Level Regulatory Criteria to the NRC for concurrence with their completeness and acceptability for the MHTGR program. The Top-Level Regulatory Criteria are defined as the standards for judging licensability that directly specify acceptable limits for protection of the public health and safety and the environment. The criteria proposed herein are for normal plant operation and a broad spectrum of anticipated events, including accidents. The approach taken is to define a set of criteria which are general as opposed to being design specific. Specifically, it is recommended that criteria be met which: 1. Are less prescriptive than current regulation, thereby encouraging maximum flexibility in design approaches. 2. Are measurable. 3. Are not more strict than the criteria for current power plants.

  7. Molecular characterization of EcCIPK24 gene of finger millet (Eleusine coracana) for investigating its regulatory role in calcium transport.

    Science.gov (United States)

    Chinchole, Mahadev; Pathak, Rajesh Kumar; Singh, Uma M; Kumar, Anil

    2017-08-01

    Finger millet grains contain exceptionally high levels of calcium which is much higher compared to other cereals and millets. Since calcium is an important macronutrient in human diet, it is necessary to explore the molecular basis of calcium accumulation in the seeds of finger millet. CIPK is a calcium sensor gene, having role in activating Ca 2+ exchanger protein by interaction with CBL proteins. To know the role of EcCIPK24 gene in seed Ca 2+ accumulation, sequence is retrieved from the transcriptome data of two finger millet genotypes GP1 (low Ca 2+ ) and GP45 (high Ca 2+ ), and the expression was determined through qRT-PCR. The higher expression was found in root, shoot, leaf and developing spike tissue of GP45 compared to GP1; structural analysis showed difference of nine SNPs and one extra beta sheet domain as well as differences in vacuolar localization was predicted; besides, the variation in amino acid composition among both the genotypes was also investigated. Molecular modeling and docking studies revealed that both EcCBL4 and EcCBL10 showed strong binding affinity with EcCIPK24 (GP1) compared to EcCIPK24 (GP45). It indicates a genotypic structural variation, which not only affects the affinity but also calcium transport efficiency after interaction of CIPK-CBL with calcium exchanger ( Ec CAX1b) to pull calcium in the vacuole. Based on the expression and in silico study, it can be suggested that by activating EcCAX1b protein, EcCIPK24 plays an important role in high seed Ca 2+ accumulation.

  8. Zooming in on regulatory intermediaries: The impact of non-state regulators on sustainable construction practice

    NARCIS (Netherlands)

    van der Heijden, J.

    2014-01-01

    Levi-Faur and Starobin (2013) have recently drawn our attention to the important role of regulatory intermediates in contemporary regulatory regimes. Among others they argue that regulatory intermediaries come in a wide variety of appearances, and that these can influence the outcomes of regulatory

  9. Coin Tossing Explains the Activity of Opposing Microtubule Motors on Phagosomes.

    Science.gov (United States)

    Sanghavi, Paulomi; D'Souza, Ashwin; Rai, Ashim; Rai, Arpan; Padinhatheeri, Ranjith; Mallik, Roop

    2018-05-07

    How the opposing activity of kinesin and dynein motors generates polarized distribution of organelles inside cells is poorly understood and hotly debated [1, 2]. Possible explanations include stochastic mechanical competition [3, 4], coordinated regulation by motor-associated proteins [5-7], mechanical activation of motors [8], and lipid-induced organization [9]. Here, we address this question by using phagocytosed latex beads to generate early phagosomes (EPs) that move bidirectionally along microtubules (MTs) in an in vitro assay [9]. Dynein/kinesin activity on individual EPs is recorded as real-time force generation of the motors against an optical trap. Activity of one class of motors frequently coincides with, or is rapidly followed by opposite motors. This leads to frequent and rapid reversals of EPs in the trap. Remarkably, the choice between dynein and kinesin can be explained by the tossing of a coin. Opposing motors therefore appear to function stochastically and independently of each other, as also confirmed by observing no effect on kinesin function when dynein is inhibited on the EPs. A simple binomial probability calculation based on the geometry of EP-microtubule contact explains the observed activity of dynein and kinesin on phagosomes. This understanding of intracellular transport in terms of a hypothetical coin, if it holds true for other cargoes, provides a conceptual framework to explain the polarized localization of organelles inside cells. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  10. Assessment of RANS and LES Turbulence Modeling for Buoyancy-Aided/Opposed Forced and Mixed Convection

    Science.gov (United States)

    Clifford, Corey; Kimber, Mark

    2017-11-01

    Over the last 30 years, an industry-wide shift within the nuclear community has led to increased utilization of computational fluid dynamics (CFD) to supplement nuclear reactor safety analyses. One such area that is of particular interest to the nuclear community, specifically to those performing loss-of-flow accident (LOFA) analyses for next-generation very-high temperature reactors (VHTR), is the capacity of current computational models to predict heat transfer across a wide range of buoyancy conditions. In the present investigation, a critical evaluation of Reynolds-averaged Navier-Stokes (RANS) and large-eddy simulation (LES) turbulence modeling techniques is conducted based on CFD validation data collected from the Rotatable Buoyancy Tunnel (RoBuT) at Utah State University. Four different experimental flow conditions are investigated: (1) buoyancy-aided forced convection; (2) buoyancy-opposed forced convection; (3) buoyancy-aided mixed convection; (4) buoyancy-opposed mixed convection. Overall, good agreement is found for both forced convection-dominated scenarios, but an overly-diffusive prediction of the normal Reynolds stress is observed for the RANS-based turbulence models. Low-Reynolds number RANS models perform adequately for mixed convection, while higher-order RANS approaches underestimate the influence of buoyancy on the production of turbulence.

  11. Finite element analysis and clinical complications in mandibular implant-overdentures opposing maxillary dentures.

    Science.gov (United States)

    Khuder, Tameem; Yunus, Norsiah; Sulaiman, Eshamsul; Dabbagh, Ali

    2017-11-01

    Denture fracture is a common clinical complication caused by improper material selection, design, or fabrication technique. This study aimed to investigate the effect of two attachment systems on fracture risk of the implant-overdentures (IOD) via finite element analysis (FEA), using the force distributions obtained from patients' occlusal analyses and to compare the obtained results with the clinical complications associated with these attachments. A three-dimensional jaw model comprised of the edentulous bones was constructed. Three types of mandibular prostheses including complete denture (CD) (model LCD), IOD with Locator attachment (model LID-L), and IOD with telescopic attachment (model LID-T), as well as a maxillary CD (model UCD) were assembled. The vertical occlusal forces at anterior and posterior quadrants were obtained from the patients wearing mandibular CDs or IODs. The FEA results were further compared with the mechanical failures of different prostheses observed at patient recalls. In overall, the fracture risk of mandibular prostheses was lower than the maxillary compartments. The UCD opposing LCD underwent higher strains than that opposing LID-L and LID-T, which was mostly concentrated at the anterior mid-palatal polished surface. On the other hand, LID-L showed the lowest strain, followed by LID-T, and LCD. The obtained results were consistent with the clinical complications observed in the patient recalls. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Wear characteristics of polished and glazed lithium disilicate ceramics opposed to three ceramic materials.

    Science.gov (United States)

    Saiki, Osamu; Koizumi, Hiroyasu; Akazawa, Nobutaka; Kodaira, Akihisa; Okamura, Kentaro; Matsumura, Hideo

    2016-01-01

    This study compared the wear characteristics of a heat-pressed lithium disilicate ceramic material opposed to feldspathic porcelain, a lithium disilicate glass ceramic, and zirconia materials. Ceramic plate specimens were prepared from feldspathic porcelain (EX-3 nA1B), lithium disilicate glass ceramics (e.max CAD MO1/C14), and zirconia (Katana KT 10) and then ground or polished. Rounded rod specimens were fabricated from heat-pressed lithium disilicate glass ceramic (e.max press LT A3) and then glazed or polished. A sliding wear testing apparatus was used for wear testing. Wear of glazed rods was greater than that of polished rods when they were abraded with ground zirconia, ground porcelain, polished porcelain, or polished lithium disilicate ceramics. For both glazed and polished rods, wear was greater when the rods were abraded with ground plates. The findings indicate that application of a polished surface rather than a glazed surface is recommended for single restorations made of heat-pressed lithium disilicate material. In addition, care must be taken when polishing opposing materials, especially those used in occlusal contact areas. (J Oral Sci 58, 117-123, 2016).

  13. Experimental studies on possible regulatory role of nitric oxide on the differential effects of chronic predictable and unpredictable stress on adaptive immune responses.

    Science.gov (United States)

    Thakur, Tarun; Gulati, Kavita; Rai, Nishant; Ray, Arunabha

    2017-09-01

    The present study was designed to investigate the effects of chronic predictable stress (CPS) and chronic unpredictable stress (CUS) on immunological responses in KLH-sensitized rats and involvement of NOergic signaling pathways mediating such responses. Male Wistar rats (200-250g) were exposed to either CPS or CUS for 14days and IgG antibody levels and delayed type hypersensitivity (DTH) response was determined to assess changes in adaptive immunity. To evaluate the role of nitric oxide during such immunomodulation, biochemical estimation of stable metabolite of nitric oxide (NOx) and 3-nitrotyrosine (3-NT, a marker of peroxynitrite formation) were done in both blood and brain. Chronic stress exposure resulted in suppression of IgG and DTH response and elevated NOx and 3-NT levels, with a difference in magnitude of response in CPS vs CUS. Pretreatment with aminoguanidine (iNOS inhibitor) caused further reduction of adaptive immune responses and attenuated the increased NOx and 3-NT levels in CPS or CUS exposed rats. On the other hand 7-NI (nNOS inhibitor) did not significantly affect these estimated parameters. The results suggest involvement of iNOS and lesser/no role of nNOS during modulation of adaptive immunity to stress. Thus, the result showed that predictability of stressors results in differential degree of modulation of immune responses and complex NO-mediated signaling mechanisms may be involved during responses. Copyright © 2017. Published by Elsevier B.V.

  14. Regulatory control of nuclear power plants

    International Nuclear Information System (INIS)

    2002-01-01

    The purpose of this book is to support IAEA training courses and workshops in the field of regulatory control of nuclear power plants as well as to support the regulatory bodies of Member States in their own training activities. The target group is the professional staff members of nuclear safety regulatory bodies supervising nuclear power plants and having duties and responsibilities in the following regulatory fields: regulatory framework; regulatory organization; regulatory guidance; licensing and licensing documents; assessment of safety; and regulatory inspection and enforcement. Important topics such as regulatory competence and quality of regulatory work as well as emergency preparedness and public communication are also covered. The book also presents the key issues of nuclear safety such as 'defence-in-depth' and safety culture and explains how these should be taken into account in regulatory work, e.g. during safety assessment and regulatory inspection. The book also reflects how nuclear safety has been developed during the years on the basis of operating experience feedback and results of safety research by giving topical examples. The examples cover development of operating procedures and accident management to cope with complicated incidents and severe accidents to stress the importance of regulatory role in nuclear safety research. The main target group is new staff members of regulatory bodies, but the book also offers good examples for more experienced inspectors to be used as comparison and discussion basis in internal workshops organized by the regulatory bodies for refreshing and continuing training. The book was originally compiled on the basis of presentations provided during the two regulatory control training courses in 1997 and 1998. The textbook was reviewed at the beginning of the years 2000 and 2002 by IAEA staff members and consistency with the latest revisions of safety standards have been ensured. The textbook was completed in the

  15. Elucidation of the regulatory role of the fructose operon reveals a novel target for enhancing the NADPH supply in Corynebacterium glutamicum

    DEFF Research Database (Denmark)

    Wang, Zhihao; Chan, Siu Hung Joshua; Sudarsan, Suresh

    2016-01-01

    is linked to redox and to the general metabolism. We here provide new insights into the regulation of the metabolism of this important platform organism by systematically characterizing mutants carrying various lesions in the fructose operon. Initially, we found that a strain where the dedicated fructose...... uptake system had been inactivated (KO-ptsF) was hampered in growth on sucrose minimal medium, and suppressor mutants appeared readily. Comparative genomic analysis in conjunction with enzymatic assays revealed that suppression was linked to inactivation of the pfkB gene, encoding a fructose-1-phosphate...... kinase. Detailed characterization of KO-ptsF, KO-pfkB and double knock-out (DKO) derivatives revealed a strong role for sugar-phosphates, especially fructose-1-phosphate (F1P), in governing sugar as well as redox metabolism due to effects on transcriptional regulation of key genes. These findings allowed...

  16. The inhibition of the mitochondrial F1FO-ATPase activity when activated by Ca2+ opens new regulatory roles for NAD.

    Science.gov (United States)

    Nesci, Salvatore; Trombetti, Fabiana; Ventrella, Vittoria; Pirini, Maurizio; Pagliarani, Alessandra

    2018-01-26

    The mitochondrial F1FO-ATPase is uncompetitively inhibited by NAD+ only when the natural cofactor Mg2+ is replaced by Ca2+, a mode putatively involved in cell death. The Ca2+-dependent F1FO-ATPase is also inhibited when NAD+ concentration in mitochondria is raised by acetoacetate. The enzyme inhibition by NAD+ cannot be ascribed to any de-ac(et)ylation or ADP-ribosylation by sirtuines, as it is not reversed by nicotinamide. Moreover, the addition of acetyl-CoA or palmitate, which would favor the enzyme ac(et)ylation, does not affect the F1FO-ATPase activity. Consistently, NAD+ may play a new role, not associated with redox and non-redox enzymatic reactions, in the Ca2+-dependent regulation of the F1FO-ATPase activity.

  17. Handling of timescales in safety assessments of geological disposal: an IRSN-GRS standpoint on the possible role of regulatory guidance

    International Nuclear Information System (INIS)

    Gay, D.; Rohlig, K.J.

    2002-01-01

    Due to the physical process of radioactive decay, the question of time is an inherent factor of any activity associated with nuclear materials. Hence time has naturally played a role in the definition of radioactive waste management strategies. This has eventually led to differences with other types of hazardous waste and notably to an earlier consideration of potential impacts in the long-term. Time has therefore been early accounted for in the basic objectives of radioactive waste management. These objectives explicitly require the protection of human beings and of the environment now and in the future. In other words this implies the need to adequately manage the waste for 'as long as it contains dangerous amounts of toxic substance', or, in the case of radioactive waste, 'until sufficient decay has occurred'. (authors)

  18. Physiological and Proteomic Analysis of the Rice Mutant cpm2 Suggests a Negative Regulatory Role of Jasmonic Acid in Drought Tolerance

    Directory of Open Access Journals (Sweden)

    Rohit Dhakarey

    2017-11-01

    Full Text Available It is widely known that numerous adaptive responses of drought-stressed plants are stimulated by chemical messengers known as phytohormones. Jasmonic acid (JA is one such phytohormone. But there are very few reports revealing its direct implication in drought related responses or its cross-talk with other phytohormones. In this study, we compared the morpho-physiological traits and the root proteome of a wild type (WT rice plant with its JA biosynthesis mutant coleoptile photomorphogenesis 2 (cpm2, disrupted in the allene oxide cyclase (AOC gene, for insights into the role of JA under drought. The mutant had higher stomatal conductance, higher water use efficiency and higher shoot ABA levels under severe drought as compared to the WT. Notably, roots of cpm2 were better developed compared to the WT under both, control and drought stress conditions. Root proteome was analyzed using the Tandem Mass Tag strategy to better understand this difference at the molecular level. Expectedly, AOC was unique but notably highly abundant under drought in the WT. Identification of other differentially abundant proteins (DAPs suggested increased energy metabolism (i.e., increased mobilization of resources and reactive oxygen species scavenging in cpm2 under drought. Additionally, various proteins involved in secondary metabolism, cell growth and cell wall synthesis were also more abundant in cpm2 roots. Proteome-guided transcript, metabolite, and histological analyses provided further insights into the favorable adaptations and responses, most likely orchestrated by the lack of JA, in the cpm2 roots. Our results in cpm2 are discussed in the light of JA crosstalk to other phytohormones. These results together pave the path for understanding the precise role of JA during drought stress in rice.

  19. RNA Sequencing and Bioinformatics Analysis Implicate the Regulatory Role of a Long Noncoding RNA-mRNA Network in Hepatic Stellate Cell Activation.

    Science.gov (United States)

    Guo, Can-Jie; Xiao, Xiao; Sheng, Li; Chen, Lili; Zhong, Wei; Li, Hai; Hua, Jing; Ma, Xiong

    2017-01-01

    To analyze the long noncoding (lncRNA)-mRNA expression network and potential roles in rat hepatic stellate cells (HSCs) during activation. LncRNA expression was analyzed in quiescent and culture-activated HSCs by RNA sequencing, and differentially expressed lncRNAs verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR) were subjected to bioinformatics analysis. In vivo analyses of differential lncRNA-mRNA expression were performed on a rat model of liver fibrosis. We identified upregulation of 12 lncRNAs and 155 mRNAs and downregulation of 12 lncRNAs and 374 mRNAs in activated HSCs. Additionally, we identified the differential expression of upregulated lncRNAs (NONRATT012636.2, NONRATT016788.2, and NONRATT021402.2) and downregulated lncRNAs (NONRATT007863.2, NONRATT019720.2, and NONRATT024061.2) in activated HSCs relative to levels observed in quiescent HSCs, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that changes in lncRNAs associated with HSC activation revealed 11 significantly enriched pathways according to their predicted targets. Moreover, based on the predicted co-expression network, the relative dynamic levels of NONRATT013819.2 and lysyl oxidase (Lox) were compared during HSC activation both in vitro and in vivo. Our results confirmed the upregulation of lncRNA NONRATT013819.2 and Lox mRNA associated with the extracellular matrix (ECM)-related signaling pathway in HSCs and fibrotic livers. Our results detailing a dysregulated lncRNA-mRNA network might provide new treatment strategies for hepatic fibrosis based on findings indicating potentially critical roles for NONRATT013819.2 and Lox in ECM remodeling during HSC activation. © 2017 The Author(s). Published by S. Karger AG, Basel.

  20. The transcription factor Ste12 mediates the regulatory role of the Tmk1 MAP kinase in mycoparasitism and vegetative hyphal fusion in the filamentous fungus Trichoderma atroviride.

    Directory of Open Access Journals (Sweden)

    Sabine Gruber

    Full Text Available Mycoparasitic species of the fungal genus Trichoderma are potent antagonists able to combat plant pathogenic fungi by direct parasitism. An essential step in this mycoparasitic fungus-fungus interaction is the detection of the fungal host followed by activation of molecular weapons in the mycoparasite by host-derived signals. The Trichoderma atroviride MAP kinase Tmk1, a homolog of yeast Fus3/Kss1, plays an essential role in regulating the mycoparasitic host attack, aerial hyphae formation and conidiation. However, the transcription factors acting downstream of Tmk1 are hitherto unknown. Here we analyzed the functions of the T. atroviride Ste12 transcription factor whose orthologue in yeast is targeted by the Fus3 and Kss1 MAP kinases. Deletion of the ste12 gene in T. atroviride not only resulted in reduced mycoparasitic overgrowth and lysis of host fungi but also led to loss of hyphal avoidance in the colony periphery and a severe reduction in conidial anastomosis tube formation and vegetative hyphal fusion events. The transcription of several orthologues of Neurospora crassa hyphal fusion genes was reduced upon ste12 deletion; however, the Δste12 mutant showed enhanced expression of mycoparasitism-relevant chitinolytic and proteolytic enzymes and of the cell wall integrity MAP kinase Tmk2. Based on the comparative analyses of Δste12 and Δtmk1 mutants, an essential role of the Ste12 transcriptional regulator in mediating outcomes of the Tmk1 MAPK pathway such as regulation of the mycoparasitic activity, hyphal fusion and carbon source-dependent vegetative growth is suggested. Aerial hyphae formation and conidiation, in contrast, were found to be independent of Ste12.

  1. An Experimental Investigation on the Combustion and Heat Release Characteristics of an Opposed-Piston Folded-Cranktrain Diesel Engine

    Directory of Open Access Journals (Sweden)

    Fukang Ma

    2015-06-01

    Full Text Available In opposed-piston folded-cranktrain diesel engines, the relative movement rules of opposed-pistons, combustion chamber components and injector position are different from those of conventional diesel engines. The combustion and heat release characteristics of an opposed-piston folded-cranktrain diesel engine under different operating conditions were investigated. Four phases: ignition delay, premixed combustion, diffusion combustion and after combustion are used to describe the heat release process of the engine. Load changing has a small effect on premixed combustion duration while it influences diffusion combustion duration significantly. The heat release process has more significant isochoric and isobaric combustion which differs from the conventional diesel engine situation, except at high exhaust pressure and temperature, due to its two-stroke and uniflow scavenging characteristics. Meanwhile, a relatively high-quality exhaust heat energy is produced in opposed-piston folded-cranktrain diesel engines.

  2. Research and regulatory review

    International Nuclear Information System (INIS)

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

    1979-01-01

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

  3. Regulatory Commission of Alaska

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2015-04-01

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

  5. Major regulatory factors in the evolution of development: the roles of goosecoid and Msx in the evolution of the direct-developing sea urchin Heliocidaris erythrogramma.

    Science.gov (United States)

    Wilson, Keen A; Andrews, Mary E; Rudolf Turner, F; Raff, Rudolf A

    2005-01-01

    The transcription factors Gsc and Msx are expressed in the oral ectoderm of the indirect-developing sea urchin Heliocidaris tuberculata. Their patterns of expression are highly modified in the direct developer Heliocidaris erythrogramma, which lacks an oral ectoderm. We here test the hypothesis that they are large effect genes responsible for the loss of the oral ectoderm module in the direct-developing larva of H. erythrogramma as well as for the restoration of an overt oral ectoderm in H.e. xH.t. hybrids. We undertook misexpression/overexpression and knockdown assays in the two species and in hybrids by mRNA injection. The results indicate that dramatic changes of function of these transcription factors has occurred. One of these genes, Gsc, has the ability when misexpressed to partially restore oral ectoderm in H. erythrogramma. On the other hand, Msx has lost any oral function and instead has a role in mesoderm proliferation and patterning. In addition, we found that the H. tuberculataGsc is up regulated in H.e. xH.t. hybrids, showing a preferential use of the indirect developing parental gene in the development of the hybrid. We suggest that Gsc qualifies as a gene of large evolutionary effect and is partially responsible for the evolution of direct development of H. erythrogramma. We discuss these results in light of modularity and genetic networks in development, as well as in their implications for the rapid evolution of large morphological changes in development.

  6. Single-base resolution maps of cultivated and wild rice methylomes and regulatory roles of DNA methylation in plant gene expression

    Directory of Open Access Journals (Sweden)

    Li Xin

    2012-07-01

    Full Text Available Abstract Background DNA methylation plays important biological roles in plants and animals. To examine the rice genomic methylation landscape and assess its functional significance, we generated single-base resolution DNA methylome maps for Asian cultivated rice Oryza sativa ssp. japonica, indica and their wild relatives, Oryza rufipogon and Oryza nivara. Results The overall methylation level of rice genomes is four times higher than that of Arabidopsis. Consistent with the results reported for Arabidopsis, methylation in promoters represses gene expression while gene-body methylation generally appears to be positively associated with gene expression. Interestingly, we discovered that methylation in gene transcriptional termination regions (TTRs can significantly repress gene expression, and the effect is even stronger than that of promoter methylation. Through integrated analysis of genomic, DNA methylomic and transcriptomic differences between cultivated and wild rice, we found that primary DNA sequence divergence is the major determinant of methylational differences at the whole genome level, but DNA methylational difference alone can only account for limited gene expression variation between the cultivated and wild rice. Furthermore, we identified a number of genes with significant difference in methylation level between the wild and cultivated rice. Conclusions The single-base resolution methylomes of rice obtained in this study have not only broadened our understanding of the mechanism and function of DNA methylation in plant genomes, but also provided valuable data for future studies of rice epigenetics and the epigenetic differentiation between wild and cultivated rice.

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

    Science.gov (United States)

    Kubis, Adriana Maria; Piwowar, Agnieszka

    2015-11-01

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

  8. Novel positive regulatory role for the SPL6 transcription factor in the N TIR-NB-LRR receptor-mediated plant innate immunity.

    Directory of Open Access Journals (Sweden)

    Meenu S Padmanabhan

    2013-03-01

    Full Text Available Following the recognition of pathogen-encoded effectors, plant TIR-NB-LRR immune receptors induce defense signaling by a largely unknown mechanism. We identify a novel and conserved role for the SQUAMOSA PROMOTER BINDING PROTEIN (SBP-domain transcription factor SPL6 in enabling the activation of the defense transcriptome following its association with a nuclear-localized immune receptor. During an active immune response, the Nicotiana TIR-NB-LRR N immune receptor associates with NbSPL6 within distinct nuclear compartments. NbSPL6 is essential for the N-mediated resistance to Tobacco mosaic virus. Similarly, the presumed Arabidopsis ortholog AtSPL6 is required for the resistance mediated by the TIR-NB-LRR RPS4 against Pseudomonas syringae carrying the avrRps4 effector. Transcriptome analysis indicates that AtSPL6 positively regulates a subset of defense genes. A pathogen-activated nuclear-localized TIR-NB-LRR like N can therefore regulate defense genes through SPL6 in a mechanism analogous to the induction of MHC genes by mammalian immune receptors like CIITA and NLRC5.

  9. Regulatory risk coherence

    International Nuclear Information System (INIS)

    Remick, F.J.

    1992-01-01

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

  10. Reconsidering examining cannabis subtypes together due to opposing effects on brain, cognition and behavior

    DEFF Research Database (Denmark)

    Thomsen, Kristine Rømer; Callesen, Mette Buhl; Ewing, Sarah W. Feeldstein

    Cannabis use represents a major public health issue throughout the globe. Yet, we still lack the most fundamental of knowledge on long-term effects of cannabis on neural, cognitive, and behavioral function. Part of this stems from how cannabis has been measured. To this end, most empirical...... examinations of cannabis have historically consolidated all types of cannabis collectively. However, this approach misses a fundamental fact about how different cannabinoids operate. Here we address the contrasting properties of tetrahydrocannabinol (THC) and cannabidiol (CBD) and their opposing effects...... on a wide array of health function. In addition, we address the increase in cannabis potency throughout the past two decades and how that impacts generalizability of early data on current public health. We put forth the urgent need for future research to disaggregate examination of THC from CBD, along...

  11. Opposing Subjective Temporal Experiences in Response to Unpredictable and Predictable Fear-Relevant Stimuli

    Directory of Open Access Journals (Sweden)

    Qian Cui

    2018-03-01

    Full Text Available Previous studies have found that the durations of fear-relevant stimuli were overestimated compared to those of neutral stimuli, even when the fear-relevant stimuli were only anticipated. The current study aimed to investigate the effect of the predictability of fear-relevant stimuli on sub-second temporal estimations. In Experiments 1a and 1b, a randomized design was employed to render the emotional valence of each trial unpredictable. In Experiments 2a and 2b, we incorporated a block design and a cueing paradigm, respectively, to render the emotional stimuli predictable. Compared with the neutral condition, the estimated blank interval was judged as being shorter under the unpredictable fear-relevant condition, while it was judged as being longer under the predictable fear-relevant condition. In other words, the unpredictable and predictable fear-relevant stimuli led to opposing temporal distortions. These results demonstrated that emotions modulate interval perception during different time processing stages.

  12. Competing initiatives: a new tobacco industry strategy to oppose statewide clean indoor air ballot measures.

    Science.gov (United States)

    Tung, Gregory J; Hendlin, Yogi H; Glantz, Stanton A

    2009-03-01

    To describe how the tobacco and gaming industries opposed clean indoor air voter initiatives in 2006, we analyzed media records and government and other publicly available documents and conducted interviews with knowledgeable individuals. In an attempt to avoid strict "smoke free" regulations pursued by health groups via voter initiatives in Arizona, Ohio, and Nevada, in 2006, the tobacco and gaming industries sponsored competing voter initiatives for alternative laws. Health groups succeeded in defeating the pro-tobacco competing initiatives because they were able to dispel confusion and create a head-to-head competition by associating each campaign with its respective backer and instructing voters to vote "no" on the pro-tobacco initiative in addition to voting "yes" on the health group initiative.

  13. Levitation Performance of Two Opposed Permanent Magnet Pole-Pair Separated Conical Bearingless Motors

    Science.gov (United States)

    Kascak, Peter; Jansen, Ralph; Dever, Timothy; Nagorny, Aleksandr; Loparo, Kenneth

    2013-01-01

    In standard motor applications, rotor suspension with traditional mechanical bearings represents the most economical solution. However, in certain high performance applications, rotor suspension without contacting bearings is either required or highly beneficial. Examples include applications requiring very high speed or extreme environment operation, or with limited access for maintenance. This paper expands upon a novel bearingless motor concept, in which two motors with opposing conical air-gaps are used to achieve full five-axis levitation and rotation of the rotor. Force in this motor is created by deliberately leaving the motor s pole-pairs unconnected, which allows the creation of different d-axis flux in each pole pair. This flux imbalance is used to create lateral force. This approach is different than previous bearingless motor designs, which require separate windings for levitation and rotation. This paper examines the predicted and achieved suspension performance of a fully levitated prototype bearingless system.

  14. Bacterial lipoprotein delays apoptosis in human neutrophils through inhibition of caspase-3 activity: regulatory roles for CD14 and TLR-2.

    LENUS (Irish Health Repository)

    Power, Colm P

    2012-02-03

    The human sepsis syndrome resulting from bacterial infection continues to account for a significant proportion of hospital mortality. Neutralizing strategies aimed at individual bacterial wall products (such as LPS) have enjoyed limited success in this arena. Bacterial lipoprotein (BLP) is a major constituent of the wall of diverse bacterial forms and profoundly influences cellular function in vivo and in vitro, and has been implicated in the etiology of human sepsis. Delayed polymorphonuclear cell (PMN) apoptosis is a characteristic feature of human sepsis arising from Gram-negative or Gram-positive bacterial infection. Bacterial wall product ligation and subsequent receptor-mediated events upstream of caspase inhibition in neutrophils remain incompletely understood. BLP has been shown to exert its cellular effects primarily through TLR-2, and it is now widely accepted that lateral associations with the TLRs represent the means by which CD14 communicates intracellular messages. In this study, we demonstrate that BLP inhibits neutrophil mitochondrial membrane depolarization with a subsequent reduction in caspase-3 processing, ultimately leading to a significant delay in PMN apoptosis. Pretreatment of PMNs with an anti-TLR-2 mAb or anti-CD14 mAb prevented BLP from delaying PMN apoptosis to such a marked degree. Combination blockade using both mAbs completely prevented the effects of BLP (in 1 and 10 ng\\/ml concentrations) on PMN apoptosis. At higher concentrations of BLP, the antiapoptotic effects were observed, but were not as pronounced. Our findings therefore provide the first evidence of a crucial role for both CD14 and TLR-2 in delayed PMN apoptosis arising from bacterial infection.

  15. Maize and Arabidopsis ARGOS Proteins Interact with Ethylene Receptor Signaling Complex, Supporting a Regulatory Role for ARGOS in Ethylene Signal Transduction[OPEN

    Science.gov (United States)

    Shi, Jinrui; Wang, Hongyu; Habben, Jeffrey E.

    2016-01-01

    The phytohormone ethylene regulates plant growth and development as well as plant response to environmental cues. ARGOS genes reduce plant sensitivity to ethylene when overexpressed in transgenic Arabidopsis (Arabidopsis thaliana) and maize (Zea mays). A previous genetic study suggested that the endoplasmic reticulum and Golgi-localized maize ARGOS1 targets the ethylene signal transduction components at or upstream of CONSTITUTIVE TRIPLE RESPONSE1, but the mechanism of ARGOS modulating ethylene signaling is unknown. Here, we demonstrate in Arabidopsis that ZmARGOS1, as well as the Arabidopsis ARGOS homolog ORGAN SIZE RELATED1, physically interacts with Arabidopsis REVERSION-TO-ETHYLENE SENSITIVITY1 (RTE1), an ethylene receptor interacting protein that regulates the activity of ETHYLENE RESPONSE1. The protein-protein interaction was also detected with the yeast split-ubiquitin two-hybrid system. Using the same yeast assay, we found that maize RTE1 homolog REVERSION-TO-ETHYLENE SENSITIVITY1 LIKE4 (ZmRTL4) and ZmRTL2 also interact with maize and Arabidopsis ARGOS proteins. Like AtRTE1 in Arabidopsis, ZmRTL4 and ZmRTL2 reduce ethylene responses when overexpressed in maize, indicating a similar mechanism for ARGOS regulating ethylene signaling in maize. A polypeptide fragment derived from ZmARGOS8, consisting of a Pro-rich motif flanked by two transmembrane helices that are conserved among members of the ARGOS family, can interact with AtRTE1 and maize RTL proteins in Arabidopsis. The conserved domain is necessary and sufficient to reduce ethylene sensitivity in Arabidopsis and maize. Overall, these results suggest a physical association between ARGOS and the ethylene receptor signaling complex via AtRTE1 and maize RTL proteins, supporting a role for ARGOS in regulating ethylene perception and the early steps of signal transduction in Arabidopsis and maize. PMID:27268962

  16. Regulatory role of tumor necrosis factor receptor-associated factor 6 in breast cancer by activating the protein kinase B/glycogen synthase kinase 3β signaling pathway.

    Science.gov (United States)

    Shen, Hongyu; Li, Liangpeng; Yang, Sujin; Wang, Dandan; Zhou, Siying; Chen, Xiu; Tang, Jinhai

    2017-08-01

    Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an endogenous adaptor of innate and adaptive immune responses, and serves a crucial role in tumor necrosis factor receptor and toll‑like/interleukin‑1 receptor signaling. Although studies have demonstrated that TRAF6 has oncogenic activity, its potential contributions to breast cancer in human remains largely uninvestigated. The present study examined the expression levels and function of TRAF6 in breast carcinoma (n=32) and adjacent healthy (n=25) tissue samples. Compared with adjacent healthy tissues, TRAF6 protein expression levels were significantly upregulated in breast cancer tissues. Reverse transcription‑quantitative polymerase chain reaction analysis revealed a significant upregulation of the cellular proliferative marker Ki‑67 and proliferation cell nuclear antigen expression levels in breast carcinoma specimens. Furthermore, protein expression levels of the accessory molecule, transforming growth factor β‑activated kinase 1 (TAK1), were significantly increased in breast cancer patients, as detected by western blot analysis. As determined by MTT assay, TRAF6 exerted profoundly proliferative effects in the MCF‑7 breast cancer cell line; however, these detrimental effects were ameliorated by TAK1 inhibition. Notably, protein kinase B (AKT)/glycogen synthase kinase (GSK)3β phosphorylation levels were markedly upregulated in breast cancer samples, compared with adjacent healthy tissues. In conclusion, an altered TRAF6‑TAK1 axis and its corresponding downstream AKT/GSK3β signaling molecules may contribute to breast cancer progression. Therefore, TRAF6 may represent a potential therapeutic target for the treatment of breast cancer.

  17. Wear resistance of a pressable low-fusing ceramic opposed by dental alloys.

    Science.gov (United States)

    Faria, Adriana Cláudia Lapria; de Oliveira, André Almeida; Alves Gomes, Érica; Silveira Rodrigues, Renata Cristina; Faria Ribeiro, Ricardo

    2014-04-01

    Dental alloys have increasingly replaced by dental ceramics in dentistry because of aesthetics. As both dental alloys and ceramics can be present in the oral cavity, the evaluation of the wear resistance of ceramics opposed by dental alloys is important. The aim of the present study was to evaluate wear resistance of a pressable low-fusing ceramic opposed by dental alloys as well as the microhardness of the alloys and the possible correlation of wear and antagonist microhardness. Fifteen stylus tips samples of pressable low-fusing ceramic were obtained, polished and glazed. Samples were divided into three groups according to the disk of alloy/metal to be used as antagonist: Nickel-Chromium (Ni-Cr), Cobalt-Chromium (Co-Cr) and commercially pure titanium (cp Ti). Vickers microhardness of antagonist disks was evaluated before wear tests. Then, antagonist disks were sandblasted until surface roughness was adjusted to 0.75μm. Wear tests were performed at a speed of 60 cycles/min and distance of 10mm, in a total of 300,000 cycles. Before and after wear tests, samples were weighted and had their profile designed in an optical comparator to evaluate weight and height loss, respectively. Ni-Cr and cp Ti caused greater wear than Co-Cr, presenting greater weight (p=.009) and height (p=.002) loss. Cp Ti microhardness was lower than Ni-Cr and Co-Cr (pceramic presents different wear according to the dental alloy used as antagonist and the wear is not affected by antagonist microhardness. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Development of multipurpose regulatory PSA model

    International Nuclear Information System (INIS)

    Lee, Chang Ju; Sung, Key Yong; Kim, Hho Jung; Yang, Joon Eon; Ha, Jae Joo

    2004-01-01

    Generally, risk information for nuclear facilities comes from the results of Probabilistic safety assessment (PSA). PSA is a systematic tool to ensure the safety of nuclear facilities, since it is based on thorough and consistent application of probability models. In particular, the PSA has been widely utilized for risk-informed regulation (RIR), including various licensee-initiated risk-informed applications (RIA). In any regulatory decision, the main goal is to make a sound safety decision based on technically defensible information. Also, due to the increased public requests for giving a safety guarantee, the regulator should provide the visible means of safety. The use of PSA by the regulator can give the answer on this problem. Therefore, in order to study the applicability of risk information for regulatory safety management, it is a demanding task to prepare a well-established regulatory PSA model and tool. In 2002, KINS and KAERI together made a research cooperation to form a working group to develop the regulatory PSA model - so-called MPAS model. The MPAS stands for multipurpose probabilistic analysis of safety. For instance, a role of the MPAS model is to give some risk insights in the preparation of various regulatory programs. Another role of this model is to provide an independent risk information to the regulator during regulatory decision-making, not depending on the licensee's information

  19. NRC Regulatory Agenda

    International Nuclear Information System (INIS)

    1991-10-01

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

  20. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1993-04-01

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

  1. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1990-01-01

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

  2. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1991-04-01

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

  3. NRC Regulatory Agenda

    International Nuclear Information System (INIS)

    1991-08-01

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

  4. Nuclear Regulatory legislation

    International Nuclear Information System (INIS)

    1984-06-01

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

  5. Improving nuclear regulatory effectiveness

    International Nuclear Information System (INIS)

    2001-01-01

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

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

    Science.gov (United States)

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

    2017-07-01

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

  7. Risk literacy for scientists. Invitation to regulatory science

    International Nuclear Information System (INIS)

    Ono, Kyoko

    2012-01-01

    This paper discusses a regulatory science, which fills a gap between scientific knowledge and regulatory actions. The author provides examples of the regulatory science employed in chemical risk assessment, such as the linear non-threshold theory. In the regulatory science, scientific data as well as scientific reasoning based on scientific knowledge - or regulatory rules - should play an important role. It is important to recognize that the rules facilitate transparent decision making under conditions of uncertainty and time constraints. Furthermore, the development of traditional or pure science results in the validation of regulatory rules, and subsequently, the regulatory science procedure develops more systematically. The concept of this science should be understood by those engaged in governmental decision making. (author)

  8. The Regulatory Roles of Toll-Like Receptor 4 in Secretions of Type 1/Type 2 Relative Cytokines by Splenocytes and Dendritic Cells Exposed to Clonorchis sinensis Excretory/Secretory Products.

    Science.gov (United States)

    Hua, Hui; Du, Ying; Ma, Rui; Zhang, Bei-Bei; Yu, Qian; Li, Bo; Xu, Jiang-Tao; Li, Xiang-Yang; Tang, Ren-Xian; Yan, Chao; Zheng, Kui-Yang

    2018-02-01

    The roles of TLR4 in mediation of innate immune response and in regulation of adaptive immune responses triggered by Clonorchis sinensis remain unknown. In the present study, splenocytes derived from C3H/HeN (TLR4 wild ) and C3H/Hej mice (TLR4 mut ) that were infected with 45 metacercariae of C. sinensis were harvested, then stimulated by C. sinensis excretory/secretory products (ESP) or medium (control) for 48 h, respectively. Meanwhile, bone marrow-derived dendritic cells (BMDCs) from normal C3H/HeN and C3H/Hej mice were prepared and stimulated with medium, ESP, LPS, or ESP+LPS for 24 h, respectively. The supernatants were collected, and the concentrations of type 1 and type 2 relative cytokines were determined by ELISA. The maturation of BMDCs indicated by surface markers of CD80, CD86, and MHC II was evaluated by flow cytometry. The results showed that the levels of IFN-γ, IL-6, TNF-α, and IL-10 in the splenocytes from C. sinensis-infected TLR4 mut mice were significantly lower than those from TLR4 wild mice when they were further exposed to ESP. For BMDCs, the productions of the cytokines IL-12p70 and IL-10, but not IL-4, in the BMDCs from TLR4 mutation mice were predominantly decreased compared with those from TLR4 wild mice when the BMDCs were co-stimulated by ESP combined with LPS. Flow cytometry analysis showed that ESP could significantly decrease the high levels of CD80, CD86, and MHC II which were elevated by LPS. In conclusion, these data suggest that TLR4 may play a regulatory role in type 1 immune responses during C. sinensis infection.

  9. Public Perceptions of Regulatory Costs, Their Uncertainty and Interindividual Distribution.

    Science.gov (United States)

    Johnson, Branden B; Finkel, Adam M

    2016-06-01

    Public perceptions of both risks and regulatory costs shape rational regulatory choices. Despite decades of risk perception studies, this article is the first on regulatory cost perceptions. A survey of 744 U.S. residents probed: (1) How knowledgeable are laypeople about regulatory costs incurred to reduce risks? (2) Do laypeople see official estimates of cost and benefit (lives saved) as accurate? (3) (How) do preferences for hypothetical regulations change when mean-preserving spreads of uncertainty replace certain cost or benefit? and (4) (How) do preferences change when unequal interindividual distributions of hypothetical regulatory costs replace equal distributions? Respondents overestimated costs of regulatory compliance, while assuming agencies underestimate costs. Most assumed agency estimates of benefits are accurate; a third believed both cost and benefit estimates are accurate. Cost and benefit estimates presented without uncertainty were slightly preferred to those surrounded by "narrow uncertainty" (a range of costs or lives entirely within a personally-calibrated zone without clear acceptance or rejection of tradeoffs). Certain estimates were more preferred than "wide uncertainty" (a range of agency estimates extending beyond these personal bounds, thus posing a gamble between favored and unacceptable tradeoffs), particularly for costs as opposed to benefits (but even for costs a quarter of respondents preferred wide uncertainty to certainty). Agency-acknowledged uncertainty in general elicited mixed judgments of honesty and trustworthiness. People preferred egalitarian distributions of regulatory costs, despite skewed actual cost distributions, and preferred progressive cost distributions (the rich pay a greater than proportional share) to regressive ones. Efficient and socially responsive regulations require disclosure of much more information about regulatory costs and risks. © 2016 Society for Risk Analysis.

  10. Impact of regulatory science on global public health

    OpenAIRE

    Meghal Patel; Margaret Ann Miller

    2012-01-01

    Regulatory science plays a vital role in protecting and promoting global public health by providing the scientific basis for ensuring that food and medical products are safe, properly labeled, and effective. Regulatory science research was first developed for the determination of product safety in the early part of the 20th Century, and continues to support innovation of the processes needed for regulatory policy decisions. Historically, public health laws and regulations were enacted followi...

  11. Regulatory guidance document

    International Nuclear Information System (INIS)

    1994-05-01

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

  12. Relevance of variations in the opposing dentition for the functionality of fixed and removable partial dentures: a systematic review.

    Science.gov (United States)

    Pommer, Bernhard; Krainhöfner, Martin; Watzek, Georg; Tepper, Gabor; Dintsios, Charalabos-Markos

    2012-01-01

    The aim of this systematic review was to evaluate the functionality of fixed and removable partial dentures as test interventions in relation to variations in the opposing dentition and their prosthetic restoration. The abstracts identified in the respective databases were screened independently by two investigators. RCTs and uncontrolled studies were considered, provided the patients were included consecutively and the confounding variables were adequately monitored. Seventeen papers were included. The study and publication quality was assessed using a "biometric quality" tool showing an overall poor quality. The reported outcomes, such as survival rates, were in each case obtained from a single study. Two possible trends could be deduced for the endpoint longevity: (a) the first trend in favor of removable partial dentures, compared to fixed partial dentures, with a fully edentulous opposing arch fitted with a removable prosthesis; (b) the second trend in favor of implant-supported partial dentures, compared to conventionally fixed partial dentures, with natural opposing dentition or with a removable partial denture in the opposing arch. No evidence could be generated as to whether, and if so how, variations in the opposing dentition have a bearing on the decision to fit a partially edentulous arch with a fixed or removable partial denture.

  13. Relevance of Variations in the Opposing Dentition for the Functionality of Fixed and Removable Partial Dentures: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Bernhard Pommer

    2012-01-01

    Full Text Available The aim of this systematic review was to evaluate the functionality of fixed and removable partial dentures as test interventions in relation to variations in the opposing dentition and their prosthetic restoration. The abstracts identified in the respective databases were screened independently by two investigators. RCTs and uncontrolled studies were considered, provided the patients were included consecutively and the confounding variables were adequately monitored. Seventeen papers were included. The study and publication quality was assessed using a “biometric quality” tool showing an overall poor quality. The reported outcomes, such as survival rates, were in each case obtained from a single study. Two possible trends could be deduced for the endpoint longevity: (a the first trend in favor of removable partial dentures, compared to fixed partial dentures, with a fully edentulous opposing arch fitted with a removable prosthesis; (b the second trend in favor of implant-supported partial dentures, compared to conventionally fixed partial dentures, with natural opposing dentition or with a removable partial denture in the opposing arch. No evidence could be generated as to whether, and if so how, variations in the opposing dentition have a bearing on the decision to fit a partially edentulous arch with a fixed or removable partial denture.

  14. Laminar mixed convection heat transfer in a vertical circular tube under buoyancy-assisted and opposed flows

    International Nuclear Information System (INIS)

    Mohammed, Hussein A.

    2008-01-01

    Laminar mixed convection heat transfer for assisted and opposed air flows in the entrance region of a vertical circular tube with the using of a uniform wall heat flux boundary condition has been experimentally investigated. The experimental setup was designed for determining the effect of flow direction and the effect of tube inclination on the surface temperature, local and average Nusselt numbers with Reynolds number ranged from 400 to 1600 and Grashof number from 2.0 x 10 5 to 6.2 x 10 6 . It was found that the circumferential surface temperature along the dimensionless tube length for opposed flow would be higher than that both of assisted flow and horizontal tube [Mohammed HA, Salman YK. Experimental investigation of combined convection heat transfer for thermally developing flow in a horizontal circular cylinder. Appl Therm Eng 2007;27(8-9):1522-33] due to the stronger free convective currents within the cross-section. The Nusselt number values would be lower for opposed flow than that for assisted flow. It was inferred that the behaviour of Nu x for opposed flow to be strongly dependent on the combination of Re and Gr numbers. Empirical equations expressing the average Nusselt numbers in terms of Grashof and Reynolds numbers were proposed for both assisted and opposed flow cases. The average heat transfer results were compared with previous literature and showed similar trend and satisfactory agreement

  15. Managing Regulatory Body Competence

    International Nuclear Information System (INIS)

    2013-01-01

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

  16. O lugar da política na atuação das agências reguladoras independentes brasileiras: reflexões sobre a separação dos poderes no Estado moderno / The Role of Politics in the Brazilian Independent Regulatory Agencies: Reflections on the Separation of Powers in the Modern State

    Directory of Open Access Journals (Sweden)

    Milton Carvalho Gomes

    2017-04-01

    Full Text Available Purpose – The purpose of the proposed article is to investigate the practice of politics in the performance of activities of Brazilian independent regulatory agencies Methodology/approach/design – ... The approach is based on the study of theories about separation of state powers and functions, evaluating the application of these theories in the understanding of the role played by independent regulatory agencies in Brazil Findings – It was concluded that the independence granted by the National Congress to the Brazilian regulatory agencies implied in the expansion of the space of politics in its operation, placing these agencies in a unique position in the context of the separation of powers, changing the traditional institutional arrangement of submission to the executive branch. Practical implications (if applicable –The conclusions permit new reflections on the limits of the influence of the President of the Republic and of the sectoral ministries in the decisions taken by the regulatory agencies, both in the decisions of a technical nature and those of a political nature, allowing the expansion of the debate on the instruments of democratic legitimation of these decisions. Originality/value (optional – The text is original, since there are few in-depth studies in Brazil about the space for politics in the field of independent regulatory agencies, usually understood as purely technical / administrative entities.

  17. As Gene Giants, os Agrotóxicos e as Sementes Transgênicas: o Papel Regulatório Brasileiro sob a perspectiva do Desenvolvimento Sustentável / The Gene Giants, Pesticides and Genetically Modified Seeds: The Brazilian Regulatory Role from the perspective of Sustainable Development

    Directory of Open Access Journals (Sweden)

    Marcus Tullius Fernandes dos Santos

    2016-10-01

    Full Text Available Purpose – The purpose of this study is to analyze the market performance of the gene giants with respect to the production and marketing of pesticides and genetically modified seeds in Brazil, checking the regulatory role regarding control and supervision by the federal government, on par with the discussion on the implementation of sustainable development. Methodology/approach/design – Research of the literature associated with data collection and documents in the period 2005-2015 was implemented at the institutions responsible for the registration, release, control and inspection of GM seeds and pesticides in Brazil, using the institutional theory of law. The main idea is that laws and institutions have not crystallized culture of sustainability, since in their application on cases involving the gene giants economic interests have overshadowed weak regulatory modeling. Findings – There is need to establish a smart regulatory model so that regulation can be implemented by abandoning the one-sided view of the preponderance of economic interest. Only with strong regulatory, social and economic pressures can address the transnational nature of sustainable development in face of the power of big business corporations. Practical implications – Regulatory criteria were developed by avoiding the preponderance of economic interests at the expense of sensitive environmental, social, cultural, and political values.

  18. Opposed-Flow Flame Spread in a Narrow Channel Apparatus over Thin PMMA Sheets

    Science.gov (United States)

    Bornand, G. R.; Olson, Sandra L.; Miller, F. J.; Pepper, J. M.; Wichman, I. S.

    2013-01-01

    Flame spread tests have been conducted over polymethylmethacrylate (PMMA) samples in San Diego State University's Narrow Channel Apparatus (SDSU NCA). The Narrow Channel Apparatus (NCA) has the ability to suppress buoyant flow in horizontally spreading flames, and is currently being investigated as a possible replacement or complement to NASA's current material flammability test standard for non-metallic solids, NASA-STD-(I)-6001B Test 1. The buoyant suppression achieved with a NCA allows for tests to be conducted in a simulated microgravity atmosphere-a characteristic that Test 1 lacks since flames present in Test 1 are buoyantly driven. The SDSU NCA allows for flame spread tests to be conducted with varying opposed flow oxidizer velocities, oxygen percent by volume, and total pressure. Also, since the test sample is placed symmetrically between two confining plates so that there is a gap above and below the sample, this gap can be adjusted. This gap height adjustment allows for a compromise between heat loss from the flame to the confining boundaries and buoyancy suppression achieved by those boundaries. This article explores the effect gap height has on the flame spread rate for 75 µm thick PMMA at 1 atm pressure and 21% oxygen concentration by volume in the SDSU NCA. Flame spread results from the SDSU NCA for thin cellulose fuels have previously been compared to results from tests in actual microgravity at various test conditions with the same sample materials and were found to be in good agreement. This article also presents results from the SDSU NCA for PMMA at 1 atm pressure, opposed oxidizer velocity ranging from 3 to 35 cm/s, oxygen concentration by volume at 21%, 30 %, and 50% and fuel thicknesses of 50 and 75 µm. These results are compared to results obtained in actual microgravity for PMMA obtained at the 4.5s drop tower of MGLAB in Gifu, Japan, and the 5.2s drop tower at NASA's Zero-Gravity Research Facility in Cleveland, OH. This comparison confirms

  19. Wear of human enamel opposing monolithic zirconia, glass ceramic, and composite resin: an in vitro study.

    Science.gov (United States)

    Sripetchdanond, Jeerapa; Leevailoj, Chalermpol

    2014-11-01

    Demand is increasing for ceramic and composite resin posterior restorations. However, ceramics are recognized for their high abrasiveness to opposing dental structure. The purpose of this study was to investigate the wear of enamel as opposed to dental ceramics and composite resin. Twenty-four test specimens (antagonists), 6 each of monolithic zirconia, glass ceramic, composite resin, and enamel, were prepared into cylindrical rods. Enamel specimens were prepared from 24 extracted human permanent molar teeth. Enamel specimens were abraded against each type of antagonist with a pin-on-disk wear tester under a constant load of 25 N at 20 rpm for 4800 cycles. The maximum depth of wear (Dmax), mean depth of wear (Da), and mean surface roughness (Ra) of the enamel specimens were measured with a profilometer. All data were statistically analyzed by 1-way ANOVA, followed by the Tukey test (α=.05). A paired t test was used to compare the Ra of enamel at baseline and after testing. The wear of both the enamel and antagonists was evaluated qualitatively with scanning electron microscopic images. No significant differences were found in enamel wear depth (Dmax, Da) between monolithic zirconia (2.17 ±0.80, 1.83 ±0.75 μm) and composite resin (1.70 ±0.92, 1.37 ±0.81 μm) or between glass ceramic (8.54 ±2.31, 7.32 ±2.06 μm) and enamel (10.72 ±6.31, 8.81 ±5.16 μm). Significant differences were found when the enamel wear depth caused by monolithic zirconia and composite resin was compared with that of glass ceramic and enamel (Pglass ceramic, and enamel (Pglass ceramic and enamel. All test materials except composite resin similarly increased the enamel surface roughness after wear testing. Copyright © 2014 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

  20. Environment and T regulatory cells in allergy.

    Science.gov (United States)

    Braga, M; Schiavone, C; Di Gioacchino, G; De Angelis, I; Cavallucci, E; Lazzarin, F; Petrarca, C; Di Gioacchino, M

    2012-04-15

    The central role of T regulatory cells in the responses against harmless environmental antigens has been confirmed by many studies. Impaired T regulatory cell function is implicated in many pathological conditions, particularly allergic diseases. The "hygiene hypothesis" suggests that infections and infestations may play a protective role for allergy, whereas environmental pollutants favor the development of allergic diseases. Developing countries suffer from a variety of infections and are also facing an increasing diffusion of environmental pollutants. In these countries allergies increase in relation to the spreading use of xenobiotics (pesticides, herbicides, pollution, etc.) with a rate similar to those of developed countries, overcoming the protective effects of infections. We review here the main mechanisms of non-self tolerance, with particular regard to relations between T regulatory cell activity, infections and infestations such as helminthiasis, and exposure to environmental xenobiotics with relevant diffusion in developing countries. Copyright © 2010 Elsevier B.V. All rights reserved.

  1. Opposing roles of LTB4 and PGE2 in regulating the inflammasome-dependent scorpion venom-induced mortality

    OpenAIRE

    Zoccal, Karina F.; Sorgi, Carlos A.; Hori, Juliana I.; Paula-Silva, Francisco W. G.; Arantes, Eliane C.; Serezani, Carlos H.; Zamboni, Dario S.; Faccioli, L?cia H.

    2016-01-01

    Tityus serrulatus sting causes thousands of deaths annually worldwide. T. serrulatus-envenomed victims exhibit local or systemic reaction that culminates in pulmonary oedema, potentially leading to death. However, the molecular mechanisms underlying T. serrulatus venom (TsV) activity remain unknown. Here we show that TsV triggers NLRP3 inflammasome activation via K+ efflux. Mechanistically, TsV triggers lung-resident cells to release PGE2, which induces IL-1? production via E prostanoid recep...

  2. Chaotic Behaviour Investigation of a Front Opposed-Hemispherical Spiral-Grooved Air Bearing System

    Directory of Open Access Journals (Sweden)

    Cheng-Chi Wang

    2017-01-01

    Full Text Available In recent years, spiral-grooved air bearing systems have attracted much attention and are especially useful in precision instruments and machines with spindles that rotate at high speed. Load support can be multidirectional and this type of bearing can also be very rigid. Studies show that some of the design problems encountered are dynamic and include critical speed, nonlinearity, gas film pressure, unbalanced rotors, and even poor design, all of which can result in the generation of chaotic aperiodic motion and instability under certain conditions. Such irregular motion on a large scale can cause severe damage to a machine or instrument. Therefore, understanding the conditions under which aperiodic behaviour and vibration arise is crucial for prevention. In this study, numerical analysis, including the Finite Difference and Differential Transformation Methods, is used to study these effects in detail in a front opposed-hemispherical spiral-grooved air bearing system. It was found that different rotor masses and bearing number could cause undesirable behaviour including periodic, subperiodic, quasi-periodic, and chaotic motion. The results obtained in this study can be used as a basis for future bearing system design and the prevention of instability.

  3. Aspects of extratropical synoptic-scale processes in opposing ENSO phases

    Science.gov (United States)

    Schwierz, C.; Wernli, H.; Hess, D.

    2003-04-01

    Energy and momentum provided by anomalous tropical heating/cooling affect the circulation on the global scale. Pacific Sea surface temperature anomalies strongly force local conditions in the equatorial Pacific, but are also known to change the climate in the extratropics, particularly over the American continent. The impact on more remote areas such as the Atlantic-European region is less clear. There the observed effects in both analyses and model studies show dependence on the resolution of the model/data, as well as on the time scales under consideration (Merkel and Latif, 2002; Compo et al., 2001). Most of the previous studies focus on larger-scale processes and seasonal time scales (or longer). Here we concentrate on the impact of opposing ENSO phases on extratropical synoptic-scale dynamics. The investigation is undertaken for the Niño/Niña events of 1972/3 and 1973/4 respectively, for 5 winter months (NDJFM) using ECMWF ERA40 data with 1o× 1o horizontal resolution and 60 vertical levels. The examination of the resulting differences in terms of standard dynamical fields (temperature, sea level pressure, precipitation, geopotential) is complemented with additional diagnostic fields (e.g. potential vorticity (PV), anti-/cyclone tracks and frequencies, PV streamers/cut-offs, blocking) in an attempt to gain more insight into aspects of extratropical synoptic-scale dynamical processes associated with ENSO SST anomalies.

  4. Evaluation of bone marrow by opposed phase T1-weighted images and enhanced MR imaging

    International Nuclear Information System (INIS)

    Amano, Yasuo; Tanabe, Yoshihiro; Miyashita, Tsuguhiro; Hayashi, Hiromitsu; Horiuchi, Junichi; Nomura, Takeo; Kumazaki, Tatsuo

    1994-01-01

    We investigated bone marrow in a control group, cases of aplastic anemia and post-irradiation patients by examining T1-weighted (T1W1), short T1 inversion recovery (STIR), opposed phase T1W1 (op-T1W1) and Gd-DTPA enhanced op-T1W1 images obtained by 0.5 T MRI. Bone marrow was classified into four types based on MR findings. Normal marrow showed low intensity on op-T1W1 and STIR images without enhancement (I). Fatty marrow, which showed high intensity on T1W1 and op-T1W1 images was observed in aplastic anemia and post-irradiation patients (II). Hematopoietic marrow (III) showed low intensity on op-T1W1 and enhanced, while active hematopoietic marrow (IV) revealed high intensity on both STIR and op-T1W1 images and was enhanced following Gd-DTPA infusion. Aplastic anemia of moderate grade included types II, III and IV. Enhanced MR was needed to differentiate between types I and III since both types showed low intensity on op-T1W1 images. Furthermore, type IV was considered as hyperplastic compared with type III. Enhanced MR and op-T1W1 images were useful in evaluating hematopoiesis of bone marrow. (author)

  5. Evaluation of bone marrow by opposed phase T1-weighted images and enhanced MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Amano, Yasuo; Tanabe, Yoshihiro; Miyashita, Tsuguhiro; Hayashi, Hiromitsu; Horiuchi, Junichi; Nomura, Takeo; Kumazaki, Tatsuo (Nippon Medical School, Tokyo (Japan))

    1994-09-01

    We investigated bone marrow in a control group, cases of aplastic anemia and post-irradiation patients by examining T1-weighted (T1W1), short T1 inversion recovery (STIR), opposed phase T1W1 (op-T1W1) and Gd-DTPA enhanced op-T1W1 images obtained by 0.5 T MRI. Bone marrow was classified into four types based on MR findings. Normal marrow showed low intensity on op-T1W1 and STIR images without enhancement (I). Fatty marrow, which showed high intensity on T1W1 and op-T1W1 images was observed in aplastic anemia and post-irradiation patients (II). Hematopoietic marrow (III) showed low intensity on op-T1W1 and enhanced, while active hematopoietic marrow (IV) revealed high intensity on both STIR and op-T1W1 images and was enhanced following Gd-DTPA infusion. Aplastic anemia of moderate grade included types II, III and IV. Enhanced MR was needed to differentiate between types I and III since both types showed low intensity on op-T1W1 images. Furthermore, type IV was considered as hyperplastic compared with type III. Enhanced MR and op-T1W1 images were useful in evaluating hematopoiesis of bone marrow. (author).

  6. Opposed-flow Flame Spread Over Solid Fuels in Microgravity: the Effect of Confined Spaces

    Science.gov (United States)

    Wang, Shuangfeng; Hu, Jun; Xiao, Yuan; Ren, Tan; Zhu, Feng

    2015-09-01

    Effects of confined spaces on flame spread over thin solid fuels in a low-speed opposing flow is investigated by combined use of microgravity experiments and computations. The flame behaviors are observed to depend strongly on the height of the flow tunnel. In particular, a non-monotonic trend of flame spread rate versus tunnel height is found, with the fastest flame occurring in the 3 cm high tunnel. The flame length and the total heat release rate from the flame also change with tunnel height, and a faster flame has a larger length and a higher heat release rate. The computation analyses indicate that a confined space modifies the flow around the spreading flame. The confinement restricts the thermal expansion and accelerates the flow in the streamwise direction. Above the flame, the flow deflects back from the tunnel wall. This inward flow pushes the flame towards the fuel surface, and increases oxygen transport into the flame. Such a flow modification explains the variations of flame spread rate and flame length with tunnel height. The present results suggest that the confinement effects on flame behavior in microgravity should be accounted to assess accurately the spacecraft fire hazard.

  7. Aromatic ring formation in opposed-flow diffusive 1,3-butadiene flames

    KAUST Repository

    Moshammer, Kai

    2016-10-17

    This paper is concerned with the formation of one- and two-ring aromatic species in near atmospheric-pressure opposed-flow diffusion flames of 1,3-butadiene (1,3-CH). The chemical structures of two different 1,3-CH/Ar-O/Ar flames were explored using flame-sampling molecular-beam mass spectrometry with both electron and single-photon ionization. We provide mole fraction profiles of 47 components as function of distance from the fuel outlet and compare them to chemically detailed modeling results. To this end, the hierarchically developed model described by Seidel et al. [16] has been updated to accurately comprise the chemistry of 1,3-butadiene. Generally a very good agreement is observed between the experimental and modeling data, allowing for a meaningful reaction path analysis. With regard to the formation of aromatic species up to naphthalene, it was essential to improve the fulvene and the C chemistry description in the mechanism. In particular, benzene is found to be formed mainly via fulvene through the reactions of the CH isomers with CH The n-CH radical reacts with CH forming 1,3-pentadiene (CH), which is subsequently oxidized to form the naphthalene precursor cyclopentadienyl (CH). Oxidation of naphthalene is predicted to be a contributor to the formation of phenylacetylene (CH), indicating that consumption reactions can be of similar importance as molecular growth reactions.

  8. Wear Resistance of 3D Printing Resin Material Opposing Zirconia and Metal Antagonists

    Directory of Open Access Journals (Sweden)

    Ji-Man Park

    2018-06-01

    Full Text Available 3D printing offers many advantages in dental prosthesis manufacturing. This study evaluated the wear resistance of 3D printing resin material compared with milling and conventional resin materials. Sixty substrate specimens were prepared with three types of resin materials: 3D printed resin, milled resin, and self-cured resin. The 3D printed specimens were printed at a build angle of 0° and 100 μm layer thickness by digital light processing 3D printing. Two kinds of abraders were made of zirconia and CoCr alloy. The specimens were loaded at 5 kg for 30,000 chewing cycles with vertical and horizontal movements under thermocycling condition. The 3D printed resin did not show significant difference in the maximal depth loss or the volume loss of wear compared to the milled and the self-cured resins. No significant difference was revealed depending on the abraders in the maximal depth loss or the volume loss of wear. In SEM views, the 3D printed resin showed cracks and separation of inter-layer bonds when opposing the metal abrader. The results suggest that the 3D printing using resin materials provides adequate wear resistance for dental use.

  9. Wear Resistance of 3D Printing Resin Material Opposing Zirconia and Metal Antagonists.

    Science.gov (United States)

    Park, Ji-Man; Ahn, Jin-Soo; Cha, Hyun-Suk; Lee, Joo-Hee

    2018-06-20

    3D printing offers many advantages in dental prosthesis manufacturing. This study evaluated the wear resistance of 3D printing resin material compared with milling and conventional resin materials. Sixty substrate specimens were prepared with three types of resin materials: 3D printed resin, milled resin, and self-cured resin. The 3D printed specimens were printed at a build angle of 0° and 100 μm layer thickness by digital light processing 3D printing. Two kinds of abraders were made of zirconia and CoCr alloy. The specimens were loaded at 5 kg for 30,000 chewing cycles with vertical and horizontal movements under thermocycling condition. The 3D printed resin did not show significant difference in the maximal depth loss or the volume loss of wear compared to the milled and the self-cured resins. No significant difference was revealed depending on the abraders in the maximal depth loss or the volume loss of wear. In SEM views, the 3D printed resin showed cracks and separation of inter-layer bonds when opposing the metal abrader. The results suggest that the 3D printing using resin materials provides adequate wear resistance for dental use.

  10. Acoustic tweezing of particles using decaying opposing travelling surface acoustic waves (DOTSAW).

    Science.gov (United States)

    Ng, Jia Wei; Devendran, Citsabehsan; Neild, Adrian

    2017-10-11

    Surface acoustic waves offer a versatile and biocompatible method of manipulating the location of suspended particles or cells within microfluidic systems. The most common approach uses the interference of identical frequency, counter propagating travelling waves to generate a standing surface acoustic wave, in which particles migrate a distance less than half the acoustic wavelength to their nearest pressure node. The result is the formation of a periodic pattern of particles. Subsequent displacement of this pattern, the prerequisite for tweezing, can be achieved by translation of the standing wave, and with it the pressure nodes; this requires changing either the frequency of the pair of waves, or their relative phase. Here, in contrast, we examine the use of two counterpropagating traveling waves of different frequency. The non-linearity of the acoustic forces used to manipulate particles, means that a small frequency difference between the two waves creates a substantially different force field, which offers significant advantages. Firstly, this approach creates a much longer range force field, in which migration takes place across multiple wavelengths, and causes particles to be gathered together in a single trapping site. Secondly, the location of this single trapping site can be controlled by the relative amplitude of the two waves, requiring simply an attenuation of one of the electrical drive signals. Using this approach, we show that by controlling the powers of the opposing incoherent waves, 5 μm particles can be migrated laterally across a fluid flow to defined locations with an accuracy of ±10 μm.

  11. Opposing effects of external gibberellin and Daminozide on Stevia growth and metabolites.

    Science.gov (United States)

    Karimi, Mojtaba; Hashemi, Javad; Ahmadi, Ali; Abbasi, Alireza; Pompeiano, Antonio; Tavarini, Silvia; Guglielminetti, Lorenzo; Angelini, Luciana G

    2015-01-01

    Steviol glycosides (SVglys) and gibberellins are originated from the shared biosynthesis pathway in Stevia (Stevia rebaudiana Bertoni). In this research, two experiments were conducted to study the opposing effects of external gibberellin (GA3) and Daminozide (a gibberellin inhibitor) on Stevia growth and metabolites. Results showed that GA3 significantly increased the stem length and stem dry weight in Stevia. Total soluble sugar content increased while the SVglys biosynthesis was decreased by external GA3 applying in Stevia leaves. In another experiment, the stem length was reduced by Daminozide spraying on Stevia shoots. The Daminozide did not affect the total SVglys content, while in 30 ppm concentration, significantly increased the soluble sugar production in Stevia leaves. Although the gibberellins biosynthesis pathway has previously invigorated in Stevia leaf, the Stevia response to external gibberellins implying on high precision regulation of gibberellins biosynthesis in Stevia and announces that Stevia is able to kept endogenous gibberellins in a low quantity away from SVglys production. Moreover, the assumption that the internal gibberellins were destroyed by Daminozide, lack of Daminozide effects on SVglys production suggests that gibberellins biosynthesis could not act as a competitive factor for SVglys production in Stevia leaves.

  12. Suicide verdicts as opposed to accidental deaths in substance-related fatalities (UK, 2001-2007).

    Science.gov (United States)

    Vento, Alessandro E; Schifano, Fabrizio; Corkery, John M; Pompili, Maurizio; Innamorati, Marco; Girardi, Paolo; Ghodse, Hamid

    2011-07-01

    Substance-related deaths account for a great number of suicides. To investigate levels and characteristics of suicide verdicts, as opposed to accidental deaths, in substance misusers. Psychological autopsy study of cases from the UK National Programme on Substance Abuse Deaths (np-SAD) during the period 2001-2007. Between January 2001 and December 2007, 2108 suicides were reported to the np-SAD. Typical suicide victims were White and older than 50 (respectively 95% and 41% of cases). Medications, especially antidepressants (44%), were prescribed to 87% of victims. Significantly fewer suicide victims than controls presented positive blood toxicological results for illicit drugs (namely: cocaine, heroin, amphetamines, ecstasy-type drugs, cannabis, and GHB/GBL) and alcohol. Suicide prevention programmes should devote specific attention to deaths among substance misusers who are at high risk of fatal intentional self-harm. Specific characteristics distinguish those at risk; caregivers should be better educated as to what these factors are. Limitations of the current study included lack of provision of comprehensive information relating to the victims' psychosocial variables. Furthermore, no differentiation between different classes of antidepressants in terms of involvement in suicide was here provided. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Dominant, Residual, and Emergent: Opposing Forces Hovering over John Dos Passos’ U.S.A

    Directory of Open Access Journals (Sweden)

    Rahmat Ollah Mahtabi

    2015-11-01

    Full Text Available This study is an attempt to investigate John Dos Passos’s U.S.A. Trilogy; The 42nd Parallel (1930; 1919 (1932; and The Big Money (1936 in the light of Raymond Williams. Analyzing the trilogy in terms of Williams’ hegemonic forces between dominant and emergent, it is recognized that the trilogy is full of tragic lives of characters living in the capitalist society of America. According to what Williams says, there are clashes between cultures in a society. He believes that the dominant culture constantly changes and it would not let other cultures to become the controlling power in the society. This tragedy is not an individual experience, but is rather like a collective consciousness. Each and every character is doing their best to change their condition into better but is opposed by the dominant. This is exactly in line with the idea of Williams that the dominant is able to project its own ideology and way of seeing the world so that the subordinated ones accept it as something natural and common. Although there are different types of hegemony including economic and cultural ones, hegemony in this trilogy is mostly the affirmation of the relations between economic and super-structural aspects of it.

  14. Manufacturing method for parts opposed to plasmas and manufacturing device therefor

    International Nuclear Information System (INIS)

    Fuse, Toshiaki; Tachikawa, Nobuo.

    1995-01-01

    The present invention provides a method of and a device for manufacturing heat insulation parts which are opposed to plasmas, such as parts in the inside of a thermonuclear reactor, which less suffer from defects such as crackings and peelings in the vicinity of the joining portion of the parts. Namely, when an armour and a heat sink are cooled to a room temperature after joining them, the upper surface of the armour and the bottom of the heat sink are pressurized. Then after restricting the convex deformation at the upper surface of the armour and the concave deformation at the bottom of the heat sink, the heat sink bottom are extended at from 600degC to a room temperature or at a room temperature. When a heat resistant material with a small heat expansion coefficient is joined with a cooling material with a large heat expansion coefficient and then cooled, deformation and residual stresses are generated by the difference of the shrinking amount. But deformation and the residual stresses can be reduced by gradually cooling them while restricting them by using a joining device compared with a case of not restricting them. As a result, occurrence of crackings and peelings in the vicinity of the joining portion can be prevented. (I.S.)

  15. Amphetamine Elicits Opposing Actions on Readily Releasable and Reserve Pools for Dopamine

    Science.gov (United States)

    Covey, Dan P.; Juliano, Steven A.; Garris, Paul A.

    2013-01-01

    Amphetamine, a highly addictive drug with therapeutic efficacy, exerts paradoxical effects on the fundamental communication modes employed by dopamine neurons in modulating behavior. While amphetamine elevates tonic dopamine signaling by depleting vesicular stores and driving non-exocytotic release through reverse transport, this psychostimulant also activates phasic dopamine signaling by up-regulating vesicular dopamine release. We hypothesized that these seemingly incongruent effects arise from amphetamine depleting the reserve pool and enhancing the readily releasable pool. This novel hypothesis was tested using in vivo voltammetry and stimulus trains of varying duration to access different vesicular stores. We show that amphetamine actions are stimulus dependent in the dorsal striatum. Specifically, amphetamine up-regulated vesicular dopamine release elicited by a short-duration train, which interrogates the readily releasable pool, but depleted release elicited by a long-duration train, which interrogates the reserve pool. These opposing actions of vesicular dopamine release were associated with concurrent increases in tonic and phasic dopamine responses. A link between vesicular depletion and tonic signaling was supported by results obtained for amphetamine in the ventral striatum and cocaine in both striatal sub-regions, which demonstrated augmented vesicular release and phasic signals only. We submit that amphetamine differentially targeting dopamine stores reconciles the paradoxical activation of tonic and phasic dopamine signaling. Overall, these results further highlight the unique and region-distinct cellular mechanisms of amphetamine and may have important implications for its addictive and therapeutic properties. PMID:23671560

  16. Variable-property effects in laminar aiding and opposing mixed convection of air in vertical tubes

    International Nuclear Information System (INIS)

    Nesreddine, H.; Galanis, N.; Nguyen, C.T.

    1997-01-01

    Mixed convection flow in tubes is encountered in many engineering applications, such as solar collectors, nuclear reactors, and compact heat exchangers. Here, a numerical investigation has been conducted in order to determine the effects of variable properties on the flow pattern and heat transfer performances in laminar developing ascending flow with mixed convection for two cases: in case 1 the fluid is heated, and in case 2 it is cooled. Calculations are performed for air at various Grashof numbers with a fixed entrance Reynolds number of 500 using both the Boussinesq approximation (constant-property model) and a variable-property model. In the latter case, the fluid viscosity and thermal conductivity are allowed to vary with absolute temperature according to simple power laws, while the density varies linearly with the temperature, and the heat capacity is assumed to be constant. The comparison between constant- and variable-property models shows a substantial difference in the temperature and velocity fields when the Grashof number |Gr| is increased. The friction factor is seen to be underpredicted by the Boussinesq approximation when the fluid is heated (case 1), while it is overpredicted for the cooling case (case 2). However, the effects on the heat transfer performance remain negligible except for cases with reverse flow. On the whole, the variable-property model predicts flow reversal at lower values of |Gr|, especially for flows with opposing buoyancy forces. The deviation in results is associated to the difference between the fluid bulk and the wall temperature

  17. Aromatic ring formation in opposed-flow diffusive 1,3-butadiene flames

    KAUST Repository

    Moshammer, Kai; Seidel, Lars; Wang, Yu; Selim, Hatem; Sarathy, Mani; Mauss, Fabian; Hansen, Nils

    2016-01-01

    This paper is concerned with the formation of one- and two-ring aromatic species in near atmospheric-pressure opposed-flow diffusion flames of 1,3-butadiene (1,3-CH). The chemical structures of two different 1,3-CH/Ar-O/Ar flames were explored using flame-sampling molecular-beam mass spectrometry with both electron and single-photon ionization. We provide mole fraction profiles of 47 components as function of distance from the fuel outlet and compare them to chemically detailed modeling results. To this end, the hierarchically developed model described by Seidel et al. [16] has been updated to accurately comprise the chemistry of 1,3-butadiene. Generally a very good agreement is observed between the experimental and modeling data, allowing for a meaningful reaction path analysis. With regard to the formation of aromatic species up to naphthalene, it was essential to improve the fulvene and the C chemistry description in the mechanism. In particular, benzene is found to be formed mainly via fulvene through the reactions of the CH isomers with CH The n-CH radical reacts with CH forming 1,3-pentadiene (CH), which is subsequently oxidized to form the naphthalene precursor cyclopentadienyl (CH). Oxidation of naphthalene is predicted to be a contributor to the formation of phenylacetylene (CH), indicating that consumption reactions can be of similar importance as molecular growth reactions.

  18. Research on the Common Rail Pressure Overshoot of Opposed-Piston Two-Stroke Diesel Engines

    Directory of Open Access Journals (Sweden)

    Yi Lu

    2017-04-01

    Full Text Available The common rail pressure has a direct influence on the working stability of Opposed-Piston Two-Stroke (OP2S diesel engines, especially on performance indexes such as power, economy and emissions. Meanwhile, the rail pressure overshoot phenomenon occurs frequently due to the operating characteristics of OP2S diesel engines, which could lead to serious consequences. In order to solve the rail pressure overshoot problem of OP2S diesel engines, a nonlinear concerted algorithm adding a speed state feedback was investigated. First, the nonlinear Linear Parameter Varying (LPV model was utilized to describe the coupling relationship between the engine speed and the rail pressure. The Linear Quadratic Regulator (LQR optimal control algorithm was applied to design the controller by the feedback of speed and rail pressure. Second, cooperating with the switching characteristics of injectors, the co-simulation of MATLAB/Simulink and GT-Power was utilized to verify the validity of the control algorithm and analyze workspaces for both normal and special sections. Finally, bench test results showed that the accuracy of the rail pressure control was in the range of ±1 MPa, in the condition of sudden 600 r/min speed increases. In addition, the fuel mass was reduced 76.3% compared with the maximum fuel supply quantity and the rail pressure fluctuation was less than 20 MPa. The algorithm could also be appropriate for other types of common rail system thanks to its universality.

  19. Numerical investigation of CAI Combustion in the Opposed- Piston Engine with Direct and Indirect Water Injection

    Science.gov (United States)

    Pyszczek, R.; Mazuro, P.; Teodorczyk, A.

    2016-09-01

    This paper is focused on the CAI combustion control in a turbocharged 2-stroke Opposed-Piston (OP) engine. The barrel type OP engine arrangement is of particular interest for the authors because of its robust design, high mechanical efficiency and relatively easy incorporation of a Variable Compression Ratio (VCR). The other advantage of such design is that combustion chamber is formed between two moving pistons - there is no additional cylinder head to be cooled which directly results in an increased thermal efficiency. Furthermore, engine operation in a Controlled Auto-Ignition (CAI) mode at high compression ratios (CR) raises a possibility of reaching even higher efficiencies and very low emissions. In order to control CAI combustion such measures as VCR and water injection were considered for indirect ignition timing control. Numerical simulations of the scavenging and combustion processes were performed with the 3D CFD multipurpose AVL Fire solver. Numerous cases were calculated with different engine compression ratios and different amounts of directly and indirectly injected water. The influence of the VCR and water injection on the ignition timing and engine performance was determined and their application in the real engine was discussed.

  20. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1990-10-01

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

  1. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1990-04-01

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

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

    African Journals Online (AJOL)

    in his role as father of the country. In modern times, the ... of self-regulatory organisations in most financial markets who thus far have ..... companies and their officers under the Act? There are as yet no clear an- swers to ..... 578 (High Court of Singapore) where Chief Justice Yong Pung How held that to establish a breach of ...

  3. Trust in regulatory regimes: scoping the field

    NARCIS (Netherlands)

    Six, F.E.; Verhoest, Koen

    2017-01-01

    This edited volume is the first endeavour to systematically investigate the role of trust in the different relations within regulatory regimes. Trust as a multifaceted concept is contested within public administration and political science in general and especially within the relation between

  4. Leukemia inhibitory factor tips the immune balance towards regulatory T cells in multiple sclerosis.

    Science.gov (United States)

    Janssens, Kris; Van den Haute, Chris; Baekelandt, Veerle; Lucas, Sophie; van Horssen, Jack; Somers, Veerle; Van Wijmeersch, Bart; Stinissen, Piet; Hendriks, Jerome J A; Slaets, Helena; Hellings, Niels

    2015-03-01

    Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS), for which current treatments are unable to prevent disease progression. Based on its neuroprotective and neuroregenerating properties, leukemia inhibitory factor (LIF), a member of the interleukin-6 (IL-6) cytokine family, is proposed as a novel candidate for MS therapy. However, its effect on the autoimmune response remains unclear. In this study, we determined how LIF modulates T cell responses that play a crucial role in the pathogenesis of MS. We demonstrate that expression of the LIF receptor was strongly increased on immune cells of MS patients. LIF treatment potently boosted the number of regulatory T cells (Tregs) in CD4(+) T cells isolated from healthy controls and MS patients with low serum levels of IL-6. Moreover, IL-6 signaling was reduced in the donors that responded to LIF treatment in vitro. Our data together with previous findings revealing that IL-6 inhibits Treg development, suggest an opposing function of LIF and IL-6. In a preclinical animal model of MS we shifted the LIF/IL-6 balance in favor of LIF by CNS-targeted overexpression. This increased the number of Tregs in the CNS during active autoimmune responses and reduced disease symptoms. In conclusion, our data show that LIF downregulates the autoimmune response by enhancing Treg numbers, providing further impetus for the use of LIF as a novel treatment for MS and other autoimmune diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Chlorpyrifos exerts opposing effects on axonal and dendritic growth in primary neuronal cultures

    International Nuclear Information System (INIS)

    Howard, Angela S.; Bucelli, Robert; Jett, David A.; Bruun, Donald; Yang, Dongren; Lein, Pamela J.

    2005-01-01

    Evidence that children are widely exposed to organophosphorus pesticides (OPs) and that OPs cause developmental neurotoxicity in animal models raises significant concerns about the risks these compounds pose to the developing human nervous system. Critical to assessing this risk is identifying specific neurodevelopmental events targeted by OPs. Observations that OPs alter brain morphometry in developing rodents and inhibit neurite outgrowth in neural cell lines suggest that OPs perturb neuronal morphogenesis. However, an important question yet to be answered is whether the dysmorphogenic effect of OPs reflects perturbation of axonal or dendritic growth. We addressed this question by quantifying axonal and dendritic growth in primary cultures of embryonic rat sympathetic neurons derived from superior cervical ganglia (SCG) following in vitro exposure to chlorpyrifos (CPF) or its metabolites CPF-oxon (CPFO) and trichloropyridinol (TCP). Axon outgrowth was significantly inhibited by CPF or CPFO, but not TCP, at concentrations ≥0.001 μM or 0.001 nM, respectively. In contrast, all three compounds enhanced BMP-induced dendritic growth. Acetylcholinesterase was inhibited only by the highest concentrations of CPF (≥1 μM) and CPFO (≥1 nM); TCP had no effect on this parameter. In summary, these compounds perturb neuronal morphogenesis via opposing effects on axonal and dendritic growth, and both effects are independent of acetylcholinesterase inhibition. These findings have important implications for current risk assessment practices of using acetylcholinesterase inhibition as a biomarker of OP neurotoxicity and suggest that OPs may disrupt normal patterns of neuronal connectivity in the developing nervous system

  6. Opposed Effects of Dityrosine Formation in Soluble and Aggregated α-Synuclein on Fibril Growth.

    Science.gov (United States)

    Wördehoff, Michael M; Shaykhalishahi, Hamed; Groß, Luca; Gremer, Lothar; Stoldt, Matthias; Buell, Alexander K; Willbold, Dieter; Hoyer, Wolfgang

    2017-10-13

    Parkinson's disease is the second most common neurodegenerative disease. It is characterized by aggregation of the protein α-synuclein (α-syn) in Lewy bodies, mitochondrial dysfunction, and increased oxidative stress in the substantia nigra. Oxidative stress leads to several modifications of biomolecules including dityrosine (DiY) crosslinking in proteins, which has recently been detected in α-syn in Lewy bodies from Parkinson's disease patients. Here we report that α-syn is highly susceptible to ultraviolet-induced DiY formation. We investigated DiY formation of α-syn and nine tyrosine-to-alanine mutants and monitored its effect on α-syn fibril formation in vitro. Ultraviolet irradiation of intrinsically disordered α-syn generates DiY-modified monomers and dimers, which inhibit fibril formation of unmodified α-syn by interfering with fibril elongation. The inhibition depends on both the DiY group and its integration into α-syn. When preformed α-syn fibrils are crosslinked by DiY formation, they gain increased resistance to denaturation. DiY-stabilized α-syn fibrils retain their high seeding efficiency even after being exposed to denaturant concentrations that completely depolymerize non-crosslinked seeds. Oxidative stress-associated DiY crosslinking of α-syn therefore entails two opposing effects: (i) inhibition of aggregation by DiY-modified monomers and dimers, and (ii) stabilization of fibrillar aggregates against potential degradation mechanisms, which can lead to promotion of aggregation, especially in the presence of secondary nucleation. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  7. Common Ground on Climate Change: Pairing Opposing Viewpoints for Conversations about Climate Change

    Science.gov (United States)

    Kirk, K. B.; Duggan-Haas, D.; Hayhoe, K.

    2017-12-01

    In American public discourse, people tend to strongly identify with the viewpoints held by their cultural and political tribes. However, entrenched positions do little to advance understanding, or work toward solving problems constructively. Worse yet, it has become commonplace to dismiss or demonize those coming from a different point of view - leading to the vitriolic stalemate that often characterizes social media and comment threads when it comes to climate change. One way to break this pattern is to invite people with opposing opinions to actually talk to one another. This presentation describes the lessons learned during the Common Ground on Climate Change project, in which people with contrasting views about climate change engage in a moderated interview with each other. Prior to the interview, participants complete a set of values-based questions. The goal is to reveal areas of common ground between apparent opposites, such as a sense of stewardship for Earth's resources, or an opinion that solutions to climate change will be more beneficial than harmful. The structure of the interviews is based on the hypothesis that if a conversation begins with an appreciation of common values, it becomes easier to broach areas of disagreement. Participants are matched up in one-on-one moderated interviews where they are encouraged to share their concerns, ideas, and priorities about the validity of climate science, the need for urgent action, and the types of solutions they find most tenable. Emerging themes from this series of interviews include the value of a diversity of outlooks, and the ability for moderated conversations to find surprising areas of agreement. Articles about the interviews also appear on the Yale Climate Connections website, https://www.yaleclimateconnections.org/author/karin/.

  8. Microsphere-Based Scaffolds Carrying Opposing Gradients of Chondroitin Sulfate and Tricalcium Phosphate

    Directory of Open Access Journals (Sweden)

    Vineet eGupta

    2015-07-01

    Full Text Available Extracellular matrix (ECM components such as chondroitin sulfate (CS and tricalcium phosphate (TCP serve as raw materials and thus spatial patterning of these raw materials may be leveraged to mimic the smooth transition of physical, chemical and mechanical properties at the bone-cartilage interface. We hypothesized that encapsulation of opposing gradients of these raw materials in high molecular weight poly(D,L-lactic-co-glycolic acid (PLGA microsphere-based scaffolds would enhance differentiation of rat bone marrow stromal cells (rBMSCs. The raw material encapsulation altered the microstructure of the microspheres and also influenced the cellular morphology that depended on the type of material encapsulated. Moreover, the mechanical properties of the raw material encapsulating microsphere-based scaffolds initially relied on the composition of the scaffolds and later on were primarily governed by the degradation of the polymer phase and newly synthesized extracellular matrix by the seeded cells. Furthermore, raw materials had a mitogenic effect on the seeded cells and led to increased glycosaminoglycan (GAG, collagen, and calcium content. Interestingly, the initial effects of raw material encapsulation on a per-cell basis might have been overshadowed by medium-regulated environment that appeared to favor osteogenesis. However, it is to be noted that in vivo, differentiation of the cells would be governed by the surrounding native environment. Thus, the results of this study demonstrated the potential of the raw materials in facilitating neo-tissue synthesis in microsphere-based scaffolds and perhaps in combination with bioactive signals, these raw materials may be able to achieve intricate cell differentiation profiles required for regenerating the osteochondral interface.

  9. Perceiving and Acting on Complex Affordances: How Children and Adults Bicycle across Two Lanes of Opposing Traffic

    Science.gov (United States)

    Grechkin, Timofey Y.; Chihak, Benjamin J.; Cremer, James F.; Kearney, Joseph K.; Plumert, Jodie M.

    2013-01-01

    This investigation examined how children and adults negotiate a challenging perceptual-motor problem with significant real-world implications--bicycling across two lanes of opposing traffic. Twelve- and 14-year-olds and adults rode a bicycling simulator through an immersive virtual environment. Participants crossed intersections with continuous…

  10. Standing in the middle: Insider/outsider positionality while conducting qualitative research with opposing military veteran political groups

    Science.gov (United States)

    David Flores

    2018-01-01

    This case study describes the process and challenges of conducting qualitative research on two opposing military veteran political groups: Iraq Veterans Against the War and Vets for Freedom. The discussion is based on a dissertation project that compelled me to reflect on my simultaneous "insider" status as a military veteran and "outsider" status...

  11. Only minor additional metabolic health benefits of high as opposed to moderate dose physical exercise in young, moderately overweight men

    DEFF Research Database (Denmark)

    Reichkendler, M H; Larsen, Mads Rosenkilde; Auerbach, P L

    2014-01-01

    % in HIGH (P health assessed by questionnaire increased similarly in MOD (P additional health benefits were found when exercising ∼3,800 as opposed to ∼2,000 kcal/week in young moderately overweight men. This finding may have important...... public health implications....

  12. Maxillary implant-supported overdentures opposed by (partial) natural dentitions : A 5-year prospective case series study

    NARCIS (Netherlands)

    Boven, G. C.; Slot, J. W. A.; Raghoebar, G. M.; Vissink, A.; Meijer, H. J. A.

    2017-01-01

    The aim of this study was to assess the 5-year treatment outcome of maxillary implant-retained overdentures opposed by natural antagonistic teeth. Fifty consecutive patients received maxillary overdentures supported by six dental implants. Implants were placed in the anterior region, if enough bone

  13. Macrophage-derived Wnt opposes notch signaling to specify hepatic progenitor cell fate in chronic liver disease

    NARCIS (Netherlands)

    Boulter, L.; Govaere, O.; Bird, T.G.; Radulescu, S.; Ramachandran, P.; Pellicoro, A.; Ridgway, R.; Seo, S.S.; Spee, B.|info:eu-repo/dai/nl/304830925; van Rooijen, N.; Sansom, O.J.; Iredale, J.P.; Lowell, S.; Roskams, T.A.; Forbes, S.J.

    2012-01-01

    Nat Med. 2012 Mar 4;18(4):572-9. doi: 10.1038/nm.2667. Macrophage-derived Wnt opposes Notch signaling to specify hepatic progenitor cell fate in chronic liver disease. Boulter L, Govaere O, Bird TG, Radulescu S, Ramachandran P, Pellicoro A, Ridgway RA, Seo SS, Spee B, Van Rooijen N, Sansom OJ,

  14. Screening for skeletal metastases of the spine and pelvis: gradient echo opposed-phase MRI compared with bone scintigraphy

    International Nuclear Information System (INIS)

    Neumann, K.; Hosten, N.; Venz, S.

    1995-01-01

    Opposed-phase gradient echo (GRE) MRI at 0.5 T was compared with T1-weighted GRE MRI and bone scintigraphy regarding the detection of malignant bone marrow infiltrates of the spine and pelvis. Seventeen control patients and 41 patients with suspected skeletal metastases were studied with plain and gadolinium-enhanced MRI. In the control group only a vertebral haemangioma showed contrast enhancement, while all metastases (confirmed histologically or by follow-up) were enhancing. Opposed-phase surface coil MRI showed a significantly higher contrast-to-noise ratio of 56 metastases than T1-weighted images. In 28 patients body coil opposed-phase MRI detected more metastatic foci of the spine and pelvis than did bone scintigraphy (84 vs 56). No scintigraphically visualised lesion was missed by MRI. In conclusion, body coil gadolinium-enhanced opposed-phase GRE MRI may be applied as a screening method for skeletal metastases of the spine and pelvis at intermediate field strengths. (orig.)

  15. Screening for skeletal metastases of the spine and pelvis: gradient echo opposed-phase MRI compared with bone scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Neumann, K. [Zentralinstitut fuer Roentgendiagnostik, Universitaetsklinikum Essen, Gesamthochschule Essen (Germany); Hosten, N. [Strahlenklinik und Poliklinik, Universitaetsklinikum Rudolf Virchow, Freie Univ. Berlin (Germany); Venz, S. [Strahlenklinik und Poliklinik, Universitaetsklinikum Rudolf Virchow, Freie Univ. Berlin (Germany)

    1995-11-01

    Opposed-phase gradient echo (GRE) MRI at 0.5 T was compared with T1-weighted GRE MRI and bone scintigraphy regarding the detection of malignant bone marrow infiltrates of the spine and pelvis. Seventeen control patients and 41 patients with suspected skeletal metastases were studied with plain and gadolinium-enhanced MRI. In the control group only a vertebral haemangioma showed contrast enhancement, while all metastases (confirmed histologically or by follow-up) were enhancing. Opposed-phase surface coil MRI showed a significantly higher contrast-to-noise ratio of 56 metastases than T1-weighted images. In 28 patients body coil opposed-phase MRI detected more metastatic foci of the spine and pelvis than did bone scintigraphy (84 vs 56). No scintigraphically visualised lesion was missed by MRI. In conclusion, body coil gadolinium-enhanced opposed-phase GRE MRI may be applied as a screening method for skeletal metastases of the spine and pelvis at intermediate field strengths. (orig.)

  16. Nuclear regulatory decision making

    International Nuclear Information System (INIS)

    Wieland, Patricia; Almeida, Ivan Pedro Salati de

    2011-01-01

    The scientific considerations upon which the nuclear regulations are based provide objective criteria for decisions on nuclear safety matters. However, the decisions that a regulatory agency takes go far beyond granting or not an operating license based on assessment of compliance. It may involve decisions about hiring experts or research, appeals, responses to other government agencies, international agreements, etc.. In all cases, top management of the regulatory agency should hear and decide the best balance between the benefits of regulatory action and undue risks and other associated impacts that may arise, including issues of credibility and reputation. The establishment of a decision framework based on well established principles and criteria ensures performance stability and consistency, preventing individual subjectivity. This article analyzes the challenges to the decision-making by regulatory agencies to ensure coherence and consistency in decisions, even in situations where there is uncertainty, lack of reliable information and even divergence of opinions among experts. The article explores the basic elements for a framework for regulatory decision-making. (author)

  17. Nuclear regulatory decision making

    International Nuclear Information System (INIS)

    2005-01-01

    The fundamental objective of all nuclear safety regulatory bodies is to ensure that nuclear utilities operate their plants at all times in an acceptably safe manner. In meeting this objective, the regulatory body should strive to ensure that its regulatory decisions are technically sound, consistent from case to case, and timely. In addition, the regulator must be aware that its decisions and the circumstances surrounding those decisions can affect how its stakeholders, such as government policy makers, the industry it regulates, and the public, view it as an effective and credible regulator. In order to maintain the confidence of those stakeholders, the regulator should make sure that its decisions are transparent, have a clear basis in law and regulations, and are seen by impartial observers to be fair to all parties. Based on the work of a Nuclear Energy Agency (NEA) expert group, this report discusses some of the basic principles and criteria that a regulatory body should consider in making decisions and describes the elements of an integrated framework for regulatory decision making. (author)

  18. 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.

  19. Nuclear Regulatory Legislation

    International Nuclear Information System (INIS)

    1989-08-01

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

  20. Improving nuclear regulation. NEA regulatory guidance booklets volumes 1-14

    International Nuclear Information System (INIS)

    2011-01-01

    A common theme throughout the series of NEA regulatory guidance reports, or 'green booklets', is the premise that the fundamental objective of all nuclear safety regulatory bodies is to ensure that nuclear facilities are continuously maintained and operated in an acceptably safe manner. In meeting this objective the regulator must bear in mind that it is the operator that has responsibility for safely operating the nuclear facility; the role of the regulator is to assess and to provide assurance regarding the operator's activities in terms of assuming that responsibility. The full series of these reports was brought together in one edition for the first time in 2009 and was widely found to be a useful resource. This second edition comprises 14 volumes, including the latest on The Nuclear Regulator's Role in Assessing Licensee Oversight of Vendor and Other Contracted Services. The reports address various challenges that could apply throughout the lifetime of a nuclear facility, including design, siting, manufacturing, construction, commissioning, operation, maintenance and decommissioning. The compilation is intended to serve as a knowledge management tool both for current regulators and the new nuclear professionals and organisations entering the regulatory field. Contents: Executive Summary; Regulatory Challenges: 1. The Role of the Nuclear Regulator in Promoting and Evaluating Safety Culture; 2. Regulatory Response Strategies for Safety Culture Problems; 3. Nuclear Regulatory Challenges Related to Human Performance; 4. Regulatory Challenges in Using Nuclear Operating Experience; 5. Nuclear Regulatory Review of Licensee Self-assessment (LSA); 6. Nuclear Regulatory Challenges Arising from Competition in Electricity Markets; 7. The Nuclear Regulatory Challenge of Judging Safety Back-fits; 8. The Regulatory Challenges of Decommissioning Nuclear Reactors; 9. The Nuclear Regulator's Role in Assessing Licensee Oversight of Vendor and Other Contracted Services

  1. Regulatory and licensee surveys

    International Nuclear Information System (INIS)

    2009-01-01

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

  2. Regulatory governance of telecommunications liberalisation in Taiwan

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Kuo-Tai [Department of Regional Studies in Humanity and Social Sciences, National Hsin-Chu University of Education, No. 521 Nan-Da Road, Hsin-Chu 300 (China); Hebenton, Bill [School of Law, University of Manchester, M13 9PP (United Kingdom)

    2008-12-15

    This paper examines the changing role of government and market in regulating the telecommunications sector from since 1996 in Taiwan. It contextualises the theoretical aspects of regulatory governance for institutional design and practices, and reviews the concepts and mechanisms for appraising privatisation and regulatory systems. Using a conceptual framework for researching privatisation and regulation, it describes the process and issues pertinent to telecommunications liberalisation and privatisation in Taiwan, supported by a brief presentation of theoretical points of view as well as practitioners' views. The paper presents results concerning criteria for appraising privatisation and regulatory governance and considers policy lessons that can be learned from the experiences of the Taiwanese telecommunications sector's liberalisation. (author)

  3. Prediction of regulatory elements

    DEFF Research Database (Denmark)

    Sandelin, Albin

    2008-01-01

    Finding the regulatory mechanisms responsible for gene expression remains one of the most important challenges for biomedical research. A major focus in cellular biology is to find functional transcription factor binding sites (TFBS) responsible for the regulation of a downstream gene. As wet......-lab methods are time consuming and expensive, it is not realistic to identify TFBS for all uncharacterized genes in the genome by purely experimental means. Computational methods aimed at predicting potential regulatory regions can increase the efficiency of wet-lab experiments significantly. Here, methods...

  4. 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.

  5. Opposing Responses of Bird Functional Diversity to Vegetation Structural Diversity in Wet and Dry Forest.

    Directory of Open Access Journals (Sweden)

    Holly Sitters

    Full Text Available Disturbance regimes are changing worldwide, and the consequences for ecosystem function and resilience are largely unknown. Functional diversity (FD provides a surrogate measure of ecosystem function by capturing the range, abundance and distribution of trait values in a community. Enhanced understanding of the responses of FD to measures of vegetation structure at landscape scales is needed to guide conservation management. To address this knowledge gap, we used a whole-of-landscape sampling approach to examine relationships between bird FD, vegetation diversity and time since fire. We surveyed birds and measured vegetation at 36 landscape sampling units in dry and wet forest in southeast Australia during 2010 and 2011. Four uncorrelated indices of bird FD (richness, evenness, divergence and dispersion were derived from six bird traits, and we investigated responses of these indices and species richness to both vertical and horizontal vegetation diversity using linear mixed models. We also considered the extent to which the mean and diversity of time since fire were related to vegetation diversity. Results showed opposing responses of FD to vegetation diversity in dry and wet forest. In dry forest, where fire is frequent, species richness and two FD indices (richness and dispersion were positively related to vertical vegetation diversity, consistent with theory relating to environmental variation and coexistence. However, in wet forest subject to infrequent fire, the same three response variables were negatively associated with vertical diversity. We suggest that competitive dominance by species results in lower FD as vegetation diversity increases in wet forest. The responses of functional evenness were opposite to those of species richness, functional richness and dispersion in both forest types, highlighting the value of examining multiple FD metrics at management-relevant scales. The mean and diversity of time since fire were uncorrelated

  6. Unsteady Extinction of Opposed Jet Ethylene/Methane HIFiRE Surrogate Fuel Mixtures vs Air

    Science.gov (United States)

    Vaden, Sarah N.; Debes, Rachel L.; Lash, E. Lara; Burk, Rachel S.; Boyd, C. Merritt; Wilson, Lloyd G.; Pellett, Gerald L.

    2009-01-01

    A unique idealized study of the subject fuel vs. air systems was conducted using an Oscillatory-input Opposed Jet Burner (OOJB) system and a newly refined analysis. Extensive dynamic-extinction measurements were obtained on unanchored (free-floating) laminar Counter Flow Diffusion Flames (CFDFs) at 1-atm, stabilized by steady input velocities (e.g., U(sub air)) and perturbed by superimposed in-phase sinusoidal velocity inputs at fuel and air nozzle exits. Ethylene (C2H4) and methane (CH4), and intermediate 64/36 and 15/85 molar percent mixtures were studied. The latter gaseous surrogates were chosen earlier to mimic ignition and respective steady Flame Strengths (FS = U(sub air)) of vaporized and cracked, and un-cracked, JP-7 "like" kerosene for a Hypersonic International Flight Research Experimentation (HIFiRE) scramjet. For steady idealized flameholding, the 100% C2H4 flame is respectively approx. 1.3 and approx.2.7 times stronger than a 64/36 mix and CH4; but is still 12.0 times weaker than a 100% H2-air flame. Limited Hot-Wire (HW) measurements of velocity oscillations at convergent-nozzle exits, and more extensive Probe Microphone (PM) measurements of acoustic pressures, were used to normalize Dynamic FSs, which decayed linearly with pk/pk U(sub air) (velocity magnitude, HW), and also pk/pk P (pressure magnitude, PM). Thus Dynamic Flame Weakening (DFW) is defined as % decrease in FS per Pascal of pk/pk P oscillation, namely, DFW = -100 d(U(sub air)/U(sub air),0Hz)/d(pkpk P). Key findings are: (1) Ethylene flames are uniquely strong and resilient to extinction by oscillating inflows below 150 Hz; (2) Methane flames are uniquely weak; (3) Ethylene / methane surrogate flames are disproportionately strong with respect to ethylene content; and (4) Flame weakening is consistent with limited published results on forced unsteady CFDFs. Thus from 0 to approx. 10 Hz and slightly higher, lagging diffusive responses of key species led to progressive phase lags (relative

  7. Opposing Responses of Bird Functional Diversity to Vegetation Structural Diversity in Wet and Dry Forest.

    Science.gov (United States)

    Sitters, Holly; York, Alan; Swan, Matthew; Christie, Fiona; Di Stefano, Julian

    2016-01-01

    Disturbance regimes are changing worldwide, and the consequences for ecosystem function and resilience are largely unknown. Functional diversity (FD) provides a surrogate measure of ecosystem function by capturing the range, abundance and distribution of trait values in a community. Enhanced understanding of the responses of FD to measures of vegetation structure at landscape scales is needed to guide conservation management. To address this knowledge gap, we used a whole-of-landscape sampling approach to examine relationships between bird FD, vegetation diversity and time since fire. We surveyed birds and measured vegetation at 36 landscape sampling units in dry and wet forest in southeast Australia during 2010 and 2011. Four uncorrelated indices of bird FD (richness, evenness, divergence and dispersion) were derived from six bird traits, and we investigated responses of these indices and species richness to both vertical and horizontal vegetation diversity using linear mixed models. We also considered the extent to which the mean and diversity of time since fire were related to vegetation diversity. Results showed opposing responses of FD to vegetation diversity in dry and wet forest. In dry forest, where fire is frequent, species richness and two FD indices (richness and dispersion) were positively related to vertical vegetation diversity, consistent with theory relating to environmental variation and coexistence. However, in wet forest subject to infrequent fire, the same three response variables were negatively associated with vertical diversity. We suggest that competitive dominance by species results in lower FD as vegetation diversity increases in wet forest. The responses of functional evenness were opposite to those of species richness, functional richness and dispersion in both forest types, highlighting the value of examining multiple FD metrics at management-relevant scales. The mean and diversity of time since fire were uncorrelated with vegetation

  8. Opposing regulation of cytochrome P450 expression by CAR and PXR in hypothyroid mice

    Energy Technology Data Exchange (ETDEWEB)

    Park, Young Joo [Department of Internal Medicine, Seoul National University College of Medicine (Korea, Republic of); Seoul National University Bundang Hospital, Seoul (Korea, Republic of); Lee, Eun Kyung [Department of Internal Medicine, Seoul National University College of Medicine (Korea, Republic of); Lee, Yoon Kwang [Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030 (United States); Park, Do Joon; Jang, Hak Chul [Department of Internal Medicine, Seoul National University College of Medicine (Korea, Republic of); Moore, David D., E-mail: moore@bcm.edu [Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030 (United States)

    2012-09-01

    Clinical hypothyroidism affects various metabolic processes including drug metabolism. CYP2B and CYP3A are important cytochrome P450 drug metabolizing enzymes that are regulated by the xenobiotic receptors constitutive androstane receptor (CAR, NR1I3) and pregnane X receptor (PXR, NR1I2). We evaluated the regulation of the hepatic expression of CYPs by CAR and PXR in the hypothyroid state induced by a low-iodine diet containing 0.15% propylthiouracil. Expression of Cyp3a11 was suppressed in hypothyroid C57BL/6 wild type (WT) mice and a further decrement was observed in hypothyroid CAR{sup −/−} mice, but not in hypothyroid PXR{sup −/−} mice. In contrast, expression of Cyp2b10 was induced in both WT and PXR{sup −/−} hypothyroid mice, and this induction was abolished in CAR{sup −/−} mice and in and CAR{sup −/−} PXR{sup −/−} double knockouts. CAR mRNA expression was increased by hypothyroidism, while PXR expression remained unchanged. Carbamazepine (CBZ) is a commonly used antiepileptic that is metabolized by CYP3A isoforms. After CBZ treatment of normal chow fed mice, serum CBZ levels were highest in CAR{sup −/−} mice and lowest in WT and PXR{sup −/−} mice. Hypothyroid WT or PXR{sup −/−} mice survived chronic CBZ treatment, but all hypothyroid CAR{sup −/−} and CAR{sup −/−} PXR{sup −/−} mice died, with CAR{sup −/−}PXR{sup −/−} mice surviving longer than CAR{sup −/−} mice (12.3 ± 3.3 days vs. 6.3 ± 2.1 days, p = 0.04). All these findings suggest that hypothyroid status affects xenobiotic metabolism, with opposing responses of CAR and PXR and their CYP targets that can cancel each other out, decreasing serious metabolic derangement in response to a xenobiotic challenge. -- Highlights: ► Hypothyroid status activates CAR in mice and induces Cyp2b10 expression. ► Hypothyroid status suppresses PXR activity in mice and represses Cyp3a11 expression. ► These responses balance each other out in normal mice.

  9. Opposing regulation of cytochrome P450 expression by CAR and PXR in hypothyroid mice

    International Nuclear Information System (INIS)

    Park, Young Joo; Lee, Eun Kyung; Lee, Yoon Kwang; Park, Do Joon; Jang, Hak Chul; Moore, David D.

    2012-01-01

    Clinical hypothyroidism affects various metabolic processes including drug metabolism. CYP2B and CYP3A are important cytochrome P450 drug metabolizing enzymes that are regulated by the xenobiotic receptors constitutive androstane receptor (CAR, NR1I3) and pregnane X receptor (PXR, NR1I2). We evaluated the regulation of the hepatic expression of CYPs by CAR and PXR in the hypothyroid state induced by a low-iodine diet containing 0.15% propylthiouracil. Expression of Cyp3a11 was suppressed in hypothyroid C57BL/6 wild type (WT) mice and a further decrement was observed in hypothyroid CAR −/− mice, but not in hypothyroid PXR −/− mice. In contrast, expression of Cyp2b10 was induced in both WT and PXR −/− hypothyroid mice, and this induction was abolished in CAR −/− mice and in and CAR −/− PXR −/− double knockouts. CAR mRNA expression was increased by hypothyroidism, while PXR expression remained unchanged. Carbamazepine (CBZ) is a commonly used antiepileptic that is metabolized by CYP3A isoforms. After CBZ treatment of normal chow fed mice, serum CBZ levels were highest in CAR −/− mice and lowest in WT and PXR −/− mice. Hypothyroid WT or PXR −/− mice survived chronic CBZ treatment, but all hypothyroid CAR −/− and CAR −/− PXR −/− mice died, with CAR −/− PXR −/− mice surviving longer than CAR −/− mice (12.3 ± 3.3 days vs. 6.3 ± 2.1 days, p = 0.04). All these findings suggest that hypothyroid status affects xenobiotic metabolism, with opposing responses of CAR and PXR and their CYP targets that can cancel each other out, decreasing serious metabolic derangement in response to a xenobiotic challenge. -- Highlights: ► Hypothyroid status activates CAR in mice and induces Cyp2b10 expression. ► Hypothyroid status suppresses PXR activity in mice and represses Cyp3a11 expression. ► These responses balance each other out in normal mice. ► Hypothyroidism sensitizes CAR null mice to toxic effects of carbamazepine.

  10. ADVANTAGES OF SURGICAL TREATMENT OF ACHILLES TENDON RUPTURE BY PERCUTANEOUS SUTURE AS OPPOSED TO NONSURGICAL TREATMENT

    Directory of Open Access Journals (Sweden)

    Goran Vidić

    2010-06-01

    Full Text Available The Achilles tendon is the strongest tendon in the body, and its rupture appears to be the most common injury of the tendomuscular apparatus. This type of injury is more frequent in sportsmen, especially those who play tennis, gymnastics, skiing, handball, football, basketball and athletics. Also, the ruptures are common in people who engage in sports activities for recreation. They appear more often in males, in proportion of 3:1. It appears reciprocally in 25- 30% of the cases. The rupture is easily diagnosed by means of clinical examination (Thompson's test and ultrasonography.The aim of the analysis was to point to the advantages of surgical treatment of a fresh Achilles tendon rupture as opposed to non-surgical treatment by plaster immobilization.The examination was performed on 35 patients, of which 16 (45,71% were treated operatively and 19 (54,29% were treated nonoperatively. The average age of the patients was 38.8 years, that is 37.1 for those treated operatively and 40.2 for those treated nonoperatively. Among the examinees, there were 29(82,86% men and 6 (17,14% women. The operative treatment method consisted of percutaneous suturing, whereas the nonoperative treatment involved the circular above the knee plaster immobilization. All operatively treated patients underwent the surgical treatment in the first 48 hours from the time when the injury had occured. Anesthesia was local and infiltrative.The obtained results showed that there were no unhealed ruptures or re-ruptures. In the group of patients who did not undergo the surgery, there was 1 re-rupture and 1 unhealed rupture, after which the surgical treatment had to be performed in both cases. In the group of operated patients there were no infections, however, 1 thromboembolism occured. Recovery of muscular strenght of the tendon and the realization of the full range of movement required less time in the operated patients. The ultrasonographic findings in the operated patients

  11. Opposing effects of fire severity on climate feedbacks in Siberian larch forests

    Science.gov (United States)

    Loranty, M. M.; Alexander, H. D.; Natali, S.; Kropp, H.; Mack, M. C.; Bunn, A. G.; Davydov, S. P.; Erb, A.; Kholodov, A. L.; Schaaf, C.; Wang, Z.; Zimov, N.; Zimov, S. A.

    2017-12-01

    may lead to opposing climate feedbacks. At effectively large scales these changes constitute positive and negative climate feedbacks, respectively. Accurate predictive understanding of terrestrial Arctic climate feedbacks requires improved knowledge regarding the ecological consequences of changing fire regimes in Siberian boreal forests.

  12. Do hedonic motives moderate regulatory focus motives? Evidence from the framing of persuasive messages.

    Science.gov (United States)

    Malaviya, Prashant; Brendl, C Miguel

    2014-01-01

    Research on regulatory focus has established a regulatory matching effect: The persuasiveness of a message is enhanced when regulatory orientations of message and perceiver match (i.e., both are promotion or both are prevention). We report evidence that varying the hedonic outcome reverses this effect. We manipulated hedonic outcome by explicitly stating pleasurable versus painful outcomes as part of the message frame as well as by priming perceivers to focus on either pleasurable or painful outcomes. When both message and perceiver were focused on pleasurable outcomes, we replicated the regulatory matching effect. However, the matching effect reversed when the hedonic outcome of the message was opposed to that of the perceiver (i.e., one was pleasurable and the other painful). Under these conditions, messages that mismatched the perceivers' regulatory orientation were more persuasive (i.e., promotion message for a prevention oriented perceiver or vice versa). We also examined the persuasion effects when both message and perceiver were focused on painful outcomes and found that the regulatory matching effect re-emerged. The reversal of the regulatory matching effect by hedonic outcome strongly suggests that hedonic motives (approach of pleasure vs. avoidance of pain) and regulatory focus motives are distinct constructs. This is important because contrary to theoretical statements these constructs have often been confounded.

  13. Discussion on building safety culture inside a nuclear safety regulatory body

    International Nuclear Information System (INIS)

    Fan Yumao

    2013-01-01

    A strong internal safety culture plays a key role in improving the performance of a nuclear regulatory body. This paper discusses the definition of internal safety culture of nuclear regulatory bodies, and explains the functions that the safety culture to facilitate the nuclear safety regulation and finally puts forward some thoughts about building internal safety culture inside regulatory bodies. (author)

  14. Regulatory Issues Surrounding Merchant Interconnection

    International Nuclear Information System (INIS)

    Kuijlaars, Kees-Jan; Zwart, Gijsbert

    2003-11-01

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

  15. 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.

  16. Scientific underpinnings of biotechnology regulatory frameworks.

    Science.gov (United States)

    Gleim, Savannah; Smyth, Stuart J

    2018-05-25

    Part of what is presently missing at domestic regulatory levels (and that is important at the international level as well) is a detailed understanding of what the rules of, and for, regulation should be, who the actors, stakeholders and major decision makers are and finally, how to get agreement about the rules. Greater insights into the system of rules that underpin regulatory frameworks for agri-food and biotechnology products in genetically modified (GM) crop- adopting nations will provide value by clarifying the evidence used to commercialize these technologies. This article examines the public documents available from Canada, the United States, the European Union and the Organisation for Economic Cooperation and Development regarding the development of regulatory risk assessment frameworks for products of biotechnology to determine what science grounds these frameworks. The documentation used to provide the initial structure to the existing regulatory frameworks identifies the linkages, connections and relationships that exist between science, risk assessment and regulatory policy. The relationship between risk and regulation has never been more critical to the commercialization of innovative agricultural products. Documenting the role of science-based risk assessment in regulations and how this has changed over the 20 years of experience in regulating GM crops will identify changes in the risk/regulation relationship. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

  17. Regulatory dendritic cells in autoimmunity: A comprehensive review.

    Science.gov (United States)

    Liu, Juan; Cao, Xuetao

    2015-09-01

    Dendritic cells (DCs) are professional antigen-presenting cells (APC) with significant phenotypic heterogeneity and functional plasticity. DCs play crucial roles in initiating effective adaptive immune responses for elimination of invading pathogens and also in inducing immune tolerance toward harmless components to maintain immune homeostasis. The regulatory capacity of DCs depends on their immature state and distinct subsets, yet not restricted to the immature state and one specialized subset. The tolerogenicity of DC is controlled by a complex network of environmental signals and cellular intrinsic mechanisms. Regulatory DCs play an important role in the maintenance of immunological tolerance via the induction of T cell unresponsiveness or apoptosis, and generation of regulatory T cells. DCs play essential roles in driving autoimmunity via promoting the activation of effector T cells such as T helper 1 and T helper 17 cells, and/or suppressing the generation of regulatory T cells. Besides, a breakdown of DCs-mediated tolerance due to abnormal environmental signals or breakdown of intrinsic regulatory mechanisms is closely linked with the pathogenesis of autoimmune diseases. Novel immunotherapy taking advantage of the tolerogenic potential of regulatory DCs is being developed for treatment of autoimmune diseases. In this review, we will describe the current understanding on the generation of regulatory DC and the role of regulatory DCs in promoting tolerogenic immune responses and suppressing autoimmune responses. The emerging roles of DCs dysfunction in the pathogenesis of autoimmune diseases and the potential application of regulatory DCs in the treatment of autoimmune diseases will also be discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. NRC Regulatory Agenda

    International Nuclear Information System (INIS)

    1992-07-01

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

  19. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1993-02-01

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

  20. NRC Regulatory Agenda

    International Nuclear Information System (INIS)

    1989-07-01

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

  1. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1992-11-01

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

  2. Comments on regulatory reform

    International Nuclear Information System (INIS)

    Hendrie, J.M.

    1982-01-01

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

  3. Comments on regulatory reform

    Energy Technology Data Exchange (ETDEWEB)

    Hendrie, J.M.

    1982-01-01

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

  4. 3 CFR - Regulatory Review

    Science.gov (United States)

    2010-01-01

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

  5. The role of self-regulatory skills and automaticity on the effectiveness of a brief weight loss habit-based intervention: secondary analysis of the 10 top tips randomised trial.

    Science.gov (United States)

    Kliemann, Nathalie; Vickerstaff, Victoria; Croker, Helen; Johnson, Fiona; Nazareth, Irwin; Beeken, Rebecca J

    2017-09-05

    Habit-interventions are designed to promote the automaticity of healthy behaviours and may also enhance self-regulatory skills during the habit-formation process. A recent trial of habit-based advice for weight loss (10 Top Tips; 10TT), found that patients allocated to 10TT lost significantly more weight over 3 months than those allocated to usual care, and reported greater increases in automaticity for the target behaviours. The current study aimed to test the hypothesis that i) 10TT increased self-regulatory skills more than usual care, and ii) that self-regulatory skills and automaticity changes mediated the effect of 10TT on weight loss. 537 obese patients from 14 primary care practices in the UK were randomized to receive 10TT or usual care. Patients in the 10TT group received a leaflet containing tips for weight loss and healthy habits formation, a self-monitoring log book and a wallet-sized shopping guide on how to read food labels. Patients were weighed and completed validated questionnaires for self-regulation and automaticity at baseline and 3-month follow-up. Within-group and Between-group effects were explored using Paired T-test and ANCOVA, respectively. Mediation was assessed using bootstrapping to estimate indirect effects and the sobel test. Over 3 months patients who were given 10TT reported greater increases in self-regulatory skills (Mean difference: .08; 95% CI .01; .15) than those who received usual care. Changes in self-regulatory skills and automaticity over 3 months mediated the effect of the intervention on weight loss (β = .52, 95% Bias Corrected CI .17; .91). As hypothesised, 10TT enhanced self-regulatory skills and changes in self-regulatory skills and automaticity mediated the effect of the intervention on weight loss. This supports the proposition that self-regulatory training and habit formation are important features of weight loss interventions. This study was prospectively registered with the International Standard Randomised

  6. The Regulatory Function of Eosinophils.

    Science.gov (United States)

    Wen, Ting; Rothenberg, Marc E

    2016-10-01

    Eosinophils are a minority circulating granulocyte classically viewed as being involved in host defense against parasites and promoting allergic reactions. However, a series of new regulatory functions for these cells have been identified in the past decade. During homeostasis, eosinophils develop in the bone marrow and migrate from the blood into target tissues following an eotaxin gradient, with interleukin-5 being a key cytokine for eosinophil proliferation, survival, and priming. In multiple target tissues, eosinophils actively regulate a variety of immune functions through their vast arsenal of granule products and cytokines, as well as direct cellular interaction with cells in proximity. The immunologic regulation of eosinophils extends from innate immunity to adaptive immunity and also involves non-immune cells. Herein, we summarize recent findings regarding novel roles of murine and human eosinophils, focusing on interactions with other hematopoietic cells. We also review new experimental tools available and remaining questions to uncover a greater understanding of this enigmatic cell.

  7. RegRNA: an integrated web server for identifying regulatory RNA motifs and elements

    OpenAIRE

    Huang, Hsi-Yuan; Chien, Chia-Hung; Jen, Kuan-Hua; Huang, Hsien-Da

    2006-01-01

    Numerous regulatory structural motifs have been identified as playing essential roles in transcriptional and post-transcriptional regulation of gene expression. RegRNA is an integrated web server for identifying the homologs of regulatory RNA motifs and elements against an input mRNA sequence. Both sequence homologs and structural homologs of regulatory RNA motifs can be recognized. The regulatory RNA motifs supported in RegRNA are categorized into several classes: (i) motifs in mRNA 5′-untra...

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

    OpenAIRE

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

    2013-01-01

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

  9. Opposed-Flow Flame Spread over Thin Solid Fuels in a Narrow Channel under Different Gravity

    Science.gov (United States)

    Zhang, Xia; Yu, Yong; Wan, Shixin; Wei, Minggang; Hu, Wen-Rui

    Flame spread over solid surface is critical in combustion science due to its importance in fire safety in both ground and manned spacecraft. Eliminating potential fuels from materials is the basic method to protect spacecraft from fire. The criterion of material screening is its flamma-bility [1]. Since gas flow speed has strong effect on flame spread, the combustion behaviors of materials in normal and microgravity will be different due to their different natural convec-tion. To evaluate the flammability of materials used in the manned spacecraft, tests should be performed under microgravity. Nevertheless, the cost is high, so apparatus to simulate mi-crogravity combustion under normal gravity was developed. The narrow channel is such an apparatus in which the buoyant flow is restricted effectively [2, 3]. The experimental results of the horizontal narrow channel are consistent qualitatively with those of Mir Space Station. Quantitatively, there still are obvious differences. However, the effect of the channel size on flame spread has only attracted little attention, in which concurrent-flow flame spread over thin solid in microgravity is numerically studied[4], while the similarity of flame spread in different gravity is still an open question. In addition, the flame spread experiments under microgravity are generally carried out in large wind tunnels without considering the effects of the tunnel size [5]. Actually, the materials are always used in finite space. Therefore, the flammability given by experiments using large wind tunnels will not correctly predict the flammability of materials in the real environment. In the present paper, the effect of the channel size on opposed-flow flame spread over thin solid fuels in both normal and microgravity was investigated and compared. In the horizontal narrow channel, the flame spread rate increased before decreased as forced flow speed increased. In low speed gas flows, flame spread appeared the same trend as that in

  10. Complications and Clinical Considerations of the Implant-Retained Zirconia Complete-Arch Prosthesis with Various Opposing Dentitions.

    Science.gov (United States)

    Gonzalez, Jorge; Triplett, Robert G

    To evaluate the performance of the implant-retained zirconia complete-arch prosthesis with various opposing dentitions. The 40 patients included in this retrospective case series study were treated with one or two implant-retained zirconia complete-arch prostheses (ZIRCAP) using the Zirkonzahn protocol. Prettau zirconia frames were created with strategic cutbacks in the structure to extend zirconia incisal coverage of the esthetic anterior sextants and complete monolithic zirconia in the molar areas; subsequent layers of porcelain were applied to nonfunctional and esthetic areas. Patients had three possible occlusal scenarios: (1) maxillary ZIRCAP and mandibular ZIRCAP, (2) maxillary ZIRCAP and mandibular natural dentition, and (3) maxillary ZIRCAP and mandibular conventional hybrid prosthesis. Complications were recorded during follow-up appointments 3, 6, and 12 months after definitive prosthesis delivery. The mean treatment observation period was 33 months. Eight prosthetic complications were noted for the 40 implant-retained zirconia complete-arch prostheses (18.18%), including six cases of minor porcelain chipping and two cases of debonding of the metal insert from the zirconia framework. Maxillary ZIRCAP opposing mandibular ZIRCAP and maxillary ZIRCAP opposing mandibular natural dentition occlusal scenarios presented the same complication ratio of 4. No complications were seen in the maxillary ZIRCAP opposing mandibular conventional hybrid prosthesis group, yet 16 complications were found as denture tooth fractures in 12 mandibular conventional hybrid prostheses (ratio of 0.75). The results indicate that the implant-retained zirconia complete-arch prosthesis offers acceptable performance for use as an alternative to the conventional titanium framework acrylic veneer prosthesis for complete edentulism with a lower incidence of prosthetic complications and fewer maintenance appointments. Chipping of veneering porcelain was the most common complication, but a

  11. Nuclear Regulatory Commission information digest

    International Nuclear Information System (INIS)

    1990-03-01

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

  12. Characteristics of regulatory regimes

    Directory of Open Access Journals (Sweden)

    Noralv Veggeland

    2013-03-01

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

  13. NRC regulatory agenda

    International Nuclear Information System (INIS)

    1993-07-01

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

  14. Opposing Effects of α2- and β-Adrenergic Receptor Stimulation on Quiescent Neural Precursor Cell Activity and Adult Hippocampal Neurogenesis

    Science.gov (United States)

    Prosper, Boris W.; Marathe, Swanand; Husain, Basma F. A.; Kernie, Steven G.; Bartlett, Perry F.; Vaidya, Vidita A.

    2014-01-01

    Norepinephrine regulates latent neural stem cell activity and adult hippocampal neurogenesis, and has an important role in modulating hippocampal functions such as learning, memory and mood. Adult hippocampal neurogenesis is a multi-stage process, spanning from the activation and proliferation of hippocampal stem cells, to their differentiation into neurons. However, the stage-specific effects of noradrenergic receptors in regulating adult hippocampal neurogenesis remain poorly understood. In this study, we used transgenic Nestin-GFP mice and neurosphere assays to show that modulation of α2- and β-adrenergic receptor activity directly affects Nestin-GFP/GFAP-positive precursor cell population albeit in an opposing fashion. While selective stimulation of α2-adrenergic receptors decreases precursor cell activation, proliferation and immature neuron number, stimulation of β-adrenergic receptors activates the quiescent precursor pool and enhances their proliferation in the adult hippocampus. Furthermore, our data indicate no major role for α1-adrenergic receptors, as we did not observe any change in either the activation and proliferation of hippocampal precursors following selective stimulation or blockade of α1-adrenergic receptors. Taken together, our data suggest that under physiological as well as under conditions that lead to enhanced norepinephrine release, the balance between α2- and β-adrenergic receptor activity regulates precursor cell activity and hippocampal neurogenesis. PMID:24922313

  15. Effects of Scavenging System Configuration on In-Cylinder Air Flow Organization of an Opposed-Piston Two-Stroke Engine

    Directory of Open Access Journals (Sweden)

    Fukang Ma

    2015-06-01

    Full Text Available In-cylinder air flow is very important from the point of view of mixture formation and combustion. In this direction, intake chamber structure and piston crown shape play a very crucial role for in-cylinder air pattern of opposed-piston two-stroke (OP2S engines. This study is concerned with the three-dimensional (3D computational fluid dynamics (CFD analysis of in-cylinder air motion coupled with the comparison of predicted results with the zero-dimensional (0D parametric model. Three configurations viz., a flat piston uniform scavenging chamber, a flat piston non-uniform scavenging chamber and a pit piston non-uniform scavenging chamber have been studied. 0D model analysis of in-cylinder air flow is consistent with 3D CFD simulation. It is concluded that a pit piston non-uniform scavenging chamber is the best design from the point of view of tumble ratio, turbulent kinetic energy and turbulent intensity, which play very important roles in imparting proper air motion. Meanwhile a flat piston uniform scavenging chamber can organize a higher swirl ratio and lower tumble ratio which is important to improve the scavenging process.

  16. A flexible regulatory framework

    International Nuclear Information System (INIS)

    Silvennoinen, T.

    2000-01-01

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

  17. Perspectives on Regulatory T Cell Therapies

    OpenAIRE

    Probst-Kepper, Michael; Kröger, Andrea; Garritsen, Henk S.P.; Buer, Jan

    2009-01-01

    Adoptive transfer in animal models clearly indicate an essential role of CD4+ CD25+ FOXP3+ regulatory T (Treg) cells in prevention and treatment of autoimmune and graft-versus-host disease. Thus, Treg cell therapies and development of drugs that specifically enhance Treg cell function and development represent promising tools to establish dominant tolerance. So far, lack of specific markers to differentiate human Treg cells from activated CD4+ CD25+ effector T cells, which also express FOXP3 ...

  18. Regulatory T cells: immune suppression and beyond

    OpenAIRE

    Wan, Yisong Y

    2010-01-01

    Foxp3-expressing regulatory T cells (Tregs) were originally identified as critical in maintaining self-tolerance and immune homeostasis. The immunosuppressive functions of Tregs are widely acknowledged and have been extensively studied. Recent studies have revealed many diverse roles of Tregs in shaping the immune system and the inflammatory response. This review will discuss our efforts as well as the efforts of others towards understanding the multifaceted function of Treg...

  19. Safety Committees for Argentinean Research Reactor - Regulatory Issues

    International Nuclear Information System (INIS)

    Perrin, Carlos D.

    2009-01-01

    In the field of radiological and nuclear safety, the Nuclear Regulatory Authority (ARN) of Argentina controls three research reactors and three critical assemblies, by means of evaluations, audits and inspections, in order to ensure the fulfillment of the requirements established in the Licenses, in the Regulatory Standards and in the Mandatory Documentation in general. From the Nuclear Regulatory Authority's point of view, within the general process of research reactors safety management, the Operational Organization self verification of radiological and nuclear safety plays an outstanding role. In this aspect the ARN has established specific requirements in the Regulatory Standards, in the Operation Licenses and in the Operational Limits and Conditions. These requirements include the figure of different safety committees, which act as reviewers or advisers in diverse situations. This paper describes the main characteristics of the committees, their function, scope and the regulatory documents where the requirements are included. (author)

  20. Even Giants Need A Club: Domestic Institutions, Market Size, And Regulatory Influence

    OpenAIRE

    DAVID BACH

    2005-01-01

    This paper show that work on international market regulation has paid insufficient attention to the critical role played by domestic political and regulatory institutions. Existing literature emphasizes the role of market power, determined by market size, in analyzing international regulatory influence. While we do not contest the importance of market power, we introduce the notion of domestic regulatory capacity to capture the domestic institutional side of international market regulation th...

  1. A gene regulatory network armature for T-lymphocyte specification

    Energy Technology Data Exchange (ETDEWEB)

    Fung, Elizabeth-sharon [Los Alamos National Laboratory

    2008-01-01

    Choice of a T-lymphoid fate by hematopoietic progenitor cells depends on sustained Notch-Delta signaling combined with tightly-regulated activities of multiple transcription factors. To dissect the regulatory network connections that mediate this process, we have used high-resolution analysis of regulatory gene expression trajectories from the beginning to the end of specification; tests of the short-term Notchdependence of these gene expression changes; and perturbation analyses of the effects of overexpression of two essential transcription factors, namely PU.l and GATA-3. Quantitative expression measurements of >50 transcription factor and marker genes have been used to derive the principal components of regulatory change through which T-cell precursors progress from primitive multipotency to T-lineage commitment. Distinct parts of the path reveal separate contributions of Notch signaling, GATA-3 activity, and downregulation of PU.l. Using BioTapestry, the results have been assembled into a draft gene regulatory network for the specification of T-cell precursors and the choice of T as opposed to myeloid dendritic or mast-cell fates. This network also accommodates effects of E proteins and mutual repression circuits of Gfil against Egr-2 and of TCF-l against PU.l as proposed elsewhere, but requires additional functions that remain unidentified. Distinctive features of this network structure include the intense dose-dependence of GATA-3 effects; the gene-specific modulation of PU.l activity based on Notch activity; the lack of direct opposition between PU.l and GATA-3; and the need for a distinct, late-acting repressive function or functions to extinguish stem and progenitor-derived regulatory gene expression.

  2. T-regulatory cells in chronic rejection versus stable grafts.

    Science.gov (United States)

    Al-Wedaie, Fatima; Farid, Eman; Tabbara, Khaled; El-Agroudy, Amgad E; Al-Ghareeb, Sumaya M

    2015-04-01

    Studying regulatory T cells in kidney allograft acceptance versus chronic rejection may help in the understanding of more mechanisms of immune tolerance and, in the future, may enable clinicians to induce immune tolerance and decrease the use of immunosuppressive drugs. The aim of the current study was to evaluate regulatory T cells in kidney transplant patients with stable graft versus transplant with biopsy-proven chronic rejection. The 3 groups that were studied included: kidney transplanted patients with no rejection episodes (n = 43); transplanted patients with biopsy-proven renal rejection (n = 27); and healthy age-matched nontransplanted individuals as controls (n = 42).The percentage of regulatory T cells (CD4+CD25+Foxp3+) in blood was determined by flow cytometry. The regulatory T cell percentage was significantly lower in chronic rejection patients than control or stable graft groups. No significant difference was observed in regulatory T cell percentage between the stable graft and control groups. In the stable graft group, patients on rapamycin had a significantly higher regulatory T cell percentage than patients on cyclosporine. No effect of donor type, infection, or duration after transplant was observed on regulatory T cell percentage. The results of the current study are consistent with previous studies addressing the function of regulatory T cells in inducing immunotolerance after kidney transplant. Considering the established role of regulatory T cells in graft maintenance and our observation of high regulatory T cell percentage in patients receiving rapamycin than cyclosporine, we recommend including rapamycin when possible in immunosuppressive protocols. The findings from the current study on the chronic rejection group support ongoing research of having treatment with regulatory T cells, which may constitute a novel, efficient antirejection therapy in the future.

  3. Industry Presentation to Regulatory Workshop

    International Nuclear Information System (INIS)

    Treasure, Mark

    2012-01-01

    Mr. Mark Treasure from EDF NGL gave a presentation on industry perspectives on safety culture oversight. Mr. Treasure is the Nuclear Inspection and Oversight Manager within the Safety and Regulation Division. The presentation started with an explanation of the role of the nuclear inspection and oversight group (internal regulator), and their current approach to internal oversight of safety culture. A key element of the current internal regulatory oversight program is Management and Leadership Assessments. These are carried out by a team including management peers from other plants to enhance credibility. Findings can be linked to safety performance, and typically identify issues in areas such as accountability arrangements and strategic focus of the leadership team. Safety indicators have also been introduced to show trends in safety management and safety performance for each EDF UK nuclear power plant. A periodic nuclear safety culture survey is also carried out to identify focus areas and progress. The presentation included discussion on views of the role of the nuclear regulator. Important aspects were identified as: - Supporting the internal regulator by seeking to understand before taking enforcement action, maintaining an open dialogue and recognising that this area is complex and that there is rarely a 'silver bullet' solution. - Communication: being visible and actively discussing safety improvement, and use of language which emphasises nuclear safety rather than legal compliance. - Positive reinforcement to recognise efforts and encourage further improvement

  4. miR-34a: Multiple Opposing Targets and One Destiny in Hepatocellular Carcinoma.

    Science.gov (United States)

    Yacoub, Radwa Alaa; Fawzy, Injie Omar; Assal, Reem Amr; Hosny, Karim Adel; Zekri, Abdel-Rahman Nabawy; Esmat, Gamal; El Tayebi, Hend Mohamed; Abdelaziz, Ahmed Ihab

    2016-12-28

    Background and Aims: The role of miR-34a in hepatocellular carcinoma (HCC) is controversial and several unresolved issues remain, including its expression pattern and relevance to tumor etiology, tumor stage and prognosis, and finally, its impact on apoptosis. Methods: miR-34a expression was assessed in hepatitis C virus (HCV)-induced non-metastatic HCC tissues by RT-Q-PCR. Huh-7 cells were transfected with miR-34a mimics and the impact of miR-34a was examined on 84 pro-apoptotic/anti-apoptotic genes using PCR array; its net effect was tested on cell viability via MTT assay. Results: miR-34a expression was up-regulated in HCC tissues. Moreover, miR-34a induced a large set of pro-apoptotic/anti-apoptotic genes, with a net result of triggering apoptosis and repressing cell viability. Conclusions: HCC-related differential expression of miR-34a could be etiology-based or stage-specific, and low expression of miR-34a may predict poor prognosis. This study's findings also emphasize the role of miR-34a in apoptosis.

  5. Opposing effects of oxidative challenge and carotenoids on antioxidant status and condition-dependent sexual signalling.

    Science.gov (United States)

    Tomášek, Oldřich; Gabrielová, Barbora; Kačer, Petr; Maršík, Petr; Svobodová, Jana; Syslová, Kamila; Vinkler, Michal; Albrecht, Tomáš

    2016-03-22

    Several recent hypotheses consider oxidative stress to be a primary constraint ensuring honesty of condition-dependent carotenoid-based signalling. The key testable difference between these hypotheses is the assumed importance of carotenoids for redox homeostasis, with carotenoids being either antioxidant, pro-oxidant or unimportant. We tested the role of carotenoids in redox balance and sexual signalling by exposing adult male zebra finches (Taeniopygia guttata) to oxidative challenge (diquat dibromide) and manipulating carotenoid intake. As the current controversy over the importance of carotenoids as antioxidants could stem from the hydrophilic basis of commonly-used antioxidant assays, we used the novel measure of in vivo lipophilic antioxidant capacity. Oxidative challenge reduced beak pigmentation but elicited an increase in antioxidant capacity suggesting resource reallocation from signalling to redox homeostasis. Carotenoids counteracted the effect of oxidative challenge on lipophilic (but not hydrophilic) antioxidant capacity, thereby supporting carotenoid antioxidant function in vivo. This is inconsistent with hypotheses proposing that signalling honesty is maintained through either ROS-induced carotenoid degradation or the pro-oxidant effect of high levels of carotenoid-cleavage products acting as a physiological handicap. Our data further suggest that assessment of lipophilic antioxidant capacity is necessary to fully understand the role of redox processes in ecology and evolution.

  6. Design reviews from a regulatory perspective

    International Nuclear Information System (INIS)

    Foster, B.D.

    1991-01-01

    This paper presents views on the role of the licensing engineer in the design process with specific emphasis on design reviews and the automated information management tools that support design reviews. The licensing engineer is seen as an important member of a design review team. The initial focus of the licensing engineer during design reviews is shown to be on ensuring that applicable regulatory requirements are addressed by the design. The utility of an automated tool, such as a commitments management system, to support regulatory requirements identification is discussed. The next responsibility of the licensing engineer is seen as verifying that regulatory requirements are transformed into measurable performance requirements. Performance requirements are shown to provide the basis for developing detailed design review criteria. Licensing engineer input during design reviews is discussed. This input is shown to be especially critical in cases where review findings may impact application of regulatory requirements. The use of automated tools in supporting design reviews is discussed. An information structure is proposed to support design reviews in a regulated environment. This information structure is shown to be useful to activities beyond design reviews. Incorporation of the proposed information structure into the Licensing Support System is proposed

  7. Methodology For Evaluation Of Regulatory Effectiveness In Physical Protection

    International Nuclear Information System (INIS)

    Izmaylov, Alexander; Valente, John; Griggs, James R.; Rexroth, Paul; Piskarev, Alexander; Babkin, Vladimir; Sokolov, Egor; Melton, Ronald B.; Cunningham, Mitchel E.; Baker, Kathryn A.; Brothers, Alan J.

    2005-01-01

    Material protection, control, and accounting (MPC and A) regulatory documents play an important role in securing and protecting nuclear material by regulating a variety of activities at different hierarchical levels. The development, implementation, and practical application of these regulatory documents requires a significant investment of financial and material resources. Therefore, it is important to evaluate the effectiveness of the regulatory development process and the extent to which regulations improve the effectiveness of MPC and A at nuclear sites. The joint Russian and U.S. Regulatory Development Project has a goal of evaluating the effectiveness of regulatory documents developed for MPC and A. As part of this joint Project, a methodology for evaluating effectiveness has been developed. This methodology was developed around physical protection objectives. The developed methodology specifies physical protection objectives to be accomplished through the implementation of a regulatory system based on the physical protection goals at the nuclear sites. It includes approaches to assessing regulatory effectiveness, the hierarchical structure of physical protection objectives to be accomplished through implementing regulations, a 'mapping' of the physical protection objectives to the regulatory framework, a list of criteria for evaluating the effectiveness of physical protection regulations and effectiveness indicators, as well as means and methods for gathering information and implementation of this evaluation.

  8. Regulatory Powers in Public Procurement Law of Peruvian Administrative Agencies

    Directory of Open Access Journals (Sweden)

    Juan Carlos Morón Urbina

    2017-12-01

    Full Text Available Peruvian law has explicitly recognized regulatory powers to administrative agencies, which allows them to have a preponderant role in the production of rules in public procurement. Although these delegations of legislative authority are positively defined, distortions in the system of legal sources arise when agencies exceed delegated powers or when measures issued by administrative entities are mistaken for regulations. This paper aims to identify regulatory powers of Peruvian administrative agencies, as well as the regulatory measures they issue, and their relation with other sources of law.

  9. Regulatory dendritic cell therapy: from rodents to clinical application

    OpenAIRE

    Raïch-Regué, Dalia; Glancy, Megan; Thomson, Angus W.

    2013-01-01

    Dendritic cells (DC) are highly-specialized, bone marrow-derived antigen-presenting cells that induce or regulate innate and adaptive immunity. Regulatory or “tolerogenic” DC play a crucial role in maintaining self tolerance in the healthy steady-state. These regulatory innate immune cells subvert naïve or memory T cell responses by various mechanisms. Regulatory DC (DCreg) also exhibit the ability to induce or restore T cell tolerance in many animal models of autoimmune disease or transplant...

  10. U.S. Nuclear Regulatory Commission natural analogue research program

    International Nuclear Information System (INIS)

    Kovach, L.A.; Ott, W.R.

    1995-01-01

    This article describes the natural analogue research program of the U.S. Nuclear Regulatory Commission (US NRC). It contains information on the regulatory context and organizational structure of the high-level radioactive waste research program plan. It also includes information on the conditions and processes constraining selection of natural analogues, describes initiatives of the US NRC, and describes the role of analogues in the licensing process

  11. Opposing effects of nitric oxide and prostaglandin inhibition on muscle mitochondrial VO2 during exercise

    DEFF Research Database (Denmark)

    Boushel, Robert C; Fuentes, Teresa; Hellsten, Ylva

    2012-01-01

    Nitric oxide (NO) and prostaglandins (PG) together play a role in regulation blood flow during exercise. NO also regulates mitochondrial oxygen consumption through competitive binding to cytochrome c oxidase. Indomethacin both uncouples and inhibits the electron transport chain in a concentration......-dependent manner, and thus inhibition of NO and PG may regulate both muscle oxygen delivery and utilization. The purpose of this study was to examine the independent and combined effects of NO and PG blockade (L-NMMA and indomethacin respectively) on mitochondrial respiration in human muscle following knee...... extension (KE) exercise. Mitochondrial respiration was measured ex-vivo by high resolution respirometry in saponin-permeabilized fibers following 6 min KE in control (CON, n=8), arterial infusion of LNMMA (n=4) and Indo (n=4) followed by combined inhibition of NO and PG (L-NMMA + Indo, n=8). ADP...

  12. Opposing effects of oxytocin on overt compliance and lasting changes to memory.

    Science.gov (United States)

    Edelson, Micah G; Shemesh, Maya; Weizman, Abraham; Yariv, Shahak; Sharot, Tali; Dudai, Yadin

    2015-03-01

    From infancy we learn to comply with societal norms. However, overt compliance is not necessarily accompanied by a change in internal beliefs. The neuromodulatory processes underlying these different phenomena are not yet understood. Here, we test the role of oxytocin in controlling overt compliance versus internalization of information delivered by a social source. After intranasal oxytocin administration, participants showed enhanced compliance to the erroneous opinion of others. However, this expression was coupled with a decrease in the influence of others on long-term memories. Our data suggest that this dissociation may result from reduced conflict in the face of social pressure, which increases immediate conforming behavior, but reduces processing required for deep encoding. These findings reveal a neurobiological control system that oppositely affects internalization and overt compliance.

  13. Simulation Modeling and Optimization of Uniflow Scavenging System Parameters on Opposed-Piston Two-Stroke Engines

    Directory of Open Access Journals (Sweden)

    Fukang Ma

    2018-04-01

    Full Text Available Based on the introduction of opposed-piston two-stroke (OP2S gasoline direct injection (GDI engines, the OP2S-GDI engine working principle and scavenging process were analyzed. GT-Power software was employed to model the working process based on the structural style and principle of OP2S-GDI engine. The tracer gas method and OP2S-GDI engine experiment were employed for model validation at full load of 6000 rpm. The OP2S-GDI engine scavenging system parameters were optimized, including intake port height stroke ratio, intake port circumference ratio, exhaust port height stroke ratio, exhaust port circumference ratio, and opposed-piston motion phase difference. At the same time, the effect of the port height stroke ratio and opposed-piston motion phase difference on effective compression ratio and expansion ratio were considered, and the indicated work was employed as the optimization objective. A three-level orthogonal experiment was applied in the calculation process to reduce the calculation work. The influence and correlation coefficient on the scavenging efficiency and delivery ratio were investigated by the orthogonal experiment analysis of intake and exhaust port height stroke ratio and circular utilization. The effect of the scavenging system parameters on delivery ratio, scavenging efficiency and indicated work were calculated to obtain the best parameters. The results show that intake port height stroke ratio is the main factor for the delivery ratio, while exhaust port height stroke ratio is the main factor to engine delivery ratio and scavenging efficiency.

  14. Schedules for Regulatory Regimes

    International Nuclear Information System (INIS)

    Austvik, Ole Gunnar

    2003-01-01

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

  15. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2009-01-01

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

  16. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2002-01-01

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

  17. Use of the geometric mean of opposing planar projections in pre-reconstruction restoration of SPECT images

    International Nuclear Information System (INIS)

    Boulfelfel, D.; Rangayyan, R.M.; Hahn, L.J.; Kloiber, R.

    1992-01-01

    This paper presents a restoration scheme for single photon emission computed tomography (SPECT) images that performs restoration before reconstruction (pre-reconstruction restoration) from planar (projection) images. In this scheme, the pixel-by-pixel geometric mean of each pair of opposing (conjugate) planar projections is computed prior to the reconstruction process. The averaging process is shown to help in making the degradation phenomenon less dependent on the distance of each point of the object from the camera. The restoration filters investigated are the Wiener and power spectrum equalization filters. (author)

  18. A paradoxical signal intensity increase in fatty livers using opposed-phase gradient echo imaging with fat-suppression pulses

    International Nuclear Information System (INIS)

    Mulkern, Robert V.; Voss, Stephan; Loeb Salsberg, Sandra; Krauel, Marta Ramon; Ludwig, David S.

    2008-01-01

    With the increase in obese and overweight children, nonalcoholic fatty liver disease has become more prevalent in the pediatric population. Appreciating subtleties of magnetic resonance (MR) signal intensity behavior from fatty livers under different imaging conditions thus becomes important to pediatric radiologists. We report an initially confusing signal behavior - increased signal from fatty livers when fat-suppression pulses are applied in an opposed-phase gradient echo imaging sequence - and seek to explain the physical mechanisms for this paradoxical signal intensity behavior. Abdominal MR imaging at 3 T with a 3-D volumetric interpolated breath-hold (VIBE) sequence in the opposed-phase condition (TR/TE 3.3/1.3 ms) was performed in five obese boys (14±2 years of age, body mass index >95th percentile for age and sex) with spectroscopically confirmed fatty livers. Two VIBE acquisitions were performed, one with and one without the use of chemical shift selective (CHESS) pulse fat suppression. The ratios of fat-suppressed over non-fat-suppressed signal intensities were assessed in regions-of-interest (ROIs) in five tissues: subcutaneous fat, liver, vertebral marrow, muscle and spleen. The boys had spectroscopically estimated hepatic fat levels between 17% and 48%. CHESS pulse fat suppression decreased subcutaneous fat signals dramatically, by more than 85% within regions of optimal fat suppression. Fatty liver signals, in contrast, were elevated by an average of 87% with CHESS pulse fat suppression. Vertebral marrow signal was also significantly elevated with CHESS pulse fat suppression, while spleen and muscle signals demonstrated only small signal increases on the order of 10%. We demonstrated that CHESS pulse fat suppression actually increases the signal intensity from fatty livers in opposed-phase gradient echo imaging conditions. The increase can be attributed to suppression of one partner of the opposed-phase pair that normally contributes to the

  19. A paradoxical signal intensity increase in fatty livers using opposed-phase gradient echo imaging with fat-suppression pulses

    Energy Technology Data Exchange (ETDEWEB)

    Mulkern, Robert V.; Voss, Stephan [Harvard Medical School, Department of Radiology, Children' s Hospital Boston, Boston, MA (United States); Loeb Salsberg, Sandra; Krauel, Marta Ramon; Ludwig, David S. [Harvard Medical School, Department of Medicine, Children' s Hospital Boston, Boston, MA (United States)

    2008-10-15

    With the increase in obese and overweight children, nonalcoholic fatty liver disease has become more prevalent in the pediatric population. Appreciating subtleties of magnetic resonance (MR) signal intensity behavior from fatty livers under different imaging conditions thus becomes important to pediatric radiologists. We report an initially confusing signal behavior - increased signal from fatty livers when fat-suppression pulses are applied in an opposed-phase gradient echo imaging sequence - and seek to explain the physical mechanisms for this paradoxical signal intensity behavior. Abdominal MR imaging at 3 T with a 3-D volumetric interpolated breath-hold (VIBE) sequence in the opposed-phase condition (TR/TE 3.3/1.3 ms) was performed in five obese boys (14{+-}2 years of age, body mass index >95th percentile for age and sex) with spectroscopically confirmed fatty livers. Two VIBE acquisitions were performed, one with and one without the use of chemical shift selective (CHESS) pulse fat suppression. The ratios of fat-suppressed over non-fat-suppressed signal intensities were assessed in regions-of-interest (ROIs) in five tissues: subcutaneous fat, liver, vertebral marrow, muscle and spleen. The boys had spectroscopically estimated hepatic fat levels between 17% and 48%. CHESS pulse fat suppression decreased subcutaneous fat signals dramatically, by more than 85% within regions of optimal fat suppression. Fatty liver signals, in contrast, were elevated by an average of 87% with CHESS pulse fat suppression. Vertebral marrow signal was also significantly elevated with CHESS pulse fat suppression, while spleen and muscle signals demonstrated only small signal increases on the order of 10%. We demonstrated that CHESS pulse fat suppression actually increases the signal intensity from fatty livers in opposed-phase gradient echo imaging conditions. The increase can be attributed to suppression of one partner of the opposed-phase pair that normally contributes to the

  20. The core to regulatory reform

    International Nuclear Information System (INIS)

    Partridge, J.W. Jr.

    1993-01-01

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