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Sample records for taar1-mediated regulatory mechanisms

  1. Protein tyrosine phosphatases: regulatory mechanisms.

    NARCIS (Netherlands)

    den Hertog, J.; Ostman, A.; Bohmer, F.D.

    2008-01-01

    Protein-tyrosine phosphatases are tightly controlled by various mechanisms, ranging from differential expression in specific cell types to restricted subcellular localization, limited proteolysis, post-translational modifications affecting intrinsic catalytic activity, ligand binding and

  2. Regulatory capital requirements and bail in mechanisms

    NARCIS (Netherlands)

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

    2015-01-01

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

  3. Epigenetic Regulatory Mechanisms Induced by Resveratrol

    Directory of Open Access Journals (Sweden)

    Guilherme Felipe Santos Fernandes

    2017-11-01

    Full Text Available Resveratrol (RVT is one of the main natural compounds studied worldwide due to its potential therapeutic use in the treatment of many diseases, including cancer, diabetes, cardiovascular diseases, neurodegenerative diseases and metabolic disorders. Nevertheless, the mechanism of action of RVT in all of these conditions is not completely understood, as it can modify not only biochemical pathways but also epigenetic mechanisms. In this paper, we analyze the biological activities exhibited by RVT with a focus on the epigenetic mechanisms, especially those related to DNA methyltransferase (DNMT, histone deacetylase (HDAC and lysine-specific demethylase-1 (LSD1.

  4. Gene regulatory mechanisms in infected fish

    DEFF Research Database (Denmark)

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

    2011-01-01

    molecules produced by the eukaryotic cell is used to program the RNA Induced Silencing Complex (RISC) for cleavage of specific mRNA transcripts and/or translational repression in the cytoplasm or even chromatin methylation in the nucleus. All processes leading to silencing of the target gene. MicroRNAs (or...... differentiation. Thus the expression of these miRNAs might be steered by different mechanisms in different cell types and have different roles in terms of the genes they target in different cell types. Thus gene regulation and function is better looked upon as a web of interactions. Data from zebrafish studies...

  5. Density-dependence as a size-independent regulatory mechanism

    NARCIS (Netherlands)

    De Vladar, H.P.

    2006-01-01

    The growth function of populations is central in biomathematics. The main dogma is the existence of density-dependence mechanisms, which can be modelled with distinct functional forms that depend on the size of the Population. One important class of regulatory functions is the theta-logistic, which

  6. Transcriptome profiling reveals regulatory mechanisms underlying Corolla Senescence in Petunia

    Science.gov (United States)

    Genetic regulatory mechanisms that govern petal natural senescence in petunia is complicated and unclear. To identify key genes and pathways that regulate the process, we initiated a transcriptome analysis in petunia petals at four developmental time points, including petal opening without anthesis ...

  7. [Neuronal and hormonal regulatory mechanisms of tears production and secretion].

    Science.gov (United States)

    Mrugacz, Małgorzata; Zywalewska, Nella; Bakunowicz-Lazarczyk, Alina

    2005-01-01

    The ocular surface, tear film, lacrimal glands act as a functional unit to preserve the quality of the refractive surface of the eye, and to resist injury and protect the eye against bodily and environmental conditions. Homeostasis of this functional unit involves neuronal and hormonal regulatory mechanisms. The eye appears to be a target organ for sex hormones particulary the androgen, as they modulate the immune system and trophic functions of the lacrimal and Meibomian glands.

  8. Regulatory mechanisms of apoptosis in regularly dividing cells

    Directory of Open Access Journals (Sweden)

    Ribal S Darwish

    2010-08-01

    Full Text Available Ribal S DarwishDepartment of Anesthesiology, Division of Critical Care Medicine, University of Maryland Medical Center, Baltimore, Maryland, USAAbstract: The balance between cell survival and death is essential for normal development and homeostasis of organisms. Apoptosis is a distinct type of cell death with ultrastructural features that are consistent with an active, inherently controlled process. Abnormalities and ­dysregulation of apoptosis contribute to the pathophysiology of multiple disease processes. Apoptosis is strictly regulated by several positive and negative feedback mechanisms that regulate cell death and determine the final outcome after cell exposure to apoptotic stimuli. Mitochondria and caspases are central components of the regulatory mechanisms of ­apoptosis. Recently, noncaspase pathways of apoptosis have been explored through the studies of ­apoptosis-inducing factor and endonuclease G. Multiple difficulties in the apoptosis research relate to apoptosis detection and imaging. This article reviews current understanding of the regulatory mechanisms of apoptosis.Keywords: caspases, apoptosis-inducing factor, apoptosis inhibitory proteins, cytochrome c, mitochondria 

  9. Regulatory Mechanisms in the P4-ATPase Complex

    DEFF Research Database (Denmark)

    Costa, Sara

    . The functionality on the P4-ATPase complex is essential for several cellular processes, such as vesicle-mediated transport. However, the specific role of flippase activity in vesicle biogenesis and the regulatory mechanism behind this process is still poorly understood. In these studies, we identified...... affordable alternative using a microscope-based cytometer. This system can simultaneously provide information on flippase activity and expression levels. Taken together, the findings described in this thesis provide new tools for P4-ATPase characterization and valuable insights into the regulation...

  10. Critical protein GAPDH and its regulatory mechanisms in cancer cells

    International Nuclear Information System (INIS)

    Zhang, Jin-Ying; Zhang, Fan; Hong, Chao-Qun; Giuliano, Armando E.; Cui, Xiao-Jiang; Zhou, Guang-Ji; Zhang, Guo-Jun; Cui, Yu-Kun

    2015-01-01

    Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), initially identified as a glycolytic enzyme and considered as a housekeeping gene, is widely used as an internal control in experiments on proteins, mRNA, and DNA. However, emerging evidence indicates that GAPDH is implicated in diverse functions independent of its role in energy metabolism; the expression status of GAPDH is also deregulated in various cancer cells. One of the most common effects of GAPDH is its inconsistent role in the determination of cancer cell fate. Furthermore, studies have described GAPDH as a regulator of cell death; other studies have suggested that GAPDH participates in tumor progression and serves as a new therapeutic target. However, related regulatory mechanisms of its numerous cellular functions and deregulated expression levels remain unclear. GAPDH is tightly regulated at transcriptional and posttranscriptional levels, which are involved in the regulation of diverse GAPDH functions. Several cancer-related factors, such as insulin, hypoxia inducible factor-1 (HIF-1), p53, nitric oxide (NO), and acetylated histone, not only modulate GAPDH gene expression but also affect protein functions via common pathways. Moreover, posttranslational modifications (PTMs) occurring in GAPDH in cancer cells result in new activities unrelated to the original glycolytic function of GAPDH. In this review, recent findings related to GAPDH transcriptional regulation and PTMs are summarized. Mechanisms and pathways involved in GAPDH regulation and its different roles in cancer cells are also described

  11. Multiple post-transcriptional regulatory mechanisms in ferritin gene expression

    International Nuclear Information System (INIS)

    Mattia, E.; Den Blaauwen, J.; Van Renswoude, J.; Ashwell, G.

    1989-01-01

    The authors have investigated the mechanisms involved in the regulation of ferritin biosynthesis in K562 human erythroleukemia cells during prolonged exposure to iron. They show that, upon addition of hemin (an efficient iron donor) to the cell culture, the rate of ferritin biosynthesis reaches a maximum after a few hours and then decreases. During a 24-hr incubation with the iron donor the concentrations of total ferritin heavy (H) and light (L) subunit mRNAs rise 2- to 5-fold and 2- to 3-fold, respectively, over the control values, while the amount of the protein increases 10- to 30-fold. The hemin-induced increment in ferritin subunit mRNA is not prevented by deferoxamine, suggesting that it is not directly mediated by chelatable iron. In vitro nuclear transcription analyses performed on nuclei isolated from control cells and cells grown in the presence of hemin indicate that the rates of synthesis of H- and L-subunit mRNAs remain constant. They conclude that iron-induced ferritin biosynthesis is governed by multiple post-transcriptional regulatory mechanisms. They propose that exposure of cells to iron leads to stabilization of ferritin mRNAs, in addition to activation and translation of stored H-and L-subunit mRNAs

  12. A conserved regulatory mechanism in bifunctional biotin protein ligases.

    Science.gov (United States)

    Wang, Jingheng; Beckett, Dorothy

    2017-08-01

    Class II bifunctional biotin protein ligases (BirA), which catalyze post-translational biotinylation and repress transcription initiation, are broadly distributed in eubacteria and archaea. However, it is unclear if these proteins all share the same molecular mechanism of transcription regulation. In Escherichia coli the corepressor biotinoyl-5'-AMP (bio-5'-AMP), which is also the intermediate in biotin transfer, promotes operator binding and resulting transcription repression by enhancing BirA dimerization. Like E. coli BirA (EcBirA), Staphylococcus aureus, and Bacillus subtilis BirA (Sa and BsBirA) repress transcription in vivo in a biotin-dependent manner. In this work, sedimentation equilibrium measurements were performed to investigate the molecular basis of this biotin-responsive transcription regulation. The results reveal that, as observed for EcBirA, Sa, and BsBirA dimerization reactions are significantly enhanced by bio-5'-AMP binding. Thus, the molecular mechanism of the Biotin Regulatory System is conserved in the biotin repressors from these three organisms. © 2017 The Protein Society.

  13. The Unexplored Mechanisms and Regulatory Functions of Ribosomal Translocation

    Science.gov (United States)

    Alejo, Jose Luis

    In every cell, protein synthesis is carried out by the ribosome, a complex macromolecular RNA-protein assembly. Decades of structural and kinetic studies have increased our understanding of ribosome initiation, decoding, translocation and termination. Yet, the underlying mechanism of these fundamental processes has yet to be fully delineated. Hence, the molecular basis of regulation remains obscure. Here, single-molecule fluorescence methods are applied to decipher the mechanism and regulatory roles of the multi-step process of directional substrate translocation on the ribosome that accompanies every round of protein synthesis. In Chapter 1, single-molecule fluorescence resonance energy transfer (smFRET) is introduced as a tool for studying bacterial ribosome translocation. Chapter 2 details the experimental methods. In Chapter 3, the elongation factor G(EF-G)-catalyzed movement of substrates through the ribosome is examined from several perspectives or signals reporting on various degrees of freedom of ribosome dynamics. Two ribosomal states interconvert in the presence of EF-G(GDP), displaying novel head domain motions, until relocking takes place. In Chapter 4, in order to test if the mentioned fluctuations leading to relocking are correlated to the engagement of the P-site by the peptidyl-tRNA, the translocation of miscoded tRNAs is studied. Severe defects in the relocking stages of translocation reveal the correlation between this new stage of translocation and P-site tRNA engagement.

  14. Posttraumatic Stress Disorder Disturbs Coronary Tone and Its Regulatory Mechanisms.

    Science.gov (United States)

    Lazuko, Svetlana S; Kuzhel, Olga P; Belyaeva, Lyudmila E; Manukhina, Eugenia B; Fred Downey, H; Tseilikman, Olga B; Komelkova, Maria V; Tseilikman, Vadim E

    2018-01-01

    Posttraumatic stress disorder (PTSD) is associated with myocardial injury, but changes in coronary regulatory mechanisms in PTSD have not been investigated. This study evaluated the effect of PTSD-inducing stress on coronary tone and its regulation by nitric oxide (NO) and voltage-gated K + channels. PTSD was induced by exposing rats to predator stress, 15 min daily for 10 days, followed by 14 stress-free days. Presence of PTSD was confirmed by the elevated plus-maze test. Coronary tone was evaluated from changes in coronary perfusion pressure of Langendorff isolated hearts. Predator stress induced significant decreases in coronary tone of isolated hearts and in blood pressure of intact rats. L-NAME, a non-selective NO synthase (NOS) inhibitor, but not S-MT, a selective iNOS inhibitor, and increased coronary tone of control rats. In PTSD rats, both L-NAME and S-MT increased coronary tone. Therefore, the stress-induced coronary vasodilation resulted from NO overproduction by both iNOS and eNOS. NOS induction was apparently due to systemic inflammation as evidenced by increased serum interleukin-1β and C-reactive protein in PTSD rats. Decreased corticosterone in PTSD rats may have contributed to inflammation and its effect on coronary tone. PTSD was also associated with voltage-gated K + channel dysfunction, which would have also reduced coronary tone.

  15. Density-dependence as a size-independent regulatory mechanism.

    Science.gov (United States)

    de Vladar, Harold P

    2006-01-21

    The growth function of populations is central in biomathematics. The main dogma is the existence of density-dependence mechanisms, which can be modelled with distinct functional forms that depend on the size of the population. One important class of regulatory functions is the theta-logistic, which generalizes the logistic equation. Using this model as a motivation, this paper introduces a simple dynamical reformulation that generalizes many growth functions. The reformulation consists of two equations, one for population size, and one for the growth rate. Furthermore, the model shows that although population is density-dependent, the dynamics of the growth rate does not depend either on population size, nor on the carrying capacity. Actually, the growth equation is uncoupled from the population size equation, and the model has only two parameters, a Malthusian parameter rho and a competition coefficient theta. Distinct sign combinations of these parameters reproduce not only the family of theta-logistics, but also the van Bertalanffy, Gompertz and Potential Growth equations, among other possibilities. It is also shown that, except for two critical points, there is a general size-scaling relation that includes those appearing in the most important allometric theories, including the recently proposed Metabolic Theory of Ecology. With this model, several issues of general interest are discussed such as the growth of animal population, extinctions, cell growth and allometry, and the effect of environment over a population.

  16. Toxin-antitoxin systems and regulatory mechanisms in Mycobacterium tuberculosis.

    Science.gov (United States)

    Slayden, Richard A; Dawson, Clinton C; Cummings, Jason E

    2018-06-01

    There has been a significant reduction in annual tuberculosis incidence since the World Health Organization declared tuberculosis a global health threat. However, treatment of M. tuberculosis infections requires lengthy multidrug therapeutic regimens to achieve a durable cure. The development of new drugs that are active against resistant strains and phenotypically diverse organisms continues to present the greatest challenge in the future. Numerous phylogenomic analyses have revealed that the Mtb genome encodes a significantly expanded repertoire of toxin-antitoxin (TA) loci that makes up the Mtb TA system. A TA loci is a two-gene operon encoding a 'toxin' protein that inhibits bacterial growth and an interacting 'antitoxin' partner that neutralizes the inhibitory activity of the toxin. The presence of multiple chromosomally encoded TA loci in Mtb raises important questions in regard to expansion, regulation and function. Thus, the functional roles of TA loci in Mtb pathogenesis have received considerable attention over the last decade. The cumulative results indicate that they are involved in regulating adaptive responses to stresses associated with the host environment and drug treatment. Here we review the TA families encoded in Mtb, discuss the duplication of TA loci in Mtb, regulatory mechanism of TA loci, and phenotypic heterogeneity and pathogenesis.

  17. The regulatory mechanism in the U.S. lessons learned

    International Nuclear Information System (INIS)

    Roberts, T.M.

    1987-01-01

    The U.S. Nuclear Regulatory Commission is responsible for the regulation of the commercial uses of nuclear power in the United States in order to protect the public health and safety. The NRC has undertaken a number of initiatives to incorporate the experience gained from the over 25 years of commercial nuclear power plant operation. These initiatives are aimed at improving the regulatory structure currently in place by providing for a more predictable and stable regulatory environment and by more efficiently and effectively focusing the activities of utilities on the safe operation of their facilities. (author)

  18. The Cellular and Molecular Mechanisms of Immuno-suppression by Human Type 1 Regulatory T cells

    Directory of Open Access Journals (Sweden)

    Silvia eGregori

    2012-02-01

    Full Text Available The immuno-regulatory mechanisms of IL-10-producing type 1 regulatory T (Tr1 cells have been widely studied over the years. However, several recent discoveries have shed new light on the cellular and molecular mechanisms that human Tr1 cells use to control immune responses and induce tolerance. In this review we outline the well-known and newly discovered regulatory properties of human Tr1 cells and provide an in-depth comparison of the known suppressor mechanisms of Tr1 cells with FOXP3+ Treg. We also highlight the role that Tr1 cells play in promoting and maintaining tolerance in autoimmunity, allergy, and transplantation.

  19. DMPD: The interferon regulatory factor family in host defense: mechanism of action. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17502370 The interferon regulatory factor family in host defense: mechanism of acti....html) (.csml) Show The interferon regulatory factor family in host defense: mechanism of action. PubmedID 1...7502370 Title The interferon regulatory factor family in host defense: mechanism

  20. Regulatory Mechanisms Controlling Maturation of Serotonin Neuron Identity and Function.

    Science.gov (United States)

    Spencer, William C; Deneris, Evan S

    2017-01-01

    The brain serotonin (5-hydroxytryptamine; 5-HT) system has been extensively studied for its role in normal physiology and behavior, as well as, neuropsychiatric disorders. The broad influence of 5-HT on brain function, is in part due to the vast connectivity pattern of 5-HT-producing neurons throughout the CNS. 5-HT neurons are born and terminally specified midway through embryogenesis, then enter a protracted period of maturation, where they functionally integrate into CNS circuitry and then are maintained throughout life. The transcriptional regulatory networks controlling progenitor cell generation and terminal specification of 5-HT neurons are relatively well-understood, yet the factors controlling 5-HT neuron maturation are only recently coming to light. In this review, we first provide an update on the regulatory network controlling 5-HT neuron development, then delve deeper into the properties and regulatory strategies governing 5-HT neuron maturation. In particular, we discuss the role of the 5-HT neuron terminal selector transcription factor (TF) Pet-1 as a key regulator of 5-HT neuron maturation. Pet-1 was originally shown to positively regulate genes needed for 5-HT synthesis, reuptake and vesicular transport, hence 5-HT neuron-type transmitter identity. It has now been shown to regulate, both positively and negatively, many other categories of genes in 5-HT neurons including ion channels, GPCRs, transporters, neuropeptides, and other transcription factors. Its function as a terminal selector results in the maturation of 5-HT neuron excitability, firing characteristics, and synaptic modulation by several neurotransmitters. Furthermore, there is a temporal requirement for Pet-1 in the control of postmitotic gene expression trajectories thus indicating a direct role in 5-HT neuron maturation. Proper regulation of the maturation of cellular identity is critical for normal neuronal functioning and perturbations in the gene regulatory networks controlling

  1. Glucose- and nitrogen sensing and regulatory mechanisms in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Rødkaer, Steven V; Færgeman, Nils J.

    2014-01-01

    Pro- and eukaryotic cells are constantly challenged by varying concentrations of nutrients in their environment. Perceiving and adapting to such changes are therefore crucial for cellular viability. Thus, numerous specialized cellular receptors continuously sense and react to the availability...... of nutrients such as glucose and nitrogen. When stimulated, these receptors initiate various cellular signaling pathways, which in concert constitute a complex regulatory network. To ensure a highly specific response, these pathways and networks cross-communicate with each other and are regulated at several...

  2. Regulatory Coherence and Standardization Mechanisms in the Trans-Pacific Partnership

    Directory of Open Access Journals (Sweden)

    Cai Phoenix X. F.

    2016-12-01

    Full Text Available This article posits a new taxonomy and framework for assessing regulatory coherence in the new generation of mega-regional, cross-cutting free trade agreements. Using the Trans-Pacific Partnership as the primary example, this article situates the rise of regulatory coherence within the current trade landscape, provides clear definitions of regulatory coherence, and argues that the real engine of regulatory coherence lies in the work of international standard setting organizations. This work has been little examined in the current literature. The article provides a detailed examination of the mechanics by which the Trans-Pacific Partnership promotes regulatory standardization and concludes with some normative implications and calls for future research.

  3. Structural imprints in vivo decode RNA regulatory mechanisms.

    Science.gov (United States)

    Spitale, Robert C; Flynn, Ryan A; Zhang, Qiangfeng Cliff; Crisalli, Pete; Lee, Byron; Jung, Jong-Wha; Kuchelmeister, Hannes Y; Batista, Pedro J; Torre, Eduardo A; Kool, Eric T; Chang, Howard Y

    2015-03-26

    Visualizing the physical basis for molecular behaviour inside living cells is a great challenge for biology. RNAs are central to biological regulation, and the ability of RNA to adopt specific structures intimately controls every step of the gene expression program. However, our understanding of physiological RNA structures is limited; current in vivo RNA structure profiles include only two of the four nucleotides that make up RNA. Here we present a novel biochemical approach, in vivo click selective 2'-hydroxyl acylation and profiling experiment (icSHAPE), which enables the first global view, to our knowledge, of RNA secondary structures in living cells for all four bases. icSHAPE of the mouse embryonic stem cell transcriptome versus purified RNA folded in vitro shows that the structural dynamics of RNA in the cellular environment distinguish different classes of RNAs and regulatory elements. Structural signatures at translational start sites and ribosome pause sites are conserved from in vitro conditions, suggesting that these RNA elements are programmed by sequence. In contrast, focal structural rearrangements in vivo reveal precise interfaces of RNA with RNA-binding proteins or RNA-modification sites that are consistent with atomic-resolution structural data. Such dynamic structural footprints enable accurate prediction of RNA-protein interactions and N(6)-methyladenosine (m(6)A) modification genome wide. These results open the door for structural genomics of RNA in living cells and reveal key physiological structures controlling gene expression.

  4. Genetic control and regulatory mechanisms of succinoglycan and curdlan biosynthesis in genus Agrobacterium.

    Science.gov (United States)

    Wu, Dan; Li, Ang; Ma, Fang; Yang, Jixian; Xie, Yutong

    2016-07-01

    Agrobacterium is a genus of gram-negative bacteria that can produce several typical exopolysaccharides with commercial uses in the food and pharmaceutical fields. In particular, succinoglycan and curdlan, due to their good quality in high yield, have been employed on an industrial scale comparatively early. Exopolysaccharide biosynthesis is a multiple-step process controlled by different functional genes, and various environmental factors cause changes in exopolysaccharide biosynthesis through regulatory mechanisms. In this mini-review, we focus on the genetic control and regulatory mechanisms of succinoglycan and curdlan produced by Agrobacterium. Some key functional genes and regulatory mechanisms for exopolysaccharide biosynthesis are described, possessing a high potential for application in metabolic engineering to modify exopolysaccharide production and physicochemical properties. This review may contribute to the understanding of exopolysaccharide biosynthesis and exopolysaccharide modification by metabolic engineering methods in Agrobacterium.

  5. Behavioural ratings of self-regulatory mechanisms and driving behaviour after an acquired brain injury.

    Science.gov (United States)

    Rike, Per-Ola; Ulleberg, Pål; Schultheis, Maria T; Lundqvist, Anna; Schanke, Anne-Kristine

    2014-01-01

    To explore whether measurements of self-regulatory mechanisms and cognition predict driving behaviour after an acquired brain injury (ABI). Consecutive follow-up study. At baseline participants included 77 persons with stroke and 32 persons with a traumatic brain injury (TBI), all of whom completed a multidisciplinary driving assessment (MDA). A follow-up cohort of 34 persons that succeeded the MDA was included. Baseline measurements: Neuropsychological tests and measurements of self-regulatory mechanisms (BRIEF-A and UPPS Impulsive Behaviour Scale), driving behaviour (DBQ) and pre-injury driving characteristics (mileage, compensatory driving strategies and accident rates). Follow-up measurements: Post-injury driving characteristics were collected by mailed questionnaires from the participants who succeeded the MDA. A MDA, which included a medical examination, neuropsychological testing and an on-road driving test, was considered in the decision for or against granting a driver's license. Self-regulatory mechanisms and driving behaviour were examined for research purposes only. At baseline, self-regulatory mechanisms were significantly associated to aberrant driving behaviour, but not with neuropsychological data or with the outcome of the on-road driving test. Aspects of self-regulation were associated to driving behaviour at follow-up. It is recommended that self-regulatory measurements should regularly be considered in the driving assessments after ABI.

  6. The beginning of a seed: regulatory mechanisms of double fertilization.

    Science.gov (United States)

    Bleckmann, Andrea; Alter, Svenja; Dresselhaus, Thomas

    2014-01-01

    THE LAUNCH OF SEED DEVELOPMENT IN FLOWERING PLANTS (ANGIOSPERMS) IS INITIATED BY THE PROCESS OF DOUBLE FERTILIZATION: two male gametes (sperm cells) fuse with two female gametes (egg and central cell) to form the precursor cells of the two major seed components, the embryo and endosperm, respectively. The immobile sperm cells are delivered by the pollen tube toward the ovule harboring the female gametophyte by species-specific pollen tube guidance and attraction mechanisms. After pollen tube burst inside the female gametophyte, the two sperm cells fuse with the egg and central cell initiating seed development. The fertilized central cell forms the endosperm while the fertilized egg cell, the zygote, will form the actual embryo and suspensor. The latter structure connects the embryo with the sporophytic maternal tissues of the developing seed. The underlying mechanisms of double fertilization are tightly regulated to ensure delivery of functional sperm cells and the formation of both, a functional zygote and endosperm. In this review we will discuss the current state of knowledge about the processes of directed pollen tube growth and its communication with the synergid cells resulting in pollen tube burst, the interaction of the four gametes leading to cell fusion and finally discuss mechanisms how flowering plants prevent multiple sperm cell entry (polyspermy) to maximize their reproductive success.

  7. Regulatory design for RES-E support mechanisms: Learning curves, market structure, and burden-sharing

    International Nuclear Information System (INIS)

    Batlle, C.; Pérez-Arriaga, I.J.; Zambrano-Barragán, P.

    2012-01-01

    Drawing from relevant experiences in power systems around the world, this paper offers a review of existing policy support mechanisms for RES-E, with a detailed analysis of their regulatory implications. While recent studies provide an account of current RES-E support systems, in this paper we focus on some of the impacts these mechanisms have on the overall energy market structure and its performance. Given the rising importance of RES-E in systems everywhere, these impacts should no longer be overlooked. - Highlights: ► This paper offers a critical review of RES-E support mechanisms and their regulatory implications. ► The discussion focuses on how the different schemes impact the performance of the energy markets. ► We propose to redesign of current RES-E mechanisms to optimize incentives and market performance. ► Our recommendation is also to gradually move from price-based mechanisms to auctions.

  8. Thick filament mechano-sensing is a calcium-independent regulatory mechanism in skeletal muscle.

    Science.gov (United States)

    Fusi, L; Brunello, E; Yan, Z; Irving, M

    2016-10-31

    Recent X-ray diffraction studies on actively contracting fibres from skeletal muscle showed that the number of myosin motors available to interact with actin-containing thin filaments is controlled by the stress in the myosin-containing thick filaments. Those results suggested that thick filament mechano-sensing might constitute a novel regulatory mechanism in striated muscles that acts independently of the well-known thin filament-mediated calcium signalling pathway. Here we test that hypothesis using probes attached to the myosin regulatory light chain in demembranated muscle fibres. We show that both the extent and kinetics of thick filament activation depend on thick filament stress but are independent of intracellular calcium concentration in the physiological range. These results establish direct control of myosin motors by thick filament mechano-sensing as a general regulatory mechanism in skeletal muscle that is independent of the canonical calcium signalling pathway.

  9. Transcriptional and Epigenetic Regulatory Mechanisms Affecting HTLV-1 Provirus

    Directory of Open Access Journals (Sweden)

    Paola Miyazato

    2016-06-01

    Full Text Available Human T-cell leukemia virus type 1 (HTLV-1 is a retrovirus associated with human diseases, such as adult T-cell leukemia (ATL and HTLV-1-associated myelopathy/Tropic spastic paraparesis (HAM/TSP. As a retrovirus, its life cycle includes a step where HTLV-1 is integrated into the host genomic DNA and forms proviral DNA. In the chronic phase of the infection, HTLV‑1 is known to proliferate as a provirus via the mitotic division of the infected host cells. There are generally tens of thousands of infected clones within an infected individual. They exist not only in peripheral blood, but also in various lymphoid organs. Viral proteins encoded in HTLV-1 genome play a role in the proliferation and survival of the infected cells. As is the case with other chronic viral infections, HTLV-1 gene expression induces the activation of the host immunity against the virus. Thus, the transcription from HTLV-1 provirus needs to be controlled in order to evade the host immune surveillance. There should be a dynamic and complex regulation in vivo, where an equilibrium between viral antigen expression and host immune surveillance is achieved. The mechanisms regulating viral gene expression from the provirus are a key to understanding the persistent/latent infection with HTLV-1 and its pathogenesis. In this article, we would like to review our current understanding on this topic.

  10. Regulatory Design of Capacity Remuneration Mechanisms in Regional and Low-Carbon Electric Power Markets

    NARCIS (Netherlands)

    Mastropietro, P.

    2016-01-01

    Capacity remuneration mechanisms (CRMs) are “climbing” regulatory agendas in all liberalised power sectors, especially in the European Union. CRMs are introduced to improve system reliability and to minimise power shortages to an economically efficient extent. These schemes will have a central role

  11. Gender Inequality and Reflexive Law: The Potential of different regulatory Mechanisms for making Employment Rights effective

    OpenAIRE

    Deakin, S.; McLaughlin, C.; Chai, D.H.

    2011-01-01

    We review the different regulatory mechanisms which have been used in the UK context to promote gender equality in employment over the past decade, including legal enforcement based on claimant-led litigation, collective bargaining, pay audits, and shareholder pressure. Evidence is drawn from case studies examining the effects of these different mechanisms on organisations in the public and private sectors, and from econometric analysis of the impact of stock market pressures on firms' human ...

  12. Electricity generation: regulatory mechanisms to incentive renewable alternative energy sources in Brazil

    International Nuclear Information System (INIS)

    Cavaliero, Carla Kazue Nakao; Silva, E.P. da

    2005-01-01

    The dissemination of renewable alternative energy sources for electricity generation has always being done through regulatory mechanisms, created and managed by the government of each country. Since these sources are more costly to generate, they have received incentives in response to worldwide environmental concerns, above all with regard to the reduction of CO 2 emissions. In Brazil, the electricity generation from renewable alternative sources is experiencing a new phase of growth. Until a short time ago, environmental appeal was the strongest incentive to these sources in Brazil but it was insufficient to attain its objective. With the electricity crisis and the rationing imposed in 2001, another important factor gained awareness: the need to diversify energy sources. Within this context, this work has the objective of analyzing the regulatory mechanisms recently developed to stimulate electricity generation from renewable alternative energy sources in Brazil by following the experience of other countries such as the United States, United Kingdom and Germany

  13. Regulatory mechanism of endothelin receptor B in the cerebral arteries after focal cerebral ischemia

    DEFF Research Database (Denmark)

    Grell, Anne-Sofie; Thigarajah, Rushani; Edvinsson, Lars

    2014-01-01

    BACKGROUND AND PURPOSE: Increased expression of endothelin receptor type B (ETBR), a vasoactive receptor, has recently been implied in the reduced cerebral blood flow and exacerbated neuronal damage after ischemia-reperfusion (I/R). The study explores the regulatory mechanisms of ETBR to identify...... drug targets to restore normal cerebral artery contractile function as part of successful neuroprotective therapy. METHODS: We have employed in vitro methods on human and rat cerebral arteries to study the regulatory mechanisms and the efficacy of target selective inhibitor, Mithramycin A (Mit...... the ETBR mRNA and protein levels. It also significantly reduced the ETBR mediated cerebrovascular contractility. Detailed analysis indicated that ERK1/2 mediated phosphorylation of Sp1 might be essential for ETBR transcription. CONCLUSION: Transcription factor Sp1 regulates the ETBR mediated...

  14. Regulatory requirements to the thermal-hydraulic and thermal-mechanical computer codes

    International Nuclear Information System (INIS)

    Vitkova, M.; Kalchev, B.; Stefanova, S.

    2006-01-01

    The paper presents an overview of the regulatory requirements to the thermal-hydraulic and thermal-mechanical computer codes, which are used for safety assessment of the fuel design and the fuel utilization. Some requirements to the model development, verification and validation of the codes and analysis of code uncertainties are also define. Questions concerning Quality Assurance during development and implementation of the codes as well as preparation of a detailed verification and validation plan are briefly discussed

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

    Science.gov (United States)

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

    2018-04-01

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

  16. A qrr noncoding RNA deploys four different regulatory mechanisms to optimize quorum-sensing dynamics.

    Science.gov (United States)

    Feng, Lihui; Rutherford, Steven T; Papenfort, Kai; Bagert, John D; van Kessel, Julia C; Tirrell, David A; Wingreen, Ned S; Bassler, Bonnie L

    2015-01-15

    Quorum sensing is a cell-cell communication process that bacteria use to transition between individual and social lifestyles. In vibrios, homologous small RNAs called the Qrr sRNAs function at the center of quorum-sensing pathways. The Qrr sRNAs regulate multiple mRNA targets including those encoding the quorum-sensing regulatory components luxR, luxO, luxM, and aphA. We show that a representative Qrr, Qrr3, uses four distinct mechanisms to control its particular targets: the Qrr3 sRNA represses luxR through catalytic degradation, represses luxM through coupled degradation, represses luxO through sequestration, and activates aphA by revealing the ribosome binding site while the sRNA itself is degraded. Qrr3 forms different base-pairing interactions with each mRNA target, and the particular pairing strategy determines which regulatory mechanism occurs. Combined mathematical modeling and experiments show that the specific Qrr regulatory mechanism employed governs the potency, dynamics, and competition of target mRNA regulation, which in turn, defines the overall quorum-sensing response. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Regulatory mechanisms for absenteeism in the health sector: a systematic review of strategies and their implementation.

    Science.gov (United States)

    Kisakye, Angela N; Tweheyo, Raymond; Ssengooba, Freddie; Pariyo, George W; Rutebemberwa, Elizeus; Kiwanuka, Suzanne N

    2016-01-01

    A systematic review was undertaken to identify regulatory mechanisms aimed at mitigating health care worker absenteeism, to describe where and how they have been implemented as well as their possible effects. The goal was to propose potential policy options for managing the problem of absenteeism among human resources for health in low- and middle-income countries. Mechanisms described in this review are at the local workplace and broader national policy level. A comprehensive online search was conducted on EMBASE, CINAHL, PubMed, Google Scholar, Google, and Social Science Citation Index using MEDLINE search terms. Retrieved studies were uploaded onto reference manager and screened by two independent reviewers. Only publications in English were included. Data were extracted and synthesized according to the objectives of the review. Twenty six of the 4,975 published articles retrieved were included. All were from high-income countries and covered all cadres of health workers. The regulatory mechanisms and possible effects include 1) organizational-level mechanisms being reported as effective in curbing absenteeism in low- and middle-income countries (LMICs); 2) prohibition of private sector activities in LMICs offering benefits but presenting a challenge for the government to monitor the health workforce; 3) contractual changes from temporary to fixed posts having been associated with no reduction in absenteeism and not being appropriate for LMICs; 4) multifaceted work interventions being implemented in most settings; 5) the possibility of using financial and incentive regulatory mechanisms in LMICs; 6) health intervention mechanisms reducing absenteeism when integrated with exercise programs; and 7) attendance by legislation during emergencies being criticized for violating human rights in the United States and not being effective in curbing absenteeism. Most countries have applied multiple strategies to mitigate health care worker absenteeism. The success of these

  18. Regulatory mechanisms for absenteeism in the health sector: a systematic review of strategies and their implementation

    Science.gov (United States)

    Kisakye, Angela N; Tweheyo, Raymond; Ssengooba, Freddie; Pariyo, George W; Rutebemberwa, Elizeus; Kiwanuka, Suzanne N

    2016-01-01

    Background A systematic review was undertaken to identify regulatory mechanisms aimed at mitigating health care worker absenteeism, to describe where and how they have been implemented as well as their possible effects. The goal was to propose potential policy options for managing the problem of absenteeism among human resources for health in low- and middle-income countries. Mechanisms described in this review are at the local workplace and broader national policy level. Methods A comprehensive online search was conducted on EMBASE, CINAHL, PubMed, Google Scholar, Google, and Social Science Citation Index using MEDLINE search terms. Retrieved studies were uploaded onto reference manager and screened by two independent reviewers. Only publications in English were included. Data were extracted and synthesized according to the objectives of the review. Results Twenty six of the 4,975 published articles retrieved were included. All were from high-income countries and covered all cadres of health workers. The regulatory mechanisms and possible effects include 1) organizational-level mechanisms being reported as effective in curbing absenteeism in low- and middle-income countries (LMICs); 2) prohibition of private sector activities in LMICs offering benefits but presenting a challenge for the government to monitor the health workforce; 3) contractual changes from temporary to fixed posts having been associated with no reduction in absenteeism and not being appropriate for LMICs; 4) multifaceted work interventions being implemented in most settings; 5) the possibility of using financial and incentive regulatory mechanisms in LMICs; 6) health intervention mechanisms reducing absenteeism when integrated with exercise programs; and 7) attendance by legislation during emergencies being criticized for violating human rights in the United States and not being effective in curbing absenteeism. Conclusion Most countries have applied multiple strategies to mitigate health care

  19. Regulatory mechanisms for absenteeism in the health sector: a systematic review of strategies and their implementation

    Directory of Open Access Journals (Sweden)

    Kisakye AN

    2016-11-01

    Full Text Available Angela N Kisakye,1 Raymond Tweheyo,1 Freddie Ssengooba,1 George W Pariyo,2 Elizeus Rutebemberwa,1 Suzanne N Kiwanuka1 1Department of Health Policy Planning and Management, Makerere University School of Public Health, Kampala, Uganda; 2Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA Background: A systematic review was undertaken to identify regulatory mechanisms aimed at mitigating health care worker absenteeism, to describe where and how they have been implemented as well as their possible effects. The goal was to propose potential policy options for managing the problem of absenteeism among human resources for health in low- and middle-income countries. Mechanisms described in this review are at the local workplace and broader national policy level. Methods: A comprehensive online search was conducted on EMBASE, CINAHL, PubMed, Google Scholar, Google, and Social Science Citation Index using MEDLINE search terms. Retrieved studies were uploaded onto reference manager and screened by two independent reviewers. Only publications in English were included. Data were extracted and synthesized according to the objectives of the review. Results: Twenty six of the 4,975 published articles retrieved were included. All were from high-income countries and covered all cadres of health workers. The regulatory mechanisms and possible effects include 1 organizational-level mechanisms being reported as effective in curbing absenteeism in low- and middle-income countries (LMICs; 2 prohibition of private sector activities in LMICs offering benefits but presenting a challenge for the government to monitor the health workforce; 3 contractual changes from temporary to fixed posts having been associated with no reduction in absenteeism and not being appropriate for LMICs; 4 multifaceted work interventions being implemented in most settings; 5 the possibility of using financial and incentive regulatory mechanisms

  20. Rac1 in human diseases: The therapeutic potential of targeting Rac1 signaling regulatory mechanisms.

    Science.gov (United States)

    Marei, Hadir; Malliri, Angeliki

    2017-07-03

    Abnormal Rac1 signaling is linked to a number of debilitating human diseases, including cancer, cardiovascular diseases and neurodegenerative disorders. As such, Rac1 represents an attractive therapeutic target, yet the search for effective Rac1 inhibitors is still underway. Given the adverse effects associated with Rac1 signaling perturbation, cells have evolved several mechanisms to ensure the tight regulation of Rac1 signaling. Thus, characterizing these mechanisms can provide invaluable information regarding major cellular events that lead to aberrant Rac1 signaling. Importantly, this information can be utilized to further facilitate the development of effective pharmacological modulators that can restore normal Rac1 signaling. In this review, we focus on the pathological role of Rac1 signaling, highlighting the benefits and potential drawbacks of targeting Rac1 in a clinical setting. Additionally, we provide an overview of available compounds that target key Rac1 regulatory mechanisms and discuss future therapeutic avenues arising from our understanding of these mechanisms.

  1. [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.

  2. Transcriptional regulatory network triggered by oxidative signals configures the early response mechanisms of japonica rice to chilling stress

    KAUST Repository

    Yun, Kil-Young; Park, Myoung Ryoul; Mohanty, Bijayalaxmi; Herath, Venura; Xu, Fuyu; Mauleon, Ramil; Wijaya, Edward; Bajic, Vladimir B.; Bruskiewich, Richard; de los Reyes, Benildo G

    2010-01-01

    -plant level analyses established a holistic view of chilling stress response mechanism of japonica rice. Early response regulatory network triggered by oxidative signals is critical for prolonged survival under sub-optimal temperature. Integration of stress

  3. Timing Embryo Segmentation: Dynamics and Regulatory Mechanisms of the Vertebrate Segmentation Clock

    Science.gov (United States)

    Resende, Tatiana P.; Andrade, Raquel P.; Palmeirim, Isabel

    2014-01-01

    All vertebrate species present a segmented body, easily observed in the vertebrate column and its associated components, which provides a high degree of motility to the adult body and efficient protection of the internal organs. The sequential formation of the segmented precursors of the vertebral column during embryonic development, the somites, is governed by an oscillating genetic network, the somitogenesis molecular clock. Herein, we provide an overview of the molecular clock operating during somite formation and its underlying molecular regulatory mechanisms. Human congenital vertebral malformations have been associated with perturbations in these oscillatory mechanisms. Thus, a better comprehension of the molecular mechanisms regulating somite formation is required in order to fully understand the origin of human skeletal malformations. PMID:24895605

  4. CD38/cADPR Signaling Pathway in Airway Disease: Regulatory Mechanisms

    Directory of Open Access Journals (Sweden)

    Deepak A. Deshpande

    2018-01-01

    Full Text Available Asthma is an inflammatory disease in which proinflammatory cytokines have a role in inducing abnormalities of airway smooth muscle function and in the development of airway hyperresponsiveness. Inflammatory cytokines alter calcium (Ca2+ signaling and contractility of airway smooth muscle, which results in nonspecific airway hyperresponsiveness to agonists. In this context, Ca2+ regulatory mechanisms in airway smooth muscle and changes in these regulatory mechanisms encompass a major component of airway hyperresponsiveness. Although dynamic Ca2+ regulation is complex, phospholipase C/inositol tris-phosphate (PLC/IP3 and CD38-cyclic ADP-ribose (CD38/cADPR are two major pathways mediating agonist-induced Ca2+ regulation in airway smooth muscle. Altered CD38 expression or enhanced cyclic ADP-ribosyl cyclase activity associated with CD38 contributes to human pathologies such as asthma, neoplasia, and neuroimmune diseases. This review is focused on investigations on the role of CD38-cyclic ADP-ribose signaling in airway smooth muscle in the context of transcriptional and posttranscriptional regulation of CD38 expression. The specific roles of transcription factors NF-kB and AP-1 in the transcriptional regulation of CD38 expression and of miRNAs miR-140-3p and miR-708 in the posttranscriptional regulation and the underlying mechanisms of such regulation are discussed.

  5. CD38/cADPR Signaling Pathway in Airway Disease: Regulatory Mechanisms

    Science.gov (United States)

    Deshpande, Deepak A.; Guedes, Alonso G. P.; Graeff, Richard; Dogan, Soner; Subramanian, Subbaya; Walseth, Timothy F.

    2018-01-01

    Asthma is an inflammatory disease in which proinflammatory cytokines have a role in inducing abnormalities of airway smooth muscle function and in the development of airway hyperresponsiveness. Inflammatory cytokines alter calcium (Ca2+) signaling and contractility of airway smooth muscle, which results in nonspecific airway hyperresponsiveness to agonists. In this context, Ca2+ regulatory mechanisms in airway smooth muscle and changes in these regulatory mechanisms encompass a major component of airway hyperresponsiveness. Although dynamic Ca2+ regulation is complex, phospholipase C/inositol tris-phosphate (PLC/IP3) and CD38-cyclic ADP-ribose (CD38/cADPR) are two major pathways mediating agonist-induced Ca2+ regulation in airway smooth muscle. Altered CD38 expression or enhanced cyclic ADP-ribosyl cyclase activity associated with CD38 contributes to human pathologies such as asthma, neoplasia, and neuroimmune diseases. This review is focused on investigations on the role of CD38-cyclic ADP-ribose signaling in airway smooth muscle in the context of transcriptional and posttranscriptional regulation of CD38 expression. The specific roles of transcription factors NF-kB and AP-1 in the transcriptional regulation of CD38 expression and of miRNAs miR-140-3p and miR-708 in the posttranscriptional regulation and the underlying mechanisms of such regulation are discussed. PMID:29576747

  6. Single nucleotide resolution RNA-seq uncovers new regulatory mechanisms in the opportunistic pathogen Streptococcus agalactiae.

    Science.gov (United States)

    Rosinski-Chupin, Isabelle; Sauvage, Elisabeth; Sismeiro, Odile; Villain, Adrien; Da Cunha, Violette; Caliot, Marie-Elise; Dillies, Marie-Agnès; Trieu-Cuot, Patrick; Bouloc, Philippe; Lartigue, Marie-Frédérique; Glaser, Philippe

    2015-05-30

    Streptococcus agalactiae, or Group B Streptococcus, is a leading cause of neonatal infections and an increasing cause of infections in adults with underlying diseases. In an effort to reconstruct the transcriptional networks involved in S. agalactiae physiology and pathogenesis, we performed an extensive and robust characterization of its transcriptome through a combination of differential RNA-sequencing in eight different growth conditions or genetic backgrounds and strand-specific RNA-sequencing. Our study identified 1,210 transcription start sites (TSSs) and 655 transcript ends as well as 39 riboswitches and cis-regulatory regions, 39 cis-antisense non-coding RNAs and 47 small RNAs potentially acting in trans. Among these putative regulatory RNAs, ten were differentially expressed in response to an acid stress and two riboswitches sensed directly or indirectly the pH modification. Strikingly, 15% of the TSSs identified were associated with the incorporation of pseudo-templated nucleotides, showing that reiterative transcription is a pervasive process in S. agalactiae. In particular, 40% of the TSSs upstream genes involved in nucleotide metabolism show reiterative transcription potentially regulating gene expression, as exemplified for pyrG and thyA encoding the CTP synthase and the thymidylate synthase respectively. This comprehensive map of the transcriptome at the single nucleotide resolution led to the discovery of new regulatory mechanisms in S. agalactiae. It also provides the basis for in depth analyses of transcriptional networks in S. agalactiae and of the regulatory role of reiterative transcription following variations of intra-cellular nucleotide pools.

  7. Elucidating the biosynthetic and regulatory mechanisms of flavonoid-derived bioactive components in Epimedium sagittatum

    Directory of Open Access Journals (Sweden)

    Wenjun eHuang

    2015-09-01

    Full Text Available Herba epimedii (Epimedium, a traditional Chinese medicine, has been widely used as a kidney tonic and antirheumatic medicine for thousands of years. In Epimedium, flavonoids have been demonstrated to be the main bioactive components (BCs. However, the molecular biosynthetic and regulatory mechanisms of flavonoid-derived BCs remain obscure. In this study, we isolated twelve structural genes and two putative transcription factors (TFs in the flavonoid pathway. Phytochemical analysis showed that the total content of four representative BCs (epimedin A, B, C and icariin decreased slightly or dramatically in two lines of E. sagittatum during leaf development. Transcriptional analysis revealed that two R2R3-MYB TFs (EsMYBA1 and EsMYBF1, together with a bHLH TF (EsGL3 and WD40 protein (EsTTG1, were supposed to coordinately regulate the anthocyanin and flavonol-derived BCs biosynthesis in leaves. Overexpression of EsFLS (flavonol synthase in tobacco resulted in increased flavonols content and decreased anthocyanins content in flowers. Moreover, EsMYB12 negatively correlated with the accumulation of the four BCs, and might act as a transcriptional repressor in the flavonoid pathway. Therefore, the anthocyanin pathway may coordinate with the flavonol-derived BCs pathway in Epimedium leaves. A better understanding of the flavonoid biosynthetic and regulatory mechanisms in E. sagittatum will facilitate functional characterization, metabolic engineering and molecular breeding studies of Epimedium species.

  8. Comparative genetic screens in human cells reveal new regulatory mechanisms in WNT signaling

    Science.gov (United States)

    Lebensohn, Andres M; Dubey, Ramin; Neitzel, Leif R; Tacchelly-Benites, Ofelia; Yang, Eungi; Marceau, Caleb D; Davis, Eric M; Patel, Bhaven B; Bahrami-Nejad, Zahra; Travaglini, Kyle J; Ahmed, Yashi; Lee, Ethan; Carette, Jan E; Rohatgi, Rajat

    2016-01-01

    The comprehensive understanding of cellular signaling pathways remains a challenge due to multiple layers of regulation that may become evident only when the pathway is probed at different levels or critical nodes are eliminated. To discover regulatory mechanisms in canonical WNT signaling, we conducted a systematic forward genetic analysis through reporter-based screens in haploid human cells. Comparison of screens for negative, attenuating and positive regulators of WNT signaling, mediators of R-spondin-dependent signaling and suppressors of constitutive signaling induced by loss of the tumor suppressor adenomatous polyposis coli or casein kinase 1α uncovered new regulatory features at most levels of the pathway. These include a requirement for the transcription factor AP-4, a role for the DAX domain of AXIN2 in controlling β-catenin transcriptional activity, a contribution of glycophosphatidylinositol anchor biosynthesis and glypicans to R-spondin-potentiated WNT signaling, and two different mechanisms that regulate signaling when distinct components of the β-catenin destruction complex are lost. The conceptual and methodological framework we describe should enable the comprehensive understanding of other signaling systems. DOI: http://dx.doi.org/10.7554/eLife.21459.001 PMID:27996937

  9. Regulatory components of carbon concentrating mechanisms in aquatic unicellular photosynthetic organisms.

    Science.gov (United States)

    Tomar, Vandana; Sidhu, Gurpreet Kaur; Nogia, Panchsheela; Mehrotra, Rajesh; Mehrotra, Sandhya

    2017-11-01

    This review provides an insight into the regulation of the carbon concentrating mechanisms (CCMs) in lower organisms like cyanobacteria, proteobacteria, and algae. CCMs evolved as a mechanism to concentrate CO 2 at the site of primary carboxylating enzyme Ribulose-1, 5-bisphosphate carboxylase oxygenase (Rubisco), so that the enzyme could overcome its affinity towards O 2 which leads to wasteful processes like photorespiration. A diverse set of CCMs exist in nature, i.e., carboxysomes in cyanobacteria and proteobacteria; pyrenoids in algae and diatoms, the C 4 system, and Crassulacean acid metabolism in higher plants. Prime regulators of CCM in most of the photosynthetic autotrophs belong to the LysR family of transcriptional regulators, which regulate the activity of the components of CCM depending upon the ambient CO 2 concentrations. Major targets of these regulators are carbonic anhydrase and inorganic carbon uptake systems (CO 2 and HCO 3 - transporters) whose activities are modulated either at transcriptional level or by changes in the levels of their co-regulatory metabolites. The article provides information on the localization of the CCM components as well as their function and participation in the development of an efficient CCM. Signal transduction cascades leading to activation/inactivation of inducible CCM components on perception of low/high CO 2 stimuli have also been brought into picture. A detailed study of the regulatory components can aid in identifying the unraveled aspects of these mechanisms and hence provide information on key molecules that need to be explored to further provide a clear understanding of the mechanism under study.

  10. Putting theory to the test: which regulatory mechanisms can drive realistic growth of a root?

    Science.gov (United States)

    De Vos, Dirk; Vissenberg, Kris; Broeckhove, Jan; Beemster, Gerrit T S

    2014-10-01

    In recent years there has been a strong development of computational approaches to mechanistically understand organ growth regulation in plants. In this study, simulation methods were used to explore which regulatory mechanisms can lead to realistic output at the cell and whole organ scale and which other possibilities must be discarded as they result in cellular patterns and kinematic characteristics that are not consistent with experimental observations for the Arabidopsis thaliana primary root. To aid in this analysis, a 'Uniform Longitudinal Strain Rule' (ULSR) was formulated as a necessary condition for stable, unidirectional, symplastic growth. Our simulations indicate that symplastic structures are robust to differences in longitudinal strain rates along the growth axis only if these differences are small and short-lived. Whereas simple cell-autonomous regulatory rules based on counters and timers can produce stable growth, it was found that steady developmental zones and smooth transitions in cell lengths are not feasible. By introducing spatial cues into growth regulation, those inadequacies could be avoided and experimental data could be faithfully reproduced. Nevertheless, a root growth model based on previous polar auxin-transport mechanisms violates the proposed ULSR due to the presence of lateral gradients. Models with layer-specific regulation or layer-driven growth offer potential solutions. Alternatively, a model representing the known cross-talk between auxin, as the cell proliferation promoting factor, and cytokinin, as the cell differentiation promoting factor, predicts the effect of hormone-perturbations on meristem size. By down-regulating PIN-mediated transport through the transcription factor SHY2, cytokinin effectively flattens the lateral auxin gradient, at the basal boundary of the division zone, (thereby imposing the ULSR) to signal the exit of proliferation and start of elongation. This model exploration underlines the value of

  11. Activation of counter-regulatory mechanisms in a rat renal acute rejection model

    Directory of Open Access Journals (Sweden)

    Salomon Daniel R

    2008-02-01

    Full Text Available Abstract Background Microarray analysis provides a powerful approach to identify gene expression alterations following transplantation. In patients the heterogeneity of graft specimens, co-morbidity, co-medications and the challenges in sample collection and preparation complicate conclusions regarding the underlying mechanisms of graft injury, rejection and immune regulation. Results We used a rat kidney transplantation model with strict transplant and sample preparation procedures to analyze genome wide changes in gene expression four days after syngeneic and allogeneic transplantation. Both interventions were associated with substantial changes in gene expression. After allogeneic transplantation, genes and pathways related to transport and metabolism were predominantly down-regulated consistent with rejection-mediated graft injury and dysfunction. Up-regulated genes were primarily related to the acute immune response including antigen presentation, T-cell receptor signaling, apoptosis, interferon signaling and complement cascades. We observed a cytokine and chemokine expression profile consistent with activation of a Th1-cell response. A novel finding was up-regulation of several regulatory and protective genes after allogeneic transplantation, specifically IL10, Bcl2a1, C4bpa, Ctla4, HO-1 and the SOCS family. Conclusion Our data indicate that in parallel with the predicted activation of immune response and tissue injury pathways, there is simultaneous activation of pathways for counter regulatory and protective mechanisms that would balance and limit the ongoing inflammatory/immune responses. The pathophysiological mechanisms behind and the clinical consequences of alterations in expression of these gene classes in acute rejection, injury and dysfunction vs. protection and immunoregulation, prompt further analyses and open new aspects for therapeutic approaches.

  12. Phenotype specific analyses reveal distinct regulatory mechanism for chronically activated p53.

    Directory of Open Access Journals (Sweden)

    Kristina Kirschner

    2015-03-01

    Full Text Available The downstream functions of the DNA binding tumor suppressor p53 vary depending on the cellular context, and persistent p53 activation has recently been implicated in tumor suppression and senescence. However, genome-wide information about p53-target gene regulation has been derived mostly from acute genotoxic conditions. Using ChIP-seq and expression data, we have found distinct p53 binding profiles between acutely activated (through DNA damage and chronically activated (in senescent or pro-apoptotic conditions p53. Compared to the classical 'acute' p53 binding profile, 'chronic' p53 peaks were closely associated with CpG-islands. Furthermore, the chronic CpG-island binding of p53 conferred distinct expression patterns between senescent and pro-apoptotic conditions. Using the p53 targets seen in the chronic conditions together with external high-throughput datasets, we have built p53 networks that revealed extensive self-regulatory 'p53 hubs' where p53 and many p53 targets can physically interact with each other. Integrating these results with public clinical datasets identified the cancer-associated lipogenic enzyme, SCD, which we found to be directly repressed by p53 through the CpG-island promoter, providing a mechanistic link between p53 and the 'lipogenic phenotype', a hallmark of cancer. Our data reveal distinct phenotype associations of chronic p53 targets that underlie specific gene regulatory mechanisms.

  13. Regulatory mechanisms of metabolic flexibility in the dark-eyed junco (Junco hyemalis).

    Science.gov (United States)

    Stager, Maria; Swanson, David L; Cheviron, Zachary A

    2015-03-01

    Small temperate birds reversibly modify their aerobic performance to maintain thermoregulatory homeostasis under seasonally changing environmental conditions and these physiological adjustments may be attributable to changes in the expression of genes in the underlying regulatory networks. Here, we report the results of an experimental procedure designed to gain insight into the fundamental mechanisms of metabolic flexibility in the dark-eyed junco (Junco hyemalis). We combined genomic transcriptional profiles with measures of metabolic enzyme activities and whole-animal thermogenic performance from juncos exposed to four 6-week acclimation treatments that varied in temperature (cold, 3°C; warm, 24°C) and photoperiod (short day, 8 h light:16 h dark; long day, 16 h light:8 h dark). Cold-acclimated birds increased thermogenic capacity compared with warm-acclimated birds, and this enhanced performance was associated with upregulation of genes involved in muscle hypertrophy, angiogenesis, and lipid transport and oxidation, as well as with catabolic enzyme activities. These physiological changes occurred over ecologically relevant timescales, suggesting that birds make regulatory adjustments to interacting, hierarchical pathways in order to seasonally enhance thermogenic capacity. © 2015. Published by The Company of Biologists Ltd.

  14. Mechanistic Basis for Plant Responses to Drought Stress : Regulatory Mechanism of Abscisic Acid Signaling

    Science.gov (United States)

    Miyakawa, Takuya; Tanokura, Masaru

    The phytohormone abscisic acid (ABA) plays a key role in the rapid adaptation of plants to environmental stresses such as drought and high salinity. Accumulated ABA in plant cells promotes stomatal closure in guard cells and transcription of stress-tolerant genes. Our understanding of ABA responses dramatically improved by the discovery of both PYR/PYL/RCAR as a soluble ABA receptor and inhibitory complex of a protein phospatase PP2C and a protein kinase SnRK2. Moreover, several structural analyses of PYR/PYL/RCAR revealed the mechanistic basis for the regulatory mechanism of ABA signaling, which provides a rational framework for the design of alternative agonists in future.

  15. 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.

  16. Interplay of cis- and trans-regulatory mechanisms in the spliceosomal RNA helicase Brr2.

    Science.gov (United States)

    Absmeier, Eva; Becke, Christian; Wollenhaupt, Jan; Santos, Karine F; Wahl, Markus C

    2017-01-02

    RNA helicase Brr2 is implicated in multiple phases of pre-mRNA splicing and thus requires tight regulation. Brr2 can be auto-inhibited via a large N-terminal region folding back onto its helicase core and auto-activated by a catalytically inactive C-terminal helicase cassette. Furthermore, it can be regulated in trans by the Jab1 domain of the Prp8 protein, which can inhibit Brr2 by intermittently inserting a C-terminal tail in the enzyme's RNA-binding tunnel or activate the helicase after removal of this tail. Presently it is unclear, whether these regulatory mechanisms functionally interact and to which extent they are evolutionarily conserved. Here, we report crystal structures of Saccharomyces cerevisiae and Chaetomium thermophilum Brr2-Jab1 complexes, demonstrating that Jab1-based inhibition of Brr2 presumably takes effect in all eukaryotes but is implemented via organism-specific molecular contacts. Moreover, the structures show that Brr2 auto-inhibition can act in concert with Jab1-mediated inhibition, and suggest that the N-terminal region influences how the Jab1 C-terminal tail interacts at the RNA-binding tunnel. Systematic RNA binding and unwinding studies revealed that the N-terminal region and the Jab1 C-terminal tail specifically interfere with accommodation of double-stranded and single-stranded regions of an RNA substrate, respectively, mutually reinforcing each other. Additionally, such analyses show that regulation based on the N-terminal region requires the presence of the inactive C-terminal helicase cassette. Together, our results outline an intricate system of regulatory mechanisms, which control Brr2 activities during snRNP assembly and splicing.

  17. MYCN-driven regulatory mechanisms controlling LIN28B in neuroblastoma

    Science.gov (United States)

    Beckers, Anneleen; Van Peer, Gert; Carter, Daniel R.; Gartlgruber, Moritz; Herrmann, Carl; Agarwal, Saurabh; Helsmoortel, Hetty H.; Althoff, Kristina; Molenaar, Jan J.; Cheung, Belamy B.; Schulte, Johannes H.; Benoit, Yves; Shohet, Jason M.; Westermann, Frank; Marshall, Glenn M.; Vandesompele, Jo; De Preter, Katleen; Speleman, Frank

    2016-01-01

    LIN28B has been identified as an oncogene in various tumor entities, including neuroblastoma, a childhood cancer that originates from neural crest-derived cells, and is characterized by amplification of the MYCN oncogene. Recently, elevated LIN28B expression levels were shown to contribute to neuroblastoma tumorigenesis via let-7 dependent de-repression of MYCN. However, additional insight in the regulation of LIN28B in neuroblastoma is lacking. Therefore, we have performed a comprehensive analysis of the regulation of LIN28B in neuroblastoma, with a specific focus on the contribution of miRNAs. We show that MYCN regulates LIN28B expression in neuroblastoma tumors via two distinct parallel mechanisms. First, through an unbiased LIN28B-3′UTR reporter screen, we found that miR-26a-5p and miR-26b-5p regulate LIN28B expression. Next, we demonstrated that MYCN indirectly affects the expression of miR-26a-5p, and hence regulates LIN28B, therefor establishing a MYCN-miR-26a-5p-LIN28B regulatory axis. Second, we provide evidence that MYCN regulates LIN28B expression via interaction with the LIN28B promotor, establishing a direct MYCN-LIN28B regulatory axis. We believe that these findings mark LIN28B as an important effector of the MYCN oncogenic phenotype and underlines the importance of MYCN-regulated miRNAs in establishing the MYCN-driven oncogenic process. PMID:26123663

  18. Functional Development of the Human Gastrointestinal Tract: Hormone- and Growth Factor-Mediated Regulatory Mechanisms

    Directory of Open Access Journals (Sweden)

    Daniel Ménard

    2004-01-01

    Full Text Available The present review focuses on the control of gastrointestinal (GI tract development. The first section addresses the differences in general mechanisms of GI development in humans versus rodents, highlighting that morphogenesis of specific digestive organs and the differentiation of digestive epithelia occur not only at different stages of ontogeny but also at different rates. The second section provides an overview of studies from the author's laboratory at the Université de Sherbrooke pertaining to the development of the human fetal small intestine and colon. While both segments share similar morphological and functional characteristics, they are nevertheless modulated by distinct regulatory mechanisms. Using the organ culture approach, the author and colleagues were able to establish that hormones and growth factors, such as glucocorticoids, epidermal growth factor, insulin and keratinocyte growth factor, not only exert differential effects within these two segments, they can also trigger opposite responses in comparison with animal models. In the third section, emphasis is placed on the functional development of human fetal stomach and its various epithelial cell types; in particular, the glandular chief cells responsible for the synthesis and secretion of gastric enzymes such as pepsinogen-5 and gastric lipase. Bearing in mind that limitations of available cell models have, until now, greatly impeded the comprehension of molecular mechanisms regulating human gastric epithelial cell functions, the last section focuses on new human gastric epithelial cell models recently developed in the author's laboratory. These models comprise a novel primary culture system of human fetal gastric epithelium including, for the first time, functional chief cells, and human gastric epithelium cell lines cloned from the parental NCI-N87 strain. These new cells lines could serve important applications in the study of pathogenic action and epithelial

  19. Building hospital capacity planning mechanisms in Poland: The impact of 2016/2017 regulatory changes.

    Science.gov (United States)

    Dubas-Jakóbczyk, Katarzyna; Sowada, Christoph; Domagała, Alicja; Więckowska, Barbara

    2018-02-07

    Capacity planning is a crucial component of modern health care governance. The aim of this paper is to analyze the requirements that need to be met to build effective hospital capacity planning mechanisms in Poland. In this context, the recent regulatory changes strongly influencing hospital sector functioning, including introduction of health care needs maps, capital investment assessment, and hospital network regulations, are analyzed. Some possible ways forward, based on review of international experiences in hospital capacity planning, are discussed. Applied methods include literature review and analysis of statistical data as well as desk analysis of key national regulations related to hospital sector. Results indicate that at the system level, the process of capacity planning involves 4 elements: capital investment in facilities, equipment, and technology; service delivery; allocation of staff; and financial resources. For hospital capacity planning to be effective, the strategic decision at the macrolevel must be complemented by appropriate management of individual hospitals. The major challenge of building hospital capacity planning mechanism in Poland is imbedding it into the overall health system strategy. Because of the lack of such a strategy, the practical implementation of the ad hoc changes, which have been introduced, shows some inconsistencies. The regulations implemented between 2016 and 2017 provided a basis for hospital capacity planning, yet still need evaluation and adjustments. Also, including a mechanism for human resources planning is of crucial importance. The regulations should provide incentives for reducing oversized hospital infrastructure with simultaneous development of the long-term and coordinated care models. Copyright © 2018 John Wiley & Sons, Ltd.

  20. Regulatory inspection practices for industrial safety (electrical, mechanical, material handling and conventional aspects)

    International Nuclear Information System (INIS)

    Agarwal, K.

    2017-01-01

    Regulatory Inspection (RI) of BARC facilities and projects are carried out under the guidance of BARC Safety Council (BSC) Secretariat. Basically facilities and projects have been divided into two board categories viz. radiological facilities and non-radiological facilities. The Rls of radiological facilities should be carried out under OPSRC and of non-radiological facilities under CFSRC. Periodicity of inspection shall be at least once in a year. The RI of projects is carried out under concerned DSRC. RI practices with industrial safety which includes electrical, mechanical, material handling and conventional aspect for these facilities starts with check lists. The inspection areas are prepared in the form of checklists which includes availability of approved documents, compliance status of previous RIT and various safety committee's recommendations, radiological status of facilities, prompt reporting of safety related unusual occurrences, major incident, site visit for verification of actual status of system/plant. The practices for inspection in the area of electrical safety shall include checking of maintenance procedure for all critical class IV system equipment's such as HT panel, LT panel, transformer and motors. Load testing of Class III system such as D.G. set etc. shall be carried out as technical specification surveillance schedule. Status of aviation lights, number of qualified staff, availability of qualified staff etc. shall be form of inspection

  1. Regulatory mechanism of the flavoprotein Tah18-dependent nitric oxide synthesis and cell death in yeast.

    Science.gov (United States)

    Yoshikawa, Yuki; Nasuno, Ryo; Kawahara, Nobuhiro; Nishimura, Akira; Watanabe, Daisuke; Takagi, Hiroshi

    2016-07-01

    Nitric oxide (NO) is a ubiquitous signaling molecule involved in the regulation of a large number of cellular functions. The regulatory mechanism of NO generation in unicellular eukaryotic yeast cells is poorly understood due to the lack of mammalian and bacterial NO synthase (NOS) orthologues, even though yeast produces NO under oxidative stress conditions. Recently, we reported that the flavoprotein Tah18, which was previously shown to transfer electrons to the iron-sulfur cluster protein Dre2, is involved in NOS-like activity in the yeast Saccharomyces cerevisiae. On the other hand, Tah18 was reported to promote apoptotic cell death after exposure to hydrogen peroxide (H2O2). Here, we showed that NOS-like activity requiring Tah18 induced cell death upon treatment with H2O2. Our experimental results also indicate that Tah18-dependent NO production and cell death are suppressed by enhancement of the interaction between Tah18 and its molecular partner Dre2. Our findings indicate that the Tah18-Dre2 complex regulates cell death as a molecular switch via Tah18-dependent NOS-like activity in response to environmental changes. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Innate immunity and effector and regulatory mechanisms involved in allergic contact dermatitis.

    Science.gov (United States)

    Silvestre, Marilene Chaves; Sato, Maria Notomi; Reis, Vitor Manoel Silva Dos

    2018-03-01

    Skin's innate immunity is the initial activator of immune response mechanisms, influencing the development of adaptive immunity. Some contact allergens are detected by Toll-like receptors (TLRs) and inflammasome NLR3. Keratinocytes participate in innate immunity and, in addition to functioning as an anatomical barrier, secrete cytokines, such as TNF, IL-1β, and IL-18, contributing to the development of Allergic Contact Dermatitis. Dendritic cells recognize and process antigenic peptides into T cells. Neutrophils cause pro-inflammatory reactions, mast cells induce migration/maturation of skin DCs, the natural killer cells have natural cytotoxic capacity, the γδ T cells favor contact with hapten during the sensitization phase, and the innate lymphoid cells act in the early stages by secreting cytokines, as well as act in inflammation and tissue homeostasis. The antigen-specific inflammation is mediated by T cells, and each subtype of T cells (Th1/Tc1, Th2/Tc2, and Th17/Tc17) activates resident skin cells, thus contributing to inflammation. Skin's regulatory T cells have a strong ability to inhibit the proliferation of hapten-specific T cells, acting at the end of the Allergic Contact Dermatitis response and in the control of systemic immune responses. In this review, we report how cutaneous innate immunity is the first line of defense and focus its role in the activation of the adaptive immune response, with effector response induction and its regulation.

  3. Innate immunity and effector and regulatory mechanisms involved in allergic contact dermatitis*

    Science.gov (United States)

    Silvestre, Marilene Chaves; Sato, Maria Notomi; dos Reis, Vitor Manoel Silva

    2018-01-01

    Skin's innate immunity is the initial activator of immune response mechanisms, influencing the development of adaptive immunity. Some contact allergens are detected by Toll-like receptors (TLRs) and inflammasome NLR3. Keratinocytes participate in innate immunity and, in addition to functioning as an anatomical barrier, secrete cytokines, such as TNF, IL-1β, and IL-18, contributing to the development of Allergic Contact Dermatitis. Dendritic cells recognize and process antigenic peptides into T cells. Neutrophils cause pro-inflammatory reactions, mast cells induce migration/maturation of skin DCs, the natural killer cells have natural cytotoxic capacity, the γδ T cells favor contact with hapten during the sensitization phase, and the innate lymphoid cells act in the early stages by secreting cytokines, as well as act in inflammation and tissue homeostasis. The antigen-specific inflammation is mediated by T cells, and each subtype of T cells (Th1/Tc1, Th2/Tc2, and Th17/Tc17) activates resident skin cells, thus contributing to inflammation. Skin's regulatory T cells have a strong ability to inhibit the proliferation of hapten-specific T cells, acting at the end of the Allergic Contact Dermatitis response and in the control of systemic immune responses. In this review, we report how cutaneous innate immunity is the first line of defense and focus its role in the activation of the adaptive immune response, with effector response induction and its regulation. PMID:29723367

  4. Take it of leave it : Mechanisms underlying bacterial bistable regulatory networks

    NARCIS (Netherlands)

    Siebring, Jeroen; Sorg, Robin; Herber, Martijn; Kuipers, Oscar; Filloux, Alain A.M.

    2012-01-01

    Bistable switches occur in regulatory networks that can exist in two distinct stable states. Such networks allow distinct switching of individual cells. In bacteria these switches coexist with regulatory networks that respond gradually to environmental input. Bistable switches play key roles in high

  5. Constitutive, Institutive and Up-Regulation of Carotenogenesis Regulatory Mechanism via In Vitro Culture Model System and Elicitors

    International Nuclear Information System (INIS)

    Rashidi Othman; Fatimah Azzahra Mohd Zaifuddin; Norazian Mohd Hassan

    2015-01-01

    Phyto hormone abscisic acid (ABA) plays a regulatory role in many physiological processes in plants and is regulated and controlled by specific key factors or genes. Different environmental stress conditions such as water, drought, cold, light, and temperature result in increased amounts of ABA. The action of ABA involves modification of gene expression and analysis of in vitro callus model system cultures revealed several potential of constitutive, institutive and up-regulation acting regulatory mechanisms. Therefore, this study was aimed at establishing in vitro cultures as potential research tools to study the regulatory mechanisms of the carotenoid biosynthesis in selected plant species through a controlled environment. The presence and absence of zeaxanthin and neoxanthin in callus cultures and intact plants could be explained by changes in gene expression in response to stress. Abiotic stress can alter gene expression and trigger cellular metabolism in plants. This study suggested that the key factors which involved in regulatory mechanisms of individual carotenoid biosynthesis in a particular biology system of plants can be either be silenced or activated. Therefore, based on the results in this study environmental stress is made possible for enhancement or enrichment of certain carotenoid of interest in food crops without altering the genes. (author)

  6. Heart Rate Variability: New Perspectives on Physiological Mechanisms, Assessment of Self-regulatory Capacity, and Health risk.

    Science.gov (United States)

    McCraty, Rollin; Shaffer, Fred

    2015-01-01

    Heart rate variability, the change in the time intervals between adjacent heartbeats, is an emergent property of interdependent regulatory systems that operates on different time scales to adapt to environmental and psychological challenges. This article briefly reviews neural regulation of the heart and offers some new perspectives on mechanisms underlying the very low frequency rhythm of heart rate variability. Interpretation of heart rate variability rhythms in the context of health risk and physiological and psychological self-regulatory capacity assessment is discussed. The cardiovascular regulatory centers in the spinal cord and medulla integrate inputs from higher brain centers with afferent cardiovascular system inputs to adjust heart rate and blood pressure via sympathetic and parasympathetic efferent pathways. We also discuss the intrinsic cardiac nervous system and the heart-brain connection pathways, through which afferent information can influence activity in the subcortical, frontocortical, and motor cortex areas. In addition, the use of real-time HRV feedback to increase self-regulatory capacity is reviewed. We conclude that the heart's rhythms are characterized by both complexity and stability over longer time scales that reflect both physiological and psychological functional status of these internal self-regulatory systems.

  7. microRNA regulatory mechanism by which PLLA aligned nanofibers influence PC12 cell differentiation

    Science.gov (United States)

    Yu, Yadong; Lü, Xiaoying; Ding, Fei

    2015-08-01

    Objective. Aligned nanofibers (AFs) are regarded as promising biomaterials in nerve tissue engineering. However, a full understanding of the biocompatibility of AFs at the molecular level is still challenging. Therefore, the present study focused on identifying the microRNA (miRNA)-mediated regulatory mechanism by which poly-L-lactic acid (PLLA) AFs influence PC12 cell differentiation. Approach. Firstly, the effects of PLLA random nanofibers (RFs)/AFs and PLLA films (control) on the biological responses of PC12 cells that are associated with neuronal differentiation were examined. Then, SOLiD sequencing and cDNA microarray were employed to profile the expressions of miRNAs and mRNAs. The target genes of the misregulated miRNAs were predicted and compared with the mRNA profile data. Functions of the matched target genes (the intersection between the predicted target genes and the experimentally-determined, misregulated genes) were analyzed. Main results. The results revealed that neurites spread in various directions in control and RF groups. In the AF group, most neurites extended in parallel with each other. The glucose consumption and lactic acid production in the RF and AF groups were higher than those in the control group. Compared with the control group, 42 and 94 miRNAs were significantly dysregulated in the RF and AF groups, respectively. By comparing the predicted target genes with the mRNA profile data, five and 87 matched target genes were found in the RF and AF groups, respectively. Three of the matched target genes in the AF group were found to be associated with neuronal differentiation, whereas none had this association in the RF group. The PLLA AFs induced the dysregulation of miRNAs that regulate many biological functions, including axonal guidance, lipid metabolism and long-term potentiation. In particular, two miRNA-matched target gene-biological function modules associated with neuronal differentiation were identified as follows: (1) miR-23b, mi

  8. RNA-Binding Proteins in Trichomonas vaginalis: Atypical Multifunctional Proteins Involved in a Posttranscriptional Iron Regulatory Mechanism

    Science.gov (United States)

    Figueroa-Angulo, Elisa E.; Calla-Choque, Jaeson S.; Mancilla-Olea, Maria Inocente; Arroyo, Rossana

    2015-01-01

    Iron homeostasis is highly regulated in vertebrates through a regulatory system mediated by RNA-protein interactions between the iron regulatory proteins (IRPs) that interact with an iron responsive element (IRE) located in certain mRNAs, dubbed the IRE-IRP regulatory system. Trichomonas vaginalis, the causal agent of trichomoniasis, presents high iron dependency to regulate its growth, metabolism, and virulence properties. Although T. vaginalis lacks IRPs or proteins with aconitase activity, possesses gene expression mechanisms of iron regulation at the transcriptional and posttranscriptional levels. However, only one gene with iron regulation at the transcriptional level has been described. Recently, our research group described an iron posttranscriptional regulatory mechanism in the T. vaginalis tvcp4 and tvcp12 cysteine proteinase mRNAs. The tvcp4 and tvcp12 mRNAs have a stem-loop structure in the 5'-coding region or in the 3'-UTR, respectively that interacts with T. vaginalis multifunctional proteins HSP70, α-Actinin, and Actin under iron starvation condition, causing translation inhibition or mRNA stabilization similar to the previously characterized IRE-IRP system in eukaryotes. Herein, we summarize recent progress and shed some light on atypical RNA-binding proteins that may participate in the iron posttranscriptional regulation in T. vaginalis. PMID:26703754

  9. Nitrous Oxide Metabolism in Nitrate-Reducing Bacteria: Physiology and Regulatory Mechanisms.

    Science.gov (United States)

    Torres, M J; Simon, J; Rowley, G; Bedmar, E J; Richardson, D J; Gates, A J; Delgado, M J

    2016-01-01

    Nitrous oxide (N2O) is an important greenhouse gas (GHG) with substantial global warming potential and also contributes to ozone depletion through photochemical nitric oxide (NO) production in the stratosphere. The negative effects of N2O on climate and stratospheric ozone make N2O mitigation an international challenge. More than 60% of global N2O emissions are emitted from agricultural soils mainly due to the application of synthetic nitrogen-containing fertilizers. Thus, mitigation strategies must be developed which increase (or at least do not negatively impact) on agricultural efficiency whilst decrease the levels of N2O released. This aim is particularly important in the context of the ever expanding population and subsequent increased burden on the food chain. More than two-thirds of N2O emissions from soils can be attributed to bacterial and fungal denitrification and nitrification processes. In ammonia-oxidizing bacteria, N2O is formed through the oxidation of hydroxylamine to nitrite. In denitrifiers, nitrate is reduced to N2 via nitrite, NO and N2O production. In addition to denitrification, respiratory nitrate ammonification (also termed dissimilatory nitrate reduction to ammonium) is another important nitrate-reducing mechanism in soil, responsible for the loss of nitrate and production of N2O from reduction of NO that is formed as a by-product of the reduction process. This review will synthesize our current understanding of the environmental, regulatory and biochemical control of N2O emissions by nitrate-reducing bacteria and point to new solutions for agricultural GHG mitigation. © 2016 Elsevier Ltd. All rights reserved.

  10. High-risk medical devices, children and the FDA: regulatory challenges facing pediatric mechanical circulatory support devices.

    Science.gov (United States)

    Almond, Christopher S D; Chen, Eric A; Berman, Michael R; Less, Joanne R; Baldwin, J Timothy; Linde-Feucht, Sarah R; Hoke, Tracey R; Pearson, Gail D; Jenkins, Kathy; Duncan, Brian W; Zuckerman, Bram D

    2007-01-01

    Pediatric mechanical circulatory support is a critical unmet need in the United States. Infant- and child-sized ventricular assist devices are currently being developed largely through federal contracts and grants through the National Heart, Lung, and Blood Institute (NHLBI). Human testing and marketing of high-risk devices for children raises epidemiologic and regulatory issues that will need to be addressed. Leaders from the US Food and Drug Administration (FDA), NHLBI, academic pediatric community, and industry convened in January 2006 for the first FDA Workshop on the Regulatory Process for Pediatric Mechanical Circulatory Support Devices. The purpose was to provide the pediatric community with an overview of the federal regulatory process for high-risk medical devices and to review the challenges specific to the development and regulation of pediatric mechanical circulatory support devices. Pediatric mechanical circulatory support present significant epidemiologic, logistic, and financial challenges to industry, federal regulators, and the pediatric community. Early interactions with the FDA, shared appreciation of challenges, and careful planning will be critical to avoid unnecessary delays in making potentially life-saving devices available for children. Collaborative efforts to address these challenges are warranted.

  11. Brucella BioR Regulator Defines a Complex Regulatory Mechanism for Bacterial Biotin Metabolism

    Science.gov (United States)

    Xu, Jie; Zhang, Huimin; Srinivas, Swaminath

    2013-01-01

    The enzyme cofactor biotin (vitamin H or B7) is an energetically expensive molecule whose de novo biosynthesis requires 20 ATP equivalents. It seems quite likely that diverse mechanisms have evolved to tightly regulate its biosynthesis. Unlike the model regulator BirA, a bifunctional biotin protein ligase with the capability of repressing the biotin biosynthetic pathway, BioR has been recently reported by us as an alternative machinery and a new type of GntR family transcriptional factor that can repress the expression of the bioBFDAZ operon in the plant pathogen Agrobacterium tumefaciens. However, quite unusually, a closely related human pathogen, Brucella melitensis, has four putative BioR-binding sites (both bioR and bioY possess one site in the promoter region, whereas the bioBFDAZ [bio] operon contains two tandem BioR boxes). This raised the question of whether BioR mediates the complex regulatory network of biotin metabolism. Here, we report that this is the case. The B. melitensis BioR ortholog was overexpressed and purified to homogeneity, and its solution structure was found to be dimeric. Functional complementation in a bioR isogenic mutant of A. tumefaciens elucidated that Brucella BioR is a functional repressor. Electrophoretic mobility shift assays demonstrated that the four predicted BioR sites of Brucella plus the BioR site of A. tumefaciens can all interact with the Brucella BioR protein. In a reporter strain that we developed on the basis of a double mutant of A. tumefaciens (the ΔbioR ΔbioBFDA mutant), the β-galactosidase (β-Gal) activity of three plasmid-borne transcriptional fusions (bioBbme-lacZ, bioYbme-lacZ, and bioRbme-lacZ) was dramatically decreased upon overexpression of Brucella bioR. Real-time quantitative PCR analyses showed that the expression of bioBFDA and bioY is significantly elevated upon removal of bioR from B. melitensis. Together, we conclude that Brucella BioR is not only a negative autoregulator but also a repressor of

  12. Retrievability of high-level nuclear waste from geologic repositories - Regulatory and rock mechanics/design considerations

    International Nuclear Information System (INIS)

    Tanious, N.S.; Nataraja, M.S.; Daemen, J.J.K.

    1987-01-01

    Retrievability of nuclear waste from high-level geologic repositories is one of the performance objectives identified in 10CFR60 (Code of Federal Regulations, 1985). 10CFR60.111 states that the geologic repository operations area shall be designed to preserve the option of waste retrieval. In designing the repository operations area, rock mechanics considerations play a major role especially in evaluating the feasibility of retrieval operations. This paper discusses generic considerations affecting retrievability as they relate to repository design, construction, and operation, with emphasis on regulatory and rock mechanics aspects

  13. Regulatory framework and development perspectives of the mechanism of public participation in the management of Russia’s forests

    Directory of Open Access Journals (Sweden)

    Nikolay Mikhaylovich Shmatkov

    2014-03-01

    Full Text Available The article dwells on the current state of the regulatory framework of the Russian Federation and the mechanism of public participation in forest management. The examples of addressing the problems of public participation in forest management in individual regions are disclosed. The article deals with the issues concerning the provision of in-interests of the local population through the voluntary forest certification system under the FSC scheme. Recommendations on improving the mechanism of public participation in solving the forest management issues are suggested

  14. Integrative Genetic and Epigenetic Analysis Uncovers Regulatory Mechanisms of Autoimmune Disease.

    Science.gov (United States)

    Shooshtari, Parisa; Huang, Hailiang; Cotsapas, Chris

    2017-07-06

    Genome-wide association studies in autoimmune and inflammatory diseases (AID) have uncovered hundreds of loci mediating risk. These associations are preferentially located in non-coding DNA regions and in particular in tissue-specific DNase I hypersensitivity sites (DHSs). While these analyses clearly demonstrate the overall enrichment of disease risk alleles on gene regulatory regions, they are not designed to identify individual regulatory regions mediating risk or the genes under their control, and thus uncover the specific molecular events driving disease risk. To do so we have departed from standard practice by identifying regulatory regions which replicate across samples and connect them to the genes they control through robust re-analysis of public data. We find significant evidence of regulatory potential in 78/301 (26%) risk loci across nine autoimmune and inflammatory diseases, and we find that individual genes are targeted by these effects in 53/78 (68%) of these. Thus, we are able to generate testable mechanistic hypotheses of the molecular changes that drive disease risk. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  15. On the evolution of the regulatory guidance for seismic qualification of electric and active mechanical equipment for nuclear power plants

    International Nuclear Information System (INIS)

    Ng, Ching Hang; Chen, Pei-Ying

    2009-01-01

    All electric and active mechanical equipment important to safety for nuclear power plants must be seismically qualified by testing, analysis, or combined analysis and testing. The general requirements for seismic qualification of electric and active mechanical equipment in nuclear power plants are delineated in Appendix S, 'Earthquake Engineering Criteria for Nuclear Power Plants,' to Title 10, Part 50, 'Domestic Licensing of Production and Utilization Facilities,' of the Code of Federal Regulations (10 CFR Part 50), item 52.47(20) of 10 CFR 52.47, 'Contents of Applications; Technical Information,' and Appendix A, 'Seismic and Geologic Siting Criteria for Nuclear Power Plants,' to 10 CFR Part 100, 'Reactor Site Criteria.' The United States Nuclear Regulatory Commission (NRC) issued Revision 2 of Regulatory Guide (RG) 1.100, 'Seismic Qualification of Electric and Mechanical for Nuclear Power Plants' in 1988, which endorsed, with restrictions, exceptions, and clarifications, Institute of Electrical and Electronics Engineers (IEEE) Standard 344-1987 'IEEE Recommended Practice for Seismic Qualification of Class 1E Equipment for Nuclear Power Generating Stations,' for use in seismic qualification of both electric and mechanical equipment. In 2008, the staff at the NRC drafted Revision 3 of RG 1.100 to endorse, with restrictions, exceptions, and clarifications, the IEEE Std 344-2004 and the American Society of Mechanical Engineers (ASME) QME-1-2007 'Qualification of Active Mechanical Equipment Used in Nuclear Power Plants.' IEEE Std 344-2004 was an update of Std 344-1987 and ASME QME-1-2007 was an update of QME-1-2002. The major changes in IEEE Std 344-2004 and ASME QME-1-2007 include the update and expansion of criteria and procedures describing the use of experience data as a method for seismic qualification of Class 1E electric equipment (including I and C components) as well as active mechanical equipment. In this paper, the staff will compare the draft Revision 3 to

  16. 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.

  17. 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.

  18. Forum of Nuclear Regulatory Bodies in Africa: A Peer Review Mechanism

    International Nuclear Information System (INIS)

    Elegba, S.B.

    2010-01-01

    Uses of Radiation Sources in Africa has Safety and Security Implications that include exposure of workers in all and exposure of Patients in Medical Application. The Safety Principle is primarily: the prevention of harm and protection of health, safety and the environment. The Security Principle recognizes the importance of preventing diversion or malicious acts. Security of Radioactive Sources during use, storage, transportation and Disposal of radioactive waste is of great concern. IAEA Model Project on the “Establishment of Radiation Protection Infrastructure” in Member Sates started in 1995. During the 49. General Conference Statements made by several African Member States revealed the desire of the various Member States to embark on nuclear power for electricity generation. This development thus expanded the original scope of the discussion from radiation protection to now include nuclear safety and nuclear security. During the 50. General Conference of September 2006 Special Event entitled “New Framework for the Utilization of Nuclear Energy in the 21. Century: Assurances of Nuclear Supply and Non-Proliferation was established. Basic Safety Fundamentals SF-1, 2006 shows those basic safety principles for nuclear safety, radiation protection; Waste management and transport safety are similar. Regional Cooperation formed an organization to be known as the Forum of Nuclear Regulatory Bodies in Africa (FNRBA) to provide for the enhancement, strengthening and harmonization of the radiation protection, nuclear safety and security regulatory infrastructure and framework among the members of FNRBA

  19. Transcriptional regulatory network triggered by oxidative signals configures the early response mechanisms of japonica rice to chilling stress

    Directory of Open Access Journals (Sweden)

    Wijaya Edward

    2010-01-01

    Full Text Available Abstract Background The transcriptional regulatory network involved in low temperature response leading to acclimation has been established in Arabidopsis. In japonica rice, which can only withstand transient exposure to milder cold stress (10°C, an oxidative-mediated network has been proposed to play a key role in configuring early responses and short-term defenses. The components, hierarchical organization and physiological consequences of this network were further dissected by a systems-level approach. Results Regulatory clusters responding directly to oxidative signals were prominent during the initial 6 to 12 hours at 10°C. Early events mirrored a typical oxidative response based on striking similarities of the transcriptome to disease, elicitor and wounding induced processes. Targets of oxidative-mediated mechanisms are likely regulated by several classes of bZIP factors acting on as1/ocs/TGA-like element enriched clusters, ERF factors acting on GCC-box/JAre-like element enriched clusters and R2R3-MYB factors acting on MYB2-like element enriched clusters. Temporal induction of several H2O2-induced bZIP, ERF and MYB genes coincided with the transient H2O2 spikes within the initial 6 to 12 hours. Oxidative-independent responses involve DREB/CBF, RAP2 and RAV1 factors acting on DRE/CRT/rav1-like enriched clusters and bZIP factors acting on ABRE-like enriched clusters. Oxidative-mediated clusters were activated earlier than ABA-mediated clusters. Conclusion Genome-wide, physiological and whole-plant level analyses established a holistic view of chilling stress response mechanism of japonica rice. Early response regulatory network triggered by oxidative signals is critical for prolonged survival under sub-optimal temperature. Integration of stress and developmental responses leads to modulated growth and vigor maintenance contributing to a delay of plastic injuries.

  20. Transcriptional regulatory network triggered by oxidative signals configures the early response mechanisms of japonica rice to chilling stress

    KAUST Repository

    Yun, Kil-Young

    2010-01-25

    Background: The transcriptional regulatory network involved in low temperature response leading to acclimation has been established in Arabidopsis. In japonica rice, which can only withstand transient exposure to milder cold stress (10C), an oxidative-mediated network has been proposed to play a key role in configuring early responses and short-term defenses. The components, hierarchical organization and physiological consequences of this network were further dissected by a systems-level approach.Results: Regulatory clusters responding directly to oxidative signals were prominent during the initial 6 to 12 hours at 10C. Early events mirrored a typical oxidative response based on striking similarities of the transcriptome to disease, elicitor and wounding induced processes. Targets of oxidative-mediated mechanisms are likely regulated by several classes of bZIP factors acting on as1/ocs/TGA-like element enriched clusters, ERF factors acting on GCC-box/JAre-like element enriched clusters and R2R3-MYB factors acting on MYB2-like element enriched clusters.Temporal induction of several H2O2-induced bZIP, ERF and MYB genes coincided with the transient H2O2spikes within the initial 6 to 12 hours. Oxidative-independent responses involve DREB/CBF, RAP2 and RAV1 factors acting on DRE/CRT/rav1-like enriched clusters and bZIP factors acting on ABRE-like enriched clusters. Oxidative-mediated clusters were activated earlier than ABA-mediated clusters.Conclusion: Genome-wide, physiological and whole-plant level analyses established a holistic view of chilling stress response mechanism of japonica rice. Early response regulatory network triggered by oxidative signals is critical for prolonged survival under sub-optimal temperature. Integration of stress and developmental responses leads to modulated growth and vigor maintenance contributing to a delay of plastic injuries. 2010 Yun et al; licensee BioMed Central Ltd.

  1. Genetic and epigenetic regulatory mechanisms of the oxytocin receptor gene (OXTR) and the (clinical) implications for social behavior.

    Science.gov (United States)

    Tops, Sanne; Habel, Ute; Radke, Sina

    2018-03-12

    Oxytocin and the oxytocin receptor (OXTR) play an important role in a large variety of social behaviors. The oxytocinergic system interacts with environmental cues and is highly dependent on interindividual factors. Deficits in this system have been linked to mental disorders associated with social impairments, such as autism spectrum disorder (ASD). This review focuses on the modulation of social behavior by alterations in two domains of the oxytocinergic system. We discuss genetic and epigenetic regulatory mechanisms and alterations in these mechanisms that were found to have clinical implications for ASD. We propose possible explanations how these alterations affect the biological pathways underlying the aberrant social behavior and point out avenues for future research. We advocate the need for integration studies that combine multiple measures covering a broad range of social behaviors and link these to genetic and epigenetic profiles. Copyright © 2018. Published by Elsevier Inc.

  2. [Phrenic nerve stimulation protects against mechanical ventilation-induced diaphragmatic dysfunction through myogenic regulatory factors].

    Science.gov (United States)

    An, G H; Chen, M; Zhan, W F; Hu, B; Zhang, H X

    2018-02-12

    Objective: To explore the protective effect of electrical stimulation of phrenic nerve on diaphragmatic function during mechanical ventilation. Methods: Forty healthy adult SD rats were randomly divided into 5 groups: blank control group (BC), spontaneous breathing group (SB), electrical stimulation group (ES), mechanical ventilation group (MV), and electrical stimulation and mechanical ventilation group (MS). The rats in each group were treated for 18 h except for the BC group. After treatment, the diaphragm muscle tissue was obtained and the diaphragm contractility including peak-to-peak value(Vpp) and maximum rate of contraction(+ dT/dt max) were measured. Expression of MyoD and myogenin were detected. Results: Except for the ES and the MS groups, there was a significant difference for peak-to-peak value (Vpp) between each 2 groups ( P mechanical ventilation induced diaphragmatic function damage, and therefore plays a protective effect on the diaphragm.

  3. Structure reveals regulatory mechanisms of a MaoC-like hydratase from Phytophthora capsici involved in biosynthesis of polyhydroxyalkanoates (PHAs).

    Science.gov (United States)

    Wang, Huizheng; Zhang, Kai; Zhu, Jie; Song, Weiwei; Zhao, Li; Zhang, Xiuguo

    2013-01-01

    Polyhydroxyalkanoates (PHAs) have attracted increasing attention as "green plastic" due to their biodegradable, biocompatible, thermoplastic, and mechanical properties, and considerable research has been undertaken to develop low cost/high efficiency processes for the production of PHAs. MaoC-like hydratase (MaoC), which belongs to (R)-hydratase involved in linking the β-oxidation and the PHA biosynthetic pathways, has been identified recently. Understanding the regulatory mechanisms of (R)-hydratase catalysis is critical for efficient production of PHAs that promise synthesis an environment-friendly plastic. We have determined the crystal structure of a new MaoC recognized from Phytophthora capsici. The crystal structure of the enzyme was solved at 2.00 Å resolution. The structure shows that MaoC has a canonical (R)-hydratase fold with an N-domain and a C-domain. Supporting its dimerization observed in structure, MaoC forms a stable homodimer in solution. Mutations that disrupt the dimeric MaoC result in a complete loss of activity toward crotonyl-CoA, indicating that dimerization is required for the enzymatic activity of MaoC. Importantly, structure comparison reveals that a loop unique to MaoC interacts with an α-helix that harbors the catalytic residues of MaoC. Deletion of the loop enhances the enzymatic activity of MaoC, suggesting its inhibitory role in regulating the activity of MaoC. The data in our study reveal the regulatory mechanism of an (R)-hydratase, providing information on enzyme engineering to produce low cost PHAs.

  4. Structure reveals regulatory mechanisms of a MaoC-like hydratase from Phytophthora capsici involved in biosynthesis of polyhydroxyalkanoates (PHAs.

    Directory of Open Access Journals (Sweden)

    Huizheng Wang

    Full Text Available Polyhydroxyalkanoates (PHAs have attracted increasing attention as "green plastic" due to their biodegradable, biocompatible, thermoplastic, and mechanical properties, and considerable research has been undertaken to develop low cost/high efficiency processes for the production of PHAs. MaoC-like hydratase (MaoC, which belongs to (R-hydratase involved in linking the β-oxidation and the PHA biosynthetic pathways, has been identified recently. Understanding the regulatory mechanisms of (R-hydratase catalysis is critical for efficient production of PHAs that promise synthesis an environment-friendly plastic.We have determined the crystal structure of a new MaoC recognized from Phytophthora capsici. The crystal structure of the enzyme was solved at 2.00 Å resolution. The structure shows that MaoC has a canonical (R-hydratase fold with an N-domain and a C-domain. Supporting its dimerization observed in structure, MaoC forms a stable homodimer in solution. Mutations that disrupt the dimeric MaoC result in a complete loss of activity toward crotonyl-CoA, indicating that dimerization is required for the enzymatic activity of MaoC. Importantly, structure comparison reveals that a loop unique to MaoC interacts with an α-helix that harbors the catalytic residues of MaoC. Deletion of the loop enhances the enzymatic activity of MaoC, suggesting its inhibitory role in regulating the activity of MaoC.The data in our study reveal the regulatory mechanism of an (R-hydratase, providing information on enzyme engineering to produce low cost PHAs.

  5. Do regulatory mechanisms promote competition and mitigate market power? Evidence from Spanish electricity market

    International Nuclear Information System (INIS)

    Moutinho, Victor; Moreira, António C.; Mota, Jorge

    2014-01-01

    This paper estimates the relationships between bidding quantities, marginal cost and market power measures in the Spanish wholesale electricity market for two different regulatory periods: 2002–2005 and 2006–2007. Using panel econometric techniques we find differences in the impacts on bidding strategies for both periods. Hence, the marginal cost and the market power measures affect bid and net quantities. The market power measures also suggest that the coefficient is consistently positive and highly significant for both periods. Moreover, the market power and marginal costs have mixed effects according to the models proposed for both periods. In addition, our results point to the effectiveness of the different effects of mitigating the market power in the Spanish electricity market. For the 2006–2007 period, the proposed causal relationships are partially validated by the cointegration results, which assumes there is a significant causality between the Lerner Index and the marginal cost. - Highlights: • Competition and regulation in the Spanish electricity market. • Net supplier and net demander behavior in the spot market. • Panel cointegration methods used: FMOLS, PMG, MG, DFE and DOLS. • The price cap regulation is effective in mitigating market power. • Market power and marginal cost have positive effects on bidding strategies

  6. Imperialism and accountability in corporate law: the limitations of incorporation law as a regulatory mechanism

    OpenAIRE

    Foster, Nicholas HD; Ball, Jane

    2006-01-01

    This article discusses the limitations of the law incorporating a corporation (‘incorporation law’) as a control or governance mechanism in a world where it is increasingly difficult to prevent corporations choosing the incorporation law which suits them best. It uses as an example of the globalising pressures in this field three important cases on the right of establishment in the European Union.

  7. Drought response in wheat: key genes and regulatory mechanisms controlling root system architecture and transpiration efficiency

    Science.gov (United States)

    Kulkarni, Manoj; Soolanayakanahally, Raju; Ogawa, Satoshi; Uga, Yusaku; Selvaraj, Michael G.; Kagale, Sateesh

    2017-12-01

    sequence and advent genome editing technologies, are expected to aid in deciphering of the functional roles of genes and regulatory networks underlying adaptive phenological traits, and utilizing the outcomes of such studies in developing drought tolerance cultivars.

  8. Transport mechanism and regulatory properties of the human amino acid transporter ASCT2 (SLC1A5).

    Science.gov (United States)

    Scalise, Mariafrancesca; Pochini, Lorena; Panni, Simona; Pingitore, Piero; Hedfalk, Kristina; Indiveri, Cesare

    2014-11-01

    The kinetic mechanism of the transport catalyzed by the human glutamine/neutral amino acid transporter hASCT2 over-expressed in P. pastoris was determined in proteoliposomes by pseudo-bi-substrate kinetic analysis of the Na(+)-glutamineex/glutaminein transport reaction. A random simultaneous mechanism resulted from the experimental analysis. Purified functional hASCT2 was chemically cross-linked to a stable dimeric form. The oligomeric structure correlated well with the kinetic mechanism of transport. Half-saturation constants (Km) of the transporter for the other substrates Ala, Ser, Asn and Thr were measured both on the external and internal side. External Km were much lower than the internal ones confirming the asymmetry of the transporter. The electric nature of the transport reaction was determined imposing a negative inside membrane potential generated by K(+) gradients in the presence of valinomycin. The transport reaction resulted to be electrogenic and the electrogenicity originated from external Na(+). Internal Na(+) exerted a stimulatory effect on the transport activity which could be explained by a regulatory, not a counter-transport, effect. Native and deglycosylated hASCT2 extracted from HeLa showed the same transport features demonstrating that the glycosyl moiety has no role in transport function. Both in vitro and in vivo interactions of hASCT2 with the scaffold protein PDZK1 were revealed.

  9. [Advance in research on regulatory mechanism and functions of neutral sphingomyelinse 2].

    Science.gov (United States)

    Zhang, Lan; Guo, Jun

    2013-10-01

    Neutral sphingomyelinase 2 (nSMase2), which located mainly on the plasma membrane, hydrolyzes sphingomyelin into ceramide and plays an important role in the physiological and pathological regulation of cell apoptosis, cell growth arrest, and inflammation. nSMase2 is also involved in the development of Alzheimer's disease and the bone growth.Under neutral pH and the presence of Ca(2+), Mg(2+), and Mn(+), the activity of nSMase2 is induced by oxidative stress through phosphorylation. Furthermore, the induced interaction of anionic phospholipids and the signaling molecules like receptor for activated C-kinase 1/embryonic ectodermal development with nSMase2 are also crucial mechanisms of protein activation. In the review, recent research advances in the structure and function of nSMase2 and its underlying mechanisms are summarized.

  10. Transcriptome profiling of a curdlan-producing Agrobacterium reveals conserved regulatory mechanisms of exopolysaccharide biosynthesis

    Directory of Open Access Journals (Sweden)

    Ruffing Anne M

    2012-02-01

    Full Text Available Abstract Background The ability to synthesize exopolysaccharides (EPS is widespread among microorganisms, and microbial EPS play important roles in biofilm formation, pathogen persistence, and applications in the food and medical industries. Although it is well established that EPS synthesis is invariably in response to environmental cues, it remains largely unknown how various environmental signals trigger activation of the biochemical synthesis machinery. Results We report here the transcriptome profiling of Agrobacterium sp. ATCC 31749, a microorganism that produces large amounts of a glucose polymer known as curdlan under nitrogen starvation. Transcriptome analysis revealed a nearly 100-fold upregulation of the curdlan synthesis operon upon transition to nitrogen starvation, thus establishing the prominent role that transcriptional regulation plays in the EPS synthesis. In addition to known mechanisms of EPS regulation such as activation by c-di-GMP, we identify novel mechanisms of regulation in ATCC 31749, including RpoN-independent NtrC regulation and intracellular pH regulation by acidocalcisomes. Furthermore, we show evidence that curdlan synthesis is also regulated by conserved cell stress responses, including polyphosphate accumulation and the stringent response. In fact, the stringent response signal, pppGpp, appears to be indispensible for transcriptional activation of curdlan biosynthesis. Conclusions This study identifies several mechanisms regulating the synthesis of curdlan, an EPS with numerous applications. These mechanisms are potential metabolic engineering targets for improving the industrial production of curdlan from Agrobacterium sp. ATCC 31749. Furthermore, many of the genes identified in this study are highly conserved across microbial genomes, and we propose that the molecular elements identified in this study may serve as universal regulators of microbial EPS synthesis.

  11. Regulatory mechanisms of anthrax toxin receptor 1-dependent vascular and connective tissue homeostasis.

    Science.gov (United States)

    Besschetnova, Tatiana Y; Ichimura, Takaharu; Katebi, Negin; St Croix, Brad; Bonventre, Joseph V; Olsen, Bjorn R

    2015-03-01

    It is well known that angiogenesis is linked to fibrotic processes in fibroproliferative diseases, but insights into pathophysiological processes are limited, due to lack of understanding of molecular mechanisms controlling endothelial and fibroblastic homeostasis. We demonstrate here that the matrix receptor anthrax toxin receptor 1 (ANTXR1), also known as tumor endothelial marker 8 (TEM8), is an essential component of these mechanisms. Loss of TEM8 function in mice causes reduced synthesis of endothelial basement membrane components and hyperproliferative and leaky blood vessels in skin. In addition, endothelial cell alterations in mutants are almost identical to those of endothelial cells in infantile hemangioma lesions, including activated VEGF receptor signaling in endothelial cells, increased expression of the downstream targets VEGF and CXCL12, and increased numbers of macrophages and mast cells. In contrast, loss of TEM8 in fibroblasts leads to increased rates of synthesis of fiber-forming collagens, resulting in progressive fibrosis in skin and other organs. Compromised interactions between TEM8-deficient endothelial and fibroblastic cells cause dramatic reduction in the activity of the matrix-degrading enzyme MMP2. In addition to insights into mechanisms of connective tissue homeostasis, our data provide molecular explanations for vascular and connective tissue abnormalities in GAPO syndrome, caused by loss-of-function mutations in ANTXR1. Furthermore, the loss of MMP2 activity suggests that fibrotic skin abnormalities in GAPO syndrome are, in part, the consequence of pathophysiological mechanisms underlying syndromes (NAO, Torg and Winchester) with multicentric skin nodulosis and osteolysis caused by homozygous loss-of-function mutations in MMP2. Copyright © 2014 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  12. 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.

  13. Drought Response in Wheat: Key Genes and Regulatory Mechanisms Controlling Root System Architecture and Transpiration Efficiency

    Directory of Open Access Journals (Sweden)

    Manoj Kulkarni

    2017-12-01

    gold-standard reference genome sequence and advent of genome editing technologies, are expected to aid in deciphering of the functional roles of genes and regulatory networks underlying adaptive phenological traits, and utilizing the outcomes of such studies in developing drought tolerant cultivars.

  14. Kinetic characterization of Vibrio cholerae ApbE: Substrate specificity and regulatory mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Fang, Xuan; Liang, Pingdong; Raba, Daniel Alexander; Rosas-Lemus, Mónica; Chakravarthy, Srinivas; Tuz, Karina; Juárez, Oscar; Permyakov, Eugene A.

    2017-10-24

    ApbE is a member of a novel family of flavin transferases that incorporates flavin mononucleotide (FMN) to subunits of diverse respiratory complexes, which fulfill important homeostatic functions. In this work a detailed characterization of Vibrio cholerae ApbE physiologic activity, substrate specificity and pH dependency was carried out. The data obtained show novel characteristics of the regulation and function of this family. For instance, our experiments indicate that divalent cations are essential for ApbE function, and that the selectivity depends largely on size and the coordination sphere of the cation. Our data also show that ApbE regulation by pH, ADP and potassium is an important mechanism that enhances the adaptation, survival and colonization of V. cholerae in the small intestine. Moreover, studies of the pH-dependency of the activity show that the reaction is favored under alkaline conditions, with a pKa of 8.4. These studies, together with sequence and structure analysis allowed us to identify His257, which is absolutely conserved in the family, as a candidate for the residue whose deprotonation controls the activity. Remarkably, the mutant H257G abolished the flavin transfer activity, strongly indicating that this residue plays an important role in the catalytic mechanism of ApbE.

  15. Dss1 interaction with Brh2 as a regulatory mechanism for recombinational repair

    DEFF Research Database (Denmark)

    Zhou, Qingwen; Kojic, Milorad; Cao, Zhimin

    2007-01-01

    Brh2, the BRCA2 ortholog in Ustilago maydis, enables recombinational repair of DNA by controlling Rad51 and is in turn regulated by Dss1. Interplay with Rad51 is conducted via the BRC element located in the N-terminal region of the protein and through an unrelated domain, CRE, at the C terminus....... Mutation in either BRC or CRE severely reduces functional activity, but repair deficiency of the brh2 mutant can be complemented by expressing BRC and CRE on different molecules. This intermolecular complementation is dependent upon the presence of Dss1. Brh2 molecules associate through the region...... overlapping with the Dss1-interacting domain to form at least dimer-sized complexes, which in turn, can be dissociated by Dss1 to monomer. We propose that cooperation between BRC and CRE domains and the Dss1-provoked dissociation of Brh2 complexes are requisite features of Brh2's molecular mechanism...

  16. The many factors that affect the success of regulatory mechanisms designed to foster investments in energy efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Zarnikau [LBJ School of Public Affairs and Division of Statistics of the College of Natural Sciences, The University of Texas at Austin, Austin, TX 78713 (United States)

    2012-08-15

    A utility's profit-maximizing level of investment in energy efficiency or demand-side management (DSM) programs and mix of programs is affected by natural load growth, the frequency of rate cases, program costs, and the structure of any mechanism designed to either compensate the utility for foregone profits or sever the link between sales and profits. Under a range of reasonable assumptions, decoupling can incent a utility to invest in DSM. However, a utility experiencing high natural load growth and little inflation is likely to resist the imposition of a decoupling mechanism, as it would tend to lower profits. A utility with low growth in per-customer sales will tend to favor decoupling, as it will tend to lead to higher profits than under traditional regulation. The results presented here are quite sensitive to the assumptions made regarding natural load growth, regulatory lag, the frequency of price changes, price elasticity of demand, and other factors. This suggests that there is not a single approach to promoting energy efficiency without penalizing utility profits that will work in all situations for all utilities.

  17. Tuning of redox regulatory mechanisms, reactive oxygen species and redox homeostasis under salinity stress

    Directory of Open Access Journals (Sweden)

    Hossain eSazzad

    2016-05-01

    Full Text Available Soil salinity is a crucial environmental constraint which limits biomass production at many sites on a global scale. Saline growth conditions cause osmotic and ionic imbalances, oxidative stress and perturb metabolism, e.g. the photosynthetic electron flow. The plant ability to tolerate salinity is determined by multiple biochemical and physiological mechanisms protecting cell functions, in particular by regulating proper water relations and maintaining ion homeostasis. Redox homeostasis is a fundamental cell property. Its regulation includes control of reactive oxygen species (ROS generation, sensing deviation from and readjustment of the cellular redox state. All these redox related functions have been recognized as decisive factors in salinity acclimation and adaptation. This review focuses on the core response of plants to overcome the challenges of salinity stress through regulation of ROS generation and detoxification systems and to maintain redox homeostasis. Emphasis is given to the role of NADH oxidase (RBOH, alternative oxidase (AOX, the plastid terminal oxidase (PTOX and the malate valve with the malate dehydrogenase isoforms under salt stress. Overwhelming evidence assigns an essential auxiliary function of ROS and redox homeostasis to salinity acclimation of plants.

  18. Regulatory mechanisms for iron transport across the blood-brain barrier.

    Science.gov (United States)

    Duck, Kari A; Simpson, Ian A; Connor, James R

    2017-12-09

    Many critical metabolic functions in the brain require adequate and timely delivery of iron. However, most studies when considering brain iron uptake have ignored the iron requirements of the endothelial cells that form the blood-brain barrier (BBB). Moreover, current models of BBB iron transport do not address regional regulation of brain iron uptake or how neurons, when adapting to metabolic demands, can acquire more iron. In this study, we demonstrate that both iron-poor transferrin (apo-Tf) and the iron chelator, deferoxamine, stimulate release of iron from iron-loaded endothelial cells in an in vitro BBB model. The role of the endosomal divalent metal transporter 1 (DMT1) in BBB iron acquisition and transport has been questioned. Here, we show that inhibition of DMT1 alters the transport of iron and Tf across the endothelial cells. These data support an endosome-mediated model of Tf-bound iron uptake into the brain and identifies mechanisms for local regional regulation of brain iron uptake. Moreover, our data provide an explanation for the disparity in the ratio of Tf to iron transport into the brain that has confounded the field. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. The Mechanisms of Water Exchange: The Regulatory Roles of Multiple Interactions in Social Wasps.

    Science.gov (United States)

    Agrawal, Devanshu; Karsai, Istvan

    2016-01-01

    Evolutionary benefits of task fidelity and improving information acquisition via multiple transfers of materials between individuals in a task partitioned system have been shown before, but in this paper we provide a mechanistic explanation of these phenomena. Using a simple mathematical model describing the individual interactions of the wasps, we explain the functioning of the common stomach, an information center, which governs construction behavior and task change. Our central hypothesis is a symmetry between foragers who deposit water and foragers who withdraw water into and out of the common stomach. We combine this with a trade-off between acceptance and resistance to water transfer. We ultimately derive a mathematical function that relates the number of interactions that foragers complete with common stomach wasps during a foraging cycle. We use field data and additional model assumptions to calculate values of our model parameters, and we use these to explain why the fullness of the common stomach stabilizes just below 50 percent, why the average number of successful interactions between foragers and the wasps forming the common stomach is between 5 and 7, and why there is a variation in this number of interactions over time. Our explanation is that our proposed water exchange mechanism places natural bounds on the number of successful interactions possible, water exchange is set to optimize mediation of water through the common stomach, and the chance that foragers abort their task prematurely is very low.

  20. The Regulatory Mechanism of MLT/MT1 Signaling on the Growth of Antler Mesenchymal Cells

    Directory of Open Access Journals (Sweden)

    Feifei Yang

    2017-10-01

    Full Text Available Melatonin (MLT plays an important role in regulating the physiological cycle of seasonal breeding animals. Melatonin receptor I (MT1 is effectively expressed in the cambium layer of deer antler. However, the function and metabolic mechanism of MLT/MT1 signaling in the mesenchymal cells of sika deer remain to be further elucidated. In this work, we detected the effects of MLT/MT1 signaling on mesenchymal cells proliferation and the interaction between MLT/MT1 and IGF1/IGF1-R signaling. The results show that (1 deer antler mesenchymal cells actually express MT1; (2 exogenous melatonin significantly promotes mesenchymal cells proliferation, while MT1 knock-down significantly impairs the positive effects of melatonin; and (3 melatonin significantly enhanced IGF1/IGF1-R signaling, as both the expression of IGF1 and IGF-1R increased, while MT1 knock-down significantly decreased IGF1-R expression and IGF1 synthesis. In summary, these data verified that MLT/MT1 signaling plays a crucial role in antler mesenchymal proliferation, which may be mediated by IGF1/IGF1-R.

  1. Molecular mechanism for differential recognition of membrane phosphatidylserine by the immune regulatory receptor Tim4.

    Science.gov (United States)

    Tietjen, Gregory T; Gong, Zhiliang; Chen, Chiu-Hao; Vargas, Ernesto; Crooks, James E; Cao, Kathleen D; Heffern, Charles T R; Henderson, J Michael; Meron, Mati; Lin, Binhua; Roux, Benot; Schlossman, Mark L; Steck, Theodore L; Lee, Ka Yee C; Adams, Erin J

    2014-04-15

    Recognition of phosphatidylserine (PS) lipids exposed on the extracellular leaflet of plasma membranes is implicated in both apoptotic cell removal and immune regulation. The PS receptor T cell immunoglobulin and mucin-domain-containing molecule 4 (Tim4) regulates T-cell immunity via phagocytosis of both apoptotic (high PS exposure) and nonapoptotic (intermediate PS exposure) activated T cells. The latter population must be removed at lower efficiency to sensitively control immune tolerance and memory cell population size, but the molecular basis for how Tim4 achieves this sensitivity is unknown. Using a combination of interfacial X-ray scattering, molecular dynamics simulations, and membrane binding assays, we demonstrate how Tim4 recognizes PS in the context of a lipid bilayer. Our data reveal that in addition to the known Ca(2+)-coordinated, single-PS binding pocket, Tim4 has four weaker sites of potential ionic interactions with PS lipids. This organization makes Tim4 sensitive to PS surface concentration in a manner capable of supporting differential recognition on the basis of PS exposure level. The structurally homologous, but functionally distinct, Tim1 and Tim3 are significantly less sensitive to PS surface density, likely reflecting the differences in immunological function between the Tim proteins. These results establish the potential for lipid membrane parameters, such as PS surface density, to play a critical role in facilitating selective recognition of PS-exposing cells. Furthermore, our multidisciplinary approach overcomes the difficulties associated with characterizing dynamic protein/membrane systems to reveal the molecular mechanisms underlying Tim4's recognition properties, and thereby provides an approach capable of providing atomic-level detail to uncover the nuances of protein/membrane interactions.

  2. The effects and regulatory mechanism of RIP3 on RGC-5 necroptosis following elevated hydrostatic pressure.

    Science.gov (United States)

    Shang, Lei; Ding, Wei; Li, Na; Liao, Lvshuang; Chen, Dan; Huang, Jufang; Xiong, Kun

    2017-02-06

    Necroptosis is a type of regulated cell death that has been implicated in various diseases. Receptor-interacting protein 3 (RIP3), a member of the RIP family, is an important mediator of the necroptotic pathway. Cleavage of RIP3 at Asp328 by caspase-8 abolishes the kinase activity of RIP3, which is critical for necroptosis. Moreover, RIP3 is significantly upregulated during the early stages of acute high intra-ocular pressure and oxygen glucose deprivation. In this study, the effects of RIP3 during elevated hydrostatic pressure (EHP) were investigated and the possible mechanism through which caspase-8 regulated RIP3 cleavage was explored. Flow cytometry analysis revealed that the number of EHP-induced necrotic retinal ganglion cell 5 (RGC-5) cells was reduced after RIP3-knockdown. Furthermore, malondialdehyde (MDA) levels and glycogen phosphorylase (PYGL) activity in normal RGC-5 cells were much higher than those in RIP3-knockdown cells after EHP. EHP-induced RGC-5 necrosis was significantly reduced after treatment with butylated hydroxyanisole (BHA), a reactive oxygen species (ROS) scavenger. MDA levels and PYGL activity were lower in normal RGC-5 cells than those in cells with caspase-8 inhibition after EHP. Western blot analysis demonstrated that the RIP3 cleavage product was upregulated in cells with caspase-8 inhibition. Additionally, flow cytometry analysis revealed that the number of EHP-induced necrotic RGC-5 cells was increased after caspase-8 inhibition. Our results suggested that RGC-5 necroptosis following EHP was mediated by RIP3 through induction of PYGL activity and subsequent ROS accumulation. Thus, caspase-8 may participate in the regulation of RGC-5 necroptosis via RIP3 cleavage. © The Author 2016. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. A Transcriptional Regulatory Mechanism Finely Tunes the Firing of Type VI Secretion System in Response to Bacterial Enemies.

    Science.gov (United States)

    Lazzaro, Martina; Feldman, Mario F; García Véscovi, Eleonora

    2017-08-22

    The ability to detect and measure danger from an environmental signal is paramount for bacteria to respond accordingly, deploying strategies that halt or counteract potential cellular injury and maximize survival chances. Type VI secretion systems (T6SSs) are complex bacterial contractile nanomachines able to target toxic effectors into neighboring bacteria competing for the same colonization niche. Previous studies support the concept that either T6SSs are constitutively active or they fire effectors in response to various stimuli, such as high bacterial density, cell-cell contact, nutrient depletion, or components from dead sibling cells. For Serratia marcescens , it has been proposed that its T6SS is stochastically expressed, with no distinction between harmless or aggressive competitors. In contrast, we demonstrate that the Rcs regulatory system is responsible for finely tuning Serratia T6SS expression levels, behaving as a transcriptional rheostat. When confronted with harmless bacteria, basal T6SS expression levels suffice for Serratia to eliminate the competitor. A moderate T6SS upregulation is triggered when, according to the aggressor-prey ratio, an unbalanced interplay between homologous and heterologous effectors and immunity proteins takes place. Higher T6SS expression levels are achieved when Serratia is challenged by a contender like Acinetobacter , which indiscriminately fires heterologous effectors able to exert lethal cellular harm, threatening the survival of the Serratia population. We also demonstrate that Serratia 's RcsB-dependent T6SS regulatory mechanism responds not to general stress signals but to the action of specific effectors from competitors, displaying an exquisite strategy to weigh risks and keep the balance between energy expenditure and fitness costs. IMPORTANCE Serratia marcescens is among the health-threatening pathogens categorized by the WHO as research priorities to develop alternative antimicrobial strategies, and it was

  4. Electrical stimulation of the substantia nigra reticulata : Detection of neuronal extracellular GABA in the ventromedial thalamus and its regulatory mechanism using microdialysis in awake rats

    NARCIS (Netherlands)

    Timmerman, W; Westerink, B.H.C.

    A combination of electrical stimulation and microdialysis was used to study the nigrothalamic gamma aminobutyric acid (GABA)ergic system and its regulatory mechanisms in awake rats. Extracellular GABA levels in the ventromedial nucleus of the thalamus were detected in S-min fractions collected

  5. Regulatory Mechanisms of the Ihh/PTHrP Signaling Pathway in Fibrochondrocytes in Entheses of Pig Achilles Tendon

    Directory of Open Access Journals (Sweden)

    Xuesong Han

    2016-01-01

    Full Text Available This study is aimed at exploring the effect of stress stimulation on the proliferation and differentiation of fibrochondrocytes in entheses mediated via the Indian hedgehog (Ihh/parathyroid hormone-related protein (PTHrP signaling pathway. Differential stress stimulation on fibrochondrocytes in entheses was imposed. Gene expression and protein levels of signaling molecules including collagen type I (Col I, Col II, Col X, Ihh, and PTHrP in the cytoplasm of fibrochondrocytes were detected. Ihh signal blocking group was set up using Ihh signaling pathway-specific blocking agent cyclopamine. PTHrP enhancement group was set up using PTHrP reagent. Ihh/PTHrP double intervention group, as well as control group, was included to study the regulatory mechanisms of the Ihh/PTHrP signaling pathway in fibrochondrocytes. Under low cyclic stress tensile (CTS, PTHrP, Col I, and Col II gene expression and protein synthesis increased. Under high CTS, Ihh and Col X gene expression and protein synthesis increased. Blocking Ihh signaling with cyclopamine resulted in reduced PTHrP gene expression and protein synthesis and increased Col X gene expression and protein synthesis. Ihh and PTHrP coregulate fibrochondrocyte proliferation and differentiation in entheses through negative feedback regulation. Fibrochondrocyte is affected by the CTS. This phenomenon is regulated by stress stimulation through the Ihh/PTHrP signaling pathway.

  6. Regulatory Mechanisms of the Ihh/PTHrP Signaling Pathway in Fibrochondrocytes in Entheses of Pig Achilles Tendon.

    Science.gov (United States)

    Han, Xuesong; Zhuang, Yanfeng; Zhang, Zhihong; Guo, Lin; Wang, Wanming

    2016-01-01

    This study is aimed at exploring the effect of stress stimulation on the proliferation and differentiation of fibrochondrocytes in entheses mediated via the Indian hedgehog (Ihh)/parathyroid hormone-related protein (PTHrP) signaling pathway. Differential stress stimulation on fibrochondrocytes in entheses was imposed. Gene expression and protein levels of signaling molecules including collagen type I (Col I), Col II, Col X, Ihh, and PTHrP in the cytoplasm of fibrochondrocytes were detected. Ihh signal blocking group was set up using Ihh signaling pathway-specific blocking agent cyclopamine. PTHrP enhancement group was set up using PTHrP reagent. Ihh/PTHrP double intervention group, as well as control group, was included to study the regulatory mechanisms of the Ihh/PTHrP signaling pathway in fibrochondrocytes. Under low cyclic stress tensile (CTS), PTHrP, Col I, and Col II gene expression and protein synthesis increased. Under high CTS, Ihh and Col X gene expression and protein synthesis increased. Blocking Ihh signaling with cyclopamine resulted in reduced PTHrP gene expression and protein synthesis and increased Col X gene expression and protein synthesis. Ihh and PTHrP coregulate fibrochondrocyte proliferation and differentiation in entheses through negative feedback regulation. Fibrochondrocyte is affected by the CTS. This phenomenon is regulated by stress stimulation through the Ihh/PTHrP signaling pathway.

  7. Thrombopoietin-induced Polyploidization of Bone Marrow Megakaryocytes Is Due to a Unique Regulatory Mechanism in Late Mitosis

    Science.gov (United States)

    Nagata, Yuka; Muro, Yoshinao; Todokoro, Kazuo

    1997-01-01

    Megakaryocytes undergo a unique differentiation program, becoming polyploid through repeated cycles of DNA synthesis without concomitant cell division. However, the mechanism underlying this polyploidization remains totally unknown. It has been postulated that polyploidization is due to a skipping of mitosis after each round of DNA replication. We carried out immunohistochemical studies on mouse bone marrow megakaryocytes during thrombopoietin- induced polyploidization and found that during this process megakaryocytes indeed enter mitosis and progress through normal prophase, prometaphase, metaphase, and up to anaphase A, but not to anaphase B, telophase, or cytokinesis. It was clearly observed that multiple spindle poles were formed as the polyploid megakaryocytes entered mitosis; the nuclear membrane broke down during prophase; the sister chromatids were aligned on a multifaced plate, and the centrosomes were symmetrically located on either side of each face of the plate at metaphase; and a set of sister chromatids moved into the multiple centrosomes during anaphase A. We further noted that the pair of spindle poles in anaphase were located in close proximity to each other, probably because of the lack of outward movement of spindle poles during anaphase B. Thus, the reassembling nuclear envelope may enclose all the sister chromatids in a single nucleus at anaphase and then skip telophase and cytokinesis. These observations clearly indicate that polyploidization of megakaryocytes is not simply due to a skipping of mitosis, and that the megakaryocytes must have a unique regulatory mechanism in anaphase, e.g., factors regulating anaphase such as microtubule motor proteins might be involved in this polyploidization process. PMID:9334347

  8. Multistructure index in revealing complexity of regulatory mechanisms of human cardiovascular system at rest and orthostatic stress in healthy humans

    Science.gov (United States)

    Makowiec, Danuta; Graff, Beata; Struzik, Zbigniew R.

    2017-02-01

    Biological regulation is sufficiently complex to pose an enduring challenge for characterization of both its equilibrium and transient non-equilibrium dynamics. Two univariate but coupled observables, heart rate and systolic blood pressure, are commonly characterized in the benchmark example of the human cardiovascular regulatory system. Asymmetric distributions of accelerations and decelerations of heart rate, as well as rises and falls in systolic blood pressure, recorded in humans during a head-up tilt test provide insights into the dynamics of cardiovascular response to a rapid, controlled deregulation of the system's homeostasis. The baroreflex feedback loop is assumed to be the fundamental physiological mechanism for ensuring homeostatic blood supply to distant organs at rest and during orthostatic stress, captured in a classical beat-to-beat autoregressive model of baroreflex by de Boer et al. (1987). For model corroboration, a multistructure index statistic is proposed, seamlessly evaluating the size spectrum of magnitudes of neural reflexes such as baroreflex, responsible for maintaining the homeostatic dynamics. The multistructure index exposes a distinctly different dynamics of multiscale asymmetry between results obtained from real-life signals recorded from healthy subjects and those simulated using both the classical and perturbed versions of the model. Nonlinear effects observed suggest the pronounced presence of complex mechanisms resulting from baroreflex regulation when a human is at rest, which is aggravated in the system's response to orthostatic stress. Using our methodology of multistructure index, we therefore show a marked difference between model and real-life scenarios, which we attribute to multiscale asymmetry of non-linear origin in real-life signals, which we are not reproducible by the classical model.

  9. The function of the RNA-binding protein TEL1 in moss reveals ancient regulatory mechanisms of shoot development.

    Science.gov (United States)

    Vivancos, Julien; Spinner, Lara; Mazubert, Christelle; Charlot, Florence; Paquet, Nicolas; Thareau, Vincent; Dron, Michel; Nogué, Fabien; Charon, Céline

    2012-03-01

    The shoot represents the basic body plan in land plants. It consists of a repeated structure composed of stems and leaves. Whereas vascular plants generate a shoot in their diploid phase, non-vascular plants such as mosses form a shoot (called the gametophore) in their haploid generation. The evolution of regulatory mechanisms or genetic networks used in the development of these two kinds of shoots is unclear. TERMINAL EAR1-like genes have been involved in diploid shoot development in vascular plants. Here, we show that disruption of PpTEL1 from the moss Physcomitrella patens, causes reduced protonema growth and gametophore initiation, as well as defects in gametophore development. Leafy shoots formed on ΔTEL1 mutants exhibit shorter stems with more leaves per shoot, suggesting an accelerated leaf initiation (shortened plastochron), a phenotype shared with the Poaceae vascular plants TE1 and PLA2/LHD2 mutants. Moreover, the positive correlation between plastochron length and leaf size observed in ΔTEL1 mutants suggests a conserved compensatory mechanism correlating leaf growth and leaf initiation rate that would minimize overall changes in plant biomass. The RNA-binding protein encoded by PpTEL1 contains two N-terminus RNA-recognition motifs, and a third C-terminus non-canonical RRM, specific to TEL proteins. Removal of the PpTEL1 C-terminus (including this third RRM) or only 16-18 amino acids within it seriously impairs PpTEL1 function, suggesting a critical role for this third RRM. These results show a conserved function of the RNA-binding PpTEL1 protein in the regulation of shoot development, from early ancestors to vascular plants, that depends on the third TEL-specific RRM.

  10. Just-in-time control of Spo0A synthesis in Bacillus subtilis by multiple regulatory mechanisms.

    Science.gov (United States)

    Chastanet, Arnaud; Losick, Richard

    2011-11-01

    The response regulator Spo0A governs multiple developmental processes in Bacillus subtilis, including most conspicuously sporulation. Spo0A is activated by phosphorylation via a multicomponent phosphorelay. Previous work has shown that the Spo0A protein is not rate limiting for sporulation. Rather, Spo0A is present at high levels in growing cells, rapidly rising to yet higher levels under sporulation-inducing conditions, suggesting that synthesis of the response regulator is subject to a just-in-time control mechanism. Transcription of spo0A is governed by a promoter switching mechanism, involving a vegetative, σ(A)-recognized promoter, P(v), and a sporulation σ(H)-recognized promoter, P(s), that is under phosphorylated Spo0A (Spo0A∼P) control. The spo0A regulatory region also contains four (including one identified in the present work) conserved elements that conform to the consensus binding site for Spo0A∼P binding sites. These are herein designated O(1), O(2), O(3), and O(4) in reverse order of their proximity to the coding sequence. Here we report that O(1) is responsible for repressing P(v) during the transition to stationary phase, that O(2) is responsible for repressing P(s) during growth, that O(3) is responsible for activating P(s) at the start of sporulation, and that O(4) is dispensable for promoter switching. We also report that Spo0A synthesis is subject to a posttranscriptional control mechanism such that translation of mRNAs originating from P(v) is impeded due to RNA secondary structure whereas mRNAs originating from P(s) are fully competent for protein synthesis. We propose that the opposing actions of O(2) and O(3) and the enhanced translatability of mRNAs originating from P(s) create a highly sensitive, self-reinforcing switch that is responsible for producing a burst of Spo0A synthesis at the start of sporulation.

  11. Bacillus subtilis as a platform for molecular characterisation of regulatory mechanisms of Enterococcus faecalis resistance against cell wall antibiotics.

    Science.gov (United States)

    Fang, Chong; Stiegeler, Emanuel; Cook, Gregory M; Mascher, Thorsten; Gebhard, Susanne

    2014-01-01

    To combat antibiotic resistance of Enterococcus faecalis, a better understanding of the molecular mechanisms, particularly of antibiotic detection, signal transduction and gene regulation is needed. Because molecular studies in this bacterium can be challenging, we aimed at exploiting the genetically highly tractable Gram-positive model organism Bacillus subtilis as a heterologous host. Two fundamentally different regulators of E. faecalis resistance against cell wall antibiotics, the bacitracin sensor BcrR and the vancomycin-sensing two-component system VanSB-VanRB, were produced in B. subtilis and their functions were monitored using target promoters fused to reporter genes (lacZ and luxABCDE). The bacitracin resistance system BcrR-BcrAB of E. faecalis was fully functional in B. subtilis, both regarding regulation of bcrAB expression and resistance mediated by the transporter BcrAB. Removal of intrinsic bacitracin resistance of B. subtilis increased the sensitivity of the system. The lacZ and luxABCDE reporters were found to both offer sensitive detection of promoter induction on solid media, which is useful for screening of large mutant libraries. The VanSB-VanRB system displayed a gradual dose-response behaviour to vancomycin, but only when produced at low levels in the cell. Taken together, our data show that B. subtilis is a well-suited host for the molecular characterization of regulatory systems controlling resistance against cell wall active compounds in E. faecalis. Importantly, B. subtilis facilitates the careful adjustment of expression levels and genetic background required for full functionality of the introduced regulators.

  12. Functional Analysis of In-frame Indel ARID1A Mutations Reveals New Regulatory Mechanisms of Its Tumor Suppressor Functions

    Directory of Open Access Journals (Sweden)

    Bin Guan

    2012-10-01

    Full Text Available AT-rich interactive domain 1A (ARID1A has emerged as a new tumor suppressor in which frequent somatic mutations have been identified in several types of human cancers. Although most ARID1A somatic mutations are frame-shift or nonsense mutations that contribute to mRNA decay and loss of protein expression, 5% of ARID1A mutations are in-frame insertions or deletions (indels that involve only a small stretch of peptides. Naturally occurring in-frame indel mutations provide unique and useful models to explore the biology and regulatory role of ARID1A. In this study, we analyzed indel mutations identified in gynecological cancers to determine how these mutations affect the tumor suppressor function of ARID1A. Our results demonstrate that all in-frame mutants analyzed lost their ability to inhibit cellular proliferation or activate transcription of CDKN1A, which encodes p21, a downstream effector of ARID1A. We also showed that ARID1A is a nucleocytoplasmic protein whose stability depends on its subcellular localization. Nuclear ARID1A is less stable than cytoplasmic ARID1A because ARID1A is rapidly degraded by the ubiquitin-proteasome system in the nucleus. In-frame deletions affecting the consensus nuclear export signal reduce steady-state protein levels of ARID1A. This defect in nuclear exportation leads to nuclear retention and subsequent degradation. Our findings delineate a mechanism underlying the regulation of ARID1A subcellular distribution and protein stability and suggest that targeting the nuclear ubiquitin-proteasome system can increase the amount of the ARID1A protein in the nucleus and restore its tumor suppressor functions.

  13. Review: Regulatory mechanisms of gonadotropin-inhibitory hormone (GnIH synthesis and release in photoperiodic animals

    Directory of Open Access Journals (Sweden)

    Kazuyoshi eTsutsui

    2013-04-01

    Full Text Available Gonadotropin-inhibitory hormone (GnIH is a novel hypothalamic neuropeptide that was discovered in quail as an inhibitory factor for gonadotropin release. GnIH inhibits gonadotropin synthesis and release in birds through actions on gonadotropin-releasing hormone (GnRH neurons and gonadotropes, mediated via the GnIH receptor (GnIH-R, GPR147. Subsequently, GnIH was identified in mammals and other vertebrates. As in birds, mammalian GnIH inhibits gonadotropin secretion, indicating a conserved role for this neuropeptide in the control of the hypothalamic-pituitary-gonadal (HPG axis across species. Identification of the regulatory mechanisms governing GnIH expression and release is important in understanding the physiological role of the GnIH system. A nocturnal hormone, melatonin, appears to act directly on GnIH neurons through its receptor to induce expression and release of GnIH in quail, a photoperiodic bird. Recently, a similar, but opposite, action of melatonin on the inhibition of expression of mammalian GnIH was shown in hamsters and sheep, photoperiodic mammals. These results in photoperiodic animals demonstrate that GnIH expression is photoperiodically modulated via a melatonin-dependent process. Recent findings indicate that GnIH may be a mediator of stress-induced reproductive disruption in birds and mammals, pointing to a broad role for this neuropeptide in assessing physiological state and modifying reproductive effort accordingly. This paper summarizes the advances made in our knowledge regarding the regulation of GnIH synthesis and release in photoperiodic birds and mammals. This paper also discusses the neuroendocrine integration of environmental signals, such as photoperiods and stress, and internal signals, such as GnIH, melatonin and glucocorticoids, to control avian and mammalian reproduction.

  14. Simulating molecular mechanisms of the MDM2-mediated regulatory interactions: a conformational selection model of the MDM2 lid dynamics.

    Directory of Open Access Journals (Sweden)

    Gennady M Verkhivker

    Full Text Available Diversity and complexity of MDM2 mechanisms govern its principal function as the cellular antagonist of the p53 tumor suppressor. Structural and biophysical studies have demonstrated that MDM2 binding could be regulated by the dynamics of a pseudo-substrate lid motif. However, these experiments and subsequent computational studies have produced conflicting mechanistic models of MDM2 function and dynamics. We propose a unifying conformational selection model that can reconcile experimental findings and reveal a fundamental role of the lid as a dynamic regulator of MDM2-mediated binding. In this work, structure, dynamics and energetics of apo-MDM2 are studied as a function of posttranslational modifications and length of the lid. We found that the dynamic equilibrium between "closed" and "semi-closed" lid forms may be a fundamental characteristic of MDM2 regulatory interactions, which can be modulated by phosphorylation, phosphomimetic mutation as well as by the lid size. Our results revealed that these factors may regulate p53-MDM2 binding by fine-tuning the thermodynamic equilibrium between preexisting conformational states of apo-MDM2. In agreement with NMR studies, the effect of phosphorylation on MDM2 interactions was more pronounced with the truncated lid variant that favored the thermodynamically dominant closed form. The phosphomimetic mutation S17D may alter the lid dynamics by shifting the thermodynamic equilibrium towards the ensemble of "semi-closed" conformations. The dominant "semi-closed" lid form and weakened dependence on the phosphorylation seen in simulations with the complete lid can provide a rationale for binding of small p53-based mimetics and inhibitors without a direct competition with the lid dynamics. The results suggested that a conformational selection model of preexisting MDM2 states may provide a robust theoretical framework for understanding MDM2 dynamics. Probing biological functions and mechanisms of MDM2

  15. Muscle and neural isoforms of agrin increase utrophin expression in cultured myotubes via a transcriptional regulatory mechanism.

    Science.gov (United States)

    Gramolini, A O; Burton, E A; Tinsley, J M; Ferns, M J; Cartaud, A; Cartaud, J; Davies, K E; Lunde, J A; Jasmin, B J

    1998-01-09

    . Furthermore, this increase in transcriptional activity in response to agrin resulted from a greater number of myonuclei expressing the 1.3-kilobase pair utrophin promoter-nlsLacZ construct. Deletion of 800 base pairs 5' from this fragment decreased the basal levels of nlsLacZ expression and abolished the sensitivity of the utrophin promoter to exogenously applied agrin. In addition, site-directed mutagenesis of an N-box motif contained within this 800-base pair fragment demonstrated its essential contribution in this regulatory mechanism. Finally, direct gene transfer studies performed in vivo further revealed the importance of this DNA element for the synapse-specific expression of the utrophin gene along multinucleated muscle fibers. These data show that both muscle and neural isoforms of agrin can regulate expression of the utrophin gene and further indicate that agrin is not only involved in the mechanisms leading to the formation of clusters containing presynthesized synaptic molecules but that it can also participate in the local regulation of genes encoding synaptic proteins. Together, these observations are therefore relevant for our basic understanding of the events involved in the assembly and maintenance of the postsynaptic membrane domain of the neuromuscular junction and for the potential use of utrophin as a therapeutic strategy to counteract the effects of Duchenne muscular dystrophy.

  16. Combined chromatin and expression analysis reveals specific regulatory mechanisms within cytokine genes in the macrophage early immune response.

    Directory of Open Access Journals (Sweden)

    Maria Jesus Iglesias

    Full Text Available Macrophages play a critical role in innate immunity, and the expression of early response genes orchestrate much of the initial response of the immune system. Macrophages undergo extensive transcriptional reprogramming in response to inflammatory stimuli such as Lipopolysaccharide (LPS.To identify gene transcription regulation patterns involved in early innate immune responses, we used two genome-wide approaches--gene expression profiling and chromatin immunoprecipitation-sequencing (ChIP-seq analysis. We examined the effect of 2 hrs LPS stimulation on early gene expression and its relation to chromatin remodeling (H3 acetylation; H3Ac and promoter binding of Sp1 and RNA polymerase II phosphorylated at serine 5 (S5P RNAPII, which is a marker for transcriptional initiation. Our results indicate novel and alternative gene regulatory mechanisms for certain proinflammatory genes. We identified two groups of up-regulated inflammatory genes with respect to chromatin modification and promoter features. One group, including highly up-regulated genes such as tumor necrosis factor (TNF, was characterized by H3Ac, high CpG content and lack of TATA boxes. The second group, containing inflammatory mediators (interleukins and CCL chemokines, was up-regulated upon LPS stimulation despite lacking H3Ac in their annotated promoters, which were low in CpG content but did contain TATA boxes. Genome-wide analysis showed that few H3Ac peaks were unique to either +/-LPS condition. However, within these, an unpacking/expansion of already existing H3Ac peaks was observed upon LPS stimulation. In contrast, a significant proportion of S5P RNAPII peaks (approx 40% was unique to either condition. Furthermore, data indicated a large portion of previously unannotated TSSs, particularly in LPS-stimulated macrophages, where only 28% of unique S5P RNAPII peaks overlap annotated promoters. The regulation of the inflammatory response appears to occur in a very specific manner at

  17. A conserved RNA structural element within the hepatitis B virus post-transcriptional regulatory element enhance nuclear export of intronless transcripts and repress the splicing mechanism.

    Science.gov (United States)

    Visootsat, Akasit; Payungporn, Sunchai; T-Thienprasert, Nattanan P

    2015-12-01

    Hepatitis B virus (HBV) infection is a primary cause of hepatocellular carcinoma and liver cirrhosis worldwide. To develop novel antiviral drugs, a better understanding of HBV gene expression regulation is vital. One important aspect is to understand how HBV hijacks the cellular machinery to export unspliced RNA from the nucleus. The HBV post-transcriptional regulatory element (HBV PRE) has been proposed to be the HBV RNA nuclear export element. However, the function remains controversial, and the core element is unclear. This study, therefore, aimed to identify functional regulatory elements within the HBV PRE and investigate their functions. Using bioinformatics programs based on sequence conservation and conserved RNA secondary structures, three regulatory elements were predicted, namely PRE 1151-1410, PRE 1520-1620 and PRE 1650-1684. PRE 1151-1410 significantly increased intronless and unspliced luciferase activity in both HepG2 and COS-7 cells. Likewise, PRE 1151-1410 significantly elevated intronless and unspliced HBV surface transcripts in liver cancer cells. Moreover, motif analysis predicted that PRE 1151-1410 contains several regulatory motifs. This study reported the roles of PRE 1151-1410 in intronless transcript nuclear export and the splicing mechanism. Additionally, these results provide knowledge in the field of HBV RNA regulation. Moreover, PRE 1151-1410 may be used to enhance the expression of other mRNAs in intronless reporter plasmids.

  18. Plasticity and innovation of regulatory mechanisms underlying seed oil content mediated by duplicated genes in the palaeopolyploid soybean.

    Science.gov (United States)

    Zhang, Dajian; Zhao, Meixia; Li, Shuai; Sun, Lianjun; Wang, Weidong; Cai, Chunmei; Dierking, Emily C; Ma, Jianxin

    2017-06-01

    Many plants have undergone whole genome duplication (WGD). However, how regulatory networks underlying a particular trait are reshaped in polyploids has not been experimentally investigated. Here we show that the regulatory pathways modulating seed oil content, which involve WRINKLED1 (WRI1), LEAFY COTYLEDON1 (LEC1), and LEC2 in Arabidopsis, have been modified in the palaeopolyploid soybean. Such modifications include functional reduction of GmWRI1b of the GmWRI1a/GmWRI1b homoeologous pair relevant to WRI1, complementary non-allelic dosage effects of the GmLEC1a/GmLEC1b homoeologous pair relevant to LEC1, pseudogenization of the singleton GmLEC2 relevant to LEC2, and the rise of the LEC2-like function of GmABI3b, contrasting to its homoeolog GmABI3a, which maintains the ABSCISIC ACID INSENSITIVE 3 (ABI3)-like function in modulating seed maturation and dormancy. The function of GmABI3b in modulating seed oil biosynthesis was fulfilled by direct binding to a RY (CATGCA) cis-regulatory element in the GmWRI1a promoter, which was absent in the GmWRI1b promoter, resulting in reduction of the GmWRI1b expression. Nevertheless, the three regulators each exhibited similar intensities of purifying selection to their respective duplicates since these pairs were formed by a WGD event that is proposed to have occurred approximately 13 million years ago (mya), suggesting that the differentiation in spatiotemporal expression between the duplicated genes is more likely to be the outcome of neutral variation in regulatory sequences. This study thus exemplifies the plasticity, dynamics, and novelty of regulatory networks mediated by WGD. © 2017 The Authors The Plant Journal © 2017 John Wiley & Sons Ltd.

  19. Heat shock protein 70 inhibits shrinkage-induced programmed cell death via mechanisms independent of effects on cell volume-regulatory membrane transport proteins

    DEFF Research Database (Denmark)

    Nylandsted, J; Jäättelä, M; Hoffmann, E K

    2004-01-01

    Cell shrinkage is a ubiquitous feature of programmed cell death (PCD), but whether it is an obligatory signalling event in PCD is unclear. Heat shock protein 70 (Hsp70) potently counteracts PCD in many cells, by mechanisms that are incompletely understood. In the present investigation, we found...... that severe hypertonic stress greatly diminished the viability of murine fibrosarcoma cells (WEHI-902) and immortalized murine embryonic fibroblasts (iMEFs). This effect was attenuated markedly by Hsp70 over-expression. To determine whether the protective effect of Hsp70 was mediated via an effect on volume...... regulatory ion transport, we compared regulatory volume decrease (RVD) and increase (RVI) in control WEHI-902 cells and after increasing Hsp70 levels by heat shock or over-expression (WEHI-912). Hsp70 levels affected neither RVD, RVI nor the relative contributions of the Na(+)/H(+)-exchanger (NHE1) and Na...

  20. α -Actinin TvACTN3 of Trichomonas vaginalis is an RNA-binding protein that could participate in its posttranscriptional iron regulatory mechanism.

    Science.gov (United States)

    Calla-Choque, Jaeson Santos; Figueroa-Angulo, Elisa Elvira; Ávila-González, Leticia; Arroyo, Rossana

    2014-01-01

    Trichomonas vaginalis is a sexually transmitted flagellated protist parasite responsible for trichomoniasis. This parasite is dependent on high levels of iron, favoring its growth and multiplication. Iron also differentially regulates some trichomonad virulence properties by unknown mechanisms. However, there is evidence to support the existence of gene regulatory mechanisms at the transcriptional and posttranscriptional levels that are mediated by iron concentration in T. vaginalis. Thus, the goal of this study was to identify an RNA-binding protein in T. vaginalis that interacts with the tvcp4 RNA stem-loop structure, which may participate in a posttranscriptional iron regulatory mechanism mediated by RNA-protein interactions. We performed RNA electrophoretic mobility shift assay (REMSA) and supershift, UV cross-linking, Northwestern blot, and western blot (WB) assays using cytoplasmic protein extracts from T. vaginalis with the tvcp4 RNA hairpin structure as a probe. We identified a 135-kDa protein isolated by the UV cross-linking assays as α-actinin 3 (TvACTN3) by MALDI-TOF-MS that was confirmed by LS-MS/MS and de novo sequencing. TvACTN3 is a cytoplasmic protein that specifically binds to hairpin RNA structures from trichomonads and humans when the parasites are grown under iron-depleted conditions. Thus, TvACTN3 could participate in the regulation of gene expression by iron in T. vaginalis through a parallel posttranscriptional mechanism similar to that of the IRE/IRP system.

  1. 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...

  2. A new regulatory mechanism controlling carotenogenesis in the fungus Mucor circinelloides as a target to generate β-carotene over-producing strains by genetic engineering.

    Science.gov (United States)

    Zhang, Yingtong; Navarro, Eusebio; Cánovas-Márquez, José T; Almagro, Lorena; Chen, Haiqin; Chen, Yong Q; Zhang, Hao; Torres-Martínez, Santiago; Chen, Wei; Garre, Victoriano

    2016-06-07

    previously unknown regulatory mechanism that represses carotenoid biosynthesis independently and in parallel to crgA. The use of a mucoral model such as M. circinelloides can allow the identification of the regulatory mechanisms that control carotenoid biosynthesis, which can then be manipulated to generate tailored strains of biotechnological interest. Mutants in the repressor crgA and in the newly identified regulatory mechanism generated in this work accumulate high levels of β-carotene and are candidates for further improvements in biotechnological β-carotene production.

  3. [Regulatory effect and mechanism of RNA binding motif protein 38 on the expression of progesterone receptor in human breast cancer ZR-75-1 cells].

    Science.gov (United States)

    Lou, P P; Li, C L; Xia, T S; Shi, L; Wu, J; Zhou, X J; Wang, Y; Ding, Q

    2016-06-23

    To investigate the regulatory mechanism of RNA binding motif protein 38 (RNPC1) on the expression of progesterone receptor (PR) in breast cancer cell line ZR-75-1. Lentiviral vector was used to induce overexpression of RNPC1 in ZR-75-1 cells. qRT-PCR and Western blot were used to assess the regulatory effect of RNPC1 on PR expression. Actinomycin was used to detect the regulatory mechanism involved. Immunohistochemical (IHC) staining was used to determine the protein expression of RNPC1 and PR in 80 breast cancer tissues. IHC staining showed that the expression of RNPC1 was significantly higher in the PR positive breast cancer tissues than that in the PR negative breast cancer tissues (P<0.05). The qRT-PCR results showed that overexpression of RNPC1 in ZR-75-1 cells significantly upregulated the mRNA level of PR (1.764±0.028 vs. 1.001±0.037, P<0.01), whereas knockdown of RNPC1 did the opposite (0.579± 0.007 vs. 1.000±0.002, P<0.01). The Western blot results also showed that overexpression of RNPC1 up-regulated PR levels, while knockdown of RNPC1 resulted in down-regulation of PR levels in the ZR-75-1 cells.The actinomycin assay showed that overexpression of RNPC1 increased the mRNA stability of PR. The half-life of PR mRNA was increased from 4.0 h to 6.5 h. Knockdown of RNPC1 decreased the mRNA stability of PR and the half-life of PR transcript was decreased from 4.1 h to 3.0 h. RNPC1 plays a crucial role in regulating the expression of PR in breast cancer ZR-75-1 cells.

  4. Detailed regulatory mechanism of the interaction between ZO-1 PDZ2 and connexin43 revealed by MD simulations.

    Directory of Open Access Journals (Sweden)

    Fei Xiao

    Full Text Available The gap junction protein connexin43 (Cx43 binds to the second PDZ domain of Zonula occludens-1 (ZO-1 through its C-terminal tail, mediating the regulation of gap junction plaque size and dynamics. Biochemical study demonstrated that the very C-terminal 12 residues of Cx43 are necessary and sufficient for ZO-1 PDZ2 binding and phosphorylation at residues Ser (-9 and Ser (-10 of the peptide can disrupt the association. However, only a crystal structure of ZO-1 PDZ2 in complex with a shorter 9 aa peptide of connexin43 was solved experimentally. Here, the interactions between ZO-1 PDZ2 and the short, long and phosphorylated Cx43 peptides were studied using molecular dynamics (MD simulations and free energy calculation. The short peptide bound to PDZ2 exhibits large structural variations, while the extension of three upstream residues stabilizes the peptide conformation and enhanced the interaction. Phosphorylation at Ser(-9 significantly weakens the binding and results in conformational flexibility of the peptide. Glu210 of ZO-1 PDZ2 was found to be a key regulatory point in Cx43 binding and phosphorylation induced dissociation.

  5. miRTrail - a comprehensive webserver for analyzing gene and miRNA patterns to enhance the understanding of regulatory mechanisms in diseases

    Directory of Open Access Journals (Sweden)

    Laczny Cedric

    2012-02-01

    Full Text Available Abstract Background Expression profiling provides new insights into regulatory and metabolic processes and in particular into pathogenic mechanisms associated with diseases. Besides genes, non-coding transcripts as microRNAs (miRNAs gained increasing relevance in the last decade. To understand the regulatory processes of miRNAs on genes, integrative computer-aided approaches are essential, especially in the light of complex human diseases as cancer. Results Here, we present miRTrail, an integrative tool that allows for performing comprehensive analyses of interactions of genes and miRNAs based on expression profiles. The integrated analysis of mRNA and miRNA data should generate more robust and reliable results on deregulated pathogenic processes and may also offer novel insights into the regulatory interactions between miRNAs and genes. Our web-server excels in carrying out gene sets analysis, analysis of miRNA sets as well as the combination of both in a systems biology approach. To this end, miRTrail integrates information on 20.000 genes, almost 1.000 miRNAs, and roughly 280.000 putative interactions, for Homo sapiens and accordingly for Mus musculus and Danio rerio. The well-established, classical Chi-squared test is one of the central techniques of our tool for the joint consideration of miRNAs and their targets. For interactively visualizing obtained results, it relies on the network analyzers and viewers BiNA or Cytoscape-web, also enabling direct access to relevant literature. We demonstrated the potential of miRTrail by applying our tool to mRNA and miRNA data of malignant melanoma. MiRTrail identified several deregulated miRNAs that target deregulated mRNAs including miRNAs hsa-miR-23b and hsa-miR-223, which target the highest numbers of deregulated mRNAs and regulate the pathway "basal cell carcinoma". In addition, both miRNAs target genes like PTCH1 and RASA1 that are involved in many oncogenic processes. Conclusions The application

  6. 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

  7. Mechanisms controlling mRNA processing and translation : decoding the regulatory layers defining gene expression through RNA sequencing

    NARCIS (Netherlands)

    Klerk, Eleonora de

    2015-01-01

    The work described in this thesis focuses on the mechanisms that give rise to alternative mRNAs and their alternative translation into proteins. Each of the described studies has been based on a specific set of high-throughput RNA sequencing technologies. An overview of the available RNA sequencing

  8. 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.

  9. Functional anatomy and ion regulatory mechanisms of the antennal gland in a semi-terrestrial crab, Ocypode stimpsoni

    Directory of Open Access Journals (Sweden)

    Jyuan-Ru Tsai

    2014-05-01

    Full Text Available Brachyuran crabs from diverse habitats show great differences in their osmoregulatory processes, especially in terms of the structural and physiological characteristics of the osmoregulatory organs. In crustaceans, the antennal glands are known to be important in osmoregulation, and they play a functional role analogous to that of the vertebrate kidney. Nevertheless, the detailed structure and function of the antennal glands in different species have rarely been described. The aim of this study is to investigate the role of the antennal gland in ion regulation by examining the ultrastructure of the cells and the distribution of the ion regulatory proteins in each cell type in the antennal gland of a semi-terrestrial crab. The results showed that Na+, K+-ATPase activity significantly increased in the antennal gland after a 4-day acclimation in dilute seawater and returned to its original (day 0 level after 7 days. Three major types of cells were identified in the antennal gland, including coelomic cells (COEs, labyrinthine cells (LBRs and end-labyrinthine cells (ELBRs. The proximal tubular region (PT and distal tubular region (DT of the antennal gland consist of LBRs and COEs, whereas the end tubular region (ET consists of all three types of cells, with fewer COEs and more ELBRs. We found a non-uniform distribution of NKA immunoreactivity, with increasing intensity from the proximal to the distal regions of the antennal gland. We summarise our study with a proposed model for the urine reprocessing pathway and the role of each cell type or segment of the antennal gland.

  10. An RNA editing/dsRNA binding-independent gene regulatory mechanism of ADARs and its clinical implication in cancer.

    Science.gov (United States)

    Qi, Lihua; Song, Yangyang; Chan, Tim Hon Man; Yang, Henry; Lin, Chi Ho; Tay, Daryl Jin Tai; Hong, HuiQi; Tang, Sze Jing; Tan, Kar Tong; Huang, Xi Xiao; Lin, Jaymie Siqi; Ng, Vanessa Hui En; Maury, Julien Jean Pierre; Tenen, Daniel G; Chen, Leilei

    2017-10-13

    Adenosine-to-inosine (A-to-I) RNA editing, catalyzed by Adenosine DeAminases acting on double-stranded RNA(dsRNA) (ADAR), occurs predominantly in the 3' untranslated regions (3'UTRs) of spliced mRNA. Here we uncover an unanticipated link between ADARs (ADAR1 and ADAR2) and the expression of target genes undergoing extensive 3'UTR editing. Using METTL7A (Methyltransferase Like 7A), a novel tumor suppressor gene with multiple editing sites at its 3'UTR, we demonstrate that its expression could be repressed by ADARs beyond their RNA editing and double-stranded RNA (dsRNA) binding functions. ADARs interact with Dicer to augment the processing of pre-miR-27a to mature miR-27a. Consequently, mature miR-27a targets the METTL7A 3'UTR to repress its expression level. In sum, our study unveils that the extensive 3'UTR editing of METTL7A is merely a footprint of ADAR binding, and there are a subset of target genes that are equivalently regulated by ADAR1 and ADAR2 through their non-canonical RNA editing and dsRNA binding-independent functions, albeit maybe less common. The functional significance of ADARs is much more diverse than previously appreciated and this gene regulatory function of ADARs is most likely to be of high biological importance beyond the best-studied editing function. This non-editing side of ADARs opens another door to target cancer. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  11. Potential of acute phase proteins as predictor of postpartum uterine infections during transition period and its regulatory mechanism in dairy cattle

    Directory of Open Access Journals (Sweden)

    A. Manimaran

    2016-01-01

    Full Text Available Among the various systemic reactions against infection or injury, the acute phase response is the cascade of reaction and mostly coordinated by cytokines-mediated acute phase proteins (APPs production. Since APPs are sensitive innate immune molecules, they are useful for early detection of inflammation in bovines and believed to be better discriminators than routine hematological parameters. Therefore, the possibility of using APPs as a diagnostic and prognostic marker of inflammation in major bovine health disorders including postpartum uterine infection has been explored by many workers. In this review, we discussed specifically importance of postpartum uterine infection, the role of energy balance in uterine infections and potential of APPs as a predictor of postpartum uterine infections during the transition period and its regulatory mechanism in dairy cattle.

  12. Bacillus subtilis as a Platform for Molecular Characterisation of Regulatory Mechanisms of Enterococcus faecalis Resistance against Cell Wall Antibiotics

    OpenAIRE

    Fang, Chong; Stiegeler, Emanuel; Cook, Gregory M.; Mascher, Thorsten; Gebhard, Susanne

    2014-01-01

    To combat antibiotic resistance of Enterococcus faecalis, a better understanding of the molecular mechanisms, particularly of antibiotic detection, signal transduction and gene regulation is needed. Because molecular studies in this bacterium can be challenging, we aimed at exploiting the genetically highly tractable Gram-positive model organism Bacillus subtilis as a heterologous host. Two fundamentally different regulators of E. faecalis resistance against cell wall antibiotics, the bacitra...

  13. The rate of hypo-osmotic challenge influences regulatory volume decrease (RVD) and mechanical properties of articular chondrocytes.

    Science.gov (United States)

    Wang, Z; Irianto, J; Kazun, S; Wang, W; Knight, M M

    2015-02-01

    Osteoarthritis (OA) is associated with a gradual reduction in the interstitial osmotic pressure within articular cartilage. The aim of this study was to compare the effects of sudden and gradual hypo-osmotic challenge on chondrocyte morphology and biomechanics. Bovine articular chondrocytes were exposed to a reduction in extracellular osmolality from 327 to 153 mOsmol/kg applied either suddenly (osmotic stress, 66% of chondrocytes exhibited an increase in diameter followed by RVD, whilst 25% showed no RVD. By contrast, cells exposed to gradual hypo-osmotic stress exhibited reduced cell swelling without subsequent RVD. There was an increase in the equilibrium modulus for cells exposed to sudden hypo-osmotic stress. However, gradual hypo-osmotic challenge had no effect on cell mechanical properties. This cell stiffening response to sudden hypo-osmotic challenge was abolished when actin organization was disrupted with cytochalasin D or RVD inhibited with REV5901. Both sudden and gradual hypo-osmotic challenge reduced cortical F-actin distribution and caused chromatin decondensation. Sudden hypo-osmotic challenge increases chondrocyte mechanics by activation of RVD and interaction with the actin cytoskeleton. Moreover, the rate of hypo-osmotic challenge is shown to have a profound effect on chondrocyte morphology and biomechanics. This important phenomenon needs to be considered when studying the response of chondrocytes to pathological hypo-osmotic stress. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  14. Study of the main regulatory mechanisms to encourage renewable and alternative energy applied internationally and in Brazil; Estudo dos principais mecanismos regulatorios de incentivo as fontes renovaveis e alternativas de energia aplicados internacionalmente e no Brasil

    Energy Technology Data Exchange (ETDEWEB)

    Martins, Juliana M.C.; Cavaliero, Carla Kazue Nakao [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Fac. de Engenharia Mecanica. Dept. de Energia], Emails: jumcm@fem.unicamp.br, cavaliero@fem.unicamp.br

    2009-07-01

    The investment in renewable and alternative energy sources has been stimulated by some countries in Europe and Americas through the introduction of encouragement regulatory mechanisms. This paper considers the most important international mechanisms such as Feed-in System, Tender System and Quota System with green certificates. In Brazil, there are three regulatory mechanisms in course: PROINFA, the 1. Tender of Renewable and 1. Tender Reserve. The carried out preliminary analysis made possible to classify PROINFA as a mechanism similar to Feed-in, while the auction of Renewable and Reserve are more like an auction system. This article points out the differences and similarities between the instruments and gives a preliminary analysis of their effectiveness, emphasizing national mechanisms, especially regarding the criteria for capacity increase and cost reduction of the technological bands, such as for biomass and small hydroelectric. (author)

  15. Regulatory Mechanisms of a Highly Pectinolytic Mutant of Penicillium occitanis and Functional Analysis of a Candidate Gene in the Plant Pathogen Fusarium oxysporum

    Directory of Open Access Journals (Sweden)

    Gustavo Bravo-Ruiz

    2017-09-01

    Full Text Available Penicillium occitanis is a model system for enzymatic regulation. A mutant strain exhibiting constitutive overproduction of different pectinolytic enzymes both under inducing (pectin or repressing conditions (glucose was previously isolated after chemical mutagenesis. In order to identify the molecular basis of this regulatory mechanism, the genomes of the wild type and the derived mutant strain were sequenced and compared, providing the first reference genome for this species. We used a phylogenomic approach to compare P. occitanis with other pectinolytic fungi and to trace expansions of gene families involved in carbohydrate degradation. Genome comparison between wild type and mutant identified seven mutations associated with predicted proteins. The most likely candidate was a mutation in a highly conserved serine residue of a conserved fungal protein containing a GAL4-like Zn2Cys6 binuclear cluster DNA-binding domain and a fungus-specific transcription factor regulatory middle homology region. To functionally characterize the role of this candidate gene, the mutation was recapitulated in the predicted orthologue Fusarium oxysporum, a vascular wilt pathogen which secretes a wide array of plant cell wall degrading enzymes, including polygalacturonases, pectate lyases, xylanases and proteases, all of which contribute to infection. However, neither the null mutant nor a mutant carrying the analogous point mutation exhibited a deregulation of pectinolytic enzymes. The availability, annotation and phylogenomic analysis of the P. occitanis genome sequence represents an important resource for understanding the evolution and biology of this species, and sets the basis for the discovery of new genes of biotechnological interest for the degradation of complex polysaccharides.

  16. The RNA-mediated, asymmetric ring regulatory mechanism of the transcription termination Rho helicase decrypted by time-resolved nucleotide analog interference probing (trNAIP).

    Science.gov (United States)

    Soares, Emilie; Schwartz, Annie; Nollmann, Marcello; Margeat, Emmanuel; Boudvillain, Marc

    2014-08-01

    Rho is a ring-shaped, ATP-dependent RNA helicase/translocase that dissociates transcriptional complexes in bacteria. How RNA recognition is coupled to ATP hydrolysis and translocation in Rho is unclear. Here, we develop and use a new combinatorial approach, called time-resolved Nucleotide Analog Interference Probing (trNAIP), to unmask RNA molecular determinants of catalytic Rho function. We identify a regulatory step in the translocation cycle involving recruitment of the 2'-hydroxyl group of the incoming 3'-RNA nucleotide by a Rho subunit. We propose that this step arises from the intrinsic weakness of one of the subunit interfaces caused by asymmetric, split-ring arrangement of primary RNA tethers around the Rho hexamer. Translocation is at highest stake every seventh nucleotide when the weak interface engages the incoming 3'-RNA nucleotide or breaks, depending on RNA threading constraints in the Rho pore. This substrate-governed, 'test to run' iterative mechanism offers a new perspective on how a ring-translocase may function or be regulated. It also illustrates the interest and versatility of the new trNAIP methodology to unveil the molecular mechanisms of complex RNA-based systems. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  17. See the forest for the trees: Whole-plant allocation patterns and regulatory mechanisms in Norway spruce

    Science.gov (United States)

    Huang, Jianbei; Behrendt, Thomas; Hammerbacher, Almuth; Weinhold, Alexander; Hellén, Heidi; Reichelt, Michael; Wisthaler, Armin; Dam, Nicole; Trumbore, Susan; Hartmann, Henrik

    2017-04-01

    acetone) decreased whereas monoterpene and sesquiterpene emissions slightly increased with decreasing [CO2]. Our experimental design provides an excellent platform for studying control mechanisms of C allocation. The range of C availabilities applied in our study will allow partitioning compensatory mechanisms (e.g., up-regulation of C storage due to sugar signalling at high C availability) from evolutionary programming (e.g., storage formation to increase long-term survival at expense of other functions with decreasing C availability). Such partitioning is corroborated via phytohormone and transcriptome analysis, and results will hopefully be available at the time of presentation.

  18. Acupuncture Alleviates Colorectal Hypersensitivity and Correlates with the Regulatory Mechanism of TrpV1 and p-ERK

    Directory of Open Access Journals (Sweden)

    Shao-Jun Wang

    2012-01-01

    Full Text Available Here we used a mouse model of zymosan-induced colorectal hypersensitivity, a similar model of IBS in our previous work, to evaluate the effectiveness of the different number of times of acupuncture and elucidate its potential mechanism of EA treatment. Colorectal distension (CRD tests show that intracolonic zymosan injection does, while saline injection does not, induce a typical colorectal hypersensitivity. EA treatment at classical acupoints Zusanli (ST36 and Shangjuxu (ST37 in both hind limbs for 15 min slightly attenuated and significantly blunted the hypersensitive responses after first and fifth acupunctures, respectively, to colorectal distention in zymosan treatment mice, but not in saline treatment mice. Western blot results indicated that ion channel and TrpV1 expression in colorectum as well as ERK1/2 MAPK pathway activation in peripheral and central nerve system might be involved in this process. Hence, we conclude that EA is a potential therapeutic tool in the treatment and alleviation of chronic abdominal pain, and the effectiveness of acupuncture analgesia is accumulative with increased number of times of acupuncture when compared to that of a single time of acupuncture.

  19. Lycopene treatment against loss of bone mass, microarchitecture and strength in relation to regulatory mechanisms in a postmenopausal osteoporosis model.

    Science.gov (United States)

    Ardawi, Mohammed-Salleh M; Badawoud, Mohammed H; Hassan, Sherif M; Rouzi, Abdulrahim A; Ardawi, Jumanah M S; AlNosani, Nouf M; Qari, Mohammed H; Mousa, Shaker A

    2016-02-01

    Lycopene supplementation decreases oxidative stress and exhibits beneficial effects on bone health, but the mechanisms through which it alters bone metabolism in vivo remain unclear. The present study aims to evaluate the effects of lycopene treatment on postmenopausal osteoporosis. Six-month-old female Wistar rats (n=264) were sham-operated (SHAM) or ovariectomized (OVX). The SHAM group received oral vehicle only and the OVX rats were randomized into five groups receiving oral daily lycopene treatment (mg/kg body weight per day): 0 OVX (control), 15 OVX, 30 OVX, and 45 OVX, and one group receiving alendronate (ALN) (2μg/kg body weight per day), for 12weeks. Bone densitometry measurements, bone turnover markers, biomechanical testing, and histomorphometric analysis were conducted. Micro computed tomography was also used to evaluate changes in microarchitecture. Lycopene treatment suppressed the OVX-induced increase in bone turnover, as indicated by changes in biomarkers of bone metabolism: serum osteocalcin (s-OC), serum N-terminal propeptide of type 1 collagen (s-PINP), serum crosslinked carboxyterminal telopeptides (s-CTX-1), and urinary deoxypyridinoline (u-DPD). Significant improvement in OVX-induced loss of bone mass, bone strength, and microarchitectural deterioration was observed in lycopene-treated OVX animals. These effects were observed mainly at sites rich in trabecular bone, with less effect in cortical bone. Lycopene treatment down-regulated osteoclast differentiation concurrent with up-regulating osteoblast together with glutathione peroxidase (GPx) catalase (CAT) and superoxide dismutase (SOD) activities. These findings demonstrate that lycopene treatment in OVX rats primarily suppressed bone turnover to restore bone strength and microarchitecture. Copyright © 2015. Published by Elsevier Inc.

  20. Integrative modeling of eQTLs and cis-regulatory elements suggests mechanisms underlying cell type specificity of eQTLs.

    Directory of Open Access Journals (Sweden)

    Christopher D Brown

    Full Text Available Genetic variants in cis-regulatory elements or trans-acting regulators frequently influence the quantity and spatiotemporal distribution of gene transcription. Recent interest in expression quantitative trait locus (eQTL mapping has paralleled the adoption of genome-wide association studies (GWAS for the analysis of complex traits and disease in humans. Under the hypothesis that many GWAS associations tag non-coding SNPs with small effects, and that these SNPs exert phenotypic control by modifying gene expression, it has become common to interpret GWAS associations using eQTL data. To fully exploit the mechanistic interpretability of eQTL-GWAS comparisons, an improved understanding of the genetic architecture and causal mechanisms of cell type specificity of eQTLs is required. We address this need by performing an eQTL analysis in three parts: first we identified eQTLs from eleven studies on seven cell types; then we integrated eQTL data with cis-regulatory element (CRE data from the ENCODE project; finally we built a set of classifiers to predict the cell type specificity of eQTLs. The cell type specificity of eQTLs is associated with eQTL SNP overlap with hundreds of cell type specific CRE classes, including enhancer, promoter, and repressive chromatin marks, regions of open chromatin, and many classes of DNA binding proteins. These associations provide insight into the molecular mechanisms generating the cell type specificity of eQTLs and the mode of regulation of corresponding eQTLs. Using a random forest classifier with cell specific CRE-SNP overlap as features, we demonstrate the feasibility of predicting the cell type specificity of eQTLs. We then demonstrate that CREs from a trait-associated cell type can be used to annotate GWAS associations in the absence of eQTL data for that cell type. We anticipate that such integrative, predictive modeling of cell specificity will improve our ability to understand the mechanistic basis of human

  1. A genome-wide analysis of the RNA-guided silencing pathway in coffee reveals insights into its regulatory mechanisms.

    Directory of Open Access Journals (Sweden)

    Christiane Noronha Fernandes-Brum

    Full Text Available microRNAs (miRNAs are derived from self-complementary hairpin structures, while small-interfering RNAs (siRNAs are derived from double-stranded RNA (dsRNA or hairpin precursors. The core mechanism of sRNA production involves DICER-like (DCL in processing the smallRNAs (sRNAs and ARGONAUTE (AGO as effectors of silencing, and siRNA biogenesis also involves action of RNA-Dependent RNA Polymerase (RDR, Pol IV and Pol V in biogenesis. Several other proteins interact with the core proteins to guide sRNA biogenesis, action, and turnover. We aimed to unravel the components and functions of the RNA-guided silencing pathway in a non-model plant species of worldwide economic relevance. The sRNA-guided silencing complex members have been identified in the Coffea canephora genome, and they have been characterized at the structural, functional, and evolutionary levels by computational analyses. Eleven AGO proteins, nine DCL proteins (which include a DCL1-like protein that was not previously annotated, and eight RDR proteins were identified. Another 48 proteins implicated in smallRNA (sRNA pathways were also identified. Furthermore, we identified 235 miRNA precursors and 317 mature miRNAs from 113 MIR families, and we characterized ccp-MIR156, ccp-MIR172, and ccp-MIR390. Target prediction and gene ontology analyses of 2239 putative targets showed that significant pathways in coffee are targeted by miRNAs. We provide evidence of the expansion of the loci related to sRNA pathways, insights into the activities of these proteins by domain and catalytic site analyses, and gene expression analysis. The number of MIR loci and their targeted pathways highlight the importance of miRNAs in coffee. We identified several roles of sRNAs in C. canephora, which offers substantial insight into better understanding the transcriptional and post-transcriptional regulation of this major crop.

  2. 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...

  3. 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.

  4. 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.

  5. Analysis of tomato plasma membrane H(+)-ATPase gene family suggests a mycorrhiza-mediated regulatory mechanism conserved in diverse plant species.

    Science.gov (United States)

    Liu, Junli; Liu, Jianjian; Chen, Aiqun; Ji, Minjie; Chen, Jiadong; Yang, Xiaofeng; Gu, Mian; Qu, Hongye; Xu, Guohua

    2016-10-01

    In plants, the plasma membrane H(+)-ATPase (HA) is considered to play a crucial role in regulating plant growth and respoding to environment stresses. Multiple paralogous genes encoding different isozymes of HA have been identified and characterized in several model plants, while limited information of the HA gene family is available to date for tomato. Here, we describe the molecular and expression features of eight HA-encoding genes (SlHA1-8) from tomato. All these genes are interrupted by multiple introns with conserved positions. SlHA1, 2, and 4 were widely expressed in all tissues, while SlHA5, 6, and 7 were almost only expressed in flowers. SlHA8, the transcripts of which were barely detectable under normal or nutrient-/salt-stress growth conditions, was strongly activated in arbuscular mycorrhizal (AM) fungal-colonized roots. Extreme lack of SlHA8 expression in M161, a mutant defective to AM fungal colonization, provided genetic evidence towards the dependence of its expression on AM symbiosis. A 1521-bp SlHA8 promoter could direct the GUS reporter expression specifically in colonized cells of transgenic tobacco, soybean, and rice mycorrhizal roots. Promoter deletion assay revealed a 223-bp promoter fragment of SlHA8 containing a variant of AM-specific cis-element MYCS (vMYCS) sufficient to confer the AM-induced activity. Targeted deletion of this motif in the corresponding promoter region causes complete abolishment of GUS staining in mycorrhizal roots. Together, these results lend cogent evidence towards the evolutionary conservation of a potential regulatory mechanism mediating the activation of AM-responsive HA genes in diverse mycorrhizal plant species.

  6. Study on the regulatory mechanism of the lipid metabolism pathways during chicken male germ cell differentiation based on RNA-seq.

    Science.gov (United States)

    Zuo, Qisheng; Li, Dong; Zhang, Lei; Elsayed, Ahmed Kamel; Lian, Chao; Shi, Qingqing; Zhang, Zhentao; Zhu, Rui; Wang, Yinjie; Jin, Kai; Zhang, Yani; Li, Bichun

    2015-01-01

    Here, we explore the regulatory mechanism of lipid metabolic signaling pathways and related genes during differentiation of male germ cells in chickens, with the hope that better understanding of these pathways may improve in vitro induction. Fluorescence-activated cell sorting was used to obtain highly purified cultures of embryonic stem cells (ESCs), primitive germ cells (PGCs), and spermatogonial stem cells (SSCs). The total RNA was then extracted from each type of cell. High-throughput analysis methods (RNA-seq) were used to sequence the transcriptome of these cells. Gene Ontology (GO) analysis and the KEGG database were used to identify lipid metabolism pathways and related genes. Retinoic acid (RA), the end-product of the retinol metabolism pathway, induced in vitro differentiation of ESC into male germ cells. Quantitative real-time PCR (qRT-PCR) was used to detect changes in the expression of the genes involved in the retinol metabolic pathways. From the results of RNA-seq and the database analyses, we concluded that there are 328 genes in 27 lipid metabolic pathways continuously involved in lipid metabolism during the differentiation of ESC into SSC in vivo, including retinol metabolism. Alcohol dehydrogenase 5 (ADH5) and aldehyde dehydrogenase 1 family member A1 (ALDH1A1) are involved in RA synthesis in the cell. ADH5 was specifically expressed in PGC in our experiments and aldehyde dehydrogenase 1 family member A1 (ALDH1A1) persistently increased throughout development. CYP26b1, a member of the cytochrome P450 superfamily, is involved in the degradation of RA. Expression of CYP26b1, in contrast, decreased throughout development. Exogenous RA in the culture medium induced differentiation of ESC to SSC-like cells. The expression patterns of ADH5, ALDH1A1, and CYP26b1 were consistent with RNA-seq results. We conclude that the retinol metabolism pathway plays an important role in the process of chicken male germ cell differentiation.

  7. [On improvement of the mechanism for establishing and changing indicators of quality and food safety in the regulatory and legal acts of the Eurasian Economical Union].

    Science.gov (United States)

    Arnautov, O V

    2016-01-01

    In accordance with the Treaty on the Eurasian Economic Union (EAEU) to ensure the sanitary and epidemiological welfare of the population within the Union, a coordinated policy in agreed policy in the sphere of application of sanitary measures is carried out. Sanitary measures are the obligatory requirements and procedures, including requirements for the final product, processing methods, production, transportation, storage and disposal, sampling procedures, methods of research (tests), risk assessment, the state registration, requirements for packaging directly aimed at ensuring the safety of products (goods) in order to protect human welfare, and they should be applied on the basis having a scientific explanation, and only to the extent that is necessary to protect human welfare. Sanitary measures applied within the Union should be based on international and regional standards, guidelines and (or) the recommendations, except when they based on appropriate scientific studies and explanations. In this case sanitary measures which could provide a higher level of sanitary protection are introduced. At present, the mechanism of the development, justification and approval of common sanitary and epidemiological requirements (ESR) and procedures of the Eurasian Economic Commission (the Commission) is not installed. The absence of a clear mechanism for the development, approval and implementation of the ESR to the products (goods) on the basis having a scientific explanation on the one hand could lead to the creation of unjustified barriers to foreign and mutual trade, on the other--to weaken the level of safety for human life and health of products (goods) placed on markets of the Union. In order to bring the regulatory legal acts of the Customs Union in accordance with the Treaty on the Eurasian Economic Union the Commission in cooperation with the competent authorities of the Member States in the field of sanitary and epidemiological welfare developed the project of

  8. 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

  9. 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....

  10. 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....

  11. Allergic contact dermatitis: epidemiology, molecular mechanisms, in vitro methods and regulatory aspects : Current knowledge assembled at an international workshop at BfR, Germany

    DEFF Research Database (Denmark)

    Peiser, M; Tralau, T; Heidler, J

    2012-01-01

    potential contact allergens. However, the local lymph node assay (LLNA) presently remains the validated method of choice for hazard identification and characterisation. At the workshop the use of the LLNA for regulatory purposes and for quantitative risk assessment was also discussed....

  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. Mechanics

    CERN Document Server

    Hartog, J P Den

    1961-01-01

    First published over 40 years ago, this work has achieved the status of a classic among introductory texts on mechanics. Den Hartog is known for his lively, discursive and often witty presentations of all the fundamental material of both statics and dynamics (and considerable more advanced material) in new, original ways that provide students with insights into mechanical relationships that other books do not always succeed in conveying. On the other hand, the work is so replete with engineering applications and actual design problems that it is as valuable as a reference to the practicing e

  14. 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.

  15. 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...

  16. 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...

  17. How short RNAs impact the human ribonuclease Dicer activity: putative regulatory feedback-loops and other RNA-mediated mechanisms controlling microRNA processing.

    Science.gov (United States)

    Koralewska, Natalia; Hoffmann, Weronika; Pokornowska, Maria; Milewski, Marek; Lipinska, Andrea; Bienkowska-Szewczyk, Krystyna; Figlerowicz, Marek; Kurzynska-Kokorniak, Anna

    2016-01-01

    Ribonuclease Dicer plays a pivotal role in RNA interference pathways by processing long double-stranded RNAs and single-stranded hairpin RNA precursors into small interfering RNAs (siRNAs) and microRNAs (miRNAs), respectively. While details of Dicer regulation by a variety of proteins are being elucidated, less is known about non-protein factors, e.g. RNA molecules, that may influence this enzyme's activity. Therefore, we decided to investigate the question of whether the RNA molecules can function not only as Dicer substrates but also as its regulators. Our previous in vitro studies indicated that the activity of human Dicer can be influenced by short RNA molecules that either bind to Dicer or interact with its substrates, or both. Those studies were carried out with commercial Dicer preparations. Nevertheless, such preparations are usually not homogeneous enough to carry out more detailed RNA-binding studies. Therefore, we have established our own system for the production of human Dicer in insect cells. In this manuscript, we characterize the RNA-binding and RNA-cleavage properties of the obtained preparation. We demonstrate that Dicer can efficiently bind single-stranded RNAs that are longer than ~20-nucleotides. Consequently, we revisit possible scenarios of Dicer regulation by single-stranded RNA species ranging from ~10- to ~60-nucleotides, in the context of their binding to this enzyme. Finally, we show that siRNA/miRNA-sized RNAs may affect miRNA production either by binding to Dicer or by participating in regulatory feedback-loops. Altogether, our studies suggest a broad regulatory role of short RNAs in Dicer functioning.

  18. 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

  19. T- and NK-cell populations with regulatory phenotype and markers of apoptosis in circulating lymphocytes of patients with CIN3 or microcarcinoma of the cervix: evidence for potential mechanisms of immune suppression.

    Science.gov (United States)

    Kurmyshkina, Olga V; Kovchur, Pavel I; Schegoleva, Ludmila V; Volkova, Tatyana O

    2017-01-01

    Processes and mechanisms responsible for systemic immune suppression in early-stage cervical cancer remain substantially underinvestigated. In this work, we focused on studying the frequencies of circulating regulatory T (CD4 and CD8 Tregs) and NK (NKregs) cells in parallel with assessment of apoptotic markers expression in T cells from patients with preinvasive and microinvasive cervical cancer, with the aim to determine whether up-regulation of apoptosis-associated markers in Т lymphocytes accompanies cervical cancer development and correlates with the change in percentages of regulatory cell populations at systemic level during the initial stages of invasive cervical cancer progression. Fourty two women with histologically confirmed cervical intraepithelial neoplasia grade 3 (CIN3, including carcinoma in situ) or cervical cancer (stage IA) and 30 healthy women (control) were enrolled in the study. Peripheral blood samples were taken immediately before surgery or any treatment and immediately subjected to multicolor flow cytometry. Analysis of a combination of CD4/CD8, CD25, CD127, and FoxP3 markers revealed a statistically significant increase in the frequencies of Tregs within both the CD4 and CD8 subsets of circulating lymphocytes in patients with CIN3 and stage IA cancer. In contrast, lower numbers of NKregs (defined as CD16 dim/neg CD56 bright subpopulation) and increased CD56 dim /CD56 bright NK ratio were found in patients compared to controls, with the percentage of CD16 bright CD56 dim cells (major subtype of circulating NKs) showing no difference. Patients also exhibited an increased expression of CD95 in total peripheral blood T lymphocytes, along with increased level of Annexin V binding to CD95-positive cells, suggesting higher susceptibility of T cells to apoptosis and potential involvement of CD95-dependent pathway in early-stage cervical cancer. Differential analysis of CD4 and CD8 T cells revealed different trends in the change of CD95

  20. Cognitive and Self-regulatory Mechanisms of Obesity Study (COSMOS): Study protocol for a randomized controlled weight loss trial examining change in biomarkers, cognition, and self-regulation across two behavioral treatments.

    Science.gov (United States)

    Hawkins, M A W; Colaizzi, Janna; Gunstad, John; Hughes, Joel W; Mullins, Larry L; Betts, Nancy; Smith, Caitlin E; Keirns, Natalie G; Vohs, Kathleen D; Moore, Shirley M; Forman, Evan M; Lovallo, William R

    2018-03-01

    Obesity is a global epidemic, yet successful interventions are rare. Up to 60% of people fail to achieve clinically meaningful, short-term weight loss (5-10% of start weight), whereas up to 72% are unsuccessful at achieving long-term weight loss (5-10% loss for ≥5years). Understanding how biological, cognitive, and self-regulatory factors work together to promote or to impede weight loss is clearly needed to optimize obesity treatment. This paper describes the methodology of the Cognitive and Self-regulatory Mechanisms of Obesity Study (the COSMOS trial). COSMOS is the first randomized controlled trial to investigate how changes in multiple biopsychosocial and cognitive factors relate to weight loss and one another across two weight loss treatments. The specific aims are to: 1) Confirm that baseline obesity-related physiological dysregulation is linked to cognitive deficits and poorer self-regulation, 2) Evaluate pre- to post-treatment change across time to assess individual differences in biomarkers, cognition, and self-regulation, and 3) Evaluate whether the acceptance-based treatment (ABT) group has greater improvements in outcomes (e.g., greater weight loss and less weight regain, improvements in biomarkers, cognition, and self-regulation), than the standard behavioral treatment group (SBT) from pre- to post-treatment and 1-year follow-up. The results of COSMOS will provide critical information about how dysregulation in biomarkers, cognition, and/or self-regulation is related to weight loss and whether weight loss treatments are differentially associated with these factors. This information will be used to identify promising treatment targets that are informed by biological, cognitive, and self-regulatory factors in order to advance obesity treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. 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

  2. Mechanics

    CERN Document Server

    Chester, W

    1979-01-01

    When I began to write this book, I originally had in mind the needs of university students in their first year. May aim was to keep the mathematics simple. No advanced techniques are used and there are no complicated applications. The emphasis is on an understanding of the basic ideas and problems which require expertise but do not contribute to this understanding are not discussed. How­ ever, the presentation is more sophisticated than might be considered appropri­ ate for someone with no previous knowledge of the subject so that, although it is developed from the beginning, some previous acquaintance with the elements of the subject would be an advantage. In addition, some familiarity with element­ ary calculus is assumed but not with the elementary theory of differential equations, although knowledge of the latter would again be an advantage. It is my opinion that mechanics is best introduced through the motion of a particle, with rigid body problems left until the subject is more fully developed. Howev...

  3. 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)

  4. Inferring the Impact of Regulatory Mechanisms that Underpin CD8+ T Cell Control of B16 Tumor Growth In vivo Using Mechanistic Models and Simulation.

    Science.gov (United States)

    Klinke, David J; Wang, Qing

    2016-01-01

    A major barrier for broadening the efficacy of immunotherapies for cancer is identifying key mechanisms that limit the efficacy of tumor infiltrating lymphocytes. Yet, identifying these mechanisms using human samples and mouse models for cancer remains a challenge. While interactions between cancer and the immune system are dynamic and non-linear, identifying the relative roles that biological components play in regulating anti-tumor immunity commonly relies on human intuition alone, which can be limited by cognitive biases. To assist natural intuition, modeling and simulation play an emerging role in identifying therapeutic mechanisms. To illustrate the approach, we developed a multi-scale mechanistic model to describe the control of tumor growth by a primary response of CD8+ T cells against defined tumor antigens using the B16 C57Bl/6 mouse model for malignant melanoma. The mechanistic model was calibrated to data obtained following adenovirus-based immunization and validated to data obtained following adoptive transfer of transgenic CD8+ T cells. More importantly, we use simulation to test whether the postulated network topology, that is the modeled biological components and their associated interactions, is sufficient to capture the observed anti-tumor immune response. Given the available data, the simulation results also provided a statistical basis for quantifying the relative importance of different mechanisms that underpin CD8+ T cell control of B16F10 growth. By identifying conditions where the postulated network topology is incomplete, we illustrate how this approach can be used as part of an iterative design-build-test cycle to expand the predictive power of the model.

  5. Potential Nociceptive Regulatory Effect of Probiotic Lactobacillus rhamnosus PB01 (DSM 14870 on Mechanical Sensitivity in Diet-Induced Obesity Model

    Directory of Open Access Journals (Sweden)

    Fereshteh Dardmeh

    2016-01-01

    Full Text Available Treatments for obesity have been shown to reduce pain secondary to weight loss. Intestinal microbiota, as an endogenous factor, influences obesity and pain sensitivity but the effect of oral probiotic supplementation on musculoskeletal pain perception has not been studied systematically. The present study examined the effect of a single daily oral dose (1 × 109 CFU of probiotics (Lactobacillus rhamnosus PB01, DSM14870 supplement on mechanical pain thresholds in behaving diet-induced obese (DIO mice and their normal weight (NW controls. The mice (N=24, 6-week-old male were randomly divided into four groups on either standard or high fat diet with and without probiotic supplementation. Both DIO and NW groups with probiotic supplementation maintained an insignificant weight gain while the control groups gained significant weight (P<0.05. Similarly, both DIO and NW probiotics supplemented groups demonstrated a significantly (P<0.05 lower sensitivity to mechanical stimulation compared to their corresponding control. The results of this study suggest a protective effect of probiotics on nociception circuits, which propose a direct result of the weight reduction or an indirect result of anti-inflammatory properties of the probiotics. Deciphering the exact underlying mechanism of the weight loss and lowering nociception effect of the probiotic applied in this study require further investigation.

  6. Visions of regulatory renewal

    International Nuclear Information System (INIS)

    Edgeworth, A.

    1998-01-01

    The economic contribution of the CEPA (Canadian Energy Pipeline Association) member companies to Canada's trade balance was discussed. CEPA member companies transport 95 per cent of the crude oil and natural gas produced in Canada to domestic and export markets. This represents a total of 5.6 Tcf of gas annually. Half of Canada's natural gas and oil production is exported to U.S. markets. All of these exports are transported by pipeline. CEPA member companies operate 90,000 km of pipeline from British Columbia to Quebec. Expansions are needed as a result of a significant increase in demand for natural gas and crude oil since 1990. Several issues exist for regulatory renewal. They include the need to create a level playing field, the overseeing of tolls and contract renewal terms, changing risk/reward trade-offs, the right to confidentiality of information and price discovery mechanism. The drivers for regulatory reform at Westcoast Energy are the need for pricing flexibility, customers desire for toll certainty, decontracting and opposition to rolled-in expansions for gathering and processing. An overview of Westcoast Energy's negotiated toll settlement, its implications, and the components of Westcoast Energy's 'light handed regulation' (LHR) was presented

  7. Pentocin MQ1: A Novel, Broad-Spectrum, Pore-Forming Bacteriocin From Lactobacillus pentosus CS2 With Quorum Sensing Regulatory Mechanism and Biopreservative Potential

    Directory of Open Access Journals (Sweden)

    Samson B. Wayah

    2018-03-01

    Full Text Available Micrococcus luteus, Listeria monocytogenes, and Bacillus cereus are major food-borne pathogenic and spoilage bacteria. Emergence of antibiotic resistance and consumer demand for foods containing less of chemical preservatives led to a search for natural antimicrobials. A study aimed at characterizing, investigating the mechanism of action and regulation of biosynthesis and evaluating the biopreservative potential of pentocin from Lactobacillus pentosus CS2 was conducted. Pentocin MQ1 is a novel bacteriocin isolated from L. pentosus CS2 of coconut shake origin. The purification strategy involved adsorption-desorption of bacteriocin followed by RP-HPLC. It has a molecular weight of 2110.672 Da as determined by MALDI-TOF mass spectrometry and a molar extinction value of 298.82 M−1 cm−1. Pentocin MQ1 is not plasmid-borne and its biosynthesis is regulated by a quorum sensing mechanism. It has a broad spectrum of antibacterial activity, exhibited high chemical, thermal and pH stability but proved sensitive to proteolytic enzymes. It is potent against M. luteus, B. cereus, and L. monocytogenes at micromolar concentrations. It is quick-acting and exhibited a bactericidal mode of action against its targets. Target killing was mediated by pore formation. We report for the first time membrane permeabilization as a mechanism of action of the pentocin from the study against Gram-positive bacteria. Pentocin MQ1 is a cell wall-associated bacteriocin. Application of pentocin MQ1 improved the microbiological quality and extended the shelf life of fresh banana. This is the first report on the biopreservation of banana using bacteriocin. These findings place pentocin MQ1 as a potential biopreservative for further evaluation in food and medical applications.

  8. RNA-Seq transcriptomics and pathway analyses reveal potential regulatory genes and molecular mechanisms in high- and low-residual feed intake in Nordic dairy cattle

    DEFF Research Database (Denmark)

    Salleh, M. S.; Mazzoni, G.; Höglund, J. K.

    2017-01-01

    -throughput RNA sequencing data of liver biopsies from 19 dairy cows were used to identify differentially expressed genes (DEGs) between high- and low-FE groups of cows (based on Residual Feed Intake or RFI). Subsequently, a profile of the pathways connecting the DEGs to FE was generated, and a list of candidate...... genes and biomarkers was derived for their potential inclusion in breeding programmes to improve FE. The bovine RNA-Seq gene expression data from the liver was analysed to identify DEGs and, subsequently, identify the molecular mechanisms, pathways and possible candidate biomarkers of feed efficiency....... On average, 57 million reads (short reads or short mRNA sequences ...

  9. Underlying mechanism of regulatory actions of diclofenac, a nonsteroidal anti-inflammatory agent, on neuronal potassium channels and firing: an experimental and theoretical study.

    Science.gov (United States)

    Huang, C W; Hung, T Y; Liao, Y K; Hsu, M C; Wu, S N

    2013-06-01

    Diclofenac (DIC), a nonsteroidal anti-inflammatory drug, is known to exert anti-nociceptive and anti-convulsant actions; however, its effects on ion currents, in neurons remain debatable. We aimed to investigate (1) potential effects of diclofenac on membrane potential and potassium currents in differentiated NSC-34 neuronal cells and dorsal root ganglion (DRG) neurons with whole-cell patch-clamp technology, and (2) firing of action potentials (APs), using a simulation model from hippocampal CA1 pyramidal neurons based on diclofenac's effects on potassium currents. In the NSC-34 cells, diclofenac exerted an inhibitory effect on delayed-rectifier K⁺ current (I(KDR)) with an IC₅₀ value of 73 μM. Diclofenac not merely inhibited the I(KDR) amplitude in response to membrane depolarization, but also accelerated the process of current inactivation. The inhibition by diclofenac of IK(DR) was not reversed by subsequent application of either naloxone. Importantly, diclofenac (300 μM) increased the amplitude of M-type K⁺ current (I)(KM)), while flupirtine (10 μM) or meclofenamic acid (10 μM) enhanced it effectively. Consistently, diclofenac (100 μM) increased the amplitude of I(KM) and diminished the I(KDR) amplitude, with a shortening of inactivation time constant in DRG neurons. Furthermore, by using the simulation modeling, we demonstrated the potential electrophysiological mechanisms underlying changes in AP firing caused by diclofenac. During the exposure to diclofenac, the actions on both I(KM) and I(KDR) could be potential mechanism through which it influences the excitability of fast-spiking neurons. Caution needs to be made in attributing the effects of diclofenac primarily to those produced by the activation of I(KM).

  10. Human muscle cells express a B7-related molecule, B7-H1, with strong negative immune regulatory potential: a novel mechanism of counterbalancing the immune attack in idiopathic inflammatory myopathies.

    Science.gov (United States)

    Wiendl, Heinz; Mitsdoerffer, Meike; Schneider, Dagmar; Chen, Lieping; Lochmüller, Hanns; Melms, Arthur; Weller, Michael

    2003-10-01

    B7-H1 is a novel B7 family protein attributed to costimulatory and immune regulatory functions. Here we report that human myoblasts cultured from control subjects and patients with inflammatory myopathies as well as TE671 muscle rhabdomyosarcoma cells express high levels of B7-H1 after stimulation with the inflammatory cytokine IFN-gamma. Coculture experiments of MHC class I/II-positive myoblasts with CD4 and CD8 T cells in the presence of antigen demonstrated the functional consequences of muscle-related B7-H1 expression: production of inflammatory cytokines, IFN-gamma and IL-2, by CD4 as well CD8 T cells was markedly enhanced in the presence of a neutralizing anti-B7-H1 antibody. This observation was paralleled by an augmented expression of the T cell activation markers CD25, ICOS, and CD69, thus showing B7-H1-mediated inhibition of T cell activation. Further, we investigated 23 muscle biopsy specimens from patients with polymyositis (PM), inclusion body myositis (IBM), dermatomyositis (DM), and nonmyopathic controls for B7-H1 expression by immunohistochemistry: B7-H1 was expressed in PM, IBM, and DM specimens but not in noninflammatory and nonmyopathic controls. Staining was predominantly localized to areas of strong inflammation and to muscle cells as well as mononuclear cells. These data highlight the immune regulatory properties of muscle cells and suggest that B7-H1 expression represents an inhibitory mechanism induced upon inflammatory stimuli and aimed at protecting muscle fibers from immune aggression.

  11. 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.

  12. DsrA regulatory RNA represses both hns and rbsD mRNAs through distinct mechanisms in Escherichia coli.

    Science.gov (United States)

    Lalaouna, David; Morissette, Audrey; Carrier, Marie-Claude; Massé, Eric

    2015-10-01

    The 87 nucleotide long DsrA sRNA has been mostly studied for its translational activation of the transcriptional regulator RpoS. However, it also represses hns mRNA, which encodes H-NS, a major regulator that affects expression of nearly 5% of Escherichia coli genes. A speculative model previously suggested that DsrA would block hns mRNA translation by binding simultaneously to start and stop codon regions of hns mRNA (coaxial model). Here, we show that DsrA efficiently blocked translation of hns mRNA by base-pairing immediately downstream of the start codon. In addition, DsrA induced hns mRNA degradation by actively recruiting the RNA degradosome complex. Data presented here led to a model of DsrA action on hns mRNA, which supports a canonical mechanism of sRNA-induced mRNA degradation by binding to the translation initiation region. Furthermore, using MS2-affinity purification coupled with RNA sequencing technology (MAPS), we also demonstrated that DsrA targets rbsD mRNA, involved in ribose utilization. Surprisingly, DsrA base pairs far downstream of rbsD start codon and induces rapid degradation of the transcript. Thus, our study enables us to draw an extended DsrA targetome. © 2015 John Wiley & Sons Ltd.

  13. 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)

  14. Thymic B cell development is controlled by the B potential of progenitors via both hematopoietic-intrinsic and thymic microenvironment-intrinsic regulatory mechanisms.

    Directory of Open Access Journals (Sweden)

    Shiyun Xiao

    Full Text Available Hematopoietic stem cells (HSCs derived from birth through adult possess differing differentiation potential for T or B cell fate in the thymus; neonatal bone marrow (BM cells also have a higher potential for B cell production in BM compared to adult HSCs. We hypothesized that this hematopoietic-intrinsic B potential might also regulate B cell development in the thymus during ontogeny.Foxn1lacZ mutant mice are a model in which down regulation of a thymic epithelial cell (TEC specific transcription factor beginning one week postnatal causes a dramatic reduction of thymocytes production. In this study, we found that while T cells were decreased, the frequency of thymic B cells was greatly increased in these mutants in the perinatal period. We used this model to characterize the mechanisms in the thymus controlling B cell development.Foxn1lacZ mutants, T cell committed intrathymic progenitors (DN1a,b were progressively reduced beginning one week after birth, while thymic B cells peaked at 3-4 weeks with pre-B-II progenitor phenotype, and originated in the thymus. Heterochronic chimeras showed that the capacity for thymic B cell production was due to a combination of higher B potential of neonatal HSCs, combined with a thymic microenvironment deficiency including reduction of DL4 and increase of IL-7 that promoted B cell fate.Our findings indicate that the capacity and time course for thymic B-cell production are primarily controlled by the hematopoietic-intrinsic potential for B cells themselves during ontogeny, but that signals from TECs microenvironment also influence the frequency and differentiation potential of B cell development in the thymus.

  15. Multiple regulatory mechanisms of hepatocyte growth factor expression in malignant cells with a short poly(dA) sequence in the HGF gene promoter.

    Science.gov (United States)

    Sakai, Kazuko; Takeda, Masayuki; Okamoto, Isamu; Nakagawa, Kazuhiko; Nishio, Kazuto

    2015-01-01

    Hepatocyte growth factor (HGF) expression is a poor prognostic factor in various types of cancer. Expression levels of HGF have been reported to be regulated by shorter poly(dA) sequences in the promoter region. In the present study, the poly(dA) mononucleotide tract in various types of human cancer cell lines was examined and compared with the HGF expression levels in those cells. Short deoxyadenosine repeat sequences were detected in five of the 55 cell lines used in the present study. The H69, IM95, CCK-81, Sui73 and H28 cells exhibited a truncated poly(dA) sequence in which the number of poly(dA) repeats was reduced by ≥5 bp. Two of the cell lines exhibited high HGF expression, determined by reverse transcription quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. The CCK-81, Sui73 and H28 cells with shorter poly(dA) sequences exhibited low HGF expression. The cause of the suppression of HGF expression in the CCK-81, Sui73 and H28 cells was clarified by two approaches, suppression by methylation and single nucleotide polymorphisms in the HGF gene. Exposure to 5-Aza-dC, an inhibitor of DNA methyltransferase 1, induced an increased expression of HGF in the CCK-81 cells, but not in the other cells. Single-nucleotide polymorphism (SNP) rs72525097 in intron 1 was detected in the Sui73 and H28 cells. Taken together, it was found that the defect of poly(dA) in the HGF promoter was present in various types of cancer, including lung, stomach, colorectal, pancreas and mesothelioma. The present study proposes the negative regulation mechanisms by methylation and SNP in intron 1 of HGF for HGF expression in cancer cells with short poly(dA).

  16. A Novel Regulatory Mechanism of Smooth Muscle α-Actin Expression by NRG-1/circACTA2/miR-548f-5p Axis.

    Science.gov (United States)

    Sun, Yan; Yang, Zhan; Zheng, Bin; Zhang, Xin-Hua; Zhang, Man-Li; Zhao, Xue-Shan; Zhao, Hong-Ye; Suzuki, Toru; Wen, Jin-Kun

    2017-09-01

    Neuregulin-1 (NRG-1) includes an extracellular epidermal growth factor-like domain and an intracellular domain (NRG-1-ICD). In response to transforming growth factor-β1, its cleavage by proteolytic enzymes releases a bioactive fragment, which suppresses the vascular smooth muscle cell (VSMC) proliferation by activating ErbB (erythroblastic leukemia viral oncogene homolog) receptor. However, NRG-1-ICD function in VSMCs remains unknown. Here, we characterize the function of NRG-1-ICD and underlying mechanisms in VSMCs. Immunofluorescence staining, Western blotting, and quantitative real-time polymerase chain reaction showed that NRG-1 was expressed in rat, mouse, and human VSMCs and was upregulated and cleaved in response to transforming growth factor-β1. In the cytoplasm of HASMCs (human aortic smooth muscle cells), the NRG-1-ICD participated in filamentous actin formation by interacting with α-SMA (smooth muscle α-actin). In the nucleus, the Nrg-1-ICD induced circular ACTA2 (alpha-actin-2; circACTA2) formation by recruitment of the zinc-finger transcription factor IKZF1 (IKAROS family zinc finger 1) to the first intron of α-SMA gene. We further confirmed that circACTA2, acting as a sponge binding microRNA (miR)-548f-5p, interacted with miR-548f-5p targeting 3' untranslated region of α-SMA mRNA, which in turn relieves miR-548f-5p repression of the α-SMA expression and thus upregulates α-SMA expression, thereby facilitating stress fiber formation and cell contraction in HASMCs. Accordingly, in vivo studies demonstrated that the localization of the interaction of circACTA2 with miR-548f-5p is significantly decreased in human intimal hyperplastic arteries compared with normal arteries, implicating that dysregulation of circACTA2 and miR-548f-5p expression is involved in intimal hyperplasia. These results suggest that circACTA2 mediates NRG-1-ICD regulation of α-SMA expression in HASMCs via the NRG-1-ICD/circACTA2/miR-548f-5p axis. Our data provide a molecular

  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. Croatian energy regulatory council - independent Croatian regulatory body

    International Nuclear Information System (INIS)

    Klepo, M.

    2002-01-01

    By means of approving five energy laws, the Republic of Croatia established an appropriate legislative framework for energy sector regulation. A series of sub-law acts is presently being elaborated as well as some additional documents in order to bring about transparent and non-discriminatory provisions for the establishment of electric energy, gas, oil/oil derivatives and thermal energy markets, i.e. for the introduction and management of market activities and public services. A considerable share of these activities relates to the definition of transparent regulatory mechanisms that would guarantee the implementation of regulation rules based on the law, and be carried out by the independent regulatory body - Croatian Energy Regulatory Council. The Council's rights and obligations include firm executive functions, which present obligations to every energy entity. A dissatisfied party may set in motion a settlement of dispute, if it maintains that the decisions are not based on the law or reveal a flaw in the procedure. Therefore, it is the Council's priority to always make careful and law-abiding decisions. This paper gives insight into the regulatory framework elements based on the laws including the Council's organisational structure and non-profit entities that will prepare act proposals for the Council and perform other professional activities. (author)

  19. 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)

  20. Cost-benefit and regulatory decision making

    International Nuclear Information System (INIS)

    Harvie, J.

    1996-01-01

    The Atomic Energy Control Board is investigating the feasibility of developing methods for factoring cost-benefit considerations into its regulatory decision-making. This initiative results, in part, from the federal government policy requiring cost-benefit considerations to be taken into account in regulatory processes, and from the recommendations of an Advisory Panel on Regulatory Review in 1993, submitted to the Minister of Natural Resources Canada. One of these recommendations stated: 'that mechanisms be developed to examine cost benefit issues and work towards some consensus of opinion among stake holders: a task force on the subject could be an appropriate starting point'. (author)

  1. A Regulatory RNA Inducing Transgenerationally Inherited Phenotypes

    DEFF Research Database (Denmark)

    Jensen, Lea Møller

    . The variation in Arabidopsis enables different regulatory networks and mechanisms to shape the phenotypic characteristics. The thesis describes the identification of regulatory RNA encoded by an enzyme encoding gene. The RNA regulates by inducing transgenerationally inherited phenotypes. The function of the RNA...... is dependent on the genetic background illustrating that polymorphisms are found in either interactors or target genes of the RNA. Furthermore, the RNA provides a mechanistic link between accumulation of glucosinolate and onset of flowering....

  2. Evolution of Regulatory Mechanisms in Bacteria

    National Research Council Canada - National Science Library

    Ornston, L

    2003-01-01

    ... and transcriptional activators associated with catabolic pathways. We now have extended this capability to genes from other organisms, in this case Pseudomonas putida, by creating a docking site that allows PCR-amplified P...

  3. Self-Regulatory Mechanisms Governing Gender Development.

    Science.gov (United States)

    Bussey, Kay; Bandura, Albert

    1992-01-01

    Groups of younger and older children in a sample of two to five year olds were assessed for gender knowledge, gender standards, and gender-linked behavior. All children exhibited more same- than cross-sex typed behavior. Older children expressed self-approval for same-sex behavior and self-criticism for cross-sex behavior. (BC)

  4. Gene regulatory networks elucidating huanglongbing disease mechanisms.

    Directory of Open Access Journals (Sweden)

    Federico Martinelli

    Full Text Available Next-generation sequencing was exploited to gain deeper insight into the response to infection by Candidatus liberibacter asiaticus (CaLas, especially the immune disregulation and metabolic dysfunction caused by source-sink disruption. Previous fruit transcriptome data were compared with additional RNA-Seq data in three tissues: immature fruit, and young and mature leaves. Four categories of orchard trees were studied: symptomatic, asymptomatic, apparently healthy, and healthy. Principal component analysis found distinct expression patterns between immature and mature fruits and leaf samples for all four categories of trees. A predicted protein - protein interaction network identified HLB-regulated genes for sugar transporters playing key roles in the overall plant responses. Gene set and pathway enrichment analyses highlight the role of sucrose and starch metabolism in disease symptom development in all tissues. HLB-regulated genes (glucose-phosphate-transporter, invertase, starch-related genes would likely determine the source-sink relationship disruption. In infected leaves, transcriptomic changes were observed for light reactions genes (downregulation, sucrose metabolism (upregulation, and starch biosynthesis (upregulation. In parallel, symptomatic fruits over-expressed genes involved in photosynthesis, sucrose and raffinose metabolism, and downregulated starch biosynthesis. We visualized gene networks between tissues inducing a source-sink shift. CaLas alters the hormone crosstalk, resulting in weak and ineffective tissue-specific plant immune responses necessary for bacterial clearance. Accordingly, expression of WRKYs (including WRKY70 was higher in fruits than in leaves. Systemic acquired responses were inadequately activated in young leaves, generally considered the sites where most new infections occur.

  5. A study of bacterial gene regulatory mechanisms

    DEFF Research Database (Denmark)

    Hansen, Sabine

    Bacterial cells are capable of rapidly changing their protein expression in response to ever-changing environments and physiological conditions. The cells are able to switch on the expression of proteins that due to changing environmental conditions have become vital to sustain life and likewise ...

  6. Epigenetic regulatory mechanisms associated with infertility

    DEFF Research Database (Denmark)

    Minocherhomji, Sheroy; Madon, Prochi F; Parikh, Firuza R

    2010-01-01

    with higher order organisation of chromatin in genes associated with infertility and pericentromeric regions of chromosomes, particularly 9 and Y, could further identify causes of idiopathic infertility. Determining the association between DNA methylation, chromatin state, and noncoding RNAs...

  7. 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)

  8. 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

  9. 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

  10. Structure-based network analysis of activation mechanisms in the ErbB family of receptor tyrosine kinases: the regulatory spine residues are global mediators of structural stability and allosteric interactions.

    Directory of Open Access Journals (Sweden)

    Kevin A James

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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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)

  19. Influence of simulated microgravity on clock genes expression rhythmicity and underlying blood circulating miRNAs-mRNA co-expression regulatory mechanism in C57BL/6J mice

    Science.gov (United States)

    Lv, Ke; Qu, Lina

    Purpose: It is vital for astronauts to maintain the optimal alertness and neurobehavioral function. Among various factors that exist in the space flight and long-duration mission environment, gravity changes may probably an essential environmental factor to interfere with internal circadian rhythms homeostasis and sleep quality, but the underlying mechanism is unclear. Mammals' biological clock is controlled by the suprachiasmatic nucleus (SCN), and peripheral organs adjust their own rhythmicity with the central signals. Nevertheless the mechanism underlying this synchronizition process is still unknown. microRNAs (miRNAs) are about 19˜22nt long regulatory RNAs that serve as critical modulators of post-transcriptional gene regulation. Recently, circulating miRNAs were found to have the regulatory role between cells and peripheral tissues, besides its function inside the cells. This study aims to investigate the regulatory signal transduction role of miRNAs between SCN and peripheral biological clock effecter tissues and to further decipher the mechanism of circadian disturbance under microgravity. Method: Firstly, based on the assumption that severe alterations in the expression of genes known to be involved in circadian rhythms may affect the expression of other genes, the labeled cDNA from liver and suprachiasmatic nucleus (SCN) of clock-knockout mice and control mice in different time points were cohybridized to microarrays. The fold change exceeding 2 (FC>2) was used to identify genes with altered expression levels in the knockout mice compared with control mice. Secondly, male C57BL/6J mice at 8 weeks of age were individually caged and acclimatized to the laboratory conditions (12h light/dark cycle) before being used for continuous core body temperature and activity monitoring. The mice were individually caged and tail suspended using a strip of adhesive surgical tape attached to a chain hanging from a pulley. Peripheral blood and liver tissues collection

  20. 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

  1. 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

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

    Directory of Open Access Journals (Sweden)

    Jinki Kim

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

  3. 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

  4. 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

  5. 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

  6. Computational challenges in modeling gene regulatory events.

    Science.gov (United States)

    Pataskar, Abhijeet; Tiwari, Vijay K

    2016-10-19

    Cellular transcriptional programs driven by genetic and epigenetic mechanisms could be better understood by integrating "omics" data and subsequently modeling the gene-regulatory events. Toward this end, computational biology should keep pace with evolving experimental procedures and data availability. This article gives an exemplified account of the current computational challenges in molecular biology.

  7. 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)

  8. 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)

  9. Modular arrangement of regulatory RNA elements.

    Science.gov (United States)

    Roßmanith, Johanna; Narberhaus, Franz

    2017-03-04

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

  10. 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

  11. 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

  12. 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.

  13. 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)

  14. 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.

  15. CFD analyses in regulatory practice

    International Nuclear Information System (INIS)

    Bloemeling, F.; Pandazis, P.; Schaffrath, A.

    2012-01-01

    Numerical software is used in nuclear regulatory procedures for many problems in the fields of neutron physics, structural mechanics, thermal hydraulics etc. Among other things, the software is employed in dimensioning and designing systems and components and in simulating transients and accidents. In nuclear technology, analyses of this kind must meet strict requirements. Computational Fluid Dynamics (CFD) codes were developed for computing multidimensional flow processes of the type occurring in reactor cooling systems or in containments. Extensive experience has been accumulated by now in selected single-phase flow phenomena. At the present time, there is a need for development and validation with respect to the simulation of multi-phase and multi-component flows. As insufficient input by the user can lead to faulty results, the validity of the results and an assessment of uncertainties are guaranteed only through consistent application of so-called Best Practice Guidelines. The authors present the possibilities now available to CFD analyses in nuclear regulatory practice. This includes a discussion of the fundamental requirements to be met by numerical software, especially the demands upon computational analysis made by nuclear rules and regulations. In conclusion, 2 examples are presented of applications of CFD analysis to nuclear problems: Determining deboration in the condenser reflux mode of operation, and protection of the reactor pressure vessel (RPV) against brittle failure. (orig.)

  16. Regulatory focus affects physician risk tolerance.

    Science.gov (United States)

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

    2014-01-01

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

  17. 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

  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. Quantitative inference of dynamic regulatory pathways via microarray data

    Directory of Open Access Journals (Sweden)

    Chen Bor-Sen

    2005-03-01

    Full Text Available Abstract Background The cellular signaling pathway (network is one of the main topics of organismic investigations. The intracellular interactions between genes in a signaling pathway are considered as the foundation of functional genomics. Thus, what genes and how much they influence each other through transcriptional binding or physical interactions are essential problems. Under the synchronous measures of gene expression via a microarray chip, an amount of dynamic information is embedded and remains to be discovered. Using a systematically dynamic modeling approach, we explore the causal relationship among genes in cellular signaling pathways from the system biology approach. Results In this study, a second-order dynamic model is developed to describe the regulatory mechanism of a target gene from the upstream causality point of view. From the expression profile and dynamic model of a target gene, we can estimate its upstream regulatory function. According to this upstream regulatory function, we would deduce the upstream regulatory genes with their regulatory abilities and activation delays, and then link up a regulatory pathway. Iteratively, these regulatory genes are considered as target genes to trace back their upstream regulatory genes. Then we could construct the regulatory pathway (or network to the genome wide. In short, we can infer the genetic regulatory pathways from gene-expression profiles quantitatively, which can confirm some doubted paths or seek some unknown paths in a regulatory pathway (network. Finally, the proposed approach is validated by randomly reshuffling the time order of microarray data. Conclusion We focus our algorithm on the inference of regulatory abilities of the identified causal genes, and how much delay before they regulate the downstream genes. With this information, a regulatory pathway would be built up using microarray data. In the present study, two signaling pathways, i.e. circadian regulatory

  6. 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

  7. 75 FR 54921 - Withdrawal of Regulatory Guides 1.38, 1.94, and 1.116

    Science.gov (United States)

    2010-09-09

    ... Guide 1.38, ``Quality Assurance Requirements for Packaging, Shipping, Receiving, Storage, and Handling....116, ``Quality Assurance Requirements for Installation, Inspection, and Testing of Mechanical... Development Branch, Division of Engineering, Office of Nuclear Regulatory Research, U.S. Nuclear Regulatory...

  8. 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

  9. 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

  10. 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)

  11. 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.

  12. Radiation and the regulatory landscape of neo2-Darwinism

    International Nuclear Information System (INIS)

    Rollo, C. David

    2006-01-01

    Several recently revealed features of eukaryotic genomes were not predicted by earlier evolutionary paradigms, including the relatively small number of genes, the very large amounts of non-functional code and its quarantine in heterochromatin, the remarkable conservation of many functionally important genes across relatively enormous phylogenetic distances, and the prevalence of extra-genomic information associated with chromatin structure and histone proteins. All of these emphasize a paramount role for regulatory evolution, which is further reinforced by recent perspectives highlighting even higher-order regulation governing epigenetics and development (EVO-DEVO). Modern neo 2 -Darwinism, with its emphasis on regulatory mechanisms and regulatory evolution provides new vision for understanding radiation biology, particularly because free radicals and redox states are central to many regulatory mechanisms and free radicals generated by radiation mimic and amplify endogenous signalling. This paper explores some of these aspects and their implications for low-dose radiation biology

  13. Radiation and the regulatory landscape of neo2-Darwinism.

    Science.gov (United States)

    Rollo, C David

    2006-05-11

    Several recently revealed features of eukaryotic genomes were not predicted by earlier evolutionary paradigms, including the relatively small number of genes, the very large amounts of non-functional code and its quarantine in heterochromatin, the remarkable conservation of many functionally important genes across relatively enormous phylogenetic distances, and the prevalence of extra-genomic information associated with chromatin structure and histone proteins. All of these emphasize a paramount role for regulatory evolution, which is further reinforced by recent perspectives highlighting even higher-order regulation governing epigenetics and development (EVO-DEVO). Modern neo2-Darwinism, with its emphasis on regulatory mechanisms and regulatory evolution provides new vision for understanding radiation biology, particularly because free radicals and redox states are central to many regulatory mechanisms and free radicals generated by radiation mimic and amplify endogenous signalling. This paper explores some of these aspects and their implications for low-dose radiation biology.

  14. 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.

  15. Regulatory T Cells: Potential Target in Anticancer Immunotherapy

    Directory of Open Access Journals (Sweden)

    Chi-Mou Juang

    2007-09-01

    Full Text Available The concept of regulatory T cells was first described in the early 1970s, and regulatory T cells were called suppressive T cells at that time. Studies that followed have demonstrated that these suppressive T cells negatively regulated tumor immunity and contributed to tumor growth in mice. Despite the importance of these studies, there was extensive skepticism about the existence of these cells, and the concept of suppressive T cells left the center stage of immunologic research for decades. Interleukin-2 receptor α-chain, CD25, was first demonstrated in 1995 to serve as a phenotypic marker for CD4+ regulatory cells. Henceforth, research of regulatory T cells boomed. Regulatory T cells are involved in the pathogenesis of cancer, autoimmune disease, transplantation immunology, and immune tolerance in pregnancy. Recent evidence has demonstrated that regulatory T cellmediated immunosuppression is one of the crucial tumor immune evasion mechanisms and the main obstacle of successful cancer immunotherapy. The mechanism and the potential clinical application of regulatory T cells in cancer immunotherapy are discussed.

  16. Cost-benefit considerations in regulatory decision-making

    International Nuclear Information System (INIS)

    Harvie, J.D.

    1996-01-01

    The Atomic Energy Control Board is investigating the feasibility of developing methods for factoring cost-benefit considerations into its regulatory decision-making. This initiative results, in part, from the federal government policy requiring cost-benefit considerations to be taken into account in regulatory processes, and from the recommendations of an Advisory Panel on Regulatory Review in 1993, submitted to the Minister of Natural Resources Canada. One of these recommendations stated: 'that mechanisms be developed to examine cost-benefit issues and work towards some consensus of opinion among stakeholders; a task force on the subject could be an appropriate starting point'. (author)

  17. 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...

  18. 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.)

  19. 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.)

  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

  1. Politically Induced Regulatory Risk and Independent Regulatory Agencies

    OpenAIRE

    Strausz, Roland

    2015-01-01

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

  2. 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...

  3. Assessment of regulatory effectiveness. Peer discussions on regulatory practices

    International Nuclear Information System (INIS)

    1999-09-01

    This report arises from the seventh series of peer discussions on regulatory practices entitled 'Assessment of Regulatory Effectiveness'. The term 'regulatory effectiveness' covers the quality of the work and level of performance of a regulatory body. In this sense, regulatory effectiveness applies to regulatory body activities aimed at preventing safety degradation and ensuring that an acceptable level of safety is being maintained by the regulated operating organizations. In addition, regulatory effectiveness encompasses the promotion of safety improvements, the timely and cost effective performance of regulatory functions in a manner which ensures the confidence of the operating organizations, the general public and the government, and striving for continuous improvements to performance. Senior regulators from 22 Member States participated in two peer group discussions during March and May 1999. The discussions were focused on the elements of an effective regulatory body, possible indicators of regulatory effectiveness and its assessment. This report presents the outcome of these meetings and recommendations of good practices identified by senior regulators, which do not necessarily reflect those of the governments of the nominating Member States, the organizations they belong to, or the International Atomic Energy Agency. In order to protect people and the environment from hazards associated with nuclear facilities, the main objective of a nuclear regulatory body is to ensure that a high level of safety in the nuclear activities under its jurisdiction is achieved, maintained and within the control of operating organizations. Even if it is possible to directly judge objective safety levels at nuclear facilities, such safety levels would not provide an exclusive indicator of regulatory effectiveness. The way the regulatory body ensures the safety of workers and the public and the way it discharges its responsibilities also determine its effectiveness. Hence the

  4. 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

  5. Regulatory inspection of BARC facilities

    International Nuclear Information System (INIS)

    Rajdeep; Jayarajan, K.

    2017-01-01

    Nuclear and radiation facilities are sited, constructed, commissioned, operated and decommissioned, in conformity with the current safety standards and codes. Regulatory bodies follow different means to ensure compliance of the standards for the safety of the personnel, the public and the environment. Regulatory Inspection (RI) is one of the important measures employed by regulatory bodies to obtain the safety status of a facility or project and to verify the fulfilment of the conditions stipulated in the consent

  6. 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.

  7. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2012-01-01

    This section gathers the following national legislative and regulatory activities sorted by country: Bulgaria: General legislation; Czech Republic: General legislation; France: General legislation, Regulatory infrastructure and activity; Germany: General legislation; India: Liability and compensation, Organisation and structure; Ireland: Radiation protection, General legislation; Korea (Republic of): Organisation and structure; Lithuania: Regulatory infrastructure and activity, Radioactive waste management, Radiation protection, international cooperation, Nuclear safety; Poland: General legislation; Romania: Environmental protection; Russian Federation: Radioactive waste management; Slovenia: Nuclear safety; Spain: Liability and compensation, Nuclear security; Sweden: Nuclear safety; Turkey: Radiation protection, Regulatory infrastructure and activity, Nuclear safety, Liability and compensation; United States: General legislation

  8. Conjugated Bilirubin Differentially Regulates CD4+ T Effector Cells and T Regulatory Cell Function through Outside-In and Inside-Out Mechanisms: The Effects of HAV Cell Surface Receptor and Intracellular Signaling

    Science.gov (United States)

    Corral-Jara, Karla F.; Gómez-Leyva, Juan F.; Rosenstein, Yvonne; Jose-Abrego, Alexis; Roman, Sonia

    2016-01-01

    We recently reported an immune-modulatory role of conjugated bilirubin (CB) in hepatitis A virus (HAV) infection. During this infection the immune response relies on CD4+ T lymphocytes (TLs) and it may be affected by the interaction of HAV with its cellular receptor (HAVCR1/TIM-1) on T cell surface. How CB might affect T cell function during HAV infection remains to be elucidated. Herein, in vitro stimulation of CD4+ TLs from healthy donors with CB resulted in a decrease in the degree of intracellular tyrosine phosphorylation and an increase in the activity of T regulatory cells (Tregs) expressing HAVCR1/TIM-1. A comparison between CD4+ TLs from healthy donors and HAV-infected patients revealed changes in the TCR signaling pathway relative to changes in CB levels. The proportion of CD4+CD25+ TLs increased in patients with low CB serum levels and an increase in the percentage of Tregs expressing HAVCR1/TIM-1 was found in HAV-infected patients relative to controls. A low frequency of 157insMTTTVP insertion in the viral receptor gene HAVCR1/TIM-1 was found in patients and controls. Our data revealed that, during HAV infection, CB differentially regulates CD4+ TLs and Tregs functions by modulating intracellular pathways and by inducing changes in the proportion of Tregs expressing HAVCR1/TIM-1. PMID:27578921

  9. Regulatory actions post - Fukushima

    International Nuclear Information System (INIS)

    Ciurea Ercau, C.

    2013-01-01

    The paper presents the results of the safety reviews performed in Romania after the Fukushima accident and the resulting actions for improving the safety. The actions taken by the National Commission for Nuclear Activities Control (CNCAN) to improve the regulatory framework include the development of new regulations and the enhancement of inspection practices, taking account of the lessons learned from the Fukushima accident. A regulation on the response to transients, accidents and emergency situations at nuclear power plants has been developed, which includes requirements on transient and accident scenarios that have to be covered by the Emergency Operating Procedures (EOPs), accident scenarios to be covered by the Severe Accident Management Guidelines (SAMGs), emergency situations to be covered by the on-site emergency response plan and emergency response procedures. (authors)

  10. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2010-01-01

    Concerning International regulatory activities, we find for the european atomic energy community an entry into force of the lisbon treaty (2009), it amends the treaty on European union and replaces the treaty establishing the European Community by the new treaty on the functioning of the European Union; more, an amendment to council regulation on the conditions governing imports of agricultural products originating in third countries following the accident at the Chernobyl nuclear power station (2009). About International atomic energy agency is reported an open-ended meeting of technical and legal experts for sharing of information on states implementation of the code of conduct on the safety and security of radioactive sources and its supplementary guidance on the import and export of radioactive sources (2010). (N.C.)

  11. Regulatory mark; Marco regulatorio

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2009-10-15

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

  12. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2003-01-01

    Among international regulatory activities we find resolutions adopted by the IAEA general conference (2003), through European Union we find proposals for directives on nuclear safety and radioactive waste management, new regulation on the application of EURATOM safeguards, control of high activity sealed radioactive sources, recommendation on the protection and information of the public with regard to the continued contamination of certain wild food products following the Chernobyl accident, proposals for decisions authorizing the Member states to sign and ratify the Protocol to amend the Paris convention, p)proposals for a directive on environment liability with regard to the prevention and remedying of environmental damage, proposal of a regulation on the law applicable to non-contractual obligation. (N.C.)

  13. Nuclear Regulatory Commission Issuances

    International Nuclear Information System (INIS)

    1992-01-01

    This is the thirty-sixth volume of issuances (1-396) of the Nuclear Regulatory Commission and its Atomic Safety and Licensing Boards, Administrative Law Judges, and Office Directors. It covers the period from July 1, 1992-December 31, 1992. Atomic Safety and Licensing Boards are authorized by Section 191 of the Atomic Energy Act of 1954. These Boards, comprised of three members conduct adjudicatory hearings on applications to construct and operate nuclear power plants and related facilities and issue initial decisions which, subject to internal review and appellate procedures, become the final Commission action with respect to those applications. Boards are drawn from the Atomic Safety and Licensing Board Panel, comprised of lawyers, nuclear physicists and engineers, environmentalists, chemists, and economists. The Atomic Energy Commission first established Licensing Boards in 1962 and the Panel in 1967

  14. Integrated systems approach identifies risk regulatory pathways and key regulators in coronary artery disease.

    Science.gov (United States)

    Zhang, Yan; Liu, Dianming; Wang, Lihong; Wang, Shuyuan; Yu, Xuexin; Dai, Enyu; Liu, Xinyi; Luo, Shanshun; Jiang, Wei

    2015-12-01

    Coronary artery disease (CAD) is the most common type of heart disease. However, the molecular mechanisms of CAD remain elusive. Regulatory pathways are known to play crucial roles in many pathogenic processes. Thus, inferring risk regulatory pathways is an important step toward elucidating the mechanisms underlying CAD. With advances in high-throughput data, we developed an integrated systems approach to identify CAD risk regulatory pathways and key regulators. Firstly, a CAD-related core subnetwork was identified from a curated transcription factor (TF) and microRNA (miRNA) regulatory network based on a random walk algorithm. Secondly, candidate risk regulatory pathways were extracted from the subnetwork by applying a breadth-first search (BFS) algorithm. Then, risk regulatory pathways were prioritized based on multiple CAD-associated data sources. Finally, we also proposed a new measure to prioritize upstream regulators. We inferred that phosphatase and tensin homolog (PTEN) may be a key regulator in the dysregulation of risk regulatory pathways. This study takes a closer step than the identification of disease subnetworks or modules. From the risk regulatory pathways, we could understand the flow of regulatory information in the initiation and progression of the disease. Our approach helps to uncover its potential etiology. We developed an integrated systems approach to identify risk regulatory pathways. We proposed a new measure to prioritize the key regulators in CAD. PTEN may be a key regulator in dysregulation of the risk regulatory pathways.

  15. 77 FR 52098 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of...

    Science.gov (United States)

    2012-08-28

    ... Exchange would announce via Regulatory Bulletin the applicable time period(s) for the Risk Limitation... Exchange would specify via Regulatory Bulletin the applicable time period(s) for the Risk Limitation... Risk Limitation Mechanisms, as well as any applicable time period(s) and order types, via Regulatory...

  16. Regulatory focus in groupt contexts

    NARCIS (Netherlands)

    Faddegon, Krispijn Johannes

    2009-01-01

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

  17. Disclosure as a regulatory tool

    DEFF Research Database (Denmark)

    Sørensen, Karsten Engsig

    2006-01-01

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

  18. 75 FR 7526 - Withdrawal of Regulatory Guide

    Science.gov (United States)

    2010-02-19

    ...'s Electronic Reading Room at http://www.nrc.gov/reading-rm/doc-collections . Regulatory guides are... NUCLEAR REGULATORY COMMISSION [NRC-2010-0052] Withdrawal of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Withdrawal of Regulatory Guide 1.56, ``Maintenance of Water Purity in Boiling...

  19. 12 CFR 562.2 - Regulatory reports.

    Science.gov (United States)

    2010-01-01

    ... § 562.2 Regulatory reports. (a) Definition and scope. This section applies to all regulatory reports, as... (TFR) are examples of regulatory reports. Regulatory reports are regulatory documents, not accounting... limited to, the accounting instructions provided in the TFR, guidance contained in OTS regulations...

  20. Virginia Power's regulatory reduction program

    International Nuclear Information System (INIS)

    Miller, G.D.

    1996-01-01

    Virginia Power has two nuclear plants, North Anna and Surry Power Stations, which have two units each for a total of four nuclear units. In 1992, the Nuclear Regulatory Commission solicited comments from the nuclear industry to obtain their ideas for reducing the regulatory burden on nuclear facilities. Pursuant to the new regulatory climate, Virginia Power developed an internal program to evaluate and assess the regulatory and self-imposed requirements to which they were committed, and to pursue regulatory relief or internal changes where possible and appropriate. The criteria were that public safety must be maintained, and savings must be significant. Up to the date of the conference, over US$22 million of one-time saving had been effected, and US$2.75 million in annual savings

  1. Anti-regulatory T cells

    DEFF Research Database (Denmark)

    Andersen, Mads Hald

    2017-01-01

    responses to tumours or inhibiting autoimmunity development. However, recent studies report the discovery of self-reactive pro-inflammatory T cells—termed anti-regulatory T cells (anti-Tregs)—that target immune-suppressive cells. Thus, regulatory cells can now be defined as both cells that suppress immune...... reactions as well as effector cells that counteract the effects of suppressor cells and support immune reactions. Self-reactive anti-Tregs have been described that specifically recognize human leukocyte antigen-restricted epitopes derived from proteins that are normally expressed by regulatory immune cells......Our initial understanding of immune-regulatory cells was based on the discovery of suppressor cells that assure peripheral T-cell tolerance and promote immune homeostasis. Research has particularly focused on the importance of regulatory T cells (Tregs) for immune modulation, e.g. directing host...

  2. The Proline Regulatory Axis and Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Phang, James Ming; Liu, Wei; Hancock, Chad; Christian, Kyle J., E-mail: phangj@mail.nih.gov [Metabolism and Cancer Susceptibility Section, Basic Research Laboratory, Center for Cancer Research, Frederick National Laboratory for Cancer Research, Frederick, MD (United States)

    2012-06-21

    Studies in metabolism and cancer have characterized changes in core pathways involving glucose and glutamine, emphasizing the provision of substrates for building cell mass. But recent findings suggest that pathways previously considered peripheral may play a critical role providing mechanisms for cell regulation. Several of these mechanisms involve the metabolism of non-essential amino acids, for example, the channeling of glycolytic intermediates into the serine pathway for one-carbon transfers. Historically, we proposed that the proline biosynthetic pathway participated in a metabolic interlock with glucose metabolism. The discovery that proline degradation is activated by p53 directed our attention to the initiation of apoptosis by proline oxidase/dehydrogenase. Now, however, we find that the biosynthetic mechanisms and the metabolic interlock may depend on the pathway from glutamine to proline, and it is markedly activated by the oncogene MYC. These findings add a new dimension to the proline regulatory axis in cancer and present attractive potential targets for cancer treatment.

  3. Development of Questionnaire for Self-Assessment of Regulatory Capture

    Energy Technology Data Exchange (ETDEWEB)

    Muhmood, Ul Hassan; Lee, Young Eal [Pakistan Nuclear Regulatory Authority, Islamabad (Pakistan); Choi, Kwang Sik [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2014-10-15

    Nuclear industry with its evolution in 60s came with a number of pros and cons. In order to avoid any accident or incident, highest safety standards and quality control mechanism were established. The relation of regulator with its licensee is critical in the sense of public safety and welfare. The situation when the regulator starts to work for the interests of the industry instead of the public interest and fails to cling with his mission is known as 'regulatory capture' which may cause a number of serious negative effects like radiological or radiation risk. According to George Stigler, as a rule regulation is acquired by the industry and is designed and operated primarily for its benefit. The phenomenon of regulatory capture may hamper the safety culture and can also be considered as regulatory failure. It is therefore necessary to clearly understand this type of government failure to avoid the happening of serious accidents like TMI and Fukushima in the future. This paper aims to explore whether the regulatory body works independently and effectively to achieve its assigned tasks and objectives. Hence we proposed a questionnaire for the self-assessment of regulatory capture within the regulatory body. It also includes the results of an experimental assessment which was carried out to check the relevance and reliability of the questions to this subject. This assessment survey was conducted with the officers and staff members of Pakistan Nuclear Regulatory Authority (PNRA). We checked the significance of the proposed questionnaire and found some of the questions like Q. 27, 30 and 33 (written in italic) are not directly related to the phenomenon of regulatory capture. However, the existence of the situation which has been asked in these questions may lead towards the hampering of regulatory culture.

  4. Development of Questionnaire for Self-Assessment of Regulatory Capture

    International Nuclear Information System (INIS)

    Muhmood, Ul Hassan; Lee, Young Eal; Choi, Kwang Sik

    2014-01-01

    Nuclear industry with its evolution in 60s came with a number of pros and cons. In order to avoid any accident or incident, highest safety standards and quality control mechanism were established. The relation of regulator with its licensee is critical in the sense of public safety and welfare. The situation when the regulator starts to work for the interests of the industry instead of the public interest and fails to cling with his mission is known as 'regulatory capture' which may cause a number of serious negative effects like radiological or radiation risk. According to George Stigler, as a rule regulation is acquired by the industry and is designed and operated primarily for its benefit. The phenomenon of regulatory capture may hamper the safety culture and can also be considered as regulatory failure. It is therefore necessary to clearly understand this type of government failure to avoid the happening of serious accidents like TMI and Fukushima in the future. This paper aims to explore whether the regulatory body works independently and effectively to achieve its assigned tasks and objectives. Hence we proposed a questionnaire for the self-assessment of regulatory capture within the regulatory body. It also includes the results of an experimental assessment which was carried out to check the relevance and reliability of the questions to this subject. This assessment survey was conducted with the officers and staff members of Pakistan Nuclear Regulatory Authority (PNRA). We checked the significance of the proposed questionnaire and found some of the questions like Q. 27, 30 and 33 (written in italic) are not directly related to the phenomenon of regulatory capture. However, the existence of the situation which has been asked in these questions may lead towards the hampering of regulatory culture

  5. Regulatory audit to the Argentine teletherapy units

    International Nuclear Information System (INIS)

    Kay, J.M.

    1995-01-01

    As a consequence of an erroneous calibration of the ionization chamber dosimeter of a new licensed 6 Mev electron lineal accelerator that caused accidental overexposures in the first patients under treatment, the Regulatory Board decided to perform an audit to every teletherapy unit (accelerator and telegammatherapy units) in Argentina. The audit was carried out at the en of 1994 in 27 accelerators and 107 telegammatherapy units. The objectives of the audit were the control of the mechanical and optical aspects of the each accelerator and telegammatherapy unit and the control of the calibration of their radiation beams. The last action was undertaken to detect as soon as possible, any eventual accidental overexposure or underexposure of patients under treatment. The audit was conducted by the author and performed for a team of 22 inspectors who worked in groups of 2 to 3 people and completed the inspection of the teletherapy units of the whole country in 3 months. As a result of the audit, the Regulatory Board had in a short period a clear panorama of the performance of each teletherapy unit of the country and also confirmed that no accidental situation had happened. The audit revealed the necessity of imposing urgent regulatory requirements not related to the calibration of the radiation beam in 5% of the cases, as well as non-urgent requirements of different importance in approximately other 60% of the cases. (author)

  6. Regulatory T cells and immunity to pathogens.

    Science.gov (United States)

    Rouse, Barry T; Suvas, Susmit

    2007-09-01

    Immune responses to pathogens are modulated by one or more types of cells that perform a regulatory function. Some cells with this function, such as CD4+ Foxp3+ natural regulatory T cells (nTreg), pre-exist prior to infections whereas others may be induced as a consequence of infection (adaptive Treg). With pathogens that have a complex pathogenesis, multiple types of regulatory cells could influence the outcome. One major property of Treg is to help minimize collateral tissue damage that can occur during immune reactions to a chronic infection. The consequence is less damage to the host but in such situations the pathogen is likely to establish persistence. In some cases, a fine balance is established between Treg responses, effector components of immunity and the pathogen. Treg responses to pathogens may also act to hamper the efficacy of immune control. This review discusses these issues as well as the likely mechanisms by which various pathogens can signal the participation of Treg during infection.

  7. 75 FR 11166 - Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission...

    Science.gov (United States)

    2010-03-10

    ... the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission; Notice of Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission March 2, 2010. The Federal Energy Regulatory Commission (FERC) and the Nuclear Regulatory Commission (NRC) will hold...

  8. 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

  9. Regulatory T Cells in Human Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Dong-Jun Peng

    2012-01-01

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

  10. Regulatory heterochronies and loose temporal scaling between sea star and sea urchin regulatory circuits.

    Science.gov (United States)

    Gildor, Tsvia; Hinman, Veronica; Ben-Tabou-De-Leon, Smadar

    2017-01-01

    It has long been argued that heterochrony, a change in relative timing of a developmental process, is a major source of evolutionary innovation. Heterochronic changes of regulatory gene activation could be the underlying molecular mechanism driving heterochronic changes through evolution. Here, we compare the temporal expression profiles of key regulatory circuits between sea urchin and sea star, representative of two classes of Echinoderms that shared a common ancestor about 500 million years ago. The morphologies of the sea urchin and sea star embryos are largely comparable, yet, differences in certain mesodermal cell types and ectodermal patterning result in distinct larval body plans. We generated high resolution temporal profiles of 17 mesodermally-, endodermally- and ectodermally-expressed regulatory genes in the sea star, Patiria miniata, and compared these to their orthologs in the Mediterranean sea urchin, Paracentrotus lividus. We found that the maternal to zygotic transition is delayed in the sea star compared to the sea urchin, in agreement with the longer cleavage stage in the sea star. Interestingly, the order of gene activation shows the highest variation in the relatively diverged mesodermal circuit, while the correlations of expression dynamics are the highest in the strongly conserved endodermal circuit. We detected loose scaling of the developmental rates of these species and observed interspecies heterochronies within all studied regulatory circuits. Thus, after 500 million years of parallel evolution, mild heterochronies between the species are frequently observed and the tight temporal scaling observed for closely related species no longer holds.

  11. 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

  12. 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...

  13. The Danish Regulatory Reform of Telecommunications

    DEFF Research Database (Denmark)

    Skouby, Knud Erik

    1998-01-01

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

  14. Strengthening Regulatory Competence in a Changing Nuclear Regulatory Environment

    International Nuclear Information System (INIS)

    Illizastigui, P.F.

    2016-01-01

    The paper addresses the approach followed by the Cuban National Center for Nuclear Safety for the management of current and new competences of its regulatory staff with the aim of allowing those staff to effectively fulfill their core regulatory functions. The approach is realized through an Integrated System for Competence Building, which is based on the IAEA recommendations, shown to be effective in ensuring the necessary competence in the relevant areas. In the author’s opinion, competence of the regulatory staff in the area of human and organizational factors is of paramount importance and needs to be further strengthened in order to be able to assess safety performance at the facilities and detect early signs of deteriorating safety performance. The former is defined by the author as the core regulatory function “Analysis” which covers the entire spectrum of assessment tasks carried out by the regulatory staff to: a) detect declining safety performance, b) diagnose latent weaknesses (root causes) and c) make effective safety culture interventions. The author suggests that competence associated with the fulfillment of the analysis function is distinctly identified and dealt with separately in the current system of managing regulatory competence. (author)

  15. Small RNA-Controlled Gene Regulatory Networks in Pseudomonas putida

    DEFF Research Database (Denmark)

    Bojanovic, Klara

    evolved numerous mechanisms to controlgene expression in response to specific environmental signals. In addition to two-component systems, small regulatory RNAs (sRNAs) have emerged as major regulators of gene expression. The majority of sRNAs bind to mRNA and regulate their expression. They often have...... multiple targets and are incorporated into large regulatory networks and the RNA chaper one Hfq in many cases facilitates interactions between sRNAs and their targets. Some sRNAs also act by binding to protein targets and sequestering their function. In this PhD thesis we investigated the transcriptional....... Detailed insights into the mechanisms through which P. putida responds to different stress conditions and increased understanding of bacterial adaptation in natural and industrial settings were gained. Additionally, we identified genome-wide transcription start sites, andmany regulatory RNA elements...

  16. International regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2004-01-01

    The 48. session of the IAEA general conference was held in Vienna from 20 to 24 september 2004 with the participation of delegates from 125 members states and representatives of various international organisations. A number of resolutions were adopted by the conference in the following fields: nuclear safety, radiation, transport and waste safety. The general conference also adopted a resolution on measures to protect against nuclear terrorism. The Director General decided in 2003 to appoint a group of experts to explore and advise on issues related to nuclear liability. This group called the International Expert Group on Nuclear Liability (I.N.L.E.X.) consists of 20 experts members from nuclear power and non nuclear power countries and from shipping and non shipping states. It serves three major functions: to create a forum of expertise to explore and advise on issues related to nuclear liability; to enhance global adherence by nuclear and non nuclear states to an effective nuclear liability regime, inter alia, on the basis of the convention on supplementary compensation for nuclear damage and the annex thereto, the Vienna convention on civil liability for nuclear damage, the Paris convention on third party liability in the field of nuclear energy, the joint protocol relating to the application of the vienna convention and the paris convention and the amendments thereto; and to assist in the development and strengthening of the national nuclear liability legal frameworks in IAEA members states to protect the public and the environment and to enhance nuclear safety. The second part of international regulatory concerns a directive on public access to environmental information made by the European Parliament. (N.C.)

  17. 78 FR 1634 - Regulatory Agenda

    Science.gov (United States)

    2013-01-08

    ... amendments include updates to organizational information, use of the term ``disability'' in lieu of the term.../00/13 Regulatory Flexibility Analysis Required: No. Agency Contact: Robert W. Cosgrove, External...

  18. 78 FR 44329 - Regulatory Agenda

    Science.gov (United States)

    2013-07-23

    ... amendments include updates to organizational information, use of the term ``disability'' in lieu of the term.../00/13 Regulatory Flexibility Analysis Required: No. Agency Contact: Robert W. Cosgrove, External...

  19. 78 FR 44279 - Regulatory Agenda

    Science.gov (United States)

    2013-07-23

    ... Vol. 78 Tuesday, No. 141 July 23, 2013 Part XI Department of Justice Semiannual Regulatory Agenda #0;#0;Federal Register / Vol. 78 , No. 141 / Tuesday, July 23, 2013 / Unified Agenda#0;#0; [[Page 44280

  20. Recent regulatory issues in Finland

    International Nuclear Information System (INIS)

    Laaksonen, J.; Tiipana, P.

    2001-01-01

    This paper presents general regulatory issues from Finland since the last WWER Regulators Forum meeting in Odessa 11-13 October 2000. More specific issues concerning Loviisa NPP are described in the Annex of this paper. (author)

  1. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2016-01-01

    This section treats of the following National legislative and regulatory activities: 1 - France: General legislation, regulations and instruments; Nuclear trade (including non-proliferation); International co-operation; 2 - India: Licensing and regulatory infrastructure; Liability and compensation; 3 - Ireland: Nuclear safety and radiological protection (including nuclear emergency planning); Transport of radioactive material; Nuclear trade (including non-proliferation); 4 - Lithuania: Licensing and regulatory infrastructure; Nuclear safety and radiological protection (including nuclear emergency planning); Radioactive waste management; 5 - Luxembourg: Nuclear safety and radiological protection (including nuclear emergency planning); 6 - Slovak Republic: International co-operation; General legislation, regulations and instruments; 7 - Spain: Radioactive materials (including physical protection); Radioactive waste management; 8 - United States: Licensing and regulatory infrastructure

  2. Quality assurance within regulatory bodies

    International Nuclear Information System (INIS)

    1999-06-01

    The IAEA directed extensive efforts during the years 1991 to 1995 to the integral revision of all NUSS quality assurance publications, which were approved and issued as Safety Series No.50-C/SG-Q, Quality Assurance for Safety in Nuclear Power Plants and other Nuclear Installations (1996). When these quality assurance publications were developed, their prime focus was on requirements against which work performed by the licensees could be measured and assessed by the regulatory bodies. In this way, they only helped to facilitate the functions of regulators. No requirements or recommendations were provided on how the regulators should ensure the effective implementation of their own activities. The present publication is a first attempt to collect, integrate and offer available experience to directly support performance of regulatory activities. It presents a comprehensive compilation on the application of quality assurance principles and methods by regulatory bodies to their activities. The aim is consistent good performance of regulatory activities through a systematic approach

  3. State/Federal Regulatory Considerations

    Science.gov (United States)

    This page contains presentations from the Brown to Green: Make the Connection to Renewable Energy workshop held in Santa Fe, New Mexico, during December 10-11, 2008, regarding State/Federal Regulatory Considerations.

  4. Regulatory competition in partnership law.

    OpenAIRE

    Siems, Mathias

    2009-01-01

    Regulatory competition in company law has been extensively debated in the last few decades, but it has rarely been discussed whether there could also be regulatory competition in partnership law. This article fills this gap. It addresses the partnership law of the US, the UK, Germany, and France, and presents empirical data on the different types of partnerships and companies established in these jurisdictions. The main focus is on the use of a limited liability partnership (LLP) outside its ...

  5. Nuclear regulatory developments in Canada

    International Nuclear Information System (INIS)

    Binder, M.

    2012-01-01

    This paper from CNSC discusses nuclear regulatory developments in Canada. It starts with the Fukushima accident and the effect on the nuclear sector. It summarises what CNSC has done, what it has learned and their plans going forward. It has made recommendations to IAEA for international enhancements to regulatory procedures. It outline the activities of Canada's nuclear power plants, Canada's uranium projects, deep geological repository and waste management as well as nuclear research in Canada.

  6. Regulatory facility guide for Ohio

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-02-28

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

  7. Steam Generator tube integrity -- US Nuclear Regulatory Commission perspective

    International Nuclear Information System (INIS)

    Murphy, E.L.; Sullivan, E.J.

    1997-01-01

    In the US, the current regulatory framework was developed in the 1970s when general wall thinning was the dominant degradation mechanism; and, as a result of changes in the forms of degradation being observed and improvements in inspection and tube repair technology, the regulatory framework needs to be updated. Operating experience indicates that the current U.S. requirements should be more stringent in some areas, while in other areas they are overly conservative. To date, this situation has been dealt with on a plant-specific basis in the US. However, the NRC staff is now developing a proposed steam generator rule as a generic framework for ensuring that the steam generator tubes are capable of performing their intended safety functions. This paper discusses the current U.S. regulatory framework for assuring steam generator (SG) tube integrity, the need to update this regulatory framework, the objectives of the new proposed rule, the US Nuclear Regulatory Commission (NRC) regulatory guide (RG) that will accompany the rule, how risk considerations affect the development of the new rule, and some outstanding issues relating to the rule that the NRC is still dealing with

  8. Computational methods to dissect cis-regulatory transcriptional ...

    Indian Academy of Sciences (India)

    The formation of diverse cell types from an invariant set of genes is governed by biochemical and molecular processes that regulate gene activity. A complete understanding of the regulatory mechanisms of gene expression is the major function of genomics. Computational genomics is a rapidly emerging area for ...

  9. Nuclear knowledge management system in the regulatory activity

    International Nuclear Information System (INIS)

    Nosovskij, A.V.; Klevtsov, A.L.; Kravchenko, N.A.

    2010-01-01

    Important issues on collection, storage and spread of knowledge among organisation dealing with the use of nuclear technologies, role of close cooperation between enterprises and organizations in developing knowledge management, general requirements for creating a nuclear knowledge management system are considered. Recommendations and the main mechanisms are identified to create the knowledge management system in technical support organizations of the regulatory authority.

  10. Steam generators regulatory practices and issues in Spain

    International Nuclear Information System (INIS)

    Mendoza, C.; Castelao, C.; Ruiz-Colino, J.; Figueras, J.M.

    1997-01-01

    This paper presents the actual status of Spanish Steam Generator tubes, actions developed by PWR plant owners and submitted to CSN, and regulatory activities related to tube degradation mechanisms analysis; NDT tube inspection techniques; tube, tubesheet and TSPs integrity studies; tube plugging/repair criteria; preventive and corrective measures including whole SGs replacement; tube leak measurement methods and other operational aspects

  11. Genomewide analyses of pathogenic and regulatory T cells of NOD ...

    Indian Academy of Sciences (India)

    Reestablishing a well-balanced population of regulatory T cells (Tregs) and pathogenic T cells (Tpaths) is necessary for diabetic patients to regain glucose control. However, the molecular mechanisms modulating functional differentiation of Tpaths and Tregs remain unclear. In this study, we anal- ysed the gene expression ...

  12. The expanding universe of regulatory T cell subsets in cancer.

    Science.gov (United States)

    Gajewski, Thomas F

    2007-08-01

    Evidence has indicated that failed antitumor immunity is dominated by immunosuppressive mechanisms within the tumor microenvironment. In this issue of Immunity, Peng et al. (2007) add to this list by describing tumor-infiltrating gammadelta T cells that have regulatory function.

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

    Science.gov (United States)

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

    2015-01-01

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

  14. 75 FR 22868 - Withdrawal of Regulatory Guide

    Science.gov (United States)

    2010-04-30

    ...'s public Web site under ``Regulatory Guides'' in the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/doc-collections . Regulatory guides are also available for inspection at the NRC's... NUCLEAR REGULATORY COMMISSION [NRC-2010-0167] Withdrawal of Regulatory Guide AGENCY: Nuclear...

  15. Sequence-based model of gap gene regulatory network.

    Science.gov (United States)

    Kozlov, Konstantin; Gursky, Vitaly; Kulakovskiy, Ivan; Samsonova, Maria

    2014-01-01

    The detailed analysis of transcriptional regulation is crucially important for understanding biological processes. The gap gene network in Drosophila attracts large interest among researches studying mechanisms of transcriptional regulation. It implements the most upstream regulatory layer of the segmentation gene network. The knowledge of molecular mechanisms involved in gap gene regulation is far less complete than that of genetics of the system. Mathematical modeling goes beyond insights gained by genetics and molecular approaches. It allows us to reconstruct wild-type gene expression patterns in silico, infer underlying regulatory mechanism and prove its sufficiency. We developed a new model that provides a dynamical description of gap gene regulatory systems, using detailed DNA-based information, as well as spatial transcription factor concentration data at varying time points. We showed that this model correctly reproduces gap gene expression patterns in wild type embryos and is able to predict gap expression patterns in Kr mutants and four reporter constructs. We used four-fold cross validation test and fitting to random dataset to validate the model and proof its sufficiency in data description. The identifiability analysis showed that most model parameters are well identifiable. We reconstructed the gap gene network topology and studied the impact of individual transcription factor binding sites on the model output. We measured this impact by calculating the site regulatory weight as a normalized difference between the residual sum of squares error for the set of all annotated sites and for the set with the site of interest excluded. The reconstructed topology of the gap gene network is in agreement with previous modeling results and data from literature. We showed that 1) the regulatory weights of transcription factor binding sites show very weak correlation with their PWM score; 2) sites with low regulatory weight are important for the model output; 3

  16. Regulatory aspects of radiation protection in Indian nuclear plants

    International Nuclear Information System (INIS)

    Chander, Vipin; Pawar, S.K.; Duraisamy, S.

    2012-01-01

    Atomic Energy Act of 1962 covers the radiation safety aspects in the development, control and use of atomic energy. To carry out certain regulatory and safety functions under this act, Atomic Energy Regulatory Board (AERB) was constituted in November 15, 1983. Operating Nuclear Power Plants (NPPs) account for about 60% of occupational collective dose and about 65% of the number of radiation workers in the nuclear fuel cycle facilities. Therefore radiation protection aspects in NPPs are of prime importance. In 1970s and 1980s the high radiation exposures in NPPs was an issue with TAPS-1 and 2 reaching annual collective dose of 50 Person-Sv. In response to this, AERB constituted an expert committee to investigate the possibility of reducing collective doses in NPPs in 1988. Subsequently the recommendations of this committee were implemented in all NPPs. In 1990, International Commission on Radiological Protection (ICRP) recommended a downward revision of occupational dose limit to 20 mSv/yr from the earlier limit of 50 mSv/yr. Regulatory body endorsed these recommendations and gradually brought down the annual dose limits from 40 mSv in 1991 to 30 mSv in 1994 with the limit of 100 mSv averaged over a five year period in line with ICRP recommendations. Over the years, the regulatory body has put in place a sound regulatory frame work and mechanism to ensure adequate protection of occupational workers, members of public and environment due to operation of NPPs. Vast experiences in the field of radiation protection vis-à-vis stringent regulatory requirements such as review of exposure cases and special regulatory inspections during Biennial Shut Down (BSD) has helped in downward trends in occupational and public doses. This paper highlights the role of regulatory body in controlling the radiation doses to both occupational workers and members of public in the NPPs through a three-tier review system. The regulatory oversight, inspections and reviews has resulted in

  17. Deciphering RNA Regulatory Elements Involved in the Developmental and Environmental Gene Regulation of Trypanosoma brucei.

    Science.gov (United States)

    Gazestani, Vahid H; Salavati, Reza

    2015-01-01

    Trypanosoma brucei is a vector-borne parasite with intricate life cycle that can cause serious diseases in humans and animals. This pathogen relies on fine regulation of gene expression to respond and adapt to variable environments, with implications in transmission and infectivity. However, the involved regulatory elements and their mechanisms of actions are largely unknown. Here, benefiting from a new graph-based approach for finding functional regulatory elements in RNA (GRAFFER), we have predicted 88 new RNA regulatory elements that are potentially involved in the gene regulatory network of T. brucei. We show that many of these newly predicted elements are responsive to both transcriptomic and proteomic changes during the life cycle of the parasite. Moreover, we found that 11 of predicted elements strikingly resemble previously identified regulatory elements for the parasite. Additionally, comparison with previously predicted motifs on T. brucei suggested the superior performance of our approach based on the current limited knowledge of regulatory elements in T. brucei.

  18. Regulatory Expectations for Safety Culture

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-05-15

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

  19. Radioactive waste below regulatory concern

    International Nuclear Information System (INIS)

    Neuder, S.M.

    1987-01-01

    The U.S. Nuclear Regulatory Commission (NRC) published two notices in the Federal Register concerning radioactive waste below regulatory concern. The first, a Commission Policy Statement and Implementation Plan published August 29, 1986, concerns petition to exempt specific radioactive waste streams from the regulations. The second, an Advanced Notice of Proposed Rulemaking published Decemger 2, 1986, addresses the concept of generic rulemaking by the NRC on radioactive wastes that are below regulatory concern. Radioactive waste determined to be below regulatory concern would not be subject to regulatory control and would not need to go to a licensed low-level radioactive waste disposal site. The Policy Statement and Implementation Plan describe (1) the information a petitioner should file in support of a petition to exempt a specific waste stream, (2) the decision criteria the Commission intends to use for judging the petition, and (3) the internal administrative procedures to use be followed in order to permit the Commission to act upon the petition in an expedited manner

  20. 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

  1. 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

  2. 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

  3. Regulatory impairments following selective 6-OHDA lesions of the neostriatum.

    Science.gov (United States)

    Dunnett, S B; Iversen, S D

    1982-02-01

    6-Hydroxydopamine lesions of the ventrolateral (VLC) but not anteromedial (AMC) caudate-putamen in rats resulted in a greater post-operative reduction in body weight and water intake than seen in animals with sham lesions. Once animals had fully resumed spontaneous food and water intake, a series of regulatory challenges were administered, and the AMC rats showed a reduced enhancement of drinking following injection of hypertonic saline. The results are interpreted in terms of a heterogeneous striatal convergence of nigrostriatal and cortical regulatory mechanisms.

  4. Regulatory immune cells and functions in autoimmunity and transplantation immunology.

    Science.gov (United States)

    Papp, Gabor; Boros, Peter; Nakken, Britt; Szodoray, Peter; Zeher, Margit

    2017-05-01

    In physiological circumstances, various tolerogenic mechanisms support the protection of self-structures during immune responses. However, quantitative and/or qualitative changes in regulatory immune cells and mediators can evoke auto-reactive immune responses, and upon susceptible genetic background, along with the presence of other concomitant etiological factors, autoimmune disease may develop. In transplant immunology, tolerogenic mechanisms are also critical, since the balance between of alloantigen-reactive effector cells and the regulatory immune cells will ultimately determine whether a graft is accepted or rejected. Better understanding of the immunological tolerance and the potential modulations of immune regulatory processes are crucial for developing effective therapies in autoimmune diseases as well as in organ transplantation. In this review, we focus on the novel insights regarding the impaired immune regulation and other relevant factors contributing to the development of auto-reactive and graft-reactive immune responses in autoimmune diseases and transplant rejection, respectively. We also address some promising approaches for modification of immune-regulatory processes and tolerogenic mechanisms in autoimmunity and solid organ transplantation, which may be beneficial in future therapeutic strategies. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Dual Nature of Translational Control by Regulatory BC RNAs ▿

    Science.gov (United States)

    Eom, Taesun; Berardi, Valerio; Zhong, Jun; Risuleo, Gianfranco; Tiedge, Henri

    2011-01-01

    In higher eukaryotes, increasing evidence suggests, gene expression is to a large degree controlled by RNA. Regulatory RNAs have been implicated in the management of neuronal function and plasticity in mammalian brains. However, much of the molecular-mechanistic framework that enables neuronal regulatory RNAs to control gene expression remains poorly understood. Here, we establish molecular mechanisms that underlie the regulatory capacity of neuronal BC RNAs in the translational control of gene expression. We report that regulatory BC RNAs employ a two-pronged approach in translational control. One of two distinct repression mechanisms is mediated by C-loop motifs in BC RNA 3′ stem-loop domains. These C-loops bind to eIF4B and prevent the factor's interaction with 18S rRNA of the small ribosomal subunit. In the second mechanism, the central A-rich domains of BC RNAs target eIF4A, specifically inhibiting its RNA helicase activity. Thus, BC RNAs repress translation initiation in a bimodal mechanistic approach. As BC RNA functionality has evolved independently in rodent and primate lineages, our data suggest that BC RNA translational control was necessitated and implemented during mammalian phylogenetic development of complex neural systems. PMID:21930783

  6. Regulatory authority information system RAIS

    International Nuclear Information System (INIS)

    Ortiz, P.; Mrabit, K.; Miaw, S.

    2000-01-01

    In this lecture the principles of the regulatory authority information system (RAIS) are presented. RAIS is a tool currently being developed by the IAEA for the Regulatory Authorities. It is a part of a set of supporting actions designed to assist member states in achieving the objectives of the Model project on radiation and waste safety infrastructure. RAIS is a tool that provides the management of the Regulatory Authority with the key information needed for the planning and implementation of activities and to ensure confidence that resources are optimally used. The RAIS contains five modules: Inventory of installations and radiation sources; Authorization process; Inspection and follow-up actions; Information on personal dosimetry; Assessment of effectiveness by means of performance indicators

  7. Transparency of nuclear regulatory activities

    International Nuclear Information System (INIS)

    2007-01-01

    One of the main missions of nuclear regulators is to protect the public, and this cannot be completely achieved without public confidence. The more a regulatory process is transparent, the more such confidence will grow. Despite important cultural differences across countries, a number of common features characterise media and public expectations regarding any activity with an associated risk. A common understanding of transparency and main stakeholders' expectations in the field of nuclear safety were identified during this workshop, together with a number of conditions and practices aimed at improving the transparency of nuclear regulatory activities. These conditions and practices are described herein, and will be of particular interest to all those working in the nuclear regulatory field. Their implementation may, however, differ from one country to another depending on national context. (authors)

  8. Regulatory authority infrastructure for Namibia

    International Nuclear Information System (INIS)

    Shangula, K.

    2001-01-01

    The Republic of Namibia is participating in the International Atomic Energy Agency's Model Project for the Improvement of National Regulatory Authority Infrastructures in Member States. The paper illustrates our experience in solving problems and difficulties confronted in establishing an effective regulatory authority operating within the existing national infrastructure that should be supported by the Government. An effective regulatory authority is seen as part of the wider administrative scope of our Government through ministerial mandates given by the State from time to time, guaranteeing its independence when implementing legal provisions under statutes. Sections of the report illustrate our experience in the following areas: 1. National radiation protection policy 2. Structure of our national regulatory authority 3. Laws and regulations 4. Provisions for notification, authorization and registration 5. In-depth security measures for radiation sources and radioactive material 6. Systems for the inspection of radiation sources, radioactive materials, enforcement of legal provisions 7. Extent of the applications of radiation sources and radioactive materials in the country. The paper provides information regarding existing Government policy on radiation protection; structure and legal aspects of the national regulatory, including statutes and regulations; the extent of application and uses of radiation sources and security of radioactive materials; human resources: strengths and constraints; management practices and financing of regulatory authority; and plans for emergency recovery of orphan sources. National plans for management of disused sources, recovery of orphan sources, abnormal emergencies, communication of information to affected persons on exposure effects, and the safety training of persons using these applications are discussed. the paper provides a summary and some suggestions of the way forward for Namibia. (author)

  9. DOE regulatory reform initiative vitrified mixed waste

    International Nuclear Information System (INIS)

    Carroll, S.J.; Holtzscheiter, E.W.

    1997-01-01

    The US Department of Energy (DOE) is charged with responsibly managing the largest volume of mixed waste in the United States. This responsibility includes managing waste in compliance with all applicable Federal and State laws and regulations, and in a cost-effective, environmentally responsible manner. Managing certain treated mixed wastes in Resource Conservation and Recovery Act (RCRA) permitted storage and disposal units (specifically those mixed wastes that pose low risks from the hazardous component) is unlikely to provide additional protection to human health and the environment beyond that afforded by managing these wastes in storage and disposal units subject to requirements for radiological control. In October, 1995, the DOE submitted a regulatory reform proposal to the Environmental Protection Agency (EPA) relating to vitrified mixed waste forms. The technical proposal supports a regulatory strategy that would allow vitrified mixed waste forms treated through a permit or other environmental compliance mechanism to be granted an exemption from RCRA hazardous waste regulation, after treatment, based upon the inherent destruction and immobilization capabilities of vitrification technology. The vitrified waste form will meet, or exceed the performance criteria of the Environmental Assessment (EA) glass that has been accepted as an international standard for immobilizing radioactive waste components and the LDR treatment standards for inorganics and metals for controlling hazardous constituents. The proposal further provides that vitrified mixed waste would be responsibly managed under the Atomic Energy Act (AEA) while reducing overall costs. Full regulatory authority by the EPA or a State would be maintained until an acceptable vitrified mixed waste form, protective of human health and the environment, is produced

  10. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2014-01-01

    This section treats of the following activities sorted by country: 1 - Belarus: International cooperation, Organisation and structure, Licensing and regulatory infrastructure, Nuclear safety and radiological protection; 2 - France: Nuclear safety and radiological protection, Radioactive waste management, Environmental protection, Liability and compensation, International co-operation; 3 - Hungary: General legislation, Radioactive waste management, Nuclear security; 4 - Ireland: Nuclear safety and radiological protection (including emergency planning); 5 - Lithuania: Licensing and regulatory infrastructure; 6 - Moldova: Nuclear safety and radiological protection; 7 - Portugal: Radioactive waste management, Nuclear safety and radiological protection; 8 - Slovak Republic: Radioactive waste management, Liability and compensation; 9 - Spain: Radioactive waste management; 10 - Ukraine: Radioactive waste management; 11 - United Kingdom: Organisation and structure

  11. Glycoconjugate Vaccines: The Regulatory Framework.

    Science.gov (United States)

    Jones, Christopher

    2015-01-01

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

  12. Regulatory frameworks for decentralised energy

    International Nuclear Information System (INIS)

    Woodman, Bridget; Baker, Philip

    2008-01-01

    This paper considers aspects of the current regulatory frameworks for markets and infrastructure which can inhibit the deployment of decentralised energy. The government has stated that decentralised energy can make a positive contribution to reducing the UK's carbon emissions, but recognises that at the moment the technologies face market and regulatory barriers. If it is to become a viable alternative to centralised generation, energy market design and the regulation of energy infrastructure will have to evolve to ensure that decentralised options are no longer locked out. (author)

  13. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2014-01-01

    This section of the Bulletin presents a summary of the recent national legislative and regulatory activities sorted by country and topic: - Algeria: Nuclear security. - France: Radioactive waste management; Nuclear safety and radiological protection; General legislation; International co-operation. - Germany: International trade. - Indonesia: Nuclear security, General legislation. - Ireland: Nuclear safety and radiological protection; General legislation. - Lithuania: Nuclear security; Nuclear safety and radiological protection. - Slovak Republic: International co-operation; Liability and compensation; Environmental protection. - Switzerland: Radioactive waste management. - United Arab Emirates: Liability and compensation. - United States: Radioactive waste management; Licensing and regulatory infrastructure

  14. Criteria of exemption of regulatory control for radioactive material

    International Nuclear Information System (INIS)

    Marco A. Medrano Lopez

    1991-01-01

    Being based on the information contained in the 10 CFR Part 20, of the section 20.301 until the 20.306 where the mechanisms by means of which can prepare the waste of low level are indicated. While the Nuclear Regulatory Commission (NRC) it amended in the year of 1985 the Act of Politics on Low level Wastes, in particular the section 10 of the amendment of the Act, relative to the concept BRC treats those groups of radioactive waste in that their activity contents are so low that they could be exempt of the regulatory control, either liberating them toward the environment or to exempt people or organizations of the regulatory control

  15. Regulatory accessibility and social influences on state self-control.

    Science.gov (United States)

    vanDellen, Michelle R; Hoyle, Rick H

    2010-02-01

    The current work examined how social factors influence self-control. Current conceptions of state self-control treat it largely as a function of regulatory capacity. The authors propose that state self-control might also be influenced by social factors because of regulatory accessibility. Studies 1 through 4 provide evidence that individuals' state self-control is influenced by the trait and state self-control of salient others such that thinking of others with good trait or state self-control leads to increases in state self-control and thinking of others with bad trait or state self-control leads to decreases in state self-control. Study 5 provides evidence that the salience of significant others influences both regulatory accessibility and state self-control. Combined, these studies suggest that the effects of social influences on state self-control occur through multiple mechanisms.

  16. 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.

  17. 76 FR 20759 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-04-13

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate..., 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange.... For more information about the rulebook consolidation process, see Information Notice, March 12, 2008...

  18. 76 FR 40412 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-07-08

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate..., Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission... a more limited application by their terms. For more information about the rulebook consolidation...

  19. 75 FR 60157 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2010-09-29

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate..., 2010, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange... information about the rulebook consolidation process, see Information Notice, March 12, 2008 (Rulebook...

  20. 75 FR 71164 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2010-11-22

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate..., 2010, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange.... For more information about the rulebook consolidation process, see Information Notice, March 12, 2008...

  1. 76 FR 12380 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2011-03-07

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of Amendment No. 1..., the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange... information about the rulebook consolidation process, see Information Notice, March 12, 2008 (Rulebook...

  2. 76 FR 66344 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2011-10-26

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change... 31, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a National Association of... consolidation process, see Information Notice, March 12, 2008 (Rulebook Consolidation Process). For convenience...

  3. 75 FR 17456 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2010-04-06

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change..., Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission... terms. For more information about the rulebook consolidation process, see Information Notice, March 12...

  4. Regulatory Control of Radiation Sources. Safety Guide

    International Nuclear Information System (INIS)

    2009-01-01

    This Safety Guide is intended to assist States in implementing the requirements established in Safety Standards Series No. GS-R-1, Legal and Governmental Infrastructure for Nuclear, Radiation, Radioactive Waste and Transport Safety, for a national regulatory infrastructure to regulate any practice involving radiation sources in medicine, industry, research, agriculture and education. The Safety Guide provides advice on the legislative basis for establishing regulatory bodies, including the effective independence of the regulatory body. It also provides guidance on implementing the functions and activities of regulatory bodies: the development of regulations and guides on radiation safety; implementation of a system for notification and authorization; carrying out regulatory inspections; taking necessary enforcement actions; and investigating accidents and circumstances potentially giving rise to accidents. The various aspects relating to the regulatory control of consumer products are explained, including justification, optimization of exposure, safety assessment and authorization. Guidance is also provided on the organization and staffing of regulatory bodies. Contents: 1. Introduction; 2. Legal framework for a regulatory infrastructure; 3. Principal functions and activities of the regulatory body; 4. Regulatory control of the supply of consumer products; 5. Functions of the regulatory body shared with other governmental agencies; 6. Organization and staffing of the regulatory body; 7. Documentation of the functions and activities of the regulatory body; 8. Support services; 9. Quality management for the regulatory system.

  5. In silico discovery of transcription regulatory elements in Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Le Roch Karine G

    2008-02-01

    Full Text Available Abstract Background With the sequence of the Plasmodium falciparum genome and several global mRNA and protein life cycle expression profiling projects now completed, elucidating the underlying networks of transcriptional control important for the progression of the parasite life cycle is highly pertinent to the development of new anti-malarials. To date, relatively little is known regarding the specific mechanisms the parasite employs to regulate gene expression at the mRNA level, with studies of the P. falciparum genome sequence having revealed few cis-regulatory elements and associated transcription factors. Although it is possible the parasite may evoke mechanisms of transcriptional control drastically different from those used by other eukaryotic organisms, the extreme AT-rich nature of P. falciparum intergenic regions (~90% AT presents significant challenges to in silico cis-regulatory element discovery. Results We have developed an algorithm called Gene Enrichment Motif Searching (GEMS that uses a hypergeometric-based scoring function and a position-weight matrix optimization routine to identify with high-confidence regulatory elements in the nucleotide-biased and repeat sequence-rich P. falciparum genome. When applied to promoter regions of genes contained within 21 co-expression gene clusters generated from P. falciparum life cycle microarray data using the semi-supervised clustering algorithm Ontology-based Pattern Identification, GEMS identified 34 putative cis-regulatory elements associated with a variety of parasite processes including sexual development, cell invasion, antigenic variation and protein biosynthesis. Among these candidates were novel motifs, as well as many of the elements for which biological experimental evidence already exists in the Plasmodium literature. To provide evidence for the biological relevance of a cell invasion-related element predicted by GEMS, reporter gene and electrophoretic mobility shift assays

  6. RNA regulatory elements and polyadenylation in plants

    Directory of Open Access Journals (Sweden)

    Arthur G. Hunt

    2012-01-01

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

  7. Promoting and assessment of safety culture within regulatory body

    International Nuclear Information System (INIS)

    Awasthi, Sumit; Bhattacharya, D.; Koley, J.; Krishnamurthy, P.R.

    2015-01-01

    Regulators have an important role to play in assisting organizations under their jurisdiction to develop positive safety cultures. It is therefore essential for the regulator to have a robust safety culture as an inherent strategy and communication of this strategy to the organizations it supervises. Atomic Energy Regulatory Board (AERB) emphasizes every utility to institute a good safety culture during various stages of a NPP. The regulatory requirement for establishing organisational safety culture within utility at different stages are delineated in the various AERB safety codes which are presented in the paper. Although the review and assessment of the safety culture is a part of AERB’s continual safety supervision through existing review mechanism, AERB do not use any specific indicators for safety culture assessment. However, establishing and nurturing a good safety culture within AERB helps in encouraging the utility to institute the same. At the induction level AERB provides training to its staffs for regulatory orientation which include a specific course on safety culture. Subsequently, the junior staffs are mentored by seniors while involving them in various regulatory processes and putting them as observers during regulatory decision making process. Further, AERB established a formal procedure for assessing and improving safety culture within its staff as a management system process. The paper describes as a case study the above safety culture assessment process established within AERB

  8. Radiation practices and regulatory control

    International Nuclear Information System (INIS)

    1997-01-01

    The general principles to be observed in the regulatory control of ionizing radiation use and practices are specified in the guide. It also takes into account of additions and alterations needed for for compliance with the European Union (EU) directives that have not been mentioned in other STUK/ST-guides. (6 refs.)

  9. Management systems for regulatory authorities

    International Nuclear Information System (INIS)

    Mpandanyama, Rujeko Lynette

    2015-02-01

    For a regulatory body to fulfil its statutory obligations, there is need to develop and implement a regulatory management system that has the necessary arrangements for achieving and maintaining high quality performance in regulating the safety of nuclear and radiation facilities under its authority. Hence, the regulatory management system needs to fully integrate the human resources, processes and physical resources of the organization. This study sought to provide an understanding of the concept, principles, policies and fundamentals of management systems as they relate to regulatory systems in the field of radiation protection and to make appropriate recommendations to ensure that an effective management system exists for the control of ionizing radiation and radiation sources and addresses all relevant stakeholders in Zimbabwe. A comparative analysis was done on the current management status and the ideal management system, which led to the identification of the gaps existing. The main key that was found to be of significance was lack of linkages between processes and management tools within the institution. (au)

  10. Private Equity and Regulatory Capital

    NARCIS (Netherlands)

    Bongaerts, D.; Charlier, E.

    2008-01-01

    Regulatory Capital requirements for European banks have been put forward in the Basel II Capital Framework and subsequently in the Capital Requirements Directive (CRD) of the EU. We provide a detailed discussion of the capital requirements for private equity investments under the simple risk weight

  11. Radiation practices and regulatory control

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-06-01

    The general principles to be observed in the regulatory control of ionizing radiation use and practices are specified in the guide. It also takes into account of additions and alterations needed for for compliance with the European Union (EU) directives that have not been mentioned in other STUK/ST-guides. (6 refs.).

  12. Regulatory perspectives of concept assessment

    International Nuclear Information System (INIS)

    Flavelle, Peter A.

    1987-09-01

    The Atomic Energy Control Board is the head agency for the regulatory review of the Assessment of the Canadian Concept for Nuclear Fuel Waste Disposal being done by Atomic Energy of Canada Limited and Ontario Hydro. This paper describes the regulatory perspective of how the Concept Assessment could demonstrate the feasibility of a disposal conforming to regulatory requirements. The long-term aspects of Concept Assessment encourage the use of various predictive techniques for different time scales. Each technique will have a different potential for establishing confidence in the predictions. The predicted performance of a facility during operation should have a very high confidence, as it can be based on standard engineering calculations and the predictions can be validated later by monitoring during operation. The predictions of the transient period following closure of the facility should achieve a medium level of confidence, since they can be based on extrapolations of predictions of operational performance, using models that can be calibrated with monitoring data and with averaged input data derived from natural analog studies. Predictions based on fundamental processes will have a medium level of confidence when made to intermediate times after closure. Long-term predictions using generic or typical input data or Monte Carlo calculations of simplified models will have the least confidence and yet they can still contribute to the confidence that the disposal concept will conform to regulatory requirements

  13. NRC regulatory information conference: Proceedings

    International Nuclear Information System (INIS)

    1989-09-01

    This volume of the report provides the proceedings from the Nuclear Regulatory Commission (NRC) Regulatory Information Conference that was held at the Mayflower Hotel, Washington, DC, on April 18, 19, and 20, 1989. This conference was held by the NRC and chaired by Dr. Thomas E. Mosley, Director, Office of Nuclear Reactor Regulations (NRR) and coordinated by S. Singh Bajwa, Chief, Technical Assistance Management Section, NRR. There were approximately 550 participants from nine countries at the conference. The countries represented were Canada, England, Italy, Japan, Mexico, Spain, Taiwan, Yugoslavia, and the United States. The NRC staff discussed with nuclear industry its regulatory philosophy and approach and the bases on which they have been established. Furthermore, the NRC staff discussed several initiatives that have been implemented recently and their bases as well as NRC's expectations for new initiatives to further improve safety. The figures contained in Appendix A to the volume correspond to the slides that were shown during the presentations. Volume 2 of this report contains the formal papers that were distributed at the beginning of the Regulatory Information Conference and other information about the conference

  14. Regulatory mechanisms of skeletal muscle protein turnover during exercise

    DEFF Research Database (Denmark)

    Rose, Adam John; Richter, Erik

    2009-01-01

    Skeletal muscle protein turnover is a relatively slow metabolic process that is altered by various physiological stimuli such as feeding/fasting and exercise. During exercise, catabolism of amino acids contributes very little to ATP turnover in working muscle. With regards to protein turnover......, there is now consistent data from tracer studies in rodents and humans showing that global protein synthesis is blunted in working skeletal muscle. Whether there is altered skeletal muscle protein breakdown during exercise remains unclear. The blunting of protein synthesis is believed to be mediated...... downstream of changes in intracellular Ca(2+) and energy turnover. In particular, a signaling cascade involving Ca(2+)-calmodulin-eEF2 kinase-eEF2 is implicated. The possible functional significance of altered protein turnover in working skeletal muscle during exercise is discussed. Further work...

  15. Regulatory mechanisms of viral hepatitis B and C

    Indian Academy of Sciences (India)

    Abstract. Of all the hepatitis viruses, only the hepatitis B virus (HBV) and hepatitis C virus (HCV) cause chronic hepatitis, which can progress to cirrhosis and hepatocellular carcinoma. In this review, we discuss how these two biologically diverse viruses use common pathways to induce oxidative stress and activation of key ...

  16. Regulatory mechanisms of viral hepatitis B and C

    Indian Academy of Sciences (India)

    Unknown

    of simple, overall patterns rather than in the analysis of patchworks”. Luria's Credo .... (B) Protein binding sites on the enahncer 1 element are shown and footprint designations are .... The in vitro interaction of HBx with components of transcriptional ... principal organelle in which ROS are generated in res- ponse to stress ...

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

    Energy Technology Data Exchange (ETDEWEB)

    Steven C. Huber

    2009-05-12

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

  18. Regulatory mechanisms for underground waste disposal in Nigeria ...

    African Journals Online (AJOL)

    Michael Horsfall

    Environmental Pollution Control in Nigeria, National Guidelines on Waste Disposal through Underground ... dead, domestic waste and, excrement in this manner. The soil and geological formations that are the waste ... waste water daily is presently seeking partnerships with the ... role in ground water quality protection from.

  19. Regulatory mechanisms of viral hepatitis B and C

    Indian Academy of Sciences (India)

    Unknown

    NS5A, nonstructural protein 5A; PDTC, pyrrolidine dithiocarbamate; PKR, double stranded RNA-dependent protein kinase; ROS, reactive oxygen ... unifying and simplifying generalization, rather than in the description of isolated situation-in the visualization of simple ... of work has focused on liver-specific aspects of HBV.

  20. Evidence of salicylic acid regulatory mechanisms of disease ...

    African Journals Online (AJOL)

    SAM

    2014-07-23

    Jul 23, 2014 ... disease resistance against banana vascular wilt. Fusarium oxysporium f.sp. ... prominent in that Central American country early last century. Cavendish ... Foc is thought to have originated in Asia, and then spread during the ...

  1. Evidence of salicylic acid regulatory mechanisms of disease ...

    African Journals Online (AJOL)

    Foc) interaction has led to the identification of signaling pathways required for plant resistance to Foc, as well as key regulators of innate immunity against this type of vascular wilt pathogens. From the in planta symptom expressions of Foc on ...

  2. Uncovering transcription factor and microRNA risk regulatory pathways associated with osteoarthritis by network analysis.

    Science.gov (United States)

    Song, Zhenhua; Zhang, Chi; He, Lingxiao; Sui, Yanfang; Lin, Xiafei; Pan, Jingjing

    2018-05-01

    Osteoarthritis (OA) is the most common form of joint disease. The development of inflammation have been considered to play a key role during the progression of OA. Regulatory pathways are known to play crucial roles in many pathogenic processes. Thus, deciphering these risk regulatory pathways is critical for elucidating the mechanisms underlying OA. We constructed an OA-specific regulatory network by integrating comprehensive curated transcription and post-transcriptional resource involving transcription factor (TF) and microRNA (miRNA). To deepen our understanding of underlying molecular mechanisms of OA, we developed an integrated systems approach to identify OA-specific risk regulatory pathways. In this study, we identified 89 significantly differentially expressed genes between normal and inflamed areas of OA patients. We found the OA-specific regulatory network was a standard scale-free network with small-world properties. It significant enriched many immune response-related functions including leukocyte differentiation, myeloid differentiation and T cell activation. Finally, 141 risk regulatory pathways were identified based on OA-specific regulatory network, which contains some known regulator of OA. The risk regulatory pathways may provide clues for the etiology of OA and be a potential resource for the discovery of novel OA-associated disease genes. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. 77 FR 52791 - Regulatory Capital Rules: Regulatory Capital, Implementation of Basel III, Minimum Regulatory...

    Science.gov (United States)

    2012-08-30

    ... the Basel Committee on Banking Supervision (BCBS) in ``Basel III: A Global Regulatory Framework for... seeking comment on the two related NPRs published elsewhere in today's Federal Register. The two related... them on Regulations.gov without change, including any business or personal information that you provide...

  4. Association of Regulatory Boards of Optometry

    Science.gov (United States)

    ... website of the Association of Regulatory Boards of Optometry (ARBO). ARBO's web site is designed to provide resources to regulatory boards of optometry throughout the world. State/Provincial/Territorial Boards of ...

  5. Small Business Administration Semiannual Regulatory Agenda

    Science.gov (United States)

    2010-12-20

    ... small business concerns owned and controlled by women, and to women wishing to start a small business... Business Administration Semiannual Regulatory Agenda] Part XVII Small Business Administration Semiannual Regulatory Agenda [[Page 79864

  6. The Political Economy of Regulatory Risk

    OpenAIRE

    Strausz, Roland

    2009-01-01

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

  7. Nuclear Regulatory Commission 1989 Information Digest

    International Nuclear Information System (INIS)

    1989-03-01

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

  8. Regulatory point of view of SAT application

    International Nuclear Information System (INIS)

    Juhasz, L.

    2002-01-01

    I present the regulatory system for monitoring operator training and check competency of operator personnel in Hungary and the effects of SAT to the regulatory framework/practice related to recruitment, training and authorisation of operating personnel. Also I introduce an application to manage the initial and refreshing training to regulatory bodies. (author)

  9. 40 CFR 92.6 - Regulatory structure.

    Science.gov (United States)

    2010-07-01

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

  10. 40 CFR 94.6 - Regulatory structure.

    Science.gov (United States)

    2010-07-01

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

  11. 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...

  12. 75 FR 21686 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2010-04-26

    ... to pay arbitration awards to remain in the securities industry presents regulatory risks and is...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of Proposed Rule... Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``SEC'' or...

  13. 76 FR 21932 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting...

    Science.gov (United States)

    2011-04-19

    ... statement therein, as follows: I. Introduction On February 4, 2011, the Financial Industry Regulatory...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Granting Approval of a... Financial Industry Regulatory Authority, Inc. (``FINRA'') to amend Rule 13806 of the Code of Arbitration...

  14. 75 FR 63878 - Self-Regulatory Organizations; Self-Regulatory Organizations; Notice of Filing and Immediate...

    Science.gov (United States)

    2010-10-18

    ...-Regulatory Organizations; Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of...(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of Substance... Public Reference Room. II. Self-Regulatory Organization's Statement of the Purpose of, and Statutory...

  15. Regulatory aspects of NPP safety

    International Nuclear Information System (INIS)

    Kastchiev, G.

    1999-01-01

    Extensive review of the NPP Safety is presented including tasks of Ministry of Health, Ministry of Internal Affairs, Ministry of Environment and Waters, Ministry of Defense in the field of national system for monitoring the nuclear power. In the frame of national nuclear safety legislation Bulgaria is in the process of approximation of the national legislation to that of EC. Detailed analysis of the status of regulatory body, its functions, organisation structure, responsibilities and future tasks is included. Basis for establishing the system of regulatory inspections and safety enforcement as well as intensification of inspections is described. Assessment of safety modifications is concerned with complex program for reconstruction of Units 1-4 of Kozloduy NPP, as well as for modernisation of Units 5 and 6. Qualification and licensing of the NPP personnel, Year 2000 problem, priorities and the need of international assistance are mentioned

  16. Regulatory aspects of mixed waste

    International Nuclear Information System (INIS)

    Boyle, R.R.; Orlando, D.A.

    1990-01-01

    Mixed waste is waste that satisfies the definition of low-level radioactive waste in the Low-Level Radioactive Waste Policy Amendments Act of 1985 (LLRWPAA) and contains hazardous waste that is either: (1) listed as a hazardous waste in 40 CFR 261, Subpart D; or (2) causes the waste to exhibit any of the characteristics identified in 40 CFR 261, Subpart C. Low-level radioactive waste is defined in the LLRWPAA as radioactive material that is not high level waste, spent nuclear fuel, or byproduct material, as defined in Section 11e(2) of the Atomic Energy Act of 1954, and is classified as low-level waste by the U.S. Nuclear Regulatory Commission (NRC). This paper discusses dual regulatory (NRC and Environmental Protection Agency) responsibility, overview of joint NRC/EPA guidance, workshops, national mixed waste survey, and principal mixed waste uncertainties

  17. Compliance. Regulatory policy P-211

    International Nuclear Information System (INIS)

    2001-05-01

    This regulatory policy describes the basic principles and directives for establishing and conducting the Canadian Nuclear Safety Commission (CNSC) Compliance Program. The program is aimed at securing compliance by regulated persons with regulatory requirements made under the Nuclear Safety and Control Act ('the Act'). The policy applies to persons who are regulated by the CNSC through the Act, regulations and licences, as well as by decisions and orders made under the Act. The policy applies to officers and employees of the CNSC, and its authorized representatives or agents, who are involved in developing and carrying out compliance activities. Compliance, in the context of this policy, means conformity by regulated persons with the legally binding requirements of the Act, and the CNSC regulations, licences, decisions, and orders made under the Act. Compliance activities are CNSC measures of promotion, verification and enforcement aimed at securing compliance by regulated person with the applicable legally binding requirements. (author)

  18. Cis-regulatory RNA elements that regulate specialized ribosome activity.

    Science.gov (United States)

    Xue, Shifeng; Barna, Maria

    2015-01-01

    Recent evidence has shown that the ribosome itself can play a highly regulatory role in the specialized translation of specific subpools of mRNAs, in particular at the level of ribosomal proteins (RP). However, the mechanism(s) by which this selection takes place has remained poorly understood. In our recent study, we discovered a combination of unique RNA elements in the 5'UTRs of mRNAs that allows for such control by the ribosome. These mRNAs contain a Translation Inhibitory Element (TIE) that inhibits general cap-dependent translation, and an Internal Ribosome Entry Site (IRES) that relies on a specific RP for activation. The unique combination of an inhibitor of general translation and an activator of specialized translation is key to ribosome-mediated control of gene expression. Here we discuss how these RNA regulatory elements provide a new level of control to protein expression and their implications for gene expression, organismal development and evolution.

  19. Regulatory aspects of emergency planning

    International Nuclear Information System (INIS)

    Jamgochian, M.T.

    1986-01-01

    The paper discusses the advances that have been made in the USA in the field of emergency planning over the past several years and considers regulatory changes that may be on the horizon. The paper examines the importance of severe accident source terms and their relationship to emergency preparedness, recent research results of work on source terms, and the experience gained from evaluation of licensee performance during annual emergency preparedness exercises. (author)

  20. Regulatory Office for Network Industries

    International Nuclear Information System (INIS)

    2005-01-01

    The main goal of the economic regulation of network industries is to ensure a balance between the interests of consumers and investors and to encourage providing high-quality goods and services. The task of the regulatory authority is to protect the interests of consumers against monopolistic behaviour of regulated enterprises. At the same time, the regulatory office has to protect the interests of investors by giving them an opportunity to achieve an adequate return on their investments. And last, but not least, the regulatory office has to provide regulated enterprises with appropriate incentives to make them function in an efficient and effective manner and to guarantee the security of delivery of energies and related services. All this creates an efficient regulatory framework that is capable of attracting the required amount and type of investments. This also means providing third party access to the grids, the opening of energy markets, the un-bundling of accounts according to production, distribution, transmission and other activities and the establishment of a transparent and stable legislative environment for regulated companies, investors and consumers. Otherwise, in the long run consumers may suffer from a serious deterioration of service quality, although in the short run they are protected against increased prices. Under the Act No. 276/2001 Coll. on Regulation of Network Industries and on amendment of some acts the Office for Regulation of Network Industries has been commissioned to implement the main objectives of regulation of network industries. By network industries the Act No. 276/2001 Coll. on Regulation means the following areas: (a) Production, purchase, transit and distribution of electricity; (b) Production, purchase, transit and distribution of gas; (c) Production, purchase and distribution of heat; (d) Water management activities relating to the operation of the public water supply system or the public sewerage system; (e) Water management

  1. The conduct of regulatory activities

    International Nuclear Information System (INIS)

    Wright, H.A.

    1975-01-01

    The main emphasis is placed on the legal responsibility of the utility in UK to build and operate its plant to avoid any nuclear hazard. The regulatory practices have endeavoured to inculcate a proper emphasis towards safety by the people who comprise the management of the utility, and to avoid any erosion of their legal responsibility as the best and possibly only practical means to achieve adequate safety standards. (orig./HP) [de

  2. Regulatory control, legislation and framework

    International Nuclear Information System (INIS)

    Parthasarathy, K.S.

    1998-01-01

    The legislation and regulations, a regulatory authority to authorise and inspect the regulated activities and to enforce the legislation and regulations, sufficient financial and man-power resources are the essential parts of a national infrastructure to implement the Basic Safety Standards. The legal framework consists of legislation (Act passed by Parliament) and the regulations (framed by the government and endorsed by the Parliament). This paper is primarily deals with the the legal framework set up in India for atomic energy activities

  3. Regulatory change and monetary policy

    OpenAIRE

    Bank for International Settlements

    2015-01-01

    Report submitted by a Working Group established by the Committee on the Global Financial System and the Markets Committee. The Group was chaired by Ulrich Bindseil (European Central Bank) and William R Nelson (Federal Reserve Board). Financial regulation is evolving, as policymakers seek to strengthen the financial system in order to make it more robust and resilient. Changes in the regulatory environment are likely to have an impact on financial system structure and on the behaviour of finan...

  4. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2009-01-01

    This part gathers the national legislative and regulatory activities. The subjects tackled are as follow: radiological protection (Belgium), transport of radioactive materials (Belgium, France), general legislation (Brazil, Ireland, Republic of Moldova, Serbia, Turkey), third part liability (Japan), radioactive waste management (Korea, Romania, Slovenia, Usa), regime of radioactive materials (Romania), organisation and structure (Switzerland), regime of nuclear installations (Usa), regulations on nuclear trade (Usa). (N.C)

  5. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2015-01-01

    This section treats of the following National legislative and regulatory activities: 1 - Canada: Liability and compensation; 2 - France: Liability and compensation; Nuclear safety and radiological protection; 3 - Greece: Organisation and structure; 4 - Hungary: General legislation; 5 - India: Liability and compensation; 6 - Japan: Liability and compensation; 7 - Korea: Liability and compensation; 8 - Lithuania: General legislation; Transport of radioactive material; 9 - Slovak Republic: International co-operation; Liability and compensation; 10 - Slovenia: General legislation; 11 - Switzerland: Liability and compensation; 12 - United States: Radioactive waste management

  6. Principles of good regulatory research

    International Nuclear Information System (INIS)

    Rogers, K.

    1991-01-01

    The Commissioner of the US Regulatory Commission addresses several important research-related subjects. The paper describes the Agency philosophy with respect to independence, openness, efficiency, clarity, and reliability; research philosophy with respect to the need for research, the need for quality, and the need for efficiency; research areas with respect to plant aging, human factors, severe accident analysis, advanced reactors, and radioactive waste management; and systems approach to reactor operations, training, licensing, and maintenance

  7. Regulatory Myeloid Cells in Transplantation

    Science.gov (United States)

    Rosborough, Brian R.; Raïch-Regué, Dàlia; Turnquist, Heth R.; Thomson, Angus W.

    2013-01-01

    Regulatory myeloid cells (RMC) are emerging as novel targets for immunosuppressive (IS) agents and hold considerable promise as cellular therapeutic agents. Herein, we discuss the ability of regulatory macrophages (Mreg), regulatory dendritic cells (DCreg) and myeloid-derived suppressor cells (MDSC) to regulate alloimmunity, their potential as cellular therapeutic agents and the IS agents that target their function. We consider protocols for the generation of RMC and the selection of donor- or recipient-derived cells for adoptive cell therapy. Additionally, the issues of cell trafficking and antigen (Ag) specificity following RMC transfer are discussed. Improved understanding of the immunobiology of these cells has increased the possibility of moving RMC into the clinic to reduce the burden of current IS agents and promote Ag-specific tolerance. In the second half of this review, we discuss the influence of established and experimental IS agents on myeloid cell populations. IS agents believed historically to act primarily on T cell activation and proliferation are emerging as important regulators of RMC function. Better insights into the influence of IS agents on RMC will enhance our ability to develop cell therapy protocols to promote the function of these cells. Moreover, novel IS agents may be designed to target RMC in situ to promote Ag-specific immune regulation in transplantation and usher in a new era of immune modulation exploiting cells of myeloid origin. PMID:24092382

  8. Regulatory difficulties in a developing country

    International Nuclear Information System (INIS)

    Jacobs, W.R. Jr.

    1978-01-01

    The regulatory agency assigned the task of regulating the initial entry into the field of nuclear power generation by a developing country has a very difficult job. Based on the authors' experience during the start-up and initial operation of Ko-Ri Unit I, the first power reactor in the Republic of Korea, observations on regulatory difficulties and recommendations for improved regulatory effectiveness are offered. The problem areas can be loosely grouped into three general categories: (1) Lack of adequate technical knowledge which is the basis for all effective regulation; (2) Difficulties with understanding and utilization of the required regulatory documentation; (3) Failure to establish the proper regulatory environment. Examples are cited from actual experience during the Ko-Ri Unit I start-up to demonstrate the impact that regulatory activities can have on a plant construction and testing programme. The problems encountered are not unique to developing countries but also exist in the United States of America. Recommendations are offered which should be beneficial to either newly formed regulatory agencies or agencies wishing to improve their abilities and effectiveness. These include: (1) Additional training of regulatory inspectors in plant operations; (2) Additional experience gained by participation in regulatory activities in other countries; (3) Increased attention given to regulatory documents, especially plant technical specifications; (4) Establishment of formal lines of communication between the utility and the regulatory agency; (5) Clear definition of regulatory responsibilities to avoid areas of overlapping jurisdiction; (6) Active participation by the regulatory staff very early in the project. It is hoped that these and other recommendations offered will greatly improve regulatory effectiveness and at the same time demonstrate that when the decision is made to 'go nuclear', a strong commitment must be made to develop and support a technically

  9. Mechanism of artificial heart

    CERN Document Server

    Yamane, Takashi

    2016-01-01

    This book first describes medical devices in relation to regenerative medicine before turning to a more specific topic: artificial heart technologies. Not only the pump mechanisms but also the bearing, motor mechanisms, and materials are described, including expert information. Design methods are described to enhance hemocompatibility: main concerns are reduction of blood cell damage and protein break, as well as prevention of blood clotting. Regulatory science from R&D to clinical trials is also discussed to verify the safety and efficacy of the devices.

  10. Adaptation of Regulatory Systems in Schoolchildren, Residing in Industrial Area

    Directory of Open Access Journals (Sweden)

    Aiman E. Konkabaeva

    2013-01-01

    Full Text Available The article presents the results of the study of heart rate variability (HRT in apparently healthy volunteers of both sexes without bad habits, aged 16-18, residing in industrial region (Temirtau and the ones, studying under innovative technologies. HRT was registered with the help of computer-controlled devices “Varikard” (Russia. The changes of HRT spectral indexes towards integral impact of vegetative regulation mechanisms and parasympathetic activity decrease and regulatory systems overexertion, demanding correction methods implementation

  11. Regulatory Oversight Program, July 1, 1993--March 3, 1997. Volume 3

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-12-31

    On July, 1993, a Regulatory Oversight (RO) organization was established within the US DOE, Oak Ridge Operations (ORO) to provide regulatory oversight of the DOE uranium enrichment facilities leased to the United States Enrichment Corporation (USEC). The purpose of the OR program was to ensure continued plant safety, safeguards and security while the plants were transitioned to regulatory oversight by the Nuclear Regulatory Commission (NRC). Volume 3 contains copies of two reports that document the DOE/ORO regulatory oversight inspection and enforcement history for each gaseous diffusion plant site. Each report provides a formal mechanism by which DOE/ORO could communicate the inspection and enforcement history to NRC. The reports encompass the inspection activities that occurred during July 1, 1993 through March 2, 1997.

  12. 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.

  13. Risk-based Regulatory Evaluation Program methodology

    International Nuclear Information System (INIS)

    DuCharme, A.R.; Sanders, G.A.; Carlson, D.D.; Asselin, S.V.

    1987-01-01

    The objectives of this DOE-supported Regulatory Evaluation Progrwam are to analyze and evaluate the safety importance and economic significance of existing regulatory guidance in order to assist in the improvement of the regulatory process for current generation and future design reactors. A risk-based cost-benefit methodology was developed to evaluate the safety benefit and cost of specific regulations or Standard Review Plan sections. Risk-based methods can be used in lieu of or in combination with deterministic methods in developing regulatory requirements and reaching regulatory decisions

  14. Regulatory pathways for vaccines for developing countries.

    Science.gov (United States)

    Milstien, Julie; Belgharbi, Lahouari

    2004-01-01

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

  15. Organization of nuclear regulatory activities

    International Nuclear Information System (INIS)

    Blidaru, Valentin

    2008-01-01

    The paper presents the structure, missions and organizational aspects of the CNCAN, the National Commission for the control of nuclear activities in Romania. The paper addresses the following main issues: 1.General aspects; 2.Organizational structure of the NRA in Romania; 3.General description of the Division for Nuclear Safety Assessments; 4.Specific activities; 5.Regulatory approaches and practices. Under the title of 'General aspects' the following three basic statements are highlighted: 1.CNCAN is a governmental organization responsible for the development of the regulatory framework, the control of its implementation and the licensing of nuclear facilities; 2.CNCAN is the national authority competent in exercising the regulatory activity, authorization and control in the nuclear field provided by the law No. 111/ 1996 republished in 1998; 3.The Commission exercises its functions independently of the ministries and other authorities of the public control administration being subordinated to the Romanian Government. The organizational structure is as follows: - President, the Managerial Council and the Advisory Council coordinating the four General Divisions that are responsible for: - Nuclear Safety with Division of Nuclear Safety Assessment and Division of Nuclear Objectives Surveillance; - Radiological Safety with Division of Radiological Safety Assessment and Division of Operational Radiation Protection; - Surveillance of Environmental Radioactivity with Division of Assessment and Analysis and Division of National Network; - Development and Resource with the Division of Economy and Division of Human Resources. In addition under direct coordination of the President operate the Division of Radiation Protection, Transport and Radioactive Waste and the Division of International Cooperation and Communication. Specific activities are listed describing among others the issues of: - Safety of nuclear installation; - Evaluation relating to licensing of nuclear

  16. A global regulatory science agenda for vaccines.

    Science.gov (United States)

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

    2013-04-18

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

  17. 77 FR 25770 - Self-Regulatory Organizations; NYSE Amex LLC; Notice of Filing of Proposed Rule Change Amending...

    Science.gov (United States)

    2012-05-01

    ... settings via Regulatory Bulletin. The Mechanism protects Market Makers from the risk associated with an...-Regulatory Organizations; NYSE Amex LLC; Notice of Filing of Proposed Rule Change Amending NYSE Amex Options Rule 928NY Specifying That the Potential Range for the Settings Applicable to the Market Maker Risk...

  18. 77 FR 45401 - Self-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of a...

    Science.gov (United States)

    2012-07-31

    ... change. All such Regulatory Bulletins will contain information regarding changes to the risk settings in...-Regulatory Organizations; NYSE Arca, Inc.; Notice of Filing and Immediate Effectiveness of a Proposed Rule... Applicable to the Market Maker Risk Limitation Mechanism Will Be Between One and 100 Executions per Second...

  19. Regulatory RNAs in Bacillus subtilis : a Gram-Positive Perspective on Bacterial RNA-Mediated Regulation of Gene Expression

    NARCIS (Netherlands)

    Mars, Ruben A. T.; Nicolas, Pierre; Denham, Emma L.; van Dijl, Jan Maarten

    2016-01-01

    Bacteria can employ widely diverse RNA molecules to regulate their gene expression. Such molecules include trans-acting small regulatory RNAs, antisense RNAs, and a variety of transcriptional attenuation mechanisms in the 5= untranslated region. Thus far, most regulatory RNA research has focused on

  20. 75 FR 79049 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2010-12-17

    ... site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . The regulatory... NUCLEAR REGULATORY COMMISSION [NRC-2008-0427] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 3.12...

  1. 75 FR 45173 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2010-08-02

    ... ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . In addition, regulatory guides are... NUCLEAR REGULATORY COMMISSION [NRC-2008-0638] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.151...

  2. 76 FR 18262 - Notice of issuance of Regulatory Guide

    Science.gov (United States)

    2011-04-01

    ... site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . The regulatory... NUCLEAR REGULATORY COMMISSION [NRC-2009-0277] Notice of issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.44...

  3. 76 FR 14107 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2011-03-15

    ... site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . The regulatory... NUCLEAR REGULATORY COMMISSION [NRC-2009-0276] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.43...

  4. 76 FR 14108 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2011-03-15

    ... site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . The regulatory... NUCLEAR REGULATORY COMMISSION [NRC-2009-0275] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.50...

  5. Regulatory brain development: balancing emotion and cognition.

    Science.gov (United States)

    Perlman, Susan B; Pelphrey, Kevin A

    2010-01-01

    Emotion regulation is a critical aspect of children's social development, yet few studies have examined the brain mechanisms involved in its development. Theoretical accounts have conceptualized emotion regulation as relying on prefrontal control of limbic regions, specifying the anterior cingulate cortex (ACC) as a key brain region. Functional magnetic resonance imaging in 5- to 11-year-olds during emotion regulation and processing of emotionally expressive faces revealed that older children preferentially recruited the more dorsal “cognitive” areas of the ACC, while younger children preferentially engaged the more ventral “emotional” areas. Additionally, children with more fearful temperaments exhibited more ventral ACC activity while less fearful children exhibited increased activity in the dorsal ACC. These findings provide insight into a potential neurobiological mechanism underlying well-documented behavioral and cognitive changes from more emotional to more cognitive regulatory strategies with increasing age, as well as individual differences in this developmental process as a function of temperament. Our results hold important implications for our understanding of normal development and should also help to inform our understanding and management of emotional disorders. © 2010 Psychology Press

  6. Radiation and the regulatory landscape of neo{sup 2}-Darwinism

    Energy Technology Data Exchange (ETDEWEB)

    Rollo, C. David [Department of Biology, Life Sciences Building, 1280 Main St. West, Hamilton, Ont., Canada L8S 4K1 (Canada)]. E-mail: rollocd@mcmaster.ca

    2006-05-11

    Several recently revealed features of eukaryotic genomes were not predicted by earlier evolutionary paradigms, including the relatively small number of genes, the very large amounts of non-functional code and its quarantine in heterochromatin, the remarkable conservation of many functionally important genes across relatively enormous phylogenetic distances, and the prevalence of extra-genomic information associated with chromatin structure and histone proteins. All of these emphasize a paramount role for regulatory evolution, which is further reinforced by recent perspectives highlighting even higher-order regulation governing epigenetics and development (EVO-DEVO). Modern neo{sup 2}-Darwinism, with its emphasis on regulatory mechanisms and regulatory evolution provides new vision for understanding radiation biology, particularly because free radicals and redox states are central to many regulatory mechanisms and free radicals generated by radiation mimic and amplify endogenous signalling. This paper explores some of these aspects and their implications for low-dose radiation biology.

  7. Hijacking Complement Regulatory Proteins for Bacterial Immune Evasion.

    Science.gov (United States)

    Hovingh, Elise S; van den Broek, Bryan; Jongerius, Ilse

    2016-01-01

    The human complement system plays an important role in the defense against invading pathogens, inflammation and homeostasis. Invading microbes, such as bacteria, directly activate the complement system resulting in the formation of chemoattractants and in effective labeling of the bacteria for phagocytosis. In addition, formation of the membrane attack complex is responsible for direct killing of Gram-negative bacteria. In turn, bacteria have evolved several ways to evade complement activation on their surface in order to be able to colonize and invade the human host. One important mechanism of bacterial escape is attraction of complement regulatory proteins to the microbial surface. These molecules are present in the human body for tight regulation of the complement system to prevent damage to host self-surfaces. Therefore, recruitment of complement regulatory proteins to the bacterial surface results in decreased complement activation on the microbial surface which favors bacterial survival. This review will discuss recent advances in understanding the binding of complement regulatory proteins to the bacterial surface at the molecular level. This includes, new insights that have become available concerning specific conserved motives on complement regulatory proteins that are favorable for microbial binding. Finally, complement evasion molecules are of high importance for vaccine development due to their dominant role in bacterial survival, high immunogenicity and homology as well as their presence on the bacterial surface. Here, the use of complement evasion molecules for vaccine development will be discussed.

  8. Regulatory dendritic cell therapy: from rodents to clinical application.

    Science.gov (United States)

    Raïch-Regué, Dalia; Glancy, Megan; Thomson, Angus W

    2014-10-01

    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 rejection. There is also evidence that adoptive transfer of DCreg can regulate T cell responses in non-human primates and humans. Important insights gained from in vitro studies and animal models have led recently to the development of clinical grade human DCreg, with potential to treat autoimmune disease or enhance transplant survival while reducing patient dependency on immunosuppressive drugs. Phase I trials have been conducted in type-1 diabetes and rheumatoid arthritis, with results that emphasize the feasibility and safety of DCreg therapy. This mini-review will outline how observations made using animal models have been translated into human use, and discuss the challenges faced in further developing this form of regulatory immune cell therapy in the fields of autoimmunity and transplantation. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Regulation of Telecommunications: The Choice Between Market and Regulatory Failures

    Directory of Open Access Journals (Sweden)

    Dmitrii Trubnikov

    2017-04-01

    Full Text Available Purpose – The paper examines the main regulatory frameworks of the telecommunications industry through the concept of market failure and analyses how and why the policy often leads to undesirable outcomes that might be considered as regulatory failure. Methodology/approach/design – The research uses the EU regulatory framework for electronic communications as a base for the analysis of the main policy objectives through the prism of the market failure theory with an eye to the interests of the main market players in the telecommunications markets. Findings – About any aspect of regulation allows to find ways to create opportunities for some groups of the industry and stifle activity of others. Despite the theory of market failure provides reasonable justifications for regulation of telecommunications markets, it is possible to argue that many of these problems are mainly the consequence of the policy and could be better solved by market mechanisms. Originality/value – The results of the research allow to look at the problems of telecommunications development and issues of the high level of concentration of the telecommunications markets as regulatory formed problems rather than consequences of the inherited industry’s characteristics.

  10. [CD4 + CD25 + regulatory T cells and their importance to human illnesses].

    Science.gov (United States)

    Kelsen, Jens; Hvas, Christian Lodberg; Agnholt, Jørgen; Dahlerup, Jens F

    2006-01-03

    Regulatory T cells ensure a balanced immune response that is competent both to fight pathogens, at the same time, to recognize self-antigens and commensals as harmless. Regulatory mechanisms are essential in preventing autoimmune disorders but may also facilitate the progression of malignant diseases and the establishment of latent infections via suppression of the host immune response. Regulatory T cells arise in the thymus, and regulatory T cell function can be induced in the periphery, so-called infectious tolerance. An absolute or relative defect in regulatory T cell function may contribute to the development of autoimmune disorders such as rheumatoid arthritis, type 1 diabetes mellitus, multiple sclerosis and chronic inflammatory bowel disease. Regulatory T cell therapy is a tempting strategy for reestablishing the immune balance and thus preventing or reversing these disorders. Reestablishment of the immune balance may be accomplished by adoptive transfer of ex vivo-propagated regulatory T cells or by induction of regulatory functions locally in the organs, although such strategies are in their infancy in human research.

  11. Regulatory Considerations for Gene Therapy Products in the US, EU, and Japan.

    Science.gov (United States)

    Halioua-Haubold, Celine-Lea; Peyer, James G; Smith, James A; Arshad, Zeeshaan; Scholz, Matthew; Brindley, David A; MacLaren, Robert E

    2017-12-01

    Developers of gene therapy products (GTPs) must adhere to additional regulation beyond that of traditional small-molecule therapeutics, due to the unique mechanism-of-action of GTPs and the subsequent novel risks arisen. We have provided herein a summary of the regulatory structure under which GTPs fall in the United States, the European Union, and Japan, and a comprehensive overview of the regulatory guidance applicable to the developer of GTP. Understanding the regulatory requirements for seeking GTP market approval in these major jurisdictions is crucial for an effective and expedient path to market. The novel challenges facing GTP developers is highlighted by a case study of alipogene tiparvovec (Glybera).

  12. Wetlands: The changing regulatory landscape

    International Nuclear Information System (INIS)

    Glick, R.M.

    1993-01-01

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

  13. Regulatory aspects of NPP safety

    International Nuclear Information System (INIS)

    Stuller, J.; Brandejs, P.; Miasnikov, A.; Svab, M.

    1999-01-01

    In beginning, a history of legislative process regulating industrial utilisation of nuclear energy is given, including detailed list of decrees issued by the first regulatory body supervising Czech nuclear installations - Czechoslovak Atomic Energy Commission (CSKAE). Current status of nuclear regulations and radiation protection, especially in connection with Atomic Act (Act No 18/1997 Coll.), is described. The Atomic Act transfers into the Czech legal system a number of obligations following from the Vienna Convention on Civil Liability for Nuclear Damage and Joint Protocol relating to the Application of the Vienna and Paris Convention, to which the Czech Republic had acceded. Actual duties and competence of current nuclear regulatory body - State Office for Nuclear Safety (SUJB) - are given in detail. Execution of the State supervision of peaceful utilisation of nuclear energy and ionising radiation is laid out in several articles of the Act, which comprises: control activities of the SUJB, remedial measures, penalties. Material and human resources are sufficient for fulfilment of the basic functions for which SUJB is authorised by the law. For 1998, the SUJB allotted staff of 149, approximately 2/3 of that number are nuclear safety and radiation protection inspectors. The SUJB budget for 1998 is approximately 180 million Czech crowns (roughly 6 million US dollars). Inspection activity of SUJB is carried out in three different ways: routine inspections, planned specialised inspections, inspections as a response to a certain situation (ad-hoc inspections). Approach to the licensing of major plant upgrades and backfittings are mainly illustrated on the Temelin NPP licensing. Regulatory position and practices concerning review activities are presented. (author)

  14. Defining Tobacco Regulatory Science Competencies.

    Science.gov (United States)

    Wipfli, Heather L; Berman, Micah; Hanson, Kacey; Kelder, Steven; Solis, Amy; Villanti, Andrea C; Ribeiro, Carla M P; Meissner, Helen I; Anderson, Roger

    2017-02-01

    In 2013, the National Institutes of Health and the Food and Drug Administration funded a network of 14 Tobacco Centers of Regulatory Science (TCORS) with a mission that included research and training. A cross-TCORS Panel was established to define tobacco regulatory science (TRS) competencies to help harmonize and guide their emerging educational programs. The purpose of this paper is to describe the Panel's work to develop core TRS domains and competencies. The Panel developed the list of domains and competencies using a semistructured Delphi method divided into four phases occurring between November 2013 and August 2015. The final proposed list included a total of 51 competencies across six core domains and 28 competencies across five specialized domains. There is a need for continued discussion to establish the utility of the proposed set of competencies for emerging TRS curricula and to identify the best strategies for incorporating these competencies into TRS training programs. Given the field's broad multidisciplinary nature, further experience is needed to refine the core domains that should be covered in TRS training programs versus knowledge obtained in more specialized programs. Regulatory science to inform the regulation of tobacco products is an emerging field. The paper provides an initial list of core and specialized domains and competencies to be used in developing curricula for new and emerging training programs aimed at preparing a new cohort of scientists to conduct critical TRS research. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Probabilistic safety assessment - regulatory perspective

    International Nuclear Information System (INIS)

    Solanki, R.B.; Paul, U.K.; Hajra, P.; Agarwal, S.K.

    2002-01-01

    Full text: Nuclear power plants (NPPs) have been designed, constructed and operated mainly based on deterministic safety analysis philosophy. In this approach, a substantial amount of safety margin is incorporated in the design and operational requirements. Additional margin is incorporated by applying the highest quality engineering codes, standards and practices, and the concept of defence-in-depth in design and operating procedures, by including conservative assumptions and acceptance criteria in plant response analysis of postulated initiating events (PIEs). However, as the probabilistic approach has been improved and refined over the years, it is possible for the designer, operator and regulator to get a more detailed and realistic picture of the safety importance of plant design features, operating procedures and operational practices by using probabilistic safety assessment (PSA) along with the deterministic methodology. At present, many countries including USA, UK and France are using PSA insights in their decision making along with deterministic basis. India has also made substantial progress in the development of methods for carrying out PSA. However, consensus on the use of PSA in regulatory decision-making has not been achieved yet. This paper emphasises on the requirements (e.g.,level of details, key modelling assumptions, data, modelling aspects, success criteria, sensitivity and uncertainty analysis) for improving the quality and consistency in performance and use of PSA that can facilitate meaningful use of the PSA insights in the regulatory decision-making in India. This paper also provides relevant information on international scenario and various application areas of PSA along with progress made in India. The PSA perspective presented in this paper may help in achieving consensus on the use of PSA for regulatory / utility decision-making in design and operation of NPPs

  16. Selected review of regulatory standards and licensing issues for nuclear power plants

    International Nuclear Information System (INIS)

    Stevenson, J.D.; Thomas, F.A.

    1982-11-01

    This report presents a compilation and description of current foreign regulatory standards and licensing issues in the areas of interest associated with Siting, Structural Engineering, Metallurgy and Materials, and Mechanical Engineering. In addition, summary comparisons of the requirements of both the US and foreign nuclear power plant regulatory standards are provided. The selected foreign countries surveyed include Canada, France, Japan, Sweden, United Kingdom of Great Britain and Northern Ireland, and the Federal Republic of Germany

  17. Regulatory guidance for license renewal

    International Nuclear Information System (INIS)

    Thoma, John A.

    1991-01-01

    The proposed 10 CFR Part 54 rule proceduralizes the process for license renewal by identifying both the administrative and technical requirements for a renewal application. To amplify and support this regulation, written guidance has been provided in the form of a draft Regulatory Guide (DG 1009) and a draft Standard Review Plan for License Renewal (NUREG 1299). This guidance is scheduled to be finalized in 1992. Similar guidance will be provided for the proposed revisions to 10 CFR Part 51 concerning the environmental aspects of license renewal. (author)

  18. Advances in Canadian regulatory practice

    International Nuclear Information System (INIS)

    Waddington, J.G.

    1993-03-01

    The new General Amendments to the Regulations, new recommendations on dose limits, developments in techniques and safety thinking, and aging of plant are all contributing to the need for a significant number of new regulatory document on a wide range of topics. this paper highlights a number of initiatives taken in response to these pressures, giving a brief background to the initiative and, where possible, outlining some of the ideas in the document licensing guides on new dose limits, dosimetry, safety analysis, reliability, fault tree analysis, reporting requirements, human factors, software, the ALARA principle, backfitting and the licensing process. (Author) 29 refs., fig., 4 tabs

  19. Pollution prevention: A regulatory update

    International Nuclear Information System (INIS)

    Walzer, A.E.; Maynard, J.W.

    1993-01-01

    Pollution prevention is the emphasis of the 1990s environmental philosophy. This new environmental era was ushered in when President Bush signed the Pollution Prevention Act in October 1990. This law, with its accompanying philosophy, was in response to the realization that end-of-the-pipe treatment, which frequently changed the media in which a pollutant or waste was discharged, was inadequate to protect the environment and human health. Pollution prevention advocates source reduction, where material substitutions and engineering solutions are sought to reduce the volume and toxicity of waste and pollutants. This proactive approach reduces environmental impacts such as those of former waste sites which have produced environmental legacies that will cost billions of dollars and take decades to remediate. This paper describes pollution prevention philosophy and summarizes regulatory pollution prevention requirements. It describes current regulatory trends in the area of pollution prevention, including voluntary programs and enforcement actions. The Pollution Prevention Act of 1990 is described, and pollution prevention initiatives embodied in other laws, including the Clean Air Act, the Clean Water Act, the Emergency Planning and Community Right-To-Know Act, the Resource Conservation and Recovery Act, and the Toxic Substances Control Act, are discussed. A historical overview of waste minimization initiatives within the Department of Energy is given, and other pollution prevention initiatives that affect federal facilities, such as Executive Order 12780, which mandates recycling and the procurement of recycled materials, are also outlined

  20. Global Banking System Regulatory Environment

    Directory of Open Access Journals (Sweden)

    Oleh Mozhovyi

    2017-03-01

    Full Text Available The international and domestic experience shows that the main factors of financial destabilization during the financial crises are in the banking sector. The article reveals that the vulnerability of the financial system is connected with functions, deposit and credit transactions, risks distribution and ensuring liquidity; banks act as a major factor in stabilisation measures in the current context of globalization processes, since the economic stability of banking activities relates directly to all the entities and only stable banking system can withstand the crisis phenomena. Therefore, as a result of the analysis, it is proved that not only reduction of risks of banks is needed, but also introduction of the effective supervision system over implementation of the requirements and standards to prevent these risks. According to modern international approaches, banks use the so-called prudential supervision, which is based on the risk management assessment policy on the part of the Bank’s management, and regulatory bodies contribute to implementation of such policy. The authors have concluded that not only modern specificity of banks, but also the impact of supervision systems and regulation of modern trends in development of the banking should be analysed. Application of the general regulatory principles and banking risks methodology is required. The task of supervision is distribution of reliable risk management practices in the banking system, taking into account national peculiarities of development.

  1. 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

  2. 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.

  3. Tolerogenic dendritic cells for regulatory T cell induction in man

    Directory of Open Access Journals (Sweden)

    Verena eRaker

    2015-11-01

    Full Text Available Dendritic cells are (DC highly specialized professional antigen-presenting cells (APC that regulate immune responses, maintaining the balance between tolerance and immunity. Mechanisms via which they can promote central and peripheral tolerance include clonal deletion, inhibition of memory T cell responses, T cell anergy and induction of regulatory T cells. These properties have led to the analysis of human tolerogenic DC as a therapeutic strategy for induction or re-establishment of tolerance. In the recent years, numerous protocols for the generation of human tolerogenic DC have been developed and their tolerogenic mechanisms, including induction of regulatory T cells, are relatively well understood. Phase I trials have been conducted in autoimmune disease, with results that emphasize the feasibility and safety of treatments with tolerogenic DC. Therefore, the scientific rationale for the use of tolerogenic DC therapy in the fields of transplantation medicine and allergic and autoimmune diseases is strong. This review will give an overview on efforts and protocols to generate human tolerogenic DC with focus on IL-10-modulated DC as inducers of regulatory T cells and discuss their clinical applications and challenges faced in further developing this form of immunotherapy.

  4. Environmental regulatory update table, March 1989

    International Nuclear Information System (INIS)

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

    1989-04-01

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

  5. Environmental Regulatory Update Table, April 1989

    International Nuclear Information System (INIS)

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

    1989-05-01

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

  6. Environmental Regulatory Update Table, August 1991

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-09-01

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

  7. Regulatory foci and the big five

    OpenAIRE

    Bak, Waclaw

    2009-01-01

    The distinction between promotion and prevention focus (Higgins, 1997) have been employed by many researchers dealing with processes of self-regulation. Little is known however about relations between regulatory orientations and more general personality traits. The present paper reports results of the study in which regulatory foci are analyzed in the context of five factor model of personality. To measure personality traits the NEO-FFI was used. Promotion and prevention regulatory foci was a...

  8. Management of the Regulatory Authority Information

    International Nuclear Information System (INIS)

    Suman, H.

    2003-01-01

    Safe Management of the Regulatory Authority Information is one of the essential elements to ensure the effectiveness of the regulatory program as a whole. This paper briefly describes the information management basis in RNRO, which is in charge of the regulatory authority tasks in Syria. SINA-2, a computational tool prepared in RNRO for managing the information related to the inventory of radiation sources and users, is also introduced

  9. Grand Gulf-prioritization of regulatory requirements

    International Nuclear Information System (INIS)

    Meisner, M.J.

    1993-01-01

    As cost pressures mount, Grand Gulf nuclear station (GGNS) is relying increasingly on various prioritization approaches to implement, modify, eliminate, or defer regulatory requirements. Regulatory requirements can be prioritized through the use of three measures: (1) safety (or risk) significance; (2) cost; and (3) public policy (or political) significance. This paper summarizes GGNS' efforts to implement solutions to regulatory issues using these three prioritization schemes to preserve a balance between cost and safety benefit

  10. Environmental Regulatory Update Table, December 1989

    International Nuclear Information System (INIS)

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

    1990-01-01

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

  11. Environmental Regulatory Update Table, December 1991

    Energy Technology Data Exchange (ETDEWEB)

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

    1992-01-01

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

  12. Regulatory control of fuel design and manufacturing

    International Nuclear Information System (INIS)

    1994-01-01

    The regulatory control of the design and manufacturing of the nuclear fuel and of the control rods aims to ensure conformance to set requirements during normal operating conditions, anticipated operational transients and postulated accident conditions. The regulatory control of design, manufacturing, receiving inspections and the start of operation of the nuclear fuel are specified in the guide. The regulatory control procedure also applies to the control rods and the shield elements

  13. Environmental Regulatory Update Table, August 1990

    International Nuclear Information System (INIS)

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

    1990-09-01

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

  14. Safety analysis - current and future regulatory challenges

    Energy Technology Data Exchange (ETDEWEB)

    Jamieson, T., E-mail: Terry.Jamieson@cnsc-ccsn.gc.ca [Canadian Nuclear Safety Commission, Ottawa, ON (Canada)

    2015-07-01

    'Full text:' The current and future regulatory challenges associated with deterministic safety analysis are reviewed, including: 1. The CNSC's and safety control areas. 2. Traditional safety analysis approach. 3. Experience gained and impact. 4. Current analysis and regulatory approaches. 5. Current status. 6. Complexity and challenges In particular, the technical, regulatory and strategic aspects of these challenges are discussed. (author)

  15. Safety analysis - current and future regulatory challenges

    International Nuclear Information System (INIS)

    Jamieson, T.

    2015-01-01

    'Full text:' The current and future regulatory challenges associated with deterministic safety analysis are reviewed, including: 1. The CNSC's and safety control areas. 2. Traditional safety analysis approach. 3. Experience gained and impact. 4. Current analysis and regulatory approaches. 5. Current status. 6. Complexity and challenges In particular, the technical, regulatory and strategic aspects of these challenges are discussed. (author)

  16. Environmental Regulatory Update Table, October 1991

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-11-01

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

  17. Environmental Regulatory Update Table, November 1991

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-12-01

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

  18. Environmental Regulatory Update Table, September 1991

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-10-01

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

  19. Environmental regulatory update table, July 1991

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-08-01

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

  20. Effects of natalizumab treatment on Foxp3+ T regulatory cells.

    Directory of Open Access Journals (Sweden)

    Max-Philipp Stenner

    Full Text Available BACKGROUND: Natalizumab, a monoclonal humanized antibody targeting the alpha-4 chain of very late activation antigen 4 (VLA-4 exerts impressive therapeutic effects in patients with relapsing-remitting multiple sclerosis. Our objective was to study impacts of Natalizumab therapy on Foxp3+ T regulatory cells (Tregs in multiple sclerosis (MS patients. METHODOLOGY: A combined approach of in vitro and ex vivo experiments using T cells isolated from the peripheral blood of healthy donors and Natalizumab treated MS patients was chosen. We determined binding of Natalizumab and its effects on the frequency, transmigratory behaviour and suppressive function of Tregs. PRINCIPAL FINDINGS: Binding of Natalizumab and expression of CD49d (alpha-4 chain of VLA-4 differed between non-regulatory and regulatory cells. Albeit Foxp3+ Tregs had lower levels of CD49d, Natalizumab blocked the transmigration of Foxp3+ Tregs similar to non-regulatory T cells. The frequency of peripheral blood Tregs was unaffected by Natalizumab treatment. Natalizumab does not alter the suppressive capacity of CD4+CD25(highCD127(lowFoxp3+ Tregs under in vitro conditions. Furthermore, the impaired function of Tregs in MS patients is not restored by Natalizumab treatment. CONCLUSIONS: We provide a first detailed analysis of Natalizumab effects on the regulatory T cell population. Our prospective study shows that Foxp3+ Tregs express lower levels of VLA-4 and bind less Natalizumab. We further the understanding of the mechanisms of action of Natalizumab by demonstrating that unlike other immunomodulatory drugs the beneficial therapeutic effects of the monoclonal antibody are largely independent of alterations in Treg frequency or function.

  1. Effects of natalizumab treatment on Foxp3+ T regulatory cells.

    Science.gov (United States)

    Stenner, Max-Philipp; Waschbisch, Anne; Buck, Dorothea; Doerck, Sebastian; Einsele, Hermann; Toyka, Klaus V; Wiendl, Heinz

    2008-10-06

    Natalizumab, a monoclonal humanized antibody targeting the alpha-4 chain of very late activation antigen 4 (VLA-4) exerts impressive therapeutic effects in patients with relapsing-remitting multiple sclerosis. Our objective was to study impacts of Natalizumab therapy on Foxp3+ T regulatory cells (Tregs) in multiple sclerosis (MS) patients. A combined approach of in vitro and ex vivo experiments using T cells isolated from the peripheral blood of healthy donors and Natalizumab treated MS patients was chosen. We determined binding of Natalizumab and its effects on the frequency, transmigratory behaviour and suppressive function of Tregs. Binding of Natalizumab and expression of CD49d (alpha-4 chain of VLA-4) differed between non-regulatory and regulatory cells. Albeit Foxp3+ Tregs had lower levels of CD49d, Natalizumab blocked the transmigration of Foxp3+ Tregs similar to non-regulatory T cells. The frequency of peripheral blood Tregs was unaffected by Natalizumab treatment. Natalizumab does not alter the suppressive capacity of CD4+CD25(high)CD127(low)Foxp3+ Tregs under in vitro conditions. Furthermore, the impaired function of Tregs in MS patients is not restored by Natalizumab treatment. We provide a first detailed analysis of Natalizumab effects on the regulatory T cell population. Our prospective study shows that Foxp3+ Tregs express lower levels of VLA-4 and bind less Natalizumab. We further the understanding of the mechanisms of action of Natalizumab by demonstrating that unlike other immunomodulatory drugs the beneficial therapeutic effects of the monoclonal antibody are largely independent of alterations in Treg frequency or function.

  2. Accountability feedback assessments for improving efficiency of nuclear regulatory institutions

    International Nuclear Information System (INIS)

    Lavarenne, Jean; Shwageraus, Eugene; Weightman, Michael

    2016-01-01

    The Fukushima-Daiichi Accident demonstrated the need of assessing and strengthening institutions involved in nuclear safety, including the accountability of regulators. There are a few problems hindering the path towards a greater understanding of accountability systems, the ensemble of mechanisms holding to account the nuclear regulator on behalf of the public. There is no consensus on what it should deliver and no systematic assessment method exists. This article proposes a method of assessing institutions based on defence in depth concepts and inspired from risk-assessment techniques used for nuclear safety. As a first step in testing the proposal, it presents a simple Monte-Carlo simulation, illustrating some of the workings of the method of assessment and demonstrating the kind of results it will be able to supply. This on-going work will assist policy-makers take better informed decisions about the size, structure and organisation of a nuclear regulator and the cost-effective funding of its accountability system. It will assist in striking a balance between efficiency and resilience of regulatory decision-making processes. It will also promote the involvement of stakeholders and allow them to have a more meaningful impact on regulatory decisions, thereby enhancing the robustness of the regulatory system and potentially trust and confidence. - Highlights: •A general introduction to regulatory accountability is given. •A definition of an effective accountability system is proposed. •A method to assess accountability systems is proposed. •A simplified simulation of a regulatory system demonstrates the method’s capabilities.

  3. Regulatory issues for nuclear power plant life management

    International Nuclear Information System (INIS)

    Roe, J.

    2000-01-01

    The workshop of 26-27 june 2000, on nuclear power Plant LIfe Management (PLIM), also included working groups in which major issues facing PLIM activities for nuclear power plants were identified and discussed. The second group was on Regulation. The Regulatory Working Group will attempt to identify some of the more pertinent issues affecting nuclear plant regulation in a changing PLIM environment, to identify some possible actions to be taken to address these issues, and to identify some of the parties responsible for taking these actions. Some preliminary regulatory issues are noted below. This is not intended to be a comprehensive list of such issues but rather is intended to stimulate discussion among the experts attending this Workshop. One of the concerns in the regulatory arena is how the structural integrity of the plants can be assured for an extended lifetime. Technological advances directed toward the following are likely to be important factors in the regulatory process of life extension. - Preventive and corrective maintenance (e.g., water chemistry control, pressure vessel annealing, and replacement of core internals). - Ageing and degradation mechanisms and evaluation (e.g., embrittlement, wear, corrosion/erosion, fatigue, and stress corrosion). - Monitoring, surveillance, and inspection (e.g., fatigue monitoring and non-destructive testing). - Optimisation of maintenance (e.g., using risk-based analysis). On the business side, there is concern about technical support by manufacturers, fuel companies, and construction companies. Maintaining a strong technical base and skilled workers in a potentially declining environment is another concern in the regulatory community. Waste management and decommissioning remain significant issue regarding PLIM. These issues affect all three areas of concern - technology, business, and regulation. It is against this background, that the issues put forth in this paper are presented. The objective of presenting these

  4. Mechanics without mechanisms

    Science.gov (United States)

    Eisenthal, Joshua

    2018-05-01

    At the time of Heinrich Hertz's premature death in 1894, he was regarded as one of the leading scientists of his generation. However, the posthumous publication of his treatise in the foundations of physics, Principles of Mechanics, presents a curious historical situation. Although Hertz's book was widely praised and admired, it was also met with a general sense of dissatisfaction. Almost all of Hertz's contemporaries criticized Principles for the lack of any plausible way to construct a mechanism from the "hidden masses" that are particularly characteristic of Hertz's framework. This issue seemed especially glaring given the expectation that Hertz's work might lead to a model of the underlying workings of the ether. In this paper I seek an explanation for why Hertz seemed so unperturbed by the difficulties of constructing such a mechanism. In arriving at this explanation, I explore how the development of Hertz's image-theory of representation framed the project of Principles. The image-theory brings with it an austere view of the "essential content" of mechanics, only requiring a kind of structural isomorphism between symbolic representations and target phenomena. I argue that bringing this into view makes clear why Hertz felt no need to work out the kinds of mechanisms that many of his readers looked for. Furthermore, I argue that a crucial role of Hertz's hypothesis of hidden masses has been widely overlooked. Far from acting as a proposal for the underlying structure of the ether, I show that Hertz's hypothesis ruled out knowledge of such underlying structure.

  5. The development of AECB regulatory documents

    International Nuclear Information System (INIS)

    Joyce, M.

    1981-01-01

    This document describes the Atomic Energy Control Board's (AECB) approach to the development and preparation of regulatory documents. The principal factors that have shaped the AECB'a regulatory approach are identified as background to the evolution of regulatory documents as are a number of current influences that affect the present and future development of these documents. Also described are the process by which regulatory documents are prepared and published and the points of contact between this process and the Canadian Standards Association program for nuclear standards. (author)

  6. Regulatory Information by Topic: Emergency Management

    Science.gov (United States)

    Regulatory information about emergencies, including chemical accident prevention, risk management plans (RMPs), chemical reporting, community right to know, and oil spills and hazardous substances releases.

  7. Annual Report 2008. Nuclear Regulatory Authority

    International Nuclear Information System (INIS)

    2009-01-01

    The present Annual Report of Activities of the Nuclear Regulatory Authority (ARN), prepared regularly from the creation as independent institution, describes across four parts and seven annexes the activities developed by the organism during 2008. The main topic are: the organization and the activity of the ARN; the regulatory standards; the licensing and inspection of nuclear power plants and critical facilities; the emergency systems; the occupational surveillance; the environmental monitoring; improved organizational and budgetary developments. Also, this publication have annexes with the following content: regulatory documents; regulatory guides; measurement and evaluation of the drinking water of Ezeiza.

  8. 75 FR 21889 - Semiannual Regulatory Agenda

    Science.gov (United States)

    2010-04-26

    ... assistance to small business concerns owned and controlled by women, and to women wishing to start a small... Part XVI Small Business Administration ###Semiannual Regulatory Agenda### [[Page 21890

  9. Canadian and international approaches to regulatory effectiveness

    International Nuclear Information System (INIS)

    Lojk, R.

    2014-01-01

    Regulatory effectiveness is an important attribute of any regulator, particularly nuclear regulators. As the nuclear industry has matured, and as the social landscape has changed, so have views on what constitutes regulatory effectiveness. Canada has evolved its regulatory structure and modernized its legislative framework and technical requirements and guidance over time. In addition, Canada continues to collaborate with international agencies, particularly the NEA and the IAEA, to ensure that there is a common understanding of the indicators and key attributes of regulatory effectiveness. This paper discusses Canadian and international views on the subject, including perspectives from other industries. (author)

  10. Federal Energy Regulatory Commission (FERC) Regions

    Data.gov (United States)

    Department of Homeland Security — Federal Energy Regulatory Commission (FERC) Regions. FERC is an independent agency that regulates the interstate transmission of electricity, natural gas, and oil....

  11. Annual Report 2007. Nuclear Regulatory Authority

    International Nuclear Information System (INIS)

    2008-01-01

    The present Annual Report of Activities of the Nuclear Regulatory Authority (ARN), prepared regularly from the creation as independent institution, describes across tree parts and seven annexes the activities developed by the organism during 2007. The main topic are: the organization and the activity of the ARN; the regulatory standards; the licensing and inspection of nuclear power plants and critical facilities; the emergency systems; the occupational surveillance; the environmental monitoring; improved organizational. Also, this publication have annexes with the following content: regulatory documents; inspections to medical, industrial and training installations; regulatory guides; measurement and evaluation of the drinking water of Ezeiza.

  12. Annual Report 2009. Nuclear Regulatory Authority

    International Nuclear Information System (INIS)

    2010-01-01

    The present Annual Report of Activities of the Nuclear Regulatory Authority (ARN), prepared regularly from the creation as independent institution, describes across four parts and seven annexes the activities developed by the organism during 2009. The main topic are: the organization and the activity of the ARN; the regulatory standards; the licensing and inspection of nuclear power plants and critical facilities; the emergency systems; the environmental monitoring; the occupational surveillance; the training and the public information; improved organizational and budgetary developments. Also, this publication have annexes with the following content: regulatory documents; inspections to medical, industrial and training installations; regulatory guides; measurement and evaluation of the drinking water of Ezeiza.

  13. Regulatory monitoring systems of fortified salt and wheat flour in selected ASEAN countries.

    Science.gov (United States)

    van den Wijngaart, Annoek; Bégin, France; Codling, Karen; Randall, Philip; Johnson, Quentin W

    2013-06-01

    assurance mechanisms in place to stimulate compliance by food producers, i.e., regulatory monitoring, having national legislation will not necessarily lead to increased coverage of fortified products and associated outcomes.

  14. Reduction of regulatory risk: a network economic approach

    OpenAIRE

    Knieps, Günter; Weiß, Hans-Jörg

    2007-01-01

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

  15. Regulatory T-Cell-Associated Cytokines in Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Akiko Okamoto

    2011-01-01

    Full Text Available Systemic lupus erythematosus (SLE is an autoimmune disease characterized by autoantibody production, complement activation, and immune complex deposition, resulting in tissue and organ damage. An understanding of the mechanisms responsible for homeostatic control of inflammation, which involve both innate and adoptive immune responses, will enable the development of novel therapies for SLE. Regulatory T cells (Treg play critical roles in the induction of peripheral tolerance to self- and foreign antigens. Naturally occurring CD4+CD25+ Treg, which characteristically express the transcription factor forkhead box protein P3 (Foxp3, have been intensively studied because their deficiency abrogates self-tolerance and causes autoimmune disease. Moreover, regulatory cytokines such as interleukin-10 (IL-10 also play a central role in controlling inflammatory processes. This paper focuses on Tregs and Treg-associated cytokines which might regulate the pathogenesis of SLE and, hence, have clinical applications.

  16. 78 FR 54502 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2013-09-04

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of a Proposed Rule... Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission (``SEC'' or ``Commission... or manipulative motivation for the trading activity at issue.\\4\\ Specifically, proposed Supplementary...

  17. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2016-01-01

    This section treats of the following National legislative and regulatory activities: 1 - Argentina: Organisation and structure; 2 - France: Radioactive waste management (Act No. 2016-1015 of 25 July 2016 specifying the procedures for creating a reversible deep geological repository for long-lived medium and high-level radioactive waste), Liability and compensation (Decree No. 2016-333 of 21 March 2016 implementing Article L. 597-28 of the French Environmental Code and relating to third party liability in the field of nuclear energy; Ministerial Order of 19 August 2016 listing the sites benefiting from a reduced amount of liability pursuant to decree No. 2016-333 of 21 March 2016 implementing Article L. 597-28 of the French Environmental Code and relating to third party liability in the field of nuclear energy), Nuclear facilities (Decree No. 2016-846 of 28 June 2016 related to the modification, final shutdown and decommissioning of basic nuclear installations, and to subcontracting); 3 - Germany: Nuclear trade - including non-proliferation (Amendments to the Foreign Trade Act and the Foreign Trade Ordinance (2015)), Radioactive waste management (Act on the Organisational Restructuring in the Field of Radioactive Waste Management (2016); Final report of the Commission to Review the Financing for the Phase-out of Nuclear Energy; Draft Bill of an Act on the Reorganisation of the Responsibility of Nuclear Waste Disposal (2016)); 4 - Lithuania: Nuclear safety and radiological protection (including nuclear emergency planning), Nuclear security (Physical security of sources of ionising radiation), Radioactive waste management, Licensing and regulatory infrastructure (Enforcement measures); 5 - Luxembourg: Radioactive waste management (Agreement between the Grand Duchy of Luxembourg and the Kingdom of Belgium on the Management and Final Disposal of the Radioactive Waste of the Grand Duchy of Luxembourg on the Territory of the Kingdom of Belgium, signed on 4 July 2016); 6

  18. 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

  19. O processo de produção normativa tributária infralegal como instrumento de intervenção regulatória: mecanismos e impactos/Tax regulatory process in Brazil as public policy intervention tool: Its mechanisms and impacts

    Directory of Open Access Journals (Sweden)

    Guilherme Cardoso Leite

    2015-04-01

    Full Text Available Purpose – This article aims to provide an inicial analysis of the regulation process in the current Brazilian tax environment. It also intends to investigate whether those tax administrative regulations have their guidelines extracted from a legal-procedural theory that allows them to be clear, simple and trusty on their rulemaking process. Methodology/approach/design – The text adopts as methodological approach the regulatory administrative procedure that is actually applied by Brazil’s Revenue Service (Portuguese acronym: SRF, Foreign Trade Chamber (Portuguese acronym: Camex, National Committee on Revenue Policy (Portuguese acronym: Confaz, and Revenue Appeal Chamber (Portuguese acronym: Carf, considered the regulatory influence and the economic consequences that they entail. As a guideline to this text, some theoretical assumptions needs to be made on public choice and public interest theories, based on Steven P. Croley criticism, and on legal analysis of economic policy developed by Marcus Faro de Castro. Findings – Debates on proposed reforms of Brazil’s tax system have brought about concerns related to excessive amount of regulations, leading to lack of perception of safety, clarity and confidence in the national legal environment. Practical implications – It provides basic guidelines to developing a regulatory rulemaking process focused on taxation. Originality/value – This article fosters the debate on the Brazilian tax system simplification, transparency, and publicity, focusing on regulatory rulemaking process and on social participating at the discussion agenda about tax public policies and regulation.

  20. Regulatory practices - United States example

    International Nuclear Information System (INIS)

    Shapar, M.

    1976-01-01

    In 1954, the Atomic Energy Act of 1946 was revised to do away with the federal state monopoly in this field and to enable private industry to develop nuclear power. This evolution led the federal authorities to give the Atomic Energy Commission the powers to control the design, licensing and operation of nuclear reactors. These powers were constantly strengthened and are now exercised by the Nuclear Regulatory Commission (NRC). Since its creation in 1975, the Commission has amended the regulations on licensing of nuclear reactors in the light of experience acquired so as to shorten the duration of this procedure. These amendments concern the standardization of nuclear power plants, limited work authorizations, the methods for issuing licenses. The objective of the Commission aim to make the licensing procedure for nuclear power plants simpler and more efficient and hence, less costly, while ensuring that a very high level for safety standards and environmental protection is maintained. (NEA) [fr

  1. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    Anon.

    2011-01-01

    This chapter of Nuclear Law Bulletin gathers some documents about national legislative and regulatory activities: - Belgium: Amendment of the Act on classification and security clearances, certifications and security notifications; Czech Republic: Resolution of the government of the Czech Republic on the time schedule of preparatory works for enlarging the nuclear power plant Temelin; Finland: Temporary Amendment to the Nuclear Liability Act; Ireland: Merchant Shipping Act; Romania: Emergency Ordinance on the identification, designation and protection of critical infrastructures; Emergency Ordinance on the control regime of dual-use items; Amendment to the Act on the safe conduct of nuclear activities; Nuclear safety norms on design and construction of nuclear power plants and nuclear safety norms on siting of nuclear power plants; United Kingdom: Establishment of the Office for Nuclear Regulation; United States: Waste Confidence Decision and Rule Update; Response to recent events in Japan

  2. Regulatory aspects of sludge management

    International Nuclear Information System (INIS)

    Sharples, F.E.

    1992-01-01

    The paper presents an overview of radioactive waste land disposal restrictions by discussing the following topics: highlights of Resource Conservation and Recovery Act history; purposes of land disposal restrictions; regulatory definition of land disposal; US Environmental Protection Agency (EPA) implementation of land disposal restrictions; schedules for implementing land disposal restrictions; solvent and dioxin wastes; classification of liquid hazardous and radioactive wastes; generator and treatment, storage, and disposal responsibilities; variances and extensions; and options for mixed waste management. Land disposal restrictions take into account the long-term uncertainties associated with land disposal, the need to manage waste right the first time they are disposed, and the persistence toxicity, mobility, propensity to bioaccumulate, and volume. In the Department of Energy system land disposal restrictions affect mixed waste management and site remedial action programs

  3. National legislative and regulatory activities

    International Nuclear Information System (INIS)

    2015-01-01

    This section treats of the following National legislative and regulatory activities: 1 - Australia: General legislation - Bill to amend the Australian Radiation Protection and Nuclear Safety Act 1998; 2 - France: General legislation - Law No. 2015-992 of 17 August 2015 on the energy transition for green growth; ASN Report on the state of nuclear safety and radiation protection in France in 2014; 3 - Germany: Radioactive waste management - First Ordinance to amend the 2005 Gorleben Development Freeze Ordinance (2015); 4 - Greece: Radioactive waste management - Joint Ministerial Decision establishing the national policy on the management of spent fuel and radioactive waste; 5 - Lithuania: Nuclear safety and radiological protection - Revised requirements for modifications, Plan for enhancement of nuclear safety, New requirements for the commissioning of nuclear power plants, Revised requirements regulating the provision of information on abnormal events; Radioactive waste management - Revised requirements for acceptance criteria for near surface repository; Nuclear security - Revised requirements for physical protection; 6 - Romania: Licensing and regulatory infrastructure - Government Decision No. 600/2014 for approval of National Nuclear Safety and Security; International co-operation - Government Decision No. 525/2014 for approval of the Co-operation Agreement on the radioactive waste management between the French National Radioactive Waste Management Agency (ANDRA) and Nuclear Agency and Radioactive Waste (ANDR) Strategy; Memorandum of Understanding for Co-operation and Exchange of Information in Nuclear Regulatory Matters between the National Commission for Nuclear Activities Control (CNCAN) of Romania and the President of National Atomic Energy Agency (PAA) of Poland; Government Decision No. 540/2015 for approval of the Agreement between the Government of Romania and the Government of the People's Republic of China regarding co-operation in the peaceful

  4. 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.

  5. NRC regulatory uses of PSA

    International Nuclear Information System (INIS)

    Murley, T.E.

    1991-01-01

    The publication in 1975 of WASH-1400, with its new probabilistic safety assessment (PSA) methodology, had the effect of presenting a pair of eyeglasses to a man with poor eyesight. Suddenly, it gave us a view of nuclear safety with a new clarity, and it allowed us to sort out the important safety issues from the unimportant. In the intervening years, PSA insights have permeated the fabric of nearly all our safety judgments. This acceptance can be seen from the following list of broad areas where the Nuclear Regulatory Commission (NRC) staff uses PSA insights and methodology: evaluating the safety significance of operating events and recommending safety improvements where warranted; requesting licensees to systematically look for design vulnerabilities in each operating reactor; evaluating the safety significance of design weaknesses or non-compliances when judging the time frame for necessary improvements; conducting sensitivity analyses to judge where safety improvements are most effective; assessing the relative safety benefits of design features for future reactors. In judging where PSA methodology can be improved to give better safety insights, it is believed that the following areas need more attention: better modeling of cognitive errors; more comprehensive modeling of accident sequences initiated from conditions other than full power; more comprehensive modeling of inter-system loss of coolant accident (ISLOCA) sequences. Although PSA is widely used in the staff's regulatory activities, the NRC deliberately chooses not to include probabilistic prescriptions in regulations or guidance documents. The staff finds the bottom line risk estimates to be one of the least reliable products of a PSA. The reason for this view is that PSA cannot adequately address cognitive errors nor assess the effects of a pervasive poor safety attitude

  6. 75 FR 59771 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving the...

    Science.gov (United States)

    2010-09-28

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving the Proposed Rule.... I. Introduction On July 27, 2010, the Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k... pertinent distribution-related information from its members in a timely fashion to facilitate its Regulation...

  7. 75 FR 53998 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2010-09-02

    ... characteristics and risks of security futures. \\6\\ 15 U.S.C. 78o-3(b)(6). B. Self-Regulatory Organization's...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Amend the Security Futures Risk Disclosure Statement August 27, 2010...

  8. 75 FR 41254 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a...

    Science.gov (United States)

    2010-07-15

    ... registered capacity, may work in other investment-related industries, such as financial planning, or may seek...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving a Proposed Rule..., 2010, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and...

  9. 77 FR 7218 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2012-02-10

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate... thereunder,\\2\\ notice is hereby given that on January 30, 2012, Financial Industry Regulatory Authority, Inc.... For more information about the rulebook consolidation process, see Information Notice, March 12, 2008...

  10. 75 FR 2897 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2010-01-19

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of Proposed Rule... hereby given that on December 23, 2009, Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a... consolidation process, see Information Notice, March 12, 2008 (Rulebook Consolidation Process). NASD Rule 2450...

  11. 76 FR 60106 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-09-28

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate... 14, 2011, Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a National Association of.... For more information about the rulebook consolidation process, see Information Notice, March 12, 2008...

  12. 75 FR 27606 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2010-05-17

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate...\\ and Rule 19b-4 thereunder,\\2\\ notice is hereby given that on April 27, 2010, the Financial Industry... restated following the formation of FINRA through the consolidation of NASD and the member regulatory...

  13. 75 FR 5157 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

    Science.gov (United States)

    2010-02-01

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change... Consolidated FINRA Rulebook January 25, 2010. On December 2, 2009, the Financial Industry Regulatory Authority... later in the rulebook consolidation process. It is therefore ordered, pursuant to Section 19(b)(2) of...

  14. 77 FR 47470 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

    Science.gov (United States)

    2012-08-08

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Withdrawal of Proposed Rule Change To Adopt FINRA Rule 2231 (Customer Account Statements) in the Consolidated FINRA Rulebook August 2, 2012. On April 22, 2009, the Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a...

  15. 76 FR 21084 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

    Science.gov (United States)

    2011-04-14

    ... Securities April 8, 2011. I. Introduction On March 3, 2011, the Financial Industry Regulatory Authority, Inc... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-64283; File No. SR-FINRA-2011-012] Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Designation of a Longer...

  16. 78 FR 62784 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

    Science.gov (United States)

    2013-10-22

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Designation of a Longer... 5210 (Publication of Transactions and Quotations) October 4, 2013. I. Introduction On August 15, 2013, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission...

  17. 76 FR 50796 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

    Science.gov (United States)

    2011-08-16

    ...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Increase the Position Limit for Options on the Standard and Poor's... Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission...

  18. 77 FR 12098 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2012-02-28

    ... 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of Substance of the Proposed Rule... FINRA and at the Commission's Public Reference Room. II. Self-Regulatory Organization's Statement of the..., and C below, of the most significant aspects of such statements. A. Self-Regulatory Organization's...

  19. 76 FR 9838 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2011-02-22

    .... 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of Substance..., and at the Commission's Public Reference Room. II. Self-Regulatory Organization's Statement of the... in sections A, B, and C below, of the most significant aspects of such statements. A. Self-Regulatory...

  20. 76 FR 9840 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing of...

    Science.gov (United States)

    2011-02-22

    .... 78s(b)(1). \\2\\ 17 CFR 240.19b-4. I. Self-Regulatory Organization's Statement of the Terms of Substance... Public Reference Room. II. Self-Regulatory Organization's Statement of the Purpose of, and Statutory..., and C below, of the most significant aspects of such statements. A. Self-Regulatory Organization's...

  1. Regulatory Aspect of an Ageing Management Program

    International Nuclear Information System (INIS)

    Basic, I.; Zabric, I.; Savli, S.

    2006-01-01

    The aspects of plant ageing management (AM) gained increasing attention over the last ten years. Numerous technical studies have been performed to study the impact of ageing mechanisms on the safe and reliable operation of nuclear power plants. National research activities have been initiated or are in progress to provide the technical basis for decision making processes. The long-term operation of nuclear power plants is influenced by economic considerations, the socio-economic environment including public acceptance, developments in research and the regulatory framework, the availability of technical infrastructure to maintain and service the systems, structures and components as well as qualified personnel. Besides national activities there are a number of international activities in particular under the umbrella of the IAEA, the OECD and the EU. The paper will provide the summary on Nuclear Plant Life Management (PLIM) (or Ageing Management Program (AMP)) and Plant Life Extension (PLEX) development in USA and European countries. Also, insights from such effort currently performing in Slovenia will be discussed.(author)

  2. Regulatory effects of fisetin on microglial activation.

    Science.gov (United States)

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

    2014-06-26

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

  3. Regulatory Effects of Fisetin on Microglial Activation

    Directory of Open Access Journals (Sweden)

    Jing-Yuan Chuang

    2014-06-01

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

  4. Pathogenic adaptation of intracellular bacteria by rewiring a cis-regulatory input function.

    Science.gov (United States)

    Osborne, Suzanne E; Walthers, Don; Tomljenovic, Ana M; Mulder, David T; Silphaduang, Uma; Duong, Nancy; Lowden, Michael J; Wickham, Mark E; Waller, Ross F; Kenney, Linda J; Coombes, Brian K

    2009-03-10

    The acquisition of DNA by horizontal gene transfer enables bacteria to adapt to previously unexploited ecological niches. Although horizontal gene transfer and mutation of protein-coding sequences are well-recognized forms of pathogen evolution, the evolutionary significance of cis-regulatory mutations in creating phenotypic diversity through altered transcriptional outputs is not known. We show the significance of regulatory mutation for pathogen evolution by mapping and then rewiring a cis-regulatory module controlling a gene required for murine typhoid. Acquisition of a binding site for the Salmonella pathogenicity island-2 regulator, SsrB, enabled the srfN gene, ancestral to the Salmonella genus, to play a role in pathoadaptation of S. typhimurium to a host animal. We identified the evolved cis-regulatory module and quantified the fitness gain that this regulatory output accrues for the bacterium using competitive infections of host animals. Our findings highlight a mechanism of pathogen evolution involving regulatory mutation that is selected because of the fitness advantage the new regulatory output provides the incipient clones.

  5. Regulatory T Cells in Radiotherapeutic Responses

    International Nuclear Information System (INIS)

    Schaue, Dörthe; Xie, Michael W.; Ratikan, Josephine A.; McBride, William H.

    2012-01-01

    Radiation therapy (RT) can extend its influence in cancer therapy beyond what can be attributed to in-field cytotoxicity by modulating the immune system. While complex, these systemic effects can help tip the therapeutic balance in favor of treatment success or failure. Engagement of the immune system is generally through recognition of damage-associated molecules expressed or released as a result of tumor and normal tissue radiation damage. This system has evolved to discriminate pathological from physiological forms of cell death by signaling “danger.” The multiple mechanisms that can be evoked include a shift toward a pro-inflammatory, pro-oxidant microenvironment that can promote maturation of dendritic cells and, in cancer treatment, the development of effector T cell responses to tumor-associated antigens. Control over these processes is exerted by regulatory T cells (Tregs), suppressor macrophages, and immunosuppressive cytokines that act in consort to maintain tolerance to self, limit tissue damage, and re-establish tissue homeostasis. Unfortunately, by the time RT for cancer is initiated the tumor-host relationship has already been sculpted in favor of tumor growth and against immune-mediated mechanisms for tumor regression. Reversing this situation is a major challenge. However, recent data show that removal of Tregs can tip the balance in favor of the generation of radiation-induced anti-tumor immunity. The clinical challenge is to do so without excessive depletion that might precipitate serious autoimmune reactions and increase the likelihood of normal tissue complications. The selective modulation of Treg biology to maintain immune tolerance and control of normal tissue damage, while releasing the “brakes” on anti-tumor immune responses, is a worthy aim with promise for enhancing the therapeutic benefit of RT for cancer.

  6. Regulatory T cells in radiotherapeutic responses

    Directory of Open Access Journals (Sweden)

    Dörthe eSchaue

    2012-08-01

    Full Text Available Radiation therapy (RT can extend its influence in cancer therapy beyond what can be attributed to in-field cytotoxicity by modulating the immune system. While complex, these systemic effects can help tip the therapeutic balance in favor of treatment success or failure. Engagement of the immune system is generally through recognition of damage-associated molecules expressed or released as a result of tumor and normal tissue radiation damage. This system has evolved to discriminate pathological from physiological forms of cell death by signaling danger. The multiple mechanisms that can be evoked include a shift towards a pro-inflammatory, pro-oxidant microenvironment that can promote maturation of dendritic cells and, in cancer treatment, the development of effector T cell responses to tumor-associated antigens. Control over these processes is exerted by regulatory T cells (Tregs, suppressor macrophages and immunosuppressive cytokines that act in consort to maintain tolerance to self, limit tissue damage, and re-establish tissue homeostasis. Unfortunately, by the time RT for cancer is initiated the tumor-host relationship has already been sculpted in favor of tumor growth and against immune-mediated mechanisms for tumor regression. Reversing this situation is a major challenge. However, recent data show that removal of Tregs can tip the balance in favor of the generation of radiation-induced anti-tumor immunity. The clinical challenge is to do so without excessive depletion that might precipitate serious autoimmune reactions and increase the likelihood of normal tissue complications. The selective modulation of Treg biology to maintain immune tolerance and control of normal tissue damage, while releasing the brakes on anti-tumor immune responses, is a worthy aim with promise for enhancing the therapeutic benefit of RT for cancer.

  7. Environment, safety, and health regulatory implementation plan

    International Nuclear Information System (INIS)

    1993-01-01

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

  8. 76 FR 6587 - Pennsylvania Regulatory Program

    Science.gov (United States)

    2011-02-07

    ... [PA-159-FOR; OSM 2010-0017] Pennsylvania Regulatory Program AGENCY: Office of Surface Mining... remove a required amendment to the Pennsylvania regulatory program (the ``Pennsylvania program'') under... program amendment codified in the Federal regulations, Pennsylvania has submitted information that it...

  9. 76 FR 64043 - Iowa Regulatory Program

    Science.gov (United States)

    2011-10-17

    ...) Requirements for permits for special categories of mining. 27--40.41(207) Permanent regulatory program--small... DEPARTMENT OF THE INTERIOR Office of Surface Mining Reclamation and Enforcement 30 CFR Part 915 [Docket No. IA-016-FOR; Docket ID: OSM-2011-0014] Iowa Regulatory Program AGENCY: Office of Surface Mining...

  10. 78 FR 44275 - Semiannual Regulatory Agenda

    Science.gov (United States)

    2013-07-23

    ... Rights. National Park Service--Completed Actions Regulation Sequence No. Title Identifier No. 200 Winter.... Timetable: Action Date FR Cite NPRM 07/00/13 Final Action 05/00/14 Regulatory Flexibility Analysis Required...: Action Date FR Cite NPRM 10/00/14 Final Action 10/00/14 Regulatory Flexibility Analysis Required: Yes...

  11. Regulatory Circuits Linking Energy Status to Growth

    NARCIS (Netherlands)

    Jansen, W.M.

    2017-01-01

    Plant growth and development critically depend on carbon nutrient status. Over the past years several core regulatory systems that link plant carbon status to growth have emerged. The core regulatory systems studied include the trehalose 6-phosphate (T6P) signaling system and the Target of Rapamycin

  12. Regulatory and technical reports (abstract index journal)

    International Nuclear Information System (INIS)

    1994-06-01

    This compilation consists of bibliographic data and abstracts for the formal regulatory and technical reports issued by the US Nuclear Regulatory Commission (NRC) Staff and its contractors. It is NRC's intention to publish this compilation quarterly and to cumulate it annually

  13. 5 CFR 880.102 - Regulatory structure.

    Science.gov (United States)

    2010-01-01

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

  14. 5 CFR 847.102 - Regulatory structure.

    Science.gov (United States)

    2010-01-01

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

  15. The regulatory framework in the UK

    International Nuclear Information System (INIS)

    O'Sullivan, R.

    1984-01-01

    The subject is covered in sections, headed: basic regulatory requirements covering the transport of radioactive material in the UK; responsibility for safety (competent authority; provision of regulations; implementation of regulations (international and national); design of transport flask; safety case; testing; assessment; approval certificate; compliance assurance; administration); advice and information on the regulatory safety standards. (U.K.)

  16. 77 FR 8082 - Regulatory Flexibility Agenda

    Science.gov (United States)

    2012-02-13

    ... Required: Yes. Agency Contact: Alicia Goldin, Division of Trading and Markets, Securities and Exchange.../01/11 Regulatory Flexibility Analysis Required: Yes. Agency Contact: Alicia Goldin, Division of... Withdrawn 10/01/11 Regulatory Flexibility Analysis Required: Yes. Agency Contact: Alicia Goldin, Division of...

  17. 75 FR 52999 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2010-08-30

    ... site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . In addition... NUCLEAR REGULATORY COMMISSION [NRC-2009-0556] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 8.35...

  18. 75 FR 12804 - Withdrawal of Regulatory Guide 8.6

    Science.gov (United States)

    2010-03-17

    ... ``Regulatory Guides'' in the NRC's Electronic Reading Room at http://www.nrc.gov/reading-rm/doc-collections... NUCLEAR REGULATORY COMMISSION [NRC-2010-0103] Withdrawal of Regulatory Guide 8.6 AGENCY: Nuclear Regulatory Commission. ACTION: Withdrawal of Regulatory Guide 8.6, ``Standard Test Procedure for Geiger-M...

  19. 75 FR 16202 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2010-03-31

    ... Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . In addition, regulatory guides are available... NUCLEAR REGULATORY COMMISSION [NRC-2008-0644] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide (RG) 1.126...

  20. 75 FR 45171 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2010-08-02

    ... ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ and through the NRC's Agencywide... NUCLEAR REGULATORY COMMISSION [NRC-2010-0072] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 3.13...

  1. 75 FR 20868 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2010-04-21

    ... available through the NRC's public Web site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc... NUCLEAR REGULATORY COMMISSION [NRC-2009-0351] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.68.2...

  2. 75 FR 42170 - Final Regulatory Guide: Issuance, Availability

    Science.gov (United States)

    2010-07-20

    ... NRC's public Web site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections... NUCLEAR REGULATORY COMMISSION [NRC-2009-0425] Final Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide...

  3. 75 FR 81675 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2010-12-28

    ... through the NRC's public Web site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc... NUCLEAR REGULATORY COMMISSION [NRC-2010-0031] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 4.16...

  4. 75 FR 48381 - Final Regulatory Guide: Issuance, Availability

    Science.gov (United States)

    2010-08-10

    ... NRC's public Web site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections... NUCLEAR REGULATORY COMMISSION [NRC-2010-0274] Final Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of issuance and availability of Regulatory Guide...

  5. 75 FR 37842 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2010-06-30

    ... site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . In addition... NUCLEAR REGULATORY COMMISSION [NRC-2009-0396] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 2.5...

  6. 75 FR 43207 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2010-07-23

    ... NRC's public Web site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections... NUCLEAR REGULATORY COMMISSION [NRC-2009-0282] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.141...

  7. 75 FR 33361 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2010-06-11

    ....gov/reading-rm/doc-collections/ . In addition, regulatory guides are available for inspection at the... NUCLEAR REGULATORY COMMISSION [NRC-2009-0308] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.28...

  8. 75 FR 20399 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2010-04-19

    ... the NRC's public Web site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections... NUCLEAR REGULATORY COMMISSION [NRC-2009-0418] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 6.9...

  9. 76 FR 31382 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2011-05-31

    ... the NRC's public Web site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections... NUCLEAR REGULATORY COMMISSION [NRC-2010-0287] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 8.2...

  10. 76 FR 24539 - Final Regulatory Guide: Issuance, Availability

    Science.gov (United States)

    2011-05-02

    ... site under ``Regulatory Guides'' at http://www.nrc.gov/reading-rm/doc-collections/ . Electronic copies... NUCLEAR REGULATORY COMMISSION [NRC-2010-0181] Final Regulatory Guide: Issuance, Availability AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide...

  11. 75 FR 16525 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2010-04-01

    ... http://www.nrc.gov/reading-rm/doc-collections/ . In addition, regulatory guides are available for... NUCLEAR REGULATORY COMMISSION [NRC-2009-0413] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of Issuance and Availability of Regulatory Guide 1.11...

  12. 75 FR 27599 - Notice of Issuance of Regulatory Guide

    Science.gov (United States)

    2010-05-17

    ...'' at http://www.nrc.gov/reading-rm/doc-collections/ . In addition, regulatory guides are available for... NUCLEAR REGULATORY COMMISSION [NRC-2009-0492] Notice of Issuance of Regulatory Guide AGENCY: Nuclear Regulatory Commission. ACTION: Notice of issuance and availability of Regulatory Guide 6.7...

  13. Fracture Mechanics

    International Nuclear Information System (INIS)

    Jang, Dong Il; Jeong, Gyeong Seop; Han, Min Gu

    1992-08-01

    This book introduces basic theory and analytical solution of fracture mechanics, linear fracture mechanics, non-linear fracture mechanics, dynamic fracture mechanics, environmental fracture and fatigue fracture, application on design fracture mechanics, application on analysis of structural safety, engineering approach method on fracture mechanics, stochastic fracture mechanics, numerical analysis code and fracture toughness test and fracture toughness data. It gives descriptions of fracture mechanics to theory and analysis from application of engineering.

  14. Annual Report 2010. Nuclear Regulatory Authority

    International Nuclear Information System (INIS)

    2010-01-01

    The present Annual Report of Activities of the Nuclear Regulatory Authority (ARN), prepared regularly from the creation as independent institution, describes across six chapters and seven annexes the activities developed by the organism during 2010. The main topic are: institutional issues; regulatory guides and standards; argentinean nuclear regulatory system; quality assurance of the ARN; the institutional communications; the licensing and inspection of nuclear power plants and critical facilities; the emergency systems; the safeguards and the physical protection; the environmental control; the institutional relations; the training and the public information. Also, this publication have annexes with the following content: the regulatory framework; regulatory documents; inspections to medical, industrial and training installations; measurement and evaluation of the drinking water of Ezeiza; international expert's report on the application of the international standards of radiological protection of the public in the zone of the Ezeiza Atomic Center; ethical code

  15. Annual Report 2011. Nuclear Regulatory Authority

    International Nuclear Information System (INIS)

    2011-01-01

    The present Annual Report of Activities of the Nuclear Regulatory Authority (ARN), prepared regularly from the creation as independent institution, describes across six chapters and seven annexes the activities developed by the organism during 2011. The main topic are: institutional issues; regulatory guides and standards; argentinean nuclear regulatory system; quality assurance of the ARN; the institutional communications; the licensing and inspection of nuclear power plants and critical facilities; the emergency systems; the safeguards and the physical protection; the environmental control; the institutional relations; the training and the public information. Also, this publication have annexes with the following content: the regulatory framework; regulatory documents; inspections to medical, industrial and training installations; measurement and evaluation of the drinking water of Ezeiza; international expert's report on the application of the international standards of radiological protection of the public in the zone of the Ezeiza Atomic Center; ethical code

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

    Directory of Open Access Journals (Sweden)

    Shahir Prajakta

    2011-05-01

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

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

    Science.gov (United States)

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

    2016-06-01

    A prospective field study conducted with runners training for an upcoming marathon (Marathon of Rome 2013) examined the relation between regulatory modes, locomotion and assessment, and stress. Integrating regulatory mode theory and the dualistic model of passion, we hypothesized that the relation between regulatory modes (evaluated 3 months before the race) and the experience of stress approaching the marathon, is mediated by the type of passion (harmonious vs obsessive) athletes experience with regard to marathoning. Results revealed that (a) locomotion positively predicted harmonious passion, which in turn reduced athletes' experience of stress; and (b) assessment positively predicted obsessive passion, which in turn enhanced athletes' experience of stress. Overall, the present results suggest that proximal psychological mechanisms such as basic regulatory mode orientations can predict distal outcomes such as stress indirectly through their relation with motivational phenomena such as passion. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. A New Algorithm for Identifying Cis-Regulatory Modules Based on Hidden Markov Model

    Directory of Open Access Journals (Sweden)

    Haitao Guo

    2017-01-01

    Full Text Available The discovery of cis-regulatory modules (CRMs is the key to understanding mechanisms of transcription regulation. Since CRMs have specific regulatory structures that are the basis for the regulation of gene expression, how to model the regulatory structure of CRMs has a considerable impact on the performance of CRM identification. The paper proposes a CRM discovery algorithm called ComSPS. ComSPS builds a regulatory structure model of CRMs based on HMM by exploring the rules of CRM transcriptional grammar that governs the internal motif site arrangement of CRMs. We test ComSPS on three benchmark datasets and compare it with five existing methods. Experimental results show that ComSPS performs better than them.

  19. A New Algorithm for Identifying Cis-Regulatory Modules Based on Hidden Markov Model

    Science.gov (United States)

    2017-01-01

    The discovery of cis-regulatory modules (CRMs) is the key to understanding mechanisms of transcription regulation. Since CRMs have specific regulatory structures that are the basis for the regulation of gene expression, how to model the regulatory structure of CRMs has a considerable impact on the performance of CRM identification. The paper proposes a CRM discovery algorithm called ComSPS. ComSPS builds a regulatory structure model of CRMs based on HMM by exploring the rules of CRM transcriptional grammar that governs the internal motif site arrangement of CRMs. We test ComSPS on three benchmark datasets and compare it with five existing methods. Experimental results show that ComSPS performs better than them. PMID:28497059

  20. A 3D bioprinting exemplar of the consequences of the regulatory requirements on customized processes.

    Science.gov (United States)

    Hourd, Paul; Medcalf, Nicholas; Segal, Joel; Williams, David J

    2015-01-01

    Computer-aided 3D printing approaches to the industrial production of customized 3D functional living constructs for restoration of tissue and organ function face significant regulatory challenges. Using the manufacture of a customized, 3D-bioprinted nasal implant as a well-informed but hypothetical exemplar, we examine how these products might be regulated. Existing EU and USA regulatory frameworks do not account for the differences between 3D printing and conventional manufacturing methods or the ability to create individual customized products using mechanized rather than craft approaches. Already subject to extensive regulatory control, issues related to control of the computer-aided design to manufacture process and the associated software system chain present additional scientific and regulatory challenges for manufacturers of these complex 3D-bioprinted advanced combination products.