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Sample records for regulated restriction-modification system

  1. A survey of Type III restriction-modification systems reveals numerous, novel epigenetic regulators controlling phase-variable regulons; phasevarions

    Science.gov (United States)

    Atack, John M; Yang, Yuedong; Jennings, Michael P

    2018-01-01

    Abstract Many bacteria utilize simple DNA sequence repeats as a mechanism to randomly switch genes on and off. This process is called phase variation. Several phase-variable N6-adenine DNA-methyltransferases from Type III restriction-modification systems have been reported in bacterial pathogens. Random switching of DNA methyltransferases changes the global DNA methylation pattern, leading to changes in gene expression. These epigenetic regulatory systems are called phasevarions — phase-variable regulons. The extent of these phase-variable genes in the bacterial kingdom is unknown. Here, we interrogated a database of restriction-modification systems, REBASE, by searching for all simple DNA sequence repeats in mod genes that encode Type III N6-adenine DNA-methyltransferases. We report that 17.4% of Type III mod genes (662/3805) contain simple sequence repeats. Of these, only one-fifth have been previously identified. The newly discovered examples are widely distributed and include many examples in opportunistic pathogens as well as in environmental species. In many cases, multiple phasevarions exist in one genome, with examples of up to 4 independent phasevarions in some species. We found several new types of phase-variable mod genes, including the first example of a phase-variable methyltransferase in pathogenic Escherichia coli. Phasevarions are a common epigenetic regulation contingency strategy used by both pathogenic and non-pathogenic bacteria. PMID:29554328

  2. Restriction-modification systems in Mycoplasma spp

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    Marcelo Brocchi

    2007-01-01

    Full Text Available Restriction and Modification (R-M systems are present in all Mycoplasma species sequenced so far. The presence of these genes poses barriers to gene transfer and could protect the cell against phage infections. The number and types of R-M genes between different Mycoplasma species are variable, which is characteristic of a polymorphism. The majority of the CDSs code for Type III R-M systems and particularly for methyltransferase enzymes, which suggests that functions other than the protection against the invasion of heterologous DNA may exist. A possible function of these enzymes could be the protection against the invasion of other but similar R-M systems. In Mycoplasma hyopneumoniae strain J, three of the putative methyltransferase genes were clustered in a region forming a genomic island. Many R-M CDSs were mapped in the vicinity of transposable elements suggesting an association between these genes and reinforcing the idea of R-M systems as mobile selfish DNA. Also, many R-M genes present repeats within their coding sequences, indicating that their expression is under the control of phase variation mechanisms. Altogether, these data suggest that R-M systems are a remarkable characteristic of Mycoplasma species and are probably involved in the adaptation of these bacteria to different environmental conditions.

  3. The role of DNA restriction-modification systems in the biology of Bacillus anthracis

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    Ramakrishnan eSitaraman

    2016-01-01

    Full Text Available Restriction-modification (R-M systems are widespread among prokaryotes and, depending on their type, may be viewed as selfish genetic elements that persist as toxin-antitoxin modules or as cellular defense systems against phage infection. Studies in the last decade have made it amply clear that these two options do not exhaust the list of possible biological roles for R-M systems. Their presence in a cell may also have a bearing on other processes such as horizontal gene transfer and gene regulation. From genome sequencing and experimental data, we know that Bacillus anthracis encodes at least three methylation-dependent (typeIV restriction endonucleases, and an orphan DNA methyltransferase. In this article, we first present an outline of our current knowledge of R-M systems in Bacillus anthracis. Based on available DNA sequence data, and on our current understanding of the functions of similar genes in other systems, we conclude with hypotheses on the possible roles of the three restriction endonucleases and the orphan DNA methyltransferase.

  4. The BsaHI restriction-modification system: Cloning, sequencing and analysis of conserved motifs

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    Roberts Richard J

    2008-05-01

    Full Text Available Abstract Background Restriction and modification enzymes typically recognise short DNA sequences of between two and eight bases in length. Understanding the mechanism of this recognition represents a significant challenge that we begin to address for the BsaHI restriction-modification system, which recognises the six base sequence GRCGYC. Results The DNA sequences of the genes for the BsaHI methyltransferase, bsaHIM, and restriction endonuclease, bsaHIR, have been determined (GenBank accession #EU386360, cloned and expressed in E. coli. Both the restriction endonuclease and methyltransferase enzymes share significant similarity with a group of 6 other enzymes comprising the restriction-modification systems HgiDI and HgiGI and the putative HindVP, NlaCORFDP, NpuORFC228P and SplZORFNP restriction-modification systems. A sequence alignment of these homologues shows that their amino acid sequences are largely conserved and highlights several motifs of interest. We target one such conserved motif, reading SPERRFD, at the C-terminal end of the bsaHIR gene. A mutational analysis of these amino acids indicates that the motif is crucial for enzymatic activity. Sequence alignment of the methyltransferase gene reveals a short motif within the target recognition domain that is conserved among enzymes recognising the same sequences. Thus, this motif may be used as a diagnostic tool to define the recognition sequences of the cytosine C5 methyltransferases. Conclusion We have cloned and sequenced the BsaHI restriction and modification enzymes. We have identified a region of the R. BsaHI enzyme that is crucial for its activity. Analysis of the amino acid sequence of the BsaHI methyltransferase enzyme led us to propose two new motifs that can be used in the diagnosis of the recognition sequence of the cytosine C5-methyltransferases.

  5. Genetic diversity of the HpyC1I restriction modification system in Helicobacter pylori.

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    Lehours, Philippe; Dupouy, Sandrine; Chaineux, Julien; Ruskoné-Fourmestraux, Agnès; Delchier, Jean-Charles; Morgner, Andrea; Mégraud, Francis; Ménard, Armelle

    2007-04-01

    Helicobacter pylori is unique because of the unusually high number and diversity of its restriction modification (R-M) systems. HpyC1I R-M was recently characterized and contains an endonuclease which is an isoschizomer of the endonuclease BccI. This R-M is involved in adherence to gastric epithelial cells, a crucial step in bacterial pathogenesis. This observation illustrates the fact that R-M systems have other putative biological functions in addition to protecting the bacterial genome from external DNA. The genomic diversity of HpyC1I R-M was evaluated more precisely on a large collection of H. pylori strains by PCR, susceptibility to BccI digestion and sequencing. The results obtained support the mechanism of gain and loss of this R-M system in the H. pylori genome, and suggest that it is an ancestral system which gradually disappears during H. pylori evolution, following successive steps: (1) inactivation of the endonuclease gene, followed or accompanied by: (2) inactivation of the methyltransferase genes, and then: (3) definitive loss, leaving only short endonuclease remnant sequences.

  6. A Novel Tool for Microbial Genome Editing Using the Restriction-Modification System.

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    Bai, Hua; Deng, Aihua; Liu, Shuwen; Cui, Di; Qiu, Qidi; Wang, Laiyou; Yang, Zhao; Wu, Jie; Shang, Xiuling; Zhang, Yun; Wen, Tingyi

    2018-01-19

    Scarless genetic manipulation of genomes is an essential tool for biological research. The restriction-modification (R-M) system is a defense system in bacteria that protects against invading genomes on the basis of its ability to distinguish foreign DNA from self DNA. Here, we designed an R-M system-mediated genome editing (RMGE) technique for scarless genetic manipulation in different microorganisms. For bacteria with Type IV REase, an RMGE technique using the inducible DNA methyltransferase gene, bceSIIM (RMGE-bceSIIM), as the counter-selection cassette was developed to edit the genome of Escherichia coli. For bacteria without Type IV REase, an RMGE technique based on a restriction endonuclease (RMGE-mcrA) was established in Bacillus subtilis. These techniques were successfully used for gene deletion and replacement with nearly 100% counter-selection efficiencies, which were higher and more stable compared to conventional methods. Furthermore, precise point mutation without limiting sites was achieved in E. coli using RMGE-bceSIIM to introduce a single base mutation of A128C into the rpsL gene. In addition, the RMGE-mcrA technique was applied to delete the CAN1 gene in Saccharomyces cerevisiae DAY414 with 100% counter-selection efficiency. The effectiveness of the RMGE technique in E. coli, B. subtilis, and S. cerevisiae suggests the potential universal usefulness of this technique for microbial genome manipulation.

  7. The highly heterogeneous methylated genomes and diverse restriction-modification systems of bloom-forming Microcystis.

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    Zhao, Liang; Song, Yulong; Li, Lin; Gan, Nanqin; Brand, Jerry J; Song, Lirong

    2018-05-01

    The occurrence of harmful Microcystis blooms is increasing in frequency in a myriad of freshwater ecosystems. Despite considerable research pertaining to the cause and nature of these blooms, the molecular mechanisms behind the cosmopolitan distribution and phenotypic diversity in Microcystis are still unclear. We compared the patterns and extent of DNA methylation in three strains of Microcystis, PCC 7806SL, NIES-2549 and FACHB-1757, using Single Molecule Real-Time (SMRT) sequencing technology. Intact restriction-modification (R-M) systems were identified from the genomes of these strains, and from two previously sequenced strains of Microcystis, NIES-843 and TAIHU98. A large number of methylation motifs and R-M genes were identified in these strains, which differ substantially among different strains. Of the 35 motifs identified, eighteen had not previously been reported. Strain NIES-843 contains a larger number of total putative methyltransferase genes than have been reported previously from any bacterial genome. Genomic comparisons reveal that methyltransferases (some partial) may have been acquired from the environment through horizontal gene transfer. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Behavior of restriction-modification systems as selfish mobile elements and their impact on genome evolution.

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    Kobayashi, I

    2001-09-15

    Restriction-modification (RM) systems are composed of genes that encode a restriction enzyme and a modification methylase. RM systems sometimes behave as discrete units of life, like viruses and transposons. RM complexes attack invading DNA that has not been properly modified and thus may serve as a tool of defense for bacterial cells. However, any threat to their maintenance, such as a challenge by a competing genetic element (an incompatible plasmid or an allelic homologous stretch of DNA, for example) can lead to cell death through restriction breakage in the genome. This post-segregational or post-disturbance cell killing may provide the RM complexes (and any DNA linked with them) with a competitive advantage. There is evidence that they have undergone extensive horizontal transfer between genomes, as inferred from their sequence homology, codon usage bias and GC content difference. They are often linked with mobile genetic elements such as plasmids, viruses, transposons and integrons. The comparison of closely related bacterial genomes also suggests that, at times, RM genes themselves behave as mobile elements and cause genome rearrangements. Indeed some bacterial genomes that survived post-disturbance attack by an RM gene complex in the laboratory have experienced genome rearrangements. The avoidance of some restriction sites by bacterial genomes may result from selection by past restriction attacks. Both bacteriophages and bacteria also appear to use homologous recombination to cope with the selfish behavior of RM systems. RM systems compete with each other in several ways. One is competition for recognition sequences in post-segregational killing. Another is super-infection exclusion, that is, the killing of the cell carrying an RM system when it is infected with another RM system of the same regulatory specificity but of a different sequence specificity. The capacity of RM systems to act as selfish, mobile genetic elements may underlie the structure and

  9. Identification of a DNA restriction-modification system in Pectobacterium carotovorum strains isolated from Poland.

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    Waleron, K; Waleron, M; Osipiuk, J; Podhajska, A J; Lojkowska, E

    2006-02-01

    Polish isolates of pectinolytic bacteria from the species Pectobacterium carotovorum were screened for the presence of a DNA restriction-modification (R-M) system. Eighty-nine strains of P. carotovorum were isolated from infected potato plants. Sixty-six strains belonged to P. carotovorum ssp. atrosepticum and 23 to P. carotovorum ssp. carotovorum. The presence of restriction enzyme Pca17AI, which is an isoschizomer of EcoRII endonuclease, was observed in all isolates of P. c. atrosepticum but not in P. c. carotovorum. The biochemical properties, PCR amplification, and sequences of the Pca17AI restriction endonuclease and methyltransferase genes were compared with the prototype EcoRII R-M system genes. Only when DNA isolated from cells of P. c. atrosepticum was used as a template, amplification of a 680 bp homologous to the gene coding EcoRII endonuclease. Endonuclease Pca17AI, having a relatively low temperature optimum, was identified. PCR amplification revealed that the nucleotide sequence of genes for EcoRII and Pca17AI R-M are different. Dcm methylation was observed in all strains of Pectobacterium and other Erwinia species tested. The sequence of a DNA fragment coding Dcm methylase in P. carotovorum was different from that of Escherichia coli. Pca17AI is the first psychrophilic isoschizomer of EcoRII endonuclease. The presence of specific Dcm methylation in chromosomal DNA isolated from P. carotovorum is described for the first time. A 680 bp PCR product, unique for P. c. atrosepticum strains, could serve as a molecular marker for detection of these bacteria in environmental samples.

  10. Comparative Genomics Reveals the Diversity of Restriction-Modification Systems and DNA Methylation Sites in Listeria monocytogenes.

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    Chen, Poyin; den Bakker, Henk C; Korlach, Jonas; Kong, Nguyet; Storey, Dylan B; Paxinos, Ellen E; Ashby, Meredith; Clark, Tyson; Luong, Khai; Wiedmann, Martin; Weimer, Bart C

    2017-02-01

    which manifests as gastroenteritis, meningoencephalitis, and abortion. Among Salmonella, Escherichia coli, Campylobacter, and Listeria-causing the most prevalent foodborne illnesses-infection by L. monocytogenes carries the highest mortality rate. The ability of L. monocytogenes to regulate its response to various harsh environments enables its persistence and transmission. Small-scale comparisons of L. monocytogenes focusing solely on genome contents reveal a highly syntenic genome yet fail to address the observed diversity in phenotypic regulation. This study provides a large-scale comparison of 302 L. monocytogenes isolates, revealing the importance of the epigenome and restriction-modification systems as major determinants of L. monocytogenes phylogenetic grouping and subsequent phenotypic expression. Further examination of virulence genes of select outbreak strains reveals an unprecedented diversity in methylation statuses despite high degrees of genome conservation. Copyright © 2017 American Society for Microbiology.

  11. Evidence for the presence of restriction/modification systems in Lactobacillus delbrueckii.

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    Suárez, Viviana; Zago, Miriam; Giraffa, Giorgio; Reinheimer, Jorge; Quiberoni, Andrea

    2009-11-01

    The bacteriophages Cb1/204 and Cb1/342 were obtained by induction from the commercial strain Lactobacillus delbrueckii subsp. lactis Cb1, and propagated on Lactobacillus delbrueckii subsp. lactis 204 (Lb.l 204) and Lactobacillus delbrueckii subsp. bulgaricus 342 (Lb.b 342), respectively. By cross sensitivity, it was possible to detect a delay in the lysis of Lb.l 204 with Cb1/342 phage, while the adsorption rate was high (99.5%). Modified and unmodified phages were isolated using phage Cb1/342 and strain Lb.l 204. The EOP (Efficiency of Plaquing) values for the four phages (Cb1/204, Cb1/342, Cb1/342modified and Cb1/342unmodified) suggested that an R/M system modified the original temperate phage, and the BglII-DNA restriction patterns of these phages might point out the presence of a Type II R/M system. Also, the existence of a Type I R/M system was demonstrated by PCR and nucleotide sequence, being the percentages of alignment homology with Type I R/M systems reported previously higher than 95%. In this study it was possible to demonstrate that the native phage resistant mechanisms and the occurrence of prophages in commercial host strains, contribute strongly to diversify the phage population in a factory environment.

  12. Is the Evolution of Salmonella enterica subsp. enterica Linked to Restriction-Modification Systems?

    DEFF Research Database (Denmark)

    Roer, Louise; Hendriksen, Rene S.; Leekitcharoenphon, Pimlapas

    2016-01-01

    Salmonella enterica subsp. enterica bacteria are highly diverse foodborne pathogens that are subdivided into more than 1,500 serovars. The diversity is believed to result from mutational evolution, as well as intra- and interspecies recombination that potentially could be influenced by restriction...... to the conjugational mode of horizontal gene transfer in Salmonella. Thus, we conclude that other factors must be involved in shaping the evolution of bacteria.......-modification (RM) systems. The aim of this study was to investigate whether RM systems were linked to the evolution of Salmonella enterica subsp. enterica. The study included 221 Salmonella enterica genomes, of which 68 were de novo sequenced and 153 were public available genomes from ENA. The data set covered 97...

  13. Comparative genome and methylome analysis reveals restriction/modification system diversity in the gut commensal Bifidobacterium breve

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    Bottacini, Francesca; Morrissey, Ruth; Roberts, Richard John; James, Kieran; van Breen, Justin; Egan, Muireann; Lambert, Jolanda; van Limpt, Kees; Knol, Jan; Motherway, Mary O’Connell; van Sinderen, Douwe

    2018-01-01

    Abstract Bifidobacterium breve represents one of the most abundant bifidobacterial species in the gastro-intestinal tract of breast-fed infants, where their presence is believed to exert beneficial effects. In the present study whole genome sequencing, employing the PacBio Single Molecule, Real-Time (SMRT) sequencing platform, combined with comparative genome analysis allowed the most extensive genetic investigation of this taxon. Our findings demonstrate that genes encoding Restriction/Modification (R/M) systems constitute a substantial part of the B. breve variable gene content (or variome). Using the methylome data generated by SMRT sequencing, combined with targeted Illumina bisulfite sequencing (BS-seq) and comparative genome analysis, we were able to detect methylation recognition motifs and assign these to identified B. breve R/M systems, where in several cases such assignments were confirmed by restriction analysis. Furthermore, we show that R/M systems typically impose a very significant barrier to genetic accessibility of B. breve strains, and that cloning of a methyltransferase-encoding gene may overcome such a barrier, thus allowing future functional investigations of members of this species. PMID:29294107

  14. Cloning and analysis of the genes encoding the type IIS restriction-modification system HphI from Haemophilus parahaemolyticus.

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    Lubys, A; Lubienè, J; Kulakauskas, S; Stankevicius, K; Timinskas, A; Janulaitis, A

    1996-07-15

    The genomic region encoding the type IIS restriction-modification (R-M) system HphI (enzymes recognizing the asymmetric sequence 5'-GGTGA-3'/5'-TCACC-3') from Haemophilus parahaemolyticus were cloned into Escherichia coli and sequenced. Sequence analysis of the R-M HphI system revealed three adjacent genes aligned in the same orientation: a cytosine 5 methyltransferase (gene hphIMC), an adenine N6 methyltransferase (hphIMA) and the HphI restriction endonuclease (gene hphIR). Either methyltransferase is capable of protecting plasmid DNA in vivo against the action of the cognate restriction endonuclease. hphIMA methylation renders plasmid DNA resistant to R.Hindill at overlapping sites, suggesting that the adenine methyltransferase modifies the 3'-terminal A residue on the GGTGA strand. Strong homology was found between the N-terminal part of the m6A methyltransferasease and an unidentified reading frame interrupted by an incomplete gaIE gene of Neisseria meningitidis. The HphI R-M genes are flanked by a copy of a 56 bp direct nucleotide repeat on each side. Similar sequences have also been identified in the non-coding regions of H.influenzae Rd DNA. Possible involvement of the repeat sequences in the mobility of the HphI R-M system is discussed.

  15. pHluorin-assisted expression, purification, crystallization and X-ray diffraction data analysis of the C-terminal domain of the HsdR subunit of the Escherichia coli type I restriction-modification system EcoR124I

    Czech Academy of Sciences Publication Activity Database

    Grinkevich, Pavel; Iermak, Iuliia; Luedtke, N.A.; Mesters, J. R.; Ettrich, Rüdiger; Ludwig, Jost

    2016-01-01

    Roč. 72, č. 9 (2016), s. 672-676 ISSN 2053-230X R&D Projects: GA ČR GAP207/12/2323; GA MŠk(CZ) LM2015055 Institutional support: RVO:61388971 Keywords : restriction-modification system * EcoR124I * HsdR Subject RIV: EE - Microbiology, Virology Impact factor: 0.799, year: 2016

  16. Type II restriction modification system methylation subunit of Alicyclobacillus acidocaldarius

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Brady D.; Newby, Deborah T.; Lacey, Jeffrey A.; Thompson, David N.; Thompson, Vicki S.; Apel, William A.; Roberto, Francisco F.; Reed, David W.

    2018-02-13

    Isolated and/or purified polypeptides and nucleic acid sequences encoding polypeptides from Alicyclobacillus acidocaldarius are provided. Further provided are methods for modulating or altering recombination inside or outside of a cell using isolated and/or purified polypeptides and/or nucleic acid sequences from Alicyclobacillus acidocaldarius.

  17. Restriction-modification mediated barriers to exogenous DNA uptake and incorporation employed by Prevotella intermedia.

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    Johnston, Christopher D; Skeete, Chelsey A; Fomenkov, Alexey; Roberts, Richard J; Rittling, Susan R

    2017-01-01

    Prevotella intermedia, a major periodontal pathogen, is increasingly implicated in human respiratory tract and cystic fibrosis lung infections. Nevertheless, the specific mechanisms employed by this pathogen remain only partially characterized and poorly understood, largely due to its total lack of genetic accessibility. Here, using Single Molecule, Real-Time (SMRT) genome and methylome sequencing, bisulfite sequencing, in addition to cloning and restriction analysis, we define the specific genetic barriers to exogenous DNA present in two of the most widespread laboratory strains, P. intermedia ATCC 25611 and P. intermedia Strain 17. We identified and characterized multiple restriction-modification (R-M) systems, some of which are considerably divergent between the two strains. We propose that these R-M systems are the root cause of the P. intermedia transformation barrier. Additionally, we note the presence of conserved Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) systems in both strains, which could provide a further barrier to exogenous DNA uptake and incorporation. This work will provide a valuable resource during the development of a genetic system for P. intermedia, which will be required for fundamental investigation of this organism's physiology, metabolism, and pathogenesis in human disease.

  18. CRISPR-Cas and Restriction-Modification Act Additively against Conjugative Antibiotic Resistance Plasmid Transfer in Enterococcus faecalis.

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    Price, Valerie J; Huo, Wenwen; Sharifi, Ardalan; Palmer, Kelli L

    2016-01-01

    Enterococcus faecalis is an opportunistic pathogen and a leading cause of nosocomial infections. Conjugative pheromone-responsive plasmids are narrow-host-range mobile genetic elements (MGEs) that are rapid disseminators of antibiotic resistance in the faecalis species. Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas and restriction-modification confer acquired and innate immunity, respectively, against MGE acquisition in bacteria. Most multidrug-resistant E. faecalis isolates lack CRISPR-Cas and possess an orphan locus lacking cas genes, CRISPR2, that is of unknown function. Little is known about restriction-modification defense in E. faecalis. Here, we explore the hypothesis that multidrug-resistant E. faecalis strains are immunocompromised. We assessed MGE acquisition by E. faecalis T11, a strain closely related to the multidrug-resistant hospital isolate V583 but which lacks the ~620 kb of horizontally acquired genome content that characterizes V583. T11 possesses the E. faecalis CRISPR3-cas locus and a predicted restriction-modification system, neither of which occurs in V583. We demonstrate that CRISPR-Cas and restriction-modification together confer a 4-log reduction in acquisition of the pheromone-responsive plasmid pAM714 in biofilm matings. Additionally, we show that the orphan CRISPR2 locus is functional for genome defense against another pheromone-responsive plasmid, pCF10, only in the presence of cas9 derived from the E. faecalis CRISPR1-cas locus, which most multidrug-resistant E. faecalis isolates lack. Overall, our work demonstrated that the loss of only two loci led to a dramatic reduction in genome defense against a clinically relevant MGE, highlighting the critical importance of the E. faecalis accessory genome in modulating horizontal gene transfer. Our results rationalize the development of antimicrobial strategies that capitalize upon the immunocompromised status of multidrug-resistant E. faecalis. IMPORTANCE

  19. Organization of the BcgI restriction-modification protein for the cleavage of eight phosphodiester bonds in DNA

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    Smith, Rachel M.; Marshall, Jacqueline J. T.; Jacklin, Alistair J.; Retter, Susan E.; Halford, Stephen E.; Sobott, Frank

    2013-01-01

    Type IIB restriction-modification systems, such as BcgI, feature a single protein with both endonuclease and methyltransferase activities. Type IIB nucleases require two recognition sites and cut both strands on both sides of their unmodified sites. BcgI cuts all eight target phosphodiester bonds before dissociation. The BcgI protein contains A and B polypeptides in a 2:1 ratio: A has one catalytic centre for each activity; B recognizes the DNA. We show here that BcgI is organized as A2B protomers, with B at its centre, but that these protomers self-associate to assemblies containing several A2B units. Moreover, like the well known FokI nuclease, BcgI bound to its site has to recruit additional protomers before it can cut DNA. DNA-bound BcgI can alternatively be activated by excess A subunits, much like the activation of FokI by its catalytic domain. Eight A subunits, each with one centre for nuclease activity, are presumably needed to cut the eight bonds cleaved by BcgI. Its nuclease reaction may thus involve two A2B units, each bound to a recognition site, with two more A2B units bridging the complexes by protein–protein interactions between the nuclease domains. PMID:23147005

  20. CRISPR-Cas and Restriction-Modification Act Additively against Conjugative Antibiotic Resistance Plasmid Transfer in Enterococcus faecalis

    OpenAIRE

    Price, Valerie J.; Huo, Wenwen; Sharifi, Ardalan; Palmer, Kelli L.

    2016-01-01

    ABSTRACT Enterococcus faecalis is an opportunistic pathogen and a leading cause of nosocomial infections. Conjugative pheromone-responsive plasmids are narrow-host-range mobile genetic elements (MGEs) that are rapid disseminators of antibiotic resistance in the faecalis species. Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas and restriction-modification confer acquired and innate immunity, respectively, against MGE acquisition in bacteria. Most multidrug-resistant E.?fa...

  1. Mapping DNA cleavage by the Type ISP restriction-modification enzymes following long-range communication between DNA sites in different orientations

    OpenAIRE

    van Aelst, Kara; Saikrishnan, Kayarat; Szczelkun, Mark D

    2015-01-01

    The prokaryotic Type ISP restriction-modification enzymes are single-chain proteins comprising an Mrr-family nuclease, a superfamily 2 helicase-like ATPase, a coupler domain, a methyltransferase, and a DNA-recognition domain. Upon recognising an unmodified DNA target site, the helicase-like domain hydrolyzes ATP to cause site release (remodeling activity) and to then drive downstream translocation consuming 1-2 ATP per base pair (motor activity). On an invading foreign DNA, double-strand brea...

  2. REGULATION OF NATIONAL QUALIFICATIONS SYSTEMS

    Directory of Open Access Journals (Sweden)

    Anna A. Muravyeva

    2014-01-01

    Full Text Available The paper looks into the diverse aspects of qualifications system regulation, designed for balancing the supply and demand in the labor and educational service markets. Both the objects and mechanisms of such regulation are described. Special attention is given to institutions, involved in regulation of qualifications, and their jurisdiction. Another emphasis is on the industry-related regulation of qualifications which proved to be effective both on the national and European level. Such structures were first established on the national levels to regulate the qualifications and ensure their comparability and compatibility, given the economic globalization and growing labor and academic mobility. The author points out the role of the ministries of education and labor in maintaining a steady qualifications system, and outlines the positive experience of Great Britain using the industry councils for continuing development of qualifications system.

  3. Function and Regulation of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR / CRISPR Associated (Cas Systems

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    Peter C. Fineran

    2012-10-01

    Full Text Available Phages are the most abundant biological entities on earth and pose a constant challenge to their bacterial hosts. Thus, bacteria have evolved numerous ‘innate’ mechanisms of defense against phage, such as abortive infection or restriction/modification systems. In contrast, the clustered regularly interspaced short palindromic repeats (CRISPR systems provide acquired, yet heritable, sequence-specific ‘adaptive’ immunity against phage and other horizontally-acquired elements, such as plasmids. Resistance is acquired following viral infection or plasmid uptake when a short sequence of the foreign genome is added to the CRISPR array. CRISPRs are then transcribed and processed, generally by CRISPR associated (Cas proteins, into short interfering RNAs (crRNAs, which form part of a ribonucleoprotein complex. This complex guides the crRNA to the complementary invading nucleic acid and targets this for degradation. Recently, there have been rapid advances in our understanding of CRISPR/Cas systems. In this review, we will present the current model(s of the molecular events involved in both the acquisition of immunity and interference stages and will also address recent progress in our knowledge of the regulation of CRISPR/Cas systems.

  4. Function and regulation of clustered regularly interspaced short palindromic repeats (CRISPR) / CRISPR associated (Cas) systems.

    Science.gov (United States)

    Richter, Corinna; Chang, James T; Fineran, Peter C

    2012-10-19

    Phages are the most abundant biological entities on earth and pose a constant challenge to their bacterial hosts. Thus, bacteria have evolved numerous 'innate' mechanisms of defense against phage, such as abortive infection or restriction/modification systems. In contrast, the clustered regularly interspaced short palindromic repeats (CRISPR) systems provide acquired, yet heritable, sequence-specific 'adaptive' immunity against phage and other horizontally-acquired elements, such as plasmids. Resistance is acquired following viral infection or plasmid uptake when a short sequence of the foreign genome is added to the CRISPR array. CRISPRs are then transcribed and processed, generally by CRISPR associated (Cas) proteins, into short interfering RNAs (crRNAs), which form part of a ribonucleoprotein complex. This complex guides the crRNA to the complementary invading nucleic acid and targets this for degradation. Recently, there have been rapid advances in our understanding of CRISPR/Cas systems. In this review, we will present the current model(s) of the molecular events involved in both the acquisition of immunity and interference stages and will also address recent progress in our knowledge of the regulation of CRISPR/Cas systems.

  5. NmeSI restriction-modification system identified by representational difference analysis of a hypervirulent Neisseria meningitidis strain

    NARCIS (Netherlands)

    Bart, A.; Pannekoek, Y.; Dankert, J.; van der Ende, A.

    2001-01-01

    Neisseria meningitidis is a gram-negative bacterium that may cause meningitis, sepsis, or both. The increase in the incidence of meningococcal disease in various countries in the past 2 decades is mainly due the genotypically related lineage III meningococci. The chromosomal DNA differences between

  6. Regulation on control systems tests

    International Nuclear Information System (INIS)

    Grau, J.; Navarro, J.M.

    1978-01-01

    Requirements under regulation applicable to the testing of control systems and controlled equipments in the case of USA nuclear projects are examined. They are reviewed, in particular, the following standards and criteria: 10 Code of Federal Regulations 50, Appendix A, General Design Criteria 20 and 21; IEEE Standards 279 and 308; IEEE Standard 338; US Regulatory Guides 1.22 and 1.118.(J.E.de C.)

  7. Selfish restriction modification genes: resistance of a resident R/M plasmid to displacement by an incompatible plasmid mediated by host killing.

    Science.gov (United States)

    Naito, Y; Naito, T; Kobayashi, I

    1998-01-01

    Previous work from this laboratory demonstrated that plasmids carrying a type II restriction-modification gene complex are not easily lost from their bacterial host because plasmid-free segregant cells are killed through chromosome cleavage. Here, we have followed the course of events that takes place when an Escherichia coli rec BC sbcA strain carrying a plasmid coding for the PaeR7I restriction-modification (R/M) gene complex is transformed by a plasmid with an identical origin of replication. The number of transformants that appeared was far fewer than with the restriction-minus (r-) control. Most of the transformants were very small. After prolonged incubation, the number and the size of the colonies increased, but this increase never attained the level of the r- control. Most of the transformed colonies retained the drug-resistance of the resident, r+ m+ plasmid. These results indicate that post-segregational host killing occurs when a plasmid bearing an R/M gene complex is displaced by an incompatible plasmid. Such cell killing eliminates the competitor plasmid along with the host and, thus, would allow persistence of the R/M plasmid in the neighboring, clonal host cells in nature. This phenomenon is reminiscent of mammalian apoptosis and other forms of altruistic cell death strategy against infection. This type of resistance to displacement was also studied in a wild type Escherichia coli strain that was normal for homologous recombination (rec+). A number of differences between the recBC sbcA strain and the rec+ strain were observed and these will be discussed.

  8. Analysis of the Portuguese building regulation system

    OpenAIRE

    Costa Branco De Oliveira Pedro, J.A.; Meijer, F.M.; Visscher, H.J.

    2008-01-01

    The Portuguese building regulation system has undergone significant changes in the last 20 years. Almost all building regulations presently in force were approved during that period. Some of those building regulations resulted from the transposition of European Directives. Other building regulations were changed due to improvements in the scientific knowledge. The changes in the building control system were mainly driven by an adaptation to more pressing circumstances of practice. The lack...

  9. Operational Management System for Regulated Water Systems

    Science.gov (United States)

    van Loenen, A.; van Dijk, M.; van Verseveld, W.; Berger, H.

    2012-04-01

    Most of the Dutch large rivers, canals and lakes are controlled by the Dutch water authorities. The main reasons concern safety, navigation and fresh water supply. Historically the separate water bodies have been controlled locally. For optimizating management of these water systems an integrated approach was required. Presented is a platform which integrates data from all control objects for monitoring and control purposes. The Operational Management System for Regulated Water Systems (IWP) is an implementation of Delft-FEWS which supports operational control of water systems and actively gives advice. One of the main characteristics of IWP is that is real-time collects, transforms and presents different types of data, which all add to the operational water management. Next to that, hydrodynamic models and intelligent decision support tools are added to support the water managers during their daily control activities. An important advantage of IWP is that it uses the Delft-FEWS framework, therefore processes like central data collection, transformations, data processing and presentation are simply configured. At all control locations the same information is readily available. The operational water management itself gains from this information, but it can also contribute to cost efficiency (no unnecessary pumping), better use of available storage and advise during (water polution) calamities.

  10. Simulation of Darlington shutdown and regulation systems

    International Nuclear Information System (INIS)

    1986-10-01

    This report describes the development of a simulation of the Darlington Nuclear Generating Station shutdown and regulating systems, DARSIM. The DARSIM program simulates the spatial neutron dynamics, the regulation of the reactor power, and Shutdown System 1, SDS1, and Shutdown System 2, SDS2, software. The DARSIM program operates in the interactive simulation (INSIM) program environment

  11. Mapping DNA cleavage by the Type ISP restriction-modification enzymes following long-range communication between DNA sites in different orientations

    Science.gov (United States)

    van Aelst, Kara; Saikrishnan, Kayarat; Szczelkun, Mark D.

    2015-01-01

    The prokaryotic Type ISP restriction-modification enzymes are single-chain proteins comprising an Mrr-family nuclease, a superfamily 2 helicase-like ATPase, a coupler domain, a methyltransferase, and a DNA-recognition domain. Upon recognising an unmodified DNA target site, the helicase-like domain hydrolyzes ATP to cause site release (remodeling activity) and to then drive downstream translocation consuming 1–2 ATP per base pair (motor activity). On an invading foreign DNA, double-strand breaks are introduced at random wherever two translocating enzymes form a so-called collision complex following long-range communication between a pair of target sites in inverted (head-to-head) repeat. Paradoxically, structural models for collision suggest that the nuclease domains are too far apart (>30 bp) to dimerise and produce a double-strand DNA break using just two strand-cleavage events. Here, we examined the organisation of different collision complexes and how these lead to nuclease activation. We mapped DNA cleavage when a translocating enzyme collides with a static enzyme bound to its site. By following communication between sites in both head-to-head and head-to-tail orientations, we could show that motor activity leads to activation of the nuclease domains via distant interactions of the helicase or MTase-TRD. Direct nuclease dimerization is not required. To help explain the observed cleavage patterns, we also used exonuclease footprinting to demonstrate that individual Type ISP domains can swing off the DNA. This study lends further support to a model where DNA breaks are generated by multiple random nicks due to mobility of a collision complex with an overall DNA-binding footprint of ∼30 bp. PMID:26507855

  12. Seed regulations and local seed systems

    NARCIS (Netherlands)

    Louwaars, N.

    2000-01-01

    Seed regulations have been introduced in most countries based on the development of formal seed production. Concerns about seed quality and about the varietal identity of the seeds have commonly led to seed laws. However, formal regulations are often inappropriate for informal seed systems, which

  13. Expert system aids transport regulation users

    International Nuclear Information System (INIS)

    Cheshire, R.D.; Straw, R.J.

    1990-01-01

    During late 1984 the IAEA Regulations were identified as an area of application for an expert system adviser which could offer many advantages. Over the following year some simple tests were carried out to examine its feasibility, but TRANAID did not get underway until 1986 when British Nuclear Fuels (BNFL) Corporate Management services were engaged on the product. By this time a greater choice of suitable software, in the form of expert system shells, had become available. After a number of trial systems the shell Leonardo was finally adopted for the final system. In order for TRANAID to emulate the expert it was necessary to spend time extracting and documenting the expert knowledge. This was a matter of investigating how the regulations are used and was achieved by a series of meetings including opportunity for the computer specialists to interview the regulations experts. There are several benefits in having an expert system advisor in this area. It is useful to both experienced and inexperienced users of regulations. For those who are learning to use the regulations it is an excellent training aid. For those who know the regulations but use them infrequently it can save time and provide a valuable reassurance. The adviser has enabled the expert user's know how to be captured and to be made widely available to those with less experience. (author)

  14. On output regulation for linear systems

    NARCIS (Netherlands)

    Saberi, Ali; Stoorvogel, Antonie Arij; Sannuti, Peddapullaiah

    For both continuous- and discrete-time systems, we revisit the output regulation problem for linear systems. We generalize the problem formulation in order • to expand the class of reference or disturbance signals, • to utilize the derivative or feedforward information of reference signals whenever

  15. Signal-regulated systems and networks

    CSIR Research Space (South Africa)

    Van Zyl, TL

    2010-07-01

    Full Text Available The article presents the use of signal regulatory networks (SRNs), a biologically inspired model based on gene regulatory networks. SRNs are a way of understanding a class of self-organizing IT systems, signal-regulated systems (SRSs). This article...

  16. Role of Osmolytes in Regulating Immune System.

    Science.gov (United States)

    Kumar, Tarun; Yadav, Manisha; Singh, Laishram Rajendrakumar

    2016-01-01

    The immune system has evolved to protect the host organism from diverse range of pathogenic microbes that are themselves constantly evolving. It is a complex network of cells, humoral factors, chemokines and cytokines. Dysregulation of immune system results in various kinds of immunological disorders. There are several external agents which govern the regulation of immune system. Recent studies have indicated the role of osmolytes in regulation of various immunological processes such as Ag-Ab interaction, Ig assembly, Ag presentation etc. In this present review, we have systematically discussed the role of osmolytes involved in regulation of several key immunological processes. Osmolytes are involved in the regulation of several key immunological processes such as immunoglobulin assembly and folding, immune cells proliferation, regulation of immune cells function, Ag-Ab interaction, antigen presentation, inflammatory response and protection against photo-immunosuppression. Hence, osmolytes and their transporters might be used as potential drug and drug targets respectively. This review is therefore designed to help clinicians in development of osmolyte based therapeutic strategies in the treatment of various immunological disorders. Appropriate future perspectives have also been included.

  17. Intraocular pressure reduction and regulation system

    Science.gov (United States)

    Baehr, E. F.; Burnett, J. E.; Felder, S. F.; Mcgannon, W. J.

    1979-01-01

    An intraocular pressure reduction and regulation system is described and data are presented covering performance in: (1) reducing intraocular pressure to a preselected value, (2) maintaining a set minimum intraocular pressure, and (3) reducing the dynamic increases in intraocular pressure resulting from external loads applied to the eye.

  18. Shigella Iron Acquisition Systems and their Regulation.

    Science.gov (United States)

    Wei, Yahan; Murphy, Erin R

    2016-01-01

    Survival of Shigella within the host is strictly dependent on the ability of the pathogen to acquire essential nutrients, such as iron. As an innate immune defense against invading pathogens, the level of bio-available iron within the human host is maintained at exceeding low levels, by sequestration of the element within heme and other host iron-binding compounds. In response to sequestration mediated iron limitation, Shigella produce multiple iron-uptake systems that each function to facilitate the utilization of a specific host-associated source of nutrient iron. As a mechanism to balance the essential need for iron and the toxicity of the element when in excess, the production of bacterial iron acquisition systems is tightly regulated by a variety of molecular mechanisms. This review summarizes the current state of knowledge on the iron-uptake systems produced by Shigella species, their distribution within the genus, and the molecular mechanisms that regulate their production.

  19. Self-regulating energy storage system

    Energy Technology Data Exchange (ETDEWEB)

    Eisenhaure, D.B.; Downer, J.R.; Bliamptis, T.E.; Oberbeck, G.A.; Hendrie, S.D.

    1986-10-14

    This patent describes a self-regulating energy storage system which consists of: an a.c. motor/generator including a rotor; a flywheel attached to the motor/generator; means for monitoring the position of the motor/generator rotor; means for resolving current to and from the motor/generator; a pulse width modulated bidirectional inverter interconnecting the motor/generator with a power supply bus having a voltage to be regulated; a summing circuit for determining differences between a reference voltage and the voltage on the power supply bus to be regulated; and a pulse width modulation switch control responsive to the summing circuit, to the means for monitoring, and to the means for resolving.

  20. Spatial Structures and Regulation in Biological Systems

    DEFF Research Database (Denmark)

    Yde, Pernille

    , and the other is the spatial regulation of biological systems, here related to different aspects of the inflammatory response. All systems are studied using computational modelling and mathematical analysis. The first part of the thesis explores different protein aggregation scenarios. In Chapter 1, we consider...... a previously studied and very general aggregation model describing frangible linear filaments. This model is especially relevant for the growth of amyloid fibres, that have been related to a number of serious human diseases, and which are known to grow in an accelerated self-enhanced manner.We derive...... model of the tissue and show how coupled cells are able to function as an excitable medium and propagate waves of high cytokine concentration through the tissue. If the internal regulation in the cells is over-productive, the model predicts a continuous amplification of cytokines, which spans the entire...

  1. Frontiers of environmental regulation: environmental management systems: a regulator`s perspective

    Energy Technology Data Exchange (ETDEWEB)

    Stone, M.J. [South Australian Dept. of Mines and Energy, Adelaide, SA (Australia)

    1996-12-31

    Leading edge companies throughout the world have embraced management systems to achieve optimal sustainable performance in the ever changing business environment of the 1990s. Given that the natural environment and environmental performance have become major issues affecting organizations, the need for integrating environmental management with all the other components of an organization`s overall management approach is now widely recognized. This paper is organized in five parts. The first explores recently released environmental standards, the interim environmental management systems (EMS) general guidelines standard AS/NZS ISO 14004 (Int) and identifies how this has dealt with the regulator/community/company interface. The second identifies company requirements for addressing environmental issues. The third, considers regulatory theory to identify current requirements for an effective regulatory system and how this can interface with a company`s EMS. These form the basis in the fourth section for identifying some opportunities which occur at the company/ regulator interface. The fifth and final section draws a number of conclusions about the current frontiers of environmental regulation. The coincidence of the requirements of a regulatory framework with the areas of interface between what is referred to in the draft International Standard for EMS as `Interested Parties`, the regulators and community, are identified. (author). 1 tab., 2 figs., 20 refs.

  2. Microprocessor system for temperature regulation and stabilization

    International Nuclear Information System (INIS)

    Nguyen Nhi Dien; Rodionov, K.G.

    1989-01-01

    Microprocessor based system for temperature regulation and stabilization of an operation external object is described. The system has the direct current amplifier working according to modulator-demodulator principle. The overal gain is 100, 1000, 2000. The maximum output signal is ±10 V. The power amplifier is a thyristor one and its line voltage is 220 V, 50 Hz. The output power is 0-2 kVA. The microcontroller has a remote display terminal. Data input is 8 and data output is one. Input and output voltage is ±(0-10) V. The preselection time for stabilization is within 1 s - 18 h. The program algorithm is given. 5 figs.; 1 tab

  3. 21 CFR 870.5900 - Thermal regulating system.

    Science.gov (United States)

    2010-04-01

    ... system. (a) Identification. A thermal regulating system is an external system consisting of a device that is placed in contact with the patient and a temperature controller for the device. The system is used... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Thermal regulating system. 870.5900 Section 870...

  4. The restriction-modification genes of Escherichia coli K-12 may not be selfish: they do not resist loss and are readily replaced by alleles conferring different specificities.

    Science.gov (United States)

    O'Neill, M; Chen, A; Murray, N E

    1997-12-23

    Type II restriction and modification (R-M) genes have been described as selfish because they have been shown to impose selection for the maintenance of the plasmid that encodes them. In our experiments, the type I R-M system EcoKI does not behave in the same way. The genes specifying EcoKI are, however, normally residents of the chromosome and therefore our analyses were extended to monitor the deletion of chromosomal genes rather than loss of plasmid vector. If EcoKI were to behave in the same way as the plasmid-encoded type II R-M systems, the loss of the relevant chromosomal genes by mutation or recombination should lead to cell death because the cell would become deficient in modification enzyme and the bacterial chromosome would be vulnerable to the restriction endonuclease. Our data contradict this prediction; they reveal that functional type I R-M genes in the chromosome are readily replaced by mutant alleles and by alleles encoding a type I R-M system of different specificity. The acquisition of allelic genes conferring a new sequence specificity, but not the loss of the resident genes, is dependent on the product of an unlinked gene, one predicted [Prakash-Cheng, A., Chung, S. S. & Ryu, J. (1993) Mol. Gen. Genet. 241, 491-496] to be relevant to control of expression of the genes that encode EcoKI. Our evidence suggests that not all R-M systems are evolving as "selfish" units; rather, the diversity and distribution of the family of type I enzymes we have investigated require an alternative selective pressure.

  5. Power supply regulation systems installed in the Fermilab accelerators

    Energy Technology Data Exchange (ETDEWEB)

    Hays, S.; Wolff, D.; Pfeffer, H.

    1991-11-01

    A variety of current and voltage regulation systems have been installed in the Fermilab large magnet system. The four major systems employ different methods to achieve the desired degree of regulation. The methods include computer control and feedback, adaptive learning, precision (10ppm) current monitoring, and the use of feed-forward signals. This paper will explain each method used and present the measured regulation of the above systems. Also an overview of planned upgrades and improvements will be presented.

  6. Safety regulation KTA 3901: Communication systems for nuclear power plants

    International Nuclear Information System (INIS)

    1981-01-01

    The regulation applies to communication systems in stationary nuclear power plants with at least one power plant unit, i.e. alarm systems, staff locator systems, communicators, and systems for external communication. The regulation determines the type and extent of staff communication systems as well as the demands to be made on layout, installation, operating systems, and testing of communication systems for nuclear power plants. (orig./HP) [de

  7. Information Processing in Auto-regulated Systems

    Directory of Open Access Journals (Sweden)

    Karl Javorszky

    2003-06-01

    Full Text Available Abstract: We present a model of information processing which is based on two concurrent ways of describing the world, where a description in one of the languages limits the possibilities for realisations in the other language. The two describing dimensions appear in our common sense as dichotomies of perspectives: subjective - objective; diversity - similarity; individual - collective. We abstract from the subjective connotations and treat the test theoretical case of an interval on which several concurrent categories can be introduced. We investigate multidimensional partitions as potential carriers of information and compare their efficiency to that of sequenced carriers. We regard the same assembly once as a contemporary collection, once as a longitudinal sequence and find promising inroads towards understanding information processing by auto-regulated systems. Information is understood to point out that what is the case from among alternatives, which could be the case. We have translated these ideas into logical operations on the set of natural numbers and have found two equivalence points on N where matches between sequential and commutative ways of presenting a state of the world can agree in a stable fashion: a flip-flop mechanism is envisioned. By following this new approach, a mathematical treatment of some poignant biomathematical problems is allowed. Also, the concepts presented in this treatise may well have relevance and applications within the information processing and the theory of language fields.

  8. A General Water Resources Regulation Software System in China

    Science.gov (United States)

    LEI, X.

    2017-12-01

    To avoid iterative development of core modules in water resource normal regulation and emergency regulation and improve the capability of maintenance and optimization upgrading of regulation models and business logics, a general water resources regulation software framework was developed based on the collection and analysis of common demands for water resources regulation and emergency management. It can provide a customizable, secondary developed and extensible software framework for the three-level platform "MWR-Basin-Province". Meanwhile, this general software system can realize business collaboration and information sharing of water resources regulation schemes among the three-level platforms, so as to improve the decision-making ability of national water resources regulation. There are four main modules involved in the general software system: 1) A complete set of general water resources regulation modules allows secondary developer to custom-develop water resources regulation decision-making systems; 2) A complete set of model base and model computing software released in the form of Cloud services; 3) A complete set of tools to build the concept map and model system of basin water resources regulation, as well as a model management system to calibrate and configure model parameters; 4) A database which satisfies business functions and functional requirements of general water resources regulation software can finally provide technical support for building basin or regional water resources regulation models.

  9. System certification progress in concept recognition in IAEA regulation

    International Nuclear Information System (INIS)

    Luna, R.E.; Pollog, T.

    1995-01-01

    System Certification is a regulatory concept which is intended to expand the scope of radioactive material transport regulations by allowing alternative means for proving compliance with the requisite standards of safety set out in transport regulations. In practice it may allow more stringent requirements in one aspect of the regulations to be substituted for less stringent application in other areas so long as the safety standard provided by regulation is preserved. The concept is widely perceived as the imposition of operational controls in exchange for relaxation of packaging standards, but that is only one possibility in the spectrum of potential actions under a System Certification provision in IAEA or national regulations

  10. Forest regulation methods and silvicultural systems: what are they?

    Science.gov (United States)

    Ivan L. Sander; Burnell C. Fischer

    1989-01-01

    "Forest regulation methods" and "silvicultural systems" are important forest resource management concepts but there is much confusion about them. They often mean different things to different individuals. Confusion exists in part because "forest regulation methods" and "silvicultural systems" often use the same terminology. Also...

  11. Limit regulation system for pressurized water nuclear reactors

    International Nuclear Information System (INIS)

    Aleite, W.; Bock, H.W.

    1976-01-01

    Described is a limit regulation system for a pressurized water nuclear reactor in combination with a steam generating system connected to a turbine, the nuclear reactor having control rods as well as an operational regulation system and a protective system, which includes reactor power limiting means operatively associated with the control rods for positioning the same and having response values between operating ranges of the operational regulation system, on the one hand, and response values of the protective system, on the other hand, and a live steam-minimal pressure regulation system cooperating with the reactor power limiting means and operatively connected to a steam inlet valve to the turbine for controlling the same

  12. Effect Mechanism of Penstock on Stability and Regulation Quality of Turbine Regulating System

    Directory of Open Access Journals (Sweden)

    Wencheng Guo

    2014-01-01

    Full Text Available This paper studies the effect mechanism of water inertia and head loss of penstock on stability and regulation quality of turbine regulating system with surge tank or not and proposes the construction method of equivalent model of regulating system. Firstly, the complete linear mathematical model of regulating system is established. Then, the free oscillation equation and time response of the frequency that describe stability and regulation quality, respectively, are obtained. Finally, the effects of penstock are analysed by using stability region and response curves. The results indicate that the stability and regulation quality of system without surge tank are determined by time response of frequency which only depends on water hammer wave in penstock, while, for system with surge tank, the time response of frequency depending on water hammer wave in penstock and water-level fluctuation in surge tank jointly determines the stability and regulation quality. Water inertia of penstock mainly affects the stability and time response of frequency of system without surge tank as well as the stability and head wave of time response of frequency with surge tank. Head loss of penstock mainly affects the stability and tail wave of time response of frequency with surge tank.

  13. The simple analytics of systemic liquidity risk regulation

    NARCIS (Netherlands)

    Perotti, E.; Suarez, J.

    2011-01-01

    How to regulate systemic risk? This column presents a new CEPR discussion paper assessing the performance of Pigouvian taxes and quantity-based regulations in containing the social costs of high-risk banking. It finds that, depending on how banks differ, the socially efficient solution may be

  14. Estimation of regulated term of technical systems further operation

    International Nuclear Information System (INIS)

    Strel'nikov, V.P.

    2008-01-01

    The technique of estimating the regulated term of technical systems further operation on the basis of data on failures during operation and use of probabilistic-physical model of failures (DN-distribution) is proposed

  15. CREBH Regulates Systemic Glucose and Lipid Metabolism

    Directory of Open Access Journals (Sweden)

    Yoshimi Nakagawa

    2018-05-01

    Full Text Available The cyclic adenosine monophosphate (cAMP-responsive element-binding protein H (CREBH, encoded by CREB3L3 is a membrane-bound transcriptional factor that primarily localizes in the liver and small intestine. CREBH governs triglyceride metabolism in the liver, which mediates the changes in gene expression governing fatty acid oxidation, ketogenesis, and apolipoproteins related to lipoprotein lipase (LPL activation. CREBH in the small intestine reduces cholesterol transporter gene Npc1l1 and suppresses cholesterol absorption from diet. A deficiency of CREBH in mice leads to severe hypertriglyceridemia, fatty liver, and atherosclerosis. CREBH, in synergy with peroxisome proliferator-activated receptor α (PPARα, has a crucial role in upregulating Fgf21 expression, which is implicated in metabolic homeostasis including glucose and lipid metabolism. CREBH binds to and functions as a co-activator for both PPARα and liver X receptor alpha (LXRα in regulating gene expression of lipid metabolism. Therefore, CREBH has a crucial role in glucose and lipid metabolism in the liver and small intestine.

  16. Numerical Simulation of Tubular Pumping Systems with Different Regulation Methods

    Science.gov (United States)

    Zhu, Honggeng; Zhang, Rentian; Deng, Dongsheng; Feng, Xusong; Yao, Linbi

    2010-06-01

    Since the flow in tubular pumping systems is basically along axial direction and passes symmetrically through the impeller, most satisfying the basic hypotheses in the design of impeller and having higher pumping system efficiency in comparison with vertical pumping system, they are being widely applied to low-head pumping engineering. In a pumping station, the fluctuation of water levels in the sump and discharge pool is most common and at most time the pumping system runs under off-design conditions. Hence, the operation of pump has to be flexibly regulated to meet the needs of flow rates, and the selection of regulation method is as important as that of pump to reduce operation cost and achieve economic operation. In this paper, the three dimensional time-averaged Navier-Stokes equations are closed by RNG κ-ɛ turbulent model, and two tubular pumping systems with different regulation methods, equipped with the same pump model but with different designed system structures, are numerically simulated respectively to predict the pumping system performances and analyze the influence of regulation device and help designers make final decision in the selection of design schemes. The computed results indicate that the pumping system with blade-adjusting device needs longer suction box, and the increased hydraulic loss will lower the pumping system efficiency in the order of 1.5%. The pumping system with permanent magnet motor, by means of variable speed regulation, obtains higher system efficiency partly for shorter suction box and partly for different structure design. Nowadays, the varied speed regulation is realized by varied frequency device, the energy consumption of which is about 3˜4% of output power of the motor. Hence, when the efficiency of variable frequency device is considered, the total pumping system efficiency will probably be lower.

  17. Development of a safety and regulation systems simulation program II

    International Nuclear Information System (INIS)

    1985-05-01

    This report describes the development of a safety and regulation systems simulation program under contract to the Atomic Energy Control Board of Canada. A systems logic interaction simulation (SLISIM) program was developed for the AECB's HP-1000 computer which operates in the interactive simulation (INSIM) program environment. The SLISIM program simulates the spatial neutron dynamics, the regulation of the reactor power and in this version the CANDU-PHW 600 MW(e) computerized shutdown systems' trip parameters. The modular concept and interactive capability of the INSIM environment provides the user with considerable flexibility of the setup and control of the simulation

  18. Incremental passivity and output regulation for switched nonlinear systems

    Science.gov (United States)

    Pang, Hongbo; Zhao, Jun

    2017-10-01

    This paper studies incremental passivity and global output regulation for switched nonlinear systems, whose subsystems are not required to be incrementally passive. A concept of incremental passivity for switched systems is put forward. First, a switched system is rendered incrementally passive by the design of a state-dependent switching law. Second, the feedback incremental passification is achieved by the design of a state-dependent switching law and a set of state feedback controllers. Finally, we show that once the incremental passivity for switched nonlinear systems is assured, the output regulation problem is solved by the design of global nonlinear regulator controllers comprising two components: the steady-state control and the linear output feedback stabilising controllers, even though the problem for none of subsystems is solvable. Two examples are presented to illustrate the effectiveness of the proposed approach.

  19. Is it possible to improve regulation system of PWR

    International Nuclear Information System (INIS)

    Bonnemay, A.; Martinez, J.M.

    1983-03-01

    This paper deals with two problems: first of all, it presents the critical analysis of usually implemented general regulation systems, on PWR plants, and derives from it same possibilities to improve the transient behavior of reactor, the second part is a proposition from an automatic control system for spatial distribution of flux

  20. Abnormal Default System Functioning in Depression: Implications for Emotion Regulation.

    Science.gov (United States)

    Messina, Irene; Bianco, Francesca; Cusinato, Maria; Calvo, Vincenzo; Sambin, Marco

    2016-01-01

    Depression is widely seen as the result of difficulties in regulating emotions. Based on neuroimaging studies on voluntary emotion regulation, neurobiological models have focused on the concept of cognitive control, considering emotion regulation as a shift toward involving controlled processes associated with activation of the prefrontal and parietal executive areas, instead of responding automatically to emotional stimuli. According to such models, the weaker executive area activation observed in depressed patients is attributable to a lack of cognitive control over negative emotions. Going beyond the concept of cognitive control, psychodynamic models describe the development of individuals' capacity to regulate their emotional states in mother-infant interactions during childhood, through the construction of the representation of the self, others, and relationships. In this mini-review, we link these psychodynamic models with recent findings regarding the abnormal functioning of the default system in depression. Consistently with psychodynamic models, psychological functions associated with the default system include self-related processing, semantic processes, and implicit forms of emotion regulation. The abnormal activation of the default system observed in depression may explain the dysfunctional aspects of emotion regulation typical of the condition, such as an exaggerated negative self-focus and rumination on self-esteem issues. We also discuss the clinical implications of these findings with reference to the therapeutic relationship as a key tool for revisiting impaired or distorted representations of the self and relational objects.

  1. Regulation of vitamin D homeostasis: implications for the immune system.

    Science.gov (United States)

    van Etten, Evelyne; Stoffels, Katinka; Gysemans, Conny; Mathieu, Chantal; Overbergh, Lut

    2008-10-01

    Vitamin D homeostasis in the immune system is the focus of this review. The production of both the activating (25- and 1alpha-hydroxylase) and the metabolizing (24-hydroxylase) enzymes by cells of the immune system itself, indicates that 1,25(OH)(2)D(3) can be produced locally in immune reaction sites. Moreover, the strict regulation of these enzymes by immune signals is highly suggestive for an autocrine/paracrine role in the immune system, and opens new treatment possibilities.

  2. Liquid hydrogen transfer pipes and level regulation systems

    International Nuclear Information System (INIS)

    Marquet, M.; Prugne, P.; Roubeau, P.

    1961-01-01

    Describes: 1) Transfer pipes - Plunging rods in liquid hydrogen Dewars; transfer pipes: knee-joint system for quick and accurate positioning of plunging Dewar rods; system's rods: combined valve and rod; valves are activated either by a bulb pressure or by a solenoid automatically or hand controlled. The latter allows intermittent filling. 2) Level regulating systems: Level bulbs: accurate to 1 or 4 m; maximum and minimum level bulbs: automatic control of the liquid hydrogen valve. (author) [fr

  3. Current state and trend of radiation regulation system in Japan

    International Nuclear Information System (INIS)

    Yonehara, Hidenori

    2004-01-01

    Japanese regulation system for safety against radiation essentially started from 'Atomic Energy Basic Law' enacted in 1955 and 'Law Concerning Prevention of Radiation Hazards due to Radioisotopes, etc' enacted in 1957, has been regarded as a central rule for radiation protection and safety. Related laws and regulations have been enacted together with their revision. Radiation Council, established in the Science and Technology Agency in 1962 and now belonging to the Ministry of Education, Culture, Sports, Science and Technology, has deliberated basically on International Commission of Radiological Protection (ICRP) statements for legal revision and has set up working groups for current problems. Activities of the groups have concerned ICRP Publication 60 (1990) and later related publications for incorporating the principle into laws as to concepts of dose limits, effective dose, and then of exemption and exclusion. International status of the Japanese regulation, problems and tasks in the regulation are also commented. (N.I.)

  4. Pressure regulation system for modern gas-filled detectors

    International Nuclear Information System (INIS)

    McDonald, R.J.

    1986-08-01

    A gas pressure and flow regulation system has been designed and constructed to service a wide variety of gas-filled detectors which operate at pressures of ∼2 to 1000 Torr and flow rate of ∼5 to 200 standard cubic centimeters per minute (sccm). Pressure regulation is done at the detector input by a pressure transducer linked to a solenoid leak valve via an electronic control system. Gas flow is controlled via a mechanical leak valve at the detector output. Interchangeable transducers, flowmeters, and leak valves allow for different pressure and flow ranges. The differential pressure transducer and control system provide automatic let-up of vacuum chambers to atmospheric pressure while maintaining a controlled overpressure in the detector. The gas system is constructed on a standard 19'' rack-mounted panel from commercially available parts. Five of these systems have been built and are routinely used for both ionization chambers and position-sensitive avalanche detectors

  5. Approaches Mediating Oxytocin Regulation of the Immune System.

    Science.gov (United States)

    Li, Tong; Wang, Ping; Wang, Stephani C; Wang, Yu-Feng

    2016-01-01

    The hypothalamic neuroendocrine system is mainly composed of the neural structures regulating hormone secretion from the pituitary gland and has been considered as the higher regulatory center of the immune system. Recently, the hypothalamo-neurohypophysial system (HNS) emerged as an important component of neuroendocrine-immune network, wherein the oxytocin (OT)-secreting system (OSS) plays an essential role. The OSS, consisting of OT neurons in the supraoptic nucleus, paraventricular nucleus, their several accessory nuclei and associated structures, can integrate neural, endocrine, metabolic, and immune information and plays a pivotal role in the development and functions of the immune system. The OSS can promote the development of thymus and bone marrow, perform immune surveillance, strengthen immune defense, and maintain immune homeostasis. Correspondingly, OT can inhibit inflammation, exert antibiotic-like effect, promote wound healing and regeneration, and suppress stress-associated immune disorders. In this process, the OSS can release OT to act on immune system directly by activating OT receptors or through modulating activities of other hypothalamic-pituitary-immune axes and autonomic nervous system indirectly. However, our understandings of the role of the OSS in neuroendocrine regulation of immune system are largely incomplete, particularly its relationship with other hypothalamic-pituitary-immune axes and the vasopressin-secreting system that coexists with the OSS in the HNS. In addition, it remains unclear about the relationship between the OSS and peripherally produced OT in immune regulation, particularly intrathymic OT that is known to elicit central immunological self-tolerance of T-cells to hypophysial hormones. In this work, we provide a brief review of current knowledge of the features of OSS regulation of the immune system and of potential approaches that mediate OSS coordination of the activities of entire neuroendocrine-immune network.

  6. USA IN THE EMERGING SYSTEM OF GLOBAL FINANCIAL REGULATION

    Directory of Open Access Journals (Sweden)

    V. K. Kulakova

    2016-01-01

    Full Text Available In the globalizing world of fi nancial and economic interdependence, a polycentric, multi-level, and hierarchical system of global financial regulation is emerging. The article highlights two vectors of recent development in international fi nancial regulation: the rise of cooperation through the mechanisms of the Group of Twenty (G-20 on the one hand, and the efforts to maintain the US leading role in global fi nance, on the other hand. In the circumstances of the global fi nancial crisis of 2008, the G-20 countries initiated an international reform of fi nancial regulation. According to G-20 decisions, international standardsetting organizations developed transnational regulatory regimes in the fi elds of banking, derivatives and bankruptcy resolution, and the states now implement these regimes in their jurisdictions. The so-called “soft law system”, which is not legally binding, allows the states to sustain national sovereignty in their fi nancial policy. The United States play a leading role in the international fi nancial reform, as well as in the shaping of the global fi nancial regulation system. The American regulators push for extraterritorial application of the US norms and take other unilateral actions on the international arena. The article also touches upon legitimacy problems of the emerging system of global fi nancial regulation. The most important constrains are the excessive infl uence of the fi nancial industry (“regulatory capture”, the weakness of civil society participation, and also the fact that for the rest of the world the American norms lack legitimacy, as they are adopted by regulators assigned by offi cials elected by population of a foreign territory.

  7. The RPI-X system of regulation and British Gas

    International Nuclear Information System (INIS)

    Spring, P.

    1992-01-01

    The RPI-X system of regulation was subject to a theoretical examination in a previous paper 'The RPI-X system of price-capping regulation re-examined'. The practical example of British Gas shows that what started out as a simple formula can become a complex hybrid lacking in transparency. The formula has properties which mean that its impact can be harsher or lighter depending on exogenous factors which the regulated company cannot be entirely or reasonably expected to predict or control. In the first five years - 1987 to 1992 -of the formula's application, when X was set at a very undemanding 2%, the surge in the RPI, resulted in a virtual windfall increase in profits. In the second five years 1992 to 1997 - X has been reset at a much more demanding 5%. Also, new terms for gas costs (GPI-Z) and energy efficiency (E) have been introduced which are quite lacking in transparency. (author)

  8. Dynamic Model of Kaplan Turbine Regulating System Suitable for Power System Analysis

    OpenAIRE

    Zhao, Jie; Wang, Li; Liu, Dichen; Wang, Jun; Zhao, Yu; Liu, Tian; Wang, Haoyu

    2015-01-01

    Accurate modeling of Kaplan turbine regulating system is of great significance for grid security and stability analysis. In this paper, Kaplan turbine regulating system model is divided into the governor system model, the blade control system model, and the turbine and water diversion system model. The Kaplan turbine has its particularity, and the on-cam relationship between the wicket gate opening and the runner blade angle under a certain water head on the whole range was obtained by high-o...

  9. Emotion regulation and conflict transformation in multi-team systems

    NARCIS (Netherlands)

    Curseu, P.L.; Meeus, M.T.H.

    2014-01-01

    Purpose The aim of this paper is to test the moderating role of emotion regulation in the transformation of both task and process conflict into relationship conflict. Design/methodology/approach A field study of multi-teams systems, in which (94) respondents are engaged in interpersonal and

  10. Osmosensory mechanisms in cellular and systemic volume regulation

    DEFF Research Database (Denmark)

    Pedersen, Stine Helene Falsig; Kapus, András; Hoffmann, Else K

    2011-01-01

    Perturbations of cellular and systemic osmolarity severely challenge the function of all organisms and are consequently regulated very tightly. Here we outline current evidence on how cells sense volume perturbations, with particular focus on mechanisms relevant to the kidneys and to extracellular...

  11. Reconstructing a Network of Stress-Response Regulators via Dynamic System Modeling of Gene Regulation

    Directory of Open Access Journals (Sweden)

    Wei-Sheng Wu

    2008-01-01

    Full Text Available Unicellular organisms such as yeasts have evolved mechanisms to respond to environmental stresses by rapidly reorganizing the gene expression program. Although many stress-response genes in yeast have been discovered by DNA microarrays, the stress-response transcription factors (TFs that regulate these stress-response genes remain to be investigated. In this study, we use a dynamic system model of gene regulation to describe the mechanism of how TFs may control a gene’s expression. Then, based on the dynamic system model, we develop the Stress Regulator Identification Algorithm (SRIA to identify stress-response TFs for six kinds of stresses. We identified some general stress-response TFs that respond to various stresses and some specific stress-response TFs that respond to one specifi c stress. The biological significance of our findings is validated by the literature. We found that a small number of TFs is probably suffi cient to control a wide variety of expression patterns in yeast under different stresses. Two implications can be inferred from this observation. First, the response mechanisms to different stresses may have a bow-tie structure. Second, there may be regulatory cross-talks among different stress responses. In conclusion, this study proposes a network of stress-response regulators and the details of their actions.

  12. Activation of ion transport systems during cell volume regulation

    International Nuclear Information System (INIS)

    Eveloff, J.L.; Warnock, D.G.

    1987-01-01

    This review discusses the activation of transport pathways during volume regulation, including their characteristics, the possible biochemical pathways that may mediate the activation of transport pathways, and the relations between volume regulation and transepithelial transport in renal cells. Many cells regulate their volume when exposed to an anisotonic medium. The changes in cell volume are caused by activation of ion transport pathways, plus the accompanying osmotically driven water movement such that cell volume returns toward normal levels. The swelling of hypertonically shrunken cells is termed regulatory volume increase (RVI) and involves an influx of NaCl into the cell via either activation of Na-Cl, Na-K-2Cl cotransport systems, or Na + -H + and Cl - -HCO 3 - exchangers. The reshrinking of hypotonically swollen cells is termed regulatory volume decrease (RVD) and involves an efflux of KCl and water from the cell by activation of either separate K + and Cl - conductances, a K-Cl cotransport system, or parallel K + -H + and Cl - -HCO 3 - exchangers. The biochemical mechanisms involved in the activation of transport systems are largely unknown, however, the phosphoinositide pathway may be implicated in RVI; phorbol esters, cGMP, and Ca 2+ affect the process of volume regulation. Renal tubular cells, as well as the blood cells that transverse the medulla, are subjected to increasing osmotic gradients from the corticomedullary junction to the papillary tip, as well as changing interstitial and tubule fluid osmolarity, depending on the diuretic state of the animal. Medullary cells from the loop of Henle and the papilla can volume regulate by activating Na-K-2Cl cotransport or Na + -H + and Cl - -HCO 3 - exchange systems

  13. The Real Culprit in Systemic Lupus Erythematosus: Abnormal Epigenetic Regulation

    Science.gov (United States)

    Wu, Haijing; Zhao, Ming; Chang, Christopher; Lu, Qianjin

    2015-01-01

    Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs and the presence of anti-nuclear antibodies. The pathogenesis of SLE has been intensively studied but remains far from clear. B and T lymphocyte abnormalities, dysregulation of apoptosis, defects in the clearance of apoptotic materials, and various genetic and epigenetic factors are attributed to the development of SLE. The latest research findings point to the association between abnormal epigenetic regulation and SLE, which has attracted considerable interest worldwide. It is the purpose of this review to present and discuss the relationship between aberrant epigenetic regulation and SLE, including DNA methylation, histone modifications and microRNAs in patients with SLE, the possible mechanisms of immune dysfunction caused by epigenetic changes, and to better understand the roles of aberrant epigenetic regulation in the initiation and development of SLE and to provide an insight into the related therapeutic options in SLE. PMID:25988383

  14. Modeling and simulation of CANDU reactor and its regulating system

    Science.gov (United States)

    Javidnia, Hooman

    Analytical computer codes are indispensable tools in design, optimization, and control of nuclear power plants. Numerous codes have been developed to perform different types of analyses related to the nuclear power plants. A large number of these codes are designed to perform safety analyses. In the context of safety analyses, the control system is often neglected. Although there are good reasons for such a decision, that does not mean that the study of control systems in the nuclear power plants should be neglected altogether. In this thesis, a proof of concept code is developed as a tool that can be used in the design. optimization. and operation stages of the control system. The main objective in the design of this computer code is providing a tool that is easy to use by its target audience and is capable of producing high fidelity results that can be trusted to design the control system and optimize its performance. Since the overall plant control system covers a very wide range of processes, in this thesis the focus has been on one particular module of the the overall plant control system, namely, the reactor regulating system. The center of the reactor regulating system is the CANDU reactor. A nodal model for the reactor is used to represent the spatial neutronic kinetics of the core. The nodal model produces better results compared to the point kinetics model which is often used in the design and analysis of control system for nuclear reactors. The model can capture the spatial effects to some extent. although it is not as detailed as the finite difference methods. The criteria for choosing a nodal model of the core are: (1) the model should provide more detail than point kinetics and capture spatial effects, (2) it should not be too complex or overly detailed to slow down the simulation and provide details that are extraneous or unnecessary for a control engineer. Other than the reactor itself, there are auxiliary models that describe dynamics of different

  15. Features of CRISPR-Cas Regulation Key to Highly Efficient and Temporally-Specific crRNA Production

    Directory of Open Access Journals (Sweden)

    Andjela Rodic

    2017-11-01

    Full Text Available Bacterial immune systems, such as CRISPR-Cas or restriction-modification (R-M systems, affect bacterial pathogenicity and antibiotic resistance by modulating horizontal gene flow. A model system for CRISPR-Cas regulation, the Type I-E system from Escherichia coli, is silent under standard laboratory conditions and experimentally observing the dynamics of CRISPR-Cas activation is challenging. Two characteristic features of CRISPR-Cas regulation in E. coli are cooperative transcription repression of cas gene and CRISPR array promoters, and fast non-specific degradation of full length CRISPR transcripts (pre-crRNA. In this work, we use computational modeling to understand how these features affect the system expression dynamics. Signaling which leads to CRISPR-Cas activation is currently unknown, so to bypass this step, we here propose a conceptual setup for cas expression activation, where cas genes are put under transcription control typical for a restriction-modification (R-M system and then introduced into a cell. Known transcription regulation of an R-M system is used as a proxy for currently unknown CRISPR-Cas transcription control, as both systems are characterized by high cooperativity, which is likely related to similar dynamical constraints of their function. We find that the two characteristic CRISPR-Cas control features are responsible for its temporally-specific dynamical response, so that the system makes a steep (switch-like transition from OFF to ON state with a time-delay controlled by pre-crRNA degradation rate. We furthermore find that cooperative transcription regulation qualitatively leads to a cross-over to a regime where, at higher pre-crRNA processing rates, crRNA generation approaches the limit of an infinitely abrupt system induction. We propose that these dynamical properties are associated with rapid expression of CRISPR-Cas components and efficient protection of bacterial cells against foreign DNA. In terms of synthetic

  16. Regulation of Neurotransmitter Responses in the Central Nervous System.

    Science.gov (United States)

    1987-05-01

    and identify by block number) FIELD GROUP SUB-GROUP J’-aminobutyric acid; yclic AM’P; neuromodulation ; brain 1ABTAT(Continue on reverse if necessary and...crucial enzyme for regulating neuromodulation in brain. Given the ultimate goal of developing novel pharmacological agents for N! manipulating...central nervous system function, the discovery of a biochemical response to a neuromodulator can be considered a major step in that direction. Thus, up to

  17. Regulation and Roles of Urocortins in the Vascular System

    Directory of Open Access Journals (Sweden)

    Kazunori Kageyama

    2012-01-01

    Full Text Available Urocortins (Ucns are members of the corticotropin-releasing factor (CRF family of peptides. Ucns would have potent effects on the cardiovascular system via the CRF receptor type 2 (CRF2 receptor. Regulation and roles of each Ucn have been determined in the vascular system. Ucns have more potent vasodilatory effects than CRF. Human umbilical vein endothelial cells (HUVECs express Ucns1-3 mRNAs, and the receptor, CRF2a receptor mRNA. Ucns1-3 mRNA levels are differentially regulated in HUVECs. Differential regulation of Ucns may suggest differential roles of those in HUVECs. Ucn1 and Ucn2 have strong effects on interleukin (IL-6 gene expression and secretion in rat aortic smooth muscle A7r5 cells. The increase that we observed in IL-6 levels following Ucn treatment of A7r5 cells suggests that smooth muscle cells may be a source of IL-6 secretion under physiological stress conditions. Ucns are important and unique modulators of vascular smooth muscle cells and act directly or indirectly as autocrine and paracrine factors in the vascular system.

  18. Regulation of bacterial virulence by Csr (Rsm) systems.

    Science.gov (United States)

    Vakulskas, Christopher A; Potts, Anastasia H; Babitzke, Paul; Ahmer, Brian M M; Romeo, Tony

    2015-06-01

    Most bacterial pathogens have the remarkable ability to flourish in the external environment and in specialized host niches. This ability requires their metabolism, physiology, and virulence factors to be responsive to changes in their surroundings. It is no surprise that the underlying genetic circuitry that supports this adaptability is multilayered and exceedingly complex. Studies over the past 2 decades have established that the CsrA/RsmA proteins, global regulators of posttranscriptional gene expression, play important roles in the expression of virulence factors of numerous proteobacterial pathogens. To accomplish these tasks, CsrA binds to the 5' untranslated and/or early coding regions of mRNAs and alters translation, mRNA turnover, and/or transcript elongation. CsrA activity is regulated by noncoding small RNAs (sRNAs) that contain multiple CsrA binding sites, which permit them to sequester multiple CsrA homodimers away from mRNA targets. Environmental cues sensed by two-component signal transduction systems and other regulatory factors govern the expression of the CsrA-binding sRNAs and, ultimately, the effects of CsrA on secretion systems, surface molecules and biofilm formation, quorum sensing, motility, pigmentation, siderophore production, and phagocytic avoidance. This review presents the workings of the Csr system, the paradigm shift that it generated for understanding posttranscriptional regulation, and its roles in virulence networks of animal and plant pathogens. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  19. What Health-Related Functions Are Regulated by the Nervous System?

    Science.gov (United States)

    ... What health-related functions are regulated by the nervous system? The nervous system plays a role in nearly every aspect of ... feeling emotions. Functions that are regulated by the nervous system include (but are not limited to): Brain growth ...

  20. Role of the Ubiquitin Proteasome System in Regulating Skin Pigmentation

    Directory of Open Access Journals (Sweden)

    Hideya Ando

    2009-10-01

    Full Text Available Pigmentation of the skin, hair and eyes is regulated by tyrosinase, the critical rate-limiting enzyme in melanin synthesis by melanocytes. Tyrosinase is degraded endogenously, at least in part, by the ubiquitin proteasome system (UPS. Several types of inherited hypopigmentary diseases, such as oculocutaneous albinism and Hermansky-Pudlak syndrome, involve the aberrant processing and/or trafficking of tyrosinase and its subsequent degradation which can occur due to the quality-control machinery. Studies on carbohydrate modifications have revealed that tyrosinase in the endoplasmic reticulum (ER is proteolyzed via ER-associated protein degradation and that tyrosinase degradation can also occur following its complete maturation in the Golgi. Among intrinsic factors that regulate the UPS, fatty acids have been shown to modulate tyrosinase degradation in contrasting manners through increased or decreased amounts of ubiquitinated tyrosinase that leads to its accelerated or decelerated degradation by proteasomes.

  1. Yersinia Type III Secretion System Master Regulator LcrF

    Science.gov (United States)

    Schwiesow, Leah; Lam, Hanh

    2015-01-01

    Many Gram-negative pathogens express a type III secretion (T3SS) system to enable growth and survival within a host. The three human-pathogenic Yersinia species, Y. pestis, Y. pseudotuberculosis, and Y. enterocolitica, encode the Ysc T3SS, whose expression is controlled by an AraC-like master regulator called LcrF. In this review, we discuss LcrF structure and function as well as the environmental cues and pathways known to regulate LcrF expression. Similarities and differences in binding motifs and modes of action between LcrF and the Pseudomonas aeruginosa homolog ExsA are summarized. In addition, we present a new bioinformatics analysis that identifies putative LcrF binding sites within Yersinia target gene promoters. PMID:26644429

  2. Dynamics Analysis for Hydroturbine Regulating System Based on Matrix Model

    Directory of Open Access Journals (Sweden)

    Jiafu Wei

    2017-01-01

    Full Text Available The hydraulic turbine model is the key factor which affects the analysis precision of the hydraulic turbine governing system. This paper discusses the basic principle of the hydraulic turbine matrix model and gives two methods to realize. Using the characteristic matrix to describe unit flow and torque and their relationship with the opening and unit speed, it can accurately represent the nonlinear characteristics of the turbine, effectively improve the convergence of simulation process, and meet the needs of high precision real-time simulation of power system. Through the simulation of a number of power stations, it indicates that, by analyzing the dynamic process of the hydraulic turbine regulating with 5-order matrix model, the calculation results and field test data will have good consistency, and it can better meet the needs of power system dynamic simulation.

  3. The international regulation of Informal Value Transfer Systems

    Directory of Open Access Journals (Sweden)

    Anand Ajay Shah

    2007-12-01

    Full Text Available After the 11th September 2001 attacks on the United States international attention quickly focused on the sources and methods of terrorist financing. Among the methods terrorists and other criminal actors use to transfer funds are Informal Value Transfer Systems (IVTS which operate either outside the formal financial sector, or through use of the formal financial sector, but without leaving a full record of the transaction. Though the vast majority of funds moved through IVTS are the earnings of migrant workers and immigrant communities, the lack of uniform worldwide regulation of IVTS provides ample opportunity for abuse and misuse. The international community primarily responded to IVTS concerns through the Financial Action Task Force on Money Laundering, which issued a series of recommendations and best practices for states in regulating IVTS operations. While these recommendations are a secure beginning to regulation of IVTS operating within ethnic communities, they fail to address the more modern forms of IVTS that have come about in the post-Cold War globalised world. Comprehensive recommendations governing all types of IVTS, as well as concerted international cooperation and coordination are necessary to address this global phenomenon.

  4. Central nervous system regulation of intestinal lipid and lipoprotein metabolism.

    Science.gov (United States)

    Farr, Sarah; Taher, Jennifer; Adeli, Khosrow

    2016-02-01

    In response to nutrient availability, the small intestine and brain closely communicate to modulate energy homeostasis and metabolism. The gut-brain axis involves complex nutrient sensing mechanisms and an integration of neuronal and hormonal signaling. This review summarizes recent evidence implicating the gut-brain axis in regulating lipoprotein metabolism, with potential implications for the dyslipidemia of insulin resistant states. The intestine and brain possess distinct mechanisms for sensing lipid availability, which triggers subsequent regulation of feeding, glucose homeostasis, and adipose tissue metabolism. More recently, central receptors, neuropeptides, and gut hormones that communicate with the brain have been shown to modulate hepatic and intestinal lipoprotein metabolism via parasympathetic and sympathetic signaling. Gut-derived glucagon-like peptides appear to be particularly important in modulating the intestinal secretion of chylomicron particles via a novel brain-gut axis. Dysregulation of these pathways may contribute to postprandial diabetic dyslipidemia. Emerging evidence implicates the central and enteric nervous systems in controlling many aspects of lipid and lipoprotein metabolism. Bidirectional communication between the gut and brain involving neuronal pathways and gut peptides is critical for regulating feeding and metabolism, and forms a neuroendocrine circuit to modulate dietary fat absorption and intestinal production of atherogenic chylomicron particles.

  5. THE PROGRAMED CELL DEATH REGULATORS OF ISOLATED MODEL SYSTEMS

    Directory of Open Access Journals (Sweden)

    D. V. Vatlitsov

    2016-06-01

    Full Text Available The technology evolution creates the prerequisites for the emergence of new informational concept and approaches to the formation of a fundamentally new principles of biological objects understanding. The aim was to study the activators of the programmed cell death in an isolated system model. Cell culture aging parameters were performed on flow cytometer. It had formed the theory that the changes in the concentrations of metal ions and increase their extracellular concentration had formed a negative gradient into the cells.regulation of cell death. It was shown that the metals ions concentrations.

  6. Capability to model reactor regulating system in RFSP

    Energy Technology Data Exchange (ETDEWEB)

    Chow, H C; Rouben, B; Younis, M H; Jenkins, D A [Atomic Energy of Canada Ltd., Mississauga, ON (Canada); Baudouin, A [Hydro-Quebec, Montreal, PQ (Canada); Thompson, P D [New Brunswick Electric Power Commission, Point Lepreau, NB (Canada). Point Lepreau Generating Station

    1996-12-31

    The Reactor Regulating System package extracted from SMOKIN-G2 was linked within RFSP to the spatial kinetics calculation. The objective is to use this new capability in safety analysis to model the actions of RRS in hypothetical events such as in-core LOCA or moderator drain scenarios. This paper describes the RRS modelling in RFSP and its coupling to the neutronics calculations, verification of the RRS control routine functions, sample applications and comparisons to SMOKIN-G2 results for the same transient simulations. (author). 7 refs., 6 figs.

  7. Optimal Scheduling of an Regional Integrated Energy System with Energy Storage Systems for Service Regulation

    Directory of Open Access Journals (Sweden)

    Hengrui Ma

    2018-01-01

    Full Text Available Ancillary services are critical to maintaining the safe and stable operation of power systems that contain a high penetration level of renewable energy resources. As a high-quality regulation resource, the regional integrated energy system (RIES with energy storage system (ESS can effectively adjust the non-negligible frequency offset caused by the renewable energy integration into the power system, and help solve the problem of power system frequency stability. In this paper, the optimization model aiming at regional integrated energy system as a participant in the regulation market based on pay-for-performance is established. Meanwhile YALMIP + CPLEX is used to simulate and analyze the total operating cost under different dispatch modes. This paper uses the actual operation model of the PJM regulation market to guide the optimal allocation of regulation resource in the regional integrated energy system, and provides a balance between the power trading revenue and regulation market revenue in order to achieve the maximum profit.

  8. The Proprioceptive System Regulates Morphologic Restoration of Fractured Bones

    Directory of Open Access Journals (Sweden)

    Ronen Blecher

    2017-08-01

    Full Text Available Successful fracture repair requires restoration of bone morphology and mechanical integrity. Recent evidence shows that fractured bones of neonatal mice undergo spontaneous realignment, dubbed “natural reduction.” Here, we show that natural reduction is regulated by the proprioceptive system and improves with age. Comparison among mice of different ages revealed, surprisingly, that 3-month-old mice exhibited more rapid and effective natural reduction than newborns. Fractured bones of null mutants for transcription factor Runx3, lacking functional proprioceptors, failed to realign properly. Blocking Runx3 expression in the peripheral nervous system, but not in limb mesenchyme, recapitulated the null phenotype, as did inactivation of muscles flanking the fracture site. Egr3 knockout mice, which lack muscle spindles but not Golgi tendon organs, displayed a less severe phenotype, suggesting that both receptor types, as well as muscle contraction, are required for this regulatory mechanism. These findings uncover a physiological role for proprioception in non-autonomous regulation of skeletal integrity.

  9. Organisational Learning and Systems of Labour Market Regulation in Europe

    DEFF Research Database (Denmark)

    Holm, Jacob Rubæk; Lorenz, Edward; Lundvall, Bengt-Åke

    This paper establishes a link between international differences in the organisation of work and modes of regulation of labour markets within Europe. The paper operates with four forms of work organisation (discretionary learning, lean production, Taylorism and simple or traditional). Through...... a factor analysis three dimensions of national labour market systems (flexible security, passive security and job support) are defined. Using a multilevel logistic regression model that takes into account both characteristics of individuals and of national labour market systems it is shown...... that there is a significant positive correlation between flexible security and the prevalence of discretionary learning. On this basis we point to an extension of flexible security in Europe’s labour markets as an adequate response to the current crisis....

  10. Past and future regulation to prevent a systemic financial crisis

    Directory of Open Access Journals (Sweden)

    Mario Sarcinelli

    2010-01-01

    Full Text Available The article is a revised and updated version of that published on the March 2010 issues of Moneta e Credito. It was there claimed that, up to now, the G20 has supervised the process to revitalize the real economy affected by the Great Recession through fiscal stimuli and a very easy monetary policy, and to rescue the battered financial system by injecting capital into giant banks and firms. The G20 is now turning its attention to financial regulation, with the FSB as its main operational arm. The ideas that are being proposed stress the need for disincentives toward too much risk taking (more capital, higher liquidity, limits to remunerations and bonuses, etc., particularly by big and complex financial institutions that are likely to entail systemic risks. The paper maintains that, as the disincentive approach is insufficient to deter financial managers looking for power, some kind of segmentation needs to be introduced, as suggested by Paul Volcker.

  11. SELF-REGULATED SHOCKS IN MASSIVE STAR BINARY SYSTEMS

    Energy Technology Data Exchange (ETDEWEB)

    Parkin, E. R.; Sim, S. A., E-mail: parkin@mso.anu.edu.au, E-mail: s.sim@qub.ac.uk [Research School of Astronomy and Astrophysics, Australian National University, ACT 2611 (Australia)

    2013-04-20

    In an early-type, massive star binary system, X-ray bright shocks result from the powerful collision of stellar winds driven by radiation pressure on spectral line transitions. We examine the influence of the X-rays from the wind-wind collision shocks on the radiative driving of the stellar winds using steady-state models that include a parameterized line force with X-ray ionization dependence. Our primary result is that X-ray radiation from the shocks inhibits wind acceleration and can lead to a lower pre-shock velocity, and a correspondingly lower shocked plasma temperature, yet the intrinsic X-ray luminosity of the shocks, L{sub X}, remains largely unaltered, with the exception of a modest increase at small binary separations. Due to the feedback loop between the ionizing X-rays from the shocks and the wind driving, we term this scenario as self-regulated shocks. This effect is found to greatly increase the range of binary separations at which a wind-photosphere collision is likely to occur in systems where the momenta of the two winds are significantly different. Furthermore, the excessive levels of X-ray ionization close to the shocks completely suppress the line force, and we suggest that this may render radiative braking less effective. Comparisons of model results against observations reveal reasonable agreement in terms of log (L{sub X}/L{sub bol}). The inclusion of self-regulated shocks improves the match for kT values in roughly equal wind momenta systems, but there is a systematic offset for systems with unequal wind momenta (if considered to be a wind-photosphere collision).

  12. SELF-REGULATED SHOCKS IN MASSIVE STAR BINARY SYSTEMS

    International Nuclear Information System (INIS)

    Parkin, E. R.; Sim, S. A.

    2013-01-01

    In an early-type, massive star binary system, X-ray bright shocks result from the powerful collision of stellar winds driven by radiation pressure on spectral line transitions. We examine the influence of the X-rays from the wind-wind collision shocks on the radiative driving of the stellar winds using steady-state models that include a parameterized line force with X-ray ionization dependence. Our primary result is that X-ray radiation from the shocks inhibits wind acceleration and can lead to a lower pre-shock velocity, and a correspondingly lower shocked plasma temperature, yet the intrinsic X-ray luminosity of the shocks, L X , remains largely unaltered, with the exception of a modest increase at small binary separations. Due to the feedback loop between the ionizing X-rays from the shocks and the wind driving, we term this scenario as self-regulated shocks. This effect is found to greatly increase the range of binary separations at which a wind-photosphere collision is likely to occur in systems where the momenta of the two winds are significantly different. Furthermore, the excessive levels of X-ray ionization close to the shocks completely suppress the line force, and we suggest that this may render radiative braking less effective. Comparisons of model results against observations reveal reasonable agreement in terms of log (L X /L bol ). The inclusion of self-regulated shocks improves the match for kT values in roughly equal wind momenta systems, but there is a systematic offset for systems with unequal wind momenta (if considered to be a wind-photosphere collision).

  13. Distributed Cooperative Regulation for Multiagent Systems and Its Applications to Power Systems: A Survey

    Science.gov (United States)

    Li, Yaping; Yong, Taiyou; Yu, Jie; Mao, Wenbo

    2014-01-01

    Cooperative regulation of multiagent systems has become an active research area in the past decade. This paper reviews some recent progress in distributed coordination control for leader-following multiagent systems and its applications in power system and mainly focuses on the cooperative tracking control in terms of consensus tracking control and containment tracking control. Next, methods on how to rank the network nodes are summarized for undirected/directed network, based on which one can determine which follower should be connected to leaders such that partial followers can perceive leaders' information. Furthermore, we present a survey of the most relevant scientific studies investigating the regulation and optimization problems in power systems based on distributed strategies. Finally, some potential applications in the frequency tracking regulation of smart grids are discussed at the end of the paper. PMID:25243199

  14. Distributed cooperative regulation for multiagent systems and its applications to power systems: a survey.

    Science.gov (United States)

    Hu, Jianqiang; Li, Yaping; Yong, Taiyou; Cao, Jinde; Yu, Jie; Mao, Wenbo

    2014-01-01

    Cooperative regulation of multiagent systems has become an active research area in the past decade. This paper reviews some recent progress in distributed coordination control for leader-following multiagent systems and its applications in power system and mainly focuses on the cooperative tracking control in terms of consensus tracking control and containment tracking control. Next, methods on how to rank the network nodes are summarized for undirected/directed network, based on which one can determine which follower should be connected to leaders such that partial followers can perceive leaders' information. Furthermore, we present a survey of the most relevant scientific studies investigating the regulation and optimization problems in power systems based on distributed strategies. Finally, some potential applications in the frequency tracking regulation of smart grids are discussed at the end of the paper.

  15. Management system for regulating transport of radioactive material

    International Nuclear Information System (INIS)

    Lopez Vietri, Jorge; Capadona, Nancy; Barenghi, Leonardo

    2008-01-01

    Full text: The objective of this paper is to describe the main characteristics and fundamentals of the Nuclear regulatory Authority's (Autoridad Regulatoria Nuclear, ARN) management system applied to the regulation of transport of radioactive material, in Argentina. In the frame of ARN's quality policy, 'Protection against ionizing radiation on transport of radioactive materials' was selected as one of the regulatory processes, named TRM process from now on. ARN's quality management system is integrally based on ISO 9000 system addressed to help organizations in designing and implementing their quality management systems. TRM process was split into five sub processes in order to facilitate the implementation of quality system. Such sub processes were defined taking account of the main functions developed by ARN in the branch of safe transport of radioactive materials and are listed below: 1) Development and updating of standards and regulatory guides; 2) Licensing of packages, special radioactive materials and consignments of radioactive materials; 3) Compliance assurance during the transport of radioactive materials, and 4) Training, advising and communications. For each of these sub processes were specified their objectives, inputs, activities and outputs, the clients and stakeholders, responsibilities, supporting documents, control of documents and records, control of non-conformances, monitoring and measurements, audits, feedback and improvement. It was decided to develop a quality plan to organize and manage activities to meet quality requirements, to optimize the use of limited resources of the organization and to be used as a basis for monitoring and assessing compliance with the requirements, both internal and external. Supporting documents for sub processes were issued, validated, reviewed and improved as an essential point to implement continuous improving. Simultaneously, some indexes were defined to monitor and measure the sub processes as a way to show

  16. Molecular mechanisms of aging and immune system regulation in Drosophila.

    Science.gov (United States)

    Eleftherianos, Ioannis; Castillo, Julio Cesar

    2012-01-01

    Aging is a complex process that involves the accumulation of deleterious changes resulting in overall decline in several vital functions, leading to the progressive deterioration in physiological condition of the organism and eventually causing disease and death. The immune system is the most important host-defense mechanism in humans and is also highly conserved in insects. Extensive research in vertebrates has concluded that aging of the immune function results in increased susceptibility to infectious disease and chronic inflammation. Over the years, interest has grown in studying the molecular interaction between aging and the immune response to pathogenic infections. The fruit fly Drosophila melanogaster is an excellent model system for dissecting the genetic and genomic basis of important biological processes, such as aging and the innate immune system, and deciphering parallel mechanisms in vertebrate animals. Here, we review the recent advances in the identification of key players modulating the relationship between molecular aging networks and immune signal transduction pathways in the fly. Understanding the details of the molecular events involved in aging and immune system regulation will potentially lead to the development of strategies for decreasing the impact of age-related diseases, thus improving human health and life span.

  17. Regulation of Central Nervous System Myelination in Higher Brain Functions

    Directory of Open Access Journals (Sweden)

    Mara Nickel

    2018-01-01

    Full Text Available The hippocampus and the prefrontal cortex are interconnected brain regions, playing central roles in higher brain functions, including learning and memory, planning complex cognitive behavior, and moderating social behavior. The axons in these regions continue to be myelinated into adulthood in humans, which coincides with maturation of personality and decision-making. Myelin consists of dense layers of lipid membranes wrapping around the axons to provide electrical insulation and trophic support and can profoundly affect neural circuit computation. Recent studies have revealed that long-lasting changes of myelination can be induced in these brain regions by experience, such as social isolation, stress, and alcohol abuse, as well as by neurological and psychiatric abnormalities. However, the mechanism and function of these changes remain poorly understood. Myelin regulation represents a new form of neural plasticity. Some progress has been made to provide new mechanistic insights into activity-independent and activity-dependent regulations of myelination in different experimental systems. More extensive investigations are needed in this important but underexplored research field, in order to shed light on how higher brain functions and myelination interplay in the hippocampus and prefrontal cortex.

  18. Hyperthyroidism differentially regulates neuropeptide S system in the rat brain.

    Science.gov (United States)

    González, Carmen R; Martínez de Morentin, Pablo B; Martínez-Sánchez, Noelia; Gómez-Díaz, Consuelo; Lage, Ricardo; Varela, Luis; Diéguez, Carlos; Nogueiras, Rubén; Castaño, Justo P; López, Miguel

    2012-04-23

    Thyroid hormones play an important role in the regulation of energy balance, sleep and emotional behaviors. Neuropeptide S (NPS) is a recently discovered neuropeptide, regulating feeding, sleep and anxiety. Here, we examined the effect of hyperthyroidism on the gene and protein expression of neuropeptide S and its receptor (NPS-R) in the hypothalamus, brainstem and amygdala of rats. Our results showed that the expression of NPS and NPS-R was differentially modulated by hyperthyroidism in the rat brain. NPS and NPS-R mRNA and protein levels were decreased in the hypothalamus of hyperthyroid rats. Conversely NPS-R expression was highly increased in the brainstem and NPS and NPS-R expression were unchanged in the amygdala of these rats. These data suggest that changes in anxiety and food intake patterns observed in hyperthyroidism could be associated with changes in the expression of NPS and NPS-R. Thus, the NPS/NPS-R system may be involved in several hyperthyroidism-associated comorbidities. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. A gene expression system offering multiple levels of regulation: the Dual Drug Control (DDC) system.

    Science.gov (United States)

    Sudomoina, Marina; Latypova, Ekaterina; Favorova, Olga O; Golemis, Erica A; Serebriiskii, Ilya G

    2004-04-29

    Whether for cell culture studies of protein function, construction of mouse models to enable in vivo analysis of disease epidemiology, or ultimately gene therapy of human diseases, a critical enabling step is the ability to achieve finely controlled regulation of gene expression. Previous efforts to achieve this goal have explored inducible drug regulation of gene expression, and construction of synthetic promoters based on two-hybrid paradigms, among others. In this report, we describe the combination of dimerizer-regulated two-hybrid and tetracycline regulatory elements in an ordered cascade, placing expression of endpoint reporters under the control of two distinct drugs. In this Dual Drug Control (DDC) system, a first plasmid expresses fusion proteins to DBD and AD, which interact only in the presence of a small molecule dimerizer; a second plasmid encodes a cassette transcriptionally responsive to the first DBD, directing expression of the Tet-OFF protein; and a third plasmid encodes a reporter gene transcriptionally responsive to binding by Tet-OFF. We evaluate the dynamic range and specificity of this system in comparison to other available systems. This study demonstrates the feasibility of combining two discrete drug-regulated expression systems in a temporally sequential cascade, without loss of dynamic range of signal induction. The efficient layering of control levels allowed by this combination of elements provides the potential for the generation of complex control circuitry that may advance ability to regulate gene expression in vivo.

  20. A gene expression system offering multiple levels of regulation: the Dual Drug Control (DDC system

    Directory of Open Access Journals (Sweden)

    Golemis Erica A

    2004-04-01

    Full Text Available Abstract Background Whether for cell culture studies of protein function, construction of mouse models to enable in vivo analysis of disease epidemiology, or ultimately gene therapy of human diseases, a critical enabling step is the ability to achieve finely controlled regulation of gene expression. Previous efforts to achieve this goal have explored inducible drug regulation of gene expression, and construction of synthetic promoters based on two-hybrid paradigms, among others. Results In this report, we describe the combination of dimerizer-regulated two-hybrid and tetracycline regulatory elements in an ordered cascade, placing expression of endpoint reporters under the control of two distinct drugs. In this Dual Drug Control (DDC system, a first plasmid expresses fusion proteins to DBD and AD, which interact only in the presence of a small molecule dimerizer; a second plasmid encodes a cassette transcriptionally responsive to the first DBD, directing expression of the Tet-OFF protein; and a third plasmid encodes a reporter gene transcriptionally responsive to binding by Tet-OFF. We evaluate the dynamic range and specificity of this system in comparison to other available systems. Conclusion This study demonstrates the feasibility of combining two discrete drug-regulated expression systems in a temporally sequential cascade, without loss of dynamic range of signal induction. The efficient layering of control levels allowed by this combination of elements provides the potential for the generation of complex control circuitry that may advance ability to regulate gene expression in vivo.

  1. The Regulation of GluN2A by Endogenous and Exogenous Regulators in the Central Nervous System.

    Science.gov (United States)

    Sun, Yongjun; Zhan, Liying; Cheng, Xiaokun; Zhang, Linan; Hu, Jie; Gao, Zibin

    2017-04-01

    The NMDA receptor is the most widely studied ionotropic glutamate receptor, and it is central to many physiological and pathophysiological processes in the central nervous system. GluN2A is one of the two main types of GluN2 NMDA receptor subunits in the forebrain. The proper activity of GluN2A is important to brain function, as the abnormal regulation of GluN2A may induce some neuropsychiatric disorders. This review will examine the regulation of GluN2A by endogenous and exogenous regulators in the central nervous system.

  2. Regulation of Body Temperature by the Nervous System.

    Science.gov (United States)

    Tan, Chan Lek; Knight, Zachary A

    2018-04-04

    The regulation of body temperature is one of the most critical functions of the nervous system. Here we review our current understanding of thermoregulation in mammals. We outline the molecules and cells that measure body temperature in the periphery, the neural pathways that communicate this information to the brain, and the central circuits that coordinate the homeostatic response. We also discuss some of the key unresolved issues in this field, including the following: the role of temperature sensing in the brain, the molecular identity of the warm sensor, the central representation of the labeled line for cold, and the neural substrates of thermoregulatory behavior. We suggest that approaches for molecularly defined circuit analysis will provide new insight into these topics in the near future. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Algorithm of dynamic regulation of a system of duct, for a high accuracy climatic system

    Science.gov (United States)

    Arbatskiy, A. A.; Afonina, G. N.; Glazov, V. S.

    2017-11-01

    Currently, major part of climatic system, are stationary in projected mode only. At the same time, many modern industrial sites, require constant or periodical changes in technological process. That is 80% of the time, the industrial site is not require ventilation system in projected mode and high precision of climatic parameters must maintain. While that not constantly is in use for climatic systems, which use in parallel for different rooms, we will be have a problem for balance of duct system. For this problem, was created the algorithm for quantity regulation, with minimal changes. Dynamic duct system: Developed of parallel control system of air balance, with high precision of climatic parameters. The Algorithm provide a permanent pressure in main duct, in different a flow of air. Therefore, the ending devises air flow have only one parameter for regulation - flaps open area. Precision of regulation increase and the climatic system provide high precision for temperature and humidity (0,5C for temperature, 5% for relative humidity). Result: The research has been made in CFD-system - PHOENICS. Results for velocity of air in duct, for pressure of air in duct for different operation mode, has been obtained. Equation for air valves positions, with different parameters for climate in room’s, has been obtained. Energy saving potential for dynamic duct system, for different types of a rooms, has been calculated.

  4. Phosphoenolpyruvate phosphotransferase system components positively regulate Klebsiella biofilm formation

    Directory of Open Access Journals (Sweden)

    Yu-Tze Horng

    2018-04-01

    Full Text Available Background/Purpose: Klebsiella pneumoniae is one of the leading causes of device-related infections (DRIs, which are associated with attachment of bacteria to these devices to form a biofilm. The latter is composed of not only bacteria but also extracellular polymeric substances (EPSes consisting of extracellular DNAs, polysaccharides, and other macromolecules. The phosphoenolpyruvate (PEP:carbohydrate phosphotransferase system (PTS regulates diverse processes of bacterial physiology. In the genome of K. pneumoniae MGH 78578, we found an uncharacterized enzyme II complex homolog of PTS: KPN00353 (EIIA homolog, KPN00352 (EIIB homolog, and KPN00351 (EIIC homolog. The aim of this study was to characterize the potential physiological role of KPN00353, KPN00352, and KPN00351 in biofilm formation by K. pneumoniae. Methods/Results: We constructed the PTS mutants and recombinant strains carrying the gene(s of PTS. The recombinant K. pneumoniae strain overexpressing KPN00353–KPN00352–KPN00351 produced more extracellular matrix than did the vector control according to transmission and scanning electron microscopy. Judging by quantification of biofilm formation, of extracellular DNA (eDNA, and of capsular polysaccharide, the recombinant strain overexpressing KPN00353-KPN00352-KPN00351 produced more biofilm and capsular polysaccharide after overnight culture and more eDNA in the log phase as compared to the vector control. Conclusion: The genes, KPN00353–KPN00352–KPN00351, encode a putative enzyme II complex in PTS and positively regulate biofilm formation by enhancing production of eDNA and capsular polysaccharide in K. pneumoniae. Five proteins related to chaperones, to the citric acid cycle, and to quorum sensing are upregulated by the KPN00353–KPN00352–KPN00351 system. Keywords: Klebsiella, PTS, Biofilm, eDNA, Polysaccharide

  5. Sensitivity Analysis of Reactor Regulating System for SMART

    International Nuclear Information System (INIS)

    Jeon, Yu Lim; Kang, Han Ok; Lee, Seong Wook; Park, Cheon Tae

    2009-01-01

    The integral reactor technology is one of the Small and Medium sized Reactor (SMR) which has recently come into a spotlight due to its suitability for various fields. SMART (System integrated Modular Advanced ReacTor), a small sized integral type PWR with a rated thermal power of 330MWt is one of the advanced SMR. SMART developed by the Korea Atomic Energy Research Institute (KAERI), has a capacity to provide 40,000 m3 per day of potable water and 90 MW of electricity (Chang et al., 2000). Figure 1 shows the SMART which adopts a sensible mixture of new innovative design features and proven technologies aimed at achieving highly enhanced safety and improved economics. Design features contributing to a safety enhancement are basically inherent safety improving features and passive safety features. Fundamental thermal-hydraulic experiments were carried out during the design concepts development to assure the fundamental behavior of major concepts of the SMART systems. A TASS/SMR is a suitable code for accident and performance analyses of SMART. In this paper, we proposed a new power control logic for stable operating outputs of Reactor Regulating System (RRS) of SMART. We analyzed the sensitivity of operating parameter for various operating conditions

  6. Homeostatic regulation of memory systems and adaptive decisions.

    Science.gov (United States)

    Mizumori, Sheri J Y; Jo, Yong Sang

    2013-11-01

    While it is clear that many brain areas process mnemonic information, understanding how their interactions result in continuously adaptive behaviors has been a challenge. A homeostatic-regulated prediction model of memory is presented that considers the existence of a single memory system that is based on a multilevel coordinated and integrated network (from cells to neural systems) that determines the extent to which events and outcomes occur as predicted. The "multiple memory systems of the brain" have in common output that signals errors in the prediction of events and/or their outcomes, although these signals differ in terms of what the error signal represents (e.g., hippocampus: context prediction errors vs. midbrain/striatum: reward prediction errors). The prefrontal cortex likely plays a pivotal role in the coordination of prediction analysis within and across prediction brain areas. By virtue of its widespread control and influence, and intrinsic working memory mechanisms. Thus, the prefrontal cortex supports the flexible processing needed to generate adaptive behaviors and predict future outcomes. It is proposed that prefrontal cortex continually and automatically produces adaptive responses according to homeostatic regulatory principles: prefrontal cortex may serve as a controller that is intrinsically driven to maintain in prediction areas an experience-dependent firing rate set point that ensures adaptive temporally and spatially resolved neural responses to future prediction errors. This same drive by prefrontal cortex may also restore set point firing rates after deviations (i.e. prediction errors) are detected. In this way, prefrontal cortex contributes to reducing uncertainty in prediction systems. An emergent outcome of this homeostatic view may be the flexible and adaptive control that prefrontal cortex is known to implement (i.e. working memory) in the most challenging of situations. Compromise to any of the prediction circuits should result in

  7. 41 CFR 101-1.101 - Federal Property Management Regulations System.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 2 2010-07-01 2010-07-01 true Federal Property Management Regulations System. 101-1.101 Section 101-1.101 Public Contracts and Property Management Federal Property Management Regulations System FEDERAL PROPERTY MANAGEMENT REGULATIONS GENERAL 1-INTRODUCTION 1.1...

  8. Hox gene regulation in the central nervous system of Drosophila

    Directory of Open Access Journals (Sweden)

    Maheshwar eGummalla

    2014-04-01

    Full Text Available Hox genes specify the structures that form along the anteroposterior (AP axis of bilateria. Within the genome, they often form clusters where, remarkably enough, their position within the clusters reflects the relative positions of the structures they specify along the AP axis. This correspondence between genomic organization and gene expression pattern has been conserved through evolution and provides a unique opportunity to study how chromosomal context affects gene regulation. In Drosophila, a general rule, often called posterior dominance, states that Hox genes specifying more posterior structures repress the expression of more anterior Hox genes. This rule explains the apparent spatial complementarity of Hox gene expression patterns in Drosophila. Here we review a noticeable exception to this rule where the more-posteriorly expressed Abd-B hox gene fails to repress the more-anterior abd-A gene in cells of the central nervous system (CNS. While Abd-B is required to repress ectopic expression of abd-A in the posterior epidermis, abd-A repression in the posterior CNS is accomplished by a different mechanism that involves a large 92kb long non-coding RNA (lncRNA encoded by the intergenic region separating abd-A and Abd-B (the iab8ncRNA. Dissection of this lncRNA revealed that abd-A is repressed by the lncRNA using two redundant mechanisms. The 1st mechanism is mediated by a microRNA (mir-iab-8 encoded by intronic sequence within the large iab8-ncRNA. Meanwhile, the second mechanism seems to involve transcriptional interference by the long iab-8 ncRNA on the abd-A promoter. Recent work demonstrating CNS-specific regulation of genes by ncRNAs in Drosophila, seem to highlight a potential role for the iab-8-ncRNA in the evolution of the Drosophila hox complexes

  9. A decision support system for the maintenance of lights of traffic regulation systems

    NARCIS (Netherlands)

    Duyn Schouten, F.A. van der; Klusener, A.S.; Vlijmen, S.F.M. van; Vos de Wael, S.L.E.

    From October 1994 to June 1995 the authors executed a project, the so called 'Lampremplace' project, in cooperation with Nederland Haarlem, a Dutch constructor and supplier of traffic regulation systems. 'Lampremplace', as it is called in traffic jargon, is the maintenance of lights of traffic

  10. A quantitative model of regulator's preference factor (RPF) in electricity-environment coordinated regulation system

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Yulong; Fu, Shijun [Economy and Business Administration School of Chongqing University, Chongqing 400030 (China)

    2010-12-15

    This paper explores quantification of regulator's preference factor (RPF) in electricity-environment coordinated regulation system. Based on social welfare economics, we articulately depict RPF's qualitative concept and its economic meaning. Then, applying abstract functions (i.e., abstract social welfare function, abstract utility function, and abstract production function), we deduce the partial-social-welfare elasticity, and build the mathematics model of maximizing social welfare. We nest this elasticity into the model's Kuhn-Tucker conditions, and obtain RPF's definition formula. By solving the Kuhn-Tucker conditions, we get RPF's quantitative formula, which solves the problem of hard to quantify regulator's preference in electricity-environment coordinated regulation system. The result shows that RPF only has relationship to subsystems' production function, and is independent of social welfare function and subsystems' utility function. Finally, we provide an empirical research based on the western region of China from year 1995 to 2004. It reveals that regulator has relative stability preference to mitigating pollutants. And validity test confirms that the empirical result is fit well to the practice. The RPF is truly a more general and valid instrument to measure regulator's preference in its regulated field. (author)

  11. DC microgrids providing frequency regulation in electrical power system - imperfect communication issues

    DEFF Research Database (Denmark)

    Bašić, Hrvoje; Dragicevic, Tomislav; Pandžić, Hrvoje

    2017-01-01

    This paper presents a model of multiple DC microgrids with battery energy storage systems and demand response capability, taking part in primary frequency regulation of electrical power system. Although DC microgrids can contribute to stability and efficiency of frequency regulation, these complex...... systems may cause serious stability issues due to the imperfect communication. This work presents possible scenarios of unstable primary frequency regulation in a simplified model of electrical power system with DC microgrids, which are controlled through communication network....

  12. Negative regulation of quorum-sensing systems in Pseudomonas aeruginosa by ATP-dependent Lon protease.

    Science.gov (United States)

    Takaya, Akiko; Tabuchi, Fumiaki; Tsuchiya, Hiroko; Isogai, Emiko; Yamamoto, Tomoko

    2008-06-01

    Lon protease, a member of the ATP-dependent protease family, regulates numerous cellular systems by degrading specific substrates. Here, we demonstrate that Lon is involved in the regulation of quorum-sensing (QS) signaling systems in Pseudomonas aeruginosa, an opportunistic human pathogen. The organism has two acyl-homoserine lactone (HSL)-mediated QS systems, LasR/LasI and RhlR/RhlI. Many reports have demonstrated that these two systems are regulated and interconnected by global regulators. We found that lon-disrupted cells overproduce pyocyanin, the biosynthesis of which depends on the RhlR/RhlI system, and show increased levels of a transcriptional regulator, RhlR. The QS systems are organized hierarchically: the RhlR/RhlI system is subordinate to LasR/LasI. To elucidate the mechanism by which Lon negatively regulates RhlR/RhlI, we examined the effect of lon disruption on the LasR/LasI system. We found that Lon represses the expression of LasR/LasI by degrading LasI, an HSL synthase, leading to negative regulation of the RhlR/RhlI system. RhlR/RhlI was also shown to be regulated by Lon independently of LasR/LasI via regulation of RhlI, an HSL synthase. In view of these findings, it is suggested that Lon protease is a powerful negative regulator of both HSL-mediated QS systems in P. aeruginosa.

  13. The Mucosal Immune System and Its Regulation by Autophagy.

    Science.gov (United States)

    Kabat, Agnieszka M; Pott, Johanna; Maloy, Kevin J

    2016-01-01

    The gastrointestinal tract presents a unique challenge to the mucosal immune system, which has to constantly monitor the vast surface for the presence of pathogens, while at the same time maintaining tolerance to beneficial or innocuous antigens. In the intestinal mucosa, specialized innate and adaptive immune components participate in directing appropriate immune responses toward these diverse challenges. Recent studies provide compelling evidence that the process of autophagy influences several aspects of mucosal immune responses. Initially described as a "self-eating" survival pathway that enables nutrient recycling during starvation, autophagy has now been connected to multiple cellular responses, including several aspects of immunity. Initial links between autophagy and host immunity came from the observations that autophagy can target intracellular bacteria for degradation. However, subsequent studies indicated that autophagy plays a much broader role in immune responses, as it can impact antigen processing, thymic selection, lymphocyte homeostasis, and the regulation of immunoglobulin and cytokine secretion. In this review, we provide a comprehensive overview of mucosal immune cells and discuss how autophagy influences many aspects of their physiology and function. We focus on cell type-specific roles of autophagy in the gut, with a particular emphasis on the effects of autophagy on the intestinal T cell compartment. We also provide a perspective on how manipulation of autophagy may potentially be used to treat mucosal inflammatory disorders.

  14. Cholesterol: Its Regulation and Role in Central Nervous System Disorders

    Directory of Open Access Journals (Sweden)

    Matthias Orth

    2012-01-01

    Full Text Available Cholesterol is a major constituent of the human brain, and the brain is the most cholesterol-rich organ. Numerous lipoprotein receptors and apolipoproteins are expressed in the brain. Cholesterol is tightly regulated between the major brain cells and is essential for normal brain development. The metabolism of brain cholesterol differs markedly from that of other tissues. Brain cholesterol is primarily derived by de novo synthesis and the blood brain barrier prevents the uptake of lipoprotein cholesterol from the circulation. Defects in cholesterol metabolism lead to structural and functional central nervous system diseases such as Smith-Lemli-Opitz syndrome, Niemann-Pick type C disease, and Alzheimer’s disease. These diseases affect different metabolic pathways (cholesterol biosynthesis, lipid transport and lipoprotein assembly, apolipoproteins, lipoprotein receptors, and signaling molecules. We review the metabolic pathways of cholesterol in the CNS and its cell-specific and microdomain-specific interaction with other pathways such as the amyloid precursor protein and discuss potential treatment strategies as well as the effects of the widespread use of LDL cholesterol-lowering drugs on brain functions.

  15. 3D simulation of CANDU reactor regulating system

    International Nuclear Information System (INIS)

    Venescu, B.; Zevedei, D.; Jurian, M.

    2013-01-01

    Present paper shows the evaluation of the performance of the 3-D modal synthesis based reactor kinetic model in a closed-loop environment in a MATLAB/SIMULINK based Reactor Regulating System (RRS) simulation platform. A notable advantage of the 3-D model is the level of details that it can reveal as compared to the coupled point kinetic model. Using the developed RRS simulation platform, the reactor internal behaviours can be revealed during load-following tests. The test results are also benchmarked against measurements from an existing (CANDU) power plant. It can be concluded that the 3-D reactor model produces more realistic view of the core neutron flux distribution, which is closer to the real plant measurements than that from a coupled point kinetic model. It is also shown that, through a vectorization process, the computational load of the 3-D model is comparable with that of the 14-zone coupled point kinetic model. Furthermore, the developed Graphical User Interface (GUI) software package for RRS implementation represents a user friendly and independent application environment for education training and industrial utilizations. (authors)

  16. Evaluating sustainability of truck weight regulations: A system dynamics view

    Directory of Open Access Journals (Sweden)

    Pei Liu

    2015-11-01

    Full Text Available Purpose: Targeting the problem of overload trucking in Highway Transportation of iron ore from Caofeidian to Tangshan (HTCT, this paper aims to assess long-term effects of alternative Truck Weight Regulation (TWR policies on sustainability of HTCT. Design/methodology/approach: A system dynamics model was established for policy evaluation. The model, composed of six interrelating modules, is able to simulate policies effects on trucking issues such as freight flow, truck traffic flow, pavement performance, highway transport capacity and trucking time, and further on the Cumulative Economic Cost (CEC including transport cost and time cost of freight owners and the Cumulative Social Cost (CSC including pavement maintenance cost, green house gas emission cost, air pollutants emission cost and traffic accidents cost, so the effects of TWR policies on sustainability of HTCT could be evaluated. Findings: According to different values of overload ratio which a TWR policy allows, alternative TWR policies are classified into three types, which are The Rigid Policy (TRP, The Moderate Policy (TMP and The Tolerant Policy (TTP. Results show that the best policy for sustainability of HTCT depends on the importance of CSC which is expected by the local government. To be specific, (1 if CSC is considered much less important than CEC, the local government should continue implementing the current TTP with the maximum overload ratio; (2 if CSC is considered much more important than CEC, then TRP is recommended; and (3 if CSC is considered slightly more important than CES, TMP with overload ratio of 80% is the best. Practical implications: Conclusions of this paper may help the local government design appropriate TWR policies to achieve sustainability of HTCT. Originality/value: To the best of our knowledge, this is the first effort to evaluate TWR policies on sustainability of regional freight transportation based on system dynamics modeling.

  17. Adolescents' Self-Regulation Development via the Sensory Room System

    Science.gov (United States)

    Kalimullin, Aydar M.; Kuvaldina, Elana A.; Koinova-Zoellner, Julia

    2016-01-01

    The urgency of the issue stated in this article is caused by the need for mastering skills and patterns of self-regulation when being an adolescent since this time is sensitive for developing processes of personal understanding and evolution. Thus, mastering skills and patterns of self-regulation as a necessary part of the whole ability of…

  18. 77 FR 11355 - Defense Federal Acquisition Regulation Supplement; Business Systems-Definition and Administration...

    Science.gov (United States)

    2012-02-24

    ...D published an initial proposed rule for Business Systems-- Definition and Administration (DFARS... the definition and administration of contractor business systems as follows: A. Contractor business..., 245, and 252 RIN 0750-AG58 Defense Federal Acquisition Regulation Supplement; Business Systems...

  19. Fundamentals of Adaptive Intelligent Tutoring Systems for Self-Regulated Learning

    Science.gov (United States)

    2015-03-01

    ARL-SR-0318 ● MAR 2015 US Army Research Laboratory Fundamentals of Adaptive Intelligent Tutoring Systems for Self-Regulated...Adaptive Intelligent Tutoring Systems for Self-Regulated Learning by Robert A Sottilare Human Research and Engineering Directorate, ARL...TITLE AND SUBTITLE Fundamentals of Adaptive Intelligent Tutoring Systems for Self-Regulated Learning 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c

  20. Robust Fuzzy Control for Fractional-Order Uncertain Hydroturbine Regulating System with Random Disturbances

    OpenAIRE

    Fengjiao Wu; Guitao Zhang; Zhengzhong Wang

    2016-01-01

    The robust fuzzy control for fractional-order hydroturbine regulating system is studied in this paper. First, the more practical fractional-order hydroturbine regulating system with uncertain parameters and random disturbances is presented. Then, on the basis of interval matrix theory and fractional-order stability theorem, a fuzzy control method is proposed for fractional-order hydroturbine regulating system, and the stability condition is expressed as a group of linear matrix inequalities. ...

  1. 75 FR 75549 - Defense Federal Acquisition Regulation Supplement; Business Systems-Definition and Administration...

    Science.gov (United States)

    2010-12-03

    ..., et al. Defense Federal Acquisition Regulation Supplement; Business Systems-- Definition and... Regulation Supplement; Business Systems--Definition and Administration (DFARS Case 2009-D038) AGENCY: Defense.... SUPPLEMENTARY INFORMATION: I. Background DoD published a proposed rule for Business Systems--Definition and...

  2. Review of Bruce A reactor regulating system software

    International Nuclear Information System (INIS)

    1995-12-01

    Each of the four reactor units at the Ontario Hydro Bruce A Nuclear Generating Station is controlled by the Reactor Regulating System (RRS) software running on digital computers. This research report presents an assessment of the quality and reliability of the RRS software based on a review of the RRS design documentation, an analysis of certain significant Event Reports (SERs), and an examination of selected software changes. We found that the RRS software requirements (i.e., what the software should do) were never clearly documented, and that design documents, which should describe how the requirements are implemented, are incomplete and inaccurate. Some RRS-related SERs (i.e., reports on unexpected incidents relating to the reactor control) implied that there were faults in the RRS, or that RRS changes should be made to help prevent certain unexpected events. The follow-up investigations were generally poorly documented, and so it could not usually be determined that problems were properly resolved. The Bruce A software change control procedures require improvement. For the software changes examined, there was insufficient evidence provided by Ontario Hydro that the required procedures regarding change approval, independent review, documentation updates, and testing were followed. Ontario Hydro relies on the expertise of their technical staff to modify the RRS software correctly; they have confidence in the software code itself, even if the documentation is not up-to-date. Ontario Hydro did not produce the documentation required for an independent formal assessment of the reliability of the RRS. (author). 37 refs., 3 figs

  3. Review of Bruce A reactor regulating system software

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-12-01

    Each of the four reactor units at the Ontario Hydro Bruce A Nuclear Generating Station is controlled by the Reactor Regulating System (RRS) software running on digital computers. This research report presents an assessment of the quality and reliability of the RRS software based on a review of the RRS design documentation, an analysis of certain significant Event Reports (SERs), and an examination of selected software changes. We found that the RRS software requirements (i.e., what the software should do) were never clearly documented, and that design documents, which should describe how the requirements are implemented, are incomplete and inaccurate. Some RRS-related SERs (i.e., reports on unexpected incidents relating to the reactor control) implied that there were faults in the RRS, or that RRS changes should be made to help prevent certain unexpected events. The follow-up investigations were generally poorly documented, and so it could not usually be determined that problems were properly resolved. The Bruce A software change control procedures require improvement. For the software changes examined, there was insufficient evidence provided by Ontario Hydro that the required procedures regarding change approval, independent review, documentation updates, and testing were followed. Ontario Hydro relies on the expertise of their technical staff to modify the RRS software correctly; they have confidence in the software code itself, even if the documentation is not up-to-date. Ontario Hydro did not produce the documentation required for an independent formal assessment of the reliability of the RRS. (author). 37 refs., 3 figs.

  4. The Kdp-ATPase system and its regulation

    Indian Academy of Sciences (India)

    Madhu Sudhan

    2007-03-15

    Mar 15, 2007 ... rice paddy fields) shows a strong dependence on K+ for normal growth ... The possible mechanism(s) of regulation of the unique kdp operons from Anabaena .... of that bacterium during osmotic stress and low temperature.

  5. Dynamic Model of Kaplan Turbine Regulating System Suitable for Power System Analysis

    Directory of Open Access Journals (Sweden)

    Jie Zhao

    2015-01-01

    Full Text Available Accurate modeling of Kaplan turbine regulating system is of great significance for grid security and stability analysis. In this paper, Kaplan turbine regulating system model is divided into the governor system model, the blade control system model, and the turbine and water diversion system model. The Kaplan turbine has its particularity, and the on-cam relationship between the wicket gate opening and the runner blade angle under a certain water head on the whole range was obtained by high-order curve fitting method. Progressively the linearized Kaplan turbine model, improved ideal Kaplan turbine model, and nonlinear Kaplan turbine model were developed. The nonlinear Kaplan turbine model considered the correction function of the blade angle on the turbine power, thereby improving the model simulation accuracy. The model parameters were calculated or obtained by the improved particle swarm optimization (IPSO algorithm. For the blade control system model, the default blade servomotor time constant given by value of one simplified the modeling and experimental work. Further studies combined with measured test data verified the established model accuracy and laid a foundation for further research into the influence of Kaplan turbine connecting to the grid.

  6. Design and Simulation of PID parameters self-tuning based on DC speed regulating system

    Directory of Open Access Journals (Sweden)

    Feng Wei Jie

    2016-01-01

    Full Text Available The DC speed regulating system has many difficult issues such as system parameters and PID control parameters are difficult to determine. On the basis of model for a single closed-loop DC speed regulating system, this paper puts forward a method of PID parameters self-tuning based on the step response detection and reduced order equivalent. First, detect system step response and get response parameters. Then equal it to a second order system model, and achieve optimal PID control parameters based on optimal second order system to realize of PID parameters self-tuning. The PID parameters self-tuning process of DC speed regulating system is simulated with the help of MATLAB/Simulink. The simulation results show that the method is simple and effective. The system can obtain good dynamic and static performance when the PID parameters are applied to DC speed regulating system.

  7. Regulation

    International Nuclear Information System (INIS)

    Ballereau, P.

    1999-01-01

    The different regulations relative to nuclear energy since the first of January 1999 are given here. Two points deserve to be noticed: the decree of the third august 1999 authorizing the national Agency for the radioactive waste management to install and exploit on the commune of Bures (Meuse) an underground laboratory destined to study the deep geological formations where could be stored the radioactive waste. The second point is about the uranium residues and the waste notion. The judgment of the administrative tribunal of Limoges ( 9. july 1998) forbidding the exploitation of a storage installation of depleted uranium considered as final waste and qualifying it as an industrial waste storage facility has been annulled bu the Court of Appeal. It stipulated that, according to the law number 75663 of the 15. july 1965, no criteria below can be applied to depleted uranium: production residue (possibility of an ulterior enrichment), abandonment of a personal property or simple intention to do it ( future use aimed in the authorization request made in the Prefecture). This judgment has devoted the primacy of the waste notion on this one of final waste. (N.C.)

  8. The Development of Innovation Systems as an Object with the State Regulation

    Directory of Open Access Journals (Sweden)

    Melnyk Alexander G.

    2017-09-01

    Full Text Available The article examines the processes of structuring the environment for the development of innovation systems in terms of the formation of a State regulated object. A methodological approach to definition of the State regulation at the primary, secondary and tertiary levels of structuring the environment of innovation systems has been suggested, based on the premise of the objective nature of the integration of social environment and market mechanisms into the structure of an object with the State regulation for the development of innovation systems. The definition of innovative systems as an object with the State regulation in terms of structural-organizational and functional areas of their expansion has been presented. A model for the progressive extension of the State regulated object by means of the development of innovation systems at the primary, secondary and tertiary levels of the structuring of environment in the process of formation of the institutional and technological structures of innovation systems has been proposed.

  9. Normative Regulation of Anti-Corruption in the System of Local Self-Government

    Directory of Open Access Journals (Sweden)

    Darya F. Kupcha

    2017-03-01

    Full Text Available In the present work authors attempt to analyze normative acts aimed at regulating relations in the sphere of counteracting corruption at the level of local self-government. In the conclusion authors summarize that despite criticism, in the Russian Federation, a system of regulatory regulation to counteract corruption (including at the local level is formed. Further improvements of this system should be made in the legal regulation at the local level.

  10. System and method for regulating EGR cooling using a rankine cycle

    Science.gov (United States)

    Ernst, Timothy C.; Morris, Dave

    2015-12-22

    This disclosure relates to a waste heat recovery (WHR) system and method for regulating exhaust gas recirculation (EGR) cooling, and more particularly, to a Rankine cycle WHR system and method, including a recuperator bypass arrangement to regulate EGR exhaust gas cooling for engine efficiency improvement and thermal management. This disclosure describes other unique bypass arrangements for increased flexibility in the ability to regulate EGR exhaust gas cooling.

  11. DC microgrids with energy storage systems and demand response for providing support to frequency regulation of electrical power systems

    DEFF Research Database (Denmark)

    Basic, Hrvoje; Dragicevic, Tomislav; Pandzic, Hrvoje

    2017-01-01

    Frequency regulation of electric power systems efficiency depends on response time and on power reserves for frequency regulation. As integration of non-dispatchable renewable generation in the power system results with increased need for power reserves from fast responding power units, the idea ...

  12. The NAD/NARB System: Advertising Self-Regulation at Work.

    Science.gov (United States)

    Hays, Robert

    Self-regulation, as defined by the National Advertising Division/National Advertising Review Board (NAD/NARB), is a process whereby the advertising industry regulates itself and turns to the federal government only if the system fails. The NAD/NARB system involves a two-step process: complaints are initially handled by the NAD and then are either…

  13. 77 FR 51496 - Federal Acquisition Regulation; Basic Safeguarding of Contractor Information Systems

    Science.gov (United States)

    2012-08-24

    ... Federal Acquisition Regulation; Basic Safeguarding of Contractor Information Systems AGENCY: Department of... Acquisition Regulation (FAR) to add a new subpart and contract clause for the basic safeguarding of contractor... information) that will be resident on or transiting through contractor information systems. DATES: Interested...

  14. 75 FR 3178 - Defense Federal Acquisition Regulation Supplement; Lead System Integrators

    Science.gov (United States)

    2010-01-20

    ... Government procurement. Amy G. Williams, Editor, Defense Acquisition Regulations System. 0 Accordingly, the..., without change, an interim rule amending the Defense Federal Acquisition Regulation Supplement (DFARS) to... limitations on the award of new contracts for lead system integrator functions in the acquisition of major DoD...

  15. Insulin Action in Brain Regulates Systemic Metabolism and Brain Function

    OpenAIRE

    Kleinridders, Andr?; Ferris, Heather A.; Cai, Weikang; Kahn, C. Ronald

    2014-01-01

    Insulin receptors, as well as IGF-1 receptors and their postreceptor signaling partners, are distributed throughout the brain. Insulin acts on these receptors to modulate peripheral metabolism, including regulation of appetite, reproductive function, body temperature, white fat mass, hepatic glucose output, and response to hypoglycemia. Insulin signaling also modulates neurotransmitter channel activity, brain cholesterol synthesis, and mitochondrial function. Disruption of insulin action in t...

  16. 75 FR 64148 - General Regulation: National Park System

    Science.gov (United States)

    2010-10-19

    ... literary giant at the Eugene O'Neill National Historical Site, California; and the artistic grace of a... that is not reasonably likely to attract a crowd or onlookers. This language is similar to the... the criteria of section 3(b)(2) requiring that all regulations be written in clear language and...

  17. Voltage regulator placement in radial distribution system using plant ...

    African Journals Online (AJOL)

    user

    location and number along with tap setting of the voltage regulators that ... can be fixed or switched type; they are considered integer multiple of a capacitor unit ..... By simulating the growth process of plant phototropism, a probability model ..... He is referee for IEE Proceedings - Generation Transmission and Distribution and ...

  18. The Kdp-ATPase system and its regulation

    Indian Academy of Sciences (India)

    2007-03-15

    Mar 15, 2007 ... K+, the dominant intracellular cation, is required for various physiological processes like turgor homeostasis, pH regulation etc. Bacterial cells have evolved many diverse K+ transporters to maintain the desired concentration of internal K+. In E. coli, the KdpATPase (comprising of the KdpFABC complex), ...

  19. Conceptual design of control rod regulating system for plate type fuels of Triga-2000 reactor

    International Nuclear Information System (INIS)

    Eko Priyono; Saminto

    2016-01-01

    Conceptual design of the control rod regulating system for plate type fuel of TRIGA-2000 reactor has been made. Conceptual design of the control rod regulating system for plate type fuel of TRIGA-2000 reactor was made with refer to study result of instrument and control system which is used in BATAN'S reactor. Conceptual design of the control rod regulating system for plate type fuel of TRIGA-2000 reactor consist of 4 segments that is control panel, translator, driver and display. Control panel is used for regulating, safety and display control rod, translator is used for signal processing from control panel, driver is used for driving control rod and display is used for display control rod level position. The translator was designed in 2 modes operation i.e operation by using PLC modules and IC TTL modules. These conceptual design can be used as one of reference of control rod regulating system detail design. (author)

  20. R and D perspectives on the advanced nuclear safety regulation system

    International Nuclear Information System (INIS)

    Lee, Chang Ju; Ahn, Sang Kyu; Park, Jong Seuk; Chung, Dae Wook; Han, Sang Hoon; Lee, Jung Won

    2009-01-01

    As current licensing process is much desired to be optimized both plant safety and regulatory efficiency, an advanced safety regulation such as risk informed regulation has been come out. Also, there is a need to have a future oriented safety regulation since a lot of new reactors are conceptualized. Keeping pace with these needs, since early 2007, Korean government has launched a new project for preparing an advanced and future oriented nuclear safety regulation system. In order to get practical achievements, the project team sets up such specific research objectives for the development of: implementation program for graded regulation using risk and performance information; multi purpose PSA models for regulatory uses; a technology neutral regulatory framework for future innovative reactors; evaluation procedure of proliferation resistance; and, performance based fire hazard analysis method and evaluation system. This paper introduces major R and D outputs of this project, and provides some perspectives for achieving effectiveness and efficiency of the nuclear regulation system in Korea

  1. R and D perspectives on the advanced nuclear safety regulation system

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Chang Ju; Ahn, Sang Kyu; Park, Jong Seuk; Chung, Dae Wook [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of); Han, Sang Hoon; Lee, Jung Won [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2009-04-15

    As current licensing process is much desired to be optimized both plant safety and regulatory efficiency, an advanced safety regulation such as risk informed regulation has been come out. Also, there is a need to have a future oriented safety regulation since a lot of new reactors are conceptualized. Keeping pace with these needs, since early 2007, Korean government has launched a new project for preparing an advanced and future oriented nuclear safety regulation system. In order to get practical achievements, the project team sets up such specific research objectives for the development of: implementation program for graded regulation using risk and performance information; multi purpose PSA models for regulatory uses; a technology neutral regulatory framework for future innovative reactors; evaluation procedure of proliferation resistance; and, performance based fire hazard analysis method and evaluation system. This paper introduces major R and D outputs of this project, and provides some perspectives for achieving effectiveness and efficiency of the nuclear regulation system in Korea.

  2. Regulation of the galanin system by repeated electroconvulsive seizures in mice

    DEFF Research Database (Denmark)

    Christiansen, S H; Woldbye, D P D

    2010-01-01

    of epileptic activity and depression, including the piriform cortex, hippocampal dentate gyrus, and amygdala. Likewise, GalR2 gene expression was up-regulated in both the central and the medial amygdala, whereas GalR1 gene expression showed a modest down-regulation in the medial amygdala. [(125) I......]galanin receptor binding in the piriform cortex, hippocampus, and amygdala was found to be significantly down-regulated. These data show that the galanin system is regulated by repeated ECS in a number of brain regions implicated in seizure regulation and depression. These changes may play a role...

  3. Leptin regulates bone formation via the sympathetic nervous system

    Science.gov (United States)

    Takeda, Shu; Elefteriou, Florent; Levasseur, Regis; Liu, Xiuyun; Zhao, Liping; Parker, Keith L.; Armstrong, Dawna; Ducy, Patricia; Karsenty, Gerard

    2002-01-01

    We previously showed that leptin inhibits bone formation by an undefined mechanism. Here, we show that hypothalamic leptin-dependent antiosteogenic and anorexigenic networks differ, and that the peripheral mediators of leptin antiosteogenic function appear to be neuronal. Neuropeptides mediating leptin anorexigenic function do not affect bone formation. Leptin deficiency results in low sympathetic tone, and genetic or pharmacological ablation of adrenergic signaling leads to a leptin-resistant high bone mass. beta-adrenergic receptors on osteoblasts regulate their proliferation, and a beta-adrenergic agonist decreases bone mass in leptin-deficient and wild-type mice while a beta-adrenergic antagonist increases bone mass in wild-type and ovariectomized mice. None of these manipulations affects body weight. This study demonstrates a leptin-dependent neuronal regulation of bone formation with potential therapeutic implications for osteoporosis.

  4. Intelligent energy systems - Regulating the electricity grid using car batteries

    International Nuclear Information System (INIS)

    Horbaty, R.

    2009-01-01

    This article takes a look at how the electricity supply industry will, in the future, be able to substantially rely on decentrally organised sources of renewable energy. As such forms of power generation are, in part, difficult to plan, the increasing importance of regulating energy is being stressed. The use of the batteries of plug-in hybrid vehicles to provide such regulating power is discussed. So-called smart grids within the framework of a deregulated energy market are discussed and examples of possible configurations are noted. The intelligent control of apparatus and generation and storage facilities is discussed. Individual mobility with lower emissions is examined. New business areas now opening up for the electricity economy and vehicle manufacturers are discussed.

  5. Cholesterol: Its Regulation and Role in Central Nervous System Disorders

    OpenAIRE

    Matthias Orth; Stefano Bellosta

    2012-01-01

    Cholesterol is a major constituent of the human brain, and the brain is the most cholesterol-rich organ. Numerous lipoprotein receptors and apolipoproteins are expressed in the brain. Cholesterol is tightly regulated between the major brain cells and is essential for normal brain development. The metabolism of brain cholesterol differs markedly from that of other tissues. Brain cholesterol is primarily derived by de novo synthesis and the blood brain barrier prevents the uptake of lipoprotein...

  6. A two-component system regulates hemin acquisition in Porphyromonas gingivalis.

    Directory of Open Access Journals (Sweden)

    Jodie C Scott

    Full Text Available Porphyromonas gingivalis is a Gram-negative oral anaerobe associated with infection of the periodontia. The organism has a small number of two-component signal transduction systems, and after comparing genome sequences of strains W83 and ATCC 33277 we discovered that the latter was mutant in histidine kinase (PGN_0752, while the cognate response regulator (PGN_0753 remained intact. Microarray-based transcriptional profiling and ChIP-seq assays were carried out with an ATCC 33277 transconjugant containing the functional histidine kinase from strain W83 (PG0719. The data showed that the regulon of this signal transduction system contained genes that were involved in hemin acquisition, including gingipains, at least three transport systems, as well as being self-regulated. Direct regulation by the response regulator was confirmed by electrophoretic mobility shift assays. In addition, the system appears to be activated by hemin and the regulator acts as both an activator and repressor.

  7. An advanced regulator for the helium pressurization systems of the Space Shuttle OMS and RCS

    Science.gov (United States)

    Wichmann, H.

    1973-01-01

    The Space Shuttle Orbit Maneuvering System and Reaction Control System are pressure-fed rocket propulsion systems utilizing earth storable hypergolic propellants and featuring engines of 6000 lbs and 900 lbs thrust, respectively. The helium pressurization system requirements for these propulsion systems are defined and the current baseline pressurization systems are described. An advanced helium pressure regulator capable of meeting both OMS and RCS helium pressurization system requirements is presented and its operating characteristics and predicted performance characteristics are discussed.

  8. Regulation of TGFβ in the immune system: An emerging role for integrins and dendritic cells

    OpenAIRE

    Worthington, John J.; Fenton, Thomas M.; Czajkowska, Beata I.; Klementowicz, Joanna E.; Travis, Mark A.

    2012-01-01

    Regulation of an immune response requires complex crosstalk between cells of the innate and adaptive immune systems, via both cell?cell contact and secretion of cytokines. An important cytokine with a broad regulatory role in the immune system is transforming growth factor-? (TGF-?). TGF-? is produced by and has effects on many different cells of the immune system, and plays fundamental roles in the regulation of immune responses during homeostasis, infection and disease. Although many cells ...

  9. Controlling chaotic and hyperchaotic systems via energy regulation

    International Nuclear Information System (INIS)

    Laval, L.; M'Sirdi, N.K.

    2003-01-01

    This paper focuses on a new control approach to steer trajectories of chaotic or hyperchaotic systems towards stable periodic orbits or stationary points of interest. This approach mainly consists in a variable structure control (VSC) that we extend by explicitly considering the system energy as basis for both controller design and system stabilization. In this paper, we present some theoretical results for a class of nonlinear (possibly chaotic or hyperchaotic) systems. Then some capabilities of the proposed approach are illustrated through examples related to a four-dimensional hyperchaotic system

  10. Child Maltreatment and Neural Systems Underlying Emotion Regulation.

    Science.gov (United States)

    McLaughlin, Katie A; Peverill, Matthew; Gold, Andrea L; Alves, Sonia; Sheridan, Margaret A

    2015-09-01

    The strong associations between child maltreatment and psychopathology have generated interest in identifying neurodevelopmental processes that are disrupted following maltreatment. Previous research has focused largely on neural response to negative facial emotion. We determined whether child maltreatment was associated with neural responses during passive viewing of negative and positive emotional stimuli and effortful attempts to regulate emotional responses. A total of 42 adolescents aged 13 to 19 years, half with exposure to physical and/or sexual abuse, participated. Blood oxygen level-dependent (BOLD) response was measured during passive viewing of negative and positive emotional stimuli and attempts to modulate emotional responses using cognitive reappraisal. Maltreated adolescents exhibited heightened response in multiple nodes of the salience network, including amygdala, putamen, and anterior insula, to negative relative to neutral stimuli. During attempts to decrease responses to negative stimuli relative to passive viewing, maltreatment was associated with greater recruitment of superior frontal gyrus, dorsal anterior cingulate cortex, and frontal pole; adolescents with and without maltreatment down-regulated amygdala response to a similar degree. No associations were observed between maltreatment and neural response to positive emotional stimuli during passive viewing or effortful regulation. Child maltreatment heightens the salience of negative emotional stimuli. Although maltreated adolescents modulate amygdala responses to negative cues to a degree similar to that of non-maltreated youths, they use regions involved in effortful control to a greater degree to do so, potentially because greater effort is required to modulate heightened amygdala responses. These findings are promising, given the centrality of cognitive restructuring in trauma-focused treatments for children. Copyright © 2015 American Academy of Child and Adolescent Psychiatry

  11. An Adaptive Regulator for Space Teleoperation System in Task Space

    Directory of Open Access Journals (Sweden)

    Chao Ge

    2014-01-01

    Full Text Available The problem of the gravity information which can not be obtained in advance for bilateral teleoperation is studied. In outer space exploration, the gravity term changes with the position changing of the slave manipulator. So it is necessary to design an adaptive regulator controller to compensate for the unknown gravity signal. Moreover, to get a more accurate position tracking performance, the controller is designed in the task space instead of the joint space. Additionally, the time delay considered in this paper is not only time varying but also unsymmetrical. Finally, simulations are presented to show the effectiveness of the proposed approach.

  12. 21 CFR 866.5900 - Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation detection system.

    Science.gov (United States)

    2010-04-01

    ... regulator (CFTR) gene mutation detection system. 866.5900 Section 866.5900 Food and Drugs FOOD AND DRUG...) gene mutation detection system. (a) Identification. The CFTR gene mutation detection system is a device... Guidance Document: CFTR Gene Mutation Detection System.” See § 866.1(e) for the availability of this...

  13. Robust Fuzzy Control for Fractional-Order Uncertain Hydroturbine Regulating System with Random Disturbances

    Directory of Open Access Journals (Sweden)

    Fengjiao Wu

    2016-01-01

    Full Text Available The robust fuzzy control for fractional-order hydroturbine regulating system is studied in this paper. First, the more practical fractional-order hydroturbine regulating system with uncertain parameters and random disturbances is presented. Then, on the basis of interval matrix theory and fractional-order stability theorem, a fuzzy control method is proposed for fractional-order hydroturbine regulating system, and the stability condition is expressed as a group of linear matrix inequalities. Furthermore, the proposed method has good robustness which can process external random disturbances and uncertain parameters. Finally, the validity and superiority are proved by the numerical simulations.

  14. Safety regulations concerning instrumentation and control systems for research reactors

    International Nuclear Information System (INIS)

    El-Shanshoury, A.I.

    2009-01-01

    A brief study on the safety and reliability issues related to instrumentation and control systems in nuclear reactor plants is performed. In response, technical and strategic issues are used to accomplish instrumentation and control systems safety. For technical issues there are ; systems aspects of digital I and C technology, software quality assurance, common-mode software, failure potential, safety and reliability assessment methods, and human factors and human machine interfaces. The strategic issues are the case-by-case licensing process and the adequacy of the technical infrastructure. The purpose of this work was to review the reliability of the safety systems related to these technical issues for research reactors

  15. Prospects for regulated competition in the health care system: what can China learn from Russia's experience?

    Science.gov (United States)

    Xu, Weiwei; Sheiman, Igor; van de Ven, Wynand P M M; Zhang, Wei

    2011-05-01

    As China explores new directions to reform its health care system, regulated competition among both insurers and providers of care might be one potential model. The Russian Federation in 1993 implemented legislation intended to stimulate such regulated competition in the health care sector. The subsequent progress and lessons learned over these 17 years can shed light on and inform the future evolution of the Chinese system. In this paper, we list the necessary pre-conditions for reaping the benefits of regulated competition in the health care sector. We indicate to what extent these conditions are being fulfilled in the post-reform Russian and current Chinese health care systems. We draw lessons from the Russian experience for the Chinese health care system, which shares a similar economic and political background with the pre-reform Russian health care system in terms of the starting point of the reform, and analyse the prospects for regulated competition in China.

  16. Fuzzy Controller for a Voltage-Regulated Solar-Powered MPPT System for Hybrid Power System Applications

    Directory of Open Access Journals (Sweden)

    Jaw-Kuen Shiau

    2015-04-01

    Full Text Available This paper presents the design of a fuzzy-logic-based voltage-regulated solar power maximum power point tracking (MPPT system for applications involving hybrid power systems. The system contains a solar power system and battery as the primary and secondary power sources, respectively. The solar system alone supplies power to the electric motor and maintains the output voltage at a predetermined level when it has sufficient power. When the solar power is insufficient, the solar system is operated at its maximum power point (MPP and the battery is engaged to compensate for the insufficiency. First, a variant of the incremental conductance MPP condition was established. Under the MPP condition, the voltage-regulated MPPT system was formulated as a feedback control system, where the MPP condition and voltage regulation requirements were used as the system inputs. Next, a fuzzy controller was developed to perform the voltage-regulated MPPT function for the hybrid power system. A simulation model based on Matrix laboratory (MATLAB/SIMULINK (a block diagram environment for multi-domain simulation and model-based design and a piecewise linear electric circuit simulation (PLECS tool for controlling the dc motor velocity was developed to verify the voltage-regulated solar power MPPT system.

  17. Implementing a Self-Regulated "WebQuest" Learning System for Chinese Elementary Schools

    Science.gov (United States)

    Hsiao, Hsien-Sheng; Tsai, Chung-Chieh; Lin, Chien-Yu; Lin, Chih-Cheng

    2012-01-01

    The rapid growth of Internet has resulted in the rise of WebQuest learning recently. Teachers encourage students to participate in the searching for knowledge on different topics. When using WebQuest, students' self-regulation is often the key to successful learning. Therefore, this study establishes a self-regulated learning system to assist…

  18. Developing the support business-processes information system for self-regulation institute

    Directory of Open Access Journals (Sweden)

    Kravchenko Anatoly Vasilevich

    2011-11-01

    Full Text Available Studying the methods of sructurization, optimization and the automation for modern self-regulation institute business-processes are considered in the article. The aim of the text is to show the strategy of modeling self-regulation information system and the strategy of the membership dues accounting and agency compensation.

  19. 75 FR 71560 - Defense Federal Acquisition Regulation Supplement; Cost and Software Data Reporting System (DFARS...

    Science.gov (United States)

    2010-11-24

    ... also asked what allowance is provided for contractors with accounting software that does not... RIN 0750-AG46 Defense Federal Acquisition Regulation Supplement; Cost and Software Data Reporting... Regulation Supplement (DFARS) to address DoD Cost and Software Data Reporting system requirements for Major...

  20. 75 FR 65439 - Defense Federal Acquisition Regulation Supplement; Electronic Subcontracting Reporting System

    Science.gov (United States)

    2010-10-25

    ... Accounting Service or Missile Defense Agency. (2) For DoD, the authority to acknowledge receipt or reject... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Parts 219 and 252 [DFARS Case 2009-D002] Defense Federal Acquisition Regulation Supplement; Electronic Subcontracting Reporting...

  1. Emotion Regulation via the Autonomic Nervous System in Children with Attention-Deficit/Hyperactivity Disorder (ADHD)

    Science.gov (United States)

    Musser, Erica D.; Backs, Richard W.; Schmitt, Colleen F.; Ablow, Jennifer C.; Measelle, Jeffery R.; Nigg, Joel T.

    2011-01-01

    Despite growing interest in conceptualizing ADHD as involving disrupted emotion regulation, few studies have examined the physiological mechanisms related to emotion regulation in children with this disorder. This study examined parasympathetic and sympathetic nervous system reactivity via measures of respiratory sinus arrhythmia (RSA) and cardiac…

  2. Financial regulation and financial system architecture in Central Europe

    NARCIS (Netherlands)

    Scholtens, B

    At the beginning of the transition, advice to Central European countries with respect to how to set up their financial systems was based on models used in western economies. This paper analyzes the experiences to set up a financial system in Central Europe. The experience in the first transition

  3. Insulin action in brain regulates systemic metabolism and brain function.

    Science.gov (United States)

    Kleinridders, André; Ferris, Heather A; Cai, Weikang; Kahn, C Ronald

    2014-07-01

    Insulin receptors, as well as IGF-1 receptors and their postreceptor signaling partners, are distributed throughout the brain. Insulin acts on these receptors to modulate peripheral metabolism, including regulation of appetite, reproductive function, body temperature, white fat mass, hepatic glucose output, and response to hypoglycemia. Insulin signaling also modulates neurotransmitter channel activity, brain cholesterol synthesis, and mitochondrial function. Disruption of insulin action in the brain leads to impairment of neuronal function and synaptogenesis. In addition, insulin signaling modulates phosphorylation of tau protein, an early component in the development of Alzheimer disease. Thus, alterations in insulin action in the brain can contribute to metabolic syndrome, and the development of mood disorders and neurodegenerative diseases. © 2014 by the American Diabetes Association.

  4. Dynamic regulation of the endocannabinoid system: implications for analgesia

    Directory of Open Access Journals (Sweden)

    Wong Amy

    2009-10-01

    Full Text Available Abstract The analgesic effects of cannabinoids are well documented, but these are often limited by psychoactive side-effects. Recent studies indicate that the endocannabinoid system is dynamic and altered under different pathological conditions, including pain states. Changes in this receptor system include altered expression of receptors, differential synthetic pathways for endocannabinoids are expressed by various cell types, multiple pathways of catabolism and the generation of biologically active metabolites, which may be engaged under different conditions. This review discusses the evidence that pain states alter the endocannabinoid receptor system at key sites involved in pain processing and how these changes may inform the development of cannabinoid-based analgesics.

  5. Direct Torque Control System for Permanent Magnet Synchronous Machine with Fuzzy Speed Pi Regulator

    Science.gov (United States)

    Nabti, K.; Abed, K.; Benalla, H.

    2008-06-01

    The Permanent Magnet Synchronous Machine (PMSM) speed regulation with a conventional PI regulator reduces the speed control precision, increase the torque fluctuation, and consequentially low performances of the whole system. With utilisation of fuzzy logic method, this paper presents the self adaptation of conventional PI regulator parameters Kp and Ki (proportional and integral coefficients respectively), using to regulate the speed in Direct Torque Control strategy (DTC). The ripples of both torque and flux are reduced remarkable, small overshooting and good dynamic of the speed and torque. Simulation results verify the proposed method validity.

  6. Phasevarion mediated epigenetic gene regulation in Helicobacter pylori.

    Directory of Open Access Journals (Sweden)

    Yogitha N Srikhanta

    Full Text Available Many host-adapted bacterial pathogens contain DNA methyltransferases (mod genes that are subject to phase-variable expression (high-frequency reversible ON/OFF switching of gene expression. In Haemophilus influenzae and pathogenic Neisseria, the random switching of the modA gene, associated with a phase-variable type III restriction modification (R-M system, controls expression of a phase-variable regulon of genes (a "phasevarion", via differential methylation of the genome in the modA ON and OFF states. Phase-variable type III R-M systems are also found in Helicobacter pylori, suggesting that phasevarions may also exist in this key human pathogen. Phylogenetic studies on the phase-variable type III modH gene revealed that there are 17 distinct alleles in H. pylori, which differ only in their DNA recognition domain. One of the most commonly found alleles was modH5 (16% of isolates. Microarray analysis comparing the wild-type P12modH5 ON strain to a P12ΔmodH5 mutant revealed that six genes were either up- or down-regulated, and some were virulence-associated. These included flaA, which encodes a flagella protein important in motility and hopG, an outer membrane protein essential for colonization and associated with gastric cancer. This study provides the first evidence of this epigenetic mechanism of gene expression in H. pylori. Characterisation of H. pylori modH phasevarions to define stable immunological targets will be essential for vaccine development and may also contribute to understanding H. pylori pathogenesis.

  7. Management System for Regulating Transport of Radioactive Material

    International Nuclear Information System (INIS)

    Lopez Vietri, J.R.; Capadona, N.M.; Barenghi, L.G.

    2011-01-01

    The objective of this paper is to describe the main characteristics of the Nuclear Regulatory Authority (Autoridad Regulatoria Nuclear - ARN) management system applied to the transport of radioactive material, in Argentina. In the frame of ARN's quality policy, 'Protection against ionizing radiation on transport of radioactive materials' was selected as one of the regulatory processes, named TMR from now on. ARN's management system is integrally based on ISO 9000 system addressed to help organizations in designing and implementing their quality management systems. TMR process was split into five sub processes in order to facilitate the implementation of the system. Such sub processes were defined taking into account of the main functions developed by ARN in the branch of safe transport of radioactive materials. For each of this processes were specified their objectives, inputs, activities and outputs, clients and stakeholders, responsibilities, supporting documents, control of documents and records, control of non-conformances, monitoring and measurements, audits, feedback and improvement. Supporting documents for sub processes were issued, validated, reviewed and improved as an essential point to achieve continuous improving. Simultaneously, some indexes were defined to monitor and measures sub processes as a way to show objective evidence of conformity with objectives. Finally, as conclusions of this paper, they will be showed the main obstacles and troubleshooting found in the design and implementation of management system as well as their solutions and state of advance. (authors)

  8. 78 FR 67927 - Foreign Trade Regulations (FTR): Mandatory Automated Export System Filing for All Shipments...

    Science.gov (United States)

    2013-11-13

    ... Internet at [email protected] ). FOR FURTHER INFORMATION CONTACT: Nick Orsini, Chief, Foreign Trade Division... 0607-AA50 Foreign Trade Regulations (FTR): Mandatory Automated Export System Filing for All Shipments... approval of new information collection requirements. [[Page 67928

  9. 75 FR 38765 - Domestic Origin Verification System Questionnaire and Regulations Governing Inspection and...

    Science.gov (United States)

    2010-07-06

    ..., facility assessment services, certifications of quantity and quality, import product inspections, and... control number. These include export certification, inspection of section 8e import products, and...] Domestic Origin Verification System Questionnaire and Regulations Governing Inspection and Certification of...

  10. Challenges of the banking regulation systems in the climate of the world economic crisis

    Directory of Open Access Journals (Sweden)

    Sedlarević Lazar

    2014-01-01

    Full Text Available At the end of the 20th century, banking systems of the developed countries have undergone multiple changes, where the basic dimensions of those changes were integration, deregulation and globalisation of activities. The resultant of these factors' actions was the creation of highly risky banking environment, which acted as a catalyst of the world economic crisis effects. These effects brought to the forefront weaknesses of the banking sector and of the banking regulation system, while emphasizing the need for their redefining. Hence this work examines in detail concrete models of the banking regulation systems in the European Union area and in the United States of America. In addition, directions of redefining regulation system were highlighted, and also the relevant differences between banking business regulation in the European Union and in the United States of America.

  11. Regulation of hippocampal neurogenesis by systemic factors including stress, glucocorticoids, sleep, and inflammation

    NARCIS (Netherlands)

    Lucassen, P.J.; Oomen, C.; van Dam, A.-M.; Czéh, B.; Gage, F.H.; Kempermann, G.; Song, H.

    2008-01-01

    This review summarizes and discusses the regulation of adult neurogenesis and hippocampal cellular plasticity by systemic factors. We focus on the role of stress, glucocorticoids, and related factors such as sleep deprivation and inflammation.

  12. Integrated cropping systems : an answer to environmental regulations imposed on nursery stock in the Netherlands

    NARCIS (Netherlands)

    Pronk, A.A.; Challa, H.

    2000-01-01

    Government regulations in the Netherlands are increasingly constraining and sometimes even banning conventional cultivation practices in nursery stock cropping systems. As a consequence, growers face problems concerning the use of manure, fertilisers and irrigation. In this study we analysed the

  13. Report: Wells Band Council Needs to Improve Its Accounting System to Comply With Federal Regulations

    Science.gov (United States)

    Report #14-2-0316, July 14, 2014. The Wells Band Council’s accounting system did not comply with federal regulations, which resulted in $390,000 of questioned costs and proposed high-risk designation for the grantee.

  14. [Regulation of sporulation by two-component system YvcPQ in Bacillus thuringiensis].

    Science.gov (United States)

    Fan, Qingyun; Zhang, Shumeng; Gong, Yujing; He, Jin

    2017-01-04

    To study the regulation of sporulation controlled by two-component system (TCS) YvcPQ. β-galactosidase experiment was used to verify the regulation of YvcP on kapD expression; bacterial one-hybrid assay, EMSA and RT-qPCR were applied to study the regulation of AbrB on yvcPQ expression; markerless gene deletion coupled with spore count was used to reveal the influence of yvcPQ and kapD expressions on sporulation. transcriptional regulator AbrB up-regulated the expression of yvcPQ; YvcP promoted the expression of kapD to inhibit sporulation. AbrB up-regulated the transcription of yvcPQ operon, then the increased YvcP strengthened the transcriptional acitivation of sporulation inhibitor gene kapD, and subsequently inhibited sporulation.

  15. The Development of Innovation Systems as an Object with the State Regulation

    OpenAIRE

    Melnyk Alexander G.

    2017-01-01

    The article examines the processes of structuring the environment for the development of innovation systems in terms of the formation of a State regulated object. A methodological approach to definition of the State regulation at the primary, secondary and tertiary levels of structuring the environment of innovation systems has been suggested, based on the premise of the objective nature of the integration of social environment and market mechanisms into the structure of an object with the St...

  16. Stimuli-Regulated Smart Polymeric Systems for Gene Therapy

    Directory of Open Access Journals (Sweden)

    Ansuja Pulickal Mathew

    2017-04-01

    Full Text Available The physiological condition of the human body is a composite of different environments, each with its own parameters that may differ under normal, as well as diseased conditions. These environmental conditions include factors, such as pH, temperature and enzymes that are specific to a type of cell, tissue or organ or a pathological state, such as inflammation, cancer or infection. These conditions can act as specific triggers or stimuli for the efficient release of therapeutics at their destination by overcoming many physiological and biological barriers. The efficacy of conventional treatment modalities can be enhanced, side effects decreased and patient compliance improved by using stimuli-responsive material that respond to these triggers at the target site. These stimuli or triggers can be physical, chemical or biological and can be internal or external in nature. Many smart/intelligent stimuli-responsive therapeutic gene carriers have been developed that can respond to either internal stimuli, which may be normally present, overexpressed or present in decreased levels, owing to a disease, or to stimuli that are applied externally, such as magnetic fields. This review focuses on the effects of various internal stimuli, such as temperature, pH, redox potential, enzymes, osmotic activity and other biomolecules that are present in the body, on modulating gene expression by using stimuli-regulated smart polymeric carriers.

  17. Development Of Linear Quadratic Regulator Design For Small UAV System

    Directory of Open Access Journals (Sweden)

    Cho Zin Myint

    2015-08-01

    Full Text Available The aim of this paper is to know the importance role of stability analysis for both unmanned aircraft system and for all control system. The objective of paper is to develop a method for dynamic stability analysis of the design process. These are categorized intoTo design model and stability analysis of UAV based on the forces and moment equations of aircraft dynamic model To choose the suitable controller for desired altitude of a particular UAV model To analyze the stability condition for aircraft using mathematical modeling and MATLAB. In this paper the analytical model of the longitudinal dynamic of flying wing UAV has been developed using aerodynamic data. The stability characteristics of UAV can be achieved from the system transfer function with LQR controller.

  18. A task management system for compliance with health, safety, and environmental regulations

    International Nuclear Information System (INIS)

    Crump, J.J.; O'Gorman, T.P.

    1992-01-01

    Shell Western E and P Inc. (SWEPI) has developed a new computer system to help it comply with health, safety, and environmental (HS and E) regulations. It is a task management system that functions at the detailed inventory level. It schedules work, instructs operations, and records compliance status. This article discusses design and development of the system

  19. 76 FR 28855 - Defense Federal Acquisition Regulation Supplement; Business Systems-Definition and Administration

    Science.gov (United States)

    2011-05-18

    ...; Business Systems-- Definition and Administration; Interim Rule #0;#0;Federal Register / Vol. 76 , No. 96...-AG58 Defense Federal Acquisition Regulation Supplement; Business Systems--Definition and Administration... an initial proposed rule for Business Systems-- Definition and Administration (DFARS Case 2009-D038...

  20. 75 FR 76692 - Defense Federal Acquisition Regulation Supplement; Business Systems-Definition and Administration...

    Science.gov (United States)

    2010-12-09

    ..., and 252 RIN 0750-AG58 Defense Federal Acquisition Regulation Supplement; Business Systems--Definition... for Business Systems--Definition and Administration (DFARS Case 2009-D038) in the Federal Register on... improve the effectiveness of DoD oversight of contractor business systems. The comment period is being...

  1. Dynamic regulation of neurotransmitter specification: Relevance to nervous system homeostasis

    Science.gov (United States)

    Borodinsky, Laura N.; Belgacem, Yesser Hadj; Swapna, Immani; Sequerra, Eduardo Bouth

    2013-01-01

    During nervous system development the neurotransmitter identity changes and coexpression of several neurotransmitters is a rather generalized feature of developing neurons. In the mature nervous system, different physiological and pathological circumstances recreate this phenomenon. The rules of neurotransmitter respecification are multiple. Among them, the goal of assuring balanced excitability appears as an important driving force for the modifications in neurotransmitter phenotype expression. The functional consequences of these dynamic revisions in neurotransmitter identity span a varied range, from fine-tuning the developing neural circuit to modifications in addictive and locomotor behaviors. Current challenges include determining the mechanisms underlying neurotransmitter phenotype respecification and how they intersect with genetic programs of neuronal specialization. PMID:23270605

  2. Studies on leptin and its feedback system for weight regulation

    International Nuclear Information System (INIS)

    Lei Chengzhi

    2002-01-01

    Recently the hormone leptin has been regarded as hormonal signal linking adipose tissue status with a number of key central nervous system circuits. The role of leptin and its feedback system in man is partly revealed. Hypothalamic centers appear to control appetite, metabolic rate and activity level in a co-ordinate manner. Within the hypothalamus, known weight regulatory molecules include leptin, neuropeptide Y and POMC. The authors integrated new information into a revised model for understanding this important regulatory process. The model of energy homeostasis propose that the interaction of leptin with various neuroendocrine pathway in the brain and in the periphery to affect food-take

  3. A study in improvement of administrative system in the nuclear safety regulation

    International Nuclear Information System (INIS)

    Yook, Dong Il; Kuk, Doe Hyeong; Lee, Seong Min; Kim, Jong Sam; Hwang, Sun Ho

    2001-03-01

    One of the most important tasks to improve nuclear safety regulation system is to separate nuclear regulatory institutes from public agencies which promote the development nuclear power. Moreover, nuclear safety regulation should be not only specialized but optimized to be adapted for new environments such as high-tech information age. Especially, it is necessary to reform the current nuclear safety regulation systems both to be effective under the local self-administration which began to operate in recent years and to be supported by local residents

  4. A study in improvement of administrative system in the nuclear safety regulation

    Energy Technology Data Exchange (ETDEWEB)

    Yook, Dong Il; Kuk, Doe Hyeong; Lee, Seong Min; Kim, Jong Sam; Hwang, Sun Ho [Chungnam National Univ., Taejon (Korea, Republic of)

    2001-03-15

    One of the most important tasks to improve nuclear safety regulation system is to separate nuclear regulatory institutes from public agencies which promote the development nuclear power. Moreover, nuclear safety regulation should be not only specialized but optimized to be adapted for new environments such as high-tech information age. Especially, it is necessary to reform the current nuclear safety regulation systems both to be effective under the local self-administration which began to operate in recent years and to be supported by local residents.

  5. System for measurement and automatic regulation of gas flow within an oil aging test device

    Directory of Open Access Journals (Sweden)

    Žigić Aleksandar

    2014-01-01

    Full Text Available This paper describes a system within an oil aging test device that serves for measurement and automatic regulation of gas flow. Following an already realized system that continuously monitors, logs, and regulates transformer oil temperature during the aging process and maintains temperature consistency within strict limits, a model of a flow meter and regulator of air or oxygen through transformer oil samples is developed. A special feature of the implemented system is the measurement of very small gas flows. A short technical description of the realized system is given with a functional block diagram. The basic technical characteristics of the system are specified, and the operating principles and application of the system are described. The paper also gives performance test results in a real exploitation environment.

  6. Multilevel Regulation of Bacterial Gene Expression with the Combined STAR and Antisense RNA System.

    Science.gov (United States)

    Lee, Young Je; Kim, Soo-Jung; Moon, Tae Seok

    2018-03-16

    Synthetic small RNA regulators have emerged as a versatile tool to predictably control bacterial gene expression. Owing to their simple design principles, small size, and highly orthogonal behavior, these engineered genetic parts have been incorporated into genetic circuits. However, efforts to achieve more sophisticated cellular functions using RNA regulators have been hindered by our limited ability to integrate different RNA regulators into complex circuits. Here, we present a combined RNA regulatory system in Escherichia coli that uses small transcription activating RNA (STAR) and antisense RNA (asRNA) to activate or deactivate target gene expression in a programmable manner. Specifically, we demonstrated that the activated target output by the STAR system can be deactivated by expressing two different types of asRNAs: one binds to and sequesters the STAR regulator, affecting the transcription process, while the other binds to the target mRNA, affecting the translation process. We improved deactivation efficiencies (up to 96%) by optimizing each type of asRNA and then integrating the two optimized asRNAs into a single circuit. Furthermore, we demonstrated that the combined STAR and asRNA system can control gene expression in a reversible way and can regulate expression of a gene in the genome. Lastly, we constructed and simultaneously tested two A AND NOT B logic gates in the same cell to show sophisticated multigene regulation by the combined system. Our approach establishes a methodology for integrating multiple RNA regulators to rationally control multiple genes.

  7. Electrical system regulations of the IEA-R1 reactor

    International Nuclear Information System (INIS)

    Mello, Jose Roberto de; Madi Filho, Tufic

    2013-01-01

    The IEA-R1 reactor of the Nuclear and Energy Research Institute (IPEN-CNEN/SP), is a research reactor open pool type, designed and built by the U.S. firm Babcock and Wilcox, having, as coolant and moderator, deionized light water and beryllium and graphite, as reflectors. Until about 1988, the reactor safety systems received power from only one source of energy. As an example, it may be cited the control desk that was powered only by the vital electrical system 220V, which, in case the electricity fails, is powered by the generator group: no-break 220V. In the years 1989 and 1990, a reform of the electrical system upgrading to increase the reactor power and, also, to meet the technical standards of the ABNT (Associacao Brasileira de Normas Tecnicas) was carried out. This work has the objective of showing the relationship between the electric power system and the IEA-R1 reactor security. Also, it demonstrates that, should some electrical power interruption occur, during the reactor operation, this occurrence would not start an accident event. (author)

  8. Systemic Model for Optimal Regulation in Public Service

    Directory of Open Access Journals (Sweden)

    Lucica Matei

    2006-05-01

    Full Text Available The current paper inscribes within those approaching the issue of public services from the interdisciplinary perspective. Public service development and imposing standards of efficiency and effectiveness, as well as for citizens’ satisfaction bring in front line the systemic modelling and establishing optimal policies for organisation and functioning of public services. The issue under discussion imposes an interface with powerful determinations of social nature. Consequently, the most adequate modelling might be that with a probabilistic and statistic nature. The fundamental idea of this paper, that obviously can be broadly developed, starts with assimilating the way of organisation and functioning of a public service with a waiting thread, to which some hypotheses are associated concerning the order of provision, performance measurement through costs or waiting time in the system etc. We emphasise the openness and dynamics of the public service system, as well as modelling by turning into account the statistic knowledge and researches, and we do not make detailed remarks on the cybernetic characteristics of this system. The optimal adjustment is achieved through analysis on the feedback and its comparison with the current standards or good practices.

  9. The tumor macroenvironment and systemic regulation of breast cancer progression.

    Science.gov (United States)

    Castaño, Zafira; Tracy, Kristin; McAllister, Sandra S

    2011-01-01

    Breast cancer is the most common malignancy among women worldwide and is the most common cause of death for women between 35 and 50 years of age. Women with breast cancer are at risk of developing metastases for their entire lifetime and, despite local and systemic therapies, approximately 30% of breast cancer patients will relapse (Jemal et al., 2010). Nearly all breast cancer related deaths are due to metastatic disease, even though metastasis is considered to be an inefficient process. In some cases, tumor cells disseminate from primary sites at an early stage, but remain indolent for protracted periods of time before becoming overt, life-threatening tumors. Little is known about the mechanisms that cause these indolent tumors to grow into malignant disease. Because of this gap in our understanding, we are unable to predict which breast cancer patients are likely to experience disease relapse or develop metastases years after treatment of their primary tumor. A better understanding of the mechanisms and signals involved in the exit of tumor cells from dormancy would not only allow for more accurate selection of patients that would benefit from systemic therapy, but could also lead to the development of more targeted therapies to inhibit the signals that promote disease progression. In this review, we address the systemic, or "macroenvironmental", contribution to tumor initiation and progression and what is known about how a pro-tumorigenic systemic environment is established.

  10. Kisspeptin system in ovariectomized mice: Estradiol and progesterone regulation.

    Science.gov (United States)

    Marraudino, Marilena; Martini, Mariangela; Trova, Sara; Farinetti, Alice; Ponti, Giovanna; Gotti, Stefano; Panzica, GianCarlo

    2018-06-01

    The kisspeptin system is clustered in two main groups of cell bodies (the periventricular region, RP3V and the arcuate nucleus, ARC) that send fibers mainly to the GnRH neurons and in a few other locations, including the paraventricular nucleus, PVN. In physiological conditions, gonadal hormones modulate the kisspeptin system with expression changes according to different phases of the estrous cycle: the highest being in estrus phase in RP3V and PVN (positive feedback), and in ARC during the diestrus phase (negative feedback). In this work we wanted to study these hormonal fluctuations during the estrous cycle, investigating the role played by progesterone (P) or estradiol (E 2 ), alone or together, on the kisspeptin system. Gonadectomized CD1 female mice were treated with P, E 2 or both (E 2  + P), following a timing of administration that emulates the different phases of estrous cycle, for two cycles of 4 days. As expected, the two cell groups were differentially affected by E 2 ; the RP3V group was positively influenced by E 2 (alone or with the P), whereas in the ARC the administration of E 2 did not affect the system. However P (alone) induced a rise in the kisspeptin immunoreactivity. All the treatments significantly affected the kisspeptin innervation of the PVN, with regional differences, suggesting that these fibers arrive from both RP3V and ARC nuclei. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Food for thought: how nutrients regulate root system architecture.

    Science.gov (United States)

    Shahzad, Zaigham; Amtmann, Anna

    2017-10-01

    The spatial arrangement of the plant root system (root system architecture, RSA) is very sensitive to edaphic and endogenous signals that report on the nutrient status of soil and plant. Signalling pathways underpinning RSA responses to individual nutrients, particularly nitrate and phosphate, have been unravelled. Researchers have now started to investigate interactive effects between two or more nutrients on RSA. Several proteins enabling crosstalk between signalling pathways have recently been identified. RSA is potentially an important trait for sustainable and/or marginal agriculture. It is generally assumed that RSA responses are adaptive and optimise nutrient uptake in a given environment, but hard evidence for this paradigm is still sparse. Here we summarize recent advances made in these areas of research. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Arabidopsis MAP kinase 4 negatively regulates systemic acquired resistance

    DEFF Research Database (Denmark)

    Petersen, M.; Brodersen, P.; Naested, H.

    2000-01-01

    Transposon inactivation of Arabidopsis MAP kinase 4 produced the mpk4 mutant exhibiting constitutive systemic acquired resistance (SAR) including elevated salicylic acid (SA) revels, increased resistance to virulent pathogens, and constitutive pathogenesis-related gene expression shown by Northern...... of NPR1. PDF1.2 and THI2.1 gene induction by jasmonate was blocked in mpk4 expressing NahG, suggesting that MPK4 is required for jasmonic acid-responsive gene expression....

  13. Stabilization and regulation of nonlinear systems a robust and adaptive approach

    CERN Document Server

    Chen, Zhiyong

    2015-01-01

    The core of this textbook is a systematic and self-contained treatment of the nonlinear stabilization and output regulation problems. Its coverage embraces both fundamental concepts and advanced research outcomes and includes many numerical and practical examples. Several classes of important uncertain nonlinear systems are discussed. The state-of-the art solution presented uses robust and adaptive control design ideas in an integrated approach which demonstrates connections between global stabilization and global output regulation allowing both to be treated as stabilization problems. Stabilization and Regulation of Nonlinear Systems takes advantage of rich new results to give students up-to-date instruction in the central design problems of nonlinear control, problems which are a driving force behind the furtherance of modern control theory and its application. The diversity of systems in which stabilization and output regulation become significant concerns in the mathematical formulation of practical contr...

  14. Modification of reference temperature program in reactor regulating system

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Sung Sik; Lee, Byung Jin; Kim, Se Chang; Cheong, Jong Sik [Korea Power Engineering Company, Inc., Seoul (Korea, Republic of); Kim, Ji In; Doo, Jin Yong [Korea Electric Power Cooperation, Yonggwang (Korea, Republic of)

    1999-12-31

    In Yonggwang nuclear units 3 and 4 currently under commercial operation, the cold temperature was very close to the technical specification limit of 298 deg C during initial startup testing, which was caused by the higher-than-expected reactor coolant system flow. Accordingly, the reference temperature (Tref) program needed to be revised to allow more flexibility for plant operations. In this study, the method of a specific test performed at Yonggwang nuclear unit 4 to revise the Tref program was described and the test results were discussed. In addition, the modified Tref program was evaluated on its potential impacts on system performance and safety. The methods of changing the Tref program and the associated pressurizer level setpoint program were also explained. Finally, for Ulchin nuclear unit 3 and 4 currently under initial startup testing, the effects of reactor coolant system flow rate on the coolant temperature were evaluated from the thermal hydraulic standpoint and an optimum Tref program was recommended. 6 refs., 4 figs., 2 tabs. (Author)

  15. Modification of reference temperature program in reactor regulating system

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Sung Sik; Lee, Byung Jin; Kim, Se Chang; Cheong, Jong Sik [Korea Power Engineering Company, Inc., Seoul (Korea, Republic of); Kim, Ji In; Doo, Jin Yong [Korea Electric Power Cooperation, Yonggwang (Korea, Republic of)

    1998-12-31

    In Yonggwang nuclear units 3 and 4 currently under commercial operation, the cold temperature was very close to the technical specification limit of 298 deg C during initial startup testing, which was caused by the higher-than-expected reactor coolant system flow. Accordingly, the reference temperature (Tref) program needed to be revised to allow more flexibility for plant operations. In this study, the method of a specific test performed at Yonggwang nuclear unit 4 to revise the Tref program was described and the test results were discussed. In addition, the modified Tref program was evaluated on its potential impacts on system performance and safety. The methods of changing the Tref program and the associated pressurizer level setpoint program were also explained. Finally, for Ulchin nuclear unit 3 and 4 currently under initial startup testing, the effects of reactor coolant system flow rate on the coolant temperature were evaluated from the thermal hydraulic standpoint and an optimum Tref program was recommended. 6 refs., 4 figs., 2 tabs. (Author)

  16. Hypothesis: the regulation of the partial pressure of oxygen by the serotonergic nervous system in hypoxia.

    Science.gov (United States)

    Devereux, Diana; Ikomi-Kumm, Julie

    2013-03-01

    The regulation of the partial pressure of oxygen by the serotonergic nervous system in hypoxia is a hypothesis, which proposes an inherent operative system in homo sapiens that allows central nervous system and endocrine-mediated vascular system adaption to variables in partial pressure of oxygen, pH and body composition, while maintaining sufficient oxygen saturation for the immune system and ensuring protection of major organs in hypoxic and suboptimal conditions. While acknowledging the importance of the Henderson-Hasselbalch equation in the regulation of acid base balance, the hypothesis seeks to define the specific neuroendocrine/vascular mechanisms at work in regulating acid base balance in hypoxia and infection. The SIA (serotonin-immune-adrenergic) system is proposed as a working model, which allows central nervous system and endocrine-mediated macro- and micro vascular 'fine tuning'. The neurotransmitter serotonin serves as a 'hypoxic sensor' in concert with other operators to orchestrate homeostatic balance in normal and pathological states. The SIA system finely regulates oxygen, fuel and metabolic buffering systems at local sites to ensure optimum conditions for the immune response. The SIA system is fragile and its operation may be affected by infection, stress, diet, environmental toxins and lack of exercise. The hypothesis provides new insight in the area of neuro-gastroenterology, and emphasizes the importance of diet and nutrition as a complement in the treatment of infection, as well as the normalization of intestinal flora following antibiotic therapy. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Systemic risk in the energy sector—Is there need for financial regulation?

    International Nuclear Information System (INIS)

    Kerste, Marco; Gerritsen, Matthijs; Weda, Jarst; Tieben, Bert

    2015-01-01

    The credit crisis points at serious systemic risks in Over The Counter derivative trading. This has resulted in new financial regulation, covering both the financial sector and non-financial sectors. The actual extent to which non-financial companies trading on OTC markets contribute to systemic risk has hardly been the subject of research. This paper investigates the need for financial regulation in the energy sector, which shows a high use of OTC derivatives, by modeling systemic risk measured by the expected fraction of additional failing firms (EAF). Contagion risk within the energy sector and from the energy sector towards the banking sector is compared with that in other non-financial sectors. This paper adds to existing systemic risk literature by specifically looking at financial interdependence between a non-financial sector showing a high usage of OTC commodity derivatives and the banking sector, while contributing to the discussion on energy sector regulation with technical systemic risk analysis. Results indicate that contagion risk from the energy towards the banking sector is not relatively high compared to other non-financial sectors. Our results provide a first indication to question the need for generalized regulation of OTC derivative transactions, as recently introduced by the European Market Infrastructure Regulation (EMIR). - Highlights: • We assess the need for regulating OTC energy commodity derivatives under EMIR. • We present a methodology to model systemic risk in non-financial sectors. • We analyse direct and indirect channels for contagion giving rise to systemic risk. • Contagion risk from the energy towards the banking sector is not relatively high. • New EU regulation for energy OTC trading not supported by analysis of systemic risk

  18. Immune Evasion, Immunopathology and the Regulation of the Immune System

    Directory of Open Access Journals (Sweden)

    Bruno Faivre

    2013-02-01

    Full Text Available Costs and benefits of the immune response have attracted considerable attention in the last years among evolutionary biologists. Given the cost of parasitism, natural selection should favor individuals with the most effective immune defenses. Nevertheless, there exists huge variation in the expression of immune effectors among individuals. To explain this apparent paradox, it has been suggested that an over-reactive immune system might be too costly, both in terms of metabolic resources and risks of immune-mediated diseases, setting a limit to the investment into immune defenses. Here, we argue that this view neglects one important aspect of the interaction: the role played by evolving pathogens. We suggest that taking into account the co-evolutionary interactions between the host immune system and the parasitic strategies to overcome the immune response might provide a better picture of the selective pressures that shape the evolution of immune functioning. Integrating parasitic strategies of host exploitation can also contribute to understand the seemingly contradictory results that infection can enhance, but also protect from, autoimmune diseases. In the last decades, the incidence of autoimmune disorders has dramatically increased in wealthy countries of the northern hemisphere with a concomitant decrease of most parasitic infections. Experimental work on model organisms has shown that this pattern may be due to the protective role of certain parasites (i.e., helminths that rely on the immunosuppression of hosts for their persistence. Interestingly, although parasite-induced immunosuppression can protect against autoimmunity, it can obviously favor the spread of other infections. Therefore, we need to think about the evolution of the immune system using a multidimensional trade-off involving immunoprotection, immunopathology and the parasitic strategies to escape the immune response.

  19. Self-regulating chemo-mechano-chemical systems

    Science.gov (United States)

    Aizenberg, Joanna; He, Ximin; Aizenberg, Michael

    2017-05-16

    A chemo-mechano-chemical (C.sub.1-M-C.sub.2) system includes a base supporting an actuatable structure, said structure comprising a functionalized portion and being embedded in an environmentally responsive gel capable of volume change in response to an environmental stimulus; a first fluid layer disposed over the base and in contact with the actuatable structure, said first fluid layer comprising the environmentally responsive gel; and a second fluid layer in contact with the actuatable structure, wherein the layers are positioned such that the functionalized portion is in contact with the second layer in a first relaxed state and in contact with the first layer in a second actuated state and wherein the functionalized portion interacts with at least one of the layers to provide a chemical or physical response.

  20. Regulation of the renin-angiotensin-aldosterone system in fibromyalgia.

    Science.gov (United States)

    Maliszewski, Anne M; Goldenberg, Don L; Hurwitz, Shelley; Adler, Gail K

    2002-07-01

    To assess the function of the renin-angiotensin-aldosterone (RAA) system in women with fibromyalgia (FM) compared to healthy women. Women with FM [n = 14, age 41.0+/-7.2 yrs, body mass index (BMI) 26.4+/-5.4 kg/m2] and healthy women (n = 13, age 40.0+/-7.7 yrs, BMI 25.0+/-5.0 kg/m2) were placed on a low sodium diet (10 mEq sodium/day) for 5 days. After being supine and fasting overnight, subjects received an intravenous infusion of angiotensin II at successive doses of 1, 3, and 10 ng/kg/min for 45 min per dose. Blood pressure (BP), plasma renin activity (PRA), aldosterone, and cortisol were measured at baseline and after each dose of angiotensin II. Prior to sodium restriction, women with FM completed the Hopkins Symptom Checklist-90, which included a question grading the extent of dizziness/faintness on a scale of 0 (none) to 4 (extremely). After dietary sodium restriction, baseline PRA, aldosterone, and supine BP were similar in healthy women and women with FM. Aldosterone and BP rose in response to infused angiotensin II; these responses did not differ significantly between healthy women and women with FM. In women with FM, symptoms of dizziness correlated inversely with BMI (r = -0.81, p < 0.001) and the systolic BP response to 10 ng/kg/min angiotensin II (r = -0.81, p < 0.001). The functioning of the RAA system, including the vascular response to angiotensin II, was intact in women with FM compared to healthy women. However, women with FM who complained of dizziness had a blunted vascular response to angiotensin II. This blunted vascular response may indicate intravascular volume depletion in women with symptoms of dizziness.

  1. The effect of some growth regulators on enzyme systems in irradiated barley grain using disinfestation doses

    International Nuclear Information System (INIS)

    Bachman, S.

    1973-01-01

    Disinfestation doses of 20 to 100 krad may cause changes in the biological systems of barley grain and, therefore, may influence undesirably the technological quality of malted grain. The effect of some growth regulators on irradiated grain has been investigated. The experiments have been carried out on brewery barley var. Visa Breuns. Following growth-regulators were used: gibberellic acid (Polish preparation ''Gibrescol''), kinetin (6-furfurylo-aminopurin), CCC (2-chloroethyl trimethyl ammonium chloride), and betaine hydrochloride. By treating the irradiated barley with solutions of growth regulators it was possible to diminish the loss of enzyme activity. A ''regenerating'' effect of growth substances, mainly gibberellic acid and betain hydrochloride in 10 -4 M solutions, was observed. Amylolytic activity decreased immediately after irradiation but in samples treated with growth regulators it was higher than in those without regulators. The results may have a practical importance since gibberellic acid has just been introduced into the brewery industry. (F.J.)

  2. Probiotics and the Gut Immune System: Indirect Regulation.

    Science.gov (United States)

    La Fata, Giorgio; Weber, Peter; Mohajeri, M Hasan

    2018-03-01

    The gastrointestinal tract (GIT) represents the largest interface between the human organism and the external environment. In the lumen and upper part of the mucus layer, this organ hosts an enormous number of microorganisms whose composition affects the functions of the epithelial barrier and the gut immune system. Consequentially, the microorganisms in the GIT influence the health status of the organism. Probiotics are living microorganisms which, in specific conditions, confer a health benefit to the host. Among others, probiotics have immunomodulatory properties that usually act directly by (a) increasing the activity of macrophages or natural killer cells, (b) modulating the secretion of immunoglobulins or cytokines, or indirectly by (c) enhancing the gut epithelial barrier, (d) altering the mucus secretion, and (e) competitive exclusion of other (pathogenic) bacteria. This review focuses on specific bacteria strains with indirect immunomodulatory properties. Particularly, we describe here the mechanisms through which specific probiotics enhance the gut epithelial barrier and modulate mucus production. Moreover, we describe the antimicrobial properties of specific bacteria strains. Recent data suggest that multiple pathologies are associated with an unbalanced gut microflora (dysbiosis). Although the cause-effect relationship between pathology and gut microflora is not yet well established, consumption of specific probiotics may represent a powerful tool to re-establish gut homeostasis and promote gut health.

  3. Coordinated Regulation of Virulence during Systemic Infection of Salmonella enterica serovar Typhimurium

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Hyunjin; McDermott, Jason E.; Porwollik, Steffen; Mcclelland, Michael; Heffron, Fred

    2009-02-20

    Salmonella must respond to a myriad of environmental cues during infection of a mouse and express specific subsets of genes in a temporal and spatial manner to subvert the host defense mechanisms but these regulatory pathways are poorly established. To unravel how micro-environmental signals are processed and integrated into coordinated action, we constructed in-frame non-polar deletions of 84 regulators inferred to play a role in Salmonella typhimurium virulence and tested them in three virulence assays (intraperitoneal (i.p.), and intragastric (i.g.) infection in BALB/c mice, and persistence in SvJ129 mice). Overall 36 regulators were identified that were less virulent in at least one assay, and of those, 15 regulators were required for systemic mouse infection in an acute infection model. As a first step towards understanding the interplay between a pathogen and its host from a systems biology standpoint we focused on these 15 genes. Transcriptional profiles were obtained for each of these 15 regulators from strains grown under four different environmental conditions. These results as well as publicly available transcriptional profiles were analyzed using both network inference and cluster analysis algorithms. The analysis predicts a regulatory network in which all 15 regulators control a specific set of genes necessary for Salmonella to cause systemic infection. We tested the regulatory model by expressing a subset of the regulators in trans and monitoring transcription of 7 known virulence factors located within Salmonella pathogenicity island 2 (SPI-2). These experiments validated the regulatory model and showed that, for these 7 genes, the response regulator SsrB and the marR type regulator SlyA co-regulate in a regulatory cascade by integrating multiple signals.

  4. Regulation and drive system for high rep-rate magnetic-pulse compressors

    International Nuclear Information System (INIS)

    Birx, D.L.; Cook, E.G.; Hawkins, S.; Meyers, A.; Reginato, L.L.; Schmidt, J.A.; Smith, M.W.

    1982-01-01

    The essentially unlimited rep-rate capability of non-linear magnetic systems has imposed strict requirements on the drive system which initiates the pulse compression. An order of magnitude increase in the rep-rates achieved by the Advanced Test Accelerator (ATA) gas blown system is not difficult to achieve in the magnetic compressor. The added requirement of having a high degree of regulation at the higher rep-rates places strict requirements on the triggerable switch for charging and de-Queing. A novel feedback technique which applies the proper bias to a magnetic core by comparing a reference voltage to the charging voltage eases considerably the regulation required to achieve low jitter in magnetic compression. The performance of the high rep-rate charging and regulation systems will be described in the following pages

  5. General organisational principles of the transcriptional regulation system: a tree or a circle?

    Science.gov (United States)

    Muskhelishvili, Georgi; Sobetzko, Patrick; Geertz, Marcel; Berger, Michael

    2010-04-01

    Recent advances of systemic approaches to gene expression and cellular metabolism provide unforeseen opportunities for relating and integrating extensive datasets describing the transcriptional regulation system as a whole. However, due to the multifaceted nature of the phenomenon, these datasets often contain logically distinct types of information determined by underlying approach and adopted methodology of data analysis. Consequently, to integrate the datasets comprising information on the states of chromatin structure, transcriptional regulatory network and cellular metabolism, a novel methodology enabling interconversion of logically distinct types of information is required. Here we provide a holistic conceptual framework for analysis of global transcriptional regulation as a system coordinated by structural coupling between the transcription machinery and DNA topology, acting as interdependent sensors and determinants of metabolic functions. In this operationally closed system any transition in physiological state represents an emergent property determined by shifts in structural coupling, whereas genetic regulation acts as a genuine device converting one logical type of information into the other.

  6. Almost output regulation of LFT systems via gain-scheduling control

    Science.gov (United States)

    Yuan, Chengzhi; Duan, Chang; Wu, Fen

    2018-05-01

    Output regulation of general uncertain systems is a meaningful yet challenging problem. In spite of the rich literature in the field, the problem has not yet been addressed adequately due to the lack of an effective design mechanism. In this paper, we propose a new design framework for almost output regulation of uncertain systems described in the general form of linear fractional transformation (LFT) with time-varying parametric uncertainties and unknown external perturbations. A novel semi-LFT gain-scheduling output regulator structure is proposed, such that the associated control synthesis conditions guaranteeing both output regulation and ? disturbance attenuation performance are formulated as a set of linear matrix inequalities (LMIs) plus parameter-dependent linear matrix equations, which can be solved separately. A numerical example has been used to demonstrate the effectiveness of the proposed approach.

  7. Calculational-theoretical studies of the system of local automated regulators and lateral ionization chambers

    International Nuclear Information System (INIS)

    Aleksakov, A.N.; Emel'yanov, I.Ya.; Nikolaev, E.V.; Panin, V.M.; Podlazov, L.N.; Rogova, V.D.

    1987-01-01

    Methods of engineering synthesis of the systems for nuclear reactor local automated power regulation and radial-azimuthal energy distribution stabilization operating according to lateral ionization chamber signals are described. Results of calculational-theoretical investigations into the system efficiency and peculiarities of its reaction to some perturbations typical of the RBMK type reactors are considered

  8. Systemic risk in the energy sector: is there need for financial regulation?

    NARCIS (Netherlands)

    Kerste, M.; Gerritsen, M.; Weda, J.; Tieben, B.

    2015-01-01

    The credit crisis points at serious systemic risks in Over The Counter derivative trading. This has resulted in new financial regulation, covering both the financial sector and non-financial sectors. The actual extent to which non-financial companies trading on OTC markets contribute to systemic

  9. A Story of Three Bank-Regulatory Legal Systems: Contract, Financial Management Regulation and Fiduciary Law

    Directory of Open Access Journals (Sweden)

    Tamar Frankel

    2016-08-01

    Full Text Available How should banks be regulated to avoid their failure? Banks must control the risks they take with depositors' money. If depositors lose their trust in their banks, and demand their money, the banks will fail. This article describes three legal bank regulatory systems: Contract with depositors (U.S.; a mix of contract and trust law, but going towards trust (Japan and a full trust-fiduciary law regulating banks (Israel. The article concludes that bank regulation, which limits the banks' risks and conflicts of interest, helps create trustworthy banks that serve their country best.

  10. Right, laws, regulations and technical building systems; Recht, Gesetze, Verordnungen und Technische Gebaeudesysteme

    Energy Technology Data Exchange (ETDEWEB)

    Kranz, H.R. [Siemens AG, Karlsruhe (Germany)

    1995-12-31

    Chapter 23 of the anthology about building control gives an overview of the laws and regulations in the field of technical building systems. The following fields are discussed: license regulations in the field of building trade, communication law, environmental responsibility law, building right, European directives, laws and regulations of the Federal Government and the Laender. (BWI) [Deutsch] Kapitel 23 des Sammelbandes ueber Building Control gibt einen Ueberblick ueber Recht, Gesetze und Verordnungen im Bereich der Technischen Gebaeudesysteme. In diesem Zusammenhang kommen folgende Bereiche in Frage: Lizenzrecht im Bauwesen; Fernmelderecht; Umwelthaftungsgesetz; Baurecht; Europaeische Richtlinien; Gesetze und Verordnungen des Bundes und der Laender. (BWI)

  11. A three-dimensional operational transient simulation of the CANDU core with typical reactor regulating system

    Energy Technology Data Exchange (ETDEWEB)

    Yeom, Choong Sub; Kim, Hyun Dae; Park, Kyung Seok; Park, Jong Woon [Institute for Advanced Engineering, Taejon (Korea, Republic of)

    1995-07-01

    This paper describes the results of simulation of a CANDU operational transient problem (re-startup after short shutdown) using the Coupled Reactor Kinetics(CRKIN) code developed previously with CANDU Reactor Regulating System (RRS) logic. The performance in the simulation is focused on investigating the behaviours of neutron power and regulating devices in accordance with the changes of xenon concentration following the operation of the RRS.

  12. Low-frequency dynamics of autonomic regulation of circulatory system in healthy subjects

    Science.gov (United States)

    Skazkina, V. V.; Borovkova, E. I.; Galushko, T. A.; Khorev, V. S.; Kiselev, A. R.

    2018-04-01

    The paper is devoted to the analysis of dynamic of interactions between signals of autonomic circulatory regulation. We investigated two-hour experimental records of 30 healthy people. Phase synchronization was studied using the signals of the electrocardiogram and the photoplethysmogram of vessels. We found the presence of long synchronous intervals in some subjects. For analysis of the dynamic we calculated autocorrelation functions. The analysis made it possible to reveal indirect signs of the influence of the humoral regulation system.

  13. Structural elements regulating amyloidogenesis: a cholinesterase model system.

    Directory of Open Access Journals (Sweden)

    Létitia Jean

    2008-03-01

    Full Text Available Polymerization into amyloid fibrils is a crucial step in the pathogenesis of neurodegenerative syndromes. Amyloid assembly is governed by properties of the sequence backbone and specific side-chain interactions, since fibrils from unrelated sequences possess similar structures and morphologies. Therefore, characterization of the structural determinants driving amyloid aggregation is of fundamental importance. We investigated the forces involved in the amyloid assembly of a model peptide derived from the oligomerization domain of acetylcholinesterase (AChE, AChE(586-599, through the effect of single point mutations on beta-sheet propensity, conformation, fibrilization, surfactant activity, oligomerization and fibril morphology. AChE(586-599 was chosen due to its fibrilization tractability and AChE involvement in Alzheimer's disease. The results revealed how specific regions and residues can control AChE(586-599 assembly. Hydrophobic and/or aromatic residues were crucial for maintaining a high beta-strand propensity, for the conformational transition to beta-sheet, and for the first stage of aggregation. We also demonstrated that positively charged side-chains might be involved in electrostatic interactions, which could control the transition to beta-sheet, the oligomerization and assembly stability. Further interactions were also found to participate in the assembly. We showed that some residues were important for AChE(586-599 surfactant activity and that amyloid assembly might preferentially occur at an air-water interface. Consistently with the experimental observations and assembly models for other amyloid systems, we propose a model for AChE(586-599 assembly in which a steric-zipper formed through specific interactions (hydrophobic, electrostatic, cation-pi, SH-aromatic, metal chelation and polar-polar would maintain the beta-sheets together. We also propose that the stacking between the strands in the beta-sheets along the fiber axis could

  14. Modeling and Performance Improvement of the Constant Power Regulator Systems in Variable Displacement Axial Piston Pump

    Science.gov (United States)

    Park, Sung Hwan; Lee, Ji Min; Kim, Jong Shik

    2013-01-01

    An irregular performance of a mechanical-type constant power regulator is considered. In order to find the cause of an irregular discharge flow at the cut-off pressure area, modeling and numerical simulations are performed to observe dynamic behavior of internal parts of the constant power regulator system for a swashplate-type axial piston pump. The commercial numerical simulation software AMESim is applied to model the mechanical-type regulator with hydraulic pump and simulate the performance of it. The validity of the simulation model of the constant power regulator system is verified by comparing simulation results with experiments. In order to find the cause of the irregular performance of the mechanical-type constant power regulator system, the behavior of main components such as the spool, sleeve, and counterbalance piston is investigated using computer simulation. The shape modification of the counterbalance piston is proposed to improve the undesirable performance of the mechanical-type constant power regulator. The performance improvement is verified by computer simulation using AMESim software. PMID:24282389

  15. Modeling and Performance Improvement of the Constant Power Regulator Systems in Variable Displacement Axial Piston Pump

    Directory of Open Access Journals (Sweden)

    Sung Hwan Park

    2013-01-01

    Full Text Available An irregular performance of a mechanical-type constant power regulator is considered. In order to find the cause of an irregular discharge flow at the cut-off pressure area, modeling and numerical simulations are performed to observe dynamic behavior of internal parts of the constant power regulator system for a swashplate-type axial piston pump. The commercial numerical simulation software AMESim is applied to model the mechanical-type regulator with hydraulic pump and simulate the performance of it. The validity of the simulation model of the constant power regulator system is verified by comparing simulation results with experiments. In order to find the cause of the irregular performance of the mechanical-type constant power regulator system, the behavior of main components such as the spool, sleeve, and counterbalance piston is investigated using computer simulation. The shape modification of the counterbalance piston is proposed to improve the undesirable performance of the mechanical-type constant power regulator. The performance improvement is verified by computer simulation using AMESim software.

  16. Modeling and performance improvement of the constant power regulator systems in variable displacement axial piston pump.

    Science.gov (United States)

    Park, Sung Hwan; Lee, Ji Min; Kim, Jong Shik

    2013-01-01

    An irregular performance of a mechanical-type constant power regulator is considered. In order to find the cause of an irregular discharge flow at the cut-off pressure area, modeling and numerical simulations are performed to observe dynamic behavior of internal parts of the constant power regulator system for a swashplate-type axial piston pump. The commercial numerical simulation software AMESim is applied to model the mechanical-type regulator with hydraulic pump and simulate the performance of it. The validity of the simulation model of the constant power regulator system is verified by comparing simulation results with experiments. In order to find the cause of the irregular performance of the mechanical-type constant power regulator system, the behavior of main components such as the spool, sleeve, and counterbalance piston is investigated using computer simulation. The shape modification of the counterbalance piston is proposed to improve the undesirable performance of the mechanical-type constant power regulator. The performance improvement is verified by computer simulation using AMESim software.

  17. A voltage regulator system with dynamic bandwidth boosting for passive UHF RFID transponders

    International Nuclear Information System (INIS)

    Shen Jinpeng; Wang Xin'an; Liu Shan; Li Shoucheng; Ruan Zhengkun

    2013-01-01

    This paper presents a voltage regulator system for passive UHF RFID transponders, which contains a rectifier, a limiter, and a regulator. The rectifier achieves power by rectifying the incoming RF energy. Due to the huge variation of the rectified voltage, a limiter at the rectifier output is used to clamp the rectified voltage. In this paper, the design of a limiter circuit is discussed in detail, which can provide a stable limiting voltage with low sensitivity to temperature variation and process dispersion. The key aspect of the voltage regulator system is the dynamic bandwidth boosting in the regulator. By sensing the excess current that is bypassed in the limiter during periods of excess energy, the bias current as well as the bandwidth of the regulator are increased, the output supply voltage can recover quickly from line transients during the periods of no RF energy to a full blast of RF energy. This voltage regulator system is implemented in a 0.18 μm CMOS process. (semiconductor integrated circuits)

  18. Activity-dependent self-regulation of viscous length scales in biological systems

    Science.gov (United States)

    Nandi, Saroj Kumar

    2018-05-01

    The cellular cortex, which is a highly viscous thin cytoplasmic layer just below the cell membrane, controls the cell's mechanical properties, which can be characterized by a hydrodynamic length scale ℓ . Cells actively regulate ℓ via the activity of force-generating molecules, such as myosin II. Here we develop a general theory for such systems through a coarse-grained hydrodynamic approach including activity in the static description of the system providing an experimentally accessible parameter and elucidate the detailed mechanism of how a living system can actively self-regulate its hydrodynamic length scale, controlling the rigidity of the system. Remarkably, we find that ℓ , as a function of activity, behaves universally and roughly inversely proportional to the activity of the system. Our theory rationalizes a number of experimental findings on diverse systems, and comparison of our theory with existing experimental data shows good agreement.

  19. "SAFE" LEVEL OF SOMATIC HEALTH IN INDICATORS REGULATION OF CARDIORESPIRATORY SYSTEM AT YOUNG MEN

    Directory of Open Access Journals (Sweden)

    Alexander P Romanchuk

    2015-12-01

    2Lviv State University Physical Culture The aim of this study was to determine the functional state cardiorespiratory system in males younger with "safe" level of somatic health (LSH. Were examined 104 males aged 20,6 ± 0,9 years, engaged in various sports, and had no existing acute and chronic diseases. The survey was conducted using spiroarteriocardiorhythmography (SACR. It is shown that in all studied systems of regulation, regulation except SBP probably marked differences between persons with "safe" and "low" LSH. At the same time, the comparison of "safe" and "medium" LSH differences relate only to the predominance of sympathetic influences on heart rate, decrease suprasegmental effects on DBP, reducing regulatory influences on spontaneous breath and their high-frequency components, reducing of baroreflex sensitivity and cardiac output. Key words: "safe" level of somatic health, regulation of the cardiorespiratory system.

  20. Asymptotic tracking and disturbance rejection of the blood glucose regulation system.

    Science.gov (United States)

    Ashley, Brandon; Liu, Weijiu

    2017-07-01

    Type 1 diabetes patients need external insulin to maintain blood glucose within a narrow range from 65 to 108 mg/dl (3.6 to 6.0 mmol/l). A mathematical model for the blood glucose regulation is required for integrating a glucose monitoring system into insulin pump technology to form a closed-loop insulin delivery system on the feedback of the blood glucose, the so-called "artificial pancreas". The objective of this paper is to treat the exogenous glucose from food as a glucose disturbance and then develop a closed-loop feedback and feedforward control system for the blood glucose regulation system subject to the exogenous glucose disturbance. For this, a mathematical model for the glucose disturbance is proposed on the basis of experimental data, and then incorporated into an existing blood glucose regulation model. Because all the eigenvalues of the disturbance model have zero real parts, the center manifold theory is used to establish blood glucose regulator equations. We then use their solutions to synthesize a required feedback and feedforward controller to reject the disturbance and asymptotically track a constant glucose reference of 90  mg/dl. Since the regulator equations are nonlinear partial differential equations and usually impossible to solve analytically, a linear approximation solution is obtained. Our numerical simulations show that, under the linear approximate feedback and feedforward controller, the blood glucose asymptotically tracks its desired level of 90 mg/dl approximately. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Personalised Learning Object System Based on Self-Regulated Learning Theories

    Directory of Open Access Journals (Sweden)

    Ali Alharbi

    2014-06-01

    Full Text Available Self-regulated learning has become an important construct in education research in the last few years. Selfregulated learning in its simple form is the learner’s ability to monitor and control the learning process. There is increasing research in the literature on how to support students become more self-regulated learners. However, the advancement in the information technology has led to paradigm changes in the design and development of educational content. The concept of learning object instructional technology has emerged as a result of this shift in educational technology paradigms. This paper presents the results of a study that investigated the potential educational effectiveness of a pedagogical framework based on the self-regulated learning theories to support the design of learning object systems to help computer science students. A prototype learning object system was developed based on the contemporary research on self-regulated learning. The system was educationally evaluated in a quasi-experimental study over two semesters in a core programming languages concepts course. The evaluation revealed that a learning object system that takes into consideration contemporary research on self-regulated learning can be an effective learning environment to support computer science education.

  2. Dual PD Control Regulation with Nonlinear Compensation for a Ball and Plate System

    Directory of Open Access Journals (Sweden)

    Sergio Galvan-Colmenares

    2014-01-01

    Full Text Available The normal proportional derivative (PD control is modified to a new dual form for the regulation of a ball and plate system. First, to analyze this controller, a novel complete nonlinear model of the ball and plate system is obtained. Second, an asymptotic stable dual PD control with a nonlinear compensation is developed. Finally, the experimental results of ball and plate system are provided to verify the effectiveness of the proposed methodology.

  3. Nutritional components regulate the gut immune system and its association with intestinal immune disease development.

    Science.gov (United States)

    Lamichhane, Aayam; Kiyono, Hiroshi; Kunisawa, Jun

    2013-12-01

    The gut is equipped with a unique immune system for maintaining immunological homeostasis, and its functional immune disruption can result in the development of immune diseases such as food allergy and intestinal inflammation. Accumulating evidence has demonstrated that nutritional components play an important role in the regulation of gut immune responses and also in the development of intestinal immune diseases. In this review, we focus on the immunological functions of lipids, vitamins, and nucleotides in the regulation of the intestinal immune system and as potential targets for the control of intestinal immune diseases. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  4. A scheme for regulating toxic substances to water quality of Chamsil upstream water system

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kang Suk; Kim, Jee Hoon [Korea Environment Institute, Seoul (Korea)

    1998-12-01

    This study asserts to reflect a concept of toxicity thoroughly in the present water quality concept. It presents an appropriate solution to control toxic substances flowing into the Chamsil upstream water system. Although a regulation of toxic substances into major rivers in Korea other than Han river is also required urgently, it will be studied in future. It is expected that this study on Chamsil upstream would be a cornerstone for establishing a national regulation policy of toxic substances into water system. 28 refs., 1 fig., 36 tabs.

  5. Post-Transcriptional Regulation by the Csr Global Regulatory System in Escherichia coli

    OpenAIRE

    Suzuki, Kazushi; 鈴木, 一史

    2007-01-01

    In many species of bacteria, the Csr (carbon storage regulator) global regulatory system coordinates the expression of various genes. In Escherichia coli, the central component of this system, CsrA, is a RNA-binding protein. The CsrA is a homodimer and binds to leader segments of target mRNAs, affecting their translation and stability. CsrA activity is regulated by two small non-coding RNAs, CsrB and CsrC. These RNAs contain multiple CsrA-binding sequences and act by sequestering CsrA. In thi...

  6. The organisation of work and systems of labour market regulation and social protection

    DEFF Research Database (Denmark)

    Lorenz, Edward; Lundvall, Bengt-Åke

    2011-01-01

    The paper demonstrates on the basis of date from 15 European countries that there is a close link between the form of labour market regulation and the systems of social protection on the one hand and modes of work organisation and learning on the other hand.......The paper demonstrates on the basis of date from 15 European countries that there is a close link between the form of labour market regulation and the systems of social protection on the one hand and modes of work organisation and learning on the other hand....

  7. Characterizing complexity in socio-technical systems: a case study of a SAMU Medical Regulation Center.

    Science.gov (United States)

    Righi, Angela Weber; Wachs, Priscila; Saurin, Tarcísio Abreu

    2012-01-01

    Complexity theory has been adopted by a number of studies as a benchmark to investigate the performance of socio-technical systems, especially those that are characterized by relevant cognitive work. However, there is little guidance on how to assess, systematically, the extent to which a system is complex. The main objective of this study is to carry out a systematic analysis of a SAMU (Mobile Emergency Medical Service) Medical Regulation Center in Brazil, based on the core characteristics of complex systems presented by previous studies. The assessment was based on direct observations and nine interviews: three of them with regulator of emergencies medical doctor, three with radio operators and three with telephone attendants. The results indicated that, to a great extent, the core characteristics of complexity are magnified) due to basic shortcomings in the design of the work system. Thus, some recommendations are put forward with a view to reducing unnecessary complexity that hinders the performance of the socio-technical system.

  8. Experience in adjusting of the level regulation system of steam generators of the Rovno NPP

    International Nuclear Information System (INIS)

    Patselyuk, S.N.; Sokolov, A.G.; Kazakov, V.I.; Dorosh, Yu.A.

    1984-01-01

    A system of feed water level control in steam generators at the Rovno NPP with WWER-440 reactors which comprises start-up as well as main regulators is described. The start-up regulator (single-pulsed with a signal by the level) keeps the level in the steam generator at loadings up to 30% of the nominal reactor power Nsub(nom.) The main regulator is connected in the three-pulsed circuit and it receives signals by steam and water flow rate and by the level in the steam generator. The main regulator has been started only at loadings above 40% Nsub(nom.). After reconstruction it was used in the 15-100% Nsub(nom.) range. Characteristics of the level control system in the steam generator at perturbations intoduced by the main circulating pump (MCP) and turbine disconnection as well as change in feed water flow rate have been studied. The studies have revealed that the system ensures necessary quality of control in stationary modes. The system operates stably at perturbations of feed water flow rate up to 50% Nsub(nom.). Perturbations by MCP connections and disconnections is most difficult for control system

  9. A REVIEW OF FINANCIAL REGULATIONS TO AVOID THE NATIONALISATION OF LOSSES IN THE BANKING SYSTEM

    Directory of Open Access Journals (Sweden)

    SORANA VĂTAVU

    2011-01-01

    Full Text Available This article investigates the regulations which should be applied in the financial system in order to minimize the losses. The subject is based on the banking policy of “privatisation of profits and nationalisation of losses” and it is debated mainly from trade articles point of view. Even when taxpayers do not agree, governments choose either to bailout influential banks or to cover their losses with a deposit insurance. Banks would take advantage of any opportunity to increase earnings, even in the insolvency stage, and thus certain regulations and limitations must be provided to minimize the moral hazard occurred. The most important problem that deepens financial regressions relates to the losses spillover effect on the worldwide economy, and although a perfect global banking model cannot be implemented, the paper suggests regulations which improve the financial systems.

  10. From early family systems to internalizing symptoms: The role of emotion regulation and peer relations.

    Science.gov (United States)

    Lindblom, Jallu; Vänskä, Mervi; Flykt, Marjo; Tolvanen, Asko; Tiitinen, Aila; Tulppala, Maija; Punamäki, Raija-Leena

    2017-04-01

    Research has demonstrated the importance of early family characteristics, such as the quality of caregiving, on children's later mental health. Information is, however, needed about the role of more holistic family systems and specific child-related socioemotional mechanisms. In this study, we conceptualize families as dynamic family system types, consisting of both marital and parenting trajectories over the transition to parenthood. First, we examine how early family system types predict children's anxiety, depression, peer exclusion, and emotion regulation. Second, we test whether couples' infertility history and other family related contextual factors moderate the effects of family system types on child outcomes. Third, we test whether children's emotion regulation and peer exclusion mediate the effects of family system types on anxiety and depression. The participants were 452 families representing cohesive, distant, authoritative, enmeshed, and discrepant family types, identified on the basis of relationship autonomy and intimacy from pregnancy to the child's age of 2 and 12 months. Children's anxiety, depression, emotion regulation, and peer exclusion were assessed at the age of 7-8 years. Structural equation modeling showed that distant, enmeshed, and discrepant families similarly predicted children's heightened anxiety and depression. Infertility history, parental education, and parity moderated the associations between certain family system types and child outcomes. Finally, emotion regulation, but not peer exclusion, was a common mediating mechanism between distant and enmeshed families and children's depression. The results emphasize the importance of early family environments on children's emotion regulation development and internalizing psychopathology. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  11. The advancement of regulation fee, budget system, and set-up time management

    Energy Technology Data Exchange (ETDEWEB)

    Jung, J. S.; Choi, E. S.; Cho, J. I.; Jung, S. C.; Lee, J. H. [Caleb and Company, Seoul (Korea, Republic of)

    2001-07-15

    Analyze the government's charging fee amendment and suggest the national regulation fee system. Suggest the future business portfolio based in the current business analysis. Design the advanced budget code structure, the performance management of the project budget and the survice level agreement between divisions. Develop the time management and the methodology of the standard man-hour calculation.

  12. Energy Management Systems and tertiary regulation in hierarchical control architectures for islanded micro-grids

    DEFF Research Database (Denmark)

    Sanseverino, Eleonora Riva; Di Silvestre, Maria Luisa; Quang, Ninh Nguyen

    2015-01-01

    In this paper, the structure of the highest level of a hierarchical control architecture for micro-grids is proposed. Such structure includes two sub-levels: the Energy Management System, EMS, and the tertiary regulation. The first devoted to energy resources allocation in each time slot based...

  13. Customizable Computer-Based Interaction Analysis for Coaching and Self-Regulation in Synchronous CSCL Systems

    Science.gov (United States)

    Lonchamp, Jacques

    2010-01-01

    Computer-based interaction analysis (IA) is an automatic process that aims at understanding a computer-mediated activity. In a CSCL system, computer-based IA can provide information directly to learners for self-assessment and regulation and to tutors for coaching support. This article proposes a customizable computer-based IA approach for a…

  14. 75 FR 391 - Medical Device Quality System Regulation Educational Forum on Risk Management Through the Product...

    Science.gov (United States)

    2010-01-05

    ...] Medical Device Quality System Regulation Educational Forum on Risk Management Through the Product Life... on Risk Management through the Product Life Cycle.'' This public workshop is intended to provide... discussed at the workshop: (1) Standards and guidance, (2) risk management in design, (3) risk management in...

  15. How Do Students Regulate their Learning of Complex Systems with Hypermedia?.

    Science.gov (United States)

    Azevedo, Roger; Seibert, Diane; Guthrie, John T.; Cromley, Jennifer G.; Wang, Huei-yu; Tron, Myriam

    This study examined the role of different goal-setting instructional interventions in facilitating students' shift to more sophisticated mental models of the circulatory system as indicated by both performance and process data. Researchers adopted the information processing model of self-regulated learning of P. Winne and colleagues (1998, 2001)…

  16. Capturing the Family Context of Emotion Regulation: A Family Systems Model Comparison Approach

    Science.gov (United States)

    Fosco, Gregory M.; Grych, John H.

    2013-01-01

    Several dimensions of family functioning are recognized as formative influences on children's emotion regulation. Historically, they have been studied separately, limiting our ability to understand how they function within the family system. The present investigation tested models including family emotional climate, interparental conflict, and…

  17. Systems analysis of multiple regulator perturbations allows discovery of virulence factors in Salmonella

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Hyunjin; Ansong, Charles; McDermott, Jason E.; Gritsenko, Marina A.; Smith, Richard D.; Heffron, Fred; Adkins, Joshua N.

    2011-06-28

    Background: Systemic bacterial infections are highly regulated and complex processes that are orchestrated by numerous virulence factors. Genes that are coordinately controlled by the set of regulators required for systemic infection are potentially required for pathogenicity. Results: In this study we present a systems biology approach in which sample-matched multi-omic measurements of fourteen virulence-essential regulator mutants were coupled with computational network analysis to efficiently identify Salmonella virulence factors. Immunoblot experiments verified network-predicted virulence factors and a subset was determined to be secreted into the host cytoplasm, suggesting that they are virulence factors directly interacting with host cellular components. Two of these, SrfN and PagK2, were required for full mouse virulence and were shown to be translocated independent of either of the type III secretion systems in Salmonella or the type III injectisome-related flagellar mechanism. Conclusions: Integrating multi-omic datasets from Salmonella mutants lacking virulence regulators not only identified novel virulence factors but also defined a new class of translocated effectors involved in pathogenesis. The success of this strategy at discovery of known and novel virulence factors suggests that the approach may have applicability for other bacterial pathogens.

  18. Control mechanisms for battery energy storage system performing primary frequency regulation and self-consumption optimization

    NARCIS (Netherlands)

    Pliatskas Stylianidis, A.

    2016-01-01

    This report contains the design of a model for the integration of a battery energy system in a household level and its use for primary frequency regulation and self-consumption optimization. The main goal of this project was to investigate what are the possible applications and the most suitable for

  19. Self-regulating insulin delivery systems I. Synthesis and characterization of glycosylated insulin

    NARCIS (Netherlands)

    Jeong, Seo Young; Kim, Sung Wan; Eenink, Martinus J.D.; Feijen, Jan

    1984-01-01

    A design for a self-regulating insulin delivery system based on the competitive binding of glucose and glycosylated insulin to the lectin Concanavalin A is proposed. A differnt approach to diabetes therapy is the attempt to effect a permanent cure of the disease by supplementing the patient's

  20. Electric Vehicle Based Battery Storages for Future Power System Regulation Services

    DEFF Research Database (Denmark)

    Pillai, Jayakrishnan Radhakrishna; Bak-Jensen, Birgitte

    2009-01-01

    supplying the reserve power requirements. This limited regulation services from conventional generators in the future power system calls for other new reserve power solutions like Electric Vehicle (EV) based battery storages. A generic aggregated EV based battery storage for long-term dynamic load frequency...

  1. Road Transport Management System (RTMS): a self regulation initiative in heavy vehicle transport in South Africa

    CSIR Research Space (South Africa)

    Nordengen, Paul A

    2007-07-01

    Full Text Available This paper describes the most recent developments of an initiative to introduce meaningful self-regulation in the heavy vehicle transport industry through a Road Transport Management System (RTMS) with the aim of contributing to the road authorities...

  2. Regulation of the galanin system in the brainstem and hypothalamus by electroconvulsive stimulation in mice

    DEFF Research Database (Denmark)

    Christiansen, S H

    2011-01-01

    Induction of seizures by electroconvulsive stimulation (ECS) is amongst the most efficacious treatments for major depression. However, the working mechanism by which ECS exerts its antidepressant effects remains elusive. The galanin system is regulated by ECS in seizure-prone brain regions and ha...... in brain regions involved in monoaminergic neurotransmission and stress modulation thus indicating a possible role of the galanin system in the therapeutic effects of ECS.......Induction of seizures by electroconvulsive stimulation (ECS) is amongst the most efficacious treatments for major depression. However, the working mechanism by which ECS exerts its antidepressant effects remains elusive. The galanin system is regulated by ECS in seizure-prone brain regions and has...... been shown to modulate depression-like behaviour. To further explore its potential role in the antidepressant effects of ECS the galanin system was investigated by in situ hybridisation and [(125)I]-galanin receptor binding during repeated ECS in the locus coeruleus, dorsal raphe and discrete nuclei...

  3. Operation of Grid -Connected Lithium-Ion Battery Energy Storage System for Primary Frequency Regulation

    DEFF Research Database (Denmark)

    Stroe, Daniel Loan; Knap, Vaclav; Swierczynski, Maciej Jozef

    2017-01-01

    Because of their characteristics, which have been continuously improved during the last years, Lithium ion batteries were proposed as an alternative viable solution to present fast-reacting conventional generating units to deliver the primary frequency regulation service. However, even though...... there are worldwide demonstration projects where energy storage systems based on Lithium-ion batteries are evaluated for such applications, the field experience is still very limited. In consequence, at present there are no very clear requirements on how the Lithium-ion battery energy storage systems should...... be operated while providing frequency regulation service and how the system has to re-establish its SOC once the frequency event has passed. Therefore, this paper aims to investigate the effect on the lifetime of the Lithium-ion batteries energy storage system of various strategies for re...

  4. Suggested Operation Grid-Connected Lithium-Ion Battery Energy Storage System for Primary Frequency Regulation

    DEFF Research Database (Denmark)

    Stroe, Daniel Ioan; Knap, Vaclav; Swierczynski, Maciej Jozef

    2015-01-01

    Because of their characteristics, which have been continuously improved during the last years, Lithium ion batteries were proposed as an alternative viable solution to present fast-reacting conventional generating units to deliver the primary frequency regulation service. However, even though...... there are worldwide demonstration projects where energy storage systems based on Lithium-ion batteries are evaluated for such applications, the field experience is still very limited. In consequence, at present there are no very clear requirements on how the Lithium-ion battery energy storage systems should...... be operated while providing frequency regulation service and how the system has to re-establish its SOC once the frequency event has passed. Therefore, this paper aims to investigate the effect on the lifetime of the Lithium-ion batteries energy storage system of various strategies for re...

  5. Updating of the program for simulation of Darlington shutdown and regulation systems

    International Nuclear Information System (INIS)

    1988-07-01

    This report describes the current status of the developments of a simulation of the Darlington Nuclear Generating Station shutdown and regulating systems, DARSIM done under contract to the Atomic Energy Control Board (AECB). The DARSIM program simulates the spatial neutron dynamics, the regulation of the reactor power, and shutdown system 1 and shutdown system 2 software. The DARSIM program operates in the interactive simulation program environment. DARSIM was installed on the APOLLO computer at the AECB and a version for an IBM-PC was also provided for the exclusive use of the AECB. Shutdown system software was updated to incorporate the latest revisions in the functional specifications. Additional developments have been provided to assist in the use and interpretation of the DARSIM results

  6. Molecular Mechanisms Underlying Renin-Angiotensin-Aldosterone System Mediated Regulation of BK Channels

    Directory of Open Access Journals (Sweden)

    Zhen-Ye Zhang

    2017-09-01

    Full Text Available Large-conductance calcium-activated potassium channels (BK channels belong to a family of Ca2+-sensitive voltage-dependent potassium channels and play a vital role in various physiological activities in the human body. The renin-angiotensin-aldosterone system is acknowledged as being vital in the body's hormone system and plays a fundamental role in the maintenance of water and electrolyte balance and blood pressure regulation. There is growing evidence that the renin-angiotensin-aldosterone system has profound influences on the expression and bioactivity of BK channels. In this review, we focus on the molecular mechanisms underlying the regulation of BK channels mediated by the renin-angiotensin-aldosterone system and its potential as a target for clinical drugs.

  7. MicroRNAs: Key Regulators in the Central Nervous System and Their Implication in Neurological Diseases

    Directory of Open Access Journals (Sweden)

    Dan-Dan Cao

    2016-05-01

    Full Text Available MicroRNAs (miRNAs are a class of small, well-conserved noncoding RNAs that regulate gene expression post-transcriptionally. They have been demonstrated to regulate a lot of biological pathways and cellular functions. Many miRNAs are dynamically regulated during central nervous system (CNS development and are spatially expressed in adult brain indicating their essential roles in neural development and function. In addition, accumulating evidence strongly suggests that dysfunction of miRNAs contributes to neurological diseases. These observations, together with their gene regulation property, implicated miRNAs to be the key regulators in the complex genetic network of the CNS. In this review, we first focus on the ways through which miRNAs exert the regulatory function and how miRNAs are regulated in the CNS. We then summarize recent findings that highlight the versatile roles of miRNAs in normal CNS physiology and their association with several types of neurological diseases. Subsequently we discuss the limitations of miRNAs research based on current studies as well as the potential therapeutic applications and challenges of miRNAs in neurological disorders. We endeavor to provide an updated description of the regulatory roles of miRNAs in normal CNS functions and pathogenesis of neurological diseases.

  8. Lvr, a Signaling System That Controls Global Gene Regulation and Virulence in Pathogenic Leptospira

    Science.gov (United States)

    Adhikarla, Haritha; Wunder, Elsio A.; Mechaly, Ariel E.; Mehta, Sameet; Wang, Zheng; Santos, Luciane; Bisht, Vimla; Diggle, Peter; Murray, Gerald; Adler, Ben; Lopez, Francesc; Townsend, Jeffrey P.; Groisman, Eduardo; Picardeau, Mathieu; Buschiazzo, Alejandro; Ko, Albert I.

    2018-01-01

    Leptospirosis is an emerging zoonotic disease with more than 1 million cases annually. Currently there is lack of evidence for signaling pathways involved during the infection process of Leptospira. In our comprehensive genomic analysis of 20 Leptospira spp. we identified seven pathogen-specific Two-Component System (TCS) proteins. Disruption of two these TCS genes in pathogenic Leptospira strain resulted in loss-of-virulence in a hamster model of leptospirosis. Corresponding genes lvrA and lvrB (leptospira virulence regulator) are juxtaposed in an operon and are predicted to encode a hybrid histidine kinase and a hybrid response regulator, respectively. Transcriptome analysis of lvr mutant strains with disruption of one (lvrB) or both genes (lvrA/B) revealed global transcriptional regulation of 850 differentially expressed genes. Phosphotransfer assays demonstrated that LvrA phosphorylates LvrB and predicted further signaling downstream to one or more DNA-binding response regulators, suggesting that it is a branched pathway. Phylogenetic analyses indicated that lvrA and lvrB evolved independently within different ecological lineages in Leptospira via gene duplication. This study uncovers a novel-signaling pathway that regulates virulence in pathogenic Leptospira (Lvr), providing a framework to understand the molecular bases of regulation in this life-threatening bacterium. PMID:29600195

  9. Regulation System for the 18 kV/90 Mvar Compensators

    CERN Document Server

    Burdet, G

    2001-01-01

    Two 18 kV/90 Mvar static compensators are involved to stabilise the voltage, filter the harmonics and compensate the reactive power generated by the power converters used to supply the SPS accelerator magnets. The in-house hardware and software used by the regulation systems, difficult to maintain and upgrade, shall be renovated. Industrial solution based on PLC will be implemented. This paper describes the future system and its integration to the Electrical Network Supervisor.

  10. Feedback loops and reciprocal regulation: recurring motifs in the systems biology of the cell cycle

    OpenAIRE

    Ferrell, James E.

    2013-01-01

    The study of eukaryotic cell cycle regulation over the last several decades has led to a remarkably detailed understanding of the complex regulatory system that drives this fundamental process. This allows us to now look for recurring motifs in the regulatory system. Among these are negative feedback loops, which underpin checkpoints and generate cell cycle oscillations; positive feedback loops, which promote oscillations and make cell cycle transitions switch-like and unidirectional; and rec...

  11. 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.

  12. Distinct brain systems mediate the effects of nociceptive input and self-regulation on pain.

    Directory of Open Access Journals (Sweden)

    Choong-Wan Woo

    2015-01-01

    Full Text Available Cognitive self-regulation can strongly modulate pain and emotion. However, it is unclear whether self-regulation primarily influences primary nociceptive and affective processes or evaluative ones. In this study, participants engaged in self-regulation to increase or decrease pain while experiencing multiple levels of painful heat during functional magnetic resonance imaging (fMRI imaging. Both heat intensity and self-regulation strongly influenced reported pain, but they did so via two distinct brain pathways. The effects of stimulus intensity were mediated by the neurologic pain signature (NPS, an a priori distributed brain network shown to predict physical pain with over 90% sensitivity and specificity across four studies. Self-regulation did not influence NPS responses; instead, its effects were mediated through functional connections between the nucleus accumbens and ventromedial prefrontal cortex. This pathway was unresponsive to noxious input, and has been broadly implicated in valuation, emotional appraisal, and functional outcomes in pain and other types of affective processes. These findings provide evidence that pain reports are associated with two dissociable functional systems: nociceptive/affective aspects mediated by the NPS, and evaluative/functional aspects mediated by a fronto-striatal system.

  13. On designing geometric motion planners to solve regulating and trajectory tracking problems for robotic locomotion systems

    International Nuclear Information System (INIS)

    Asnafi, Alireza; Mahzoon, Mojtaba

    2011-01-01

    Based on a geometric fiber bundle structure, a generalized method to solve both regulation and trajectory tracking problems for locomotion systems is presented. The method is especially applied to two case studies of robotic locomotion systems; a three link articulated fish-like robot as a prototype of locomotion systems with symmetry, and the snakeboard as a prototype of mixed locomotion systems. Our results show that although these motion planners have an open loop structure, due to their generalities, they can steer case studies with negligible errors for almost any complicated path.

  14. On designing geometric motion planners to solve regulating and trajectory tracking problems for robotic locomotion systems

    Energy Technology Data Exchange (ETDEWEB)

    Asnafi, Alireza [Hydro-Aeronautical Research Center, Shiraz University, Shiraz, 71348-13668 (Iran, Islamic Republic of); Mahzoon, Mojtaba [Department of Mechanical Engineering, School of Engineering, Shiraz University, Shiraz, 71348-13668 (Iran, Islamic Republic of)

    2011-09-15

    Based on a geometric fiber bundle structure, a generalized method to solve both regulation and trajectory tracking problems for locomotion systems is presented. The method is especially applied to two case studies of robotic locomotion systems; a three link articulated fish-like robot as a prototype of locomotion systems with symmetry, and the snakeboard as a prototype of mixed locomotion systems. Our results show that although these motion planners have an open loop structure, due to their generalities, they can steer case studies with negligible errors for almost any complicated path.

  15. An automatic regulating control system for a graphite moderated reactor using digital techniques

    International Nuclear Information System (INIS)

    Carvalho Goncalves Junior, J. de.

    1989-01-01

    The work propose an automatic regulating control system for a graphite moderated reactor using digital techniques. The system uses a microcomputer to monitor the power and the period, to run the control algorithm, and to generate electronic signals to excite the motor, which moves vertically the control rod banks. A nuclear reactor simulator was developed to test the control system. The simulator consists of a software based on the point kinetic equations and implanted in an analogical computer. The results show that this control system has a good performance and versatility. In addition, the simulator is capable of reproducing with accuracy the behavior of a nuclear reactor. (author)

  16. Energy conservation. Purposeful regulation and control systems for gas infrared radiation heating

    Energy Technology Data Exchange (ETDEWEB)

    Reitsch, L [GoGaS Goch G.m.b.H. und Co., Dortmund (Germany, F.R.)

    1978-01-01

    Gas infrared radiators have been in use for a long time for heating large halls of trade and industrial buildings as well as sport centers. The success of this heating system is based mainly on considerably reduced energy consumption as against convective heating systems. However, the biggest energy savings can be achieved when heating systems of this kind are equipped with regulation and control systems which are adapted to the way the rooms are used. Solutions to problems are described and information is given for planning.

  17. Primary frequency regulation supported by battery storage systems in power systems dominated by renewable energy sources

    DEFF Research Database (Denmark)

    Turk, Ana; Sandelic, Monika; Noto, Giancarlo

    2018-01-01

    replaced by intermittent renewable generators. Therefore, maintaining system quality and stability in terms of power system frequency control is one of the major challenges that requires new resources and their system integration. Battery energy storage systems (BESS), as fast-acting energy storage systems...

  18. Output regulation control for switched stochastic delay systems with dissipative property under error-dependent switching

    Science.gov (United States)

    Li, L. L.; Jin, C. L.; Ge, X.

    2018-01-01

    In this paper, the output regulation problem with dissipative property for a class of switched stochastic delay systems is investigated, based on an error-dependent switching law. Under the assumption that none subsystem is solvable for the problem, a sufficient condition is derived by structuring multiple Lyapunov-Krasovskii functionals with respect to multiple supply rates, via designing error feedback regulators. The condition is also established when dissipative property reduces to passive property. Finally, two numerical examples are given to demonstrate the feasibility and efficiency of the present method.

  19. The UK system for regulating the long-term safety of radioactive waste disposal

    International Nuclear Information System (INIS)

    Duncan, A.

    1997-01-01

    The general system is described for regulation of disposal of solid, long-lived radioactive wastes. The relevant Government policy is outlined, and the framework of legislation and arrangements for implementation, the associated guidance produced by regulatory bodies and the approach to assessment by regulators of a safety case for radioactive waste disposal are reported. Also, for the purposes of discussion in the Workshop, some of the practical issues are considered which are still in development in the UK in regard to regulatory methodology. (author)

  20. Regulation of TGFβ in the immune system: an emerging role for integrins and dendritic cells.

    Science.gov (United States)

    Worthington, John J; Fenton, Thomas M; Czajkowska, Beata I; Klementowicz, Joanna E; Travis, Mark A

    2012-12-01

    Regulation of an immune response requires complex crosstalk between cells of the innate and adaptive immune systems, via both cell-cell contact and secretion of cytokines. An important cytokine with a broad regulatory role in the immune system is transforming growth factor-β (TGF-β). TGF-β is produced by and has effects on many different cells of the immune system, and plays fundamental roles in the regulation of immune responses during homeostasis, infection and disease. Although many cells can produce TGFβ, it is always produced as an inactive complex that must be activated to bind to the TGFβ receptor complex and promote downstream signalling. Thus, regulation of TGFβ activation is a crucial step in controlling TGFβ function. This review will discuss how TGFβ controls diverse immune responses and how TGFβ function is regulated, with a focus on recent work highlighting a critical role for the integrin αvβ8 expressed by dendritic cells in activating TGFβ. Copyright © 2012 Elsevier GmbH. All rights reserved.

  1. Regulation of lipid metabolism by energy availability: a role for the central nervous system.

    Science.gov (United States)

    Nogueiras, R; López, M; Diéguez, C

    2010-03-01

    The central nervous system (CNS) is crucial in the regulation of energy homeostasis. Many neuroanatomical studies have shown that the white adipose tissue (WAT) is innervated by the sympathetic nervous system, which plays a critical role in adipocyte lipid metabolism. Therefore, there are currently numerous reports indicating that signals from the CNS control the amount of fat by modulating the storage or oxidation of fatty acids. Importantly, some CNS pathways regulate adipocyte metabolism independently of food intake, suggesting that some signals possess alternative mechanisms to regulate energy homeostasis. In this review, we mainly focus on how neuronal circuits within the hypothalamus, such as leptin- ghrelin-and resistin-responsive neurons, as well as melanocortins, neuropeptide Y, and the cannabinoid system exert their actions on lipid metabolism in peripheral tissues such as WAT, liver or muscle. Dissecting the complicated interactions between peripheral signals and neuronal circuits regulating lipid metabolism might open new avenues for the development of new therapies preventing and treating obesity and its associated cardiometabolic sequelae.

  2. Regulated open multi-agent systems (ROMAS) a multi-agent approach for designing normative open systems

    CERN Document Server

    Garcia, Emilia; Botti, Vicente

    2015-01-01

    Addressing the open problem of engineering normative open systems using the multi-agent paradigm, normative open systems are explained as systems in which heterogeneous and autonomous entities and institutions coexist in a complex social and legal framework that can evolve to address the different and often conflicting objectives of the many stakeholders involved. Presenting  a software engineering approach which covers both the analysis and design of these kinds of systems, and which deals with the open issues in the area, ROMAS (Regulated Open Multi-Agent Systems) defines a specific multi-agent architecture, meta-model, methodology and CASE tool. This CASE tool is based on Model-Driven technology and integrates the graphical design with the formal verification of some properties of these systems by means of model checking techniques. Utilizing tables to enhance reader insights into the most important requirements for designing normative open multi-agent systems, the book also provides a detailed and easy t...

  3. Tumor necrosis factor-alpha regulates the Hypocretin system via mRNA degradation and ubiquitination.

    Science.gov (United States)

    Zhan, Shuqin; Cai, Guo-Qiang; Zheng, Anni; Wang, Yuping; Jia, Jianping; Fang, Haotian; Yang, Youfeng; Hu, Meng; Ding, Qiang

    2011-04-01

    Recent studies recognize that Hypocretin system (also known as Orexin) plays a critical role in sleep/wake disorders and feeding behaviors. However, little is known about the regulation of the Hypocretin system. It is also known that tumor necrosis factor alpha (TNF-α) is involved in the regulation of sleep/wake cycle. Here, we test our hypothesis that the Hypocretin system is regulated by TNF-α. Prepro-Hypocretin and Hypocretin receptor 2 (HcrtR2) can be detected at a very low level in rat B35 neuroblastoma cells. In response to TNF-α, Prepro-Hypocretin mRNA and protein levels are down-regulated, and also HcrtR2 protein level is down-regulated in B35 cells. To investigate the mechanism, exogenous rat Prepro-Hypocretin and rat HcrtR2 were overexpressed in B35 cells. In response to TNF-α, protein and mRNA of Prepro-Hypocretin are significantly decreased (by 93% and 94%, respectively), and the half-life of Prepro-Hypocretin mRNA is decreased in a time- and dose-dependent manner. The level of HcrtR2 mRNA level is not affected by TNF-α treatment; however, HcrtR2 protein level is significantly decreased (by 86%) through ubiquitination in B35 cells treated with TNF-α. Downregulation of cellular inhibitor of apoptosis protein-1 and -2 (cIAP-1 and -2) abrogates the HcrtR2 ubiquitination induced by TNF-α. The control green fluorescent protein (GFP) expression is not affected by TNF-α treatment. These studies demonstrate that TNF-α can impair the function of the Hypocretin system by reducing the levels of both Prepro-Hypocretin and HcrtR2. Copyright © 2010 Elsevier B.V. All rights reserved.

  4. An analog RF gap voltage regulation system for the Advanced Photon Source storage ring

    International Nuclear Information System (INIS)

    Horan, D.

    1999-01-01

    An analog rf gap voltage regulation system has been designed and built at Argonne National Laboratory to maintain constant total storage ring rf gap voltage, independent of beam loading and cavity tuning effects. The design uses feedback control of the klystron mod-anode voltage to vary the amount of rf power fed to the storage ring cavities. The system consists of two independent feedback loops, each regulating the combined rf gap voltages of eight storage ring cavities by varying the output power of either one or two rf stations, depending on the mode of operation. It provides full operator control and permissive logic to permit feedback control of the rf system output power only if proper conditions are met. The feedback system uses envelope-detected cavity field probe outputs as the feedback signal. Two different methods of combining the individual field probe signals were used to generate a relative DC level representing one-half of the total storage ring rf voltage, an envelope-detected vector sum of the field probe rf signals, and the DC sum of individual field probe envelope detector outputs. The merits of both methods are discussed. The klystron high-voltage power supply (HVPS) units are fitted with an analog interface for external control of the mod-anode voltage level, using a four-quadrant analog multiplier to modulate the HVPS mod-anode voltage regulator set-point in response to feedback system commands

  5. In defense of a regulated system of compensation for living donation.

    Science.gov (United States)

    Matas, Arthur J; Hippen, Benjamin; Satel, Sally

    2008-08-01

    The organ shortage is the major problem in kidney transplantation today. Despite aggressive organ procurement efforts, the supply of donated kidneys, living and deceased, has not matched the growing demand; as a consequence, more and more qualified candidates are suffering on dialysis and then dying before being transplanted. Herein, we provide justification for a regulated system of compensation for donation. The main argument in favor of compensation is simple-financial incentives will increase donation, so fewer transplant candidates will suffer and die while waiting. In addition, development of a regulated system of compensation is the most effective means of crippling the core economic support for transplant tourism. Because dialysis is so much more expensive than a transplant, compensated donation could be cost-neutral to the healthcare system. Importantly, opinion polls suggest that the public would support compensation. As uncompensated kidney donation is widely accepted, persuasive arguments against compensation must explain why such a system would be morally distinguishable from uncompensated donation. We suggest that the potential advantages of a regulated system of compensation for donation far outweigh any potential disadvantages. It is time to advocate for a change in the law so that trials can be done.

  6. Tachykinin-1 in the central nervous system regulates adiposity in rodents.

    Science.gov (United States)

    Trivedi, Chitrang; Shan, Xiaoye; Tung, Yi-Chun Loraine; Kabra, Dhiraj; Holland, Jenna; Amburgy, Sarah; Heppner, Kristy; Kirchner, Henriette; Yeo, Giles S H; Perez-Tilve, Diego

    2015-05-01

    Ghrelin is a circulating hormone that targets the central nervous system to regulate feeding and adiposity. The best-characterized neural system that mediates the effects of ghrelin on energy balance involves the activation of neuropeptide Y/agouti-related peptide neurons, expressed exclusively in the arcuate nucleus of the hypothalamus. However, ghrelin receptors are expressed in other neuronal populations involved in the control of energy balance. We combined laser capture microdissection of several nuclei of the central nervous system expressing the ghrelin receptor (GH secretagoge receptor) with microarray gene expression analysis to identify additional neuronal systems involved in the control of central nervous system-ghrelin action. We identified tachykinin-1 (Tac1) as a gene negatively regulated by ghrelin in the hypothalamus. Furthermore, we identified neuropeptide k as the TAC1-derived peptide with more prominent activity, inducing negative energy balance when delivered directly into the brain. Conversely, loss of Tac1 expression enhances the effectiveness of ghrelin promoting fat mass gain both in male and in female mice and increases the susceptibility to diet-induced obesity in ovariectomized mice. Taken together, our data demonstrate a role TAC1 in the control energy balance by regulating the levels of adiposity in response to ghrelin administration and to changes in the status of the gonadal function.

  7. Quality management system in radiotherapy in the light of regulations applicable in Poland

    Science.gov (United States)

    2012-01-01

    The need to establish conditions for safe irradiation was noted in Poland back in 1986 in the Atomic Law, but for over 16 years no regulations regarding this aspect were passed. The radiological incident in Bialystok (Poland) in 2001 undeniably accelerated the implementation of new legal regulations. Nevertheless, in the absence of national guidelines until 2002, most health care institutions resorted to the quality management system (QMS) model proposed by the ISO norm 9001:2000. Eventually, practice proved the theory and the aforementioned model was also implemented into Polish acts of law defining basic requirements for QMS in radiotherapy. The aim of this work is to review current national regulations regarding QMS in radiotherapy, in particular those referring to standard procedures, the establishment of a commission for procedures and performance of external and internal clinical audits in oncological radiotherapy, as well as to present the process of their implementation into the practice of health care institutions. PMID:23788867

  8. Zebrafish as a Model System for Investigating the Compensatory Regulation of Ionic Balance during Metabolic Acidosis

    Directory of Open Access Journals (Sweden)

    Lletta Lewis

    2018-04-01

    Full Text Available Zebrafish (Danio rerio have become an important model for integrative physiological research. Zebrafish inhabit a hypo-osmotic environment; to maintain ionic and acid-base homeostasis, they must actively take up ions and secrete acid to the water. The gills in the adult and the skin at larval stage are the primary sites of ionic regulation in zebrafish. The uptake of ions in zebrafish is mediated by specific ion transporting cells termed ionocytes. Similarly, in mammals, ion reabsorption and acid excretion occur in specific cell types in the terminal region of the renal tubules (distal convoluted tubule and collecting duct. Previous studies have suggested that functional regulation of several ion transporters/channels in the zebrafish ionocytes resembles that in the mammalian renal cells. Additionally, several mechanisms involved in regulating the epithelial ion transport during metabolic acidosis are found to be similar between zebrafish and mammals. In this article, we systemically review the similarities and differences in ionic regulation between zebrafish and mammals during metabolic acidosis. We summarize the available information on the regulation of epithelial ion transporters during acidosis, with a focus on epithelial Na+, Cl− and Ca2+ transporters in zebrafish ionocytes and mammalian renal cells. We also discuss the neuroendocrine responses to acid exposure, and their potential role in ionic compensation. Finally, we identify several knowledge gaps that would benefit from further study.

  9. Molecular system bioenergetics: regulation of substrate supply in response to heart energy demands.

    Science.gov (United States)

    Saks, Valdur; Favier, Roland; Guzun, Rita; Schlattner, Uwe; Wallimann, Theo

    2006-12-15

    This review re-evaluates regulatory aspects of substrate supply in heart. In aerobic heart, the preferred substrates are always free fatty acids, and workload-induced increase in their oxidation is observed at unchanged global levels of ATP, phosphocreatine and AMP. Here, we evaluate the mechanisms of regulation of substrate supply for mitochondrial respiration in muscle cells, and show that a system approach is useful also for revealing mechanisms of feedback signalling within the network of substrate oxidation and particularly for explaining the role of malonyl-CoA in regulation of fatty acid oxidation in cardiac muscle. This approach shows that a key regulator of fatty acid oxidation is the energy demand. Alterations in malonyl-CoA would not be the reason for, but rather the consequence of, the increased fatty acid oxidation at elevated workloads, when the level of acetyl-CoA decreases due to shifts in the kinetics of the Krebs cycle. This would make malonyl-CoA a feedback regulator that allows acyl-CoA entry into mitochondrial matrix space only when it is needed. Regulation of malonyl-CoA levels by AMPK does not seem to work as a master on-off switch, but rather as a modulator of fatty acid import.

  10. Decision support tool to evaluate alternative policies regulating wind integration into autonomous energy systems

    International Nuclear Information System (INIS)

    Zouros, N.; Contaxis, G.C.; Kabouris, J.

    2005-01-01

    Integration of wind power into autonomous electricity systems strongly depends on the specific technical characteristics of these systems; the regulations applied should take into account physical system constraints. Introduction of market rules makes the issue even more complicated since the interests of the market participants often conflict each other. In this paper, an integrated tool for the comparative assessment of alternative regulatory policies is presented along with a methodology for decision-making, based on alternative scenarios analysis. The social welfare concept is followed instead of the traditional Least Cost Planning

  11. A study on environmental regulation and public inquiry system of nuclear facilities

    International Nuclear Information System (INIS)

    Lee, Sang Hun; Kang, Chang Sun; Son, Ki Yon; Cho, Young Ho; Yang, Ji Won; Lee, Young Wook; Ko, Hyun Suk

    2000-03-01

    Public hearing system for domestic and foreign nuclear facilities are investigated and analyzed. As a result, Korean public hearing system are developed. Atomic Energy Act, Environmental Impact Assessment Act and Administrative Procedure Act of Korea are reviewed and appropriate acts, regulations, procedures and mandates of foreign countries including U.S.A are reviewed and analyzed. On the basis of these results the role of device to collect public opinion is identified for nuclear facility of Korea and the elementary principle of the system and recommendations are developed

  12. A study on environmental regulation and public inquiry system of nuclear facilities

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang Hun [Korea Association for Nuclear Technology, Taejon (Korea, Republic of); Kang, Chang Sun; Son, Ki Yon; Cho, Young Ho; Yang, Ji Won; Lee, Young Wook; Ko, Hyun Suk [Seoul National Univ., Seoul (Korea, Republic of)

    2000-03-15

    Public hearing system for domestic and foreign nuclear facilities are investigated and analyzed. As a result, Korean public hearing system are developed. Atomic Energy Act, Environmental Impact Assessment Act and Administrative Procedure Act of Korea are reviewed and appropriate acts, regulations, procedures and mandates of foreign countries including U.S.A are reviewed and analyzed. On the basis of these results the role of device to collect public opinion is identified for nuclear facility of Korea and the elementary principle of the system and recommendations are developed.

  13. A new power regulator control system based on verilog for electrostatic precipitators

    International Nuclear Information System (INIS)

    Zhang, Zisheng; Li, Guan; Liu, Taotao; Ge, Pengbo; Liu, Zhiqiang

    2013-01-01

    In order to improve the inefficient response of the power system in traditional electrostatic precipitators, such as long design cycles and low safety, a new power regulator control system is designed to tackle the deficiencies. The working voltage system of an electrostatic precipitator consists of an L-C component, a rectifier bridge group and a step-up transformer. The Verilog hardware description language is used to complete the design of the feedback systems. Continuous steady current can be obtained automatically through changing the number of steady voltage control units. The results show that control systems can accurately feed back the changes of the voltage signal of the electrostatic precipitator. Comparing with other control systems, it has the advantages of faster response, higher accuracy, better monitoring performance and superior anti-interference capacity.

  14. THE THIOREDOXIN SYSTEM IN REGULATING MCF-7 CELL PROLIFERATION UNDER REDOX STATUS MODULATION

    Directory of Open Access Journals (Sweden)

    E. A. Stepovaya

    2016-01-01

    Full Text Available Introduction. Despite the available data on tumor cell functioning under the conditions of free radical-mediated oxidation, the mechanisms of redox regulation, cell proliferation management and apoptosis avoidance remain understudied.The objective of the study was to identify the role of the thioredoxin system in regulating MCF-7 breast cancer cell proliferation under redox status modulation with 1.4-dithioerythritol.Material and methods. The studies were conducted on the MCF-7 breast cancer cell line, grown in adherent cell culture. Cell redox status was modulated with5 mM N-ethylmaleimide – an SH group and peptide inhibitor and5 mM 1.4-dithioerythritol – a thiol group protector. The cell cycle was evaluated by flow cytometry, the same technique was used to measure the reactive oxygen species concentration. The levels of reduced and oxidized glutathione and the activity of thioredoxin reductase were identified by spectrophotometry. The intracellular concentrations of thioredoxin, cyclin E and cyclin-dependent kinase 2 were determined by Western blot analysis.Results and discussion. The essential role of the thioredoxin system in regulating MCF-7 breast cancer cell proliferation was exhibited. S-phase arrest under the effect of N-ethylmaleimide and G0/G1-phase arrest under the effect of 1.4-dithioerythritol are associated with the changes in the activity of redox-sensitive protein complexes (cyclins and cyclin-dependent kinases that regulate cell proliferation.Conclusion. Redoxdependent modulation of proliferation regulating intracellular protein activity occurs due to the thioredoxin system. This is a promising research area for seeking molecular targets of breast cell malignization. 

  15. Frequency Regulation of a Hybrid Wind–Hydro Power Plant in an Isolated Power System

    Directory of Open Access Journals (Sweden)

    Guillermo Martínez-Lucas

    2018-01-01

    Full Text Available Currently, some small islands with high wind potential are trying to reduce the environmental and economic impact of fossil fuels by using renewable resources. Nevertheless, the characteristics of these renewable resources negatively affect the quality of the electrical energy, causing frequency disturbances, especially in isolated systems. In this study, the combined contribution to frequency regulation of variable speed wind turbines (VSWT and a pump storage hydropower plant (PSHP is analyzed. Different control strategies, using the kinetic energy stored in the VSWT, are studied: inertial, proportional, and their combination. In general, the gains of the VSWT controller for interconnected systems proposed in the literature are not adequate for isolated systems. Therefore, a methodology to adjust the controllers, based on exhaustive searches, is proposed for each of the control strategies. The control strategies and methodology have been applied to a hybrid wind–hydro power plant on El Hierro Island in the Canary archipelago. At present, in this isolated power system, frequency regulation is only provided by the PSHP and diesel generators. The improvements in the quality of frequency regulation, including the VSWT contribution, have been proven based on simulating different events related to wind speed, or variations in the power demand.

  16. Depository Accounting of Securities in the Ukrainian Stock Market Regulation System

    Directory of Open Access Journals (Sweden)

    Veriha Hanna V.

    2016-02-01

    Full Text Available The aim of the article is to study the procedures, technologies, prudential regulation of depository accounting of securities in the system of the Ukrainian stock market infrastructure and identify directions of its improvement. The article analyzes the dynamics of the number of licenses issued by types of professional activity in the stock market. The necessity for further improvement of mechanisms of the updated system of depository accounting of securities in Ukraine has been proved. There have been developed the following recommendations: to improve the unified rules of accounting and regulation support of the system of risk management of depository activity; develop tools for prudential regulation of depository activity and strengthen the control over fulfillment of prudential standards by the Central Depository and depository institutions; create the necessary conditions for the practical implementation of legal norms concerning establishment of clearing institutions and increase in the level of competition between depositaries; expand the correspondent relations of the Central Depository in relation to the establishment of international depositary relations for the liberalization of the international movement of securities; use segregated accounts providing the possibility of storage of client funds separately from the funds of the transfer bank to protect the capital of the issuer and investor from risks of any force majeure situations; mediate the movement of funds at implementing dividend payments through participants of the accounting system: issuer-the Central Depository-depository institution-depositor.

  17. Liberating and regulating of active effect reserves in the Norwegian power system

    International Nuclear Information System (INIS)

    Bakken, Bjoern H.

    2000-01-01

    This report is a summary of the work done in the project ''Active reserves and current control of the effect situation'' in the period 1997 - 99. The project is one of the 7 partial projects in the project '' Operational safety planning and control'' in the Norges forskningsraad's (The Research Council of Norway) EFFEKT program. The aim of the project has been to study and test methods for liberating and regulating active reserves in the Norwegian power system. Traditionally Norway has been rich in effect reserves but in the present deregulated system it will no longer obvious that these reserves are available as the micro economy is more focussed upon in an increasingly pressured operational situation. In the recent years the margins between the available generator effects and the systems maximum load have become increasingly smaller. With the various problems discussed in this report in mind, recommendations may be given with respect to specific measures in order to improve the systems operator possibilities for current control of the effect situation as well as recommendations regarding interesting concepts that ought to be continued in new research projects. The systems operators have implemented some of the proposed measures while others are being studied further. The following specific measures are proposed to the systems operators: 1) To implements graphical survey of the production and the reported reserves in the systems operator EMS tool. 2) To implement tools of the type ''gradual load flow'' in order to prepare possible regulations in critical periods. 3) Reserved instantaneous reserves are introduced as a systems service. 4) The systems operator can reserve effect up to the operational time. 5) Introduce incentives in order to activate the end user more strongly in the ''RK'' market. 5) To modify the methodology corresponding to ''Simultaneous load'' for forecasting bottlenecks in future operation weeks. 6) The systems service ''ramping'' is

  18. Legal Challenges Related to the Regulation of a Domain Name System

    Directory of Open Access Journals (Sweden)

    Marius Kalinauskas

    2012-12-01

    Full Text Available Purpose—to review and analyse the problematic aspects related to domain name allocation and further usage processes, highlighting legal regulation of a domain name system.Design/methodology/approach—based on the comparison analysis of scientific literature, authors discuss problematic issues related to the legal regulation of domain name allocation and usage processes, analyse practical approaches and collision cases in the context of a domain name system. The authors examine the positive and negative aspects of a domain naming system and conflicting regulatory specifics. This paper describes the development of institutional bodies responsible for DNS management, supervision approaches and inner functionality policies.Findings—the authors examine domain naming system models and dispute resolution mechanisms, their evolution in the context of Internet development and the structural changes of the Internet governance institutions. The authors analyse tendencies related to DNS regulation and the possible effect of new regulation models in practice, while reflecting interests of stakeholders in the subject field.Research limitations/implications—agreements on the registration of domain names are based on self-regulation principles. A number of different interests may collide when speaking about domain name registration or usage and this issue becomes a major challenge to scientists and lawyers who are seeking an optimal domain-naming regulatory mechanism. The article does not address trademark conflicts within domain names in this respect. This should be considered as an object for separate study, which requires deeper analysis.Practical implications—the authors review key aspects of the domain name system and describe tendencies for the regulatory models.Value—the article emphasizes potential domain naming conflicts and disputes concerning the usage of common terms and phrases in order to manipulate information for illicit purposes. The

  19. Legal Challenges Related to the Regulation of a Domain Name System

    Directory of Open Access Journals (Sweden)

    Marius Kalinauskas

    2013-02-01

    Full Text Available Purpose—to review and analyse the problematic aspects related to domain name allocation and further usage processes, highlighting legal regulation of a domain name system. Design/methodology/approach—based on the comparison analysis of scientific literature, authors discuss problematic issues related to the legal regulation of domain name allocation and usage processes, analyse practical approaches and collision cases in the context of a domain name system. The authors examine the positive and negative aspects of a domain naming system and conflicting regulatory specifics. This paper describes the development of institutional bodies responsible for DNS management, supervision approaches and inner functionality policies. Findings—the authors examine domain naming system models and dispute resolution mechanisms, their evolution in the context of Internet development and the structural changes of the Internet governance institutions. The authors analyse tendencies related to DNS regulation and the possible effect of new regulation models in practice, while reflecting interests of stakeholders in the subject field. Research limitations/implications—agreements on the registration of domain names are based on self-regulation principles. A number of different interests may collide when speaking about domain name registration or usage and this issue becomes a major challenge to scientists and lawyers who are seeking an optimal domain-naming regulatory mechanism. The article does not address trademark conflicts within domain names in this respect. This should be considered as an object for separate study, which requires deeper analysis. Practical implications—the authors review key aspects of the domain name system and describe tendencies for the regulatory models. Value—the article emphasizes potential domain naming conflicts and disputes concerning the usage of common terms and phrases in order to manipulate information for illicit purposes

  20. Regional tourist industry in context of principles of regional socioeconomic systems self-regulation

    Directory of Open Access Journals (Sweden)

    Andrey Gennadyevich Shelomentsev

    2011-03-01

    Full Text Available This paper deals with basic principles of self-regulation of tourist complexes as regional socio-economic systems on the example of Sverdlovsk region. These include the principles of goal setting and the necessary diversity of economic entropy: in this case, these are important for the tourism industry and the human and natural resource and ecological potential. Is it shown how a tourist complex influences the socio-economic development of regional economic systems. In particular, tourism influences some of migration processes. Tourism development strategy in the Russian Federation at the tourist center level is analyzed. The need to develop such a strategy is due to the transition to market relations and, as a consequence, complexity of governmental regulation. It is substantiated that Sverdlovsk region is a subject to following strategy and might be successful in various sectors of tourism: business and congress and exhibition, urban entertainment, family and shopping tourism, sports, medical and recreational tourism.

  1. Analysis of expediency to set regulators of high-pressure emergency core cooling system of WWER 1000 (B-320)

    International Nuclear Information System (INIS)

    Skalozubov, V.I.; Komarov, Yu.A.; Tikhonova, G.G.; Nikiforov, S.N.; Bogodist, V.V.; Fol'tov, I.M.; Khadzh Faradzhallakh Dabbakh, A.

    2011-01-01

    The work shows that setting regulative valves in high-pressure emergency core cooling system of WWER 1000/B-320 can be effective only involving the additional tuning to account traverse speed of operating elements of regulator and configuration of the systems providing cooling of primary loop.

  2. MicroRNAs (MiRs) Precisely Regulate Immune System Development and Function in Immunosenescence Process.

    Science.gov (United States)

    Aalaei-Andabili, Seyed Hossein; Rezaei, Nima

    2016-01-01

    Human aging is a complex process with pivotal changes in gene expression of biological pathways. Immune system dysfunction has been recognized as one of the most important abnormalities induced by senescent names immunosenescence. Emerging evidences suggest miR role in immunosenescence. We aimed to systemically review all relevant reports to clearly state miR effects on immunosenescence process. Sensitive electronic searches carried out. Quality assessment has been performed. Since majority of the included studies were laboratory works, and therefore heterogen, we discussed miR effects on immunological aging process nonstatically. Forty-six articles were found in the initial search. After exclusion of 34 articles, 12 studies enrolled to the final stage. We found that miRs have crucial roles in exact function of immune system. MiRs are involved in the regulation of the aging process in the immune system components and target certain genes, promoting or inhibiting immune system reaction to invasion. Also, miRs control life span of the immune system members by regulation of the genes involved in the apoptosis. Interestingly, we found that immunosenescence is controllable by proper manipulation of the various miRs expression. DNA methylation and histone acetylation have been discovered as novel strategies, altering NF-κB binding ability to the miR promoter sites. Effect of miRs on impairment of immune system function due to the aging is emerging. Although it has been accepted that miRs have determinant roles in the regulation of the immunosenescence; however, most of the reports are concluded from animal/laboratory works, suggesting the necessity of more investigations in human.

  3. The Csr System Regulates Escherichia coli Fitness by Controlling Glycogen Accumulation and Energy Levels.

    Science.gov (United States)

    Morin, Manon; Ropers, Delphine; Cinquemani, Eugenio; Portais, Jean-Charles; Enjalbert, Brice; Cocaign-Bousquet, Muriel

    2017-10-31

    In the bacterium Escherichia coli , the posttranscriptional regulatory system Csr was postulated to influence the transition from glycolysis to gluconeogenesis. Here, we explored the role of the Csr system in the glucose-acetate transition as a model of the glycolysis-to-gluconeogenesis switch. Mutations in the Csr system influence the reorganization of gene expression after glucose exhaustion and disturb the timing of acetate reconsumption after glucose exhaustion. Analysis of metabolite concentrations during the transition revealed that the Csr system has a major effect on the energy levels of the cells after glucose exhaustion. This influence was demonstrated to result directly from the effect of the Csr system on glycogen accumulation. Mutation in glycogen metabolism was also demonstrated to hinder metabolic adaptation after glucose exhaustion because of insufficient energy. This work explains how the Csr system influences E. coli fitness during the glycolysis-gluconeogenesis switch and demonstrates the role of glycogen in maintenance of the energy charge during metabolic adaptation. IMPORTANCE Glycogen is a polysaccharide and the main storage form of glucose from bacteria such as Escherichia coli to yeasts and mammals. Although its function as a sugar reserve in mammals is well documented, the role of glycogen in bacteria is not as clear. By studying the role of posttranscriptional regulation during metabolic adaptation, for the first time, we demonstrate the role of sugar reserve played by glycogen in E. coli Indeed, glycogen not only makes it possible to maintain sufficient energy during metabolic transitions but is also the key component in the capacity of cells to resume growth. Since the essential posttranscriptional regulatory system Csr is a major regulator of glycogen accumulation, this work also sheds light on the central role of posttranscriptional regulation in metabolic adaptation. Copyright © 2017 Morin et al.

  4. On the modelling of linear-assisted DC-DC voltage regulators for photovoltaic solar energy systems

    Science.gov (United States)

    Martínez-García, Herminio; García-Vílchez, Encarna

    2017-11-01

    This paper shows the modelling of linear-assisted or hybrid (linear & switching) DC/DC voltage regulators. In this kind of regulators, an auxiliary linear regulator is used, which objective is to cancel the ripple at the output voltage and provide fast responses for load variations. On the other hand, a switching DC/DC converter, connected in parallel with the linear regulator, allows to supply almost the whole output current demanded by the load. The objective of this topology is to take advantage of the suitable regulation characteristics that series linear voltage regulators have, but almost achieving the high efficiency that switching DC/DC converters provide. Linear-assisted DC/DC regulators are feedback systems with potential instability. Therefore, their modelling is mandatory in order to obtain design guidelines and assure stability of the implemented power supply system.

  5. Regulation of the corticosteroid signalling system in rainbow trout HPI axis during confinement stress.

    Science.gov (United States)

    Kiilerich, Pia; Servili, Arianna; Péron, Sandrine; Valotaire, Claudiane; Goardon, Lionel; Leguen, Isabelle; Prunet, Patrick

    2018-03-01

    This study aims to shed light on corticosteroid regulation of stress in teleost fish with focus on the corticosteroid signalling system. The role of the mineralocorticoid-like hormone 11-deoxycorticosterone (DOC) in fish is still enigmatic, as is the function of the mineralocorticoid receptor, MR. Low plasma DOC levels and ubiquitous tissue distribution of MR question the physiological relevance of the mineralocorticoid-axis. Furthermore, the particular purpose of each of the three corticosteroid receptors in fish, the glucocorticoid receptors, GR1 and GR2, and the MR, is still largely unknown. Therefore we investigate the regulation of cortisol and DOC in plasma and mRNA levels of MR, GR1 and GR2 in the HPI-axis tissues (hypothalamus, pituitary and interrenal gland) during a detailed confinement stress time-course. Here we show a sustained up-regulation of plasma DOC levels during a confinement stress time-course. However, the low DOC levels compared to cortisol measured in the plasma do not favour an activity of DOC through MR receptors. Furthermore, we show differential contribution of the CRs in regulation and control of HPI axis activity following confinement stress. Judged by the variation of mRNA levels negative feedback regulation of cortisol release occurs on the level of the pituitary via MR and on the level of the interrenal gland via GR2. Finally, asa significant effect of confinement stress on CR expressions was observed in the pituitary gland, we completed this experiment by demonstrating that corticosteroid receptors (GR1, GR2 and MR) are co-expressed in the ACTH cells located in the adenohypophysis. Overall, these data suggest the involvement of these receptors in the regulation of the HPI axis activity by cortisol. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. DESIGN AND TESTING OF A DIGITAL REGULATOR FOR FERMILAB MAGNET POWER SYSTEMS

    Energy Technology Data Exchange (ETDEWEB)

    Li Vigni, Vincenzo [Palermo U.

    2012-01-01

    In this thesis, the design of a digitally controlled DC power system for testing conventional and superconducting magnets is proposed. The designed PID controller performances have been tested by the 30kA test stand for superconducting magnets, Vertical Magnet Test Facility (VMTF), which is hosted at the Fermilab Magnet Test Facility (MTF). The system is implemented on a National Instruments CompactRIO and both real-time and FPGA targets are programmed. A full 24-bit PID algorithm is coded and successfully tested by a manual tuning approach. An automated tuning algorithm is then introduced. As it will be shown by simulation and experimental results, the proposed system meets all design specifications. The current loop stability is up to 14 times better than the existing regulator and a control accuracy less than 4 ppm is achieved. Shorted-bus tests of the PID regulator have been successfully performed on the VMTF power system. In order to test the generalization capability of the designed system towards different types of magnets, the system has been easily adapted to and tested on the 10kA conventional magnet test stand (Stand C at Fermilab). As shown by experimental results, the designed PID controller features really high performancesin terms of steady-state accuracy and effectiveness of the tuning algorithm.

  7. New pre-heating system for natural gas pressure regulating stations

    International Nuclear Information System (INIS)

    Zullo, G.; Vertuani, C.; Borghesani, O.; Vignoli, F.

    1999-01-01

    Costs for running natural gas pressure regulating stations are mainly due to operation and maintenance of a natural gas preheating system, usually equipment with a hot water boiler or an armour-plated electric resistance immersed in a fluid. The article describe a system, considering a natural circulation boiler which uses steam/condensate (at 100 degrees C and 0,5 bar) as a thermal conductor, in thermodynamic balance and in absence of un condensable. This new boiler, already operating with satisfactory results in heating system for industrial buildings, does not require testing, notifications, periodical inspections by the competent authorities, constant monitoring by trained or patented staff. Besides, it allows easier installations procedures and running cost savings. The system, to be considered as static because it has no moving parts, is a good alternative to conventional forced hot water circulation or electric heating system [it

  8. Contribution of VSC-HVDC to Frequency Regulation of Power Systems With Offshore Wind Generation

    DEFF Research Database (Denmark)

    Liu, Hongzhi; Chen, Zhe

    2015-01-01

    to the onshore system grid through voltage-source converter-based–high voltage direct current (VSC-HVdc) transmission systems. Due to the decoupling of VSC-HVdc and signal transmission delay, offshore wind farms may not be able to respond to the onshore grid frequency excursion in time and, consequently......, the stability and security of the power system will be put at risk, especially for those with high wind penetration. This paper proposes a coordinated control scheme to allow VSC-HVdc link to contribute to the system frequency regulation by adjusting its dc-link voltage. By means of this approach, the dc...... capacitors of VSC-HVdc are controlled to absorb or release energy so as to provide frequency support. To further enhance the system frequency response, the frequency support from VSC-HVdc is also finely coordinated with that from offshore wind farm according to the latency of offshore wind farm responding...

  9. Short-Term State Forecasting-Based Optimal Voltage Regulation in Distribution Systems: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Rui; Jiang, Huaiguang; Zhang, Yingchen

    2017-05-17

    A novel short-term state forecasting-based optimal power flow (OPF) approach for distribution system voltage regulation is proposed in this paper. An extreme learning machine (ELM) based state forecaster is developed to accurately predict system states (voltage magnitudes and angles) in the near future. Based on the forecast system states, a dynamically weighted three-phase AC OPF problem is formulated to minimize the voltage violations with higher penalization on buses which are forecast to have higher voltage violations in the near future. By solving the proposed OPF problem, the controllable resources in the system are optimally coordinated to alleviate the potential severe voltage violations and improve the overall voltage profile. The proposed approach has been tested in a 12-bus distribution system and simulation results are presented to demonstrate the performance of the proposed approach.

  10. Types of adaptation of the system of enterprise economic security to the impact of subjects of tax regulation

    Directory of Open Access Journals (Sweden)

    Pohorelov Yurii S.

    2014-01-01

    Full Text Available The article offers the authors’ approach to identification of types of adaptation of the system of enterprise economic security to negative influence of subjects of tax regulation. It determines composition of these subjects and, separately, regulation subjects that form fundamental grounds of the tax sphere and subjects of effective influence, which directly interact with entrepreneurial structures and realise tax regulation of their activity in practice. As regards direct adaptation of the system of enterprise economic security, the article offers to mark out its individual types with respect to the set goal, essence of changes in the system of economic security, degree of its manageability and nature of accumulated changes. Moreover, the article offers a list of catalysts and inhibitors of adaptation of the system of enterprise economic security to impact of subjects of tax regulation. It also marks out adaptation parameters of the system of enterprise economic security to the impact of subjects of tax regulation and provides their gradations.

  11. Possible Involvement of Photoperiodic Regulation in Reproductive Endocrine System of Female Olive Flounder Paralichthys olivaceus.

    Science.gov (United States)

    Kim, Hyun Chul; Lee, Chi Hoon; Hur, Sung Pyu; Kim, Byeong Hoon; Park, Jun Young; Lee, Young Don

    2015-03-01

    This study investigated possible involvement of photoperiodic regulation in reproductive endocrine system of female olive flounder. To investigate the influence on brain-pituitary axis in endocrine system by regulating photoperiod, compared expression level of Kisspeptin and sbGnRH mRNA in brain and FSH-β, LH-β and GH mRNA in pituitary before and after spawning. Photoperiod was treated natural photoperiod and long photoperiod (15L:9D) conditions from Aug. 2013 to Jun. 2014. Continuous long photoperiod treatment from Aug. (post-spawning phase) was inhibited gonadal development of female olive flounder. In natural photoperiod group, the Kiss2 expression level a significant declined in Mar. (spawning period). And also, FSH-β, LH-β and GH mRNA expression levels were increasing at this period. However, in long photoperiod group, hypothalamic Kiss2, FSH-β, LH-β and GH mRNA expression levels did not show any significant fluctuation. These results suggest that expression of hypothalamic Kiss2, GtH and GH in the pituitary would change in response to photoperiod and their possible involvement of photoperiodic regulation in reproductive endocrine system of the BPG axis.

  12. An Optimal Control Strategy for DC Bus Voltage Regulation in Photovoltaic System with Battery Energy Storage

    Directory of Open Access Journals (Sweden)

    Muhamad Zalani Daud

    2014-01-01

    Full Text Available This paper presents an evaluation of an optimal DC bus voltage regulation strategy for grid-connected photovoltaic (PV system with battery energy storage (BES. The BES is connected to the PV system DC bus using a DC/DC buck-boost converter. The converter facilitates the BES power charge/discharge to compensate for the DC bus voltage deviation during severe disturbance conditions. In this way, the regulation of DC bus voltage of the PV/BES system can be enhanced as compared to the conventional regulation that is solely based on the voltage-sourced converter (VSC. For the grid side VSC (G-VSC, two control methods, namely, the voltage-mode and current-mode controls, are applied. For control parameter optimization, the simplex optimization technique is applied for the G-VSC voltage- and current-mode controls, including the BES DC/DC buck-boost converter controllers. A new set of optimized parameters are obtained for each of the power converters for comparison purposes. The PSCAD/EMTDC-based simulation case studies are presented to evaluate the performance of the proposed optimized control scheme in comparison to the conventional methods.

  13. An optimal control strategy for DC bus voltage regulation in photovoltaic system with battery energy storage.

    Science.gov (United States)

    Daud, Muhamad Zalani; Mohamed, Azah; Hannan, M A

    2014-01-01

    This paper presents an evaluation of an optimal DC bus voltage regulation strategy for grid-connected photovoltaic (PV) system with battery energy storage (BES). The BES is connected to the PV system DC bus using a DC/DC buck-boost converter. The converter facilitates the BES power charge/discharge to compensate for the DC bus voltage deviation during severe disturbance conditions. In this way, the regulation of DC bus voltage of the PV/BES system can be enhanced as compared to the conventional regulation that is solely based on the voltage-sourced converter (VSC). For the grid side VSC (G-VSC), two control methods, namely, the voltage-mode and current-mode controls, are applied. For control parameter optimization, the simplex optimization technique is applied for the G-VSC voltage- and current-mode controls, including the BES DC/DC buck-boost converter controllers. A new set of optimized parameters are obtained for each of the power converters for comparison purposes. The PSCAD/EMTDC-based simulation case studies are presented to evaluate the performance of the proposed optimized control scheme in comparison to the conventional methods.

  14. Regulating Critical Period Plasticity: Insight from the Visual System to Fear Circuitry for Therapeutic Interventions

    Directory of Open Access Journals (Sweden)

    Elisa M. Nabel

    2013-11-01

    Full Text Available Early temporary windows of heightened brain plasticity called critical periods developmentally sculpt neural circuits and contribute to adult behavior. Regulatory mechanisms of visual cortex development –the preeminent model of experience-dependent critical period plasticity- actively limit adult plasticity and have proved fruitful therapeutic targets to reopen plasticity and rewire faulty visual system connections later in life. Interestingly, these molecular mechanisms have been implicated in the regulation of plasticity in other functions beyond vision. Applying mechanistic understandings of critical period plasticity in the visual cortex to fear circuitry may provide a conceptual framework for developing novel therapeutic tools to mitigate aberrant fear responses in post traumatic stress disorder. In this review, we turn to the model of experience-dependent visual plasticity to provide novel insights for the mechanisms regulating plasticity in the fear system. Fear circuitry, particularly fear memory erasure, also undergoes age-related changes in experience-dependent plasticity. We consider the contributions of molecular brakes that halt visual critical period plasticity to circuitry underlying fear memory erasure. A major molecular brake in the visual cortex, perineuronal net formation, recently has been identified in the development of fear systems that are resilient to fear memory erasure. The roles of other molecular brakes, myelin-related Nogo receptor signaling and Lynx family proteins– endogenous inhibitors for nicotinic acetylcholine receptor, are explored in the context of fear memory plasticity. Such fear plasticity regulators, including epigenetic effects, provide promising targets for therapeutic interventions.

  15. Status, Antimicrobial Mechanism, and Regulation of Natural Preservatives in Livestock Food Systems.

    Science.gov (United States)

    Lee, Na-Kyoung; Paik, Hyun-Dong

    2016-01-01

    This review discusses the status, antimicrobial mechanisms, application, and regulation of natural preservatives in livestock food systems. Conventional preservatives are synthetic chemical substances including nitrates/nitrites, sulfites, sodium benzoate, propyl gallate, and potassium sorbate. The use of artificial preservatives is being reconsidered because of concerns relating to headache, allergies, and cancer. As the demand for biopreservation in food systems has increased, new natural antimicrobial compounds of various origins are being developed, including plant-derived products (polyphenolics, essential oils, plant antimicrobial peptides (pAMPs)), animal-derived products (lysozymes, lactoperoxidase, lactoferrin, ovotransferrin, antimicrobial peptide (AMP), chitosan and others), and microbial metabolites (nisin, natamycin, pullulan, ε-polylysine, organic acid, and others). These natural preservatives act by inhibiting microbial cell walls/membranes, DNA/RNA replication and transcription, protein synthesis, and metabolism. Natural preservatives have been recognized for their safety; however, these substances can influence color, smell, and toxicity in large amounts while being effective as a food preservative. Therefore, to evaluate the safety and toxicity of natural preservatives, various trials including combinations of other substances or different food preservation systems, and capsulation have been performed. Natamycin and nisin are currently the only natural preservatives being regulated, and other natural preservatives will have to be legally regulated before their widespread use.

  16. Neural networks for combined control of capacitor banks and voltage regulators in distribution systems

    Energy Technology Data Exchange (ETDEWEB)

    Gu, Z.; Rizy, D.T.

    1996-02-01

    A neural network for controlling shunt capacitor banks and feeder voltage regulators in electric distribution systems is presented. The objective of the neural controller is to minimize total I{sup 2}R losses and maintain all bus voltages within standard limits. The performance of the neural network for different input selections and training data is discussed and compared. Two different input selections are tried, one using the previous control states of the capacitors and regulator along with measured line flows and voltage which is equivalent to having feedback and the other with measured line flows and voltage without previous control settings. The results indicate that the neural net controller with feedback can outperform the one without. Also, proper selection of a training data set that adequately covers the operating space of the distribution system is important for achieving satisfactory performance with the neural controller. The neural controller is tested on a radially configured distribution system with 30 buses, 5 switchable capacitor banks an d one nine tap line regulator to demonstrate the performance characteristics associated with these principles. Monte Carlo simulations show that a carefully designed and relatively compact neural network with a small but carefully developed training set can perform quite well under slight and extreme variation of loading conditions.

  17. Monitoring of heavy metals in selected Water Supply Systems in Poland, in relation to current regulations

    Science.gov (United States)

    Szuster-Janiaczyk, Agnieszka; Zeuschner, Piotr; Noga, Paweł; Skrzypczak, Marta

    2018-02-01

    The study presents an analysis of water quality monitoring in terms of the content of heavy metals, which is conducted in three independent water supply systems in Poland. The analysis showed that the monitoring of heavy metals isn't reliable - both the quantity of tested water samples and the location of the monitoring points are the problem. The analysis of changes in water quality from raw water to tap water was possible only for one of the analysed systems and indicate a gradual deterioration of water quality, although still within acceptable limits of legal regulations.

  18. The system of radiation protection: views from the Australian regulator (Arpansa)

    International Nuclear Information System (INIS)

    Prosser, S.

    2004-01-01

    Of those issues identified by the EGRP at previous meetings, there are a number of areas where, from the Australian perspective, the current system of radiological protection could benefit from change. These include stakeholder issues, the environment, inconsistencies in numerical values and risk comparison with more common hazards. Implementing any recommended changes would present some bureaucratic challenges but would also provide an opportunity for increasing national uniformity of regulation. However it is recognised that the current system does not provide an unacceptable level of protection and it is therefore important that any proposed changes are thoroughly tested in practice to ensure a real net benefit. (author)

  19. Photovoltaic System Regulation Based on a PID Fuzzy Controller to Ensure a Fixed Settling Time

    Directory of Open Access Journals (Sweden)

    Paula A. Ortiz-Valencia

    2013-11-01

    Full Text Available The main objective of the controllers in photovoltaic systems (PV is to ensure the maximum extraction of the available power. Those controllers usually combine the action of a maximum power point tracking algorithm (MPPT with a voltage regulator, which has the function of rejecting disturbances at the panel terminals. Such controllers are commonly based on PI and PID structures, it requiring linearized models at an operating point. But, due to disturbances generated by the environment and the load, the operating point of the system changes drastically, which hinder to obtain the desired system performance. This paper proposes to regulate the PV system using a Fuzzy PID controller, which adapts to changes in solar irradiance and load oscillations. This characteristic guarantees a constant settling time, which is required to precisely define the period of the MPPT algorithm. In the case of classical linear controllers, the period of the MPPT algorithm is set to the worst case (longest period which generates additional power losses by slowing down the tracking of the optimal operating point. Therefore, the solution proposed in this paper improves the overall system efficiency. Finally, such a solution is validated through simulations in Matlab®.

  20. Consolidated permit regulations and hazardous waste management system: Environmental Protection Agency. Notice of issuance of regulation interpretation memorandum.

    Science.gov (United States)

    1981-12-10

    The Environmental Protection Agency (EPA) is issuing today a Regulation Interpretation Memorandum (RIM) which provides official interpretation of the issue of whether a generator who accumulates hazardous waste pursuant to 40 CFR 262.34, may qualify for interim status after November 19, 1980. This issue arose when the requirements for submitting a Part A permit application (one of the prerequisites to qualifying for interim status) were amended on November 19, 1980. The provisions interpreted today are part of the Consolidated Permit Regulations promulgated under Subtitle C of the Solid Waste Disposal Act, as amended by the Resource Conservation and Recovery Act, as amended (RCRA).

  1. Suboptimal Regulation of a Class of Bilinear Interconnected Systems with Finite-Time Sliding Planning Horizons

    Directory of Open Access Journals (Sweden)

    M. de la Sen

    2008-01-01

    Full Text Available This paper focuses on the suboptimization of a class of multivariable discrete-time bilinear systems consisting of interconnected bilinear subsystems with respect to a linear quadratic optimal regulation criterion which involves the use of state weighting terms only. Conditions which ensure the controllability of the overall system are given as a previous requirement for optimization. Three transformations of variables are made on the system equations in order to implement the scheme on an equivalent linear system. This leads to an equivalent representation of the used quadratic performance index that involves the appearance of quadratic weighting terms related to both transformed input and state variables. In this way, a Riccati-matrix sequence, allowing the synthesis of a standard feedback control law, is obtained. Finally, the proposed control scheme is tested on realistic examples.

  2. Modeling of a New Structure of Precision Air Conditioning System Using Secondary Condenser for Rh Regulation

    Directory of Open Access Journals (Sweden)

    Aries Subiantoro

    2012-05-01

    Full Text Available A dynamic mathematical model for a new structure of precision air conditioning (PAC has been developed. The proposed PAC uses an additional secondary condenser for relative humidity regulation compared to a basic refrigeration system. The work mechanism for this system and a vapour-compression cycle process of the system are illustrated using psychrometric chart and pressure-enthalpy diagram. A non-linear system model is derived based on the conservation of mass and energy balance principles and then linearized at steady state operating point for developing a 8th-order state space model suited for multivariable controller design. The quality of linearized model is analyzed in terms of transient response, controllability, observability, and interaction between input-output variables. The developed model is verified through simulation showing its ability for imitating the nonlinear behavior and the interaction of input-output variables.

  3. Workshop on environmental assessment. [Regulation of applications of nuclear energy and related ancillary systems

    Energy Technology Data Exchange (ETDEWEB)

    Watson, E.C. (comp.)

    1982-07-01

    Objectives of the workshop were: to review and evaluate the state-of-the-art of environmental impact assessments as applied to the regulation of applications of nuclear energy and related ancillary systems; to identify areas where existing technology allows establishing acceptable methods or standard practices that will meet the requirements of the NRC regulations, standards and guides for both normal operations and off-standard conditions including accident considerations; to illuminate topics where existing models or analytical methods are deficient because of unverified assumptions, a paucity of empirical data, conflicting results reported in the literature or a need for observation of operation systems; to compile, analyze and synthesize a prioritized set of research needs to advance the state-of-the-art to the level which will meet all of the requirements of the Commission's regulations, standards and guides; and to develop bases for maintaining the core of regulatory guidance at the optimum level balancing technical capabilities with practical considerations of cost and value to the regulatory process. The discussion held in small group sessions on aquatic, atmospheric, and terrestrial pathways are presented. The following research needs were identified as common to all three groups: validation of models; characterization of source terms; development of screening techniques; basis for de minimis levels of contamination; and updating of objectives for environmental monitoring programs.

  4. Mono- and Digalactosyldiacylglycerol Lipids Function Nonredundantly to Regulate Systemic Acquired Resistance in Plants

    Directory of Open Access Journals (Sweden)

    Qing-ming Gao

    2014-12-01

    Full Text Available Summary: The plant galactolipids monogalactosyldiacylglycerol (MGDG and digalactosyldiacylglycerol (DGDG have been linked to the anti-inflammatory and cancer benefits of a green leafy vegetable diet in humans due to their ability to regulate the levels of free radicals like nitric oxide (NO. Here, we show that DGDG contributes to plant NO as well as salicylic acid biosynthesis and is required for the induction of systemic acquired resistance (SAR. In contrast, MGDG regulates the biosynthesis of the SAR signals azelaic acid (AzA and glycerol-3-phosphate (G3P that function downstream of NO. Interestingly, DGDG is also required for AzA-induced SAR, but MGDG is not. Notably, transgenic expression of a bacterial glucosyltransferase is unable to restore SAR in dgd1 plants even though it does rescue their morphological and fatty acid phenotypes. These results suggest that MGDG and DGDG are required at distinct steps and function exclusively in their individual roles during the induction of SAR. : The galactolipids monogalactosyldiacylglycerol (MGDG and digalactosyldiacylglycerol (DGDG constitute ∼80% of total membrane lipids in plants. Gao et al. now show that these galactolipids function nonredundantly to regulate systemic acquired resistance (SAR. Furthermore, they show that the terminal galactose on the α-galactose-β-galactose head group of DGDG is critical for SAR.

  5. Vibrio tapetis Displays an Original Type IV Secretion System in Strains Pathogenic for Bivalve Molluscs

    Directory of Open Access Journals (Sweden)

    Graciela M. Dias

    2018-02-01

    Full Text Available The Brown Ring Disease (BRD caused high mortality rates since 1986 in the Manila clam Venerupis philippinarum introduced and cultured in Western Europe from the 1970s. The causative agent of BRD is a Gram-Negative bacterium, Vibrio tapetis, which is also pathogenic to fish. Here we report the first assembly of the complete genome of V. tapetis CECT4600T, together with the genome sequences of 16 additional strains isolated across a broad host and geographic range. Our extensive genome dataset allowed us to describe the pathogen pan- and core genomes and to identify putative virulence factors. The V. tapetis core genome consists of 3,352 genes, including multiple potential virulence factors represented by haemolysins, transcriptional regulators, Type I restriction modification system, GGDEF domain proteins, several conjugative plasmids, and a Type IV secretion system. Future research on the coevolutionary arms race between V. tapetis virulence factors and host resistance mechanisms will improve our understanding of how pathogenicity develops in this emerging pathogen.

  6. Regulation of G protein-coupled receptor signalling: focus on the cardiovascular system and regulator of G protein signalling proteins

    NARCIS (Netherlands)

    Hendriks-Balk, Mariëlle C.; Peters, Stephan L. M.; Michel, Martin C.; Alewijnse, Astrid E.

    2008-01-01

    G protein-coupled receptors (GPCRs) are involved in many biological processes. Therefore, GPCR function is tightly controlled both at receptor level and at the level of signalling components. Well-known mechanisms by which GPCR function can be regulated comprise desensitization/resensitization

  7. Analysis of Driving Safety Criteria Based on National Regulations for the Suspension Systems of NGVs

    Directory of Open Access Journals (Sweden)

    Ronald Mauricio Martinod

    2015-01-01

    Full Text Available The work analyses the technical evaluation process of the suspension system for vehicles that have been adapted to natural-gas-fuelled engines from power light-duty gasoline, and diesel vehicles; this evaluation is done through a mechanical review established by national regulations. The development of this analysis is focused on establishing the relationship between the natural-gas-fuelled equipment and the dynamic effect caused by the extra-weight, according to two measuring criteria that determine the safety and driving comfort, these are: (i tire-road adhesion index; and (ii tire excitation phase angle. The paper also proposes new elements that can be added to the current national regulations and that are currently applied to assess the suspension of natural gas vehicles, recorded using a test standard benchmark for the evaluation of the suspension.

  8. The relationship of self-regulation and aggression: an empirical test of personality systems interaction theory.

    Science.gov (United States)

    Ross, Thomas; Fontao, María Isabel

    2008-10-01

    On the basis of personality systems interaction (PSI) theory, the authors examine self-regulation, conflict behaviour, behavioural resources, and personality disorders in a sample of 83 male offenders and explore the role self-regulatory variables play with respect to aggressive behaviour. Although substantial correlations between self-regulatory functions and aggressive behaviour were found, these variables did not predict aggression in a subsequent regression analysis with measures of self-regulation, conflict behaviour, and personality disorders as independent variables. Antisocial behaviour, behavioural self-control, and affect were among the strongest predictors of aggression. Specific predictions based on PSI theory could not be confirmed. Theoretical implications of the findings are discussed and put into relation with treatment issues of offenders.

  9. Lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis in the adult central nervous system.

    Science.gov (United States)

    Liu, Qiang; Zhang, Juan; Zerbinatti, Celina; Zhan, Yan; Kolber, Benedict J; Herz, Joachim; Muglia, Louis J; Bu, Guojun

    2011-01-11

    Obesity is a growing epidemic characterized by excess fat storage in adipocytes. Although lipoprotein receptors play important roles in lipid uptake, their role in controlling food intake and obesity is not known. Here we show that the lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis. Conditional deletion of the Lrp1 gene in the brain resulted in an obese phenotype characterized by increased food intake, decreased energy consumption, and decreased leptin signaling. LRP1 directly binds to leptin and the leptin receptor complex and is required for leptin receptor phosphorylation and Stat3 activation. We further showed that deletion of the Lrp1 gene specifically in the hypothalamus by Cre lentivirus injection is sufficient to trigger accelerated weight gain. Together, our results demonstrate that the lipoprotein receptor LRP1, which is critical in lipid metabolism, also regulates food intake and energy homeostasis in the adult central nervous system.

  10. Lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis in the adult central nervous system.

    Directory of Open Access Journals (Sweden)

    Qiang Liu

    2011-01-01

    Full Text Available Obesity is a growing epidemic characterized by excess fat storage in adipocytes. Although lipoprotein receptors play important roles in lipid uptake, their role in controlling food intake and obesity is not known. Here we show that the lipoprotein receptor LRP1 regulates leptin signaling and energy homeostasis. Conditional deletion of the Lrp1 gene in the brain resulted in an obese phenotype characterized by increased food intake, decreased energy consumption, and decreased leptin signaling. LRP1 directly binds to leptin and the leptin receptor complex and is required for leptin receptor phosphorylation and Stat3 activation. We further showed that deletion of the Lrp1 gene specifically in the hypothalamus by Cre lentivirus injection is sufficient to trigger accelerated weight gain. Together, our results demonstrate that the lipoprotein receptor LRP1, which is critical in lipid metabolism, also regulates food intake and energy homeostasis in the adult central nervous system.

  11. International regulations in capital standards in insurance companies and banking system of Serbia

    Directory of Open Access Journals (Sweden)

    Milić Dragana

    2014-01-01

    Full Text Available The emergence and expansion of the recent financial crisis has renewed the question of regulation and supervision of the financial system. Therefore, the question of managing financial risks is becoming increasingly popular and gaining more and more importance. Regulators have in recent years introduced capital standards based on specific sensitivity to risk. Based on defined issues, the starting point is the general hypothesis that the capital adequacy is a key base for measuring the resistance of the banking and insurance sector to market shocks. This paper will present the analytical, synthetic and general scientific methods. The comparative method is used in this paper to highlight the similarities and differences between Solvency II and Basel III and their operational efficiency.

  12. Neuronal expression of glucosylceramide synthase in central nervous system regulates body weight and energy homeostasis.

    Science.gov (United States)

    Nordström, Viola; Willershäuser, Monja; Herzer, Silke; Rozman, Jan; von Bohlen Und Halbach, Oliver; Meldner, Sascha; Rothermel, Ulrike; Kaden, Sylvia; Roth, Fabian C; Waldeck, Clemens; Gretz, Norbert; de Angelis, Martin Hrabě; Draguhn, Andreas; Klingenspor, Martin; Gröne, Hermann-Josef; Jennemann, Richard

    2013-01-01

    Hypothalamic neurons are main regulators of energy homeostasis. Neuronal function essentially depends on plasma membrane-located gangliosides. The present work demonstrates that hypothalamic integration of metabolic signals requires neuronal expression of glucosylceramide synthase (GCS; UDP-glucose:ceramide glucosyltransferase). As a major mechanism of central nervous system (CNS) metabolic control, we demonstrate that GCS-derived gangliosides interacting with leptin receptors (ObR) in the neuronal membrane modulate leptin-stimulated formation of signaling metabolites in hypothalamic neurons. Furthermore, ganglioside-depleted hypothalamic neurons fail to adapt their activity (c-Fos) in response to alterations in peripheral energy signals. Consequently, mice with inducible forebrain neuron-specific deletion of the UDP-glucose:ceramide glucosyltransferase gene (Ugcg) display obesity, hypothermia, and lower sympathetic activity. Recombinant adeno-associated virus (rAAV)-mediated Ugcg delivery to the arcuate nucleus (Arc) significantly ameliorated obesity, specifying gangliosides as seminal components for hypothalamic regulation of body energy homeostasis.

  13. Harnessing CRISPR/Cas systems for programmable transcriptional and post-transcriptional regulation

    KAUST Repository

    Mahas, Ahmed

    2017-11-29

    Genome editing has enabled broad advances and novel approaches in studies of gene function and structure; now, emerging methods aim to precisely engineer post-transcriptional processes. Developing precise, efficient molecular tools to alter the transcriptome holds great promise for biotechnology and synthetic biology applications. Different approaches have been employed for targeted degradation of RNA species in eukaryotes, but they lack programmability and versatility, thereby limiting their utility for diverse applications. The CRISPR/Cas9 system has been harnessed for genome editing in many eukaryotic species and, using a catalytically inactive Cas9 variant, the CRISPR/dCas9 system has been repurposed for transcriptional regulation. Recent studies have used other CRISPR/Cas systems for targeted RNA degradation and RNA-based manipulations. For example, Cas13a, a Type VI-A endonuclease, has been identified as an RNA-guided RNA ribonuclease and used for manipulation of RNA. Here, we discuss different modalities for targeted RNA interference with an emphasis on the potential applications of CRISPR/Cas systems as programmable transcriptional regulators for broad uses, including functional biology, biotechnology, and synthetic biology applications.

  14. Primary frequency regulation with Li-ion battery energy storage system: A case study for Denmark

    DEFF Research Database (Denmark)

    Swierczynski, Maciej Jozef; Stroe, Daniel Ioan; Stan, Ana-Irina

    2013-01-01

    Meeting ambitious goals of transition to distributed and environmentally-friendly renewable energy generation can be difficult to achieve without energy storage systems due to technical and economical challenges. Moreover, energy storage systems have a high potential of not only smoothing and imp...... electricity market. Moreover, in this paper a possible improvement of the Li-ion BESS energy management strategy is shown, which allows for obtaining the higher NPV....... lifetime, which introduces significant risk into the business model. This paper deals with the investigation of the lifetime of LiFeP04/C battery systems when they are used to provide primary frequency regulation service. A semi-empirical lifetime model for these battery cells was developed based...... on the results obtained from accelerated lifetime testing. The developed Li­-ion battery lifetime model is later a base for the analyses of the economic profitability of the investment in the Li-ion battery energy storage system (BESS), which delivers the primary frequency regulation service on the Danish...

  15. Harnessing CRISPR/Cas systems for programmable transcriptional and post-transcriptional regulation

    KAUST Repository

    Mahas, Ahmed; Neal Stewart, C.; Mahfouz, Magdy M.

    2017-01-01

    Genome editing has enabled broad advances and novel approaches in studies of gene function and structure; now, emerging methods aim to precisely engineer post-transcriptional processes. Developing precise, efficient molecular tools to alter the transcriptome holds great promise for biotechnology and synthetic biology applications. Different approaches have been employed for targeted degradation of RNA species in eukaryotes, but they lack programmability and versatility, thereby limiting their utility for diverse applications. The CRISPR/Cas9 system has been harnessed for genome editing in many eukaryotic species and, using a catalytically inactive Cas9 variant, the CRISPR/dCas9 system has been repurposed for transcriptional regulation. Recent studies have used other CRISPR/Cas systems for targeted RNA degradation and RNA-based manipulations. For example, Cas13a, a Type VI-A endonuclease, has been identified as an RNA-guided RNA ribonuclease and used for manipulation of RNA. Here, we discuss different modalities for targeted RNA interference with an emphasis on the potential applications of CRISPR/Cas systems as programmable transcriptional regulators for broad uses, including functional biology, biotechnology, and synthetic biology applications.

  16. Deployment strategy for battery energy storage system in distribution network based on voltage violation regulation

    Science.gov (United States)

    Wu, H.; Zhou, L.; Xu, T.; Fang, W. L.; He, W. G.; Liu, H. M.

    2017-11-01

    In order to improve the situation of voltage violation caused by the grid-connection of photovoltaic (PV) system in a distribution network, a bi-level programming model is proposed for battery energy storage system (BESS) deployment. The objective function of inner level programming is to minimize voltage violation, with the power of PV and BESS as the variables. The objective function of outer level programming is to minimize the comprehensive function originated from inner layer programming and all the BESS operating parameters, with the capacity and rated power of BESS as the variables. The differential evolution (DE) algorithm is applied to solve the model. Based on distribution network operation scenarios with photovoltaic generation under multiple alternative output modes, the simulation results of IEEE 33-bus system prove that the deployment strategy of BESS proposed in this paper is well adapted to voltage violation regulation invariable distribution network operation scenarios. It contributes to regulating voltage violation in distribution network, as well as to improve the utilization of PV systems.

  17. Reward, addiction, and emotion regulation systems associated with rejection in love.

    Science.gov (United States)

    Fisher, Helen E; Brown, Lucy L; Aron, Arthur; Strong, Greg; Mashek, Debra

    2010-07-01

    Romantic rejection causes a profound sense of loss and negative affect. It can induce clinical depression and in extreme cases lead to suicide and/or homicide. To begin to identify the neural systems associated with this natural loss state, we used functional magnetic resonance imaging to study 10 women and 5 men who had recently been rejected by a partner but reported they were still intensely "in love." Participants alternately viewed a photograph of their rejecting beloved and a photograph of a familiar, individual, interspersed with a distraction-attention task. Their responses while looking at their rejecter included love, despair, good, and bad memories, and wondering why this happened. Activation specific to the image of the beloved occurred in areas associated with gains and losses, craving and emotion regulation and included the ventral tegmental area (VTA) bilaterally, ventral striatum, medial and lateral orbitofrontal/prefrontal cortex, and cingulate gyrus. Compared with data from happily-in-love individuals, the regional VTA activation suggests that mesolimbic reward/survival systems are involved in romantic passion regardless of whether one is happily or unhappily in love. Forebrain activations associated with motivational relevance, gain/loss, cocaine craving, addiction, and emotion regulation suggest that higher-order systems subject to experience and learning also may mediate the rejection reaction. The results show activation of reward systems, previously identified by monetary stimuli, in a natural, endogenous, negative emotion state. Activation of areas involved in cocaine addiction may help explain the obsessive behaviors associated with rejection in love.

  18. Improved gravitational search algorithm for parameter identification of water turbine regulation system

    International Nuclear Information System (INIS)

    Chen, Zhihuan; Yuan, Xiaohui; Tian, Hao; Ji, Bin

    2014-01-01

    Highlights: • We propose an improved gravitational search algorithm (IGSA). • IGSA is applied to parameter identification of water turbine regulation system (WTRS). • WTRS is modeled by considering the impact of turbine speed on torque and water flow. • Weighted objective function strategy is applied to parameter identification of WTRS. - Abstract: Parameter identification of water turbine regulation system (WTRS) is crucial in precise modeling hydropower generating unit (HGU) and provides support for the adaptive control and stability analysis of power system. In this paper, an improved gravitational search algorithm (IGSA) is proposed and applied to solve the identification problem for WTRS system under load and no-load running conditions. This newly algorithm which is based on standard gravitational search algorithm (GSA) accelerates convergence speed with combination of the search strategy of particle swarm optimization and elastic-ball method. Chaotic mutation which is devised to stepping out the local optimal with a certain probability is also added into the algorithm to avoid premature. Furthermore, a new kind of model associated to the engineering practices is built and analyzed in the simulation tests. An illustrative example for parameter identification of WTRS is used to verify the feasibility and effectiveness of the proposed IGSA, as compared with standard GSA and particle swarm optimization in terms of parameter identification accuracy and convergence speed. The simulation results show that IGSA performs best for all identification indicators

  19. Responses of grapevine rootstocks to drought through altered root system architecture and root transcriptomic regulations.

    Science.gov (United States)

    Yıldırım, Kubilay; Yağcı, Adem; Sucu, Seda; Tunç, Sümeyye

    2018-06-01

    Roots are the major interface between the plant and various stress factors in the soil environment. Alteration of root system architecture (RSA) (root length, spread, number and length of lateral roots) in response to environmental changes is known to be an important strategy for plant adaptation and productivity. In light of ongoing climate changes and global warming predictions, the breeding of drought-tolerant grapevine cultivars is becoming a crucial factor for developing a sustainable viticulture. Root-trait modeling of grapevine rootstock for drought stress scenarios, together with high-throughput phenotyping and genotyping techniques, may provide a valuable background for breeding studies in viticulture. Here, tree grafted grapevine rootstocks (110R, 5BB and 41B) having differential RSA regulations and drought tolerance were investigated to define their drought dependent root characteristics. Root area, root length, ramification and number of root tips reduced less in 110R grafted grapevines compared to 5BB and 41B grafted ones during drought treatment. Root relative water content as well as total carbohydrate and nitrogen content were found to be much higher in the roots of 110R than it was in the roots of other rootstocks under drought. Microarray-based root transcriptome profiling was also conducted on the roots of these rootstocks to identify their gene regulation network behind drought-dependent RSA alterations. Transcriptome analysis revealed totally 2795, 1196 and 1612 differentially expressed transcripts at the severe drought for the roots of 110R, 5BB and 41B, respectively. According to this transcriptomic data, effective root elongation and enlargement performance of 110R were suggested to depend on three transcriptomic regulations. First one is the drought-dependent induction in sugar and protein transporters genes (SWEET and NRT1/PTR) in the roots of 110R to facilitate carbohydrate and nitrogen accumulation. In the roots of the same rootstock

  20. Systems biology of adipose tissue metabolism: regulation of growth, signaling and inflammation.

    Science.gov (United States)

    Manteiga, Sara; Choi, Kyungoh; Jayaraman, Arul; Lee, Kyongbum

    2013-01-01

    Adipose tissue (AT) depots actively regulate whole body energy homeostasis by orchestrating complex communications with other physiological systems as well as within the tissue. Adipocytes readily respond to hormonal and nutritional inputs to store excess nutrients as intracellular lipids or mobilize the stored fat for utilization. Co-ordinated regulation of metabolic pathways balancing uptake, esterification, and hydrolysis of lipids is accomplished through positive and negative feedback interactions of regulatory hubs comprising several pleiotropic protein kinases and nuclear receptors. Metabolic regulation in adipocytes encompasses biogenesis and remodeling of uniquely large lipid droplets (LDs). The regulatory hubs also function as energy and nutrient sensors, and integrate metabolic regulation with intercellular signaling. Over-nutrition causes hypertrophic expansion of adipocytes, which, through incompletely understood mechanisms, initiates a cascade of metabolic and signaling events leading to tissue remodeling and immune cell recruitment. Macrophage activation and polarization toward a pro-inflammatory phenotype drives a self-reinforcing cycle of pro-inflammatory signals in the AT, establishing an inflammatory state. Sustained inflammation accelerates lipolysis and elevates free fatty acids in circulation, which robustly correlates with development of obesity-related diseases. The adipose regulatory network coupling metabolism, growth, and signaling of multiple cell types is exceedingly complex. While components of the regulatory network have been individually studied in exquisite detail, systems approaches have rarely been utilized to comprehensively assess the relative engagements of the components. Thus, need and opportunity exist to develop quantitative models of metabolic and signaling networks to achieve a more complete understanding of AT biology in both health and disease. Copyright © 2013 Wiley Periodicals, Inc.

  1. Regulation of sleep by neuropeptide Y-like system in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Chunxia He

    Full Text Available Sleep is important for maintenance of normal physiology in animals. In mammals, neuropeptide Y (NPY, a homolog of Drosophila neuropeptide F (NPF, is involved in sleep regulation, with different effects in human and rat. However, the function of NPF on sleep in Drosophila melanogaster has not yet been described. In this study, we investigated the effects of NPF and its receptor-neuropeptide F receptor (NPFR1 on Drosophila sleep. Male flies over-expressing NPF or NPFR1 exhibited increased sleep during the nighttime. Further analysis demonstrated that sleep episode duration during nighttime was greatly increased and sleep latency was significantly reduced, indicating that NPF and NPFR1 promote sleep quality, and their action on sleep is not because of an impact of the NPF signal system on development. Moreover, the homeostatic regulation of flies after sleep deprivation was disrupted by altered NPF signaling, since sleep deprivation decreased transcription of NPF in control flies, and there were less sleep loss during sleep deprivation and less sleep gain after sleep deprivation in flies overexpressing NPF and NPFR1 than in control flies, suggesting that NPF system auto-regulation plays an important role in sleep homeostasis. However, these effects did not occur in females, suggesting a sex-dependent regulatory function in sleep for NPF and NPFR1. NPF in D1 brain neurons showed male-specific expression, providing the cellular locus for male-specific regulation of sleep by NPF and NPFR1. This study brings a new understanding into sleep studies of a sexually dimorphic regulatory mode in female and male flies.

  2. An Extended System Frequency Response Model Considering Wind Power Participation in Frequency Regulation

    Directory of Open Access Journals (Sweden)

    Yi Tang

    2017-11-01

    Full Text Available With increasing penetration of wind power into the power system, wind power participation in frequency regulation is regarded as a beneficial strategy to improve the dynamic frequency response characteristics of power systems. The traditional power system frequency response (SFR model, which only includes synchronous generators, is no longer suitable for power systems with high penetrated wind power. An extended SFR model, based on the reduced-order model of wind turbine generator (WTG and the traditional SFR model, is presented in this paper. In the extended SFR model, the reduced-order model of WTG with combined frequency control is deduced by employing small signal analysis theory. Afterwards, the stability analysis of a closed-loop control system for the extended SFR model is carried out. Time-domain simulations using a test system are performed to validate the effectiveness of the extended SFR model; this model can provide a simpler, clearer and faster way to analyze the dynamic frequency response characteristic for a high-wind integrated power systems. The impact of additional frequency control parameters and wind speed disturbances on the system dynamic frequency response characteristics are investigated.

  3. The Pseudomonas aeruginosa Chp Chemosensory System Regulates Intracellular cAMP Levels by Modulating Adenylate Cyclase Activity

    Science.gov (United States)

    Fulcher, Nanette B.; Holliday, Phillip M.; Klem, Erich; Cann, Martin J.; Wolfgang, Matthew C.

    2010-01-01

    Summary Multiple virulence systems in the opportunistic pathogen Pseudomonas aeruginosa are regulated by the second messenger signaling molecule adenosine 3’, 5’-cyclic monophosphate (cAMP). Production of cAMP by the putative adenylate cyclase enzyme CyaB represents a critical control point for virulence gene regulation. To identify regulators of CyaB, we screened a transposon insertion library for mutants with reduced intracellular cAMP. The majority of insertions resulting in reduced cAMP mapped to the Chp gene cluster encoding a putative chemotaxis-like chemosensory system. Further genetic analysis of the Chp system revealed that it has both positive and negative effects on intracellular cAMP and that it regulates cAMP levels by modulating CyaB activity. The Chp system was previously implicated in the production and function of type IV pili (TFP). Given that cAMP and the cAMP-dependent transcriptional regulator Vfr control TFP biogenesis gene expression, we explored the relationship between cAMP, the Chp system and TFP regulation. We discovered that the Chp system controls TFP production through modulation of cAMP while control of TFP-dependent twitching motility is cAMP-independent. Overall, our data define a novel function for a chemotaxis-like system in controlling cAMP production and establish a regulatory link between the Chp system, TFP and other cAMP-dependent virulence systems. PMID:20345659

  4. Blood pressure regulation III: what happens when one system must serve two masters: temperature and pressure regulation?

    Science.gov (United States)

    Kenney, W Larry; Stanhewicz, Anna E; Bruning, Rebecca S; Alexander, Lacy M

    2014-03-01

    When prolonged intense exercise is performed at high ambient temperatures, cardiac output must meet dual demands for increased blood flow to contracting muscle and to the skin. The literature has commonly painted this scenario as a fierce competition, wherein one circulation preserves perfusion at the expense of the other, with the regulated maintenance of blood pressure as the ultimate goal. This review redefines this scenario as commensalism, an integrated balance of regulatory control where one circulation benefits with little functional effect on the other. In young, healthy subjects, arterial pressure rarely falls to any great extent during either extreme passive heating or prolonged dynamic exercise in the heat, nor does body temperature rise disproportionately due to a compromised skin blood flow. Rather, it often takes the superimposition of additional stressors--e.g., dehydration or simulated hemorrhage--upon heat stress to substantially impact blood pressure regulation.

  5. The Csr system regulates genome-wide mRNA stability and transcription and thus gene expression in Escherichia coli.

    Science.gov (United States)

    Esquerré, Thomas; Bouvier, Marie; Turlan, Catherine; Carpousis, Agamemnon J; Girbal, Laurence; Cocaign-Bousquet, Muriel

    2016-04-26

    Bacterial adaptation requires large-scale regulation of gene expression. We have performed a genome-wide analysis of the Csr system, which regulates many important cellular functions. The Csr system is involved in post-transcriptional regulation, but a role in transcriptional regulation has also been suggested. Two proteins, an RNA-binding protein CsrA and an atypical signaling protein CsrD, participate in the Csr system. Genome-wide transcript stabilities and levels were compared in wildtype E. coli (MG1655) and isogenic mutant strains deficient in CsrA or CsrD activity demonstrating for the first time that CsrA and CsrD are global negative and positive regulators of transcription, respectively. The role of CsrA in transcription regulation may be indirect due to the 4.6-fold increase in csrD mRNA concentration in the CsrA deficient strain. Transcriptional action of CsrA and CsrD on a few genes was validated by transcriptional fusions. In addition to an effect on transcription, CsrA stabilizes thousands of mRNAs. This is the first demonstration that CsrA is a global positive regulator of mRNA stability. For one hundred genes, we predict that direct control of mRNA stability by CsrA might contribute to metabolic adaptation by regulating expression of genes involved in carbon metabolism and transport independently of transcriptional regulation.

  6. Royal Military College of Canada SLOWPOKE-2 facility. Integrated regulating and instrumentation system (SIRCIS) upgrade project

    International Nuclear Information System (INIS)

    Corcoran, W.P.; Nielsen, K.S.; Kelly, D.G.; Weir, R.D.

    2013-01-01

    The SLOWPOKE-2 Facility at the Royal Military College of Canada has operated the only digitally controlled SLOWPOKE reactor since 2001 (Version 1.0). The present work describes ongoing project development to provide a robust digital reactor control system that is consistent with Aging Management as summarized in the Facility's Life Cycle Management and Maintenance Plan. The project has transitioned from a post-graduate research activity to a comprehensively managed project supported by a team of RMCC professional and technical staff who have delivered an update of the V1.1 system software and hardware implementation that is consistent with best Canadian nuclear industry practice. The challenges associated with the implementation of Version 2.0 in February 2012, the lessons learned from this implementation, and the applications of these lessons to a redesign and rewrite of the RMCC SLOWPOKE-2 digital instrumentation and regulating system (Version 3) are discussed. (author)

  7. Engineering FKBP-Based Destabilizing Domains to Build Sophisticated Protein Regulation Systems.

    Directory of Open Access Journals (Sweden)

    Wenlin An

    Full Text Available Targeting protein stability with small molecules has emerged as an effective tool to control protein abundance in a fast, scalable and reversible manner. The technique involves tagging a protein of interest (POI with a destabilizing domain (DD specifically controlled by a small molecule. The successful construction of such fusion proteins may, however, be limited by functional interference of the DD epitope with electrostatic interactions required for full biological function of proteins. Another drawback of this approach is the remaining endogenous protein. Here, we combined the Cre-LoxP system with an advanced DD and generated a protein regulation system in which the loss of an endogenous protein, in our case the tumor suppressor PTEN, can be coupled directly with a conditionally fine-tunable DD-PTEN. This new system will consolidate and extend the use of DD-technology to control protein function precisely in living cells and animal models.

  8. Main tasks of studying strong regulation of excitation of complex electrical system generators

    Energy Technology Data Exchange (ETDEWEB)

    Gruzdev, I.A.; Yekimova, M.M.

    1982-01-01

    A survey is made of the current state of studies of the damping properties of complex electricity systems. The calculation programs of stability are based on frequency methods using the method of D-division. Now, when ARV of strong effect dominates at the SG, the task of coordinating their adjustments develops. Consequently, the following questions are discussed: study of the properties of quality functional with several points of regulation in the circuits of different structure; development of the efficient procedures for coordinating the ARV adjustment of the related energy systems; and creation of resources for solving these tasks. Results are presented of coordinating the ARV adjustments of the generators of the 3-machine electricity system. As an example, nonlinear relationships are shown between the obtained degree of stability and the coefficient of stabilization.

  9. A new hydraulic regulation method on district heating system with distributed variable-speed pumps

    International Nuclear Information System (INIS)

    Wang, Hai; Wang, Haiying; Zhu, Tong

    2017-01-01

    Highlights: • A hydraulic regulation method was presented for district heating with distributed variable speed pumps. • Information and automation technologies were utilized to support the proposed method. • A new hydraulic model was developed for distributed variable speed pumps. • A new optimization model was developed based on genetic algorithm. • Two scenarios of a multi-source looped system was illustrated to validate the method. - Abstract: Compared with the hydraulic configuration based on the conventional central circulating pump, a district heating system with distributed variable-speed-pumps configuration can often save 30–50% power consumption on circulating pumps with frequency inverters. However, the hydraulic regulations on distributed variable-speed-pumps configuration could be more complicated than ever while all distributed pumps need to be adjusted to their designated flow rates. Especially in a multi-source looped structure heating network where the distributed pumps have strongly coupled and severe non-linear hydraulic connections with each other, it would be rather difficult to maintain the hydraulic balance during the regulations. In this paper, with the help of the advanced automation and information technologies, a new hydraulic regulation method was proposed to achieve on-site hydraulic balance for the district heating systems with distributed variable-speed-pumps configuration. The proposed method was comprised of a new hydraulic model, which was developed to adapt the distributed variable-speed-pumps configuration, and a calibration model with genetic algorithm. By carrying out the proposed method step by step, the flow rates of all distributed pumps can be progressively adjusted to their designated values. A hypothetic district heating system with 2 heat sources and 10 substations was taken as a case study to illustrate the feasibility of the proposed method. Two scenarios were investigated respectively. In Scenario I, the

  10. The multiple functions of the endocannabinoid system: a focus on the regulation of food intake

    Directory of Open Access Journals (Sweden)

    Tibiriça Eduardo

    2010-01-01

    Full Text Available Abstract Background Cannabis sativa (also known as marijuana has been cultivated by man for more than 5,000 years. However, there was a rise in its use in the 20th century for recreational, religious or spiritual, and medicinal purposes. The main psychoactive constituent of cannabis, whose structure was identified in the 1960's, is Δ9-tetrahydrocannabinol. On the other hand, the discovery of cannabinoid receptors and their endogenous agonists took place only very recently. In fact, the first cannabinoid receptor (CB1 was cloned in 1990, followed 3 years later by the characterization of a second cannabinoid receptor (CB2. Since the 19th century, the use of cannabis has been reported to stimulate appetite and increase the consumption of sweet and tasty food, sometimes resulting in significant weight gain. The recent description of the endocannabinoid system, not only in the central nervous system but also in peripheral tissues, points to its involvement in the regulation of appetite, food intake and energy metabolism. Consequently, the pharmacological modulation of the over-activity of this system could be useful in the treatment of the metabolic syndrome. Conclusions The endocannabinoid system has important physiological functions not only in the central nervous system but also in peripheral tissues. The activation of central CB1 receptors, particularly in hypothalamic nuclei and in the limbic system, is involved in the regulation of feeding behavior, and especially in the control of the intake of palatable food. In the periphery, cannabinoid receptors are present in adipocytes, skeletal muscle, gastrointestinal tract and liver, modulating energy metabolism.

  11. Dicarbonyl stress and glyoxalase enzyme system regulation in human skeletal muscle.

    Science.gov (United States)

    Mey, Jacob T; Blackburn, Brian K; Miranda, Edwin R; Chaves, Alec B; Briller, Joan; Bonini, Marcelo G; Haus, Jacob M

    2018-02-01

    Skeletal muscle insulin resistance is a hallmark of Type 2 diabetes (T2DM) and may be exacerbated by protein modifications by methylglyoxal (MG), known as dicarbonyl stress. The glyoxalase enzyme system composed of glyoxalase 1/2 (GLO1/GLO2) is the natural defense against dicarbonyl stress, yet its protein expression, activity, and regulation remain largely unexplored in skeletal muscle. Therefore, this study investigated dicarbonyl stress and the glyoxalase enzyme system in the skeletal muscle of subjects with T2DM (age: 56 ± 5 yr.; BMI: 32 ± 2 kg/m 2 ) compared with lean healthy control subjects (LHC; age: 27 ± 1 yr.; BMI: 22 ± 1 kg/m 2 ). Skeletal muscle biopsies obtained from the vastus lateralis at basal and insulin-stimulated states of the hyperinsulinemic (40 mU·m -2 ·min -1 )-euglycemic (5 mM) clamp were analyzed for proteins related to dicarbonyl stress and glyoxalase biology. At baseline, T2DM had increased carbonyl stress and lower GLO1 protein expression (-78.8%), which inversely correlated with BMI, percent body fat, and HOMA-IR, while positively correlating with clamp-derived glucose disposal rates. T2DM also had lower NRF2 protein expression (-31.6%), which is a positive regulator of GLO1, while Keap1 protein expression, a negative regulator of GLO1, was elevated (207%). Additionally, insulin stimulation during the clamp had a differential effect on NRF2, Keap1, and MG-modified protein expression. These data suggest that dicarbonyl stress and the glyoxalase enzyme system are dysregulated in T2DM skeletal muscle and may underlie skeletal muscle insulin resistance. Whether these phenotypic differences contribute to the development of T2DM warrants further investigation.

  12. Bim: guardian of tissue homeostasis and critical regulator of the immune system, tumorigenesis and bone biology.

    Science.gov (United States)

    Akiyama, Toru; Tanaka, Sakae

    2011-08-01

    One of the most important roles of apoptosis is the maintenance of tissue homeostasis. Impairment of apoptosis leads to a number of pathological conditions. In response to apoptotic signals, various proteins are activated in a pathway and signal-specific manner. Recently, the pro-apoptotic molecule Bim has attracted increasing attention as a pivotal regulator of tissue homeostasis. The Bim expression level is strictly controlled in both transcriptional and post-transcriptional levels. This control is dependent on cell, tissue and apoptotic stimuli. The phenotype of Bim-deficient mice is a systemic lupus erythematosus-like autoimmune disease with an abnormal accumulation of hematopoietic cells. Bim is thus a critical regulator of hematopoietic cells and immune system. Further studies have revealed the critical roles of Bim in various normal and pathological conditions, including bone homeostasis and tumorigenesis. The current understanding of Bim signaling and roles in the maintenance of tissue homeostasis is reviewed in this paper, focusing on the immune system, bone biology and tumorigenesis to illustrate the diversified role of Bim.

  13. Analysing stratified medicine business models and value systems: innovation-regulation interactions.

    Science.gov (United States)

    Mittra, James; Tait, Joyce

    2012-09-15

    Stratified medicine offers both opportunities and challenges to the conventional business models that drive pharmaceutical R&D. Given the increasingly unsustainable blockbuster model of drug development, due in part to maturing product pipelines, alongside increasing demands from regulators, healthcare providers and patients for higher standards of safety, efficacy and cost-effectiveness of new therapies, stratified medicine promises a range of benefits to pharmaceutical and diagnostic firms as well as healthcare providers and patients. However, the transition from 'blockbusters' to what might now be termed 'niche-busters' will require the adoption of new, innovative business models, the identification of different and perhaps novel types of value along the R&D pathway, and a smarter approach to regulation to facilitate innovation in this area. In this paper we apply the Innogen Centre's interdisciplinary ALSIS methodology, which we have developed for the analysis of life science innovation systems in contexts where the value creation process is lengthy, expensive and highly uncertain, to this emerging field of stratified medicine. In doing so, we consider the complex collaboration, timing, coordination and regulatory interactions that shape business models, value chains and value systems relevant to stratified medicine. More specifically, we explore in some depth two convergence models for co-development of a therapy and diagnostic before market authorisation, highlighting the regulatory requirements and policy initiatives within the broader value system environment that have a key role in determining the probable success and sustainability of these models. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. The Impact of Transactive Memory System and Interaction Platform in Collaborative Knowledge Construction on Social Presence and Self-Regulation

    Science.gov (United States)

    Yilmaz, Ramazan; Karaoglan Yilmaz, Fatma Gizem; Kilic Cakmak, Ebru

    2017-01-01

    The purpose of this study is to examine the impacts of transactive memory system (TMS) and interaction platforms in computer-supported collaborative learning (CSCL) on social presence perceptions and self-regulation skills of learners. Within the scope of the study, social presence perceptions and self-regulation skills of students in…

  15. A Sliding Mode LCO Regulation Strategy for Dual-Parallel Underactuated UAV Systems Using Synthetic Jet Actuators

    Directory of Open Access Journals (Sweden)

    N. Ramos-Pedroza

    2015-01-01

    careful algebraic manipulation in the regulation error system development, along with innovative design of the sliding surface. A detailed model of the UAV LCO dynamics is utilized, and a rigorous analysis is provided to prove asymptotic regulation of the pitching and plunging displacements. Numerical simulation results are provided to demonstrate the performance of the control law.

  16. Long non-coding RNAs as regulators of the endocrine system.

    Science.gov (United States)

    Knoll, Marko; Lodish, Harvey F; Sun, Lei

    2015-03-01

    Long non-coding RNAs (lncRNAs) are a large and diverse group of RNAs that are often lineage-specific and that regulate multiple biological functions. Many are nuclear and are essential parts of ribonucleoprotein complexes that modify chromatin segments and establish active or repressive chromatin states; others are cytosolic and regulate the stability of mRNA or act as microRNA sponges. This Review summarizes the current knowledge of lncRNAs as regulators of the endocrine system, with a focus on the identification and mode of action of several endocrine-important lncRNAs. We highlight lncRNAs that have a role in the development and function of pancreatic β cells, white and brown adipose tissue, and other endocrine organs, and discuss the involvement of these molecules in endocrine dysfunction (for example, diabetes mellitus). We also address the associations of lncRNAs with nuclear receptors involved in major hormonal signalling pathways, such as estrogen and androgen receptors, and the relevance of these associations in certain endocrine cancers.

  17. Systems assessment of transcriptional regulation on central carbon metabolism by Cra and CRP.

    Science.gov (United States)

    Kim, Donghyuk; Seo, Sang Woo; Gao, Ye; Nam, Hojung; Guzman, Gabriela I; Cho, Byung-Kwan; Palsson, Bernhard O

    2018-04-06

    Two major transcriptional regulators of carbon metabolism in bacteria are Cra and CRP. CRP is considered to be the main mediator of catabolite repression. Unlike for CRP, in vivo DNA binding information of Cra is scarce. Here we generate and integrate ChIP-exo and RNA-seq data to identify 39 binding sites for Cra and 97 regulon genes that are regulated by Cra in Escherichia coli. An integrated metabolic-regulatory network was formed by including experimentally-derived regulatory information and a genome-scale metabolic network reconstruction. Applying analysis methods of systems biology to this integrated network showed that Cra enables optimal bacterial growth on poor carbon sources by redirecting and repressing glycolysis flux, by activating the glyoxylate shunt pathway, and by activating the respiratory pathway. In these regulatory mechanisms, the overriding regulatory activity of Cra over CRP is fundamental. Thus, elucidation of interacting transcriptional regulation of core carbon metabolism in bacteria by two key transcription factors was possible by combining genome-wide experimental measurement and simulation with a genome-scale metabolic model.

  18. A multi-scale model of hepcidin promoter regulation reveals factors controlling systemic iron homeostasis.

    Directory of Open Access Journals (Sweden)

    Guillem Casanovas

    2014-01-01

    Full Text Available Systemic iron homeostasis involves a negative feedback circuit in which the expression level of the peptide hormone hepcidin depends on and controls the iron blood levels. Hepcidin expression is regulated by the BMP6/SMAD and IL6/STAT signaling cascades. Deregulation of either pathway causes iron-related diseases such as hemochromatosis or anemia of inflammation. We quantitatively analyzed how BMP6 and IL6 control hepcidin expression. Transcription factor (TF phosphorylation and reporter gene expression were measured under co-stimulation conditions, and the promoter was perturbed by mutagenesis. Using mathematical modeling, we systematically analyzed potential mechanisms of cooperative and competitive promoter regulation by the transcription factors, and experimentally validated the model predictions. Our results reveal that hepcidin cross-regulation primarily occurs by combinatorial transcription factor binding to the promoter, whereas signaling crosstalk is insignificant. We find that the presence of two BMP-responsive elements enhances the steepness of the promoter response towards the iron-sensing BMP signaling axis, which promotes iron homeostasis in vivo. IL6 co-stimulation reduces the promoter sensitivity towards the BMP signal, because the SMAD and STAT transcription factors compete for recruiting RNA polymerase to the transcription start site. This may explain why inflammatory signals disturb iron homeostasis in anemia of inflammation. Taken together, our results reveal why the iron homeostasis circuit is sensitive to perturbations implicated in disease.

  19. Interaction and developmental activation of two neuroendocrine systems that regulate light-mediated skin pigmentation.

    Science.gov (United States)

    Bertolesi, Gabriel E; Song, Yi N; Atkinson-Leadbeater, Karen; Yang, Jung-Lynn J; McFarlane, Sarah

    2017-07-01

    Lower vertebrates use rapid light-regulated changes in skin colour for camouflage (background adaptation) or during circadian variation in irradiance levels. Two neuroendocrine systems, the eye/alpha-melanocyte-stimulating hormone (α-MSH) and the pineal complex/melatonin circuits, regulate the process through their respective dispersion and aggregation of pigment granules (melanosomes) in skin melanophores. During development, Xenopus laevis tadpoles raised on a black background or in the dark perceive less light sensed by the eye and darken in response to increased α-MSH secretion. As embryogenesis proceeds, the pineal complex/melatonin circuit becomes the dominant regulator in the dark and induces lightening of the skin of larvae. The eye/α-MSH circuit continues to mediate darkening of embryos on a black background, but we propose the circuit is shut down in complete darkness in part by melatonin acting on receptors expressed by pituitary cells to inhibit the expression of pomc, the precursor of α-MSH. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Transport systems of Ventricaria ventricosa: asymmetry of the hyper- and hypotonic regulation mechanisms.

    Science.gov (United States)

    Bisson, M A; Beilby, M J

    2008-01-01

    Hyper- and hypotonic stresses elicit apparently symmetrical responses in the alga Ventricaria. With hypertonic stress, membrane potential difference (PD) between the vacuole and the external medium becomes more positive, conductance at positive PDs (Gmpos) increases and KCl is actively taken up to increase turgor. With hypotonic stress, the membrane PD becomes more negative, conductance at negative PDs (Gmneg) increases and KCl is lost to decrease turgor. We used inhibitors that affect active transport to determine whether agents that inhibit the K(+) pump and hypertonic regulation also inhibit hypotonic regulatory responses. Cells whose turgor pressure was held low by the pressure probe (turgor-clamped) exhibited the same response as cells challenged by hyperosmotic medium, although the response was maintained longer than in osmotically challenged cells, which regulate turgor. The role of active K(+) transport was confirmed by the effects of decreased light, dichlorophenyldimethyl urea and diethylstilbestrol, which induced a uniformly low conductance (quiet state). Cells clamped to high turgor exhibited the same response as cells challenged by hypo-osmotic medium, but the response was similarly transient, making effects of inhibitors hard to determine. Unlike clamped cells, cells challenged by hypo-osmotic medium responded to inhibitors with rapid, transient, negative-going PDs, with decreased Gmneg and increased Gmpos (linearized I-V), achieving the quiet state as PD recovered. These changes are different from those exerted on the pump state, indicating that different transport systems are responsible for turgor regulation in the two cases.

  1. The regulation of visitors conduction activity in the State System os Brazilian Conservation Units

    Directory of Open Access Journals (Sweden)

    Cristina Alves Nascimento

    2016-08-01

    Full Text Available Beyond to conserving biodiversity, conservation units must promote public use in contact with nature, assisting in increasing the economic resource of the area, approximating the society to nature and promoting their sustainable use. In Brazil, there are rules of the Ministry of Environment and Chico Mendes Institute for Biodiversity Conservation that regulate the conduction of visitors in federal conservation units. Remains to know how the activity is regulated in other spheres of the National Conservation Units System. Therefore, this article purpose to identify the legal basis for the conduction of visitors in the state conservation units and their adherence to guidelines of the Ministry of Environment. The methodology consisted in documentary research and data survey of the legal basis, done through visits to websites and sending e-mails to state management agencies. Adherence to the guidelines of the regulations was done through the evaluation to fulfillment or not from them. Legal basis were found in 18.5% of federal units of Brazil, being that only Espírito Santo and Rio de Janeiro meet almost all of the guideline. The conclusion was that there is a long way to go forward as the creation of rules and procedures that simultaneously encourage visitation accompanied to qualified conductors and biodiversity conservation. It is recommended greater efforts of state management agencies for the development of these legal basis, promoting improvements in desenvolviment of the activity and awareness of society.

  2. A Phosphorylation Switch on Lon Protease Regulates Bacterial Type III Secretion System in Host

    Directory of Open Access Journals (Sweden)

    Xiaofeng Zhou

    2018-01-01

    Full Text Available Most pathogenic bacteria deliver virulence factors into host cytosol through type III secretion systems (T3SS to perturb host immune responses. The expression of T3SS is often repressed in rich medium but is specifically induced in the host environment. The molecular mechanisms underlying host-specific induction of T3SS expression is not completely understood. Here we demonstrate in Xanthomonas citri that host-induced phosphorylation of the ATP-dependent protease Lon stabilizes HrpG, the master regulator of T3SS, conferring bacterial virulence. Ser/Thr/Tyr phosphoproteome analysis revealed that phosphorylation of Lon at serine 654 occurs in the citrus host. In rich medium, Lon represses T3SS by degradation of HrpG via recognition of its N terminus. Genetic and biochemical data indicate that phosphorylation at serine 654 deactivates Lon proteolytic activity and attenuates HrpG proteolysis. Substitution of alanine for Lon serine 654 resulted in repression of T3SS gene expression in the citrus host through robust degradation of HrpG and reduced bacterial virulence. Our work reveals a novel mechanism for distinct regulation of bacterial T3SS in different environments. Additionally, our data provide new insight into the role of protein posttranslational modification in the regulation of bacterial virulence.

  3. Design of power auto-regulating system's high reliability controller for 200 MW nuclear heating reactor

    International Nuclear Information System (INIS)

    An Zhencai; Liu Longzhi; Chen Yuan

    1996-01-01

    The paper mainly introduces power auto-regulating system's high reliability controller for 200 MW Nuclear Heating Reactor. The controller is implemented with excellent performance 16 bit single chip microcomputer 8097. Master controller and 10 digit samplers are blocked. Each and every block's hardware is identical. These blocks communicate each other through 8 bit BUS and operate synchronously by united clock and reset signal and are designed with three redundancies. The identity comparison principle through two-out-of three is also introduced. The test proves that designing scheme is feasible

  4. The role of volume-sensitive ion transport systems in regulation of epithelial transport

    DEFF Research Database (Denmark)

    Hoffmann, Else Kay; Schettino, T; Marshall, W S

    2007-01-01

    This review focuses on using the knowledge on volume-sensitive transport systems in Ehrlich ascites tumour cells and NIH-3T3 cells to elucidate osmotic regulation of salt transport in epithelia. Using the intestine of the European eel (Anguilla anguilla) (an absorptive epithelium of the type...... on the apical side and the Na+/K+ ATPase, NKCC1 and a K+ channel on the basolateral side. Osmotic control of Cl- secretion across the operculum epithelium includes: (i) hyperosmotic shrinkage activation of NKCC1 via PKC, MLCK, p38, OSR1 and SPAK; (ii) deactivation of NKCC by hypotonic cell swelling...

  5. MODERN APPROACHES TO THE IMPLEMENTATION OF MONETARY POLICY AND THE REGULATION OF FINANCIAL SYSTEMS

    Directory of Open Access Journals (Sweden)

    Radu CUHAL

    2013-01-01

    Full Text Available This study determines the modern approaches to the implementation of monetary policy and regulation of financial systems. Set of measures to prevent and overcome the financial crisis is grounded taking into consideration different areas of research and the IMF. New tasks of monetary policy in central banks are specified and they are intended to ensure the financial stability of the state (within the common fiscal policy. The main directions of elaboration and implementation of new monetary policy mechanism, which is intended to ensure the effective solution of problems in macro prudential supervision and financial stability, are examined.

  6. Modern approaches to the implementation of monetary policy and the regulation of financial systems

    Directory of Open Access Journals (Sweden)

    Basistîi Nicolae

    2013-01-01

    Full Text Available This study determines the modern approaches to the implementation of monetary policy and regulation of financial systems. Set of measures to prevent and overcome the financial crisis is grounded taking into consideration different areas of research and the IMF.New tasks of monetary policy in central banks are specified and they are intended to ensure the financial stability of the state (within the common fiscal policy.The main directions of elaboration and implementation of new monetary policy mechanism, which is intended to ensure the effective solution of problems in macro prudential supervision and financial stability, are examined.

  7. Pressure Regulators as Valves for Saving Compressed Air and their Influence on System Dynamics

    Directory of Open Access Journals (Sweden)

    Dvořák Lukáš

    2015-01-01

    Full Text Available Pressure regulators in the field of pneumatic mechanisms can be used as valves for saving compressed air. For example it can be used to reduce the pressure when the piston rod is retracting unloaded and thus it is possible to save some energy. However the problem is that saving valve can significantly affect the dynamics of the pneumatic system. The lower pressure in the piston rod chamber causes extension of time for retraction of the piston rod. This article compare the air consumption experimentally determined and calculated, measured curves of pressure in cylinder chambers and piston speed when saving valve is set up differently.

  8. Pressure Regulators as Valves for Saving Compressed Air and their Influence on System Dynamics

    Science.gov (United States)

    Dvořák, Lukáš; Fojtášek, Kamil

    2015-05-01

    Pressure regulators in the field of pneumatic mechanisms can be used as valves for saving compressed air. For example it can be used to reduce the pressure when the piston rod is retracting unloaded and thus it is possible to save some energy. However the problem is that saving valve can significantly affect the dynamics of the pneumatic system. The lower pressure in the piston rod chamber causes extension of time for retraction of the piston rod. This article compare the air consumption experimentally determined and calculated, measured curves of pressure in cylinder chambers and piston speed when saving valve is set up differently.

  9. Zonulin as prehaptoglobin2 regulates lung permeability and activates the complement system

    OpenAIRE

    Rittirsch, Daniel; Flierl, Michael A.; Nadeau, Brian A.; Day, Danielle E.; Huber-Lang, Markus S.; Grailer, Jamison J.; Zetoune, Firas S.; Andjelkovic, Anuska V.; Fasano, Alessio; Ward, Peter A.

    2013-01-01

    Zonulin is a protein involved in the regulation of tight junctions (TJ) in epithelial or endothelial cells. Zonulin is known to affect TJ in gut epithelial cells, but little is known about its influences in other organs. Prehaptoglobin2 has been identified as zonulin and is related to serine proteases (MASPs, C1qrs) that activate the complement system. The current study focused on the role of zonulin in development of acute lung injury (ALI) in C57BL/6 male mice following intrapulmonary depos...

  10. Patterns, structures and regulations of domestic water cycle systems in China

    Science.gov (United States)

    Chu, Junying; Wang, Hao; Wang, Jianhua; Qin, Dayong

    2010-05-01

    management efforts typically fail in China, because the approach is generally narrowly-focused and fragmented. This paper put forward a total-process control framework following the water and pollutants (or nutrients) flows along the dualistic domestic water cycle process. Five key objectives of domestic water cycle system regulation are identified including water use safety, water use equity, water saving, wastewater reduction and nutrient recycling. Comprehensive regulatory framework regarding administrative, economic, technical and social measures is recommended to promote sustainable domestic water usage and demand management. Considering the relatively low affordability in rural area, economic measures should be mainly applied in urban domestic water systems and metropolitan domestic water systems. Engineering or technological measures which are suitable to the three domestic water cycle systems are discussed respectively.

  11. Interaction of the endocrine system with inflammation: a function of energy and volume regulation.

    Science.gov (United States)

    Straub, Rainer H

    2014-02-13

    During acute systemic infectious disease, precisely regulated release of energy-rich substrates (glucose, free fatty acids, and amino acids) and auxiliary elements such as calcium/phosphorus from storage sites (fat tissue, muscle, liver, and bone) are highly important because these factors are needed by an energy-consuming immune system in a situation with little or no food/water intake (sickness behavior). This positively selected program for short-lived infectious diseases is similarly applied during chronic inflammatory diseases. This review presents the interaction of hormones and inflammation by focusing on energy storage/expenditure and volume regulation. Energy storage hormones are represented by insulin (glucose/lipid storage and growth-related processes), insulin-like growth factor-1 (IGF-1) (muscle and bone growth), androgens (muscle and bone growth), vitamin D (bone growth), and osteocalcin (bone growth, support of insulin, and testosterone). Energy expenditure hormones are represented by cortisol (breakdown of liver glycogen/adipose tissue triglycerides/muscle protein, and gluconeogenesis; water retention), noradrenaline/adrenaline (breakdown of liver glycogen/adipose tissue triglycerides, and gluconeogenesis; water retention), growth hormone (glucogenic, lipolytic; has also growth-related aspects; water retention), thyroid gland hormones (increase metabolic effects of adrenaline/noradrenaline), and angiotensin II (induce insulin resistance and retain water). In chronic inflammatory diseases, a preponderance of energy expenditure pathways is switched on, leading to typical hormonal changes such as insulin/IGF-1 resistance, hypoandrogenemia, hypovitaminosis D, mild hypercortisolemia, and increased activity of the sympathetic nervous system and the renin-angiotensin-aldosterone system. Though necessary during acute inflammation in the context of systemic infection or trauma, these long-standing changes contribute to increased mortality in chronic

  12. Regulation of brain reward by the endocannabinoid system: a critical review of behavioral studies in animals.

    Science.gov (United States)

    Vlachou, S; Panagis, G

    2014-01-01

    The endocannabinoid system has been implicated in the regulation of a variety of physiological processes, including a crucial involvement in brain reward systems and the regulation of motivational processes. Behavioral studies have shown that cannabinoid reward may involve the same brain circuits and similar brain mechanisms with other drugs of abuse, such as nicotine, cocaine, alcohol and heroin, as well as natural rewards, such as food, water and sucrose, although the conditions under which cannabinoids exert their rewarding effects may be more limited. The purpose of the present review is to briefly describe and evaluate the behavioral and pharmacological research concerning the major components of the endocannabinoid system and reward processes. Special emphasis is placed on data received from four procedures used to test the effects of the endocannabinoid system on brain reward in animals; namely, the intracranial self-stimulation paradigm, the self-administration procedure, the conditioned place preference procedure and the drug-discrimination procedure. The effects of cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptor agonists, antagonists and endocannabinoid modulators in these procedures are examined. Further, the involvement of CB1 and CB2 receptors, as well the fatty acid amid hydrolase (FAAH) enzyme in reward processes is investigated through presentation of respective genetic ablation studies in mice. We suggest that the endocannabinoid system plays a major role in modulating motivation and reward processes. Further research will provide us with a better understanding of these processes and, thus, could lead to the development of potential therapeutic compounds for the treatment of reward-related disorders.

  13. Research on natural gas fuel injection system. Development of high-performance pressure regulator; Tennen gas yo nenryo funsha system no kenkyu kaihatsu. 1. Tennen gas nenryo funshayo no koseino regulator kaihatsu

    Energy Technology Data Exchange (ETDEWEB)

    Kato, S; Ishii, M; Takigawa, B; Makabe, K; Harada, S; Ono, H [Nippon Carburetor Co. Ltd., Tokyo (Japan)

    1997-10-01

    With the aim of further reducing the exhaust emissions of natural-gas vehicles, vigorous research and development work is under way today on multi point gas injection (MPGI) system. In this studies, a high-performance pressure regulator, which is one of the main components of this MPGI system, has been newly developed. The results showed that a significantly better accuracy of the regulated pressure level using this regulator was obtained under the wide range of operating conditions, including instantaneously greater changes of fuel flow rate. In addition, the advanced studies of gaseous fuel injectors (GFIs) would be also conducted. 4 refs., 8 figs.

  14. CRISPR/Cas systems: new players in gene regulation and bacterial physiology

    Directory of Open Access Journals (Sweden)

    David eWeiss

    2014-04-01

    Full Text Available CRISPR-Cas systems are bacterial defenses against foreign nucleic acids derived from bacteriophages, plasmids or other sources. These systems are targeted in an RNA-dependent, sequence-specific manner, and are also adaptive, providing protection against previously encountered foreign elements. In addition to their canonical function in defense against foreign nucleic acid, their roles in various aspects of bacterial physiology are now being uncovered. We recently revealed a role for a Cas9-based Type II CRISPR-Cas system in the control of endogenous gene expression, a novel form of prokaryotic gene regulation. Cas9 functions in association with two small RNAs to target and alter the stability of an endogenous transcript encoding a bacterial lipoprotein (BLP. Since BLPs are recognized by the host innate immune protein Toll-like Receptor 2 (TLR2, CRISPR-Cas-mediated repression of BLP expression facilitates evasion of TLR2 by the intracellular bacterial pathogen Francisella novicida, and is essential for its virulence. Here we describe the Cas9 regulatory system in detail, as well as data on its role in controlling virulence traits of Neisseria meningitidis and Campylobacter jejuni. We also discuss potential roles of CRISPR-Cas systems in the response to envelope stress and other aspects of bacterial physiology. Since ~45% of bacteria and ~83% of Archaea encode these machineries, the newly appreciated regulatory functions of CRISPR-Cas systems are likely to play broad roles in controlling the pathogenesis and physiology of diverse prokaryotes.

  15. Dynamic simulation platform to verify the performance of the reactor regulating system for a research reactor

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2015-07-01

    Digital instrumentation and controls system technique is being introduced in new constructed research reactor or life extension of older research reactor. Digital systems are easy to change and optimize but the validated process for them is required. Also, to reduce project risk or cost, we have to make it sure that configuration and control functions is right before the commissioning phase on research reactor. For this purpose, simulators have been widely used in developing control systems in automotive and aerospace industries. In these literatures, however, very few of these can be found regarding test on the control system of research reactor with simulator. Therefore, this paper proposes a simulation platform to verify the performance of RRS (Reactor Regulating System) for research reactor. This simulation platform consists of the reactor simulation model and the interface module. This simulation platform is applied to I and C upgrade project of TRIGA reactor, and many problems of RRS configuration were found and solved. And it proved that the dynamic performance testing based on simulator enables significant time saving and improves economics and quality for RRS in the system test phase. (authors)

  16. Coordination and decision making of regulation, operation, and market activities in power systems

    Science.gov (United States)

    Nakashima, Tomoaki

    Electric power has been traditionally supplied to customers at regulated rates by vertically integrated utilities (VIUs), which own generation, transmission, and distribution systems. However, the regulatory authorities of VIUs are promoting competition in their businesses to lower the price of electric energy. Consequently, in new deregulated circumstances, many suppliers and marketers compete in the generation market, and conflict of interest may often occur over transmission. Therefore, a neutral entity, called an independent system operator (ISO), which operates the power system independently, has been established to give market participants nondiscriminatory access to transmission sectors with a natural monopoly, and to facilitate competition in generation sectors. Several types of ISOs are established at present, with their respective regions and authorities. The ISO receives many requests from market participants to transfer power, and must evaluate the feasibility of their requests under the system's condition. In the near future, regulatory authorities may impose various objectives on the ISOs. Then, based on the regulators' policies, the ISO must determine the optimal schedules from feasible solutions, or change the market participants' requests. In a newly developed power market, market participants will conduct their transactions in order to maximize their profit. The most crucial information in conducting power transactions is price and demand. A direct transaction between suppliers and consumers may become attractive because of its stability of price, while in a power exchange market, gaming and speculation of participants may push up electricity prices considerably. To assist the consumers in making effective decisions, suitable methods for forecasting volatile market price are necessary. This research has been approached from three viewpoints: Firstly, from the system operator's point of view, desirable system operation and power market structure

  17. Two-Component Signal Transduction Systems That Regulate the Temporal and Spatial Expression of Myxococcus xanthus Sporulation Genes.

    Science.gov (United States)

    Sarwar, Zaara; Garza, Anthony G

    2016-02-01

    When starved for nutrients, Myxococcus xanthus produces a biofilm that contains a mat of rod-shaped cells, known as peripheral rods, and aerial structures called fruiting bodies, which house thousands of dormant and stress-resistant spherical spores. Because rod-shaped cells differentiate into spherical, stress-resistant spores and spore differentiation occurs only in nascent fruiting bodies, many genes and multiple levels of regulation are required. Over the past 2 decades, many regulators of the temporal and spatial expression of M. xanthus sporulation genes have been uncovered. Of these sporulation gene regulators, two-component signal transduction circuits, which typically contain a histidine kinase sensor protein and a transcriptional regulator known as response regulator, are among the best characterized. In this review, we discuss prototypical two-component systems (Nla6S/Nla6 and Nla28S/Nla28) that regulate an early, preaggregation phase of sporulation gene expression during fruiting body development. We also discuss orphan response regulators (ActB and FruA) that regulate a later phase of sporulation gene expression, which begins during the aggregation stage of fruiting body development. In addition, we summarize the research on a complex two-component system (Esp) that is important for the spatial regulation of sporulation. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  18. To Problem of Heat Load Distribution among Boilers with Various Systems for Regulation of Draught Machinery Productivity

    Directory of Open Access Journals (Sweden)

    V. I. Nazarov

    2010-01-01

    Full Text Available The paper shows that while distributing loads among boilers an account of the power consumed by draught machinery with various regulation systems shifts an optimum point of load distribution by 2–5%.

  19. [Self-regulation systems to control tobacco advertising. An empirical analysis].

    Science.gov (United States)

    Martín, Marta; Quiles, M del Carmen; López, Carmen

    2004-01-01

    Against the background of the debate aroused by the tobacco advertising ban as a result of Directive 98/43/EC and of the Proposed Directive of 5/9/2001, we aimed to evaluate how self-regulation of tobacco advertising systems has worked in the last 5 years and to evaluate its effectiveness and relevance as a potential tool in public health prevention. We performed a content and discourse analysis of all advertisements appearing in the Sunday supplements of the three weekly newspapers with the widest circulation in Spain (El Pais, El Mundo, and ABC) between January 1995 and January 2000 to detect infractions of the norms of the self-regulation code of the Spanish Tobacco Association (Asociacion Espanola de Tabaco [AET]) regarding: a) the identity of models used in advertising; b) direct or indirect claims for the therapeutic properties of smoking; c) depiction of cigarettes in advertisements, and d) printed warnings on advertisements. We examined 910 banners and 369 advertisements. Very few advertisements displayed rational arguments on elements such as price (13%) or product components (7%). Although the AET's code was generally respected, the advertisements displayed a series of subtleties that allowed the industry to get around the code: 10 of the 369 advertisements reviewed depicted famous people (mainly pilots and artists) and one third of them used iconic personages (Joe Camel or Marlboro Man); one advertisement suggested the therapeutic properties of tobacco and almost all linked smoking with social success and leisure. Although cigarettes were not depicted, 18% of the advertisements showed substitutes for cigarettes in various places (12%) and a large percentage infringed the code's recommendations on printed warnings. The industry's use of creative subtleties infringing its self-imposed norms begs the question of how far self-regulation is viable when a failure in the system can have serious consequences for public health.

  20. Regulation of virulence by a two-component system in group B streptococcus.

    Science.gov (United States)

    Jiang, Sheng-Mei; Cieslewicz, Michael J; Kasper, Dennis L; Wessels, Michael R

    2005-02-01

    Group B Streptococcus (GBS) is frequently carried in the gastrointestinal or genitourinary tract as a commensal organism, yet it has the potential to cause life-threatening infection in newborn infants, pregnant women, and individuals with chronic illness. Regulation of virulence factor expression may affect whether GBS behaves as an asymptomatic colonizer or an invasive pathogen, but little is known about how such factors are controlled in GBS. We now report the characterization of a GBS locus that encodes a two-component regulatory system similar to CsrRS (or CovRS) in Streptococcus pyogenes. Inactivation of csrR, encoding the putative response regulator, in two unrelated wild-type strains of GBS resulted in a marked increase in production of beta-hemolysin/cytolysin and a striking decrease in production of CAMP factor, an unrelated cytolytic toxin. Quantitative RNA hybridization experiments revealed that these two phenotypes were associated with a marked increase and decrease in expression of the corresponding genes, cylE and cfb, respectively. The CsrR mutant strains also displayed increased expression of scpB encoding C5a peptidase. Similar, but less marked, changes in gene expression were observed in CsrS (putative sensor component) mutants, evidence that CsrR and CsrS constitute a functional two-component system. Experimental infection studies in mice demonstrated reduced virulence of both CsrR and CsrS mutant strains relative to the wild type. Together, these results indicate that CsrRS regulates expression of multiple GBS virulence determinants and is likely to play an important role in GBS pathogenesis.

  1. Two-Component Signal Transduction System SaeRS Positively Regulates Staphylococcus epidermidis Glucose Metabolism

    Directory of Open Access Journals (Sweden)

    Qiang Lou

    2014-01-01

    Full Text Available Staphylococcus epidermidis, which is a causative pathogen of nosocomial infection, expresses its virulent traits such as biofilm and autolysis regulated by two-component signal transduction system SaeRS. In this study, we performed a proteomic analysis of differences in expression between the S. epidermidis 1457 wild-type and saeRS mutant to identify candidates regulated by saeRS using two-dimensional gel electrophoresis (2-DE combined with matrix-assisted laser desorption/lonization mass spectrometry (MALDI-TOF-MS. Of 55 identified proteins that significantly differed in expression between the two strains, 15 were upregulated and 40 were downregulated. The downregulated proteins included enzymes related to glycolysis and TCA cycle, suggesting that glucose is not properly utilized in S. epidermidis when saeRS was deleted. The study will be helpful for treatment of S. epidermidis infection from the viewpoint of metabolic modulation dependent on two-component signal transduction system SaeRS.

  2. Fault-tolerant cooperative output regulation for multi-vehicle systems with sensor faults

    Science.gov (United States)

    Qin, Liguo; He, Xiao; Zhou, D. H.

    2017-10-01

    This paper presents a unified framework of fault diagnosis and fault-tolerant cooperative output regulation (FTCOR) for a linear discrete-time multi-vehicle system with sensor faults. The FTCOR control law is designed through three steps. A cooperative output regulation (COR) controller is designed based on the internal mode principle when there are no sensor faults. A sufficient condition on the existence of the COR controller is given based on the discrete-time algebraic Riccati equation (DARE). Then, a decentralised fault diagnosis scheme is designed to cope with sensor faults occurring in followers. A residual generator is developed to detect sensor faults of each follower, and a bank of fault-matching estimators are proposed to isolate and estimate sensor faults of each follower. Unlike the current distributed fault diagnosis for multi-vehicle systems, the presented decentralised fault diagnosis scheme in each vehicle reduces the communication and computation load by only using the information of the vehicle. By combing the sensor fault estimation and the COR control law, an FTCOR controller is proposed. Finally, the simulation results demonstrate the effectiveness of the FTCOR controller.

  3. Integrated proteomics and metabolomics suggests symbiotic metabolism and multimodal regulation in a fungal-endobacterial system.

    Science.gov (United States)

    Li, Zhou; Yao, Qiuming; Dearth, Stephen P; Entler, Matthew R; Castro Gonzalez, Hector F; Uehling, Jessie K; Vilgalys, Rytas J; Hurst, Gregory B; Campagna, Shawn R; Labbé, Jessy L; Pan, Chongle

    2017-03-01

    Many plant-associated fungi host endosymbiotic endobacteria with reduced genomes. While endobacteria play important roles in these tri-partite plant-fungal-endobacterial systems, the active physiology of fungal endobacteria has not been characterized extensively by systems biology approaches. Here, we use integrated proteomics and metabolomics to characterize the relationship between the endobacterium Mycoavidus sp. and the root-associated fungus Mortierella elongata. In nitrogen-poor media, M. elongata had decreased growth but hosted a large and growing endobacterial population. The active endobacterium likely extracted malate from the fungal host as the primary carbon substrate for energy production and biosynthesis of phospho-sugars, nucleobases, peptidoglycan and some amino acids. The endobacterium obtained nitrogen by importing a variety of nitrogen-containing compounds. Further, nitrogen limitation significantly perturbed the carbon and nitrogen flows in the fungal metabolic network. M. elongata regulated many pathways by concordant changes on enzyme abundances, post-translational modifications, reactant concentrations and allosteric effectors. Such multimodal regulations may be a general mechanism for metabolic modulation. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

  4. Chaperones and the Proteasome System: Regulating the Construction and Demolition of Striated Muscle

    Directory of Open Access Journals (Sweden)

    Casey Carlisle

    2017-12-01

    Full Text Available Protein folding factors (chaperones are required for many diverse cellular functions. In striated muscle, chaperones are required for contractile protein function, as well as the larger scale assembly of the basic unit of muscle, the sarcomere. The sarcomere is complex and composed of hundreds of proteins and the number of proteins and processes recognized to be regulated by chaperones has increased dramatically over the past decade. Research in the past ten years has begun to discover and characterize the chaperones involved in the assembly of the sarcomere at a rapid rate. Because of the dynamic nature of muscle, wear and tear damage is inevitable. Several systems, including chaperones and the ubiquitin proteasome system (UPS, have evolved to regulate protein turnover. Much of our knowledge of muscle development focuses on the formation of the sarcomere but recent work has begun to elucidate the requirement and role of chaperones and the UPS in sarcomere maintenance and disease. This review will cover the roles of chaperones in sarcomere assembly, the importance of chaperone homeostasis and the cooperation of chaperones and the UPS in sarcomere integrity and disease.

  5. REVIEW ARTICLE: How do biomolecular systems speed up and regulate rates?

    Science.gov (United States)

    Zhou, Huan-Xiang

    2005-09-01

    The viability of a biological system depends upon careful regulation of the rates of various processes. These rates have limits imposed by intrinsic chemical or physical steps (e.g., diffusion). These limits can be expanded by interactions and dynamics of the biomolecules. For example, (a) a chemical reaction is catalyzed when its transition state is preferentially bound to an enzyme; (b) the folding of a protein molecule is speeded up by specific interactions within the transition-state ensemble and may be assisted by molecular chaperones; (c) the rate of specific binding of a protein molecule to a cellular target can be enhanced by mechanisms such as long-range electrostatic interactions, nonspecific binding and folding upon binding; (d) directional movement of motor proteins is generated by capturing favorable Brownian motion through intermolecular binding energy; and (e) conduction and selectivity of ions through membrane channels are controlled by interactions and the dynamics of channel proteins. Simple physical models are presented here to illustrate these processes and provide a unifying framework for understanding speed attainment and regulation in biomolecular systems.

  6. Future wind power forecast errors, need for regulating power, and costs in the Swedish system

    Energy Technology Data Exchange (ETDEWEB)

    Carlsson, Fredrik [Vattenfall Research and Development AB, Stockholm (Sweden). Power Technology

    2011-07-01

    Wind power is one of the renewable energy sources in the electricity system that grows most rapid in Sweden. There are however two market challenges that need to be addressed with a higher proportion of wind power - that is variability and predictability. Predictability is important since the spot market Nord Pool Spot requires forecasts of production 12 - 36 hours ahead. The forecast errors must be regulated with regulating power, which is expensive for the actors causing the forecast errors. This paper has investigated a number of scenarios with 10 - 55 TWh of wind power installed in the Swedish system. The focus has been on a base scenario with 10 TWh new wind power consisting of 3,5 GW new wind power and 1,5 GW already installed power, which gives 5 GW. The results show that the costs for the forecast errors will increase as more intermittent production is installed. However, the increase can be limited by for instance trading on intraday market or increase quality of forecasts. (orig.)

  7. Main results on the RF amplitude and phase regulation systems in operation at GANIL

    International Nuclear Information System (INIS)

    Joubert, A.; Ducoudret, B.; Labiche, J.C.; Loyant, J.M.

    1984-06-01

    The general features of the amplitude and phase regulations and their control systems are briefly reviewed. These feedback control systems are fully under the control of the main computer aided by dedicated CAMAC microprocessors for actions such as starting, parameters tuning or phase stability surveying. Numerous results obtained with spectrum analysis method give the actual RF purity and the residual modulation and crossmodulation noise level for all RF signals picked up in the RF resonators. A typical value for the noise immunity is 80 dB below the carrier at 100 Hz deviation. Another set of results gives the actual long term phase drift between resonators (< 0.2 RF degree within 6 hours). The stability of the RF phases is confirmed by on line beam phase measurements

  8. Systems Level Regulation of Rhythmic Growth Rate and Biomass Accumulation in Grasses

    Energy Technology Data Exchange (ETDEWEB)

    Kay, Steve A. [Univ. of Southern California, Los Angeles, CA (United States)

    2017-10-20

    Objectives: Several breakthroughs have been recently made in our understanding of plant growth and biomass accumulation. It was found that plant growth is rhythmically controlled throughout the day by the circadian clock through a complex interplay of light and phytohormone signaling pathways. While plants such as the C4 energy crop sorghum (Sorghum bicolor (L.) Moench) and possibly the C3 grass Brachypodium distachyon also exhibit daily rhythms in growth rate, the molecular details of its regulation remain to be explored. A better understanding of diurnally regulated growth behavior in grasses may lead to species-specific mechanisms highly relevant to future strategies to optimize energy crop biomass yield. Here we propose to devise a systems approach to identify, in parallel, regulatory hubs associated with rhythmic growth in C3 and C4 plants. We propose to use rhythmicity in daily growth patterns to drive the discovery of regulatory network modules controlling biomass accumulation. Description: The project is divided in three main parts: 1) Performing time-lapse imaging and growth measurement in B. distachyon and S. bicolor to determine growth rate dynamic during the day/night cycle. Identifying growth-associated genes whose expression patterns follow the observed growth dynamics using deep sequencing technology, 2) identifying regulators of these genes by screening for DNA-binding proteins interacting with the growth-associated gene promoters identified in Aim 1. Screens will be performed using a validated yeast-one hybrid strategy paired with a specifically designed B. distachyon and S. bicolor transcription factor libraries (1000 clones each), and 3) Selecting 50 potential growth regulators from the screen for downstream characterization. The selection will be made by using a sytems biology approach by calculating the connectivity between growth rate, rhythmic gene expression profiles and TF expression profile and determine which TF is likely part of a hub

  9. Xiaoyaosan Improves Depressive-Like Behaviors in Mice through Regulating Apelin-APJ System in Hypothalamus.

    Science.gov (United States)

    Yan, Zhiyi; Jiao, Haiyan; Ding, Xiufang; Ma, Qingyu; Li, Xiaojuan; Pan, Qiuxia; Wang, Tingye; Hou, Yajing; Jiang, Youming; Liu, Yueyun; Chen, Jiaxu

    2018-05-03

    Background: The apelin-APJ system has been considered to play a crucial role in HPA axis function, and how the traditional Chinese compound prescription Xiaoyaosan regulates the apelin-APJ system as a supplement to treat depressive disorders. Objective: To investigate the depression-like behaviors and expression of apelin and APJ in hypothalamus of chronic unpredictable mild stress (CUMS) mice and study whether these changes related to the regulation of Xiaoyaosan. Methods: 60 adult C57BL/6J mice were randomly divided into four groups, including control group, CUMS group, Xiaoyaosan treatment group and fluoxetine treatment group. Mice in the control group and CUMS group received 0.5 mL physiological saline once a day by intragastric administration. Mice in two treatment groups received Xiaoyaosan (0.25 g/kg/d) and fluoxetine (2.6 mg/kg/d), respectively. After 21 days of modeling with CUMS, the expression of apelin and APJ in hypothalamus were measured by real-time fluorescence quantitative PCR, western blot and immunohistochemical staining. The physical condition, body weight, food intake and behavior tests such as open field test, sucrose preference test and force swimming test were measured to evaluate depressive-like behaviors. Results: In this study, significant behavioral changes were found in CUMS-induced mice, meanwhile the expressions of apelin and APJ in the hypothalamus were changed after modeling. The body weight, food-intake and depressive-like behaviors in CUMS-induced mice could be improved by Xiaoyaosan treatment which is similar with the efficacy of fluoxetine, while the expressions of apelin and APJ in hypothalamus were modified by Xiaoyaosan. Conclusions: The data suggest that apelin-APJ system changes in the hypothalamus may be a target of depressive disorders, and the beneficial effects of Chinese compound prescription Xiaoyaosan on depressive-like behaviors may be mediated by the apelin-APJ system.

  10. Tetracycline-inducible system for regulation of skeletal muscle-specific gene expression in transgenic mice

    Science.gov (United States)

    Grill, Mischala A.; Bales, Mark A.; Fought, Amber N.; Rosburg, Kristopher C.; Munger, Stephanie J.; Antin, Parker B.

    2003-01-01

    Tightly regulated control of over-expression is often necessary to study one aspect or time point of gene function and, in transgenesis, may help to avoid lethal effects and complications caused by ubiquitous over-expression. We have utilized the benefits of an optimized tet-on system and a modified muscle creatine kinase (MCK) promoter to generate a skeletal muscle-specific, doxycycline (Dox) controlled over-expression system in transgenic mice. A DNA construct was generated in which the codon optimized reverse tetracycline transactivator (rtTA) was placed under control of a skeletal muscle-specific version of the mouse MCK promoter. Transgenic mice containing this construct expressed rtTA almost exclusively in skeletal muscles. These mice were crossed to a second transgenic line containing a bi-directional promoter centered on a tet responder element driving both a luciferase reporter gene and a tagged gene of interest; in this case the calpain inhibitor calpastatin. Compound hemizygous mice showed high level, Dox dependent muscle-specific luciferase activity often exceeding 10,000-fold over non-muscle tissues of the same mouse. Western and immunocytochemical analysis demonstrated similar Dox dependent muscle-specific induction of the tagged calpastatin protein. These findings demonstrate the effectiveness and flexibility of the tet-on system to provide a tightly regulated over-expression system in adult skeletal muscle. The MCKrtTA transgenic lines can be combined with other transgenic responder lines for skeletal muscle-specific over-expression of any target gene of interest.

  11. Regulation of aortic extracellular matrix synthesis via noradrenergic system and angiotensin II in juvenile rats.

    Science.gov (United States)

    Dab, Houcine; Hachani, Rafik; Dhaouadi, Nedra; Sakly, Mohsen; Hodroj, Wassim; Randon, Jacques; Bricca, Giampiero; Kacem, Kamel

    2012-10-01

    Extracellular matrix (ECM) synthesis regulation by sympathetic nervous system (SNS) or angiotensin II (ANG II) was widely reported, but interaction between the two systems on ECM synthesis needs further investigation. We tested implication of SNS and ANG II on ECM synthesis in juvenile rat aorta. Sympathectomy with guanethidine (50 mg/kg, subcutaneous) and blockade of the ANG II AT1 receptors (AT1R) blocker with losartan (20 mg/kg/day in drinking water) were performed alone or in combination in rats. mRNA and protein synthesis of collagen and elastin were examined by Q-RT-PCR and immunoblotting. Collagen type I and III mRNA were increased respectively by 62 and 43% after sympathectomy and decreased respectively by 31 and 60% after AT1R blockade. Combined treatment increased collagen type III by 36% but not collagen type I. The same tendency of collagen expression was observed at mRNA and protein levels after the three treatments. mRNA and protein level of elastin was decreased respectively by 63 and 39% and increased by 158 and 15% after losartan treatment. Combined treatment abrogates changes induced by single treatments. The two systems act as antagonists on ECM expression in the aorta and combined inhibition of the two systems prevents imbalance of mRNA and protein level of collagen I and elastin induced by single treatment. Combined inhibition of the two systems prevents deposit or excessive reduction of ECM and can more prevent cardiovascular disorders.

  12. The software safety analysis based on SFTA for reactor power regulating system in nuclear power plant

    International Nuclear Information System (INIS)

    Liu Zhaohui; Yang Xiaohua; Liao Longtao; Wu Zhiqiang

    2015-01-01

    The digitalized Instrumentation and Control (I and C) system of Nuclear power plants can provide many advantages. However, digital control systems induce new failure modes that differ from those of analog control systems. While the cost effectiveness and flexibility of software is widely recognized, it is very difficult to achieve and prove high levels of dependability and safety assurance for the functions performed by process control software, due to the very flexibility and potential complexity of the software itself. Software safety analysis (SSA) was one way to improve the software safety by identify the system hazards caused by software failure. This paper describes the application of a software fault tree analysis (SFTA) at the software design phase. At first, we evaluate all the software modules of the reactor power regulating system in nuclear power plant and identify various hazards. The SFTA was applied to some critical modules selected from the previous step. At last, we get some new hazards that had not been identified in the prior processes of the document evaluation which were helpful for our design. (author)

  13. A Decentralized Multivariable Robust Adaptive Voltage and Speed Regulator for Large-Scale Power Systems

    Science.gov (United States)

    Okou, Francis A.; Akhrif, Ouassima; Dessaint, Louis A.; Bouchard, Derrick

    2013-05-01

    This papter introduces a decentralized multivariable robust adaptive voltage and frequency regulator to ensure the stability of large-scale interconnnected generators. Interconnection parameters (i.e. load, line and transormer parameters) are assumed to be unknown. The proposed design approach requires the reformulation of conventiaonal power system models into a multivariable model with generator terminal voltages as state variables, and excitation and turbine valve inputs as control signals. This model, while suitable for the application of modern control methods, introduces problems with regards to current design techniques for large-scale systems. Interconnection terms, which are treated as perturbations, do not meet the common matching condition assumption. A new adaptive method for a certain class of large-scale systems is therefore introduces that does not require the matching condition. The proposed controller consists of nonlinear inputs that cancel some nonlinearities of the model. Auxiliary controls with linear and nonlinear components are used to stabilize the system. They compensate unknown parametes of the model by updating both the nonlinear component gains and excitation parameters. The adaptation algorithms involve the sigma-modification approach for auxiliary control gains, and the projection approach for excitation parameters to prevent estimation drift. The computation of the matrix-gain of the controller linear component requires the resolution of an algebraic Riccati equation and helps to solve the perturbation-mismatching problem. A realistic power system is used to assess the proposed controller performance. The results show that both stability and transient performance are considerably improved following a severe contingency.

  14. Ethical self-regulation systems for Non-Governmental Organizations (NGOs

    Directory of Open Access Journals (Sweden)

    Mario Aguiló

    2014-06-01

    Full Text Available The article presents the theoretical results of a study focusing on self-regulatory systems as the evaluative approach to the ethical performance of NGOs. Its aim is to analyse the current self-regulatory systems in NGOs in order to report their scope, identify the evaluative dimensions and variables used, and clarify their role in relation to other strategies and other apparently similar resources, such as quality control systems. From the literature survey and content analysis of the major databases and institutional documents of authors and managers of various self-regulatory systems, the current practices are described, compared and analysed. The results lead us to conclude that through self-regulation, primarily codes of conduct and certifications of good practices, a growing number of organizations are developing standards and shared rules of conduct to address and channel the emerging demand for transparency and accountability to their stakeholders. However, there is great disparity in the way they are used, along with their geographical distribution and content. Finally, we offer an integrative proposal of the different variables used to evaluate ethical management in the leading certification systems analysed.

  15. THE IMPACT OF NEW REGULATION ON FOUR EUROPEAN BANKING SYSTEMS. A BASEL III APPROACH

    Directory of Open Access Journals (Sweden)

    Anamaria AVADANEI

    2013-12-01

    Full Text Available One of the solutions designed to rebuild the banking system is the reconfiguration of the regulatory framework. Still active, the episodes of liquidity shortage and bank failure ask for solid measures in order to increase the solidity of individual institutions, to protect the financial stability of the banking systems and to maintain confidence on the markets. The aim of this paper is to analyze the situation of four European banking systems (Czech Republic, Poland, Romania and Croatia in terms of Basel III standards. Structured on three parts, the study points out the real concerns regarding Basel III effectiveness; analyzes the evolutions of capital, leverage and liquidity indicators and highlights the future possible scenarios/actions for aligning to the new regulation. To conclude, we determine the white and the black spots of the selected banking systems related to Basel III implementation. The results show good levels of capital in Poland, Czech Republic, Croatia and Romania, and some liquidity issues in Poland. The Czech and the Croatian banking systems are the best prepared for shocks.

  16. Characterization of an archaeal two-component system that regulates methanogenesis in Methanosaeta harundinacea.

    Directory of Open Access Journals (Sweden)

    Jie Li

    Full Text Available Two-component signal transduction systems (TCSs are a major mechanism used by bacteria in response to environmental changes. Although many sequenced archaeal genomes encode TCSs, they remain poorly understood. Previously, we reported that a methanogenic archaeon, Methanosaeta harundinacea, encodes FilI, which synthesizes carboxyl-acyl homoserine lactones, to regulate transitions of cellular morphology and carbon metabolic fluxes. Here, we report that filI, the cotranscribed filR2, and the adjacent filR1 constitute an archaeal TCS. FilI possesses a cytoplasmic kinase domain (histidine kinase A and histidine kinase-like ATPase and its cognate response regulator. FilR1 carries a receiver (REC domain coupled with an ArsR-related domain with potential DNA-binding ability, while FilR2 carries only a REC domain. In a phosphorelay assay, FilI was autophosphorylated and specifically transferred the phosphoryl group to FilR1 and FilR2, confirming that the three formed a cognate TCS. Through chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR using an anti-FilR1 antibody, FilR1 was shown to form in vivo associations with its own promoter and the promoter of the filI-filR2 operon, demonstrating a regulatory pattern common among TCSs. ChIP-qPCR also detected FilR1 associations with key genes involved in acetoclastic methanogenesis, acs4 and acs1. Electrophoretic mobility shift assays confirmed the in vitro tight binding of FilR1 to its own promoter and those of filI-filR2, acs4, and mtrABC. This also proves the DNA-binding ability of the ArsR-related domain, which is found primarily in Archaea. The archaeal promoters of acs4, filI, acs1, and mtrABC also initiated FilR1-modulated expression in an Escherichia coli lux reporter system, suggesting that FilR1 can up-regulate both archaeal and bacterial transcription. In conclusion, this work identifies an archaeal FilI/FilRs TCS that regulates the methanogenesis of M. harundinacea.

  17. Sox9b is a key regulator of pancreaticobiliary ductal system development.

    Directory of Open Access Journals (Sweden)

    Marion Delous

    Full Text Available The pancreaticobiliary ductal system connects the liver and pancreas to the intestine. It is composed of the hepatopancreatic ductal (HPD system as well as the intrahepatic biliary ducts and the intrapancreatic ducts. Despite its physiological importance, the development of the pancreaticobiliary ductal system remains poorly understood. The SRY-related transcription factor SOX9 is expressed in the mammalian pancreaticobiliary ductal system, but the perinatal lethality of Sox9 heterozygous mice makes loss-of-function analyses challenging. We turned to the zebrafish to assess the role of SOX9 in pancreaticobiliary ductal system development. We first show that zebrafish sox9b recapitulates the expression pattern of mouse Sox9 in the pancreaticobiliary ductal system and use a nonsense allele of sox9b, sox9b(fh313, to dissect its function in the morphogenesis of this structure. Strikingly, sox9b(fh313 homozygous mutants survive to adulthood and exhibit cholestasis associated with hepatic and pancreatic duct proliferation, cyst formation, and fibrosis. Analysis of sox9b(fh313 mutant embryos and larvae reveals that the HPD cells appear to mis-differentiate towards hepatic and/or pancreatic fates, resulting in a dysmorphic structure. The intrahepatic biliary cells are specified but fail to assemble into a functional network. Similarly, intrapancreatic duct formation is severely impaired in sox9b(fh313 mutants, while the embryonic endocrine and acinar compartments appear unaffected. The defects in the intrahepatic and intrapancreatic ducts of sox9b(fh313 mutants worsen during larval and juvenile stages, prompting the adult phenotype. We further show that Sox9b interacts with Notch signaling to regulate intrahepatic biliary network formation: sox9b expression is positively regulated by Notch signaling, while Sox9b function is required to maintain Notch signaling in the intrahepatic biliary cells. Together, these data reveal key roles for SOX9 in the

  18. Conserved ABC Transport System Regulated by the General Stress Response Pathways of Alpha- and Gammaproteobacteria

    Energy Technology Data Exchange (ETDEWEB)

    Herrou, Julien; Willett, Jonathan W.; Czy; #380; , Daniel M.; Babnigg, Gyorgy; Kim, Youngchang; Crosson, Sean (UC)

    2016-12-19

    ABSTRACT

    Brucella abortusσE1is an EcfG family sigma factor that regulates the transcription of dozens of genes in response to diverse stress conditions and is required for maintenance of chronic infection in a mouse model. A putative ATP-binding cassette transporter operon,bab1_0223-bab1_0226, is among the most highly activated gene sets in the σE1regulon. The proteins encoded by the operon resemble quaternary ammonium-compatible solute importers but are most similar in sequence to the broadly conserved YehZYXW system, which remains largely uncharacterized. Transcription ofyehZYXWis activated by the general stress sigma factor σSinEnterobacteriaceae, which suggests a functional role for this transport system in bacterial stress response across the classesAlphaproteobacteriaandGammaproteobacteria. We present evidence thatB. abortusYehZYXW does not function as an importer of known compatible solutes under physiological conditions and does not contribute to the virulence defect of a σE1-null strain. The solein vitrophenotype associated with genetic disruption of this putative transport system is reduced growth in the presence of high Li+ion concentrations. A crystal structure ofB. abortusYehZ revealed a class II periplasmic binding protein fold with significant structural homology toArchaeoglobus fulgidusProX, which binds glycine betaine. However, the structure

  19. Phylogenetic footprint of the plant clock system in angiosperms: evolutionary processes of Pseudo-Response Regulators

    Directory of Open Access Journals (Sweden)

    Saito Shigeru

    2010-05-01

    Full Text Available Abstract Background Plant circadian clocks regulate many photoperiodic and diurnal responses that are conserved among plant species. The plant circadian clock system has been uncovered in the model plant, Arabidopsis thaliana, using genetics and systems biology approaches. However, it is still not clear how the clock system had been organized in the evolutionary history of plants. We recently revealed the molecular phylogeny of LHY/CCA1 genes, one of the essential components of the clock system. The aims of this study are to reconstruct the phylogenetic relationships of angiosperm clock-associated PRR genes, the partner of the LHY/CCA1 genes, and to clarify the evolutionary history of the plant clock system in angiosperm lineages. Results In the present study, to investigate the molecular phylogeny of PRR genes, we performed two approaches: reconstruction of phylogenetic trees and examination of syntenic relationships. Phylogenetic analyses revealed that PRR genes had diverged into three clades prior to the speciation of monocots and eudicots. Furthermore, copy numbers of PRR genes have been independently increased in monocots and eudicots as a result of ancient chromosomal duplication events. Conclusions Based on the molecular phylogenies of both PRR genes and LHY/CCA1 genes, we inferred the evolutionary process of the plant clock system in angiosperms. This scenario provides evolutionary information that a common ancestor of monocots and eudicots had retained the basic components required for reconstructing a clock system and that the plant circadian clock may have become a more elaborate mechanism after the speciation of monocots and eudicots because of the gene expansion that resulted from polyploidy events.

  20. Reciprocal regulation of A-to-I RNA editing and the vertebrate nervous system

    Directory of Open Access Journals (Sweden)

    Andrew Charles Penn

    2013-04-01

    Full Text Available The fine control of molecules mediating communication in the nervous system is key to adjusting neuronal responsiveness during development and in maintaining the stability of established networks in the face of altered sensory input. To prevent culmination of pathological recurrent network excitation or debilitating periods of quiescence, adaptive alterations occur in the signalling molecules and ion channels that control membrane excitability and synaptic transmission. However, rather than encoding (and thus ‘hardwiring’ modified gene copies, the nervous systems of metazoa have opted for expanding on post-transcriptional pre-mRNA splicing by altering key encoded amino acids using a conserved mechanism of A-to-I RNA editing: the enzymatic deamination of adenosine resulting in a change in the nucleotide to inosine. Inosine exhibits similar base-pairing properties to guanosine with respect to tRNA codon recognition, replication by polymerases and RNA secondary structure forming capacity. In addition to recoding within the open reading frame, adenosine deamination also occurs with high frequency throughout the non-coding transcriptome, where it affects multiple aspects of RNA metabolism and gene expression. We will describe here the recoding function of key RNA editing targets in the mammalian central nervous system (CNS and their potential to be regulated. We will then discuss how interactions of A-to-I editing with gene expression and alternative splicing could play a wider role in regulating the neuronal transcriptome. Finally, we will highlight the increasing complexity of this multifaceted control hub by summarising new findings from high-throughput studies.

  1. Adaptive Regulation of the Northern California Reservoir System for Water, Energy, and Environmental Management

    Science.gov (United States)

    Georgakakos, A. P.; Kistenmacher, M.; Yao, H.; Georgakakos, K. P.

    2014-12-01

    The 2014 National Climate Assessment of the US Global Change Research Program emphasizes that water resources managers and planners in most US regions will have to cope with new risks, vulnerabilities, and opportunities, and recommends the development of adaptive capacity to effectively respond to the new water resources planning and management challenges. In the face of these challenges, adaptive reservoir regulation is becoming all the more ncessary. Water resources management in Northern California relies on the coordinated operation of several multi-objective reservoirs on the Trinity, Sacramento, American, Feather, and San Joaquin Rivers. To be effective, reservoir regulation must be able to (a) account for forecast uncertainty; (b) assess changing tradeoffs among water uses and regions; and (c) adjust management policies as conditions change; and (d) evaluate the socio-economic and environmental benefits and risks of forecasts and policies for each region and for the system as a whole. The Integrated Forecast and Reservoir Management (INFORM) prototype demonstration project operated in Northern California through the collaboration of several forecast and management agencies has shown that decision support systems (DSS) with these attributes add value to stakeholder decision processes compared to current, less flexible management practices. Key features of the INFORM DSS include: (a) dynamically downscaled operational forecasts and climate projections that maintain the spatio-temporal coherence of the downscaled land surface forcing fields within synoptic scales; (b) use of ensemble forecast methodologies for reservoir inflows; (c) assessment of relevant tradeoffs among water uses on regional and local scales; (d) development and evaluation of dynamic reservoir policies with explicit consideration of hydro-climatic forecast uncertainties; and (e) focus on stakeholder information needs.This article discusses the INFORM integrated design concept, underlying

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

    Science.gov (United States)

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

    2008-06-01

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

  3. Strengthening global health security by embedding the International Health Regulations requirements into national health systems.

    Science.gov (United States)

    Kluge, Hans; Martín-Moreno, Jose Maria; Emiroglu, Nedret; Rodier, Guenael; Kelley, Edward; Vujnovic, Melitta; Permanand, Govin

    2018-01-01

    The International Health Regulations (IHR) 2005, as the overarching instrument for global health security, are designed to prevent and cope with major international public health threats. But poor implementation in countries hampers their effectiveness. In the wake of a number of major international health crises, such as the 2014 Ebola and 2016 Zika outbreaks, and the findings of a number of high-level assessments of the global response to these crises, it has become clear that there is a need for more joined-up thinking between health system strengthening activities and health security efforts for prevention, alert and response. WHO is working directly with its Member States to promote this approach, more specifically around how to better embed the IHR (2005) core capacities into the main health system functions. This paper looks at how and where the intersections between the IHR and the health system can be best leveraged towards developing greater health system resilience. This merging of approaches is a key component in pursuit of Universal Health Coverage and strengthened global health security as two mutually reinforcing agendas.

  4. Toward a workable biosafety system for regulating genetically modified organisms in Ethiopia: balancing conservation and competitiveness.

    Science.gov (United States)

    Abraham, Adane

    2013-01-01

    On September 9, 2009, Ethiopia enacted a highly restrictive biosafety law firmly based on precautionary principles as a foundation for its GMO regulation system. Its drafting process, led by the country's Environmental Protection Authority, was judged as biased, focusing only on protecting the environment from perceived risks, giving little attention to potential benefits of GMOs. Many of its provisions are very stringent, exceeding those of Cartagena Protocol on Biosafety, while others cannot be fulfilled by applicants, collectively rendering the emerged biosafety system unworkable. These provisions include requirements for advance informed agreement and rigorous socioeconomic assessment in risk evaluation for all GMO transactions, including contained research use-which requires the head of the competent national authority of the exporting country to take full responsibility for GMO-related information provided-and stringent labeling, insurance and monitoring requirements for all GMO activities. Furthermore, there is no provision to establish an independent national biosafety decision-making body(ies). As a result, foreign technology owners that provide highly demanded technologies like Bt cotton declined to work with Ethiopia. There is a fear that the emerged biosafety system might also continue to suppress domestic genetic engineering research and development. Thus, to benefit from GMOs, Ethiopia has to revise its biosafety system, primarily by making changes to some provisions of the law in a way that balances its diverse interests of conserving biodiversity, protecting the environment and enhancing competition in agricultural and other economic sectors.

  5. Research on Vehicle Temperature Regulation System Based on Air Convection Principle

    Science.gov (United States)

    Zhuge, Muzi; Li, Xiang; Liang, Caifeng

    2018-03-01

    The long time parking outdoors in the summer will lead to too high temperature in the car, and the harmful gas produced by the vehicle engine will stay in the confined space for a long time during the parking process, which will do great harm to the human body. If the air conditioning system is turned on before driving, the cooling rate is slow and the battery loss is large. To solve the above problems, we designed a temperature adjusting system based on the principle of air convection. We can choose the automatic mode or manual mode to achieve control of a convection window. In the automatic mode, the system will automatically detect the environmental temperature, through the sensor to complete the detection, and the signal is transmitted to the microcontroller to control the window open or close, in manual mode, the remote control of the window can be realized by Bluetooth. Therefore, the system has important practical significance to effectively regulate temperature, prolong battery life, and improve the safety and comfort of traffic vehicles.

  6. Post-transcriptional regulation on a global scale: form and function of Csr/Rsm systems.

    Science.gov (United States)

    Romeo, Tony; Vakulskas, Christopher A; Babitzke, Paul

    2013-02-01

    Originally described as a repressor of gene expression in the stationary phase of growth, CsrA (RsmA) regulates primary and secondary metabolic pathways, biofilm formation, motility, virulence circuitry of pathogens, quorum sensing and stress response systems by binding to conserved sequences in its target mRNAs and altering their translation and/or turnover. While the binding of CsrA to RNA is understood at an atomic level, new mechanisms of gene activation and repression by this protein are still emerging. In the γ-proteobacteria, small non-coding RNAs (sRNAs) use molecular mimicry to sequester multiple CsrA dimers away from mRNA. In contrast, the FliW protein of Bacillus subtilis inhibits CsrA activity by binding to this protein, thereby establishing a checkpoint in flagellum morphogenesis. Turnover of CsrB and CsrC sRNAs in Escherichia coli requires a specificity protein of the GGDEF-EAL domain superfamily, CsrD, in addition to the housekeeping nucleases RNase E and PNPase. The Csr system of E. coli contains extensive autoregulatory circuitry, which governs the expression and activity of CsrA. Interaction of the Csr system with transcriptional regulatory networks results in a variety of complex response patterns. This minireview will highlight basic principles and new insights into the workings of these complex eubacterial regulatory systems. © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.

  7. Closed-form solutions for linear regulator design of mechanical systems including optimal weighting matrix selection

    Science.gov (United States)

    Hanks, Brantley R.; Skelton, Robert E.

    1991-01-01

    Vibration in modern structural and mechanical systems can be reduced in amplitude by increasing stiffness, redistributing stiffness and mass, and/or adding damping if design techniques are available to do so. Linear Quadratic Regulator (LQR) theory in modern multivariable control design, attacks the general dissipative elastic system design problem in a global formulation. The optimal design, however, allows electronic connections and phase relations which are not physically practical or possible in passive structural-mechanical devices. The restriction of LQR solutions (to the Algebraic Riccati Equation) to design spaces which can be implemented as passive structural members and/or dampers is addressed. A general closed-form solution to the optimal free-decay control problem is presented which is tailored for structural-mechanical system. The solution includes, as subsets, special cases such as the Rayleigh Dissipation Function and total energy. Weighting matrix selection is a constrained choice among several parameters to obtain desired physical relationships. The closed-form solution is also applicable to active control design for systems where perfect, collocated actuator-sensor pairs exist.

  8. [Melatonin: its role in the system of neurohumoral regulation in man. Part 2].

    Science.gov (United States)

    Baksheev, V I; Kolomoets, N M

    2011-01-01

    Part 2 of this review concerns the application of melatonin (Mt) to the treatment of aged patients with cardiovascular diseases and other pathology with reference to its genoprotective and anticarcinogenic action. Effects of Mt on the cardiovascular system are underlain by its antioxidative, vasodilating, and sedative activities, the ability to regulate the heart rate and inhibit platelet aggregation. Certain authors report negative correlation between Mt production and blood cholesterol level. Mt was shown to protect from cardiac lesions associated with ischemia and reperfusion. Mt inhibits carcinogenesis and is active at systemic, tissue, cellular and subcellular levels. At the systemic level, Mt decreases hormonal production, stimulates immune activity, and prevents the development of metabolic syndrome. It inhibits cell proliferation and promotes apoptosis of tumour cells but suppresses it the nervous tissue. Mt activates telomerase. It decreases expression of oncogens and interferes with the action of mutagens and clastogens at the genetic level. Extensive studies of Mt protective action in nervous diseases are underway with special reference to spinal cord, brain, neuron and glial cell lesions; experimental cerebral stroke, Parkinson's and Alzheimer's diseases. Similar studies concern the role of Mt in the protection against ionizing radiation, the development of renal pathology, and ophthalmology (glaucoma, cataract). Mt is shown to influence practically all organ systems by inhibiting mutagenesis and maintaining correlation between circadian rhythms of different biological processes throughout human evolution.

  9. DEVELOPMENT OF PROTOTYPE SYSTEM FOR REGULATING THERMAL CONDITIONS OF TELECOMMUNICATIONS EQUIPMENT CABINETS

    Directory of Open Access Journals (Sweden)

    A. T. Rashidkhanov

    2017-01-01

    Full Text Available Objectives. The main objective of the study was to regulate the thermal regime and ensure the reliability of electronic equipmentMethods. In order to conduct experimental studies of the thermoelectric cooling system using heat pipes, a stand was assembled on which the developed and manufactured prototype was studied. The object of the experimental studies was a prototype cooling system, consisting of a thermoelectric battery made of conventional unified thermoelectric materials of ICE-71 type. The solution of the research problems carried out by the method of reduction to ordinary differential equations (Kantorovich method provides acceptable accuracy for such a class of problems.Results. A design of a telecommunication equipment cabinet with a thermal management system based on the use of heat pipes and thermoelectric cooling units is proposed. A mathematical model for the determination of the thermal field in the cabinet volume is considered; an experimental stand for the prototype study is described; the results of experimental studies for various power sources of heat release are presented.Conclusion. Experimental studies confirm the operability of the developed cooling system for cabinets with telecommunication equipment; this cooling method has advantages over conventional forced or natural cooling; the temperature in the block volume and the peak values of the heat sources are significantly reduced; at dissipation powers on one board within 50 W there is no need to use special means to remove heat from hot junctions of the thermoelectric battery.

  10. Identification of an elaborate NK-specific system regulating HLA-C expression.

    Directory of Open Access Journals (Sweden)

    Hongchuan Li

    2018-01-01

    Full Text Available The HLA-C gene appears to have evolved in higher primates to serve as a dominant source of ligands for the KIR2D family of inhibitory MHC class I receptors. The expression of NK cell-intrinsic MHC class I has been shown to regulate the murine Ly49 family of MHC class I receptors due to the interaction of these receptors with NK cell MHC in cis. However, cis interactions have not been demonstrated for the human KIR and HLA proteins. We report the discovery of an elaborate NK cell-specific system regulating HLA-C expression, indicating an important role for HLA-C in the development and function of NK cells. A large array of alternative transcripts with differences in intron/exon content are generated from an upstream NK-specific HLA-C promoter, and exon content varies between HLA-C alleles due to SNPs in splice donor/acceptor sites. Skipping of the first coding exon of HLA-C generates a subset of untranslatable mRNAs, and the proportion of untranslatable HLA-C mRNA decreases as NK cells mature, correlating with increased protein expression by mature NK cells. Polymorphism in a key Ets-binding site of the NK promoter has generated HLA-C alleles that lack significant promoter activity, resulting in reduced HLA-C expression and increased functional activity. The NK-intrinsic regulation of HLA-C thus represents a novel mechanism controlling the lytic activity of NK cells during development.

  11. Na/K pump regulation of cardiac repolarization: insights from a systems biology approach

    KAUST Repository

    Bueno-Orovio, Alfonso

    2013-05-15

    The sodium-potassium pump is widely recognized as the principal mechanism for active ion transport across the cellular membrane of cardiac tissue, being responsible for the creation and maintenance of the transarcolemmal sodium and potassium gradients, crucial for cardiac cell electrophysiology. Importantly, sodium-potassium pump activity is impaired in a number of major diseased conditions, including ischemia and heart failure. However, its subtle ways of action on cardiac electrophysiology, both directly through its electrogenic nature and indirectly via the regulation of cell homeostasis, make it hard to predict the electrophysiological consequences of reduced sodium-potassium pump activity in cardiac repolarization. In this review, we discuss how recent studies adopting the systems biology approach, through the integration of experimental and modeling methodologies, have identified the sodium-potassium pump as one of the most important ionic mechanisms in regulating key properties of cardiac repolarization and its rate dependence, from subcellular to whole organ levels. These include the role of the pump in the biphasic modulation of cellular repolarization and refractoriness, the rate control of intracellular sodium and calcium dynamics and therefore of the adaptation of repolarization to changes in heart rate, as well as its importance in regulating pro-arrhythmic substrates through modulation of dispersion of repolarization and restitution. Theoretical findings are consistent across a variety of cell types and species including human, and widely in agreement with experimental findings. The novel insights and hypotheses on the role of the pump in cardiac electrophysiology obtained through this integrative approach could eventually lead to novel therapeutic and diagnostic strategies. © 2013 Springer-Verlag Berlin Heidelberg.

  12. Na/K pump regulation of cardiac repolarization: insights from a systems biology approach.

    Science.gov (United States)

    Bueno-Orovio, Alfonso; Sánchez, Carlos; Pueyo, Esther; Rodriguez, Blanca

    2014-02-01

    The sodium-potassium pump is widely recognized as the principal mechanism for active ion transport across the cellular membrane of cardiac tissue, being responsible for the creation and maintenance of the transarcolemmal sodium and potassium gradients, crucial for cardiac cell electrophysiology. Importantly, sodium-potassium pump activity is impaired in a number of major diseased conditions, including ischemia and heart failure. However, its subtle ways of action on cardiac electrophysiology, both directly through its electrogenic nature and indirectly via the regulation of cell homeostasis, make it hard to predict the electrophysiological consequences of reduced sodium-potassium pump activity in cardiac repolarization. In this review, we discuss how recent studies adopting the systems biology approach, through the integration of experimental and modeling methodologies, have identified the sodium-potassium pump as one of the most important ionic mechanisms in regulating key properties of cardiac repolarization and its rate dependence, from subcellular to whole organ levels. These include the role of the pump in the biphasic modulation of cellular repolarization and refractoriness, the rate control of intracellular sodium and calcium dynamics and therefore of the adaptation of repolarization to changes in heart rate, as well as its importance in regulating pro-arrhythmic substrates through modulation of dispersion of repolarization and restitution. Theoretical findings are consistent across a variety of cell types and species including human, and widely in agreement with experimental findings. The novel insights and hypotheses on the role of the pump in cardiac electrophysiology obtained through this integrative approach could eventually lead to novel therapeutic and diagnostic strategies.

  13. Circulating Blood eNOS Contributes to the Regulation of Systemic Blood Pressure and Nitrite Homeostasis

    Science.gov (United States)

    Wood, Katherine C.; Cortese-Krott, Miriam M.; Kovacic, Jason C.; Noguchi, Audrey; Liu, Virginia B.; Wang, Xunde; Raghavachari, Nalini; Boehm, Manfred; Kato, Gregory J.; Kelm, Malte; Gladwin, Mark T.

    2013-01-01

    Objective Mice genetically deficient in endothelial nitric oxide synthase (eNOS−/−) are hypertensive with lower circulating nitrite levels, indicating the importance of constitutively produced nitric oxide (NO•) to blood pressure regulation and vascular homeostasis. While the current paradigm holds that this bioactivity derives specifically from expression of eNOS in endothelium, circulating blood cells also express eNOS protein. A functional red cell eNOS that modulates vascular NO• signaling has been proposed. Approach and Results To test the hypothesis that blood cells contribute to mammalian blood pressure regulation via eNOS-dependent NO• generation, we cross-transplanted WT and eNOS−/− mice, producing chimeras competent or deficient for eNOS expression in circulating blood cells. Surprisingly, we observed a significant contribution of both endothelial and circulating blood cell eNOS to blood pressure and systemic nitrite levels, the latter being a major component of the circulating NO• reservoir. These effects were abolished by the NOS inhibitor L-NAME and repristinated by the NOS substrate L-Arginine, and were independent of platelet or leukocyte depletion. Mouse erythrocytes were also found to carry an eNOS protein and convert 14C-Arginine into 14C-Citrulline in a NOS-dependent fashion. Conclusions These are the first studies to definitively establish a role for a blood borne eNOS, using cross transplant chimera models, that contributes to the regulation of blood pressure and nitrite homeostasis. This work provides evidence suggesting that erythrocyte eNOS may mediate this effect. PMID:23702660

  14. Kallikrein–Kinin System Suppresses Type I Interferon Responses: A Novel Pathway of Interferon Regulation

    Directory of Open Access Journals (Sweden)

    Alecia Seliga

    2018-02-01

    Full Text Available The Kallikrein–Kinin System (KKS, comprised of kallikreins (klks, bradykinins (BKs angiotensin-converting enzyme (ACE, and many other molecules, regulates a number of physiological processes, including inflammation, coagulation, angiogenesis, and control of blood pressure. In this report, we show that KKS regulates Type I IFN responses, thought to be important in lupus pathogenesis. We used CpG (TLR9 ligand, R848 (TLR7 ligand, or recombinant IFN-α to induce interferon-stimulated genes (ISGs and proteins, and observed that this response was markedly diminished by BKs, klk1 (tissue kallikrein, or captopril (an ACE inhibitor. BKs significantly decreased the ISGs induced by TLRs in vitro and in vivo (in normal and lupus-prone mice, and in human PBMCs, especially the induction of Irf7 gene (p < 0.05, the master regulator of Type I IFNs. ISGs induced by IFN-α were also suppressed by the KKS. MHC Class I upregulation, a classic response to Type I IFNs, was reduced by BKs in murine dendritic cells (DCs. BKs decreased phosphorylation of STAT2 molecules that mediate IFN signaling. Among the secreted pro-inflammatory cytokines/chemokines analyzed (IL-6, IL12p70, and CXCL10, the strongest suppressive effect was on CXCL10, a highly Type I IFN-dependent cytokine, upon CpG stimulation, both in normal and lupus-prone DCs. klks that break down into BKs, also suppressed CpG-induced ISGs in murine DCs. Captopril, a drug that inhibits ACE and increases BK, suppressed ISGs, both in mouse DCs and human PBMCs. The effects of BK were reversed with indomethacin (compound that inhibits production of PGE2, suggesting that BK suppression of IFN responses may be mediated via prostaglandins. These results highlight a novel regulatory mechanism in which members of the KKS control the Type I IFN response and suggest a role for modulators of IFNs in the pathogenesis of lupus and interferonopathies.

  15. Estradiol Synthesis in Gut-Associated Lymphoid Tissue: Leukocyte Regulation by a Sexually Monomorphic System.

    Science.gov (United States)

    Oakley, Oliver R; Kim, Kee Jun; Lin, Po-Ching; Barakat, Radwa; Cacioppo, Joseph A; Li, Zhong; Whitaker, Alexandra; Chung, Kwang Chul; Mei, Wenyan; Ko, CheMyong

    2016-12-01

    17β-estradiol is a potent sex hormone synthesized primarily by gonads in females and males that regulates development and function of the reproductive system. Recent studies show that 17β-estradiol is locally synthesized in nonreproductive tissues and regulates a myriad of events, including local inflammatory responses. In this study, we report that mesenteric lymph nodes (mLNs) and Peyer's patches (Pps) are novel sites of de novo synthesis of 17β-estradiol. These secondary lymphoid organs are located within or close to the gastrointestinal tract, contain leukocytes, and function at the forefront of immune surveillance. 17β-estradiol synthesis was initially identified using a transgenic mouse with red fluorescent protein coexpressed in cells that express aromatase, the enzyme responsible for 17β-estradiol synthesis. Subsequent immunohistochemistry and tissue culture experiments revealed that aromatase expression was localized to high endothelial venules of these lymphoid organs, and these high endothelial venule cells synthesized 17β-estradiol when isolated and cultured in vitro. Both mLNs and Pps contained 17β-estradiol with concentrations that were significantly higher than those of peripheral blood. Furthermore, the total amount of 17β-estradiol in these organs exceeded that of the gonads. Mice lacking either aromatase or estrogen receptor-β had hypertrophic Pps and mLNs with more leukocytes than their wild-type littermates, demonstrating a role for 17β-estradiol in leukocyte regulation. Importantly, we did not observe any sex-dependent differences in aromatase expression, 17β-estradiol content, or steroidogenic capacity in these lymphoid organs.

  16. ORACLS- OPTIMAL REGULATOR ALGORITHMS FOR THE CONTROL OF LINEAR SYSTEMS (DEC VAX VERSION)

    Science.gov (United States)

    Frisch, H.

    1994-01-01

    This control theory design package, called Optimal Regulator Algorithms for the Control of Linear Systems (ORACLS), was developed to aid in the design of controllers and optimal filters for systems which can be modeled by linear, time-invariant differential and difference equations. Optimal linear quadratic regulator theory, currently referred to as the Linear-Quadratic-Gaussian (LQG) problem, has become the most widely accepted method of determining optimal control policy. Within this theory, the infinite duration time-invariant problems, which lead to constant gain feedback control laws and constant Kalman-Bucy filter gains for reconstruction of the system state, exhibit high tractability and potential ease of implementation. A variety of new and efficient methods in the field of numerical linear algebra have been combined into the ORACLS program, which provides for the solution to time-invariant continuous or discrete LQG problems. The ORACLS package is particularly attractive to the control system designer because it provides a rigorous tool for dealing with multi-input and multi-output dynamic systems in both continuous and discrete form. The ORACLS programming system is a collection of subroutines which can be used to formulate, manipulate, and solve various LQG design problems. The ORACLS program is constructed in a manner which permits the user to maintain considerable flexibility at each operational state. This flexibility is accomplished by providing primary operations, analysis of linear time-invariant systems, and control synthesis based on LQG methodology. The input-output routines handle the reading and writing of numerical matrices, printing heading information, and accumulating output information. The basic vector-matrix operations include addition, subtraction, multiplication, equation, norm construction, tracing, transposition, scaling, juxtaposition, and construction of null and identity matrices. The analysis routines provide for the following

  17. ORACLS- OPTIMAL REGULATOR ALGORITHMS FOR THE CONTROL OF LINEAR SYSTEMS (CDC VERSION)

    Science.gov (United States)

    Armstrong, E. S.

    1994-01-01

    This control theory design package, called Optimal Regulator Algorithms for the Control of Linear Systems (ORACLS), was developed to aid in the design of controllers and optimal filters for systems which can be modeled by linear, time-invariant differential and difference equations. Optimal linear quadratic regulator theory, currently referred to as the Linear-Quadratic-Gaussian (LQG) problem, has become the most widely accepted method of determining optimal control policy. Within this theory, the infinite duration time-invariant problems, which lead to constant gain feedback control laws and constant Kalman-Bucy filter gains for reconstruction of the system state, exhibit high tractability and potential ease of implementation. A variety of new and efficient methods in the field of numerical linear algebra have been combined into the ORACLS program, which provides for the solution to time-invariant continuous or discrete LQG problems. The ORACLS package is particularly attractive to the control system designer because it provides a rigorous tool for dealing with multi-input and multi-output dynamic systems in both continuous and discrete form. The ORACLS programming system is a collection of subroutines which can be used to formulate, manipulate, and solve various LQG design problems. The ORACLS program is constructed in a manner which permits the user to maintain considerable flexibility at each operational state. This flexibility is accomplished by providing primary operations, analysis of linear time-invariant systems, and control synthesis based on LQG methodology. The input-output routines handle the reading and writing of numerical matrices, printing heading information, and accumulating output information. The basic vector-matrix operations include addition, subtraction, multiplication, equation, norm construction, tracing, transposition, scaling, juxtaposition, and construction of null and identity matrices. The analysis routines provide for the following

  18. Coordinated control of wind generation and energy storage for power system frequency regulation

    Science.gov (United States)

    Baone, Chaitanya Ashok

    Large-scale centralized synchronous generators have long been the primary actors in exercising active power and frequency control, and much of the existing grid control framework is predicated upon their dynamic terminal characteristics. Important among these characteristics is the inertia of such generators. These play key roles in determining the electromechanical stability of the electric power grid. Modern wind generator systems are partially or fully connected to the grid through power electronic interfaces, and hence do not present the same level of inertial coupling. The absence of inertial frequency response from modern wind generator systems is a topic of growing concern in power engineering practice, as the penetration of wind generation is expected to grow dramatically in the next few years. Solutions proposed in the literature have sought to address this problem by seeking to mimic the inherent inertial response characteristics of traditional synchronous generators via control loops added to wind generators. Recent literature has raised concerns regarding this approach, and the work here will further examine its shortcomings, motivating approaches that seek to optimally design for the characteristics of the equipment exercising the control, rather than forcing new technologies to mimic the characteristics of synchronous machines. In particular, this work will develop a new approach to power system frequency regulation, with features suited to distributed energy storage devices such as grid-scale batteries and wind turbine speed and blade pitch control. The dynamic characteristics of these new technologies are treated along with existing mechanisms, such as synchronous machine governor control, to develop a comprehensive multi-input control design approach. To make the method practically feasible for geographically distributed power systems, an observer-based distributed control design utilizing phasor measurement unit (PMU) signals along with local

  19. A Systems-Level Analysis Reveals Circadian Regulation of Splicing in Colorectal Cancer.

    Science.gov (United States)

    El-Athman, Rukeia; Fuhr, Luise; Relógio, Angela

    2018-06-20

    Accumulating evidence points to a significant role of the circadian clock in the regulation of splicing in various organisms, including mammals. Both dysregulated circadian rhythms and aberrant pre-mRNA splicing are frequently implicated in human disease, in particular in cancer. To investigate the role of the circadian clock in the regulation of splicing in a cancer progression context at the systems-level, we conducted a genome-wide analysis and compared the rhythmic transcriptional profiles of colon carcinoma cell lines SW480 and SW620, derived from primary and metastatic sites of the same patient, respectively. We identified spliceosome components and splicing factors with cell-specific circadian expression patterns including SRSF1, HNRNPLL, ESRP1, and RBM 8A, as well as altered alternative splicing events and circadian alternative splicing patterns of output genes (e.g., VEGFA, NCAM1, FGFR2, CD44) in our cellular model. Our data reveals a remarkable interplay between the circadian clock and pre-mRNA splicing with putative consequences in tumor progression and metastasis. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  20. Structural analysis of DNA–protein complexes regulating the restriction–modification system Esp1396I

    International Nuclear Information System (INIS)

    Martin, Richard N. A.; McGeehan, John E.; Ball, Neil J.; Streeter, Simon D.; Thresh, Sarah-Jane; Kneale, G. G.

    2013-01-01

    Comparison of bound and unbound DNA in protein–DNA co-crystal complexes reveals insights into controller-protein binding and DNA distortion in transcriptional regulation. The controller protein of the type II restriction–modification (RM) system Esp1396I binds to three distinct DNA operator sequences upstream of the methyltransferase and endonuclease genes in order to regulate their expression. Previous biophysical and crystallographic studies have shown molecular details of how the controller protein binds to the operator sites with very different affinities. Here, two protein–DNA co-crystal structures containing portions of unbound DNA from native operator sites are reported. The DNA in both complexes shows significant distortion in the region between the conserved symmetric sequences, similar to that of a DNA duplex when bound by the controller protein (C-protein), indicating that the naked DNA has an intrinsic tendency to bend when not bound to the C-protein. Moreover, the width of the major groove of the DNA adjacent to a bound C-protein dimer is observed to be significantly increased, supporting the idea that this DNA distortion contributes to the substantial cooperativity found when a second C-protein dimer binds to the operator to form the tetrameric repression complex

  1. Tetraspanin CD9: A Key Regulator of Cell Adhesion in the Immune System

    Directory of Open Access Journals (Sweden)

    Raquel Reyes

    2018-04-01

    Full Text Available The tetraspanin CD9 is expressed by all the major subsets of leukocytes (B cells, CD4+ T cells, CD8+ T cells, natural killer cells, granulocytes, monocytes and macrophages, and immature and mature dendritic cells and also at a high level by endothelial cells. As a typical member of the tetraspanin superfamily, a prominent feature of CD9 is its propensity to engage in a multitude of interactions with other tetraspanins as well as with different transmembrane and intracellular proteins within the context of defined membranal domains termed tetraspanin-enriched microdomains (TEMs. Through these associations, CD9 influences many cellular activities in the different subtypes of leukocytes and in endothelial cells, including intracellular signaling, proliferation, activation, survival, migration, invasion, adhesion, and diapedesis. Several excellent reviews have already covered the topic of how tetraspanins, including CD9, regulate these cellular processes in the different cells of the immune system. In this mini-review, however, we will focus particularly on describing and discussing the regulatory effects exerted by CD9 on different adhesion molecules that play pivotal roles in the physiology of leukocytes and endothelial cells, with a particular emphasis in the regulation of adhesion molecules of the integrin and immunoglobulin superfamilies.

  2. Design and Application of Drought Indexes in Highly Regulated Mediterranean Water Systems

    Science.gov (United States)

    Castelletti, A.; Zaniolo, M.; Giuliani, M.

    2017-12-01

    Costs of drought are progressively increasing due to the undergoing alteration of hydro-meteorological regimes induced by climate change. Although drought management is largely studied in the literature, most of the traditional drought indexes fail in detecting critical events in highly regulated systems, which generally rely on ad-hoc formulations and cannot be generalized to different context. In this study, we contribute a novel framework for the design of a basin-customized drought index. This index represents a surrogate of the state of the basin and is computed by combining the available information about the water available in the system to reproduce a representative target variable for the drought condition of the basin (e.g., water deficit). To select the relevant variables and combinatione thereof, we use an advanced feature extraction algorithm called Wrapper for Quasi Equally Informative Subset Selection (W-QEISS). W-QEISS relies on a multi-objective evolutionary algorithm to find Pareto-efficient subsets of variables by maximizing the wrapper accuracy, minimizing the number of selected variables, and optimizing relevance and redundancy of the subset. The accuracy objective is evaluated trough the calibration of an extreme learning machine of the water deficit for each candidate subset of variables, with the index selected from the resulting solutions identifying a suitable compromise between accuracy, cardinality, relevance, and redundancy. The approach is tested on Lake Como, Italy, a regulated lake mainly operated for irrigation supply. In the absence of an institutional drought monitoring system, we constructed the combined index using all the hydrological variables from the existing monitoring system as well as common drought indicators at multiple time aggregations. The soil moisture deficit in the root zone computed by a distributed-parameter water balance model of the agricultural districts is used as target variable. Numerical results show that

  3. Delivery of circulating lipoproteins to specific neurons in the Drosophila brain regulates systemic insulin signaling.

    Science.gov (United States)

    Brankatschk, Marko; Dunst, Sebastian; Nemetschke, Linda; Eaton, Suzanne

    2014-10-02

    The Insulin signaling pathway couples growth, development and lifespan to nutritional conditions. Here, we demonstrate a function for the Drosophila lipoprotein LTP in conveying information about dietary lipid composition to the brain to regulate Insulin signaling. When yeast lipids are present in the diet, free calcium levels rise in Blood Brain Barrier glial cells. This induces transport of LTP across the Blood Brain Barrier by two LDL receptor-related proteins: LRP1 and Megalin. LTP accumulates on specific neurons that connect to cells that produce Insulin-like peptides, and induces their release into the circulation. This increases systemic Insulin signaling and the rate of larval development on yeast-containing food compared with a plant-based food of similar nutritional content.

  4. Regulating incentives: the past and present role of the state in health care systems.

    Science.gov (United States)

    Saltman, Richard B

    2002-06-01

    The desire of national policymakers to encourage entrepreneurial behavior in the health sector has generated not only a new structure of market-oriented incentives, but also a new regulatory role for the State. To ensure that entrepreneurial behavior will be directed toward achieving planned market objectives, the State must shift modalities from staid bureaucratic models of command-and-control to more sensitive and sophisticated systems of oversight and supervision. Available evidence suggests that this structural transformation is currently occurring in several Northern European countries. Successful implementation of that shift will require a new, intensive, and expensive strategy for human resources development, raising questions about the financial feasibility of this incentives-plus-regulation model for less-well-off CEE/CIS and developing countries.

  5. Passive containment cooling system with drywell pressure regulation for boiling water reactor

    Science.gov (United States)

    Hill, P.R.

    1994-12-27

    A boiling water reactor is described having a regulating valve for placing the wetwell in flow communication with an intake duct of the passive containment cooling system. This subsystem can be adjusted to maintain the drywell pressure at (or slightly below or above) wetwell pressure after the initial reactor blowdown transient is over. This addition to the PCCS design has the benefit of eliminating or minimizing steam leakage from the drywell to the wetwell in the longer-term post-LOCA time period and also minimizes the temperature difference between drywell and wetwell. This in turn reduces the rate of long-term pressure buildup of the containment, thereby extending the time to reach the design pressure limit. 4 figures.

  6. Porcine models for the study of local and systemic regulation of innate immune factors in obesity

    DEFF Research Database (Denmark)

    Højbøge, Tina Rødgaard

    state of low-grade inflammation in the adipose tissues, which involves several factors of the innate immune response having a range of systemic effects and which has been implicated in the development of the metabolic syndrome. To investigate the impact of obesity and obesity-related diseases good...... translational animal models are needed, and as such pigs have been proposed as relevant models for human obesity-induced inflammation as pigs share many genetic, anatomical and physiological features with humans. In this project the up- and downregulation of genes and proteins involved in the innate immune...... the number of animals to be used in a trial to obtain statistical power. For the gene regulation analysis, two platforms for quantitative real-time PCR (qPCR) were employed: The Rotor-Gene Q instrument and the microfluidics-based high-throughput Bio-Mark. For the serum protein concentrations analysis several...

  7. Bifurcation Regulations Governed by Delay Self-Control Feedback in a Stochastic Birhythmic System

    Science.gov (United States)

    Ma, Zhidan; Ning, Lijuan

    2017-12-01

    We aim to investigate bifurcation behaviors in a stochastic birhythmic van der Pol (BVDP) system subjected to delay self-control feedback. First, the harmonic approximation is adopted to drive the delay self-control feedback to state variables without delay. Then, Fokker-Planck-Kolmogorov (FPK) equation and stationary probability density function (SPDF) for amplitude are obtained by applying stochastic averaging method. Finally, dynamical scenarios of the change of delay self-control feedback as well as noise that markedly influence bifurcation performance are observed. It is found that: the big feedback strength and delay will suppress the large amplitude limit cycle (LC) while the relatively big noise strength facilitates the large amplitude LC, which imply the proposed regulation strategies are feasible. Interestingly enough, the inner LC is never destroyed due to noise. Furthermore, the validity of analytical results was verified by Monte Carlo simulation of the dynamics.

  8. SPECIFIC REGULATIONS REGARDING THE SOLVING OF LABOR DISPUTES IN ROMANIAN LEGAL SYSTEM

    Directory of Open Access Journals (Sweden)

    Onica -Chipea Lavinia

    2012-01-01

    Full Text Available The paper aims to briefly review specific provisions of labor legislation for the solving of labor disputes. Those rules are found in matters of discrimination in the payment settlements, the public sector staff as well as some personnel status or disciplinary (work stops at Status of Teachers and established a derogationfrom the common law (Labor Code Law nr.62/2011 of Social Dialogue in resolving individual labor conflicts(former conflicts of rights. The role and importance of these regulations is that they give the parties the employment relationship, particularly employees, way, way more for rights enshrined in law. Appeals, complaints or expressions of individual grievances be settled outside the judicial system organ (the courts,authorizing officers, judicial administrative organs, which aim at restoring order violated.

  9. Validation and simulation of a regulated survey system through Monte Carlo techniques

    Directory of Open Access Journals (Sweden)

    Asier Lacasta Soto

    2015-07-01

    Full Text Available Channel flow covers long distances and obeys to variable temporal behaviour. It is usually regulated by hydraulic elements as lateralgates to provide a correct of water supply. The dynamics of this kind of flow is governed by a partial differential equations systemnamed shallow water model. They have to be complemented with a simplified formulation for the gates. All the set of equations forma non-linear system that can only be solved numerically. Here, an explicit upwind numerical scheme in finite volumes able to solveall type of flow regimes is used. Hydraulic structures (lateral gates formulation introduces parameters with some uncertainty. Hence,these parameters will be calibrated with a Monte Carlo algorithm obtaining associated coefficients to each gate. Then, they will bechecked, using real cases provided by the monitorizing equipment of the Pina de Ebro channel located in Zaragoza.

  10. Modernization of the Light generators voltage regulation systems and evaluation of the necessity of stabilizers

    Energy Technology Data Exchange (ETDEWEB)

    Barros, Paulo R.G.M. de; Oliveira Aires, Joao C. de; Nascimento, Anselmo R; Almeida, Antonio J.B. de [Light Servicos de Eletricidade SA, Rio de Janeiro, RJ (Brazil); Souza Pedroso, Alquindar de [Centro de Pesquisas de Energia Eletrica, Rio de Janeiro, RJ (Brazil)

    1988-12-31

    This paper presents the studies and solutions adopted by Light to mitigate the problems relative to the lack of power and voltage oscillation damping in the Rio de Janeiro area (Southeast Brazil) for the contingencies of South/Southeast interconnection loss and 500 kV transmission line loss. The characteristics of Light generating system, comprised of the Fontes Velha, Fontes Nova, Ilha dos Pombos, Nilo Pecanha, and Pereira Passos hydroelectric plants are shown. Excitation/Voltage regulation alternatives are also presented. The performance of proposed equipment is discussed based on some simulation analysis. Finally, some alternatives for improvement of Rio de Janeiro area dynamic performance are suggested. 4 refs., 3 tabs., 5 figs.

  11. Regulation of antiapoptotic MCL-1 function by gossypol: mechanistic insights from in vitro reconstituted systems.

    Science.gov (United States)

    Etxebarria, Aitor; Landeta, Olatz; Antonsson, Bruno; Basañez, Gorka

    2008-12-01

    Small-molecule drugs that induce apoptosis in tumor cells by activation of the BCL-2-regulated mitochondrial outer membrane permeabilization (MOMP) pathway hold promise for rational anticancer therapies. Accumulating evidence indicates that the natural product gossypol and its derivatives can kill tumor cells by targeting antiapoptotic BCL-2 family members in such a manner as to trigger MOMP. However, due to the inherent complexity of the cellular apoptotic network, the precise mechanisms by which interactions between gossypol and individual BCL-2 family members lead to MOMP remain poorly understood. Here, we used simplified systems bearing physiological relevance to examine the impact of gossypol on the function of MCL-1, a key determinant for survival of various human malignancies that has become a highly attractive target for anticancer drug design. First, using a reconstituted liposomal system that recapitulates basic aspects of the BCL-2-regulated MOMP pathway, we demonstrate that MCL-1 inhibits BAX permeabilizing function via a "dual-interaction" mechanism, while submicromolar concentrations of gossypol reverse MCL-1-mediated inhibition of functional BAX activation. Solution-based studies showed that gossypol competes with BAX/BID BH3 ligands for binding to MCL-1 hydrophobic groove, thereby providing with a mechanistic explanation for how gossypol restores BAX permeabilizing function in the presence of MCL-1. By contrast, no evidence was found indicating that gossypol transforms MCL-1 into a BAX-like pore-forming molecule. Altogether, our findings validate MCL-1 as a direct target of gossypol, and highlight that making this antiapoptotic protein unable to inhibit BAX-driven MOMP may represent one important mechanism by which gossypol exerts its cytotoxic effect in selected cancer cells.

  12. An Innovative Adaptive Control System to Regulate Microclimatic Conditions in a Greenhouse

    Directory of Open Access Journals (Sweden)

    Giuseppina Nicolosi

    2017-05-01

    Full Text Available In the recent past home automation has been expanding its objectives towards new solutions both inside the smart home and in its outdoor spaces, where several new technologies are available. This work has developed an approach to integrate intelligent microclimatic greenhouse control into integrated home automation. Microclimatic control of greenhouses is a critical issue in agricultural practices, due to often common sudden daily variation of climatic conditions, and to its potentially detrimental effect on plant growth. A greenhouse is a complex thermodynamic system where indoor temperature and relative humidity have to be closely monitored to facilitate plant growth and production. This work shows an adaptive control system tailored to regulate microclimatic conditions in a greenhouse, by using an innovative combination of soft computing applications. In particular, a neural network solution has been proposed in order to forecast the climatic behavior of greenhouse, while a parallel fuzzy scheme approach is carried out in order to adjust the air speed of fan-coil and its temperature. The proposed combined approach provides a better control of greenhouse climatic conditions due to the system’s capability to base instantaneous solutions both on real measured variables and on forecasted climatic change. Several simulation campaigns were carried out to perform accurate neural network and fuzzy schemes, aimed at obtaining respectively a minimum forecasted error value and a more appropriate fuzzification and de-fuzzification process. A Matlab/Simulink solution implemented with a combined approach and its relevant obtained performance is also shown in present study, demonstrating that through controlled parameters it will be possible to maintain a better level of indoor climatic conditions. In the present work we prove how with a forecast of outside temperature at the next time-instant and rule-based controller monitoring of cooling or heating air

  13. Nitrogen assimilation system in maize is regulated by developmental and tissue-specific mechanisms

    KAUST Repository

    Plett, Darren

    2016-08-10

    Key message: We found metabolites, enzyme activities and enzyme transcript abundances vary significantly across the maize lifecycle, but weak correlation exists between the three groups. We identified putative genes regulating nitrate assimilation. Abstract: Progress in improving nitrogen (N) use efficiency (NUE) of crop plants has been hampered by the complexity of the N uptake and utilisation systems. To understand this complexity we measured the activities of seven enzymes and ten metabolites related to N metabolism in the leaf and root tissues of Gaspe Flint maize plants grown in 0.5 or 2.5 mM NO3 − throughout the lifecycle. The amino acids had remarkably similar profiles across the lifecycle except for transient responses, which only appeared in the leaves for aspartate or in the roots for asparagine, serine and glycine. The activities of the enzymes for N assimilation were also coordinated to a certain degree, most noticeably with a peak in root activity late in the lifecycle, but with wide variation in the activity levels over the course of development. We analysed the transcriptional data for gene sets encoding the measured enzymes and found that, unlike the enzyme activities, transcript levels of the corresponding genes did not exhibit the same coordination across the lifecycle and were only weakly correlated with the levels of various amino acids or individual enzyme activities. We identified gene sets which were correlated with the enzyme activity profiles, including seven genes located within previously known quantitative trait loci for enzyme activities and hypothesise that these genes are important for the regulation of enzyme activities. This work provides insights into the complexity of the N assimilation system throughout development and identifies candidate regulatory genes, which warrant further investigation in efforts to improve NUE in crop plants. © 2016, Springer Science+Business Media Dordrecht.

  14. CARF and WYL domains: ligand-binding regulators of prokaryotic defense systems

    Directory of Open Access Journals (Sweden)

    Kira eMakarova

    2014-04-01

    Full Text Available CRISPR-Cas adaptive immunity systems of bacteria and archaea insert fragments of virus or plasmid DNA as spacer sequences into CRISPR repeat loci. Processed transcripts encompassing these spacers guide the cleavage of the cognate foreign DNA or RNA. Most CRISPR-Cas loci, in addition to recognized cas genes, also include genes that are not directly implicated in spacer acquisition, CRISPR transcript processing or interference. Here we comprehensively analyze sequences, structures and genomic neighborhoods of one of the most widespread groups of such genes that encode proteins containing a predicted nucleotide-binding domain with a Rossmann-like fold, which we denote CARF (CRISPR-associated Rossmann fold. Several CARF protein structures have been determined but functional characterization of these proteins is lacking. The CARF domain is most frequently combined with a C-terminal winged helix-turn-helix DNA-binding domain and effector domains most of which are predicted to possess DNase or RNase activity. Divergent CARF domains are also found in RtcR proteins, sigma-54 dependent regulators of the rtc RNA repair operon. CARF genes frequently co-occur with those coding for proteins containing the WYL domain with the Sm-like SH3 β-barrel fold, which is also predicted to bind ligands. CRISPR-Cas and possibly other defense systems are predicted to be transcriptionally regulated by multiple ligand-binding proteins containing WYL and CARF domains which sense modified nucleotides and nucleotide derivatives generated during virus infection. We hypothesize that CARF domains also transmit the signal from the bound ligand to the fused effector domains which attack either alien or self nucleic acids, resulting, respectively, in immunity complementing the CRISPR-Cas action or in dormancy/programmed cell death.

  15. Nitrogen assimilation system in maize is regulated by developmental and tissue-specific mechanisms

    KAUST Repository

    Plett, Darren; Holtham, Luke; Baumann, Ute; Kalashyan, Elena; Francis, Karen; Enju, Akiko; Toubia, John; Roessner, Ute; Bacic, Antony; Rafalski, Antoni; Dhugga, Kanwarpal S.; Tester, Mark A.; Garnett, Trevor; Kaiser, Brent N.

    2016-01-01

    Key message: We found metabolites, enzyme activities and enzyme transcript abundances vary significantly across the maize lifecycle, but weak correlation exists between the three groups. We identified putative genes regulating nitrate assimilation. Abstract: Progress in improving nitrogen (N) use efficiency (NUE) of crop plants has been hampered by the complexity of the N uptake and utilisation systems. To understand this complexity we measured the activities of seven enzymes and ten metabolites related to N metabolism in the leaf and root tissues of Gaspe Flint maize plants grown in 0.5 or 2.5 mM NO3 − throughout the lifecycle. The amino acids had remarkably similar profiles across the lifecycle except for transient responses, which only appeared in the leaves for aspartate or in the roots for asparagine, serine and glycine. The activities of the enzymes for N assimilation were also coordinated to a certain degree, most noticeably with a peak in root activity late in the lifecycle, but with wide variation in the activity levels over the course of development. We analysed the transcriptional data for gene sets encoding the measured enzymes and found that, unlike the enzyme activities, transcript levels of the corresponding genes did not exhibit the same coordination across the lifecycle and were only weakly correlated with the levels of various amino acids or individual enzyme activities. We identified gene sets which were correlated with the enzyme activity profiles, including seven genes located within previously known quantitative trait loci for enzyme activities and hypothesise that these genes are important for the regulation of enzyme activities. This work provides insights into the complexity of the N assimilation system throughout development and identifies candidate regulatory genes, which warrant further investigation in efforts to improve NUE in crop plants. © 2016, Springer Science+Business Media Dordrecht.

  16. Regulation of ICAM-1 in Cells of the Monocyte/Macrophage System in Microgravity

    Directory of Open Access Journals (Sweden)

    Katrin Paulsen

    2015-01-01

    Full Text Available Cells of the immune system are highly sensitive to altered gravity, and the monocyte as well as the macrophage function is proven to be impaired under microgravity conditions. In our study, we investigated the surface expression of ICAM-1 protein and expression of ICAM-1 mRNA in cells of the monocyte/macrophage system in microgravity during clinostat, parabolic flight, sounding rocket, and orbital experiments. In murine BV-2 microglial cells, we detected a downregulation of ICAM-1 expression in clinorotation experiments and a rapid and reversible downregulation in the microgravity phase of parabolic flight experiments. In contrast, ICAM-1 expression increased in macrophage-like differentiated human U937 cells during the microgravity phase of parabolic flights and in long-term microgravity provided by a 2D clinostat or during the orbital SIMBOX/Shenzhou-8 mission. In nondifferentiated U937 cells, no effect of microgravity on ICAM-1 expression could be observed during parabolic flight experiments. We conclude that disturbed immune function in microgravity could be a consequence of ICAM-1 modulation in the monocyte/macrophage system, which in turn could have a strong impact on the interaction with T lymphocytes and cell migration. Thus, ICAM-1 can be considered as a rapid-reacting and sustained gravity-regulated molecule in mammalian cells.

  17. Construction of a global pain systems network highlights phospholipid signaling as a regulator of heat nociception.

    Directory of Open Access Journals (Sweden)

    G Gregory Neely

    Full Text Available The ability to perceive noxious stimuli is critical for an animal's survival in the face of environmental danger, and thus pain perception is likely to be under stringent evolutionary pressure. Using a neuronal-specific RNAi knock-down strategy in adult Drosophila, we recently completed a genome-wide functional annotation of heat nociception that allowed us to identify α2δ3 as a novel pain gene. Here we report construction of an evolutionary-conserved, system-level, global molecular pain network map. Our systems map is markedly enriched for multiple genes associated with human pain and predicts a plethora of novel candidate pain pathways. One central node of this pain network is phospholipid signaling, which has been implicated before in pain processing. To further investigate the role of phospholipid signaling in mammalian heat pain perception, we analysed the phenotype of PIP5Kα and PI3Kγ mutant mice. Intriguingly, both of these mice exhibit pronounced hypersensitivity to noxious heat and capsaicin-induced pain, which directly mapped through PI3Kγ kinase-dead knock-in mice to PI3Kγ lipid kinase activity. Using single primary sensory neuron recording, PI3Kγ function was mechanistically linked to a negative regulation of TRPV1 channel transduction. Our data provide a systems map for heat nociception and reinforces the extraordinary conservation of molecular mechanisms of nociception across different species.

  18. Robust Takagi-Sugeno Fuzzy Dynamic Regulator for Trajectory Tracking of a Pendulum-Cart System

    Directory of Open Access Journals (Sweden)

    Miguel A. Llama

    2015-01-01

    Full Text Available Starting from a nonlinear model for a pendulum-cart system, on which viscous friction is considered, a Takagi-Sugeno (T-S fuzzy augmented model (TSFAM as well as a TSFAM with uncertainty (TSFAMwU is proposed. Since the design of a T-S fuzzy controller is based on the T-S fuzzy model of the nonlinear system, then, to address the trajectory tracking problem of the pendulum-cart system, three T-S fuzzy controllers are proposed via parallel distributed compensation: (1 a T-S fuzzy servo controller (TSFSC designed from the TSFAM; (2 a robust TSFSC (RTSFSC designed from the TSFAMwU; and (3 a robust T-S fuzzy dynamic regulator (RTSFDR designed from the RTSFSC with the addition of a T-S fuzzy observer, which estimates cart and pendulum velocities. Both TSFAM and TSFAMwU are comprised of two fuzzy rules and designed via local approximation in fuzzy partition spaces technique. Feedback gains for the three fuzzy controllers are obtained via linear matrix inequalities approach. A swing-up controller is developed to swing the pendulum up from its pendant position to its upright position. Real-time experiments validate the effectiveness of the proposed schemes, keeping the pendulum in its upright position while the cart follows a reference signal, standing out the RTSFDR.

  19. Sex differences in the locus coeruleus-norepinephrine system and its regulation by stress.

    Science.gov (United States)

    Bangasser, Debra A; Wiersielis, Kimberly R; Khantsis, Sabina

    2016-06-15

    Women are more likely than men to suffer from post-traumatic stress disorder (PTSD) and major depression. In addition to their sex bias, these disorders share stress as an etiological factor and hyperarousal as a symptom. Thus, sex differences in brain arousal systems and their regulation by stress could help explain increased vulnerability to these disorders in women. Here we review preclinical studies that have identified sex differences in the locus coeruleus (LC)-norepinephrine (NE) arousal system. First, we detail how structural sex differences in the LC can bias females towards increased arousal in response to emotional events. Second, we highlight studies demonstrating that estrogen can increase NE in LC target regions by enhancing the capacity for NE synthesis, while reducing NE degradation, potentially increasing arousal in females. Third, we review data revealing how sex differences in the stress receptor, corticotropin releasing factor 1 (CRF1), can increase LC neuronal sensitivity to CRF in females compared to males. This effect could translate into hyperarousal in women under conditions of CRF hypersecretion that occur in PTSD and depression. The implications of these sex differences for the treatment of stress-related psychiatric disorders are discussed. Moreover, the value of using information regarding biological sex differences to aid in the development of novel pharmacotherapies to better treat men and women with PTSD and depression is also highlighted. This article is part of a Special Issue entitled SI: Noradrenergic System. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Construction of a Global Pain Systems Network Highlights Phospholipid Signaling as a Regulator of Heat Nociception

    Science.gov (United States)

    Mair, Norbert; Racz, Ildiko; Milinkeviciute, Giedre; Meixner, Arabella; Nayanala, Swetha; Griffin, Robert S.; Belfer, Inna; Dai, Feng; Smith, Shad; Diatchenko, Luda; Marengo, Stefano; Haubner, Bernhard J.; Novatchkova, Maria; Gibson, Dustin; Maixner, William; Pospisilik, J. Andrew; Hirsch, Emilio; Whishaw, Ian Q.; Zimmer, Andreas; Gupta, Vaijayanti; Sasaki, Junko; Kanaho, Yasunori; Sasaki, Takehiko; Kress, Michaela; Woolf, Clifford J.; Penninger, Josef M.

    2012-01-01

    The ability to perceive noxious stimuli is critical for an animal's survival in the face of environmental danger, and thus pain perception is likely to be under stringent evolutionary pressure. Using a neuronal-specific RNAi knock-down strategy in adult Drosophila, we recently completed a genome-wide functional annotation of heat nociception that allowed us to identify α2δ3 as a novel pain gene. Here we report construction of an evolutionary-conserved, system-level, global molecular pain network map. Our systems map is markedly enriched for multiple genes associated with human pain and predicts a plethora of novel candidate pain pathways. One central node of this pain network is phospholipid signaling, which has been implicated before in pain processing. To further investigate the role of phospholipid signaling in mammalian heat pain perception, we analysed the phenotype of PIP5Kα and PI3Kγ mutant mice. Intriguingly, both of these mice exhibit pronounced hypersensitivity to noxious heat and capsaicin-induced pain, which directly mapped through PI3Kγ kinase-dead knock-in mice to PI3Kγ lipid kinase activity. Using single primary sensory neuron recording, PI3Kγ function was mechanistically linked to a negative regulation of TRPV1 channel transduction. Our data provide a systems map for heat nociception and reinforces the extraordinary conservation of molecular mechanisms of nociception across different species. PMID:23236288

  1. Tuning of PID controller for an automatic regulator voltage system using chaotic optimization approach

    International Nuclear Information System (INIS)

    Santos Coelho, Leandro dos

    2009-01-01

    Despite the popularity, the tuning aspect of proportional-integral-derivative (PID) controllers is a challenge for researchers and plant operators. Various controllers tuning methodologies have been proposed in the literature such as auto-tuning, self-tuning, pattern recognition, artificial intelligence, and optimization methods. Chaotic optimization algorithms as an emergent method of global optimization have attracted much attention in engineering applications. Chaotic optimization algorithms, which have the features of easy implementation, short execution time and robust mechanisms of escaping from local optimum, is a promising tool for engineering applications. In this paper, a tuning method for determining the parameters of PID control for an automatic regulator voltage (AVR) system using a chaotic optimization approach based on Lozi map is proposed. Since chaotic mapping enjoys certainty, ergodicity and the stochastic property, the proposed chaotic optimization introduces chaos mapping using Lozi map chaotic sequences which increases its convergence rate and resulting precision. Simulation results are promising and show the effectiveness of the proposed approach. Numerical simulations based on proposed PID control of an AVR system for nominal system parameters and step reference voltage input demonstrate the good performance of chaotic optimization.

  2. Regulation and Supervision of The Global Financial System. A Proposal for Institutional Reform

    NARCIS (Netherlands)

    Denters, H.M.G.

    2009-01-01

    nternational financial markets are supervised primarily by national authorities. However, national authorities are inherently incapable to regulate and supervise seamless globalised financial markets. To the extent international regulators exist, they constitute a disorderly patchwork of

  3. Regulation of taurine transport systems by protein kinase CK2 in mammalian cells

    DEFF Research Database (Denmark)

    Lambert, Ian Henry; Hansen, Daniel Bloch

    2011-01-01

    regulate the cellular content of the major cellular organic osmolyte, taurine with emphasis on CK2 mediated regulation of active taurine uptake and volume-sensitive taurine release. Furthermore, we discuss how CK2-mediated regulation of taurine homeostasis is potentially involved in cellular functions...

  4. Improving public transportation systems with self-organization: A headway-based model and regulation of passenger alighting and boarding.

    Science.gov (United States)

    Carreón, Gustavo; Gershenson, Carlos; Pineda, Luis A

    2017-01-01

    The equal headway instability-the fact that a configuration with regular time intervals between vehicles tends to be volatile-is a common regulation problem in public transportation systems. An unsatisfactory regulation results in low efficiency and possible collapses of the service. Computational simulations have shown that self-organizing methods can regulate the headway adaptively beyond the theoretical optimum. In this work, we develop a computer simulation for metro systems fed with real data from the Mexico City Metro to test the current regulatory method with a novel self-organizing approach. The current model considers overall system's data such as minimum and maximum waiting times at stations, while the self-organizing method regulates the headway in a decentralized manner using local information such as the passenger's inflow and the positions of neighboring trains. The simulation shows that the self-organizing method improves the performance over the current one as it adapts to environmental changes at the timescale they occur. The correlation between the simulation of the current model and empirical observations carried out in the Mexico City Metro provides a base to calculate the expected performance of the self-organizing method in case it is implemented in the real system. We also performed a pilot study at the Balderas station to regulate the alighting and boarding of passengers through guide signs on platforms. The analysis of empirical data shows a delay reduction of the waiting time of trains at stations. Finally, we provide recommendations to improve public transportation systems.

  5. Sensing the environment: regulation of local and global homeostasis by the skin's neuroendocrine system.

    Science.gov (United States)

    Slominski, Andrzej T; Zmijewski, Michal A; Skobowiat, Cezary; Zbytek, Blazej; Slominski, Radomir M; Steketee, Jeffery D

    2012-01-01

    Skin, the body's largest organ, is strategically located at the interface with the external environment where it detects, integrates, and responds to a diverse range of stressors including solar radiation. It has already been established that the skin is an important peripheral neuro-endocrine-immune organ that is tightly networked to central regulatory systems. These capabilities contribute to the maintenance of peripheral homeostasis. Specifically, epidermal and dermal cells produce and respond to classical stress neurotransmitters, neuropeptides, and hormones. Such production is stimulated by ultraviolet radiation (UVR), biological factors (infectious and noninfectious), and other physical and chemical agents. Examples of local biologically active products are cytokines, biogenic amines (catecholamines, histamine, serotonin, and N-acetyl-serotonin), melatonin, acetylocholine, neuropeptides including pituitary (proopiomelanocortin-derived ACTH, beta-endorphin or MSH peptides, thyroid-stimulating hormone) and hypothalamic (corticotropin-releasing factor and related urocortins, thyroid-releasing hormone) hormones as well as enkephalins and dynorphins, thyroid hormones, steroids (glucocorticoids, mineralocorticoids, sex hormones, 7-delta steroids), secosteroids, opioids, and endocannabinoids. The production of these molecules is hierarchical, organized along the algorithms of classical neuroendocrine axes such as hypothalamic-pituitary-adrenal axis (HPA), hypothalamic-thyroid axis (HPT), serotoninergic, melatoninergic, catecholaminergic, cholinergic, steroid/secosteroidogenic, opioid, and endocannbinoid systems. Dysregulation of these axes or of communication between them may lead to skin and/ or systemic diseases. These local neuroendocrine networks are also addressed at restricting maximally the effect of noxious environmental agents to preserve local and consequently global homeostasis. Moreover, the skin-derived factors/systems can also activate cutaneous nerve

  6. Redox regulation and pro-oxidant reactions in the physiology of circadian systems.

    Science.gov (United States)

    Méndez, Isabel; Vázquez-Martínez, Olivia; Hernández-Muñoz, Rolando; Valente-Godínez, Héctor; Díaz-Muñoz, Mauricio

    2016-05-01

    Rhythms of approximately 24 h are pervasive in most organisms and are known as circadian. There is a molecular circadian clock in each cell sustained by a feedback system of interconnected "clock" genes and transcription factors. In mammals, the timing system is formed by a central pacemaker, the suprachiasmatic nucleus, in coordination with a collection of peripheral oscillators. Recently, an extensive interconnection has been recognized between the molecular circadian clock and the set of biochemical pathways that underlie the bioenergetics of the cell. A principle regulator of metabolic networks is the flow of electrons between electron donors and acceptors. The concomitant reduction and oxidation (redox) reactions directly influence the balance between anabolic and catabolic processes. This review summarizes and discusses recent findings concerning the mutual and dynamic interactions between the molecular circadian clock, redox reactions, and redox signaling. The scope includes the regulatory role played by redox coenzymes (NAD(P)+/NAD(P)H, GSH/GSSG), reactive oxygen species (superoxide anion, hydrogen peroxide), antioxidants (melatonin), and physiological events that modulate the redox state (feeding condition, circadian rhythms) in determining the timing capacity of the molecular circadian clock. In addition, we discuss a purely metabolic circadian clock, which is based on the redox enzymes known as peroxiredoxins and is present in mammalian red blood cells and in other biological systems. Both the timing system and the metabolic network are key to a better understanding of widespread pathological conditions such as the metabolic syndrome, obesity, and diabetes. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  7. The HO-1/CO system regulates mitochondrial-capillary density relationships in human skeletal muscle.

    Science.gov (United States)

    Pecorella, Shelly R H; Potter, Jennifer V F; Cherry, Anne D; Peacher, Dionne F; Welty-Wolf, Karen E; Moon, Richard E; Piantadosi, Claude A; Suliman, Hagir B

    2015-10-15

    The heme oxygenase-1 (HO-1)/carbon monoxide (CO) system induces mitochondrial biogenesis, but its biological impact in human skeletal muscle is uncertain. The enzyme system generates CO, which stimulates mitochondrial proliferation in normal muscle. Here we examined whether CO breathing can be used to produce a coordinated metabolic and vascular response in human skeletal muscle. In 19 healthy subjects, we performed vastus lateralis muscle biopsies and tested one-legged maximal O2 uptake (V̇o2max) before and after breathing air or CO (200 ppm) for 1 h daily for 5 days. In response to CO, there was robust HO-1 induction along with increased mRNA levels for nuclear-encoded mitochondrial transcription factor A (Tfam), cytochrome c, cytochrome oxidase subunit IV (COX IV), and mitochondrial-encoded COX I and NADH dehydrogenase subunit 1 (NDI). CO breathing did not increase V̇o2max (1.96 ± 0.51 pre-CO, 1.87 ± 0.50 post-CO l/min; P = not significant) but did increase muscle citrate synthase, mitochondrial density (139.0 ± 34.9 pre-CO, 219.0 ± 36.2 post-CO; no. of mitochondrial profiles/field), myoglobin content and glucose transporter (GLUT4) protein level and led to GLUT4 localization to the myocyte membrane, all consistent with expansion of the tissue O2 transport system. These responses were attended by increased cluster of differentiation 31 (CD31)-positive muscle capillaries (1.78 ± 0.16 pre-CO, 2.37 ± 0.59 post-CO; capillaries/muscle fiber), implying the enrichment of microvascular O2 reserve. The findings support that induction of the HO-1/CO system by CO not only improves muscle mitochondrial density, but regulates myoglobin content, GLUT4 localization, and capillarity in accordance with current concepts of skeletal muscle plasticity. Copyright © 2015 the American Physiological Society.

  8. Regulation of host-pathogen interactions via the post-transcriptional Csr/Rsm system.

    Science.gov (United States)

    Kusmierek, Maria; Dersch, Petra

    2018-02-01

    A successful colonization of specific hosts requires a rapid and efficient adaptation of the virulence-relevant gene expression program by bacterial pathogens. An important element in this endeavor is the Csr/Rsm system. This multi-component, post-transcriptional control system forms a central hub within complex regulatory networks and coordinately adjusts virulence properties with metabolic and physiological attributes of the pathogen. A key function is elicited by the RNA-binding protein CsrA/RsmA. CsrA/RsmA interacts with numerous target mRNAs, many of which encode crucial virulence factors, and alters their translation, stability or elongation of transcription. Recent studies highlighted that important colonization factors, toxins, and bacterial secretion systems are under CsrA/RsmA control. CsrA/RsmA deficiency impairs host colonization and attenuates virulence, making this post-transcriptional regulator a suitable drug target. The CsrA/RsmA protein can be inactivated through sequestration by non-coding RNAs, or via binding to specific highly abundant mRNAs and interacting proteins. The wide range of interaction partners and RNA targets, as well as the overarching, interlinked genetic control circuits illustrate the complexity of this regulatory system in the different pathogens. Future work addressing spatio-temporal changes of Csr/Rsm-mediated control during the course of an infection will help us to understand how bacteria reprogram their expression profile to cope with continuous changes experienced in colonized niches. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. The role of nitric oxide in regulation of the cardiovascular system in reptiles.

    Science.gov (United States)

    Skovgaard, Nini; Galli, Gina; Abe, Augusto; Taylor, Edwin W; Wang, Tobias

    2005-10-01

    The roles that nitric oxide (NO) plays in the cardiovascular system of reptiles are reviewed, with particular emphasis on its effects on central vascular blood flows in the systemic and pulmonary circulations. New data is presented that describes the effects on hemodynamic variables in varanid lizards of exogenously administered NO via the nitric oxide donor sodium nitroprusside (SNP) and inhibition of nitric oxide synthase (NOS) by l-nitroarginine methyl ester (l-NAME). Furthermore, preliminary data on the effects of SNP on hemodynamic variables in the tegu lizard are presented. The findings are compared with previously published data from our laboratory on three other species of reptiles: pythons (), rattlesnakes () and turtles (). These five species of reptiles possess different combinations of division of the heart and structural complexity of the lungs. Comparison of their responses to NO donors and NOS inhibitors may reveal whether the potential contribution of NO to vascular tone correlates with pulmonary complexity and/or with blood pressure. All existing studies on reptiles have clearly established a potential role for NO in regulating vascular tone in the systemic circulation and NO may be important for maintaining basal systemic vascular tone in varanid lizards, pythons and turtles, through a continuous release of NO. In contrast, the pulmonary circulation is less responsive to NO donors or NOS inhibitors, and it was only in pythons and varanid lizards that the lungs responded to SNP. Both species have a functionally separated heart, so it is possible that NO may exert a larger role in species with low pulmonary blood pressures, irrespective of lung complexity.

  10. Molecular Regulation of Alternative Polyadenylation (APA) within the Drosophila Nervous System.

    Science.gov (United States)

    Vallejos Baier, Raul; Picao-Osorio, Joao; Alonso, Claudio R

    2017-10-27

    Alternative polyadenylation (APA) is a widespread gene regulatory mechanism that generates mRNAs with different 3'-ends, allowing them to interact with different sets of RNA regulators such as microRNAs and RNA-binding proteins. Recent studies have shown that during development, neural tissues produce mRNAs with particularly long 3'UTRs, suggesting that such extensions might be important for neural development and function. Despite this, the mechanisms underlying neural APA are not well understood. Here, we investigate this problem within the Drosophila nervous system, focusing on the roles played by general cleavage and polyadenylation factors (CPA factors). In particular, we examine the model that modulations in CPA factor concentration may affect APA during development. For this, we first analyse the expression of the Drosophila orthologues of all mammalian CPA factors and note that their expression decreases during embryogenesis. In contrast to this global developmental decrease in CPA factor expression, we see that cleavage factor I (CFI) expression is actually elevated in the late embryonic central nervous system, suggesting that CFI might play a special role in neural tissues. To test this, we use the UAS/Gal4 system to deplete CFI proteins from neural tissue and observe that in this condition, multiple genes switch their APA patterns, demonstrating a role of CFI in APA control during Drosophila neural development. Furthermore, analysis of genes with 3'UTR extensions of different length leads us to suggest a novel relation between 3'UTR length and sensitivity to CPA factor expression. Our work thus contributes to the understanding of the mechanisms of APA control within the developing central nervous system. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. A response regulator interfaces between the Frz chemosensory system and the MglA/MglB GTPase/GAP module to regulate polarity in Myxococcus xanthus.

    Directory of Open Access Journals (Sweden)

    Daniela Keilberg

    2012-09-01

    Full Text Available How cells establish and dynamically change polarity are general questions in cell biology. Cells of the rod-shaped bacterium Myxococcus xanthus move on surfaces with defined leading and lagging cell poles. Occasionally, cells undergo reversals, which correspond to an inversion of the leading-lagging pole polarity axis. Reversals are induced by the Frz chemosensory system and depend on relocalization of motility proteins between the poles. The Ras-like GTPase MglA localizes to and defines the leading cell pole in the GTP-bound form. MglB, the cognate MglA GTPase activating protein, localizes to and defines the lagging pole. During reversals, MglA-GTP and MglB switch poles and, therefore, dynamically localized motility proteins switch poles. We identified the RomR response regulator, which localizes in a bipolar asymmetric pattern with a large cluster at the lagging pole, as important for motility and reversals. We show that RomR interacts directly with MglA and MglB in vitro. Furthermore, RomR, MglA, and MglB affect the localization of each other in all pair-wise directions, suggesting that RomR stimulates motility by promoting correct localization of MglA and MglB in MglA/RomR and MglB/RomR complexes at opposite poles. Moreover, localization analyses suggest that the two RomR complexes mutually exclude each other from their respective poles. We further show that RomR interfaces with FrzZ, the output response regulator of the Frz chemosensory system, to regulate reversals. Thus, RomR serves at the functional interface to connect a classic bacterial signalling module (Frz to a classic eukaryotic polarity module (MglA/MglB. This modular design is paralleled by the phylogenetic distribution of the proteins, suggesting an evolutionary scheme in which RomR was incorporated into the MglA/MglB module to regulate cell polarity followed by the addition of the Frz system to dynamically regulate cell polarity.

  12. Accurate calibration of steam turbine speed control system and its influence on primary regulation at electric grid

    Energy Technology Data Exchange (ETDEWEB)

    Irrazabal Bohorquez, Washington Orlando; Barbosa, Joao Roberto [Technological Institute of Aeronautics (ITA/CTA), Sao Jose dos Campos, SP (Brazil). Center for Reference on Gas Turbine and Energy], E-mail: barbosa@ita.br

    2010-07-01

    In an interconnected electric system there are two very important parameters: the field voltage and the frequency system. The frequency system is very important for the primary regulation of the electric grid. Each turbomachine actuating as generator interconnected to the grid has an automatic speed regulator to keep the rotational speed and mechanical power of the prime machine operating at the set conditions and stable frequency. The electric grid is a dynamical system and in every moment the power units are exposed to several types of disturbances, which cause unbalance of the mechanical power developed by prime machine and the consumed electric power at the grid. The steam turbine speed control system controls the turbine speed to support the electric grid primary frequency at the same time it controls the frequency of the prime machine. Using a mathematical model for the speed control system, the transfer functions were calculated, as well as the proportionality constants of each element of the steam turbine automatic speed regulator. Among other parameters, the droop characteristic of steam turbine and the dynamic characteristics of the automatic speed regulator elements were calculated. Another important result was the determination of the behavior of the speed control when disturbances occur with the improvement of the calibration precision of the control system. (author)

  13. Central and peripheral mechanisms of the NPY system in the regulation of bone and adipose tissue.

    Science.gov (United States)

    Shi, Yan-Chuan; Baldock, Paul A

    2012-02-01

    Skeletal research is currently undergoing a period of marked expansion. The boundaries of "bone" research are being re-evaluated and with this, a growing recognition of a more complex and interconnected biology than previously considered. One aspect that has become the focus of particular attention is the relationship between bone and fat homeostasis. Evidence from a number of avenues indicates that bone and adipose regulation are both related and interdependent. This review examines the neuropeptide Y (NPY) system, known to exert powerful control over both bone and fat tissue. The actions of this system are characterized by signaling both within specific nuclei of the hypothalamus and also the target tissues, mediated predominantly through two G-protein coupled receptors (Y1 and Y2). In bone tissue, elevated NPY levels act consistently to repress osteoblast activity. Moreover, both central Y2 receptor and osteoblastic Y1 receptor signaling act similarly to repress bone formation. Conversely, loss of NPY expression or receptor signaling induces increased osteoblast activity and bone mass in both cortical and cancellous envelopes. In fat tissue, NPY action is more complex. Energy homeostasis is powerfully altered by elevations in hypothalamic NPY, resulting in increases in fat accretion and body-wide energy conservation, through the action of locally expressed Y1 receptors, while local Y2 receptors act to inhibit NPY-ergic tone. Loss of central NPY expression has a markedly reduced effect, consistent with a physiological drive to promote fat accretion. In fat tissue, NPY and Y1 receptors act to promote lipogenesis, consistent with their roles in the brain. Y2 receptors expressed in adipocytes also act in this manner, showing an opposing action to their role in the hypothalamus. While direct investigation of these processes has yet to be completed, these responses appear to be interrelated to some degree. The starvation-based signal of elevated central NPY inducing

  14. Automatic design of basin-specific drought indexes for highly regulated water systems

    Science.gov (United States)

    Zaniolo, Marta; Giuliani, Matteo; Castelletti, Andrea Francesco; Pulido-Velazquez, Manuel

    2018-04-01

    Socio-economic costs of drought are progressively increasing worldwide due to undergoing alterations of hydro-meteorological regimes induced by climate change. Although drought management is largely studied in the literature, traditional drought indexes often fail at detecting critical events in highly regulated systems, where natural water availability is conditioned by the operation of water infrastructures such as dams, diversions, and pumping wells. Here, ad hoc index formulations are usually adopted based on empirical combinations of several, supposed-to-be significant, hydro-meteorological variables. These customized formulations, however, while effective in the design basin, can hardly be generalized and transferred to different contexts. In this study, we contribute FRIDA (FRamework for Index-based Drought Analysis), a novel framework for the automatic design of basin-customized drought indexes. In contrast to ad hoc empirical approaches, FRIDA is fully automated, generalizable, and portable across different basins. FRIDA builds an index representing a surrogate of the drought conditions of the basin, computed by combining all the relevant available information about the water circulating in the system identified by means of a feature extraction algorithm. We used the Wrapper for Quasi-Equally Informative Subset Selection (W-QEISS), which features a multi-objective evolutionary algorithm to find Pareto-efficient subsets of variables by maximizing the wrapper accuracy, minimizing the number of selected variables, and optimizing relevance and redundancy of the subset. The preferred variable subset is selected among the efficient solutions and used to formulate the final index according to alternative model structures. We apply FRIDA to the case study of the Jucar river basin (Spain), a drought-prone and highly regulated Mediterranean water resource system, where an advanced drought management plan relying on the formulation of an ad hoc state index is used

  15. The Campylobacter jejuni Oxidative Stress Regulator RrpB Is Associated with a Genomic Hypervariable Region and Altered Oxidative Stress Resistance.

    Science.gov (United States)

    Gundogdu, Ozan; da Silva, Daiani T; Mohammad, Banaz; Elmi, Abdi; Wren, Brendan W; van Vliet, Arnoud H M; Dorrell, Nick

    2016-01-01

    Campylobacter jejuni is the leading cause of bacterial foodborne diarrhoeal disease worldwide. Despite the microaerophilic nature of the bacterium, C. jejuni can survive the atmospheric oxygen conditions in the environment. Bacteria that can survive either within a host or in the environment like C. jejuni require variable responses to survive the stresses associated with exposure to different levels of reactive oxygen species. The MarR-type transcriptional regulators RrpA and RrpB have recently been shown to play a role in controlling both the C. jejuni oxidative and aerobic stress responses. Analysis of 3,746 C. jejuni and 486 C. coli genome sequences showed that whilst rrpA is present in over 99% of C. jejuni strains, the presence of rrpB is restricted and appears to correlate with specific MLST clonal complexes (predominantly ST-21 and ST-61). C. coli strains in contrast lack both rrpA and rrpB . In C. jejuni rrpB + strains, the rrpB gene is located within a variable genomic region containing the IF subtype of the type I Restriction-Modification ( hsd ) system, whilst this variable genomic region in C. jejuni rrpB - strains contains the IAB subtype hsd system and not the rrpB gene. C. jejuni rrpB - strains exhibit greater resistance to peroxide and aerobic stress than C. jejuni rrpB + strains. Inactivation of rrpA resulted in increased sensitivity to peroxide stress in rrpB + strains, but not in rrpB - strains. Mutation of rrpA resulted in reduced killing of Galleria mellonella larvae and enhanced biofilm formation independent of rrpB status. The oxidative and aerobic stress responses of rrpB - and rrpB + strains suggest adaptation of C. jejuni within different hosts and niches that can be linked to specific MLST clonal complexes.

  16. Microbial-immune cross-talk and regulation of the immune system.

    Science.gov (United States)

    Cahenzli, Julia; Balmer, Maria L; McCoy, Kathy D

    2013-01-01

    We are all born germ-free. Following birth we enter into a lifelong relationship with microbes residing on our body's surfaces. The lower intestine is home to the highest microbial density in our body, which is also the highest microbial density known on Earth (up to 10(12) /g of luminal contents). With our indigenous microbial cells outnumbering our human cells by an order of magnitude our body is more microbial than human. Numerous immune adaptations confine these microbes within the mucosa, enabling most of us to live in peaceful homeostasis with our intestinal symbionts. Intestinal epithelial cells not only form a physical barrier between the bacteria-laden lumen and the rest of the body but also function as multi-tasking immune cells that sense the prevailing microbial (apical) and immune (basolateral) milieus, instruct the underlying immune cells, and adapt functionally. In the constant effort to ensure intestinal homeostasis, the immune system becomes educated to respond appropriately and in turn immune status can shape the microbial consortia. Here we review how the dynamic immune-microbial dialogue underlies maturation and regulation of the immune system and discuss recent findings on the impact of diet on both microbial ecology and immune function. © 2012 The Authors. Immunology © 2012 Blackwell Publishing Ltd.

  17. Study of the impacts of regulations affecting the acceptance of integrated community energy systems. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Feurer, Duane A.; Weaver, Clifford L.; Rielley, Kevin J.; Gallagher, Kevin C.; Harmon, Susan B.; Hejna, David T.; Kitch, Edmund W.

    1981-01-01

    A detailed description is presented of the laws and programs of the State of North Carolina governing the regulation of public energy utilities, the siting of energy generating and transmission facilities, the municipal franchising of public energy utilities, and the prescription of rates to be charged by utilities including attendant problems of cost allocations, rate base and operating expense determinations, and rate of return allowances. These laws and programs are analyzed to identify impediments which they may present to the implementation of Integrated Community Energy Systems (ICES). This report is one of fifty-one separate volumes which describe such regulatory programs at the Federal level and in each state as background to the report entitled Community Energy Systems and the Law of Public Utilities - Volume One: An Overview. This report also contains a summary of a strategy described in Volume One - An Overview for overcoming these impediments by working within the existing regulatory framework and by making changes in the regulatory programs to enhance the likelihood of ICES implementation.

  18. [Changes in the regulation and government of the health system. SESPAS report 2014].

    Science.gov (United States)

    Repullo, José R

    2014-06-01

    The economic and fiscal crisis of 2008 has erupted into the debate on the sustainability of health systems; some countries, such as Spain, have implemented strong policies of fiscal consolidation and austerity. The institutional framework and governance model of the national health system (NHS) after its devolution to regions in 2002 had significant weaknesses, which were not apparent in the rapid growth stage but which have been clearly visible since 2010. In this article, we describe the changes in government regulation from the national and NHS perspective: both general changes (clearly prompted by the economic authorities), and those more specifically addressed to healthcare. The Royal Decree-Law 16/2012 represents the centerpiece of austerity policies in healthcare but also implies a rupture with existing political consensus and a return to social security models. Our characterization of austerity in healthcare explores impacts on savings, services, and on the healthcare model itself, although the available information only allows some indications. The conclusions highlight the need to change the path of linear, rapid and radical budget cuts, providing a time-frame for implementing key reforms in terms of internal sustainability; to do so, it is appropriate to restore political and institutional consensus, to emphasize "clinical management" and divestment of inappropriate services (approach to the medical profession and its role as micro-manager), and to create frameworks of good governance and organizational innovations that support these structural reforms. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

  19. Do regulators pay attention? An assessment of IT governance implementation in systemically important banks

    Directory of Open Access Journals (Sweden)

    Mehrdad Sepahvand

    2017-03-01

    Full Text Available The large size and complexity of Information Technology systems in systematically important banks raise the need for creating an IT governance architecture that could make IT strategy aligned with business strategy and delivers value while it effectively identifies and manages IT risk. This study traces the links between IT governance and two more applied risk management frameworks, COSO and BCBS’s principles for managing IT risk. Then it argues due to the magnitude of potential losses caused by any weakness in IT governance in D-SIBs, the assessment of IT governance in these banks should be one of the main concerns of local regulators and supervisors. As a case study, it assesses the relative rank of D-SIBs in Iranian banking system to see where these banks would stand in an ordered list of the banks including both private and public banks in terms of IT governance implementation. The application of the Fuzzy AHP technique shows that IT governance practice in Iranian D-SIBs is not as good as the private banks while it outperforms some state-owned banks.

  20. Carnosine reverses the aging-induced down regulation of brain regional serotonergic system.

    Science.gov (United States)

    Banerjee, Soumyabrata; Ghosh, Tushar K; Poddar, Mrinal K

    2015-12-01

    The purpose of the present investigation was to study the role of carnosine, an endogenous dipeptide biomolecule, on brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) serotonergic system during aging. Results showed an aging-induced brain region specific significant (a) increase in Trp (except cerebral cortex) and their 5-HIAA steady state level with an increase in their 5-HIAA accumulation and declination, (b) decrease in their both 5-HT steady state level and 5-HT accumulation (except cerebral cortex). A significant decrease in brain regional 5-HT/Trp ratio (except cerebral cortex) and increase in 5-HIAA/5-HT ratio were also observed during aging. Carnosine at lower dosages (0.5-1.0μg/Kg/day, i.t. for 21 consecutive days) didn't produce any significant response in any of the brain regions, but higher dosages (2.0-2.5μg/Kg/day, i.t. for 21 consecutive days) showed a significant response on those aging-induced brain regional serotonergic parameters. The treatment with carnosine (2.0μg/Kg/day, i.t. for 21 consecutive days), attenuated these brain regional aging-induced serotonergic parameters and restored towards their basal levels that observed in 4 months young control rats. These results suggest that carnosine attenuates and restores the aging-induced brain regional down regulation of serotonergic system towards that observed in young rats' brain regions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Proposed Regulation System for the Use of Small Quantities of Nuclear Material in Korea

    International Nuclear Information System (INIS)

    So, D. S.; Kim, H. S.; Lee, B. D.

    2007-01-01

    The Atomic Energy legislation does not require a person who intends to use or possess SQM(small quantities of nuclear material, below 300 grams of an uranium equivalent) to obtain a license or permit to use or possess such material. The absence of this requirement is an obstacle to the SSAC's (state system of accounting for and control) ability to effectively account for and control all nuclear material. Due to the differences of the meanings of some terminology used in the Korean Atomic Energy Law and its related regulations to those of safeguards agreement and its Protocol, there is a possibility of a difficulty occurring in the implementation of safeguards obligations. The objectives of this work are to establish an effective and rational control system for the SQM not required to obtain a license for its use or possession in Korea, and to review the definitions of some terminology used in the Atomic Energy legislation, IAEA's legal documents and guidelines to avoid any confusion in the implementation of international obligations in the nuclear control area

  2. Gap junctions in cells of the immune system: structure, regulation and possible functional roles

    Directory of Open Access Journals (Sweden)

    J.C. Sáez

    2000-04-01

    Full Text Available Gap junction channels are sites of cytoplasmic communication between contacting cells. In vertebrates, they consist of protein subunits denoted connexins (Cxs which are encoded by a gene family. According to their Cx composition, gap junction channels show different gating and permeability properties that define which ions and small molecules permeate them. Differences in Cx primary sequences suggest that channels composed of different Cxs are regulated differentially by intracellular pathways under specific physiological conditions. Functional roles of gap junction channels could be defined by the relative importance of permeant substances, resulting in coordination of electrical and/or metabolic cellular responses. Cells of the native and specific immune systems establish transient homo- and heterocellular contacts at various steps of the immune response. Morphological and functional studies reported during the last three decades have revealed that many intercellular contacts between cells in the immune response present gap junctions or "gap junction-like" structures. Partial characterization of the molecular composition of some of these plasma membrane structures and regulatory mechanisms that control them have been published recently. Studies designed to elucidate their physiological roles suggest that they might permit coordination of cellular events which favor the effective and timely response of the immune system.

  3. Design of protein-responsive micro-sized hydrogels for self-regulating microfluidic systems

    Science.gov (United States)

    Hirayama, Mayu; Tsuruta, Kazuhiro; Kawamura, Akifumi; Ohara, Masayuki; Shoji, Kan; Kawano, Ryuji; Miyata, Takashi

    2018-03-01

    Diagnosis sensors using micro-total analysis systems (µ-TAS) have been developed for detecting target biomolecules such as proteins and saccharides because they are signal biomolecules for monitoring body conditions and diseases. In this study, biomolecularly stimuli-responsive micro-sized hydrogels that exhibited quick shrinkage in response to lectin concanavalinA (ConA) were prepared in a microchannel by photopolymerization using a fluorescence microscope. In preparing the micro-size hydrogels, glycosyloxyethyl methacrylate (GEMA) as a ligand monomer was copolymerized with a crosslinker in the presence of template ConA in molecular imprinting. The ConA-imprinted micro-hydrogel showed greater shrinkage in response to target ConA than nonimprinted micro-hydrogel. When a buffer solution was switched to an aqueous ConA solution in the Y-shaped microchannel, the flow rates changed quickly because of the responsive shrinkage of the micro-hydrogel prepared in the microchannel. These results suggest that the ConA-imprinted micro-hydrogel acted as a self-regulated microvalve in microfluidic systems.

  4. Role of the endocannabinoid system in food intake, energy homeostasis and regulation of the endocrine pancreas.

    Science.gov (United States)

    Li, Chen; Jones, Peter M; Persaud, Shanta J

    2011-03-01

    The endocannabinoid system (ECS) is a signalling cascade consisting of CB1 and CB2 receptors, and enzymes for the synthesis and degradation of endogenous ligands for these receptors. Central CB1 receptors have been most widely studied since they play key roles in energy homeostasis and rimonabant, a CB1 receptor antagonist, was used clinically to treat obesity. Less is known about CB2 receptors, but their abundant expression by lymphocytes and macrophages has led to suggestions of their importance in immune and inflammatory reactions. More recently, it has become apparent that both CB1 and CB2 receptors are more widely expressed than originally thought, and the capacity of endocannabinoids to regulate energy balance also occurs through their interactions with cannabinoid receptors on a variety of peripheral tissues. In general, pathological overactivation of the ECS contributes to weight gain, reduced sensitivity to insulin and glucose intolerance, and blockade of CB1 receptors reduces body weight through increased secretion of anorectic signals and improved insulin sensitivity. However, the notion that the ECS per se is detrimental to energy homeostasis is an oversimplification, since activation of cannabinoid receptors expressed by islet cells can stimulate insulin secretion, which is obviously beneficial under conditions of impaired glucose tolerance or type 2 diabetes. We propose that under normal physiological conditions cannabinoid signalling in the endocrine pancreas is a bona fide mechanism of regulating insulin secretion to maintain blood glucose levels, but that energy balance becomes dysregulated with excessive food intake, leading to adipogenesis and fat accumulation through enhanced cannabinoid synthesis. Copyright © 2010 Elsevier Inc. All rights reserved.

  5. SERPINA3K plays antioxidant roles in cultured pterygial epithelial cells through regulating ROS system.

    Directory of Open Access Journals (Sweden)

    Chengpeng Zhu

    Full Text Available We recently demonstrated that SERPINA3K, a serine proteinase inhibitor, has antioxidant activity in the cornea. Here we investigated the antioxidant effects of SERPINA3K on the pterygial, which is partially caused by oxidative stress in pathogenesis. The head part of primary pterygial tissue was dissected and then cultured in keratinocyte serum-free defined medium (KSFM. The cultured pterygial epithelial cells (PECs were treated with SERPINA3K. The cell proliferation and migration of PECs were measured and analyzed. Western blot and quantitative real-time polymerase chain reaction (PCR assay were performed. It showed that SERPINA3K significantly suppressed the cell proliferation of PECs in a concentration-dependent manner, compared with cultured human conjunctival epithelial cells. SERPINA3K also inhibited the cell migration of PECs. Towards its underlying mechanism, SERPINA3K had antioxidant activities on the PECs by significantly inhibiting NADPH oxidase 4 (NOX4, which is an important enzyme of ROS generation, and by elevating the levels of key antioxidant factors of ROS: such as NAD(PH dehydrogenase (quinone 1 (NQO1, NF-E2-related factor-2 (NRF2 and superoxide dismutases (SOD2. Meanwhile, SERPINA3K down-regulated the key effectors of Wnt signaling pathway: β-catenin, nonphospho-β-catenin, and low-density lipoprotein receptor-related protein 6 (LRP6. We provided novel evidence that SERPINA3K had inhibitory effects on pterygium and SERPINA3K played antioxidant role via regulating the ROS system and antioxidants.

  6. Non-classical mechanisms of transcriptional regulation by the vitamin D receptor: insights into calcium homeostasis, immune system regulation and cancer chemoprevention.

    Science.gov (United States)

    Dimitrov, Vassil; Salehi-Tabar, Reyhaneh; An, Beum-Soo; White, John H

    2014-10-01

    Hormonal 1,25-dihydroxyvitamin D [1,25(OH)2D] signals through the nuclear vitamin D receptor (VDR), a ligand-regulated transcription factor. Gene expression profiling studies have revealed that 1,25(OH)2D signaling through the VDR can lead to activation or repression of target gene transcription in roughly equal proportions. Classically, transcriptional regulation by the VDR, similar to other nuclear receptors, has been characterized by its capacity to recognize high affinity cognate vitamin D response elements (VDREs), located in the regulatory regions of target genes. Several biochemical studies revealed that the VDRE-bound receptor recruits a series of coregulatory proteins, leading to transactivation of adjacent target genes. However, genome-wide and other analyses of VDR binding have revealed that a subset of VDR binding sites does not contain VDREs, and that VDREs are not associated with transcriptionally repressed VDR target genes. Work over the last ∼20 years and in particular recent findings have revealed a diverse array of mechanisms by which VDR can form complexes with several other classes of transcriptional activators, leading to repression of gene transcription. Moreover, these efforts have led to several insights into the molecular basis for the physiological regulation of calcium homeostasis, immune system function and cancer chemoprevention by 1,25(OH)2D/VDR signaling. This article is part of a Special Issue entitled '16th Vitamin D Workshop'. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Soft Regulation with Crowd Recommendation: Coordinating Self-Interested Agents in Sociotechnical Systems under Imperfect Information.

    Science.gov (United States)

    Luo, Yu; Iyengar, Garud; Venkatasubramanian, Venkat

    2016-01-01

    Regulating emerging industries is challenging, even controversial at times. Under-regulation can result in safety threats to plant personnel, surrounding communities, and the environment. Over-regulation may hinder innovation, progress, and economic growth. Since one typically has limited understanding of, and experience with, the novel technology in practice, it is difficult to accomplish a properly balanced regulation. In this work, we propose a control and coordination policy called soft regulation that attempts to strike the right balance and create a collective learning environment. In soft regulation mechanism, individual agents can accept, reject, or partially accept the regulator's recommendation. This non-intrusive coordination does not interrupt normal operations. The extent to which an agent accepts the recommendation is mediated by a confidence level (from 0 to 100%). Among all possible recommendation methods, we investigate two in particular: the best recommendation wherein the regulator is completely informed and the crowd recommendation wherein the regulator collects the crowd's average and recommends that value. We show by analysis and simulations that soft regulation with crowd recommendation performs well. It converges to optimum, and is as good as the best recommendation for a wide range of confidence levels. This work sheds a new theoretical perspective on the concept of the wisdom of crowds.

  8. Endocannabinoid system acts as a regulator of immune homeostasis in the gut.

    Science.gov (United States)

    Acharya, Nandini; Penukonda, Sasi; Shcheglova, Tatiana; Hagymasi, Adam T; Basu, Sreyashi; Srivastava, Pramod K

    2017-05-09

    Endogenous cannabinoids (endocannabinoids) are small molecules biosynthesized from membrane glycerophospholipid. Anandamide (AEA) is an endogenous intestinal cannabinoid that controls appetite and energy balance by engagement of the enteric nervous system through cannabinoid receptors. Here, we uncover a role for AEA and its receptor, cannabinoid receptor 2 (CB2), in the regulation of immune tolerance in the gut and the pancreas. This work demonstrates a major immunological role for an endocannabinoid. The pungent molecule capsaicin (CP) has a similar effect as AEA; however, CP acts by engagement of the vanilloid receptor TRPV1, causing local production of AEA, which acts through CB2. We show that the engagement of the cannabinoid/vanilloid receptors augments the number and immune suppressive function of the regulatory CX3CR1 hi macrophages (Mϕ), which express the highest levels of such receptors among the gut immune cells. Additionally, TRPV1 -/- or CB2 -/- mice have fewer CX3CR1 hi Mϕ in the gut. Treatment of mice with CP also leads to differentiation of a regulatory subset of CD4 + cells, the Tr1 cells, in an IL-27-dependent manner in vitro and in vivo. In a functional demonstration, tolerance elicited by engagement of TRPV1 can be transferred to naïve nonobese diabetic (NOD) mice [model of type 1 diabetes (T1D)] by transfer of CD4 + T cells. Further, oral administration of AEA to NOD mice provides protection from T1D. Our study unveils a role for the endocannabinoid system in maintaining immune homeostasis in the gut/pancreas and reveals a conversation between the nervous and immune systems using distinct receptors.

  9. Central nervous system: a conductor orchestrating metabolic regulations harmed by both hyperglycaemia and hypoglycaemia.

    Science.gov (United States)

    Scheen, A J

    2010-10-01

    Recent evidence suggests that the brain has a key role in the control of energy metabolism, body fat content and glucose metabolism. Neuronal systems, which regulate energy intake, energy expenditure, and endogenous glucose production, sense and respond to input from hormonal and nutrient-related signals that convey information regarding both body energy stores and current energy availability. In response to this input, adaptive changes occur that promote energy homeostasis and the maintenance of blood glucose levels in the normal range. Defects in this control system are implicated in the link between obesity and type 2 diabetes mellitus. The central nervous system may be considered the conductor of an orchestra involving many peripheral organs involved in these homeostatic processes. However, the brain is mainly a glucose-dependent organ, which can be damaged by both hypoglycaemia and hyperglycaemia. Hypoglycaemia unawareness is a major problem in clinical practice and is associated with an increased risk of coma. Stroke is another acute complication associated with diabetes mellitus, especially in elderly people, and the control of glucose level in this emergency situation remains challenging. The prognosis of stroke is worse in diabetic patients and both its prevention and management in at-risk patients should be improved. Finally, chronic diabetic encephalopathies, which may lead to cognitive dysfunction and even dementia, are also recognized. They may result from recurrent hypoglycaemia and/or from chronic hyperglycaemia leading to cerebral vascular damage. Functional imaging is of interest for exploring diabetes-associated cerebral abnormalities. Thus, the intimate relationship between the brain and diabetes is increasingly acknowledged in both research and clinical practice. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  10. Cardiac arrest during gamete release in chum salmon regulated by the parasympathetic nerve system.

    Directory of Open Access Journals (Sweden)

    Yuya Makiguchi

    Full Text Available Cardiac arrest caused by startling stimuli, such as visual and vibration stimuli, has been reported in some animals and could be considered as an extraordinary case of bradycardia and defined as reversible missed heart beats. Variability of the heart rate is established as a balance between an autonomic system, namely cholinergic vagus inhibition, and excitatory adrenergic stimulation of neural and hormonal action in teleost. However, the cardiac arrest and its regulating nervous mechanism remain poorly understood. We show, by using electrocardiogram (ECG data loggers, that cardiac arrest occurs in chum salmon (Oncorhynchus keta at the moment of gamete release for 7.39+/-1.61 s in females and for 5.20+/-0.97 s in males. The increase in heart rate during spawning behavior relative to the background rate during the resting period suggests that cardiac arrest is a characteristic physiological phenomenon of the extraordinarily high heart rate during spawning behavior. The ECG morphological analysis showed a peaked and tall T-wave adjacent to the cardiac arrest, indicating an increase in potassium permeability in cardiac muscle cells, which would function to retard the cardiac action potential. Pharmacological studies showed that the cardiac arrest was abolished by injection of atropine, a muscarinic receptor antagonist, revealing that the cardiac arrest is a reflex response of the parasympathetic nerve system, although injection of sotalol, a beta-adrenergic antagonist, did not affect the cardiac arrest. We conclude that cardiac arrest during gamete release in spawning release in spawning chum salmon is a physiological reflex response controlled by the parasympathetic nervous system. This cardiac arrest represents a response to the gaping behavior that occurs at the moment of gamete release.

  11. The PhoBR two-component system regulates antibiotic biosynthesis in Serratia in response to phosphate

    Science.gov (United States)

    2009-01-01

    Background Secondary metabolism in Serratia sp. ATCC 39006 (Serratia 39006) is controlled via a complex network of regulators, including a LuxIR-type (SmaIR) quorum sensing (QS) system. Here we investigate the molecular mechanism by which phosphate limitation controls biosynthesis of two antibiotic secondary metabolites, prodigiosin and carbapenem, in Serratia 39006. Results We demonstrate that a mutation in the high affinity phosphate transporter pstSCAB-phoU, believed to mimic low phosphate conditions, causes upregulation of secondary metabolism and QS in Serratia 39006, via the PhoBR two-component system. Phosphate limitation also activated secondary metabolism and QS in Serratia 39006. In addition, a pstS mutation resulted in upregulation of rap. Rap, a putative SlyA/MarR-family transcriptional regulator, shares similarity with the global regulator RovA (regulator of virulence) from Yersina spp. and is an activator of secondary metabolism in Serratia 39006. We demonstrate that expression of rap, pigA-O (encoding the prodigiosin biosynthetic operon) and smaI are controlled via PhoBR in Serratia 39006. Conclusion Phosphate limitation regulates secondary metabolism in Serratia 39006 via multiple inter-linked pathways, incorporating transcriptional control mediated by three important global regulators, PhoB, SmaR and Rap. PMID:19476633

  12. The PhoBR two-component system regulates antibiotic biosynthesis in Serratia in response to phosphate

    Directory of Open Access Journals (Sweden)

    Everson Lee

    2009-05-01

    Full Text Available Abstract Background Secondary metabolism in Serratia sp. ATCC 39006 (Serratia 39006 is controlled via a complex network of regulators, including a LuxIR-type (SmaIR quorum sensing (QS system. Here we investigate the molecular mechanism by which phosphate limitation controls biosynthesis of two antibiotic secondary metabolites, prodigiosin and carbapenem, in Serratia 39006. Results We demonstrate that a mutation in the high affinity phosphate transporter pstSCAB-phoU, believed to mimic low phosphate conditions, causes upregulation of secondary metabolism and QS in Serratia 39006, via the PhoBR two-component system. Phosphate limitation also activated secondary metabolism and QS in Serratia 39006. In addition, a pstS mutation resulted in upregulation of rap. Rap, a putative SlyA/MarR-family transcriptional regulator, shares similarity with the global regulator RovA (regulator of virulence from Yersina spp. and is an activator of secondary metabolism in Serratia 39006. We demonstrate that expression of rap, pigA-O (encoding the prodigiosin biosynthetic operon and smaI are controlled via PhoBR in Serratia 39006. Conclusion Phosphate limitation regulates secondary metabolism in Serratia 39006 via multiple inter-linked pathways, incorporating transcriptional control mediated by three important global regulators, PhoB, SmaR and Rap.

  13. Opioid systems in the lateral hypothalamus regulate feeding behavior through orexin and GABA neurons.

    Science.gov (United States)

    Ardianto, C; Yonemochi, N; Yamamoto, S; Yang, L; Takenoya, F; Shioda, S; Nagase, H; Ikeda, H; Kamei, J

    2016-04-21

    The hypothalamus controls feeding behavior. Since central opioid systems may regulate feeding behavior, we examined the role of μ-, δ- and κ-opioid receptors in the lateral hypothalamus (LH), the hunger center, in feeding behavior of mice. Non-selective (naloxone; 3 mg/kg, s.c.) and selective μ- (β-funaltrexamine, β-FNA; 10 mg/kg, s.c.), δ- (naltrindole; 3 mg/kg, s.c.) and κ- (norbinaltorphimine, norBNI; 20 mg/kg, s.c.) opioid receptor antagonists significantly decreased food intake in food-deprived mice. The injection of naloxone (20 μg/side) into the LH significantly decreased food intake whereas the injection of naloxone (20 μg/side) outside of the LH did not affect food intake. The injection of β-FNA (2 μg/side), naltrindole (1 μg/side) or norBNI (2 μg/side) into the LH significantly decreased food intake. Furthermore, all these antagonists significantly decreased the mRNA level of preproorexin, but not those of other hypothalamic neuropeptides. In addition, the injection of the GABAA receptor agonist muscimol (5 μg/side) into the LH significantly decreased food intake, and this effect was abolished by the GABAA receptor antagonist bicuculline (50 μg/side). Muscimol (1mg/kg, i.p.) decreased the mRNA level of preproorexin in the hypothalamus. Naloxone (3mg/kg, s.c.) significantly increased the GABA level in the LH and both bicuculline and the GABA release inhibitor 3-mercaptopropionic acid (3-MP, 5 μg/side) attenuated the inhibitory effect of naloxone on feeding behavior. 3-MP also attenuated the effects of β-FNA and norBNI, but not that of naltrindole. These results show that opioid systems in the LH regulate feeding behavior through orexin neurons. Moreover, μ- and κ-, but not δ-, opioid receptor antagonists inhibit feeding behavior by activating GABA neurons in the LH. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  14. Macoilin, a conserved nervous system-specific ER membrane protein that regulates neuronal excitability.

    Directory of Open Access Journals (Sweden)

    Fausto Arellano-Carbajal

    2011-03-01

    Full Text Available Genome sequence comparisons have highlighted many novel gene families that are conserved across animal phyla but whose biological function is unknown. Here, we functionally characterize a member of one such family, the macoilins. Macoilins are characterized by several highly conserved predicted transmembrane domains towards the N-terminus and by coiled-coil regions C-terminally. They are found throughout Eumetazoa but not in other organisms. Mutants for the single Caenorhabditis elegans macoilin, maco-1, exhibit a constellation of behavioral phenotypes, including defects in aggregation, O₂ responses, and swimming. MACO-1 protein is expressed broadly and specifically in the nervous system and localizes to the rough endoplasmic reticulum; it is excluded from dendrites and axons. Apart from subtle synapse defects, nervous system development appears wild-type in maco-1 mutants. However, maco-1 animals are resistant to the cholinesterase inhibitor aldicarb and sensitive to levamisole, suggesting pre-synaptic defects. Using in vivo imaging, we show that macoilin is required to evoke Ca²(+ transients, at least in some neurons: in maco-1 mutants the O₂-sensing neuron PQR is unable to generate a Ca²(+ response to a rise in O₂. By genetically disrupting neurotransmission, we show that pre-synaptic input is not necessary for PQR to respond to O₂, indicating that the response is mediated by cell-intrinsic sensory transduction and amplification. Disrupting the sodium leak channels NCA-1/NCA-2, or the N-,P/Q,R-type voltage-gated Ca²(+ channels, also fails to disrupt Ca²(+ responses in the PQR cell body to O₂ stimuli. By contrast, mutations in egl-19, which encodes the only Caenorhabditis elegans L-type voltage-gated Ca²(+ channel α1 subunit, recapitulate the Ca²(+ response defect we see in maco-1 mutants, although we do not see defects in localization of EGL-19. Together, our data suggest that macoilin acts in the ER to regulate assembly or

  15. Clinical value of the major types of reactions of the body’s stress-regulating systems in ischemic stroke

    Directory of Open Access Journals (Sweden)

    Aleksandr Mikhailovich Dolgov

    2013-01-01

    Full Text Available The time course of changes in the parameters reflecting the status of different components of the body’s regulatory systems was studied in 125patients with hemispheric ischemic stroke via comprehensive evaluation of the hypothalamo-pituitary axes and some endocrine glands. There were three types of reactions of the body’s stress-regulating systems: 1 normergic; 2 hyperergic; 3 disergic, which characterized adaptive and disadaptive reactions in stroke. The changes in the nitroxydergic mechanisms of vascular tone regulation, which constrain the possible involvement of the vascular wall endothelium in the body’s adaptive reactions, progress as the condition becomes severe.

  16. Soft Regulation with Crowd Recommendation: Coordinating Self-Interested Agents in Sociotechnical Systems under Imperfect Information

    Science.gov (United States)

    2016-01-01

    Regulating emerging industries is challenging, even controversial at times. Under-regulation can result in safety threats to plant personnel, surrounding communities, and the environment. Over-regulation may hinder innovation, progress, and economic growth. Since one typically has limited understanding of, and experience with, the novel technology in practice, it is difficult to accomplish a properly balanced regulation. In this work, we propose a control and coordination policy called soft regulation that attempts to strike the right balance and create a collective learning environment. In soft regulation mechanism, individual agents can accept, reject, or partially accept the regulator’s recommendation. This non-intrusive coordination does not interrupt normal operations. The extent to which an agent accepts the recommendation is mediated by a confidence level (from 0 to 100%). Among all possible recommendation methods, we investigate two in particular: the best recommendation wherein the regulator is completely informed and the crowd recommendation wherein the regulator collects the crowd’s average and recommends that value. We show by analysis and simulations that soft regulation with crowd recommendation performs well. It converges to optimum, and is as good as the best recommendation for a wide range of confidence levels. This work sheds a new theoretical perspective on the concept of the wisdom of crowds. PMID:26977699

  17. The crosstalk between the kidney and the central nervous system: the role of renal nerves in blood pressure regulation.

    Science.gov (United States)

    Nishi, Erika E; Bergamaschi, Cássia T; Campos, Ruy R

    2015-04-20

    What is the topic of this review? This review describes the role of renal nerves as the key carrier of signals from the kidneys to the CNS and vice versa; the brain and kidneys communicate through this carrier to maintain homeostasis in the body. What advances does it highlight? Whether renal or autonomic dysfunction is the predominant contributor to systemic hypertension is still debated. In this review, we focus on the role of the renal nerves in a model of renovascular hypertension. The sympathetic nervous system influences the renal regulation of arterial pressure and body fluid composition. Anatomical and physiological evidence has shown that sympathetic nerves mediate changes in urinary sodium and water excretion by regulating the renal tubular water and sodium reabsorption throughout the nephron, changes in the renal blood flow and the glomerular filtration rate by regulating the constriction of renal vasculature, and changes in the activity of the renin-angiotensin system by regulating the renin release from juxtaglomerular cells. Additionally, renal sensory afferent fibres project to the autonomic central nuclei that regulate blood pressure. Hence, renal nerves play a key role in the crosstalk between the kidneys and the CNS to maintain homeostasis in the body. Therefore, the increased sympathetic nerve activity to the kidney and the renal afferent nerve activity to the CNS may contribute to the outcome of diseases, such as hypertension. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

  18. Linear Modeling and Regulation Quality Analysis for Hydro-Turbine Governing System with an Open Tailrace Channel

    Directory of Open Access Journals (Sweden)

    Jiandong Yang

    2015-10-01

    Full Text Available On the basis of the state–space method (SSM, a novel linear mathematical model of the unsteady flow for the tailrace system with an open channel is proposed. This novel model is an elastic linearized model of water hammer. The validity of the model has been verified by several examples of numerical simulation, which are based on a finite difference technique. Then, the complete mathematical model for the hydro-turbine governing system of hydropower station with an open tailrace channel, which is used for simulating the transient process of the hydro-turbine governing system under load disturbance, is established by combining the models of hydro-turbine, generator, governor and open tailrace channel. Finally, according to the complete model, the regulation quality for hydro-turbine governing system with an open tailrace channel under load disturbance is studied, and the effects of open tailrace channel and tailrace surge tank on regulation quality are analyzed. The results indicate that: The open tailrace channel has a strong influence on the regulation quality by observing the water level fluctuations in tailrace surge tank. The surge shows a piecewise periodical change along with the variation in the length of an open channel. The open tailrace channel can be used to improve the regulation quality of hydro-turbine governing system.

  19. The Theory of Grid Investment and Governance from the Perspective of New Regulation: Enlightenment on China's Electric Power System Reform

    Institute of Scientific and Technical Information of China (English)

    FENG Yong-sheng

    2016-01-01

    The main contents of theoretical studies on grid investment and governance include the business investment patterns,the regulated investment patterns,and the incentive and efficiency issues of the power grid ownership and the operating right under the implementation of the integrated structure and separated structure.The commercial investment mode relies on the assumption of near-perfect competition and the separated structure of the grid ownership and the system operating right,which in reality is prone to distorted incentives for grid investment and easy to generate team moral hazards,thus it is difficult to ensure effective grid investment in the competitive electricity market.By relying on incentive regulation,the integrated structure of the grid ownership and the system operating right under the regulated investment mode can avoid moral hazard in the teams and various distorted investment incentives.Comparatively speaking,the regulated investment mode is a more appropriate one to be the main target pattern for the grid investment during China's power market reform.The power grid governance should focus on the release of the potential efficiency under the integrated structure of the grid ownership and the right to operate the system.The power system reform must take a coordinated promotion of the construction of a competitive market and the reform of the grid management system,so as to avoid becoming a simple interest re-adjustment.

  20. Impact of environmental regulations on control of copper ion concentration in the DIII-D cooling water system

    International Nuclear Information System (INIS)

    Gootgeld, A.M.

    1993-10-01

    Tokamaks and industrial users are faced with the task of maintaining closed-loop, low conductivity, low impurity, cooling water systems. Operating these systems concentrates the impurities in the water requiring subsequent disposal. Environmental regulations are making this increasingly difficult. This paper will discuss the solution to the problem of removing and disposing of copper ions in the DIII-D low conductivity water system. Since the commissioning of the Doublet facility, the quality of the water in the 3000 gpm system that cools the DIII-D vacuum vessel coils, power supplies and auxiliary heating components has been controlled with mixed-bed ion exchangers. Low ion levels, particularly copper, are required to operate this equipment. In early 1992, the company that leases and regenerates DIII-D ion exchangers said they no longer can accept these resin beds for regeneration due to the level of copper ion on the resin. This change in policy, a change that has been adopted throughout their industry, was necessary to assure that the Metropolitan Sewerage System of the City of San Diego stays in compliance with State of California regulations and EPA-mandated national pretreatment standards and regulations. A cost effective solution was implemented which utilizes a reverse osmosis filtration system with the ion exchangers for make-up water. Levels of copper ion disposed to the sewer are in compliance with government standards. These measures have thus far proved effective in maintaining low conductivity and overall good quality cooling water. Specifically, this paper discusses DIII-D deionized cooling water quality requirements and an affective means to meet these requirements in order to be in compliance with government regulations for copper ion disposal. The problems discussed, the alternatives considered and the approach taken would be readily applicable to any deionized cooling water system containing copper where EPA standards and regulations are mandated

  1. Regulation of axonal development by the nuclear protein hindsight (pebbled) in the Drosophila visual system.

    Science.gov (United States)

    Oliva, Carlos; Sierralta, Jimena

    2010-08-15

    The molecules and networks involved in the process of acquisition and maintenance of the form of a mature neuron are not completely known. Using a misexpression screen we identified the gene hindsight as a gene involved in the process of acquisition of the neuronal morphogenesis in the Drosophila adult nervous system. hindsight encodes a transcription factor known for its role in early developmental processes such as embryonic germ band retraction and dorsal closure, as well as in the establishment of cell morphology, planar cell polarity, and epithelial integrity during retinal development. We describe here a novel function for HNT by showing that both loss and gain of function of HNT affects the pathfinding of the photoreceptors axons. By manipulating the timing and level of HNT expression, together with the number of cells manipulated we show here that the function of HNT in axonal guidance is independent of the HNT functions previously reported in retinal cells. Based on genetic interaction experiments we show that part of HNT function in axonal development is exerted through the regulation of genes involved in the dynamics of the actin cytoskeleton. Copyright 2010 Elsevier Inc. All rights reserved.

  2. Regulation of protamine gene expression in an in vitro homologous system

    International Nuclear Information System (INIS)

    Jankowski, Jacek M.; Wasilewska, Lidia D.; Hoorn Frans van der; Wong, Norman C.W.; Dixon, Gordon H.

    1996-01-01

    An ''in vitro'' transcription system from the trout testis nuclei was developed to study trout protamine gene expression. The protamine promoter contains, among others, two regulatory elements: 1) a cAMP-responsive element or CRE element (TGACGTCA) which is present in position 5' to TATA box, and 2) GC box (CCGCCC) which is present in position 3' to TATA box. The removal of the CRE-binding protein by titration (by the addition of appropriate oligonucleotides to the incubation mixture) resulted in a decrease in transcription of the protamine gene. These results were confirmed by experiments in which the pure CRE-binding factor (TPBP1) was used, as well as by those where a stimulatory effect of cAMP on protamine promoter transcription was observed. On the other hand, addition of oligonucleotides containing the GC-box sequence enhanced the protamine gene transcription indicating that the protein (Sp1 like) which binds to this sequence acts a repressor of protamine gene expression. These results confirm the previously proposed model which suggested that the GC box played a role in negative regulation of the protamine gene expression. Involvement of some other factors in this process was also discussed. (author). 34 refs, 7 figs

  3. A role for central nervous system PPAR-γ in the regulation of energy balance.

    Science.gov (United States)

    Ryan, Karen K; Li, Bailing; Grayson, Bernadette E; Matter, Emily K; Woods, Stephen C; Seeley, Randy J

    2011-05-01

    The peroxisome proliferator-activated receptor-γ (PPAR-γ) is a nuclear receptor that is activated by lipids to induce the expression of genes involved in lipid and glucose metabolism, thereby converting nutritional signals into metabolic consequences. PPAR-γ is the target of the thiazolidinedione (TZD) class of insulin-sensitizing drugs, which have been widely prescribed to treat type 2 diabetes mellitus. A common side effect of treatment with TZDs is weight gain. Here we report a previously unknown role for central nervous system (CNS) PPAR-γ in the regulation of energy balance. We found that both acute and chronic activation of CNS PPAR-γ, by either TZDs or hypothalamic overexpression of a fusion protein consisting of PPAR-γ and the viral transcriptional activator VP16 (VP16-PPAR-γ), led to positive energy balance in rats. Blocking the endogenous activation of CNS PPAR-γ with pharmacological antagonists or reducing its expression with shRNA led to negative energy balance, restored leptin sensitivity in high-fat-diet (HFD)-fed rats and blocked the hyperphagic response to oral TZD treatment. These findings have implications for the widespread clinical use of TZD drugs and for understanding the etiology of diet-induced obesity.

  4. Characterization of the oxytocin system regulating affiliative behavior in female prairie voles.

    Science.gov (United States)

    Ross, H E; Cole, C D; Smith, Y; Neumann, I D; Landgraf, R; Murphy, A Z; Young, L J

    2009-09-15

    Oxytocin regulates partner preference formation and alloparental behavior in the socially monogamous prairie vole (Microtus ochrogaster) by activating oxytocin receptors in the nucleus accumbens of females. Mating facilitates partner preference formation, and oxytocin-immunoreactive fibers in the nucleus accumbens have been described in prairie voles. However, there has been no direct evidence of oxytocin release in the nucleus accumbens during sociosexual interactions, and the origin of the oxytocin fibers is unknown. Here we show for the first time that extracellular concentrations of oxytocin are increased in the nucleus accumbens of female prairie vole during unrestricted interactions with a male. We further show that the distribution of oxytocin-immunoreactive fibers in the nucleus accumbens is conserved in voles, mice and rats, despite remarkable species differences in oxytocin receptor binding in the region. Using a combination of site-specific and peripheral infusions of the retrograde tracer Fluorogold, we demonstrate that the nucleus accumbens oxytocin-immunoreactive fibers likely originate from paraventricular and supraoptic hypothalamic neurons. This distribution of retrogradely labeled neurons is consistent with the hypothesis that striatal oxytocin fibers arise from collaterals of magnocellular neurons of the neurohypophysial system. If correct, this may serve to coordinate peripheral and central release of oxytocin with appropriate behavioral responses associated with reproduction, including pair bonding after mating, and maternal responsiveness following parturition and during lactation.

  5. Thermal conductance and basal metabolic rate are part of a coordinated system for heat transfer regulation

    Science.gov (United States)

    Naya, Daniel E.; Spangenberg, Lucía; Naya, Hugo; Bozinovic, Francisco

    2013-01-01

    Thermal conductance measures the ease with which heat leaves or enters  an organism's body. Although the analysis of this physiological variable in relation to climatic and ecological factors can be traced to studies by Scholander and colleagues, only small advances have occurred ever since. Here, we analyse the relationship between minimal thermal conductance estimated during summer (Cmin) and several ecological, climatic and geographical factors for 127 rodent species, in order to identify the exogenous factors that have potentially affected the evolution of thermal conductance. In addition, we evaluate whether there is compensation between Cmin and basal metabolic rate (BMR)—in such a way that a scale-invariant ratio between both variables is equal to one—as could be expected from the Scholander–Irving model of heat transfer. Our major findings are (i) annual mean temperature is the best single predictor of mass-independent Cmin. (ii) After controlling for the effect of body mass, there is a strong positive correlation between log10 (Cmin) and log10 (BMR). Further, the slope of this correlation is close to one, indicating an almost perfect compensation between both physiological variables. (iii) Structural equation modelling indicated that Cmin values are adjusted to BMR values and not the other way around. Thus, our results strongly suggest that BMR and thermal conductance integrate a coordinated system for heat regulation in endothermic animals and that summer conductance values are adjusted (in an evolutionary sense) to track changes in BMRs. PMID:23902915

  6. Thermal conductance and basal metabolic rate are part of a coordinated system for heat transfer regulation.

    Science.gov (United States)

    Naya, Daniel E; Spangenberg, Lucía; Naya, Hugo; Bozinovic, Francisco

    2013-09-22

    Thermal conductance measures the ease with which heat leaves or enters an organism's body. Although the analysis of this physiological variable in relation to climatic and ecological factors can be traced to studies by Scholander and colleagues, only small advances have occurred ever since. Here, we analyse the relationship between minimal thermal conductance estimated during summer (Cmin) and several ecological, climatic and geographical factors for 127 rodent species, in order to identify the exogenous factors that have potentially affected the evolution of thermal conductance. In addition, we evaluate whether there is compensation between Cmin and basal metabolic rate (BMR)-in such a way that a scale-invariant ratio between both variables is equal to one-as could be expected from the Scholander-Irving model of heat transfer. Our major findings are (i) annual mean temperature is the best single predictor of mass-independent Cmin. (ii) After controlling for the effect of body mass, there is a strong positive correlation between log10 (Cmin) and log10 (BMR). Further, the slope of this correlation is close to one, indicating an almost perfect compensation between both physiological variables. (iii) Structural equation modelling indicated that Cmin values are adjusted to BMR values and not the other way around. Thus, our results strongly suggest that BMR and thermal conductance integrate a coordinated system for heat regulation in endothermic animals and that summer conductance values are adjusted (in an evolutionary sense) to track changes in BMRs.

  7. The function regulation of protein C system and novel high risk of venous thrombosis

    International Nuclear Information System (INIS)

    Jin Jian; Tao Yonghui; Zhang Lianfen; Zhang Rongjun; Zhang Manda; Wang Bocheng; He Yang; Bai Xia; Ruan Changgeng

    1999-12-01

    The procedures for isolation and purification of PC, PS, PCI and antithrombin III(ATIII) from human plasma and TM from human urine were developed. Five RIAs were also developed, on the equilibrium method, by raising the antisera in rabbits. 125 I-PC, 125 I-PS and 125 I-ATIII were prepared using the chloramine-T method, 125 I-PCI by Iodogen method and 125 I-TM by Bolton-Hunter method. All of their sensitivities were below 10 μg/L, and the ranges of recovery rates were 94.30% to 105.22%. The cross reactivities of these methods with factor II and thrombin (Th) were negligible. The functional regulation of protein C system with flow cytometry and the five RIAs was investigated. On the basis of the five RIAs. The technique of APC-APTT was developed, which is a simple and reliable method to detect APC-resistance. A PCR was also developed for identification and verification of G1691A transition or point mutation of factor V on homozygotes and heterozygotes. Even though the diagnostic level of APC-APTT were the same as. It is observed that factor V G1691A mutation incidence on Chinese is much lower than on North European. There may be other factors about APC-resistance, such as factor VIII mutation or factor V mutation but not on G1691 A in Chinese

  8. Australia; Financial System Stability Assessment, including Reports on the Observance of Standards and Codes on the following topics: Banking Supervision, Insurance Regulation, Securities Regulation, and Payment Systems

    OpenAIRE

    International Monetary Fund

    2006-01-01

    The Australian banking system, which holds approximately half of total financial systems assets, and is dominated by four major banks, is sound with high earnings, high asset growth, and low levels of problem assets. Stress tests did not reveal near-term stability concerns, suggesting the banking system is likely to be resilient to adverse shocks. Australia’s financial supervisory structure of prudential authority and market conduct authority is sound overall. The medium-term challenges facin...

  9. Regulating outdoor advertisement boards; employing spatial decision support system to control urban visual pollution

    Science.gov (United States)

    Wakil, K.; Hussnain, MQ; Tahir, A.; Naeem, M. A.

    2016-06-01

    Unmanaged placement, size, location, structure and contents of outdoor advertisement boards have resulted in severe urban visual pollution and deterioration of the socio-physical living environment in urban centres of Pakistan. As per the regulatory instruments, the approval decision for a new advertisement installation is supposed to be based on the locational density of existing boards and their proximity or remoteness to certain land- uses. In cities, where regulatory tools for the control of advertisement boards exist, responsible authorities are handicapped in effective implementation due to the absence of geospatial analysis capacity. This study presents the development of a spatial decision support system (SDSS) for regularization of advertisement boards in terms of their location and placement. The knowledge module of the proposed SDSS is based on provisions and restrictions prescribed in regulatory documents. While the user interface allows visualization and scenario evaluation to understand if the new board will affect existing linear density on a particular road and if it violates any buffer restrictions around a particular land use. Technically the structure of the proposed SDSS is a web-based solution which includes open geospatial tools such as OpenGeo Suite, GeoExt, PostgreSQL, and PHP. It uses three key data sets including road network, locations of existing billboards and building parcels with land use information to perform the analysis. Locational suitability has been calculated using pairwise comparison through analytical hierarchy process (AHP) and weighted linear combination (WLC). Our results indicate that open geospatial tools can be helpful in developing an SDSS which can assist solving space related iterative decision challenges on outdoor advertisements. Employing such a system will result in effective implementation of regulations resulting in visual harmony and aesthetic improvement in urban communities.

  10. The effects of chromium(VI) on the thioredoxin system: Implications for redox regulation

    Science.gov (United States)

    Myers, Charles R.

    2014-01-01

    Hexavalent chromium [Cr(VI)] compounds are highly redox active and have long been recognized as potent cytotoxins and carcinogens. The intracellular reduction of Cr(VI) generates reactive Cr intermediates, which are themselves strong oxidants, as well as superoxide, hydrogen peroxide, and hydroxyl radical. These probably contribute to the oxidative damage and effects on redox-sensitive transcription factors that have been reported. However, the identification of events that initiate these signaling changes has been elusive. More recent studies show that Cr(VI) causes irreversible inhibition of thioredoxin reductase (TrxR) and oxidation of thioredoxin (Trx) and peroxiredoxin (Prx). Mitochondrial Trx2/Prx3 are more sensitive to Cr(VI) treatment than cytosolic Trx1/Prx1, although both compartments show thiol oxidation with higher doses or longer treatments. Thiol redox proteomics demonstrate that Trx2, Prx3, and Trx1 are among the most sensitive proteins in cells to Cr(VI) treatment. Their oxidation could therefore represent initiating events that have widespread implications for protein thiol redox control and for multiple aspects of redox signaling. This review summarizes the effects of Cr(VI) on the TrxR/Trx system and how these events could influence a number of downstream redox signaling systems that are influenced by Cr(VI) exposure. Some of the signaling events discussed include the activation of apoptosis signal regulating kinase and MAP kinases (p38 and JNK) and the modulation of a number of redox-sensitive transcription factors including AP-1, NF-κB, p53, and Nrf2. PMID:22542445

  11. Development of System Regulating and Support for Nuclear Security in Belarus

    International Nuclear Information System (INIS)

    Lobach, D.; Astashka, R.; Lugovskaya, O.

    2015-01-01

    A safeguards strengthening in Belarus is realized as complex for measures of legal authorities building, advance staff education and international cooperation. The main scope of complex coordinated activities is to provide the sustainable development of national regulatory system and support for current and future challenges in a more globalized world to assure relevant safeguards measures and implements, to get the sustainable international and regional cooperation. Collected and implemented information and knowledge, analytical thinking of involved specialists will improve cooperation between IAEA and States to optimize technical support and experience exchange. Some authorities are responsible in regulating and oversighting for nuclear security in Belarus. The main challenge of national system development is realization the conception of effective coordination. The nuclear regulatory authority (the Ministry for Emergency Situations/ Gosatomnadzor) has the responsibility either to build up own technical capabilities for detailed review and assessment of processes and activities of the NPP operator or to make sure that a technical support organization equipped with sufficient knowledge and structural capabilities is involved in assessment and analysis of processes at all phases of the NPP use. There is developed the conception for creation of analytical and technical support laboratory including both stationary and mobile equipment and techniques for nuclear security prevention and control measures and arrangements. It is actually the realization of conception the Joint Center for Nuclear Security Competence in Belarus for national and cooperational purposes. The implementation of strengthening plans and put-up arrangements will lead to integrated regulatory activities in order to allow practical optimization of the resources to get benefits from exchange of experience and issues from safety analysis and oversighting as synergy effect. (author)

  12. Harzianolide, a novel plant growth regulator and systemic resistance elicitor from Trichoderma harzianum.

    Science.gov (United States)

    Cai, Feng; Yu, Guanghui; Wang, Ping; Wei, Zhong; Fu, Lin; Shen, Qirong; Chen, Wei

    2013-12-01

    A detailed understanding of the effect of natural products on plant growth and protection will underpin new product development for plant production. The isolation and characterization of a known secondary metabolite named harzianolide from Trichoderma harzianum strain SQR-T037 were described, and the bioactivity of the purified compound as well as the crude metabolite extract in plant growth promotion and systemic resistance induction was investigated in this study. The results showed that harzianolide significantly promoted tomato seedling growth by up to 2.5-fold (dry weight) at a concentration of 0.1 ppm compared with the control. The result of root scan suggested that Trichoderma secondary metabolites may influence the early stages of plant growth through better root development for the enhancement of root length and tips. Both of the purified harzianolide and crude metabolite extract increased the activity of some defense-related enzymes to response to oxidative stress. Examination of six defense-related gene expression by real-time reverse transcription-PCR analysis revealed that harzianolide induces the expression of genes involved in the salicylic acid (PR1 and GLU) and jasmonate/ethylene (JERF3) signaling pathways while crude metabolite extract inhibited some gene expression (CHI-II and PGIP) related to basal defense in tomato plants. Further experiment showed that a subsequent challenge of harzianolide-pretreated plants with the pathogen Sclerotinia sclerotiorum resulted in higher systemic resistance by the reduction of lesion size. These results indicate that secondary metabolites of Trichoderma spp., like harzianolide, may play a novel role in both plant growth regulation and plant defense responses. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  13. Counterbalancing Regulation in Response Memory of a Positively Autoregulated Two-Component System.

    Science.gov (United States)

    Gao, Rong; Godfrey, Katherine A; Sufian, Mahir A; Stock, Ann M

    2017-09-15

    Fluctuations in nutrient availability often result in recurrent exposures to the same stimulus conditions. The ability to memorize the past event and use the "memory" to make adjustments to current behaviors can lead to a more efficient adaptation to the recurring stimulus. A short-term phenotypic memory can be conferred via carryover of the response proteins to facilitate the recurrent response, but the additional accumulation of response proteins can lead to a deviation from response homeostasis. We used the Escherichia coli PhoB/PhoR two-component system (TCS) as a model system to study how cells cope with the recurrence of environmental phosphate (Pi) starvation conditions. We discovered that "memory" of prior Pi starvation can exert distinct effects through two regulatory pathways, the TCS signaling pathway and the stress response pathway. Although carryover of TCS proteins can lead to higher initial levels of transcription factor PhoB and a faster initial response in prestarved cells than in cells not starved, the response enhancement can be overcome by an earlier and greater repression of promoter activity in prestarved cells due to the memory of the stress response. The repression counterbalances the carryover of the response proteins, leading to a homeostatic response whether or not cells are prestimulated. A computational model based on sigma factor competition was developed to understand the memory of stress response and to predict the homeostasis of other PhoB-regulated response proteins. Our insight into the history-dependent PhoBR response may provide a general understanding of how TCSs respond to recurring stimuli and adapt to fluctuating environmental conditions. IMPORTANCE Bacterial cells in their natural environments experience scenarios that are far more complex than are typically replicated in laboratory experiments. The architectures of signaling systems and the integration of multiple adaptive pathways have evolved to deal with such complexity

  14. Counterbalancing Regulation in Response Memory of a Positively Autoregulated Two-Component System

    Science.gov (United States)

    Gao, Rong; Godfrey, Katherine A.; Sufian, Mahir A.

    2017-01-01

    ABSTRACT Fluctuations in nutrient availability often result in recurrent exposures to the same stimulus conditions. The ability to memorize the past event and use the “memory” to make adjustments to current behaviors can lead to a more efficient adaptation to the recurring stimulus. A short-term phenotypic memory can be conferred via carryover of the response proteins to facilitate the recurrent response, but the additional accumulation of response proteins can lead to a deviation from response homeostasis. We used the Escherichia coli PhoB/PhoR two-component system (TCS) as a model system to study how cells cope with the recurrence of environmental phosphate (Pi) starvation conditions. We discovered that “memory” of prior Pi starvation can exert distinct effects through two regulatory pathways, the TCS signaling pathway and the stress response pathway. Although carryover of TCS proteins can lead to higher initial levels of transcription factor PhoB and a faster initial response in prestarved cells than in cells not starved, the response enhancement can be overcome by an earlier and greater repression of promoter activity in prestarved cells due to the memory of the stress response. The repression counterbalances the carryover of the response proteins, leading to a homeostatic response whether or not cells are prestimulated. A computational model based on sigma factor competition was developed to understand the memory of stress response and to predict the homeostasis of other PhoB-regulated response proteins. Our insight into the history-dependent PhoBR response may provide a general understanding of how TCSs respond to recurring stimuli and adapt to fluctuating environmental conditions. IMPORTANCE Bacterial cells in their natural environments experience scenarios that are far more complex than are typically replicated in laboratory experiments. The architectures of signaling systems and the integration of multiple adaptive pathways have evolved to deal

  15. On the Use of Energy Storage Technologies for Regulation Services in Electric Power Systems with Significant Penetration of Wind Energy

    DEFF Research Database (Denmark)

    Yang, Bo; Makarov, Yuri; Desteese, John

    2008-01-01

    Energy produced by intermittent renewable resources is sharply increasing in the United States. At high penetration levels, volatility of wind power production could cause additional problems for the power system balancing functions such as regulation. This paper reports some partial results...... and frequently changing regulation signal. Several energy storage options have been analyzed based on thirteen selection criteria. The evaluation process resulted in the selection of flywheels, pumped hydro electric power (or conventional hydro electric power) plant and sodium sulfur or nickel cadmium batteries...... of a project work, recently conducted by the Pacific Northwest National Laboratory (PNNL) for Bonneville Power Administration (BPA). The project proposes to mitigate additional intermittency with the help of Wide Area Energy Management System (WAEMS) that would provide a two-way simultaneous regulation service...

  16. Hypothalamic-Pituitary-Adrenal and Sympathetic Nervous System Activity and Children's Behavioral Regulation

    Science.gov (United States)

    Lisonbee, Jared A.; Pendry, Patricia; Mize, Jacquelyn; Gwynn, Eugenia Parrett

    2010-01-01

    Self-regulation ability is an important component of children's academic success. Physiological reactivity may relate to brain activity governing attention and behavioral regulation. Saliva samples collected from 186 preschool children (101 boys, mean age = 53 months, 34% minority) before and after a series of mildly challenging games and again 30…

  17. Systemic acquired resistance in soybean is regulated by two proteins, Orthologous to Arabidopsis NPR1

    Directory of Open Access Journals (Sweden)

    Sandhu Devinder

    2009-08-01

    Full Text Available Abstract Background Systemic acquired resistance (SAR is induced in non-inoculated leaves following infection with certain pathogenic strains. SAR is effective against many pathogens. Salicylic acid (SA is a signaling molecule of the SAR pathway. The development of SAR is associated with the induction of pathogenesis related (PR genes. Arabidopsis non-expressor of PR1 (NPR1 is a regulatory gene of the SA signal pathway 123. SAR in soybean was first reported following infection with Colletotrichum trancatum that causes anthracnose disease. We investigated if SAR in soybean is regulated by a pathway, similar to the one characterized in Arabidopsis. Results Pathogenesis-related gene GmPR1 is induced following treatment of soybean plants with the SAR inducer, 2,6-dichloroisonicotinic acid (INA or infection with the oomycete pathogen, Phytophthora sojae. In P. sojae-infected plants, SAR was induced against the bacterial pathogen, Pseudomonas syringae pv. glycinea. Soybean GmNPR1-1 and GmNPR1-2 genes showed high identities to Arabidopsis NPR1. They showed similar expression patterns among the organs, studied in this investigation. GmNPR1-1 and GmNPR1-2 are the only soybean homologues of NPR1and are located in homoeologous regions. In GmNPR1-1 and GmNPR1-2 transformed Arabidopsis npr1-1 mutant plants, SAR markers: (i PR-1 was induced following INA treatment and (ii BGL2 following infection with Pseudomonas syringae pv. tomato (Pst, and SAR was induced following Pst infection. Of the five cysteine residues, Cys82, Cys150, Cys155, Cys160, and Cys216 involved in oligomer-monomer transition in NPR1, Cys216 in GmNPR1-1 and GmNPR1-2 proteins was substituted to Ser and Leu, respectively. Conclusion Complementation analyses in Arabidopsis npr1-1 mutants revealed that homoeologous GmNPR1-1 and GmNPR1-2 genes are orthologous to Arabidopsis NPR1. Therefore, SAR pathway in soybean is most likely regulated by GmNPR1 genes. Substitution of Cys216 residue, essential

  18. Systemic acquired resistance in soybean is regulated by two proteins, Orthologous to Arabidopsis NPR1.

    Science.gov (United States)

    Sandhu, Devinder; Tasma, I Made; Frasch, Ryan; Bhattacharyya, Madan K

    2009-08-05

    Systemic acquired resistance (SAR) is induced in non-inoculated leaves following infection with certain pathogenic strains. SAR is effective against many pathogens. Salicylic acid (SA) is a signaling molecule of the SAR pathway. The development of SAR is associated with the induction of pathogenesis related (PR) genes. Arabidopsis non-expressor of PR1 (NPR1) is a regulatory gene of the SA signal pathway 123. SAR in soybean was first reported following infection with Colletotrichum trancatum that causes anthracnose disease. We investigated if SAR in soybean is regulated by a pathway, similar to the one characterized in Arabidopsis. Pathogenesis-related gene GmPR1 is induced following treatment of soybean plants with the SAR inducer, 2,6-dichloroisonicotinic acid (INA) or infection with the oomycete pathogen, Phytophthora sojae. In P. sojae-infected plants, SAR was induced against the bacterial pathogen, Pseudomonas syringae pv. glycinea. Soybean GmNPR1-1 and GmNPR1-2 genes showed high identities to Arabidopsis NPR1. They showed similar expression patterns among the organs, studied in this investigation. GmNPR1-1 and GmNPR1-2 are the only soybean homologues of NPR1and are located in homoeologous regions. In GmNPR1-1 and GmNPR1-2 transformed Arabidopsis npr1-1 mutant plants, SAR markers: (i) PR-1 was induced following INA treatment and (ii) BGL2 following infection with Pseudomonas syringae pv. tomato (Pst), and SAR was induced following Pst infection. Of the five cysteine residues, Cys82, Cys150, Cys155, Cys160, and Cys216 involved in oligomer-monomer transition in NPR1, Cys216 in GmNPR1-1 and GmNPR1-2 proteins was substituted to Ser and Leu, respectively. Complementation analyses in Arabidopsis npr1-1 mutants revealed that homoeologous GmNPR1-1 and GmNPR1-2 genes are orthologous to Arabidopsis NPR1. Therefore, SAR pathway in soybean is most likely regulated by GmNPR1 genes. Substitution of Cys216 residue, essential for oligomer-monomer transition of Arabidopsis NPR1

  19. The Relationship of Behavioral Activation and Inhibition Systems (BAS/BIS, Difficulty of Emotional Regulation, Metacognition with Worry

    Directory of Open Access Journals (Sweden)

    S. Soltan Mohammadlou

    2014-11-01

    Full Text Available Worry is a popular phenomenon and a common feature of many disorders, especially anxiety disorders. The objective of the study was to predict worry by using three predictive factors related to biological, emotional and cognition areas. In this study, behavioral inhibition, behavioral activation system, difficulties in emotion regulation and metacognition were examined as predictive variables. In a correlation cross-sectional design, 234 Medical Group students [BA and MA] of Tehran University of Medical Sciences participated in this study by using cluster sampling. The students completed these scales: Behavioral Inhibition and Behavioral Activation Systems (BAS/BIS, Difficulty of Emotion Regulation Scale (DERS, Metacognition Questionnaire-30 (MCQ-30 and Penn State Worry Questionnaire (PSWQ. Behavioral inhibition system, difficulty of emotion rgulation and metacognition variables were significantly positively correlated with worry (P<0/0 1(. Behavioral activation system variable was not significantly associated with worry. Stepwise multiple regression analysis indicated a predictive model for worry in which behavioral inhibition system, difficulty of emotional regulation and metacognition were its components respectively. Behavioral activation system was not included in the model. The findings of this study that worry should be studied in different biological, emotional, and metacognitive aspects. The results also emphasize the role of behavioral inhibition system as a temperamental and biological factor in psychopathology of worry in adult population.

  20. The society-supporting self: system justification and cultural worldview defense as different forms of self-regulation

    NARCIS (Netherlands)

    Rutjens, B.T.; Loseman, A.

    2010-01-01

    Justifying social systems and defending cultural worldviews may seem to resemble the same human need to protect what is known and predictable. The current paper would like to argue that these society-supporting tendencies concern two different forms of self-regulation: the need for control and the

  1. Iron-regulated metabolites of plant growth-promoting Pseudomonas fluorescens WCS374 : Their role in induced systemic resistance

    NARCIS (Netherlands)

    Djavaheri, M.

    2007-01-01

    The plant growth-promoting rhizobacterium Pseudomonas fluorescens WCS374r effectively suppresses fusarium wilt in radish by induced systemic resistance (ISR). In radish, WCS374r-mediated ISR depends partly on iron-regulated metabolites. Under iron-limiting conditions, P. fluorescens WCS374r produces

  2. AUTOMATIC CONTROL SYSTEM FOR REGULATED HIGH TEMPERATURE MAIN COMBUSTION CHAMBER OF MANEUVERABLE AIRCRAFT MULTIMODE GAS TURBINE ENGINE

    Directory of Open Access Journals (Sweden)

    T. V. Gras’Ko

    2014-01-01

    Full Text Available The paper describes choosing and substantiating the control laws, forming the appearance the automatic control system for regulated high temperature main combustion chamber of maneuverable aircraft multimode gas turbine engine aimed at sustainable and effective functioning of main combustion chamber within a broad operation range.

  3. Regulation and role of epiphytic nitrification and denitrification in macrophyte-dominated systems

    Energy Technology Data Exchange (ETDEWEB)

    Eriksson, Peder G.

    2000-02-01

    This thesis examines mechanisms regulating bacterial nitrification and denitrification in attached microbial communities on surfaces of aquatic macrophytes. It also evaluates the role of epiphytic nitrification and denitrification for the nitrogen turnover in macrophyte-dominated nutrient-rich freshwater. Epiphytic nitrification is promoted in light and epiphytic denitrification occurs mainly in dark, because the metabolic activity of the aquatic macrophyte and its epiphytes induce in light high and in dark low oxygen concentrations in epiphytic communities. Epiphytic nitrification and denitrification are also affected by the physical and chemical characteristics of the aquatic macrophyte. The spatial distribution of nitrification in emergent macrophyte wetlands is related to the species composition of the emergent vegetation, possibly because of a macrophyte species-related release of organic nitrification inhibitors. Contrasting to nitrifying bacteria, which are lithotrophic, denitrifying bacteria use organic substances as an energy source and are therefore stimulated by the release of organic matter from aquatic macrophytes. Epiphytic communities support more denitrification in nutrient-rich than in nutrient-poor environments. In lakes and ponds, epiphytic denitrification is higher at sheltered locations than at locations exposed to wind-induced water movements or currents. In flowing water, epiphytic denitrification occurs mainly at low oxygen concentrations in the surrounding water. However, because aquatic macrophytes impede water flow and induce low oxygen concentrations in dark, epiphytic denitrification can be present within dense vegetation despite of high oxygen concentrations in the surrounding water. Epiphytic nitrification is almost unaffected by flow conditions, and can occur both in light and in dark. In shallow-water systems such as treatment wetlands, aquatic macrophytes often provide most of the accessible surface area for attached nitrifying and

  4. Market, Regulation, Market, Regulation

    DEFF Research Database (Denmark)

    Frankel, Christian; Galland, Jean-Pierre

    2015-01-01

    barriers to trade in Europe, realized the free movement of products by organizing progressively several orders of markets and regulation. Based on historical and institutional documents, on technical publications, and on interviews, this article relates how the European Commission and the Member States had......This paper focuses on the European Regulatory system which was settled both for opening the Single Market for products and ensuring the consumers' safety. It claims that the New Approach and Standardization, and the Global Approach to conformity assessment, which suppressed the last technical...... alternatively recourse to markets and to regulations, at the three main levels of the New Approach Directives implementation. The article focuses also more specifically on the Medical Devices sector, not only because this New Approach sector has long been controversial in Europe, and has recently been concerned...

  5. Experience in connecting the power generating units of thermal power plants to automatic secondary frequency regulation within the united power system of Russia

    International Nuclear Information System (INIS)

    Zhukov, A. V.; Komarov, A. N.; Safronov, A. N.; Barsukov, I. V.

    2009-01-01

    The principles of central control of the power generating units of thermal power plants by automatic secondary frequency and active power overcurrent regulation systems, and the algorithms for interactions between automatic power control systems for the power production units in thermal power plants and centralized systems for automatic frequency and power regulation, are discussed. The order of switching the power generating units of thermal power plants over to control by a centralized system for automatic frequency and power regulation and by the Central Coordinating System for automatic frequency and power regulation is presented. The results of full-scale system tests of the control of power generating units of the Kirishskaya, Stavropol, and Perm GRES (State Regional Electric Power Plants) by the Central Coordinating System for automatic frequency and power regulation at the United Power System of Russia on September 23-25, 2008, are reported.

  6. The role of the apelinergic and vasopressinergic systems in the regulation of the cardiovascular system and the pathogenesis of cardiovascular disease.

    Science.gov (United States)

    Czarzasta, Katarzyna; Cudnoch-Jedrzejewska, Agnieszka

    2014-01-01

    Research studies indicate a role of the apelinergic and vasopressinergic systems both in the regulation of the cardiovascular system and the pathogenesis of CVD, including in such settings as obesity and stress. Based on these data, it may be suggested that interactions between these systems underlie numerous physiological and pathophysiological processes, some of them related to the cardiovascular system. Better understanding of the role of these systems and their interactions, both physiological and related to the pathogenesis of CVD, will allow further advances in prevention and drug therapy.

  7. Climate Change Impacts on Stream Temperature in Regulated River Systems: A Case Study in the Southeastern United States

    Science.gov (United States)

    Cheng, Y.; Niemeyer, R. J.; Zhang, X.; Yearsley, J. R.; Voisin, N.; Nijssen, B.

    2017-12-01

    Climate change and associated changes in air temperature and precipitation are projected to impact natural water resources quantity, quality and timing. In the past century, over 280 major dams were built in the Southeastern United States (SEUS) (GRanD database). Regulation of the river system greatly alters natural streamflow as well as stream temperature. Understanding the impacts of climate change on regulated systems, particularly within the context of the Clean Water Act, can inform stakeholders how to maintain and adapt water operations (e.g. regulation, withdrawals). In this study, we use a new modeling framework to study climate change impacts on stream temperatures of a regulated river system. We simulate runoff with the Variable Infiltration Capacity (VIC) macroscale hydrological model, regulated streamflow and reservoir operations with a large-scale river routing-reservoir model (MOSART-WM), and stream temperature using the River Basin Model (RBM). We enhanced RBM with a two-layer thermal stratification reservoir module. This modeling framework captures both the impact of reservoir regulation on streamflow and the reservoir stratification effects on downstream temperatures. We evaluate changes in flow and stream temperatures based on climate projections from two representative concentration pathways (RCPs; RCP4.5 and RCP8.5) from the Coupled Model Intercomparison Project Phase 5 (CMIP5). We simulate river temperature with meteorological forcings that have been downscaled with the Multivariate Constructed Analogs (MACA) method. We are specifically interested in analyzing extreme periods during which stream temperature exceeds water quality standards. In this study, we focus on identifying whether these extreme temperature periods coincide with low flows, and whether the frequency and duration of these operationally-relevant periods will increase under future climate change.

  8. The Monetary Policy in the System of State Regulation of the Indian Economy

    Directory of Open Access Journals (Sweden)

    Natalia V. Galistcheva

    2015-01-01

    Full Text Available The main task of this research is the analysis of India's monetary policy and its place in the system of state regulation of the economy. The article highlights the main directions of the Indian monetary policy in 1990-2000s aiming to raise competitiveness of the Indian goods on the foreign markets as well as stimulating the inflow of foreign capital in necessary volumes into the national economy. The author focuses on the main instruments of the modern Indian monetary policy, pursued in line with providing the undervalued rupee, which include the manipulating of the bank rate and currency interventions, directed mainly at sterilization of excessive inflow of foreign currency to the country. The article also underlines all the advantages and costs of the monetary policy. One of its main advantages is stimulation of national production's exports and among costs there are difficulties of importing machines and equipment into the country, increase of inflation rate as a result of massive inflow of export revenue, difficulties at external debt's service. The author notes the gradual nature of introduction of current account rupee convertibility and reasons for delay in achieving its full convertibility. Among them there are rather high level of fiscal deficit of the consolidated budget, essential average annual level of inflation, problems of non-performed assets in the economy, high liquidity ratio for commercial banks. The article also presents statistical data on the present state of the Indian foreign exchange reserves as well as dynamics in nominal and real effective exchange rate of rupee in 2005/06 - 2013/14 fiscal year.

  9. Staphylococcus aureus sarA regulates inflammation and colonization during central nervous system biofilm formation.

    Directory of Open Access Journals (Sweden)

    Jessica N Snowden

    Full Text Available Infection is a frequent and serious complication following the treatment of hydrocephalus with CSF shunts, with limited therapeutic options because of biofilm formation along the catheter surface. Here we evaluated the possibility that the sarA regulatory locus engenders S. aureus more resistant to immune recognition in the central nervous system (CNS based on its reported ability to regulate biofilm formation. We utilized our established model of CNS catheter-associated infection, similar to CSF shunt infections seen in humans, to compare the kinetics of bacterial titers, cytokine production and inflammatory cell influx elicited by wild type S. aureus versus an isogenic sarA mutant. The sarA mutant was more rapidly cleared from infected catheters compared to its isogenic wild type strain. Consistent with this finding, several pro-inflammatory cytokines and chemokines, including IL-17, CXCL1, and IL-1β were significantly increased in the brain following infection with the sarA mutant versus wild type S. aureus, in agreement with the fact that the sarA mutant displayed impaired biofilm growth and favored a planktonic state. Neutrophil influx into the infected hemisphere was also increased in the animals infected with the sarA mutant compared to wild type bacteria. These changes were not attributable to extracellular protease activity, which is increased in the context of SarA mutation, since similar responses were observed between sarA and a sarA/protease mutant. Overall, these results demonstrate that sarA plays an important role in attenuating the inflammatory response during staphylococcal biofilm infection in the CNS via a mechanism that remains to be determined.

  10. Epigenetic Regulation in Particulate Matter-Mediated Cardiopulmonary Toxicities: A Systems Biology Perspective.

    Science.gov (United States)

    Wang, Ting; Garcia, Joe Gn; Zhang, Wei

    2012-12-01

    Particulate matter (PM) air pollution exerts significant adverse health effects in global populations, particularly in developing countries with extensive air pollution. Understanding of the mechanisms of PM-induced health effects including the risk for cardiovascular diseases remains limited. In addition to the direct cellular physiological responses such as mitochondrial dysfunction and oxidative stress, PM mediates remarkable dysregulation of gene expression, especially in cardiovascular tissues. The PM-mediated gene dysregulation is likely to be a complex mechanism affected by various genetic and non-genetic factors. Notably, PM is known to alter epigenetic markers (e.g., DNA methylation and histone modifications), which may contribute to air pollution-mediated health consequences including the risk for cardiovascular diseases. Notably, epigenetic changes induced by ambient PM exposure have emerged to play a critical role in gene regulation. Though the underlying mechanism(s) are not completely clear, the available evidence suggests that the modulated activities of DNA methyltransferase (DNMT), histone acetylase (HAT) and histone deacetylase (HDAC) may contribute to the epigenetic changes induced by PM or PM-related chemicals. By employing genome-wide epigenomic and systems biology approaches, PM toxicogenomics could conceivably progress greatly with the potential identification of individual epigenetic loci associated with dysregulated gene expression after PM exposure, as well the interactions between epigenetic pathways and PM. Furthermore, novel therapeutic targets based on epigenetic markers could be identified through future epigenomic studies on PM-mediated cardiopulmonary toxicities. These considerations collectively inform the future population health applications of genomics in developing countries while benefiting global personalized medicine at the same time.

  11. Auxins differentially regulate root system architecture and cell cycle protein levels in maize seedlings.

    Science.gov (United States)

    Martínez-de la Cruz, Enrique; García-Ramírez, Elpidio; Vázquez-Ramos, Jorge M; Reyes de la Cruz, Homero; López-Bucio, José

    2015-03-15

    Maize (Zea mays) root system architecture has a complex organization, with adventitious and lateral roots determining its overall absorptive capacity. To generate basic information about the earlier stages of root development, we compared the post-embryonic growth of maize seedlings germinated in water-embedded cotton beds with that of plants obtained from embryonic axes cultivated in liquid medium. In addition, the effect of four different auxins, namely indole-3-acetic acid (IAA), 1-naphthaleneacetic acid (NAA), indole-3-butyric acid (IBA) and 2,4-dichlorophenoxyacetic acid (2,4-D) on root architecture and levels of the heat shock protein HSP101 and the cell cycle proteins CKS1, CYCA1 and CDKA1 were analyzed. Our data show that during the first days after germination, maize seedlings develop several root types with a simultaneous and/or continuous growth. The post-embryonic root development started with the formation of the primary root (PR) and seminal scutellar roots (SSR) and then continued with the formation of adventitious crown roots (CR), brace roots (BR) and lateral roots (LR). Auxins affected root architecture in a dose-response fashion; whereas NAA and IBA mostly stimulated crown root formation, 2,4-D showed a strong repressing effect on growth. The levels of HSP101, CKS1, CYCA1 and CDKA in root and leaf tissues were differentially affected by auxins and interestingly, HSP101 registered an auxin-inducible and root specific expression pattern. Taken together, our results show the timing of early branching patterns of maize and indicate that auxins regulate root development likely through modulation of the HSP101 and cell cycle proteins. Copyright © 2014 Elsevier GmbH. All rights reserved.

  12. Zonulin as prehaptoglobin2 regulates lung permeability and activates the complement system.

    Science.gov (United States)

    Rittirsch, Daniel; Flierl, Michael A; Nadeau, Brian A; Day, Danielle E; Huber-Lang, Markus S; Grailer, Jamison J; Zetoune, Firas S; Andjelkovic, Anuska V; Fasano, Alessio; Ward, Peter A

    2013-06-15

    Zonulin is a protein involved in the regulation of tight junctions (TJ) in epithelial or endothelial cells. Zonulin is known to affect TJ in gut epithelial cells, but little is known about its influences in other organs. Prehaptoglobin2 has been identified as zonulin and is related to serine proteases (MASPs, C1qrs) that activate the complement system. The current study focused on the role of zonulin in development of acute lung injury (ALI) in C57BL/6 male mice following intrapulmonary deposition of IgG immune complexes. A zonulin antagonist (AT-1001) and a related peptide with permeability agonist activities (AT-1002) were employed and given intratracheally or intravenously. Also, zonulin was blocked in lung with a neutralizing antibody. In a dose-dependent manner, AT-1001 or zonulin neutralizing antibody attenuated the intensity of ALI (as quantitated by albumin leak, neutrophil accumulation, and proinflammatory cytokines). A similar pattern was found using the bacterial lipopolysaccharide model of ALI. Using confocal microscopy on sections of injured lungs, staining patterns for TJ proteins were discontinuous, reduced, and fragmented. As expected, the leak of blood products into the alveolar space confirmed the passage of 3 and 20 kDa dextran, and albumin. In contrast to AT-1001, application of the zonulin agonist AT-1002 intensified ALI. Zonulin both in vitro and in vivo induced generation of complement C3a and C5a. Collectively, these data suggest that zonulin facilitates development of ALI both by enhancing albumin leak and complement activation as well as increased buildup of neutrophils and cytokines during development of ALI.

  13. Are separable aromatase systems involved in hormonal regulation of the male brain

    International Nuclear Information System (INIS)

    Hutchison, J.B.; Schumacher, M.; Steimer, T.; Gahr, M.

    1990-01-01

    In vitro study of testosterone (T) metabolism shows that formation of estradiol-17 beta (E2) is regionally specific within the preoptic area (POA) of the male ring dove. The POA is known to be involved in the formation of E2 required for specific components of male sexual behavior. Two sub-areas of high aromatase activity, anterior (aPOA) and posterior preoptic (pPOA) areas, have been identified. Aromatase activity is higher in aPOA than in pPOA. The aromatase activity within the aPOA is also more sensitive to the inductive effects of low circulating T, derived from subcutaneous silastic implants, than the enzyme activity in pPOA. Kinetic analysis of preoptic fractions indicates that a similar high-affinity enzyme occurs in both areas (apparent Km less than 14 nM), but the Vmax of aPOA enzyme activity is higher than pPOA. Cells containing estrogen receptors (ER) are localized in areas of high aromatase activity. There is overlap between immunostained cells in the aPOA and in samples containing inducible aromatase activity measured in vitro. Within the aPOA there is a higher density of ER cells in the nucleus preopticus medialis. The pPOA area also contains ER, notably in the nucleus interstitialis, but at a lower density. We conclude that the hormonal regulation of the male preoptic-anterior hypothalamic region, which is a target for the behavioral action of T, involves at least two inducible aromatase systems with associated estrogen receptor cells

  14. Vasopressin and oxytocin receptor systems in the brain: Sex differences and sex-specific regulation of social behavior.

    Science.gov (United States)

    Dumais, Kelly M; Veenema, Alexa H

    2016-01-01

    The neuropeptides vasopressin (VP) and oxytocin (OT) and their receptors in the brain are involved in the regulation of various social behaviors and have emerged as drug targets for the treatment of social dysfunction in several sex-biased neuropsychiatric disorders. Sex differences in the VP and OT systems may therefore be implicated in sex-specific regulation of healthy as well as impaired social behaviors. We begin this review by highlighting the sex differences, or lack of sex differences, in VP and OT synthesis in the brain. We then discuss the evidence showing the presence or absence of sex differences in VP and OT receptors in rodents and humans, as well as showing new data of sexually dimorphic V1a receptor binding in the rat brain. Importantly, we find that there is lack of comprehensive analysis of sex differences in these systems in common laboratory species, and we find that, when sex differences are present, they are highly brain region- and species-specific. Interestingly, VP system parameters (VP and V1aR) are typically higher in males, while sex differences in the OT system are not always in the same direction, often showing higher OT expression in females, but higher OT receptor expression in males. Furthermore, VP and OT receptor systems show distinct and largely non-overlapping expression in the rodent brain, which may cause these receptors to have either complementary or opposing functional roles in the sex-specific regulation of social behavior. Though still in need of further research, we close by discussing how manipulations of the VP and OT systems have given important insights into the involvement of these neuropeptide systems in the sex-specific regulation of social behavior in rodents and humans. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Vasopressin and oxytocin receptor systems in the brain: sex differences and sex-specific regulation of social behavior

    Science.gov (United States)

    Dumais, Kelly M.; Veenema, Alexa H.

    2015-01-01

    The neuropeptides vasopressin (VP) and oxytocin (OT) and their receptors in the brain are involved in the regulation of various social behaviors and have emerged as drug targets for the treatment of social dysfunction in several sex-biased neuropsychiatric disorders. Sex differences in the VP and OT systems may therefore be implicated in sex-specific regulation of healthy as well as impaired social behaviors. We begin this review by highlighting the sex differences, or lack of sex differences, in VP and OT synthesis in the brain. We then discuss the evidence showing the presence or absence of sex differences in VP and OT receptors in rodents and humans, as well as showing new data of sexually dimorphic V1a receptor binding in the rat brain. Importantly, we find that there is lack of comprehensive analysis of sex differences in these systems in common laboratory species, and we find that, when sex differences are present, they are highly brain region- and species- specific. Interestingly, VP system parameters (VP and V1aR) are typically higher in males, while sex differences in the OT system are not always in the same direction, often showing higher OT expression in females, but higher OT receptor expression in males. Furthermore, VP and OT receptor systems show distinct and largely non-overlapping expression in the rodent brain, which may cause these receptors to have either complementary or opposing functional roles in the sex-specific regulation of social behavior. Though still in need of further research, we close by discussing how manipulations of the VP and OT systems have given important insights into the involvement of these neuropeptide systems in the sex-specific regulation of social behavior in rodents and humans. PMID:25951955

  16. Romantic passion as output from a self-regulating, intimacy-seeking system: a model for understanding passionate love.

    Science.gov (United States)

    Troy, Adam B

    2005-06-01

    This article presents a model of why individuals experience the feeling of passionate love in intimate relationships. Previous models have been limited because they do not describe the purpose and function of passionate love, do not incorporate basic emotion and personality theory, or are not applicable to help couples in distress. The present model reinterprets and integrates previous findings. New predictions are made about the functioning of passionate love in relationships by hypothesizing a self-regulating, intimacy-seeking system that produces passionate love as its outcome. A self-regulation model proposed by Carver and Scheier in 1998 is the template on which this model is based.

  17. Towards a multi-agent system for regulated information exchange in crime investigations

    NARCIS (Netherlands)

    Dijkstra, Pieter; Prakken, H.; Vey Mestdagh, C.N.J. de

    2005-01-01

    This paper outlines a multi-agent architecture for regulated information exchange of crime investigation data between police forces. Interactions between police officers about information exchange are analysed as negotiation dialogues with embedded persuasion dialogues. An architecture is then

  18. Size-Dependent Regulation of Intracellular Trafficking of Polystyrene Nanoparticle-Based Drug-Delivery Systems.

    Science.gov (United States)

    Wang, Ting; Wang, Lu; Li, Xiaoming; Hu, Xingjie; Han, Yuping; Luo, Yao; Wang, Zejun; Li, Qian; Aldalbahi, Ali; Wang, Lihua; Song, Shiping; Fan, Chunhai; Zhao, Yun; Wang, Maolin; Chen, Nan

    2017-06-07

    Nanoparticles (NPs) have shown great promise as intracellular imaging probes or nanocarriers and are increasingly being used in biomedical applications. A detailed understanding of how NPs get "in and out" of cells is important for developing new nanomaterials with improved selectivity and less cytotoxicity. Both physical and chemical characteristics have been proven to regulate the cellular uptake of NPs. However, the exocytosis process and its regulation are less explored. Herein, we investigated the size-regulated endocytosis and exocytosis of carboxylated polystyrene (PS) NPs. PS NPs with a smaller size were endocytosed mainly through the clathrin-dependent pathway, whereas PS NPs with a larger size preferred caveolae-mediated endocytosis. Furthermore, our results revealed exocytosis of larger PS NPs and tracked the dynamic process at the single-particle level. These results indicate that particle size is a key factor for the regulation of intracellular trafficking of NPs and provide new insight into the development of more effective cellular nanocarriers.

  19. Metabolic Regulation of a Bacterial Cell System with Emphasis on Escherichia coli Metabolism

    Science.gov (United States)

    Shimizu, Kazuyuki

    2013-01-01

    It is quite important to understand the overall metabolic regulation mechanism of bacterial cells such as Escherichia coli from both science (such as biochemistry) and engineering (such as metabolic engineering) points of view. Here, an attempt was made to clarify the overall metabolic regulation mechanism by focusing on the roles of global regulators which detect the culture or growth condition and manipulate a set of metabolic pathways by modulating the related gene expressions. For this, it was considered how the cell responds to a variety of culture environments such as carbon (catabolite regulation), nitrogen, and phosphate limitations, as well as the effects of oxygen level, pH (acid shock), temperature (heat shock), and nutrient starvation. PMID:25937963

  20. A Unique Fungal Two-Component System Regulates Stress Responses, Drug Sensitivity, Sexual Development, and Virulence of Cryptococcus neoformans

    Science.gov (United States)

    Bahn, Yong-Sun; Kojima, Kaihei; Cox, Gary M.

    2006-01-01

    The stress-activated mitogen-activated protein kinase (MAPK) pathway is widely used by eukaryotic organisms as a central conduit via which cellular responses to the environment effect growth and differentiation. The basidiomycetous human fungal pathogen Cryptococcus neoformans uniquely uses the stress-activated Pbs2-Hog1 MAPK system to govern a plethora of cellular events, including stress responses, drug sensitivity, sexual reproduction, and virulence. Here, we characterized a fungal “two-component” system that controls these fundamental cellular functions via the Pbs2-Hog1 MAPK cascade. A typical response regulator, Ssk1, modulated all Hog1-dependent phenotypes by controlling Hog1 phosphorylation, indicating that Ssk1 is the major upstream signaling component of the Pbs2-Hog1 pathway. A second response regulator, Skn7, governs sensitivity to Na+ ions and the antifungal agent fludioxonil, negatively controls melanin production, and functions independently of Hog1 regulation. To control these response regulators, C. neoformans uses multiple sensor kinases, including two-component–like (Tco) 1 and Tco2. Tco1 and Tco2 play shared and distinct roles in stress responses and drug sensitivity through the Hog1 MAPK system. Furthermore, each sensor kinase mediates unique cellular functions for virulence and morphological differentiation. Our findings highlight unique adaptations of this global two-component MAPK signaling cascade in a ubiquitous human fungal pathogen. PMID:16672377