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Sample records for regulated restriction-modification system

  1. IS-linked movement of a restriction-modification system.

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    Noriko Takahashi

    Full Text Available Potential mobility of restriction-modification systems has been suggested by evolutionary/bioinformatic analysis of prokaryotic genomes. Here we demonstrate in vivo movement of a restriction-modification system within a genome under a laboratory condition. After blocking replication of a temperature-sensitive plasmid carrying a PaeR7I restriction-modification system in Escherichia coli cells, the plasmid was found integrated into the chromosome of the surviving cells. Sequence analysis revealed that, in the majority of products, the restriction-modification system was linked to chromosomal insertion sequences (ISs. Three types of products were: (I apparent co-integration of the plasmid and the chromosome at a chromosomal IS1 or IS5 copy (24/28 analyzed; (II de novo insertion of IS1 with the entire plasmid except for a 1-3 bp terminal deletion (2/28; and (III reciprocal crossing-over between the plasmid and the chromosome involving 1-3 bp of sequence identity (2/28. An R-negative mutation apparently decreased the efficiency of successful integration by two orders of magnitude. Reconstruction experiments demonstrated that the restriction-dependence was mainly due to selection against cells without proper integration: their growth was inhibited by the restriction enzyme action. These results demonstrate collaboration of a mobile element and a restriction-modification system for successful joint migration. This collaboration may have promoted the spread and, therefore, the long-term persistence of these complexes and restriction-modification systems in a wide range of prokaryotes.

  2. Interplay Between Bacteriophages and Restriction-Modification Systems in Enterococci

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    Pristas Peter

    2014-06-01

    Full Text Available The complete genomes of Enterococcus faecalis bacteriophages were analyzed for tetranucleotide words avoidance. Very similar tetranucleotide composition was found in all tested genomes with strong underrepresentation of palindromic GATC and GGCC words. This avoidance could be explained as a protection mechanism against host restriction-modification systems as a clear correlation was found between avoidance of palindromic words and the specificity of E. faecalis restriction and modification systems. No similar avoidance of tetranucleotide words was observed for non-palindromic words. A weak correlation was observed between avoidance of tetranucleotide palindromes in bacteriophage genomes and the possession of phage encoded DNA methyltransferases confirming the interrelation between bacteriophage genomes composition and restriction and modification systems in enterococci

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

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    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......-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...... of pangenes. The topology of the trees was compared to the presence of RM systems, antimicrobial resistance (AMR) genes, Salmonella pathogenicity islands (SPIs), and plasmid replicons. We did not observe any correlation between evolution and the RM systems in S. enterica subsp. enterica. However, sublineage...

  6. MutL homologs in restriction-modification systems and the origin of eukaryotic MORC ATPases

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    Aravind L

    2008-03-01

    Full Text Available Abstract The provenance and biochemical roles of eukaryotic MORC proteins have remained poorly understood since the discovery of their prototype MORC1, which is required for meiotic nuclear division in animals. The MORC family contains a combination of a gyrase, histidine kinase, and MutL (GHKL and S5 domains that together constitute a catalytically active ATPase module. We identify the prokaryotic MORCs and establish that the MORC family belongs to a larger radiation of several families of GHKL proteins (paraMORCs in prokaryotes. Using contextual information from conserved gene neighborhoods we show that these proteins primarily function in restriction-modification systems, in conjunction with diverse superfamily II DNA helicases and endonucleases. The common ancestor of these GHKL proteins, MutL and topoisomerase ATPase modules appears to have catalyzed structural reorganization of protein complexes and concomitant DNA-superstructure manipulations along with fused or standalone nuclease domains. Furthermore, contextual associations of the prokaryotic MORCs and their relatives suggest that their eukaryotic counterparts are likely to carry out chromatin remodeling by DNA superstructure manipulation in response to epigenetic signals such as histone and DNA methylation. Reviewers This article was reviewed by Arcady Mushegian and Gaspar Jekely.

  7. Restriction-modification system with methyl-inhibited base excision and abasic-site cleavage activities.

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    Fukuyo, Masaki; Nakano, Toshiaki; Zhang, Yingbiao; Furuta, Yoshikazu; Ishikawa, Ken; Watanabe-Matsui, Miki; Yano, Hirokazu; Hamakawa, Takeshi; Ide, Hiroshi; Kobayashi, Ichizo

    2015-03-11

    The restriction-modification systems use epigenetic modification to distinguish between self and nonself DNA. A modification enzyme transfers a methyl group to a base in a specific DNA sequence while its cognate restriction enzyme introduces breaks in DNA lacking this methyl group. So far, all the restriction enzymes hydrolyze phosphodiester bonds linking the monomer units of DNA. We recently reported that a restriction enzyme (R.PabI) of the PabI superfamily with half-pipe fold has DNA glycosylase activity that excises an adenine base in the recognition sequence (5'-GTAC). We now found a second activity in this enzyme: at the resulting apurinic/apyrimidinic (AP) (abasic) site (5'-GT#C, # = AP), its AP lyase activity generates an atypical strand break. Although the lyase activity is weak and lacks sequence specificity, its covalent DNA-R.PabI reaction intermediates can be trapped by NaBH4 reduction. The base excision is not coupled with the strand breakage and yet causes restriction because the restriction enzyme action can impair transformation ability of unmethylated DNA even in the absence of strand breaks in vitro. The base excision of R.PabI is inhibited by methylation of the target adenine base. These findings expand our understanding of genetic and epigenetic processes linking those in prokaryotes and eukaryotes.

  8. Genome-wide analysis of restriction-modification system in unicellular and filamentous cyanobacteria.

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    Zhao, Fangqing; Zhang, Xiaowen; Liang, Chengwei; Wu, Jinyu; Bao, Qiyu; Qin, Song

    2006-02-14

    Cyanobacteria are an ancient group of gram-negative bacteria with strong genome size variation ranging from 1.6 to 9.1 Mb. Here, we first retrieved all the putative restriction-modification (RM) genes in the draft genome of Spirulina and then performed a range of comparative and bioinformatic analyses on RM genes from unicellular and filamentous cyanobacterial genomes. We have identified 6 gene clusters containing putative Type I RMs and 11 putative Type II RMs or the solitary methyltransferases (MTases). RT-PCR analysis reveals that 6 of 18 MTases are not expressed in Spirulina, whereas one hsdM gene, with a mutated cognate hsdS, was detected to be expressed. Our results indicate that the number of RM genes in filamentous cyanobacteria is significantly higher than in unicellular species, and this expansion of RM systems in filamentous cyanobacteria may be related to their wide range of ecological tolerance. Furthermore, a coevolutionary pattern is found between hsdM and hsdR, with a large number of site pairs positively or negatively correlated, indicating the functional importance of these pairing interactions between their tertiary structures. No evidence for positive selection is found for the majority of RMs, e.g., hsdM, hsdS, hsdR, and Type II restriction endonuclease gene families, while a group of MTases exhibit a remarkable signature of adaptive evolution. Sites and genes identified here to have been under positive selection would provide targets for further research on their structural and functional evaluations.

  9. The EcoKI Type I Restriction-Modification System in Escherichia coli Affects but Is Not an Absolute Barrier for Conjugation

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    Roer, Louise; Aarestrup, Frank Møller; Hasman, Henrik

    2015-01-01

    results about restriction-modification systems based on phenotypic studies have been presented as reasons for a barrier to conjugation with and other means of uptake of exogenous DNA. In this study, we show that inactivation of the R.EcoKI restriction enzyme in strain Escherichia coli K-12 strain MG1655...... of the mutant recipient with a disrupted hsdR gene. This leads to the conclusion that EcoKI restriction-modification affects the uptake of DNA by conjugation but is not a major barrier to plasmid transfer....

  10. The HaeIV restriction modification system of Haemophilus aegyptius is encoded by a single polypeptide.

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    Piekarowicz, A; Golaszewska, M; Sunday, A O; Siwińska, M; Stein, D C

    1999-11-12

    The HaeIV restriction endonuclease (ENase) belongs to a distinct class of ENases, characterized by its ability to cleave double-stranded DNA on both sides of its recognition sequence, excising a short DNA fragment that includes the recognition sequence. The gene encoding the HaeIV ENase was cloned from Haemophilus aegyptius into pUC19 using a previously described system that does not need the knowledge that a particular ENase is produced by a bacterial strain. DNA sequence analysis of the insert contained on this plasmid identified a single open reading frame (ORF), with the predicted protein having an apparent molecular mass of approximately 110 kDa. The protein encoded by this ORF was purified to homogeneity from Escherichia coli strain ER1944 carrying the haeIVRM gene on a recombinant plasmid under the control of the inducible ara promoter. The protein possessed both ENase and methyltransferase (MTase) activities. Amino acid sequence analysis was able to identify several conserved motifs found in DNA MTases, located in the middle of the protein. The enzyme recognizes the interrupted palindromic sequence 5' GAPyNNNNNPuTC 3', cleaving double-stranded DNA on both strands upstream and downstream of the recognition sequence, releasing an approximately 33 bp fragment. The ENase possessed an absolute requirement only for Mg(+2). ATP had no influence on ENase or MTase activities. The ENase made the first strand cleavage randomly on either side of the recognition sequence, but the second cleavage occurred more slowly. The MTase activity modified symmetrically located adenine residues on both strands within the recognition sequence yielding N6-methyl adenine. Furthermore, the MTase was active as a dimer.

  11. The AplI restriction-modification system in an edible cyanobacterium, Arthrospira (Spirulina) platensis NIES-39, recognizes the nucleotide sequence 5'-CTGCAG-3'.

    OpenAIRE

    2013-01-01

    The degradation of foreign DNAs by restriction enzymes in an edible cyanobacterium, Arthrospira platensis, is a potential barrier for gene-transfer experiments in this economically valuable organism. We overproduced in Escherichia coli the proteins involved in a putative restriction-modification system of A. platensis NIES-39. The protein produced from the putative type II restriction enzyme gene NIES39_K04640 exhibited an endonuclease activity that cleaved DNA within the sequence 5'-CTGCAG-3...

  12. Restriction/modification polypeptides, polynucleotides, and methods

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    Westpheling, Janet; Chung, DaeHwan; Huddleston, Jennifer; Farkas, Joel A

    2015-02-24

    The present invention relates to the discovery of a novel restriction/modification system in Caldicellulosiruptor bescii. The discovered restriction enzyme is a HaeIII-like restriction enzyme that possesses a thermophilic activity profile. The restriction/modification system also includes a methyltransferase, M.CbeI, that methylates at least one cytosine residue in the CbeI recognition sequence to m.sup.4C. Thus, the invention provides, in various aspects, isolated CbeI or M.CbeI polypeptides, or biologically active fragments thereof; isolated polynucleotides that encode the CbeI or M.CbeI polypeptides or biologically active fragments thereof, including expression vectors that include such polynucleotide sequences; methods of digesting DNA using a CbeI polypeptide; methods of treating a DNA molecule using a M.CbeI polypeptide; and methods of transforming a Caldicellulosiruptor cell.

  13. Identification of restriction-modification systems of Bifidobacterium animalis subsp. lactis CNCM I-2494 by SMRT sequencing and associated methylome analysis.

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    O' Connell Motherway, Mary; Watson, Debbie; Bottacini, Francesca; Clark, Tyson A; Roberts, Richard J; Korlach, Jonas; Garault, Peggy; Chervaux, Christian; van Hylckama Vlieg, Johan E T; Smokvina, Tamara; van Sinderen, Douwe

    2014-01-01

    Bifidobacterium animalis subsp. lactis CNCM I-2494 is a component of a commercialized fermented dairy product for which beneficial effects on health has been studied by clinical and preclinical trials. To date little is known about the molecular mechanisms that could explain the beneficial effects that bifidobacteria impart to the host. Restriction-modification (R-M) systems have been identified as key obstacles in the genetic accessibility of bifidobacteria, and circumventing these is a prerequisite to attaining a fundamental understanding of bifidobacterial attributes, including the genes that are responsible for health-promoting properties of this clinically and industrially important group of bacteria. The complete genome sequence of B. animalis subsp. lactis CNCM I-2494 is predicted to harbour the genetic determinants for two type II R-M systems, designated BanLI and BanLII. In order to investigate the functionality and specificity of these two putative R-M systems in B. animalis subsp. lactis CNCM I-2494, we employed PacBio SMRT sequencing with associated methylome analysis. In addition, the contribution of the identified R-M systems to the genetic accessibility of this strain was assessed.

  14. hsdS, Belonging to the Type I Restriction-Modification System, Contributes to the Streptococcus suis Serotype 2 Survival Ability in Phagocytes

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    Xu, Bin; Zhang, Ping; Li, Weiyi; Liu, Rui; Tang, Jinsheng; Fan, Hongjie

    2017-01-01

    Streptococcus suis serotype 2 (SS2) is an important zoonotic agent in swine and humans. Anti-phagocytosis and survival in phagocytic cells and whole blood is essential for bacteria to be pathogenic. In this study, the host specificity determinant specificity subunit (coded by hsdS) of the Type I Restriction-Modification system and two peptidoglycan-binding proteins (coded by lysM and lysM′, respectively), which were simultaneously found to be subjected to transcript-level influence by hsdS, were identified to facilitate the anti-phagocytosis of SS2 to a microglia cell line BV2. Furthermore, they significantly enhanced its survival in BV2, whole blood, and a peroxidation environment (H2O2) (p < 0.05), yet not in the acidic condition based on statistical analysis of the characteristic differences between gene mutants and wild-type SS2. In contrast, another specificity subunit, coded by hsdS′, that belonged to the same Type I Restriction-Modification system, only significantly reduced the survival ability of SS2 in the acidic condition when in the form of a gene-deleted mutant (p < 0.05), but it did not significantly influence the survival ability in other conditions mentioned above or have enhanced anti-phagocytosis action when compared with wild-type SS2. In addition, the mutation of hsdS significantly enhanced the secretion of nitric oxide and TNF-α by BV2 with SS2 incubation (p < 0.05). The SS2 was tested, and it failed to stimulate BV2 to produce IFN-γ. These results demonstrated that hsdS contributed to bacterial anti-phagocytosis and survival in adverse host environments through positively impacting the transcription of two peptidoglycan-binding protein genes, enhancing resistance to reactive oxygen species, and reducing the secretion of TNF-α and nitric oxide by phagocytes. These findings revealed new mechanisms of SS2 pathogenesis. PMID:28848531

  15. hsdS, Belonging to the Type I Restriction-Modification System, Contributes to the Streptococcus suis Serotype 2 Survival Ability in Phagocytes

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    Bin Xu

    2017-08-01

    Full Text Available Streptococcus suis serotype 2 (SS2 is an important zoonotic agent in swine and humans. Anti-phagocytosis and survival in phagocytic cells and whole blood is essential for bacteria to be pathogenic. In this study, the host specificity determinant specificity subunit (coded by hsdS of the Type I Restriction-Modification system and two peptidoglycan-binding proteins (coded by lysM and lysM′, respectively, which were simultaneously found to be subjected to transcript-level influence by hsdS, were identified to facilitate the anti-phagocytosis of SS2 to a microglia cell line BV2. Furthermore, they significantly enhanced its survival in BV2, whole blood, and a peroxidation environment (H2O2 (p < 0.05, yet not in the acidic condition based on statistical analysis of the characteristic differences between gene mutants and wild-type SS2. In contrast, another specificity subunit, coded by hsdS′, that belonged to the same Type I Restriction-Modification system, only significantly reduced the survival ability of SS2 in the acidic condition when in the form of a gene-deleted mutant (p < 0.05, but it did not significantly influence the survival ability in other conditions mentioned above or have enhanced anti-phagocytosis action when compared with wild-type SS2. In addition, the mutation of hsdS significantly enhanced the secretion of nitric oxide and TNF-α by BV2 with SS2 incubation (p < 0.05. The SS2 was tested, and it failed to stimulate BV2 to produce IFN-γ. These results demonstrated that hsdS contributed to bacterial anti-phagocytosis and survival in adverse host environments through positively impacting the transcription of two peptidoglycan-binding protein genes, enhancing resistance to reactive oxygen species, and reducing the secretion of TNF-α and nitric oxide by phagocytes. These findings revealed new mechanisms of SS2 pathogenesis.

  16. 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

    Listeria monocytogenes is a bacterial pathogen that is found in a wide variety of anthropogenic and natural environments. Genome sequencing technologies are rapidly becoming a powerful tool in facilitating our understanding of how genotype, classification phenotypes, and virulence phenotypes interact to predict the health risks of individual bacterial isolates. Currently, 57 closed L. monocytogenes genomes are publicly available, representing three of the four phylogenetic lineages, and they suggest that L. monocytogenes has high genomic synteny. This study contributes an additional 15 closed L. monocytogenes genomes that were used to determine the associations between the genome and methylome with host invasion magnitude. In contrast to previous findings, large chromosomal inversions and rearrangements were detected in five isolates at the chromosome terminus and within rRNA genes, including a previously undescribed inversion within rRNA-encoding regions. Each isolate's epigenome contained highly diverse methyltransferase recognition sites, even within the same serotype and methylation pattern. Eleven strains contained a single chromosomally encoded methyltransferase, one strain contained two methylation systems (one system on a plasmid), and three strains exhibited no methylation, despite the occurrence of methyltransferase genes. In three isolates a new, unknown DNA modification was observed in addition to diverse methylation patterns, accompanied by a novel methylation system. Neither chromosome rearrangement nor strain-specific patterns of epigenome modification observed within virulence genes were correlated with serotype designation, clonal complex, or in vitro infectivity. These data suggest that genome diversity is larger than previously considered in L. monocytogenes and that as more genomes are sequenced, additional structure and methylation novelty will be observed in this organism.

  17. Gene Loss and Lineage-Specific Restriction-Modification Systems Associated with Niche Differentiation in the Campylobacter jejuni Sequence Type 403 Clonal Complex.

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    Morley, Laura; McNally, Alan; Paszkiewicz, Konrad; Corander, Jukka; Méric, Guillaume; Sheppard, Samuel K; Blom, Jochen; Manning, Georgina

    2015-06-01

    Campylobacter jejuni is a highly diverse species of bacteria commonly associated with infectious intestinal disease of humans and zoonotic carriage in poultry, cattle, pigs, and other animals. The species contains a large number of distinct clonal complexes that vary from host generalist lineages commonly found in poultry, livestock, and human disease cases to host-adapted specialized lineages primarily associated with livestock or poultry. Here, we present novel data on the ST403 clonal complex of C. jejuni, a lineage that has not been reported in avian hosts. Our data show that the lineage exhibits a distinctive pattern of intralineage recombination that is accompanied by the presence of lineage-specific restriction-modification systems. Furthermore, we show that the ST403 complex has undergone gene decay at a number of loci. Our data provide a putative link between the lack of association with avian hosts of C. jejuni ST403 and both gene gain and gene loss through nonsense mutations in coding sequences of genes, resulting in pseudogene formation.

  18. The AplI restriction-modification system in an edible cyanobacterium, Arthrospira (Spirulina) platensis NIES-39, recognizes the nucleotide sequence 5'-CTGCAG-3'.

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    Shiraishi, Hideaki; Tabuse, Yosuke

    2013-01-01

    The degradation of foreign DNAs by restriction enzymes in an edible cyanobacterium, Arthrospira platensis, is a potential barrier for gene-transfer experiments in this economically valuable organism. We overproduced in Escherichia coli the proteins involved in a putative restriction-modification system of A. platensis NIES-39. The protein produced from the putative type II restriction enzyme gene NIES39_K04640 exhibited an endonuclease activity that cleaved DNA within the sequence 5'-CTGCAG-3' between the A at the fifth position and the G at the sixth position. We designated this enzyme AplI. The protein from the adjacent gene NIES39_K04650, which encodes a putative DNA (cytosine-5-)-methyltransferase, rendered DNA molecules resistant to AplI by modifying the C at the fourth position (but not the C at the first position) in the recognition sequence. This modification enzyme, M.AplI, should be useful for converting DNA molecules into AplI-resistant forms for use in gene-transfer experiments. A summary of restriction enzymes in various Arthrospira strains is also presented in this paper.

  19. The LspC3-41I restriction-modification system is the major determinant for genetic manipulations of Lysinibacillus sphaericus C3-41.

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    Fu, Pan; Ge, Yong; Wu, Yiming; Zhao, Ni; Yuan, Zhiming; Hu, Xiaomin

    2017-05-19

    Lysinibacillus sphaericus has been widely used in integrated mosquito control program and it is one of the minority bacterial species unable to metabolize carbohydrates. In consideration of the high genetic conservation at genomic level and difficulty of genetic horizontal transfer, it is hypothesized that effective restriction-modification (R-M) systems existed in mosquitocidal L. sphaericus. In this study, six type II R-M systems including LspC3-41I were predicted in L. sphaericus C3-41 genome. It was found that the cell free extracts (CFE) from this strain shown similar restriction and methylation activity on exogenous Bacillus/Escherichia coli shuttle vector pBU4 as the HaeIII, which is an isoschizomer of BspRI. The Bsph_0498 (encoding the predicted LspC3-41IR) knockout mutant Δ0498 and the complement strain RC0498 were constructed. It was found that the unmethylated pBU4 can be digested by the CFE of C3-41 and RC0498, but not by that of Δ0498. Furthermore, the exogenous plasmid pBU4 can be transformed at very high efficacy into Δ0498, low efficacy into RC0498, but no transformation into C3-41, indicating that LspC3-41I might be a major determinant for the genetic restriction barrier of strain C3-41. Besides, lspC3-41IR and lspC3-41IM genes are detected in other two strains besides C3-41 of the tested 16 L. sphaericus strains, which all belonging to serotype H5 and MLST sequence type (ST) 1. Furthermore, the three strains are not horizontal transferred, and this restriction could be overcome by in vitro methylation either by the host CFE or by commercial methytransferase M. HaeIII. The results provide an insight to further study the genetic restriction, modification and evolution of mosquitocidal L. sphaericus, also a theoretical basis and a method for the genetic manipulations of L. sphaericus. LspC3-41I is identified as the major determinant for the restriction barrier of L. sphaericus C3-41. Only three strains of the tested 16 L. sphaericus strains

  20. Plasmid pP62BP1 isolated from an Arctic Psychrobacter sp. strain carries two highly homologous type II restriction-modification systems and a putative organic sulfate metabolism operon.

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    Lasek, Robert; Dziewit, Lukasz; Bartosik, Dariusz

    2012-05-01

    The complete nucleotide sequence of plasmid pP62BP1 (34,467 bp), isolated from Arctic Psychrobacter sp. DAB_AL62B, was determined and annotated. The conserved plasmid backbone is composed of several genetic modules, including a replication system (REP) with similarities to the REP region of the iteron-containing plasmid pPS10 of Pseudomonas syringae. The additional genetic load of pP62BP1 includes two highly related type II restriction-modification systems and a set of genes (slfRCHSL) encoding enzymes engaged in the metabolism of organic sulfates, plus a putative transcriptional regulator (SlfR) of the AraC family. The pP62BP1 slf locus has a compact and unique structure. It is predicted that the enzymes SlfC, SlfH, SlfS and SlfL carry out a chain of reactions leading to the transformation of alkyl sulfates into acyl-CoA, with dodecyl sulfate (SDS) as a possible starting substrate. Comparative analysis of the nucleotide sequences of pP62BP1 and other Psychrobacter spp. plasmids revealed their structural diversity. However, the presence of a few highly conserved DNA segments in pP62BP1, plasmid 1 of P. cryohalolentis K5 and pRWF-101 of Psychrobacter sp. PRwf-1 is indicative of recombinational shuffling of genetic information, and is evidence of lateral gene transfer in the Arctic environment.

  1. PsasM2I, a type II restriction-modification system in Pseudomonas savastanoi pv. savastanoi: differential distribution of carrier strains in the environment and the evolutionary history of homologous RM systems in the Pseudomonas syringae complex.

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    Cinelli, Tamara; Moscetti, Ilaria; Marchi, Guido

    2014-11-01

    A type II restriction-modification system was found in a native plasmid of Pseudomonas savastanoi pv. savastanoi MLLI2. Functional analysis of the methyltransferase showed that the enzyme acts by protecting the DNA sequence CTGCAG from cleavage. Restriction endonuclease expression in recombinant Escherichia coli cells resulted in mutations in the REase sequence or transposition of insertion sequence 1A in the coding sequence, preventing lethal gene expression. Population screening detected homologous RM systems in other P. savastanoi strains and in the Pseudomonas syringae complex. An epidemiological survey carried out by sampling olive and oleander knots in two Italian regions showed an uneven diffusion of carrier strains, whose presence could be related to a selective advantage in maintaining the RM system in particular environments or subpopulations. Moreover, carrier strains can coexist in the same orchards, plants, and knot tissues with non-carriers, revealing unexpected genetic variability on a very small spatial scale. Phylogenetic analysis of the RM system and housekeeping gene sequences in the P. syringae complex demonstrated the ancient acquisition of the RM systems. However, the evolutionary history of the gene complex also showed the involvement of horizontal gene transfer between related strains and recombination events.

  2. [Antirestriction proteins ardA and Ocr as effective inhibitors of the type I restriction-modification enzymes].

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    Zavil'gel'skiĭ, G B; Rastorguev, S M

    2009-01-01

    Genes encoding antirestriction proteins (antirestrictases, inasmuch as the antirestriction proteins inhibit the activity of restriction-modification systems, but have no proper enzyme activity, the name antirestrictase is only tentative) are included in the composition of conjugative plasmids (genes ardABC) and some bacteriophages (genes ocr and darA). Antirestriction proteins inhibit of the type I restriction-modification enzymes and thus protect unmodified DNA of plasmids and bacteriophages from degradation. Antirestriction proteins belong to the "protein mimicry of DNA" family: the spatial structure is like the B-form of DNA, and therefore the antirestriction proteins operated on the principle of concurrent inhibition replacing DNA in the complex with the restriction-modification enzyme. Based on the prepared in vitro mutant forms of ArdA and Ocr, and also on natural proteins ArdA selectively inhibiting restriction activity of the type I enzymes, but not affecting their methylase activity, we have developed a model of complex formation between the antirestriction proteins and the restriction-modification enzymes R2M2S. Antirestriction proteins are capable of competing displacement of the DNA strand from two sites which are situated as follows: 1) in S-subunit (enzyme contact with the specific DNA site) and 2) in R-subunit (through this unit translocation of the DNA strand occurs followed by its degradation). Analysis of estriction and antimodification activities of proteins ArdA and Ocr depending on the expression level of genes ardA and ocr was performed (the cloning of the genes was done under strictly regulated promoter).

  3. Type III restriction-modification enzymes: a historical perspective.

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    Rao, Desirazu N; Dryden, David T F; Bheemanaik, Shivakumara

    2014-01-01

    Restriction endonucleases interact with DNA at specific sites leading to cleavage of DNA. Bacterial DNA is protected from restriction endonuclease cleavage by modifying the DNA using a DNA methyltransferase. Based on their molecular structure, sequence recognition, cleavage position and cofactor requirements, restriction-modification (R-M) systems are classified into four groups. Type III R-M enzymes need to interact with two separate unmethylated DNA sequences in inversely repeated head-to-head orientations for efficient cleavage to occur at a defined location (25-27 bp downstream of one of the recognition sites). Like the Type I R-M enzymes, Type III R-M enzymes possess a sequence-specific ATPase activity for DNA cleavage. ATP hydrolysis is required for the long-distance communication between the sites before cleavage. Different models, based on 1D diffusion and/or 3D-DNA looping, exist to explain how the long-distance interaction between the two recognition sites takes place. Type III R-M systems are found in most sequenced bacteria. Genome sequencing of many pathogenic bacteria also shows the presence of a number of phase-variable Type III R-M systems, which play a role in virulence. A growing number of these enzymes are being subjected to biochemical and genetic studies, which, when combined with ongoing structural analyses, promise to provide details for mechanisms of DNA recognition and catalysis.

  4. Cloning and expression of the HpaI restriction-modification genes.

    OpenAIRE

    Ito, H; Shimato, H; Sadaoka, A; Kotani, H; Kimizuka, F; Kato, I

    1992-01-01

    The genes from Haemophilus parainfluenzae encoding the HpaI restriction-modification system were cloned and expressed in Escherichia coli. From the DNA sequence, we predicted the HpaI endonuclease (R.HpaI) to have 254 amino acid residues (Mr 29,630) and the HpaI methyltransferase (M.HpaI) to have 314 amino acid residues (37,390). The R.HpaI and M.HpaI genes overlapped by 16 base pairs on the chromosomal DNA. The genes had the same orientation. The clone, named E. coli HB101-HPA2, overproduced...

  5. 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.

    2017-02-14

    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.

  6. The other face of restriction: modification-dependent enzymes.

    Science.gov (United States)

    Loenen, Wil A M; Raleigh, Elisabeth A

    2014-01-01

    The 1952 observation of host-induced non-hereditary variation in bacteriophages by Salvador Luria and Mary Human led to the discovery in the 1960s of modifying enzymes that glucosylate hydroxymethylcytosine in T-even phages and of genes encoding corresponding host activities that restrict non-glucosylated phage DNA: rglA and rglB (restricts glucoseless phage). In the 1980's, appreciation of the biological scope of these activities was dramatically expanded with the demonstration that plant and animal DNA was also sensitive to restriction in cloning experiments. The rgl genes were renamed mcrA and mcrBC (modified cytosine restriction). The new class of modification-dependent restriction enzymes was named Type IV, as distinct from the familiar modification-blocked Types I-III. A third Escherichia coli enzyme, mrr (modified DNA rejection and restriction) recognizes both methylcytosine and methyladenine. In recent years, the universe of modification-dependent enzymes has expanded greatly. Technical advances allow use of Type IV enzymes to study epigenetic mechanisms in mammals and plants. Type IV enzymes recognize modified DNA with low sequence selectivity and have emerged many times independently during evolution. Here, we review biochemical and structural data on these proteins, the resurgent interest in Type IV enzymes as tools for epigenetic research and the evolutionary pressures on these systems.

  7. DNA cleavage and methylation specificity of the single polypeptide restriction-modification enzyme LlaGI.

    Science.gov (United States)

    Smith, Rachel M; Diffin, Fiona M; Savery, Nigel J; Josephsen, Jytte; Szczelkun, Mark D

    2009-11-01

    LlaGI is a single polypeptide restriction-modification enzyme encoded on the naturally-occurring plasmid pEW104 isolated from Lactococcus lactis ssp. cremoris W10. Bioinformatics analysis suggests that the enzyme contains domains characteristic of an mrr endonuclease, a superfamily 2 DNA helicase and a gamma-family adenine methyltransferase. LlaGI was expressed and purified from a recombinant clone and its properties characterised. An asymmetric recognition sequence was identified, 5'-CTnGAyG-3' (where n is A, G, C or T and y is C or T). Methylation of the recognition site occurred on only one strand (the non-degenerate dA residue of 5'-CrTCnAG-3' being methylated at the N6 position). Double strand DNA breaks at distant, random sites were only observed when two head-to-head oriented, unmethylated copies of the site were present; single sites or pairs in tail-to-tail or head-to-tail repeat only supported a DNA nicking activity. dsDNA nuclease activity was dependent upon the presence of ATP or dATP. Our results are consistent with a directional long-range communication mechanism that is necessitated by the partial site methylation. In the accompanying manuscript [Smith et al. (2009) The single polypeptide restriction-modification enzyme LlaGI is a self-contained molecular motor that translocates DNA loops], we demonstrate that this communication is via 1-dimensional DNA loop translocation. On the basis of this data and that in the third accompanying manuscript [Smith et al. (2009) An Mrr-family nuclease motif in the single polypeptide restriction-modification enzyme LlaGI], we propose that LlaGI is the prototype of a new sub-classification of Restriction-Modification enzymes, named Type I SP (for Single Polypeptide).

  8. Analysis of the Campylobacter jejuni genome by SMRT DNA sequencing identifies restriction-modification motifs.

    Directory of Open Access Journals (Sweden)

    Jason L O'Loughlin

    Full Text Available Campylobacter jejuni is a leading bacterial cause of human gastroenteritis. The goal of this study was to analyze the C. jejuni F38011 strain, recovered from an individual with severe enteritis, at a genomic and proteomic level to gain insight into microbial processes. The C. jejuni F38011 genome is comprised of 1,691,939 bp, with a mol.% (G+C content of 30.5%. PacBio sequencing coupled with REBASE analysis was used to predict C. jejuni F38011 genomic sites and enzymes that may be involved in DNA restriction-modification. A total of five putative methylation motifs were identified as well as the C. jejuni enzymes that could be responsible for the modifications. Peptides corresponding to the deduced amino acid sequence of the C. jejuni enzymes were identified using proteomics. This work sets the stage for studies to dissect the precise functions of the C. jejuni putative restriction-modification enzymes. Taken together, the data generated in this study contributes to our knowledge of the genomic content, methylation profile, and encoding capacity of C. jejuni.

  9. Recycling of protein subunits during DNA translocation and cleavage by Type I restriction-modification enzymes.

    Science.gov (United States)

    Simons, Michelle; Szczelkun, Mark D

    2011-09-01

    The Type I restriction-modification enzymes comprise three protein subunits; HsdS and HsdM that form a methyltransferase (MTase) and HsdR that associates with the MTase and catalyses Adenosine-5'-triphosphate (ATP)-dependent DNA translocation and cleavage. Here, we examine whether the MTase and HsdR components can 'turnover' in vitro, i.e. whether they can catalyse translocation and cleavage events on one DNA molecule, dissociate and then re-bind a second DNA molecule. Translocation termination by both EcoKI and EcoR124I leads to HsdR dissociation from linear DNA but not from circular DNA. Following DNA cleavage, the HsdR subunits appear unable to dissociate even though the DNA is linear, suggesting a tight interaction with the cleaved product. The MTases of EcoKI and EcoAI can dissociate from DNA following either translocation or cleavage and can initiate reactions on new DNA molecules as long as free HsdR molecules are available. In contrast, the MTase of EcoR124I does not turnover and additional cleavage of circular DNA is not observed by inclusion of RecBCD, a helicase-nuclease that degrades the linear DNA product resulting from Type I cleavage. Roles for Type I restriction endonuclease subunit dynamics in restriction alleviation in the cell are discussed.

  10. Structural insights into DNA sequence recognition by Type ISP restriction-modification enzymes.

    Science.gov (United States)

    Kulkarni, Manasi; Nirwan, Neha; van Aelst, Kara; Szczelkun, Mark D; Saikrishnan, Kayarat

    2016-05-19

    Engineering restriction enzymes with new sequence specificity has been an unaccomplished challenge, presumably because of the complexity of target recognition. Here we report detailed analyses of target recognition by Type ISP restriction-modification enzymes. We determined the structure of the Type ISP enzyme LlaGI bound to its target and compared it with the previously reported structure of a close homologue that binds to a distinct target, LlaBIII. The comparison revealed that, although the two enzymes use almost a similar set of structural elements for target recognition, the residues that read the bases vary. Change in specificity resulted not only from appropriate substitution of amino acids that contacted the bases but also from new contacts made by positionally distinct residues directly or through a water bridge. Sequence analyses of 552 Type ISP enzymes showed that the structural elements involved in target recognition of LlaGI and LlaBIII were structurally well-conserved but sequentially less-conserved. In addition, the residue positions within these structural elements were under strong evolutionary constraint, highlighting the functional importance of these regions. The comparative study helped decipher a partial consensus code for target recognition by Type ISP enzymes.

  11. Translocation-coupled DNA cleavage by the Type ISP restriction-modification enzymes.

    Science.gov (United States)

    Chand, Mahesh K; Nirwan, Neha; Diffin, Fiona M; van Aelst, Kara; Kulkarni, Manasi; Pernstich, Christian; Szczelkun, Mark D; Saikrishnan, Kayarat

    2015-11-01

    Production of endonucleolytic double-strand DNA breaks requires separate strand cleavage events. Although catalytic mechanisms for simple, dimeric endonucleases are known, there are many complex nuclease machines that are poorly understood. Here we studied the single polypeptide Type ISP restriction-modification (RM) enzymes, which cleave random DNA between distant target sites when two enzymes collide after convergent ATP-driven translocation. We report the 2.7-Å resolution X-ray crystal structure of a Type ISP enzyme-DNA complex, revealing that both the helicase-like ATPase and nuclease are located upstream of the direction of translocation, an observation inconsistent with simple nuclease-domain dimerization. Using single-molecule and biochemical techniques, we demonstrate that each ATPase remodels its DNA-protein complex and translocates along DNA without looping it, leading to a collision complex in which the nuclease domains are distal. Sequencing of the products of single cleavage events suggests a previously undescribed endonuclease model, where multiple, stochastic strand-nicking events combine to produce DNA scission.

  12. Individual- and Population-based Diversity in Restriction-modification Systems

    NARCIS (Netherlands)

    Pagie, L.; Hogeweg, P.

    2002-01-01

    In the grass genus Poa a wide variation in final leaf size and leaf growth rate exists. In this thesis leaf growth was analyzed at different levels. At the cellular level, inherent variation in leaf elongation rate and final leaf size was correlated to the length of the elongation zone and to merist

  13. 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

    2013-10-29

    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.

  14. 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

    2015-05-12

    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.

  15. DNA cleavage by Type ISP Restriction-Modification enzymes is initially targeted to the 3'-5' strand.

    Science.gov (United States)

    van Aelst, Kara; Šišáková, Eva; Szczelkun, Mark D

    2013-01-01

    The mechanism by which a double-stranded DNA break is produced following collision of two translocating Type I Restriction-Modification enzymes is not fully understood. Here, we demonstrate that the related Type ISP Restriction-Modification enzymes LlaGI and LlaBIII can cooperate to cleave DNA following convergent translocation and collision. When one of these enzymes is a mutant protein that lacks endonuclease activity, DNA cleavage of the 3'-5' strand relative to the wild-type enzyme still occurs, with the same kinetics and at the same collision loci as for a reaction between two wild-type enzymes. The DNA nicking activity of the wild-type enzyme is still activated by a protein variant entirely lacking the Mrr nuclease domain and by a helicase mutant that cannot translocate. However, the helicase mutant cannot cleave the DNA despite the presence of an intact nuclease domain. Cleavage by the wild-type enzyme is not activated by unrelated protein roadblocks. We suggest that the nuclease activity of the Type ISP enzymes is activated following collision with another Type ISP enzyme and requires adenosine triphosphate binding/hydrolysis but, surprisingly, does not require interaction between the nuclease domains. Following the initial rapid endonuclease activity, additional DNA cleavage events then occur more slowly, leading to further processing of the initial double-stranded DNA break.

  16. An Mrr-family nuclease motif in the single polypeptide restriction-modification enzyme LlaGI.

    Science.gov (United States)

    Smith, Rachel M; Josephsen, Jytte; Szczelkun, Mark D

    2009-11-01

    Bioinformatic analysis of the putative nuclease domain of the single polypeptide restriction-modification enzyme LlaGI reveals amino acid motifs characteristic of the Escherichia coli methylated DNA-specific Mrr endonuclease. Using mutagenesis, we examined the role of the conserved residues in both DNA translocation and cleavage. Mutations in those residues predicted to play a role in DNA hydrolysis produced enzymes that could translocate on DNA but were either unable to cleave the polynucleotide track or had reduced nuclease activity. Cleavage by LlaGI is not targeted to methylated DNA, suggesting that the conserved motifs in the Mrr domain are a conventional sub-family of the PD-(D/E)XK superfamily of DNA nucleases.

  17. Functional analysis of MmeI from methanol utilizer Methylophilus methylotrophus, a subtype IIC restriction-modification enzyme related to type I enzymes.

    Science.gov (United States)

    Nakonieczna, Joanna; Kaczorowski, Tadeusz; Obarska-Kosinska, Agnieszka; Bujnicki, Janusz M

    2009-01-01

    MmeI from Methylophilus methylotrophus belongs to the type II restriction-modification enzymes. It recognizes an asymmetric DNA sequence, 5'-TCCRAC-3' (R indicates G or A), and cuts both strands at fixed positions downstream of the specific site. This particular feature has been exploited in transcript profiling of complex genomes (using serial analysis of gene expression technology). We have shown previously that the endonucleolytic activity of MmeI is strongly dependent on the presence of S-adenosyl-l-methionine (J. Nakonieczna, J. W. Zmijewski, B. Banecki, and A. J. Podhajska, Mol. Biotechnol. 37:127-135, 2007), which puts MmeI in subtype IIG. The same cofactor is used by MmeI as a methyl group donor for modification of an adenine in the upper strand of the recognition site to N(6)-methyladenine. Both enzymatic activities reside in a single polypeptide (919 amino acids [aa]), which puts MmeI also in subtype IIC of the restriction-modification systems. Based on a molecular model, generated with the use of bioinformatic tools and validated by site-directed mutagenesis, we were able to localize three functional domains in the structure of the MmeI enzyme: (i) the N-terminal portion containing the endonucleolytic domain with the catalytic Mg2+-binding motif D(70)-X(9)-EXK(82), characteristic for the PD-(D/E)XK superfamily of nucleases; (ii) a central portion (aa 310 to 610) containing nine sequence motifs conserved among N(6)-adenine gamma-class DNA methyltransferases; (iii) the C-terminal portion (aa 610 to 919) containing a putative target recognition domain. Interestingly, all three domains showed highest similarity to the corresponding elements of type I enzymes rather than to classical type II enzymes. We have found that MmeI variants deficient in restriction activity (D70A, E80A, and K82A) can bind and methylate specific nucleotide sequence. This suggests that domains of MmeI responsible for DNA restriction and modification can act independently. Moreover, we

  18. Cloning and analysis of the four genes coding for Bpu10I restriction-modification enzymes.

    OpenAIRE

    Stankevicius, K; Lubys, A; Timinskas, A; Vaitkevicius, D; Janulaitis, A

    1998-01-01

    The Bpu 10I R-M system from Bacillus pumilus 10, which recognizes the asymmetric 5'-CCTNAGC sequence, has been cloned, sequenced and expressed in Escherichia coli . The system comprises four adjacent, similarly oriented genes encoding two m5C MTases and two subunits of Bpu 10I ENase (34.5 and 34 kDa). Both bpu10IR genes either in cis or trans are needed for the manifestation of R. Bpu 10I activity. Subunits of R. Bpu 10I, purified to apparent homogeneity, are both required for cleavage activi...

  19. Cloning and analysis of the four genes coding for Bpu10I restriction-modification enzymes.

    Science.gov (United States)

    Stankevicius, K; Lubys, A; Timinskas, A; Vaitkevicius, D; Janulaitis, A

    1998-02-15

    The Bpu 10I R-M system from Bacillus pumilus 10, which recognizes the asymmetric 5'-CCTNAGC sequence, has been cloned, sequenced and expressed in Escherichia coli . The system comprises four adjacent, similarly oriented genes encoding two m5C MTases and two subunits of Bpu 10I ENase (34.5 and 34 kDa). Both bpu10IR genes either in cis or trans are needed for the manifestation of R. Bpu 10I activity. Subunits of R. Bpu 10I, purified to apparent homogeneity, are both required for cleavage activity. This heterosubunit structure distinguishes the Bpu 10I restriction endonuclease from all other type II restriction enzymes described previously. The subunits reveal 25% amino acid identity. Significant similarity was also identified between a 43 amino acid region of R. Dde I and one of the regions of higher identity shared between the Bpu 10I subunits, a region that could possibly include the catalytic/Mg2+binding center. The similarity between Bpu 10I and Dde I MTases is not limited to the conserved motifs (CM) typical for m5C MTases. It extends into the variable region that lies between CMs VIII and IX. Duplication of a progenitor gene, encoding an enzyme recognizing a symmetric nucleotide sequence, followed by concerted divergent evolution, may provide a possible scenario leading to the emergence of the Bpu 10I ENase, which recognizes an overall asymmetric sequence and cleaves within it symmetrically.

  20. Dissociation from DNA of Type III Restriction-Modification enzymes during helicase-dependent motion and following endonuclease activity.

    Science.gov (United States)

    Tóth, Júlia; van Aelst, Kara; Salmons, Hannah; Szczelkun, Mark D

    2012-08-01

    DNA cleavage by the Type III Restriction-Modification (RM) enzymes requires the binding of a pair of RM enzymes at two distant, inversely orientated recognition sequences followed by helicase-catalysed ATP hydrolysis and long-range communication. Here we addressed the dissociation from DNA of these enzymes at two stages: during long-range communication and following DNA cleavage. First, we demonstrated that a communicating species can be trapped in a DNA domain without a recognition site, with a non-specific DNA association lifetime of ∼ 200 s. If free DNA ends were present the lifetime became too short to measure, confirming that ends accelerate dissociation. Secondly, we observed that Type III RM enzymes can dissociate upon DNA cleavage and go on to cleave further DNA molecules (they can 'turnover', albeit inefficiently). The relationship between the observed cleavage rate and enzyme concentration indicated independent binding of each site and a requirement for simultaneous interaction of at least two enzymes per DNA to achieve cleavage. In light of various mechanisms for helicase-driven motion on DNA, we suggest these results are most consistent with a thermally driven random 1D search model (i.e. 'DNA sliding').

  1. Magnetostrictive Pressure Regulating System

    Science.gov (United States)

    Richard, James A. (Inventor); Pickens, Herman L. (Inventor)

    2013-01-01

    A magnetostrictive pressure regulating system includes a magnetostrictive valve that incorporates a magnetostrictive actuator with at least one current-carrying coil disposed thereabout. A pressure force sensor, in fluid communication with the fluid exiting the valve, includes (i) a magnetostrictive material, (ii) a magnetic field generator in proximity to the magnetostrictive material for inducing a magnetic field in and surrounding the magnetostrictive material wherein lines of magnetic flux passing through the magnetostrictive material are defined, and (iii) a sensor positioned adjacent to the magnetostrictive material and in the magnetic field for measuring changes in at least one of flux angle and flux density when the magnetostrictive material experiences an applied force that is aligned with the lines of magnetic flux. The pressure of the fluid exiting the valve causes the applied force. A controller coupled to the sensor and to the current-carrying coil adjusts a current supplied to the current-carrying coil based on the changes so-measured.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. 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.

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

    OpenAIRE

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

    2012-01-01

    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....

  5. Voltage Regulators for Photovoltaic Systems

    Science.gov (United States)

    Delombard, R.

    1986-01-01

    Two simple circuits developed to provide voltage regulation for highvoltage (i.e., is greater than 75 volts) and low-voltage (i.e., is less than 36 volts) photovoltaic/battery power systems. Use of these circuits results in voltage regulator small, low-cost, and reliable, with very low power dissipation. Simple oscillator circuit controls photovoltaic-array current to regulate system voltage and control battery charging. Circuit senses battery (and system) voltage and adjusts array current to keep battery voltage from exceeding maximum voltage.

  6. 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.

  7. Positively regulated bacterial expression systems.

    Science.gov (United States)

    Brautaset, Trygve; Lale, Rahmi; Valla, Svein

    2009-01-01

    Regulated promoters are useful tools for many aspects related to recombinant gene expression in bacteria, including for high-level expression of heterologous proteins and for expression at physiological levels in metabolic engineering applications. In general, it is common to express the genes of interest from an inducible promoter controlled either by a positive regulator or by a repressor protein. In this review, we discuss established and potentially useful positively regulated bacterial promoter systems, with a particular emphasis on those that are controlled by the AraC-XylS family of transcriptional activators. The systems function in a wide range of microorganisms, including enterobacteria, soil bacteria, lactic bacteria and streptomycetes. The available systems that have been applied to express heterologous genes are regulated either by sugars (L-arabinose, L-rhamnose, xylose and sucrose), substituted benzenes, cyclohexanone-related compounds, ε-caprolactam, propionate, thiostrepton, alkanes or peptides. It is of applied interest that some of the inducers require the presence of transport systems, some are more prone than others to become metabolized by the host and some have been applied mainly in one or a limited number of species. Based on bioinformatics analyses, the AraC-XylS family of regulators contains a large number of different members (currently over 300), but only a small fraction of these, the XylS/Pm, AraC/P(BAD), RhaR-RhaS/rhaBAD, NitR/PnitA and ChnR/Pb regulator/promoter systems, have so far been explored for biotechnological applications.

  8. Output Regulation of the Arneodo Chaotic System

    OpenAIRE

    Sundarapandian Vaidyanathan

    2010-01-01

    This paper solves the problem of regulating the output of the Arneodo chaotic system (1981), which is one of the paradigms of chaotic dynamical systems. Explicitly, using the state feedback control laws, the output of the Arneodo chaotic system is regulated so as to track constant reference signals as well as to track periodic reference signals. The control laws are derived using the regulator equations of Byrnes and Isidori (1990), which provide the solution of the output regulation problem ...

  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. 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

    2015-12-02

    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.

  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. Output Regulation of the Arneodo Chaotic System

    Directory of Open Access Journals (Sweden)

    Sundarapandian Vaidyanathan

    2010-08-01

    Full Text Available This paper solves the problem of regulating the output of the Arneodo chaotic system (1981, which is one of the paradigms of chaotic dynamical systems. Explicitly, using the state feedback control laws, the output of the Arneodo chaotic system is regulated so as to track constant reference signals as well as to track periodic reference signals. The control laws are derived using the regulator equations of Byrnes and Isidori (1990, which provide the solution of the output regulation problem for nonlinear control systems involving neutrally stable exosystem dynamics. Numerical results are shown to verify the results.

  13. Institutions and Regulations in Innovation Systems

    DEFF Research Database (Denmark)

    Borrás, Susana; Edquist, Charles

    Institutions (including regulations) are constitutive elements of innovation systems, and therefore cornerstones of innovation policy. Focusing on (soft and hard) regulation, the paper identifies the most salient regulatory areas from the perspective of the innovation system. When asking about th...... and re-design of innovation policy, so that policy makers may analyse empirically the social dynamics actually generated by regulation rather than simply assuming deductively their effects....... the effects of regulation on innovation, the paper argues that there are three key issues that need careful empirical analysis; namely, whether regulation is effective and efficient in terms of reducing uncertainty and generating incentives, whether it is able to generate ultimately wider social benefits...... for the innovativeness of the society at large; and the extent to which regulation is adapting to new (social, economic and technological) contexts and is socially legitimate and accepted. These are potentially the three problems that innovation policy needs to address in this area. This provides guidance for the design...

  14. 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

  15. Towards Systems Biology of Mycotoxin Regulation

    OpenAIRE

    Christof Rampitsch; Rajagopal Subramaniam

    2013-01-01

    Systems biology is a scientific approach that integrates many scientific disciplines to develop a comprehensive understanding of biological phenomena, thus allowing the prediction and accurate simulation of complex biological behaviors. It may be presumptuous to write about toxin regulation at the level of systems biology, but the last decade of research is leading us closer than ever to this approach. Past research has delineated multiple levels of regulation in the pathways leading to the b...

  16. APPROXIMATE OUTPUT REGULATION FOR AFFINE NONLINEAR SYSTEMS

    Institute of Scientific and Technical Information of China (English)

    Yali DONG; Daizhan CHENG; Huashu QIN

    2003-01-01

    Output regulation for affine nonlinear systems driven by an exogenous signal is investigated in this paper. In the absence of the standard exosystem hypothesis, we assume availability of the instantaneous values of the exogenous signal and its first time-derivative for use in the control law.For affine nonlinear systems, the necessary and sufficient conditions of the solvability of approximate output regulation problem are obtained. The precise form of the control law is presented under some suitable assumptions.

  17. Systemic crisis and financial regulation

    OpenAIRE

    ULGEN, Faruk

    2010-01-01

    One of the privileged explanations of the current crisis is the sophistication and the weak transparency of financial markets which would have allowed speculative behavior to elude authorities’ supervision. This article develops a different view by putting the emphasis on the model of organization of financial systems. This is established on the predominance of micro-prudential supervision schemes following the hypothesis of free market efficiency. From 1980-90, prudential mechanisms have wor...

  18. System biology of gene regulation.

    Science.gov (United States)

    Baitaluk, Michael

    2009-01-01

    ) questions of biological relevance. Thus systems biology could be treated as such a socioscientific phenomenon and a new approach to both experiments and theory that is defined by the strategy of pursuing integration of complex data about the interactions in biological systems from diverse experimental sources using interdisciplinary tools and personnel.

  19. On output regulation for linear systems

    NARCIS (Netherlands)

    Saberi, Ali; Stoorvogel, Anton A.; Sannuti, Peddapullaiah

    2001-01-01

    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 wheneve

  20. Evolution of DNA Double-Strand Break Repair by Gene Conversion: Coevolution Between a Phage and a Restriction-Modification System

    Science.gov (United States)

    Yahara, Koji; Horie, Ryota; Kobayashi, Ichizo; Sasaki, Akira

    2007-01-01

    The necessity to repair genome damage has been considered to be an immediate factor responsible for the origin of sex. Indeed, attack by a cellular restriction enzyme of invading DNA from several bacteriophages initiates recombinational repair by gene conversion if there is homologous DNA. In this work, we modeled the interaction between a bacteriophage and a bacterium carrying a restriction enzyme as antagonistic coevolution. We assume a locus on the bacteriophage genome has either a restriction-sensitive or a restriction-resistant allele, and another locus determines whether it is recombination/repair proficient or defective. A restriction break can be repaired by a co-infecting phage genome if one of them is recombination/repair proficient. We define the fitness of phage (resistant/sensitive and repair-positive/-negative) genotypes and bacterial (restriction-positive/-negative) genotypes by assuming random encounter of the genotypes, with given probabilities of single and double infections, and the costs of resistance, repair, and restriction. Our results show the evolution of the repair allele depends on \\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}b_{1}/b_{0},\\end{equation*}\\end{document} the ratio of the burst size \\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}b_{1}\\end{equation*}\\end{document} under damage to host cell physiology induced by an unrepaired double-strand break to the default burst size \\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}b_{0}.\\end{equation*}\\end{document} It was not until this effect was taken into account that the evolutionary advantage of DNA repair became apparent. PMID:17409094

  1. On optimal output regulation for linear systems

    NARCIS (Netherlands)

    Saberi, Ali; Stoorvogel, Anton A.; Sannuti, Peddapullaiah; Shi, Guoyong

    2003-01-01

    The classical output regulation problem formulation for linear systems has a number of shortcomings; among them a primary one is that it does not take into account the transient response. Although this problem has been studied since the 1970s, a complete picture has not emerged yet. We formulate and

  2. ADAPTIVE REGULATION OF HIGH ORDER NONHOLONOMIC SYSTEMS

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    The problem of adaptive regulation of a class of high-order parametric nonholonomic systems in chained-form was discussed. Using adding a power integrator technique and state scaling with discontinuous projection technique, a discontinuous adaptive dynamic controller was constructed. The controller guarantees the estimated value of unknown parameter is in the prescribed extent.

  3. 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.

  4. ESSENTIAL PRACTICE OF SYSTEMICALLY IMPORTANT BANKS REGULATION

    Directory of Open Access Journals (Sweden)

    V. Trokhymenko

    2014-12-01

    Full Text Available The paper analyzes specific features of establishment of new regulatory standards of systemically important banks as one of the most priority directions of post-crisis improvement of supranational financial regulation. The essense of active and prearranged initiatives to secure constant activity of global and domestic powerful super-big banking institutions is investigated as well as some approaches as to recovery measures implementation without involvement of taxpayers' funds in case of their financial failure are considered. In particular, the main points are focused on introduction of additional requirements to the sufficiency of capital of global systemically important banks, development of the regulatory mechanisms of domestic systemically important banks by domestic authorities taking into account the specific peculiarities of certain national economies, structural reforms as to separation of traditional banking from the securities transactions for the depositors protection (Volcker rule, USA; Vickers rule, UK, establishment of the Single Supervisory Mechanism for the Eurozone banks, and declaration of necessity to form the Single mechanism for bank bankruptcy resolution etc. Some proposals concerning transformation of domestic system of financial regulation and supervision in Ukraine, like strengthening control of systemically important banks activity and introduction of mega-regulator model are characterized.

  5. Reliable regulation in decentralised control systems

    Science.gov (United States)

    Locatelli, Arturo; Schiavoni, Nicola

    2011-03-01

    This article addresses the design of decentralised regulators which supply the control systems with signal tracking and disturbance rejection. This property has to be attained, to the maximum possible extent, even when instrumentation faults occur, thus causing the opening of some feedback loops. The problem is tackled for LTI asymptotically stable plants, subject to perturbations, under the assumption that the Laplace transforms of the exogenous signals have multiple poles on the imaginary axis. The proposed regulator is composed of an LTI nominal controller supervised by a reconfiguration block. Once the actions of the reconfiguration block have been settled, the synthesis of the nominal controller is reformulated as a suitable regulation problem. A constructive sufficient condition for its solvability is established. This condition turns out to be also necessary if the exogenous signals are polynomial in time.

  6. Gender differences in sympathetic nervous system regulation.

    Science.gov (United States)

    Hinojosa-Laborde, C; Chapa, I; Lange, D; Haywood, J R

    1999-02-01

    1. Females are protected against the development of hypertension. The purpose of the current review is to present the evidence for gender differences in the regulation of the sympatho-adrenal nervous system and to determine if these differences support the hypothesis that, in females, the regulation of the sympathetic nervous system (SNS) is altered such that sympatho-adrenal activation is attenuated or sympatho-adrenal inhibition is augmented. 2. The central control of sympatho-adrenal function is different in females and responses vary during the oestral and menstrual cycles. Pathways regulating the SNS appear to be less sensitive to excitatory stimuli and more sensitive to inhibitory stimuli in females compared with males. 3. Gender differences in arterial baroreflex sensitivity suggest that females may have a greater baroreflex sensitivity, such that alterations in blood pressure are more efficiently controlled than in males. Cardiopulmonary reflex inhibition of sympathetic nerve activity is greater in females, possibly resulting in a greater renal excretory function. 4. An attenuated sensitivity to adrenergic nerve stimulation, but not to noradrenaline (NA), suggests that gender differences in noradrenergic neurotransmission may protect females against sympathetic hyperactivity. Gender differences in the regulation of NA release via presynaptic alpha 2-adrenoceptors, the vasoconstrictor response to the cotransmitter neuropeptide Y and the clearance of catecholamines are consistent with this hypothesis. 5. Similarly, attenuated stress-induced increases in plasma catecholamines in women suggest that females are less sensitive and/or less responsive to adrenal medullary activation. This is supported by findings of gender differences in adrenal medullary catecholamine content, release and degradation. 6. We conclude that there is strong evidence that supports the hypothesis that, in females, the regulation of the SNS is altered such that sympatho

  7. Spatial Structures and Regulation in Biological Systems

    DEFF Research Database (Denmark)

    Yde, Pernille

    Spatial arrangements are very important for many biological systems. This thesis presents several different studies of biological systems, which are related to spatial arrangements at two different levels: one is the growth of biological macromolecules, here related to protein aggregation......, 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...... an approximate analytical mathematical expression for the time evolution of the length distribution of the aggregate population, and we discuss the accuracy of the analytical expression. We also compare the model of frangible linear aggregation to experimentally obtained length distributions of growing insulin...

  8. The TRANSFAC system on gene expression regulation.

    Science.gov (United States)

    Wingender, E; Chen, X; Fricke, E; Geffers, R; Hehl, R; Liebich, I; Krull, M; Matys, V; Michael, H; Ohnhäuser, R; Prüss, M; Schacherer, F; Thiele, S; Urbach, S

    2001-01-01

    The TRANSFAC database on transcription factors and their DNA-binding sites and profiles (http://www.gene-regulation.de/) has been quantitatively extended and supplemented by a number of modules. These modules give information about pathologically relevant mutations in regulatory regions and transcription factor genes (PathoDB), scaffold/matrix attached regions (S/MARt DB), signal transduction (TRANSPATH) and gene expression sources (CYTOMER). Altogether, these distinct database modules constitute the TRANSFAC system. They are accompanied by a number of program routines for identifying potential transcription factor binding sites or for localizing individual components in the regulatory network of a cell.

  9. Cholinergic regulation of the vasopressin neuroendocrine system

    Energy Technology Data Exchange (ETDEWEB)

    Michels, K.M.

    1987-01-01

    To clarify the physical and functional relationship between the cholinergic system, and the neurodocrine cells of the supraoptic nucleus, a combination of experiments on receptor binding, localization and function were carried out. The putative nicotinic receptor probe (/sup 125/I)alpha bungarotoxin ((/sup 125/I)alpha BTX) bound with high affinity and specificity to the vasopressin and oxytocin magnocellular neurons of the supraoptic nucleus, nucleus circularis, and paraventricular nucleus. Binding of (/sup 125/I)alpha BTX within the neural lobe was very low. In contrast, the muscarinic cholinergic receptor probe (/sup 3/H)quinuclidinylbenzilate ((/sup 3/H)QNB) did not bind to magnocellular vasopressin and oxytocin cell groups. The median eminence, which contains the neurosecretory axons, and the neural lobe of the pituitary contain low levels of (/sup 3/H)QNB binding. The physiological significance of these cholinergic receptors in regulation of vasopressin release was tested using an in vitro preparation of the supraoptic - neural lobe system.

  10. Fractional-order Systems and Synchronous Generator Voltage Regulator

    Directory of Open Access Journals (Sweden)

    Wojciech Lubośny

    2015-03-01

    Full Text Available Modern regulators of synchronous generators, including voltage regulators, are digital systems, in their vast majority with standard structures contained in the IEEE standard. These are systems described with stationary differential equations of integral order. Differential equations of fractional order are not employed in regulators for synchronous generator control. This paper presents an analysis of the possibilities of using a system of fractional differential equations in the voltage regulator of an synchronous generator with a static excitation system.

  11. How the ubiquitin proteasome system regulates the regulators of transcription.

    Science.gov (United States)

    Ee, Gary; Lehming, Norbert

    2012-01-01

    The ubiquitin proteasome system plays an important role in transcription. Monoubiquitination of activators is believed to aid their function, while the 26S proteasomal degradation of repressors is believed to restrict their function. What remains controversial is the question of whether the degradation of activators aids or restricts their function.

  12. 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.

  13. Fractional-order Systems and Synchronous Generator Voltage Regulator

    OpenAIRE

    2015-01-01

    Modern regulators of synchronous generators, including voltage regulators, are digital systems, in their vast majority with standard structures contained in the IEEE standard. These are systems described with stationary differential equations of integral order. Differential equations of fractional order are not employed in regulators for synchronous generator control. This paper presents an analysis of the possibilities of using a system of fractional differential equations in the volta...

  14. Low-frequency switching voltage regulators for terrestrial photovoltaic systems

    Science.gov (United States)

    Delombard, R.

    1984-01-01

    The photovoltaic technology project and the stand alone applications project are discussed. Two types of low frequency switching type regulators were investigated. The design, operating characteristics and field application of these regulators is described. The regulators are small in size, low in cost, very low in power dissipation, reliable and allow considerable flexibility in system design.

  15. The Type ISP Restriction-Modification enzymes LlaBIII and LlaGI use a translocation-collision mechanism to cleave non-specific DNA distant from their recognition sites.

    Science.gov (United States)

    Šišáková, Eva; van Aelst, Kara; Diffin, Fiona M; Szczelkun, Mark D

    2013-01-01

    The Type ISP Restriction-Modification (RM) enzyme LlaBIII is encoded on plasmid pJW566 and can protect Lactococcus lactis strains against bacteriophage infections in milk fermentations. It is a single polypeptide RM enzyme comprising Mrr endonuclease, DNA helicase, adenine methyltransferase and target-recognition domains. LlaBIII shares >95% amino acid sequence homology across its first three protein domains with the Type ISP enzyme LlaGI. Here, we determine the recognition sequence of LlaBIII (5'-TnAGCC-3', where the adenine complementary to the underlined base is methylated), and characterize its enzyme activities. LlaBIII shares key enzymatic features with LlaGI; namely, adenosine triphosphate-dependent DNA translocation (∼309 bp/s at 25°C) and a requirement for DNA cleavage of two recognition sites in an inverted head-to-head repeat. However, LlaBIII requires K(+) ions to prevent non-specific DNA cleavage, conditions which affect the translocation and cleavage properties of LlaGI. By identifying the locations of the non-specific dsDNA breaks introduced by LlaGI or LlaBIII under different buffer conditions, we validate that the Type ISP RM enzymes use a common translocation-collision mechanism to trigger endonuclease activity. In their favoured in vitro buffer, both LlaGI and LlaBIII produce a normal distribution of random cleavage loci centred midway between the sites. In contrast, LlaGI in K(+) ions produces a far more distributive cleavage profile.

  16. Individual versus systemic risk and the Regulator's Dilemma

    National Research Council Canada - National Science Library

    Nicholas Beale; David G. Rand; Heather Battey; Karen Croxson; Robert M. May; Martin A. Nowak

    2011-01-01

    .... Many proposals for financial reform address the need for systemic regulation—that is, regulation focused on the soundness of the whole financial system and not just that of individual institutions...

  17. 78 FR 18083 - Regulation Systems Compliance and Integrity

    Science.gov (United States)

    2013-03-25

    ... Compliance and Integrity; Proposed Rule #0;#0;Federal Register / Vol. 78 , No. 57 / Monday, March 25, 2013... Systems Compliance and Integrity AGENCY: Securities and Exchange Commission. ACTION: Proposed rule and... proposing Regulation Systems Compliance and Integrity (``Regulation SCI'') under the Securities Exchange Act...

  18. Hydrogen sulfide and nervous system regulation

    Institute of Scientific and Technical Information of China (English)

    ZHOU Cheng-fang; TANG Xiao-qing

    2011-01-01

    Objective This review discusses the current status and progress in studies on the roles of hydrogen sulfide (H2S) in regulation of neurotoxicity,neuroprotection,and neuromodulator,as well as its therapeutic potential for neurodegenerative disorders.Data sources The data used in this review were mainly from Medline and PubMed published in English from 2001 to August 2011.The search terms were “hydrogen sulfide”,“neuron”,and “neurodegenerative disorders”.Study selection Articles regarding the regulation of neuronal function,the protection against neuronal damage and neurological diseases,and their possible cellular and molecular mechanisms associated with H2S were selected.Results The inhibited generation of endogenous H2S is implicated in 1-methy-4-phenylpyridinium ion,6-OHDA,and homocysteine-triggered neurotoxicity.H2S elicits neuroprotection in Alzheimer's disease and Parkinson's disease models as well as protecting neurons against oxidative stress,ischemia,and hypoxia-induced neuronal death.H2S offers anti-oxidant,anti-inflammatory and anti-apoptotic effects,as well as activates ATP-sensitive potassium channels and cystic fibrosis transmembrane conductance regulator Cl- channels.H2S regulates the long-term potentiation (LTP) and GABAB receptors in the hippocampus,as well as intracellular calcium and pH homeostasis in neurons and glia cells.Conclusions These articles suggest that endogenous H2S may regulate the toxicity of neurotoxin.H2S not only acts as a neuroprotectant but also serves as a novel neuromodulator.

  19. A practical guide to geometric regulation for distributed parameter systems

    CERN Document Server

    Aulisa, Eugenio

    2015-01-01

    A Practical Guide to Geometric Regulation for Distributed Parameter Systems provides an introduction to geometric control design methodologies for asymptotic tracking and disturbance rejection of infinite-dimensional systems. The book also introduces several new control algorithms inspired by geometric invariance and asymptotic attraction for a wide range of dynamical control systems. The first part of the book is devoted to regulation of linear systems, beginning with the mathematical setup, general theory, and solution strategy for regulation problems with bounded input and output operators.

  20. 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.

  1. Spatial Structures and Regulation in Biological Systems

    DEFF Research Database (Denmark)

    Yde, Pernille

    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...... inflammation and over-production of the cytokine IL-1β are characteristic features of islets in patients with type II diabetes. We expand the model of Chapter 4 in order to study the inflammatory response in islets of Langerhans, with a special focus on the influence imposed by the spatial conditions - namely...

  2. Ionic regulation in genetic translation systems.

    Science.gov (United States)

    Douzou, P; Maurel, P

    1977-03-01

    The polyelectrolyte theory can provide an interpretation of the interdependence of pH, ionic strength, and polyamines one observes in the activity of ribonuclease acting on RNA. According to this theory: (i) A nucleic acid-enzyme complex and the suspending medium may be considered as two phases in equilibrium, even though within limits, the complex is soluble in water. (ii) The enzymatic catalysis is under tight control of the electrostatic potential generated by the system. Consequently, modification in electrostatic potential will induce a concomitant change in activity. (iii) The electrostatic potential can be modified through action on the system of "modulators", either "external" (ionic strength, pH, temperature, etc.) or "internal" (specific ligands, substrates, protein factors, etc.). Similarities between the reaction of ribonuclease (ribonuclease 3'-pyrimidino-oligonucleotidohydrolase; EC 3.1.4.22) and RNA and those observed with highly organized systems catalyzing DNA, RNA, and protein synthesis suggest that the electrostatic potential also provides an important regulatory mechanism in genetic translation. In this view, an essential function of nucleic acids is to provide their enzyme partners with polyanionic microenvironments within which their catalytic activities are controlled by variation in physicochemical parameters, including the proton concentration induced through "modulation" of the local electrostatic potential.

  3. The brain endocannabinoid system in the regulation of energy balance.

    Science.gov (United States)

    Richard, Denis; Guesdon, Benjamin; Timofeeva, Elena

    2009-02-01

    The role played by the endocannabinoid system in the regulation of energy balance is currently generating a great amount of interest among several groups of investigators. This interest in large part comes from the urgent need to develop anti-obesity and anti-cachexia drugs around target systems (such as the endocannabinoid system), which appears to be genuinely involved in energy balance regulation. When activated, the endocannabinoid system favors energy deposition through increasing energy intake and reducing energy expenditure. This system is activated in obesity and following food deprivation, which further supports its authentic function in energy balance regulation. The cannabinoid receptor type 1 (CB1), one of the two identified cannabinoid receptors, is expressed in energy-balance brain structures that are also able to readily produce or inactivate N-arachidonoyl ethanolamine (anandamide) and 2-arachidonoylglycerol (2AG), the most abundantly formed and released endocannabinoids. The brain action of endocannabinoid system on energy balance seems crucial and needs to be delineated in the context of the homeostatic and hedonic controls of food intake and energy expenditure. These controls require the coordinated interaction of the hypothalamus, brainstem and limbic system and it appears imperative to unravel those interplays. It is also critical to investigate the metabolic endocannabinoid system while considering the panoply of functions that the endocannabinoid system fulfills in the brain and other tissues. This article aims at reviewing the potential mechanisms whereby the brain endocannabinoid system influences the regulation energy balance.

  4. Individual versus systemic risk and the Regulator's Dilemma.

    Science.gov (United States)

    Beale, Nicholas; Rand, David G; Battey, Heather; Croxson, Karen; May, Robert M; Nowak, Martin A

    2011-08-02

    The global financial crisis of 2007-2009 exposed critical weaknesses in the financial system. Many proposals for financial reform address the need for systemic regulation--that is, regulation focused on the soundness of the whole financial system and not just that of individual institutions. In this paper, we study one particular problem faced by a systemic regulator: the tension between the distribution of assets that individual banks would like to hold and the distribution across banks that best supports system stability if greater weight is given to avoiding multiple bank failures. By diversifying its risks, a bank lowers its own probability of failure. However, if many banks diversify their risks in similar ways, then the probability of multiple failures can increase. As more banks fail simultaneously, the economic disruption tends to increase disproportionately. We show that, in model systems, the expected systemic cost of multiple failures can be largely explained by two global parameters of risk exposure and diversity, which can be assessed in terms of the risk exposures of individual actors. This observation hints at the possibility of regulatory intervention to promote systemic stability by incentivizing a more diverse diversification among banks. Such intervention offers the prospect of an additional lever in the armory of regulators, potentially allowing some combination of improved system stability and reduced need for additional capital.

  5. Global Transient Stability and Voltage Regulation for Multimachine Power Systems

    DEFF Research Database (Denmark)

    Gordon, Mark; Hill, David J.

    2008-01-01

    This paper addresses simultaneously the major fundamental and difficult issues of nonlinearity, uncertainty, dimensionality and globality to derive performance enhancing power system stability control. The main focus is on simultaneous enhancement of transient stability and voltage regulation...... law is implemented to coordinate transient stabilizer and voltage regulator for each machine. Digital simulation studies show that global control scheme achieves unified transient stability and voltage regulation in the presence of parametric uncertainties and significant sudden changes in the network...... of power systems. This problem arises from the practical concern that both frequency and voltage control are important indices of power system control and operation but they are ascribed to different stages of system operation, i.e. the transient and post transient period respectively. The Direct Feedback...

  6. Two-component systems and toxinogenesis regulation in Clostridium botulinum.

    Science.gov (United States)

    Connan, Chloé; Popoff, Michel R

    2015-05-01

    Botulinum neurotoxins (BoNTs) are the most potent toxins ever known. They are mostly produced by Clostridium botulinum but also by other clostridia. BoNTs associate with non-toxic proteins (ANTPs) to form complexes of various sizes. Toxin production is highly regulated through complex networks of regulatory systems involving an alternative sigma factor, BotR, and at least 6 recently described two-component systems (TCSs). TCSs allow bacteria to sense environmental changes and to respond to various stimuli by regulating the expression of specific genes at a transcriptional level. Several environmental stimuli have been identified to positively or negatively regulate toxin synthesis; however, the link between environmental stimuli and TCSs is still elusive. This review aims to highlight the role of TCSs as a central point in the regulation of toxin production in C. botulinum.

  7. Output regulation problem for a class of regular hyperbolic systems

    Science.gov (United States)

    Xu, Xiaodong; Dubljevic, Stevan

    2016-01-01

    This paper investigates the output regulation problem for a class of regular first-order hyperbolic partial differential equation (PDE) systems. A state feedback and an error feedback regulator are considered to force the output of the hyperbolic PDE plant to track a periodic reference trajectory generated by a neutrally stable exosystem. A new explanation is given to extend the results in the literature to solve the regulation problem associated with the first-order hyperbolic PDE systems. Moreover, in order to provide the closed-loop stability condition for the solvability of the regulator problems, the design of stabilising feedback gain and its dual problem design of stabilising output injection gain are considered in this paper. This paper develops an easy method to obtain an adjustable stabilising feedback gain and stabilising output injection gain with the aid of the operator Riccati equation.

  8. Cooperative Control for Uncertain Multiagent Systems via Distributed Output Regulation

    Directory of Open Access Journals (Sweden)

    Lu Yu

    2013-01-01

    Full Text Available The distributed robust output regulation problem for multiagent systems is considered. For heterogeneous uncertain linear systems and a linear exosystem, the controlling aim is to stabilize the closed-loop system and meanwhile let the regulated outputs converge to the origin asymptotically, by the help of local interaction. The communication topology considered is directed acyclic graphs, which means directed graphs without loops. With distributed dynamic state feedback controller and output feedback controller, respectively, the solvability of the problem and the algorithm of controller design are both investigated. The solvability conditions are given in terms of linear matrix inequalities (LMIs. It is shown that, for polytopic uncertainties, the distributed controllers constructed by solving LMIs can satisfy the requirements of output regulation property.

  9. Crosstalk between chloroplast thioredoxin systems in regulation of photosynthesis.

    Science.gov (United States)

    Nikkanen, Lauri; Toivola, Jouni; Rintamäki, Eevi

    2016-08-01

    Thioredoxins (TRXs) mediate light-dependent activation of primary photosynthetic reactions in plant chloroplasts by reducing disulphide bridges in redox-regulated enzymes. Of the two plastid TRX systems, the ferredoxin-TRX system consists of ferredoxin-thioredoxin reductase (FTR) and multiple TRXs, while the NADPH-dependent thioredoxin reductase (NTRC) contains a complete TRX system in a single polypeptide. Using Arabidopsis plants overexpressing or lacking a functional NTRC, we have investigated the redundancy and interaction between the NTRC and Fd-TRX systems in regulation of photosynthesis in vivo. Overexpression of NTRC raised the CO2 fixation rate and lowered non-photochemical quenching and acceptor side limitation of PSI in low light conditions by enhancing the activation of chloroplast ATP synthase and TRX-regulated enzymes in Calvin-Benson cycle (CBC). Overexpression of NTRC with an inactivated NTR or TRX domain partly recovered the phenotype of knockout plants, suggesting crosstalk between the plastid TRX systems. NTRC interacted in planta with fructose-1,6-bisphosphatase, phosphoribulokinase and CF1 γ subunit of the ATP synthase and with several chloroplast TRXs. These findings indicate that NTRC-mediated regulation of the CBC and ATP synthesis occurs both directly and through interaction with the ferredoxin-TRX system and is crucial when availability of light is limiting photosynthesis. © 2016 The Authors. Plant, Cell & Environment published by John Wiley & Sons Ltd.

  10. Robust output regulation problem for linear time-delay systems

    Science.gov (United States)

    Lu, Maobin; Huang, Jie

    2015-06-01

    In this paper, we study the robust output regulation problem for linear systems with input time-delay. By extending the internal model design method to linear time-delay systems, we have established solvability conditions for the problem by both dynamic state feedback control and dynamic output feedback control. The advantages of internal model approach over the feedforward design approach are that it can handle perturbations of the uncertain parameters in the plant and the control law, and it does not need to solve the regulator equations.

  11. Motor Control and Regulation for a Flywheel Energy Storage System

    Science.gov (United States)

    Kenny, Barbara; Lyons, Valerie

    2003-01-01

    This talk will focus on the motor control algorithms used to regulate the flywheel system at the NASA Glenn Research Center. First a discussion of the inner loop torque control technique will be given. It is based on the principle of field orientation and is implemented without a position or speed sensor (sensorless control). Then the outer loop charge and discharge algorithm will be presented. This algorithm controls the acceleration of the flywheel during charging and the deceleration while discharging. The algorithm also allows the flywheel system to regulate the DC bus voltage during the discharge cycle.

  12. Nicotine regulates cocaine-amphetamine-Regulated Transcript (Cart) in the mesocorticolimbic system.

    Science.gov (United States)

    Kaya, Egemen; Gozen, Oguz; Ugur, Muzeyyen; Koylu, Ersin O; Kanit, Lutfiye; Balkan, Burcu

    2016-07-01

    Cocaine-and-Amphetamine Regulated Transcript (CART) mRNA and peptides are intensely expressed in the brain regions comprising mesocorticolimbic system. Studies suggest that CART peptides may have a role in the regulation of reward circuitry. The present study aimed to examine the effect of nicotine on CART expression in the mesocorticolimbic system. Three different doses of nicotine (0.2, 0.4, 0.6 mg/kg free base) were injected subcutaneously for 5 days, and on day 6, rats were decapitated following a challenge dose. CART mRNA and peptide levels in medial prefrontal cortex (mPFC), nucleus accumbens (NAc), dorsal striatum (DST), amygdala (AMG), lateral hypothalamic area (LHA), and ventral tegmental area (VTA) were measured by quantitative real-time PCR (qPCR) and Western Blot analysis, respectively. In the mPFC, 0.4 and 0.6 mg/kg nicotine, decreased CART peptide levels whereas there was no effect on CART mRNA levels. In the VTA, a down-regulation of CART peptide expression was observed with 0.2 and 0.6 mg/kg nicotine. Conversely, 0.4 and 0.6 mg/kg nicotine increased CART mRNA levels in the AMG without affecting the CART peptide expression. Nicotine did not regulate CART mRNA or CART peptide expression in the NAc, DST, and LHA. We conclude that nicotine regulates CART expression in the mesocorticolimbic system and this regulation may play an important role in nicotine reward. Synapse 70:283-292, 2016. © 2016 Wiley Periodicals, Inc.

  13. Small systems and regulator dependence in relativistic hydrodynamics

    CERN Document Server

    Spalinski, Michal

    2016-01-01

    Consistent theories of hydrodynamics necessarily include nonhydrodynamic modes, which can be viewed as a regulator necessary to ensure causality. Under many circumstances the choice of regulator is not relevant, but this is not always the case. In particular, for sufficiently small systems (such as those arising in pA or pp collisions) such dependence may be inevitable. We address this issue in the context of M\\"uller-Israel-Stewart theory of relativistic hydrodynamics. In this case, by demanding that the nonhydrodynamic modes do not dominate, we find that regulator dependence becomes inevitable only for multiplicities $dN/dY$ of the order of a few. This conclusion supports earlier studies based on hydrodynamic simulations of small systems, at the same time providing a simple physical picture of how hydrodynamics can be reliable even in such seemingly extreme conditions.

  14. Web-Based Expert System for Civil Service Regulations: RCSES

    CERN Document Server

    Hogo, Mofreh; Mousa, Fouad

    2010-01-01

    Internet and expert systems have offered new ways of sharing and distributing knowledge, but there is a lack of researches in the area of web based expert systems. This paper introduces a development of a web-based expert system for the regulations of civil service in the Kingdom of Saudi Arabia named as RCSES. It is the first time to develop such system (application of civil service regulations) as well the development of it using web based approach. The proposed system considers 17 regulations of the civil service system. The different phases of developing the RCSES system are presented, as knowledge acquiring and selection, ontology and knowledge representations using XML format. XML Rule-based knowledge sources and the inference mechanisms were implemented using ASP.net technique. An interactive tool for entering the ontology and knowledge base, and the inferencing was built. It gives the ability to use, modify, update, and extend the existing knowledge base in an easy way. The knowledge was validated by ...

  15. Cooperative mechanism of self-regulation in hierarchical living systems

    CERN Document Server

    Lubashevsky, I A

    1998-01-01

    We study the problem of how a ``living'' system complex in structure can respond perfectly to local changes in the environment. Such a system is assumed to consist of a distributed ``living'' medium and a hierarchical ``supplying'' network that provides this medium with ``nutritious'' products. Because of the hierarchical organization each element of the supplying network has to behave in a self-consistent way for the system can adapt to changes in the environment. We propose a cooperative mechanism of self-regulation by which the system as a whole can react perfectly. This mechanism is based on an individual response of each element to the corresponding small piece of the information on the state of the ``living'' medium. The conservation of flux through the supplying network gives rise to a certain processing of information and the self-consistent behavior of the elements, leading to the perfect self-regulation. The corresponding equations governing the ``living'' medium state are obtained.

  16. 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...

  17. Output Regulation Problem for Differentiable Families of Linear Systems

    Science.gov (United States)

    Compta, Albert; Ferrer, Josep; Peña, Marta

    2009-09-01

    Given a family of linear systems depending on a parameter varying in a differentiable manifold, we obtain sufficient conditions for the existence of a (global or local) differentiable family of controllers solving the output regulation problem for the given family. Moreover, we construct it when these conditions hold.

  18. Systemic regulation of photosynthetic function in field-grown sorghum.

    Science.gov (United States)

    Li, Tao; Liu, Yujun; Shi, Lei; Jiang, Chuangdao

    2015-09-01

    The photosynthetic characteristics of developing leaves of plants grown under artificial conditions are, to some extent, regulated systemically by mature leaves; however, whether systemic regulation of photosynthesis occurs in field-grown crops is unclear. To explore this question, we investigated the effects of planting density on growth characteristics, gas exchange, leaf nitrogen concentration and chlorophyll a fluorescence in field-grown sorghum (Sorghum bicolor L.). Our results showed that close planting resulted in a marked decline in light intensity in lower canopy. Sorghum plants grown at a high planting density had lower net photosynthetic rate (Pn), stomatal conductance (Gs), and transpiration rate (E) than plants grown at a low planting density. Moreover, in the absence of mineral deficiency, close planting induced a slight increase in leaf nitrogen concentration. The decreased photosynthesis in leaves of the lower canopy at high planting density was caused mainly by the low light. However, newly developed leaves exposed to high light in the upper canopy of plants grown at high planting density also exhibited a distinct decline in photosynthesis relative to plants grown at low planting density. Based on these results, the photosynthetic function of the newly developed leaves in the upper canopy was not determined fully by their own high light environment. Accordingly, we suggest that the photosynthetic function of newly developed leaves in the upper canopy of field-grown sorghum plants is regulated systemically by the lower canopy leaves. The differences in systemic regulation of photosynthesis were also discussed between field conditions and artificial conditions.

  19. Gene regulation by engineered CRISPR-Cas systems.

    Science.gov (United States)

    Fineran, Peter C; Dy, Ron L

    2014-04-01

    The clustered regularly interspaced short palindromic repeat (CRISPR) arrays and their CRISPR associated (Cas) proteins constitute adaptive immune systems in bacteria and archaea that provide protection from bacteriophages, plasmids and other mobile genetic elements (MGEs). Recently, the ability to direct these systems to DNA in a sequence-specific manner has led to the emergence of new technologies for engineered gene regulation in bacteria and eukaryotes. These systems have the potential to enable facile high-throughput functional genomics studies aimed at identifying gene function and will be a crucial tool for synthetic biology. Here, we review the recent engineering of these systems for controlling gene expression.

  20. In search of a human self-regulation system.

    Science.gov (United States)

    Kelley, William M; Wagner, Dylan D; Heatherton, Todd F

    2015-07-08

    The capacity for self-regulation allows people to control their thoughts, behaviors, emotions, and desires. In spite of this impressive ability, failures of self-regulation are common and contribute to numerous societal problems, from obesity to drug addiction. Such failures frequently occur following exposure to highly tempting cues, during negative moods, or after self-regulatory resources have been depleted. Here we review the available neuroscientific evidence regarding self-regulation and its failures. At its core, self-regulation involves a critical balance between the strength of an impulse and an individual's ability to inhibit the desired behavior. Although neuroimaging and patient studies provide consistent evidence regarding the reward aspects of impulses and desires, the neural mechanisms that underlie the capacity for control have eluded consensus, with various executive control regions implicated in different studies. We outline the necessary properties for a self-regulation control system and suggest that the use of resting-state functional connectivity analyses may be useful for understanding how people regulate their behavior and why they sometimes fail in their attempts.

  1. Signaling mechanisms regulating myelination in the central nervous system

    Institute of Scientific and Technical Information of China (English)

    Jared T.Ahrendsen; Wendy Macklin

    2013-01-01

    The precise and coordinated production of myelin is essential for proper development and function of the nervous system.Diseases that disrupt myelin,including multiple sclerosis,cause significant functional disability.Current treatment aims to reduce the inflammatory component of the disease,thereby preventing damage resulting from demyelination.However,therapies are not yet available to improve natural repair processes after damage has already occurred.A thorough understanding of the signaling mechanisms that regulate myelin generation will improve our ability to enhance repair.In this review,we summarize the positive and negative regulators of myelination,focusing primarily on central nervous system myelination.Axon-derived signals,extracellular signals from both diffusible factors and the extracellular matrix,and intracellular signaling pathways within myelinating oligodendrocytes are discussed.Much is known about the positive regulators that drive myelination,while less is known about the negative regulators that shift active myelination to myelin maintenance at the appropriate time.Therefore,we also provide new data on potential negative regulators of CNS myelination.

  2. 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.

  3. Reconstructing a network of stress-response regulators via dynamic system modeling of gene regulation.

    Science.gov (United States)

    Wu, Wei-Sheng; Li, Wen-Hsiung; Chen, Bor-Sen

    2008-02-10

    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 specific stress. The biological significance of our findings is validated by the literature. We found that a small number of TFs is probably sufficient 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.

  4. The teenager's confession: regulating shame in internal family systems therapy.

    Science.gov (United States)

    Sweezy, Martha

    2011-01-01

    This case study explores the clinical relevance of the differences among shame, guilt that is linked with shame, and pure guilt. Empirical literature on emotion suggests that shame is instrumental in a host of psychiatric symptoms while pure guilt is prosocial and adaptive. Regulating shame and being able to feel pure guilt may be especially important for trauma patients like the one described here, who have transgressors as well as victims. The protocol of internal family systems (IFS), a mode of therapy that utilizes psychic multiplicity and actively recruits internal compassion, is described as a treatment for regulating shame and facilitating adaptive guilt.

  5. Danish landfill gas plants with automatic measuring and regulation system

    Energy Technology Data Exchange (ETDEWEB)

    Willumsen, H. [Danish Land Development Service (Denmark)

    1996-12-31

    The first landfill gas plants in the USA were established on large and deep landfills. A number of wells were made and connected to a horizontal suction pipe through which the gas was sucked from the landfill. Most of the gas extraction systems are still constructed that way. However, control and optimising of the gas extraction can be problematic when a great number of drillings are connected to the same suction pipe. Since 1981 the Danish Ministry of Energy has supported selected research and development projects in connection with extraction and utilisation of landfill gas from Danish landfills, including a pilot plant implemented in 1983. In 1985 a EU-financed demonstration plant was established in Viborg, Denmark. In connection with the pilot and EU demonstration plant an automatic measuring and regulation system was developed to secure optimal gas recovery, identical gas quality and furthermore, it has the advantage of remote monitoring and regulation which save operational costs. The automatic measuring and regulation system is in particular well-suited when the landfill is of a relatively low depth and where regulation of the extraction may cause problems embodied in atmospheric air being sucked down in the landfill causing fluctuation of the gas quality and consequently of the gas quantity. (Author)

  6. [Psychoneuroimmunology--regulation of immunity at the systemic level].

    Science.gov (United States)

    Boranić, Milivoj; Sabioncello, Ante; Gabrilovac, Jelka

    2008-01-01

    Innate and acquired immune reactions are controlled by their intrinsic regulatory mechanisms, ie. by an array of cytokines that mediate communication among cells of the immune system itself and with other cells and tissues, e. g. in areas of inflammation. In addition, the immune system is also subjected to systemic regulation by the vegetative and endocrine systems since immune cells express receptors for neurotransmitters and hormones. Neuroendocrine signals may enhance or suppress the immune reaction, accelerate or slow it, but do not affect specificity. Various stressful factors, including the psychosocial ones, affect immunity. In turn, cytokines generated by the immune system influence hormonal secretion and central nervous system, producing specific behavioral changes (the "sickness behavior") accompanying infectious and inflammatory diseases. That includes somnolence, loss of apetite, depression or anxiety and decrease of cognitive abilities, attention and memory. Local immune systems in skin and mucosa are also subjected to systemic neuroendocrine regulation and possess intrinsic neuroregulatory networks as well. These mechanisms render skin and respiratory and digestive tracts responsive to various forms of stress. Examples are neurodermitis, asthma and ulcerative colitis. In children, the immune and the neuroendocrine systems are still developing, particularly in fetal, neonatal and early infant periods, and exposure to stressful experiences at that time may result in late consequences in the form of deficient immunity or greater risks for allergic or autoimmune reactions. Recognition of the participation of neuroendocrine mechanisms in regulation of immunity helps us understand alterations and disturbances of immune reactions under the influence of stressful factors but so far has not produced reliable therapeutic implications. Psychosocial interventions involving the child and its family may be useful.

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

    Directory of Open Access Journals (Sweden)

    Haijing Wu

    2015-05-01

    Full Text Available 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.

  8. Gene Regulation System of Vasopressin and Corticotoropin-Releasing Hormone

    Directory of Open Access Journals (Sweden)

    Masanori Yoshida

    2008-01-01

    Full Text Available The neurohypophyseal hormones, arginine vasopressin and corticotropin-releasing hormone (CRH, play a crucial role in the physiological and behavioral response to various kinds of stresses. Both neuropeptides activate the hypophysialpituitary-adrenal (HPA axis, which is a central mediator of the stress response in the body. Conversely, they receive the negative regulation by glucocorticoid, which is an end product of the HPA axis. Vasopressin and CRH are closely linked to immune response; they also interact with pro-inflammatory cytokines. Moreover, as for vasopressin, it has another important role, which is the regulation of water balance through its potent antidiuretic effect. Hence, it is conceivable that vasopressin and CRH mediate the homeostatic responses for survival and protect organisms from the external world. A tight and elaborate regulation system of the vasopressin and CRH gene is required for the rapid and flexible response to the alteration of the surrounding environments. Several important regulatory elements have been identified in the proximal promoter region in the vasopressin and CRH gene. Many transcription factors and intracellular signaling cascades are involved in the complicated gene regulation system. This review focuses on the current status of the basic research of vasopressin and CRH. In addition to the numerous known facts about their divergent physiological roles, the recent topics of promoter analyses will be discussed.

  9. The logic of kinetic regulation in the thioredoxin system

    Directory of Open Access Journals (Sweden)

    Hofmeyr Jan-Hendrik S

    2011-01-01

    Full Text Available Abstract Background The thioredoxin system consisting of NADP(H, thioredoxin reductase and thioredoxin provides reducing equivalents to a large and diverse array of cellular processes. Despite a great deal of information on the kinetics of individual thioredoxin-dependent reactions, the kinetic regulation of this system as an integrated whole is not known. We address this by using kinetic modeling to identify and describe kinetic behavioral motifs found within the system. Results Analysis of a realistic computational model of the Escherichia coli thioredoxin system revealed several modes of kinetic regulation in the system. In keeping with published findings, the model showed that thioredoxin-dependent reactions were adaptable (i.e. changes to the thioredoxin system affected the kinetic profiles of these reactions. Further and in contrast to other systems-level descriptions, analysis of the model showed that apparently unrelated thioredoxin oxidation reactions can affect each other via their combined effects on the thioredoxin redox cycle. However, the scale of these effects depended on the kinetics of the individual thioredoxin oxidation reactions with some reactions more sensitive to changes in the thioredoxin cycle and others, such as the Tpx-dependent reduction of hydrogen peroxide, less sensitive to these changes. The coupling of the thioredoxin and Tpx redox cycles also allowed for ultrasensitive changes in the thioredoxin concentration in response to changes in the thioredoxin reductase concentration. We were able to describe the kinetic mechanisms underlying these behaviors precisely with analytical solutions and core models. Conclusions Using kinetic modeling we have revealed the logic that underlies the functional organization and kinetic behavior of the thioredoxin system. The thioredoxin redox cycle and associated reactions allows for a system that is adaptable, interconnected and able to display differential sensitivities to changes

  10. Regulation of cadherin expression in nervous system development.

    Science.gov (United States)

    Paulson, Alicia F; Prasad, Maneeshi S; Thuringer, Amanda Henke; Manzerra, Pasquale

    2014-01-01

    This review addresses our current understanding of the regulatory mechanisms for classical cadherin expression during development of the vertebrate nervous system. The complexity of the spatial and temporal expression patterns is linked to morphogenic and functional roles in the developing nervous system. While the regulatory networks controlling cadherin expression are not well understood, it is likely that the multiple signaling pathways active in the development of particular domains also regulate the specific cadherins expressed at that time and location. With the growing understanding of the broader roles of cadherins in cell-cell adhesion and non-adhesion processes, it is important to understand both the upstream regulation of cadherin expression and the downstream effects of specific cadherins within their cellular context.

  11. Complement system part I - molecular mechanisms of activation and regulation

    Directory of Open Access Journals (Sweden)

    Nicolas eMerle

    2015-06-01

    Full Text Available Complement is a complex innate immune surveillance system, playing a key role in defense against pathogens and in host homeostasis. The complement system is initiated by conformational changes in recognition molecular complexes upon sensing danger signals. The subsequent cascade of enzymatic reactions is tightly regulated to assure that complement is activated only at specific locations requiring defense against pathogens, thus avoiding host tissue damage. Here we discuss the recent advances describing the molecular and structural basis of activation and regulation of the complement pathways and their implication on physiology and pathology. This article will review the mechanisms of activation of alternative, classical and lectin pathways, the formation of C3 and C5 convertases, the action of anaphylatoxins and the membrane attack complex. We will also discuss the importance of structure-function relationships using the example of atypical hemolytic uremic syndrome. Lastly we will discuss the development and benefits of therapies using complement inhibitors.

  12. Optimization of Regulation Valve Location for Heating System

    Institute of Scientific and Technical Information of China (English)

    LIU Ling-ling; CHEN Hong-bing; LI De-ying

    2009-01-01

    This paper mainly studied how to determine the best location of the self-operated flow control valve at the heating system entrance.Since the location of regulating valve directly affects the pipe network per-formance,the simulation and analysis of pressure change in heating system WaS carried out with ComputationalFluid Dynamics(CFD)software.The study shows the best location of regulating valve varies with the change of the supply and return pipe length when the heating area of each user is small,and when the heating area of each user is large(2000000~3000000m2),the best location is on the supply pipe.

  13. Improved applications of the tetracycline-regulated gene depletion system.

    Science.gov (United States)

    Nishijima, Hitoshi; Yasunari, Takami; Nakayama, Tatsuo; Adachi, Noritaka; Shibahara, Kei-ichi

    2009-10-01

    Tightly controlled expression of transgenes in mammalian cells is an important tool for biological research, drug discovery, and future genetic therapies. The tetracycline-regulated gene depletion (Tet-Off) system has been widely used to control gene activities in mammalian cells, because it allows strict regulation of transgenes but no pleiotropic effects of prokaryotic regulatory proteins. However, the Tet-Off system is not compatible with every cell type and this is the main remaining obstacle left for this system. Recently, we overcame this problem by inserting an internal ribosome entry site (IRES) to drive a selectable marker from the same tetracycline-responsive promoter for the transgene. We also employed a CMV immediate early enhancer/beta-actin (CAG) promoter to express a Tet-controlled transactivator. Indeed, the Tet-Off system with these technical modifications was applied successfully to the human pre-B Nalm-6 cell line in which conventional Tet-Off systems had not worked efficiently. These methodological improvements should be applicable for many other mammalian proliferating cells. In this review we give an overview and introduce a new method for the improved application of the Tet-Off system.

  14. Cooperative Output Regulation of Singular Heterogeneous Multiagent Systems.

    Science.gov (United States)

    Ma, Qian; Xu, Shengyuan; Lewis, Frank L; Zhang, Baoyong; Zou, Yun

    2016-06-01

    This paper investigates the cooperative output regulation problem of singular heterogeneous multiagent systems. General distributed observers are proposed for every agent obtaining the estimated state of the exosystem. The feedforward control technique and reduced-order approach are used to design distributed singular output feedback controllers and distributed normal output feedback controllers. The proposed cooperative dynamic controller is dependent on the plant parameters and the interaction topologies. A simulation example is provided to demonstrate the effectiveness of the proposed design method.

  15. Novel pathogenesis: regulation of apoptosis by Apelin/APJ system.

    Science.gov (United States)

    Liu, Jiaqi; Liu, Meiqing; Chen, Linxi

    2017-06-01

    Apelin is the endogenous peptide APJ receptor, while APJ is a member of the G protein-coupled receptors family. Recent evidence strongly suggests that Apelin/APJ system influences apoptosis in various diseases through different signal pathways. In this review, we discuss the possible mechanisms by which the Apelin/APJ system inhibits apoptosis, including the phosphatidylinositol-3-kinase (PI3K)/Akt, ERK1/2, caspase signaling, and autophagy pathway. We also summarize the role of Apelin/APJ system in apoptosis in myocardial ischemia-reperfusion (I/R) injury, pulmonary artery hypertension, retinal neovascular disease, acute renal injury, skeletal homeostasis, and gastrointestinal diseases. Apelin/APJ system decreases myocardial infarction size and alleviates myocardial I/R injury by inhibiting cardiomyocytes apoptosis. However, Apelin/APJ system improves pulmonary artery hypertension via increasing apoptosis. Apelin/APJ system exerts neuroprotective effect by blocking apoptosis and participates in the recovery of retinal neovascular disease by suppressing apoptosis. Apelin/APJ system also shows anti-apoptotic effect against acute renal injury and plays a role in regulating skeletal homeostasis. In gastrointestinal disease, Apelin/APJ system plays a potential physiological role in gastrointestinal cytoprotection by regulating apoptosis. We hope that a better understanding of the Apelin/APJ system will help to discover new disease pathogenesis and find possible therapeutic targets of the Apelin/APJ system essential for various diseases. © The Author 2017. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. 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.

  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. DC Bus Regulation with a Flywheel Energy Storage System

    Science.gov (United States)

    Kenny, Barbara H.; Kascak, Peter E.

    2003-01-01

    This paper describes the DC bus regulation control algorithm for the NASA flywheel energy storage system during charge, charge reduction and discharge modes of operation. The algorithm was experimentally verified with results given in a previous paper. This paper presents the necessary models for simulation with detailed block diagrams of the controller algorithm. It is shown that the flywheel system and the controller can be modeled in three levels of detail depending on the type of analysis required. The three models are explained and then compared using simulation results.

  19. Regulation of System xc− by Pharmacological Manipulation of Cellular Thiols

    Science.gov (United States)

    Albano, Rebecca; Raddatz, Nicholas J.; Hjelmhaug, Julie; Baker, David A.; Lobner, Doug

    2015-01-01

    The cystine/glutamate exchanger (system xc−) mediates the transport of cystine into the cell in exchange for glutamate. By releasing glutamate, system xc− can potentially cause excitotoxicity. However, through providing cystine to the cell, it regulates the levels of cellular glutathione (GSH), the main endogenous intracellular antioxidant, and may protect cells against oxidative stress. We tested two different compounds that deplete primary cortical cultures containing both neurons and astrocytes of intracellular GSH, L-buthionine-sulfoximine (L-BSO), and diethyl maleate (DEM). Both compounds caused significant concentration and time dependent decreases in intracellular GSH levels. However; DEM caused an increase in radiolabeled cystine uptake through system xc−, while unexpectedly BSO caused a decrease in uptake. The compounds caused similar low levels of neurotoxicity, while only BSO caused an increase in oxidative stress. The mechanism of GSH depletion by these two compounds is different, DEM directly conjugates to GSH, while BSO inhibits γ-glutamylcysteine synthetase, a key enzyme in GSH synthesis. As would be expected from these mechanisms of action, DEM caused a decrease in intracellular cysteine, while BSO increased cysteine levels. The results suggest that negative feedback by intracellular cysteine is an important regulator of system xc− in this culture system. PMID:25949770

  20. Adaptive Output Regulation for Nonlinear Systems with Unknown Periodic Disturbances

    Science.gov (United States)

    Tsuruoka, Hidenobu; Ohmori, Hiromitsu

    Many mechanical systems are subjected to periodic disturbances which may adversely influence control performance. When the plants are nonlinear systems with unknown parameters, this disturbance compensation problem has been considered as adaptive output regulation problem. This paper discusses the problem about adaptive output regulation for nonlinear systems with arbitrary relative degree, which can be transformed into the output feedback form. The nonlinear plant is affected by unknown constant parameters and periodic disturbances with unknown frequencies, magnitudes and phases. The periodic disturbances are considered as signals generated from a linear time invariant exosystem. It is not assumed that the disturbances meet the matching condition for the control input. The design method of the adaptive controller and its parameter update law is based on adaptive backstepping manner for the coordinates-changed extended system, which is generated from the nonlinear plant and the exosystem. Then, it can be achieved that the output asymptotically converges to the output reference and that all signals in the closed-loop system are bounded.

  1. Regulation of System xc- by Pharmacological Manipulation of Cellular Thiols

    Directory of Open Access Journals (Sweden)

    Rebecca Albano

    2015-01-01

    Full Text Available The cystine/glutamate exchanger (system xc- mediates the transport of cystine into the cell in exchange for glutamate. By releasing glutamate, system xc- can potentially cause excitotoxicity. However, through providing cystine to the cell, it regulates the levels of cellular glutathione (GSH, the main endogenous intracellular antioxidant, and may protect cells against oxidative stress. We tested two different compounds that deplete primary cortical cultures containing both neurons and astrocytes of intracellular GSH, L-buthionine-sulfoximine (L-BSO, and diethyl maleate (DEM. Both compounds caused significant concentration and time dependent decreases in intracellular GSH levels. However; DEM caused an increase in radiolabeled cystine uptake through system xc-, while unexpectedly BSO caused a decrease in uptake. The compounds caused similar low levels of neurotoxicity, while only BSO caused an increase in oxidative stress. The mechanism of GSH depletion by these two compounds is different, DEM directly conjugates to GSH, while BSO inhibits γ-glutamylcysteine synthetase, a key enzyme in GSH synthesis. As would be expected from these mechanisms of action, DEM caused a decrease in intracellular cysteine, while BSO increased cysteine levels. The results suggest that negative feedback by intracellular cysteine is an important regulator of system xc- in this culture system.

  2. Regulation of System xc(-) by Pharmacological Manipulation of Cellular Thiols.

    Science.gov (United States)

    Albano, Rebecca; Raddatz, Nicholas J; Hjelmhaug, Julie; Baker, David A; Lobner, Doug

    2015-01-01

    The cystine/glutamate exchanger (system xc (-)) mediates the transport of cystine into the cell in exchange for glutamate. By releasing glutamate, system xc (-) can potentially cause excitotoxicity. However, through providing cystine to the cell, it regulates the levels of cellular glutathione (GSH), the main endogenous intracellular antioxidant, and may protect cells against oxidative stress. We tested two different compounds that deplete primary cortical cultures containing both neurons and astrocytes of intracellular GSH, L-buthionine-sulfoximine (L-BSO), and diethyl maleate (DEM). Both compounds caused significant concentration and time dependent decreases in intracellular GSH levels. However; DEM caused an increase in radiolabeled cystine uptake through system xc (-), while unexpectedly BSO caused a decrease in uptake. The compounds caused similar low levels of neurotoxicity, while only BSO caused an increase in oxidative stress. The mechanism of GSH depletion by these two compounds is different, DEM directly conjugates to GSH, while BSO inhibits γ-glutamylcysteine synthetase, a key enzyme in GSH synthesis. As would be expected from these mechanisms of action, DEM caused a decrease in intracellular cysteine, while BSO increased cysteine levels. The results suggest that negative feedback by intracellular cysteine is an important regulator of system xc (-) in this culture system.

  3. 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.

  4. 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

  5. Yersinia Type III Secretion System Master Regulator LcrF.

    Science.gov (United States)

    Schwiesow, Leah; Lam, Hanh; Dersch, Petra; Auerbuch, Victoria

    2015-12-07

    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.

  6. Prokaryotic toxin-antitoxin systems: novel regulations of the toxins.

    Science.gov (United States)

    Otsuka, Yuichi

    2016-05-01

    Toxin-antitoxin (TA) systems are widely conserved in prokaryotic plasmids and chromosomes and are linked to many roles in cell physiology, including plasmid maintenance, stress response, persistence and protection from phage infection. A TA system is composed of a stable toxin and a labile antitoxin that inhibits a harmful effect of the cognate toxin. When gene expression from the TA loci is repressed under certain conditions such as nutrient starvation, the toxin is freed from the rapidly degrading antitoxin and obstructs an essential cellular process, such as DNA replication, translation and peptidoglycan synthesis, which subsequently causes growth arrest. TA systems are classified into five types according to the nature and the function of antitoxins, and the activity of toxins is tightly regulated in a variety of ways. This short-review highlights several novel regulatory mechanisms for Escherichia coli toxins that we recently discovered.

  7. Vibrio cholerae Response Regulator VxrB Controls Colonization and Regulates the Type VI Secretion System.

    Directory of Open Access Journals (Sweden)

    Andrew T Cheng

    2015-05-01

    Full Text Available Two-component signal transduction systems (TCS are used by bacteria to sense and respond to their environment. TCS are typically composed of a sensor histidine kinase (HK and a response regulator (RR. The Vibrio cholerae genome encodes 52 RR, but the role of these RRs in V. cholerae pathogenesis is largely unknown. To identify RRs that control V. cholerae colonization, in-frame deletions of each RR were generated and the resulting mutants analyzed using an infant mouse intestine colonization assay. We found that 12 of the 52 RR were involved in intestinal colonization. Mutants lacking one previously uncharacterized RR, VCA0566 (renamed VxrB, displayed a significant colonization defect. Further experiments showed that VxrB phosphorylation state on the predicted conserved aspartate contributes to intestine colonization. The VxrB regulon was determined using whole genome expression analysis. It consists of several genes, including those genes that create the type VI secretion system (T6SS. We determined that VxrB is required for T6SS expression using several in vitro assays and bacterial killing assays, and furthermore that the T6SS is required for intestinal colonization. vxrB is encoded in a four gene operon and the other vxr operon members also modulate intestinal colonization. Lastly, though ΔvxrB exhibited a defect in single-strain intestinal colonization, the ΔvxrB strain did not show any in vitro growth defect. Overall, our work revealed that a small set of RRs is required for intestinal colonization and one of these regulators, VxrB affects colonization at least in part through its regulation of T6SS genes.

  8. Vibrio cholerae Response Regulator VxrB Controls Colonization and Regulates the Type VI Secretion System.

    Science.gov (United States)

    Cheng, Andrew T; Ottemann, Karen M; Yildiz, Fitnat H

    2015-05-01

    Two-component signal transduction systems (TCS) are used by bacteria to sense and respond to their environment. TCS are typically composed of a sensor histidine kinase (HK) and a response regulator (RR). The Vibrio cholerae genome encodes 52 RR, but the role of these RRs in V. cholerae pathogenesis is largely unknown. To identify RRs that control V. cholerae colonization, in-frame deletions of each RR were generated and the resulting mutants analyzed using an infant mouse intestine colonization assay. We found that 12 of the 52 RR were involved in intestinal colonization. Mutants lacking one previously uncharacterized RR, VCA0566 (renamed VxrB), displayed a significant colonization defect. Further experiments showed that VxrB phosphorylation state on the predicted conserved aspartate contributes to intestine colonization. The VxrB regulon was determined using whole genome expression analysis. It consists of several genes, including those genes that create the type VI secretion system (T6SS). We determined that VxrB is required for T6SS expression using several in vitro assays and bacterial killing assays, and furthermore that the T6SS is required for intestinal colonization. vxrB is encoded in a four gene operon and the other vxr operon members also modulate intestinal colonization. Lastly, though ΔvxrB exhibited a defect in single-strain intestinal colonization, the ΔvxrB strain did not show any in vitro growth defect. Overall, our work revealed that a small set of RRs is required for intestinal colonization and one of these regulators, VxrB affects colonization at least in part through its regulation of T6SS genes.

  9. Zeb2: A multifunctional regulator of nervous system development.

    Science.gov (United States)

    Hegarty, Shane V; Sullivan, Aideen M; O'Keeffe, Gerard W

    2015-09-01

    Zinc finger E-box binding homeobox (Zeb) 2 is a transcription factor, identified due its ability to bind Smad proteins, and consists of multiple functional domains which interact with a variety of transcriptional co-effectors. The complex nature of the Zeb2, both at its genetic and protein levels, underlie its multifunctional properties, with Zeb2 capable of acting individually or as part of a transcriptional complex to repress, and occasionally activate, target gene expression. This review introduces Zeb2 as an essential regulator of nervous system development. Zeb2 is expressed in the nervous system throughout its development, indicating its importance in neurogenic and gliogenic processes. Indeed, mutation of Zeb2 has dramatic neurological consequences both in animal models, and in humans with Mowat-Wilson syndrome, which results from heterozygous ZEB2 mutations. The mechanisms by which Zeb2 regulates the induction of the neuroectoderm (CNS primordium) and the neural crest (PNS primordium) are reviewed herein. We then describe how Zeb2 acts to direct the formation, delamination, migration and specification of neural crest cells. Zeb2 regulation of the development of a number of cerebral regions, including the neocortex and hippocampus, are then described. The diverse molecular mechanisms mediating Zeb2-directed development of various neuronal and glial populations are reviewed. The role of Zeb2 in spinal cord and enteric nervous system development is outlined, while its essential function in CNS myelination is also described. Finally, this review discusses how the neurodevelopmental defects of Zeb2 mutant mice delineate the developmental dysfunctions underpinning the multiple neurological defects observed in Mowat-Wilson syndrome patients.

  10. 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.

  11. Iron acquisition and regulation systems in Streptococcus species.

    Science.gov (United States)

    Ge, Ruiguang; Sun, Xuesong

    2014-05-01

    Gram-positive Streptococcus species are responsible for millions of cases of meningitis, bacterial pneumonia, endocarditis, erysipelas and necrotizing fasciitis. Iron is essential for the growth and survival of Streptococcus in the host environment. Streptococcus species have developed various mechanisms to uptake iron from an environment with limited available iron. Streptococcus can directly extract iron from host iron-containing proteins such as ferritin, transferrin, lactoferrin and hemoproteins, or indirectly by relying on the employment of specialized secreted hemophores (heme chelators) and small siderophore molecules (high affinity ferric chelators). This review presents the most recent discoveries in the iron acquisition system of Streptococcus species - the transporters as well as the regulators.

  12. 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.

  13. 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.

  14. 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.

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

    Directory of Open Access Journals (Sweden)

    Jianqiang Hu

    2014-01-01

    Full Text Available 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.

  16. 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.

  17. Output regulation problem for discrete-time linear time-delay systems by output feedback control

    Institute of Scientific and Technical Information of China (English)

    Yamin YAN; Jie HUANG

    2016-01-01

    In this paper, we study the output regulation problem of discrete linear time-delay systems by output feedback control. We have established some results parallel to those for the output regulation problem of continuous linear time-delay systems.

  18. The Kdp-ATPase system and its regulation

    Indian Academy of Sciences (India)

    Anand Ballal; Bhakti Basu; Shree Kumar Apte

    2007-04-01

    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), encoded by the kdpFABC operon, is an inducible high-affinity K+ transporter that is synthesised under conditions of severe K+ limitation or osmotic upshift. The E. coli kdp expression is transcriptionally regulated by the KdpD and KdpE proteins, which together constitute a typical bacterial two-component signal transduction system. The Kdp system is widely dispersed among the different classes of bacteria including the cyanobacteria. The ordering of the kdpA, kdpB and kdpC is relatively fixed but the kdpD/E genes show different arrangements in distantly related bacteria. Our studies have shown that the cyanobacterium Anabaena sp. strain L-31 possesses two kdp operons, kdp1 and kdp2, of which, the later is expressed under K+ deficiency and desiccation. Among the regulatory genes, the kdpD ORF of Anabaena L-31 is truncated when compared to the kdpD of other bacteria, while a kdpE-like gene is absent. The extremely radio-resistant bacterium, Deinococcus radiodurans strain R1, also shows the presence of a naturally short kdpD ORF similar to Anabaena in its kdp operon. The review elaborates the expression of bacterial kdp operons in response to various environmental stress conditions, with special emphasis on Anabaena. The possible mechanism(s) of regulation of the unique kdp operons from Anabaena and Deinococcus are also discussed.

  19. 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.

  20. Cooperative Output Regulation of Multiagent Linear Parameter-Varying Systems

    Directory of Open Access Journals (Sweden)

    Afshin Mesbahi

    2017-01-01

    Full Text Available The output regulation problem is examined in this paper for a class of heterogeneous multiagent systems whose dynamics are governed by polytopic linear parameter-varying (LPV models. The dynamics of the agents are decoupled from each other but the agents’ controllers are assumed to communicate. To design the cooperative LPV controllers, analysis conditions for closed-loop system are first established to ensure stability and reference tracking. Then, the LPV control synthesis problem is addressed, where the offline solution to a time-varying Sylvester equation will be used to determine and update in real time the controller state-space matrices. Two numerical examples will be finally given to demonstrate the efficacy of the proposed cooperative design method.

  1. The plasma carboxypeptidases and the regulation of the plasminogen system.

    Science.gov (United States)

    Plow, E F; Allampallam, K; Redlitz, A

    1997-04-01

    Central to the regulation of the plasminogen system, a proteolytic network that mediates degradation of fibrin and facilitates cell migration, is the binding of plasminogen to carboxy-terminal lysines. These residues occur either naturally on plasmin substrates or cell surfaces or are generated as a consequence of partial plasmin degradation. The basic carboxypeptidases of plasma are capable of removing such carboxy-terminal lysines. Carboxypeptidase N, which is constitutively active, suppresses plasminogen binding to cell surfaces; plasma carboxypeptidase B, which must be proteolytically activated, not only suppresses cellular binding of plasminogen but also dampens fibrinolysis. Thus, the plasma carboxypeptidases may constitute an important regulatory pathway for controlling the activity of the plasminogen system in physiologic, pathophysiologic, and pharmacologic circumstances. (Trends Cardiovasc Med 1997;7:71-75). © 1997, Elsevier Science Inc.

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

    DEFF Research Database (Denmark)

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

    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......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...... 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....

  3. 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....

  4. Regulation of ovarian function by the matrix metalloproteinase system

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    @@ In most organs of mammals, cyclic remodelling of tissues after morphogenesis is minimal; however, repro-ductive tissues of female animals including endometrium, mammary gland, ovarian follicle and corpus luteum un-dergo growth, maturation and involution at various stages in the reproductive cycle or lifespan of the animal. Recon-struction of the extracellular matrix (ECM) is required for the dynamic tissue reorganization characteristic of these tissues. The ECM consists of proteinaceous and nonpro-teinaceous molecules that provide the tissue-specific, ex-tracellular architecture to which cells attach. Furthermore, interaction of cellular receptors with proteins of the ECM can regulate cellular structure, second messenger genera-tion and gene expression. Maintenance of ECM homeo-stasis depends largely on coordinated action of matrix metalloproteinases (MMPs) and tissue inhibitors of met-alloproteinases (TIMPs)-- an important proteinase sys-tem responsible for degradating and remodelling of ECM[1]. MMPs/TIMPs have been recognized as the cru-cial role players in regulating follicular and luteal function for their extensive involvements in the cyclic changes of dynamic ovarian tissues. In recent years, literature that MMP system has important roles in ovary is accumulating. The focus of this review is on the effects of MMPs and their inhibitors, TIMPs on follicular growth, atresia, ovu-lation, luteal development, and luteolysis. Emphasis has been given to the recent progress in the new field when-ever possible.

  5. 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.

  6. An optimized, chemically regulated gene expression system for Chlamydomonas.

    Directory of Open Access Journals (Sweden)

    Paola Ferrante

    Full Text Available BACKGROUND: Chlamydomonas reinhardtii is a model system for algal and cell biology and is used for biotechnological applications, such as molecular farming or biological hydrogen production. The Chlamydomonas metal-responsive CYC6 promoter is repressed by copper and induced by nickel ions. However, induction by nickel is weak in some strains, poorly reversible by chelating agents like EDTA, and causes, at high concentrations, toxicity side effects on Chlamydomonas growth. Removal of these bottlenecks will encourage the wide use of this promoter as a chemically regulated gene expression system. METHODOLOGY: Using a codon-optimized Renilla luciferase as a reporter gene, we explored several strategies to improve the strength and reversibility of CYC6 promoter induction. Use of the first intron of the RBCS2 gene or of a modified TAP medium increases the strength of CYC6 induction up to 20-fold. In the modified medium, induction is also obtained after addition of specific copper chelators, like TETA. At low concentrations (up to 10 microM TETA is a more efficient inducer than Ni, which becomes a very efficient inducer at higher concentrations (50 microM. Neither TETA nor Ni show toxicity effects at the concentrations used. Unlike induction by Ni, induction by TETA is completely reversible by micromolar copper concentrations, thus resulting in a transient "wave" in luciferase activity, which can be repeated in subsequent growth cycles. CONCLUSIONS: We have worked out a chemically regulated gene expression system that can be finely tuned to produce temporally controlled "waves" in gene expression. The use of cassettes containing the CYC6 promoter, and of modified growth media, is a reliable and economically sustainable system for the temporally controlled expression of foreign genes in Chlamydomonas.

  7. Photovoltaic-powered regulated cathodic-protection system

    Science.gov (United States)

    Anis, Wagdy R.; Alfons, Hany A.

    The objective of a cathodic protection system is to protect metallic structures against corrosion. To achieve this, a sacrificial anode is connected to the protected structure (which acts as a cathode) through a d.c. power supply. To stop the corrosion, the protected structure requires a constant current. The current is determined by the metal and area of the structure, as well as the surrounding medium. The major difficulty in achieving a constant current is the variation in the resistivity of the surrounding medium that is caused by changes in the climatic conditions. Conventional cathodic-protection systems resolve this problem by manual adjustment of the d.c. voltage periodically to obtain a constant current. Such adjustment depends on the experience of the technician and the accuracy of the measuring equipment. Moreover if the interval between successive adjustments is relative long, the corrosion could become excessive. To overcome such difficulties, an automatically regulated system has been developed. The proposed system senses variations is the resistivity of the surrounding medium and adjusts the d.c. voltage accordingly so that the current is kept constant at the required level. The design of a solar photovoltaic system to supply the required d.c. power is discussed in this communication.

  8. Management of the Spring Snowmelt Recession in Regulated Systems

    Science.gov (United States)

    Yarnell, S. M.; Lind, A.; Epke, G.; Viers, J. H.

    2013-12-01

    In unregulated rivers in the Sierra Nevada mountains of California, the spring snowmelt recession links high winter flows to low summer baseflow and is a consistent and predictable portion of the annual hydrograph. Consequently, it is an important resource to both riverine ecosystems and California's water supply. In regulated river systems where the spring snowmelt recession is often captured behind dams or diverted for hydropower, restoration of a more natural spring flow regime can provide distinct ecological benefits, such as breeding and migration cues for native species, increased habitat availability, and greater hydraulic habitat diversity. However, knowledge of how to create and manage an ecologically beneficial spring snowmelt recession in a regulated river system has been lacking. This study defined a methodology by which spring flow regimes can be modeled in regulated systems from the quantifiable characteristics of spring snowmelt recessions in unregulated rivers. Using fundamental flow components such as magnitude, timing, and rate of change, the spring snowmelt recession in eight unregulated rivers across the Sierra Nevada range was quantified to gain a better understanding of the predictability and variability across watersheds. The analysis found that unregulated Sierran systems behaved similarly with respect to seasonal patterns and flow recession shape (i.e., recession limb curvature), and thus flows could be modeled in a manner that mimics those predictable characteristics. Using this methodology that quantifies spring recession flows in terms of a daily percent decrease in flow, a series of flow recession scenarios were then created for application on a regulated Sierran river. Four scenarios, ranging from a slow natural recession to a short fast recession typically observed in regulated rivers following cessation of high flow spills, were evaluated within a 2D hydrodynamic model. The effects of the flows on suitable habitat for Foothill yellow

  9. Regulation on radial position deviation for vertical AMB systems

    Science.gov (United States)

    Tsai, Nan-Chyuan; Kuo, Chien-Hsien; Lee, Rong-Mao

    2007-10-01

    As a source of model uncertainty, gyroscopic effect, depending on rotor speed, is studied for the vertical active magnetic bearing (VAMB) systems which are increasingly used in various industries such as clean rooms, compressors and satellites. This research applies H∞ controller to regulate the rotor position deviations of the VAMB systems in four degrees of freedom. The performance of H∞ controller is examined by experimental simulations to inspect its closed-loop stiffness, rise time and capability to suppress the high frequency disturbances. Although the H∞ is inferior to the LQR in position deviation regulation, the required control current in the electromagnetic bearings is much less than that for LQR or PID and the performance robustness is well retained. In order to ensure the stability robustness of H∞ controller, two approaches, by Kharitonov polynomials and TITO (two inputs & two outputs) Nyquist Stability Criterion, are employed to synthesize the control feedback loop. A test rig is built to further verify the efficacy of the proposed H∞ controller experimentally. Two Eddy-current types of gap sensors, perpendicular to each other, are included to the realistic rotor-bearing system. A four-pole magnetic bearing is used as the actuator for generation of control force. The commercial I/O module unit with A/D and D/A converters, dSPACE DS1104, is integrated to the VAMB, gap sensors, power amplifiers and signal processing circuits. The H∞ is designed on the basis of rotor speed 10 K rpm but in fact it is significantly robust with respect to the rotor speed, varying from 6.5 to 13.5 K rpm.

  10. 75 FR 76692 - Defense Federal Acquisition Regulation Supplement; Business Systems-Definition and Administration...

    Science.gov (United States)

    2010-12-09

    ... Federal Acquisition Regulation Supplement; Business Systems--Definition and Administration (DFARS Case... INFORMATION: I. Background DoD published a proposed rule for Business Systems--Definition and...

  11. The Zinc Transport Systems and Their Regulation in Pathogenic Fungi.

    Science.gov (United States)

    Jung, Won Hee

    2015-09-01

    Zinc is an essential micronutrient required for many enzymes that play essential roles in a cell. It was estimated that approximately 3% of the total cellular proteins are required for zinc for their functions. Zinc has long been considered as one of the key players in host-pathogen interactions. The host sequesters intracellular zinc by utilizing multiple cellular zinc importers and exporters as a means of nutritional immunity. To overcome extreme zinc limitation within the host environment, pathogenic microbes have successfully evolved a number of mechanisms to secure sufficient concentrations of zinc for their survival and pathogenesis. In this review, we briefly discuss the zinc uptake systems and their regulation in the model fungus Saccharomyces cerevisiae and in major human pathogenic fungi such as Aspergillus fumigatus, Candida albicans, and Cryptococcus gattii.

  12. Regulation of stem cells in the zebra fish hematopoietic system.

    Science.gov (United States)

    Huang, H-T; Zon, L I

    2008-01-01

    Hematopoietic stem cells (HSCs) have been used extensively as a model for stem cell biology. Stem cells share the ability to self-renew and differentiate into multiple cell types, making them ideal candidates for tissue regeneration or replacement therapies. Current applications of stem cell technology are limited by our knowledge of the molecular mechanisms that control their proliferation and differentiation, and various model organisms have been used to fill these gaps. This chapter focuses on the contributions of the zebra fish model to our understanding of stem cell regulation within the hematopoietic system. Studies in zebra fish have been valuable for identifying new genetic and signaling factors that affect HSC formation and development with important implications for humans, and new advances in the zebra fish toolbox will allow other aspects of HSC behavior to be investigated as well, including migration, homing, and engraftment.

  13. Systemic inflammation regulates microglial responses to tissue damage in vivo

    Science.gov (United States)

    Gyoneva, Stefka; Davalos, Dimitrios; Biswas, Dipankar; Swanger, Sharon A.; Garnier-Amblard, Ethel; Loth, Francis; Akassoglou, Katerina; Traynelis, Stephen F.

    2015-01-01

    Microglia, the resident immune cells of the central nervous system, exist in either a “resting” state associated with physiological tissue surveillance or an “activated” state in neuroinflammation. We recently showed that ATP is the primary chemoattractor to tissue damage in vivo and elicits opposite effects on the motility of activated microglia in vitro through activation of adenosine A2A receptors. However, whether systemic inflammation affects microglial responses to tissue damage in vivo remains largely unknown. Using in vivo two-photon imaging of mice, we show that injection of lipopolysaccharide (LPS) at levels that can produce both clear neuroinflammation and some features of sepsis significantly reduced the rate of microglial response to laser-induced ablation injury in vivo. Under pro-inflammatory conditions, microglial processes initially retracted from the ablation site, but subsequently moved toward and engulfed the damaged area. Analyzing the process dynamics in 3D cultures of primary microglia indicated that only A2A, but not A1 or A3 receptors, mediate process retraction in LPS-activated microglia. The A2A receptor antagonists caffeine and preladenant reduced adenosine-mediated process retraction in activated microglia in vitro. Finally, administration of preladenant before induction of laser ablation in vivo accelerated the microglial response to injury following systemic inflammation. The regulation of rapid microglial responses to sites of injury by A2A receptors could have implications for their ability to respond to the neuronal death occurring under conditions of neuroinflammation in neurodegenerative disorders. PMID:24807189

  14. Stabilization and set-point regulation of underactuated mechanical systems

    Science.gov (United States)

    Loccufier, Mia

    2016-09-01

    Mechanical systems are referred to as underactuated if the number of independent actuators are fewer than the number of degrees of freedom, a general encountered problem in engineering applications. The considered mechanical systems belong to the class of Euler- Lagrange systems where both kinetic energy and potential energy are modeled in their most general form and energy dissipation is modeled according to the dissipation function of Rayleigh, i.e. viscous damping forces are assumed. The control objectives are stabilization and set-point regulation. The structure of the controller is a parallel combination of static output feedback with dynamic output feedback where nonlinear amplifiers are included. An energy based approach with Liapunov functions and the Kalman-Yacubovich-Popov main lemma yields alternative stability theorems. A number of conditions are introduced with respect to the controller's structure in order to guarantee stability. However, sufficient design freedom is left to choose a proper tuning principle and obtain the specified control objectives such as fast convergence to a set-point combined with disturbance rejection. A restriction on the control input energy can be incorporated as well. The applicability of the method will be illustrated with planar manipulators. The main contribution is that a methodology is developed which incorporates many controllers and tuning facilities.

  15. CRISPR-Cas systems for editing, regulating and targeting genomes.

    Science.gov (United States)

    Sander, Jeffry D; Joung, J Keith

    2014-04-01

    Targeted genome editing using engineered nucleases has rapidly gone from being a niche technology to a mainstream method used by many biological researchers. This widespread adoption has been largely fueled by the emergence of the clustered, regularly interspaced, short palindromic repeat (CRISPR) technology, an important new approach for generating RNA-guided nucleases, such as Cas9, with customizable specificities. Genome editing mediated by these nucleases has been used to rapidly, easily and efficiently modify endogenous genes in a wide variety of biomedically important cell types and in organisms that have traditionally been challenging to manipulate genetically. Furthermore, a modified version of the CRISPR-Cas9 system has been developed to recruit heterologous domains that can regulate endogenous gene expression or label specific genomic loci in living cells. Although the genome-wide specificities of CRISPR-Cas9 systems remain to be fully defined, the power of these systems to perform targeted, highly efficient alterations of genome sequence and gene expression will undoubtedly transform biological research and spur the development of novel molecular therapeutics for human disease.

  16. Regulation of autonomic nervous system in space and magnetic storms

    Science.gov (United States)

    Baevsky, R. M.; Petrov, V. M.; Chernikova, A. G.

    Variations in the earth's magnetic field and magnetic storms are known to be a risk factor for the development of cardiovascular disorders. The main ``targets'' for geomagnetic perturbations are the central nervous system and the neural regulation of vascular tone and heart rate variability. This paper presents the data about effect of geomagnetic fluctuations on human body in space. As a method for research the analysis of heart rate variability was used, which allows evaluating the state of the sympathetic and parasympathetic parts of the autonomic nervous system, vasomotor center and subcortical neural centers activity. Heart rate variability data were analyzed for 30 cosmonauts at the 2-nd day of space flight on transport spaceship Soyuz (32nd orbit). There were formed three groups of cosmonauts: without magnetic storm (n=9), on a day with magnetic storm (n=12) and 1-2 days after magnetic storm (n=9). The present study was the first to demonstrate a specific impact of geomagnetic perturbations on the system of autonomic circulatory control in cosmonauts during space flight. The increasing of highest nervous centers activity was shown for group with magnetic storms, which was more significant on 1-2 days after magnetic storm. The use of discriminate analysis allowed to classify indicated three groups with 88 % precision. Canonical variables are suggested to be used as criterions for evaluation of specific and non-specific components of cardiovascular reactions to geomagnetic perturbations. The applied aspect of the findings from the present study should be emphasized. They show, in particular, the need to supplement the medical monitoring of cosmonauts with predictions of probable geomagnetic perturbations in view of the prevention of unfavorable states appearances if the adverse reactions to geomagnetic perturbations are added to the tension experienced by regulatory systems during various stresses situations (such as work in the open space).

  17. 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

  18. 75 FR 65439 - Defense Federal Acquisition Regulation Supplement; Electronic Subcontracting Reporting System

    Science.gov (United States)

    2010-10-25

    ...-602-0350. Mail: Defense Acquisition Regulations System, Attn: Ms. Cassandra R. Freeman, OUSD (AT&L... be posted to http://www.regulations.gov . FOR FURTHER INFORMATION CONTACT: Ms. Cassandra R. Freeman... procurement. Clare M. Zebrowski, Editor, Defense Acquisition Regulations System. 0 Therefore, 48 CFR parts 219...

  19. 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...

  20. Mechanisms regulating caste differentiation in an aphid social system.

    Science.gov (United States)

    Shibao, Harunobu; Kutsukake, Mayako; Matsuyama, Shigeru; Fukatsu, Takema; Shimada, Masakazu

    2010-01-01

    For evolution and maintenance of the social systems of insect colonies, caste production should be controlled in response to external cues so that caste ratio in the colony is kept at an optimal range. Recent developments using artificial diet rearing techniques have revealed an underlying mechanism for adaptive control of caste production in a social aphid, Tuberaphis styraci, which has a sterile soldier caste in the 2(nd) instar. Aphid density was the proximate cue that acts on 1(st) instar nymphs and embryos to induce soldier differentiation. The final determination of soldier differentiation occurred postnatally, probably at a late 1(st) instar stage. Direct contact stimuli from live non-soldier aphids mediated the density effect. While coexisting non-soldiers facilitated soldier differentiation in 1(st) instar nymphs, coexisting soldiers acted to suppress such differentiation. These results suggest that caste production in aphid colonies is controlled by positive and negative feedback mechanisms consisting of density-dependent induction and suppression of soldier differentiation. Here, we demonstrate the mechanisms that coordinate aphid society, and provide a striking case of clonal superorganism system where simple responses of colony members to local extrinsic stimuli are integrated into a highly organized regulation of the whole colony.

  1. Self Regulated Shocks in Massive Star Binary Systems

    CERN Document Server

    Parkin, E R

    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, LX 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 m...

  2. Systemic regulation of soybean nodulation by acidic growth conditions.

    Science.gov (United States)

    Lin, Meng-Han; Gresshoff, Peter M; Ferguson, Brett J

    2012-12-01

    Mechanisms inhibiting legume nodulation by low soil pH, although highly prevalent and economically significant, are poorly understood. We addressed this in soybean (Glycine max) using a combination of physiological and genetic approaches. Split-root and grafting studies using an autoregulation-of-nodulation-deficient mutant line, altered in the autoregulation-of-nodulation receptor kinase GmNARK, determined that a systemic, shoot-controlled, and GmNARK-dependent mechanism was critical for facilitating the inhibitory effect. Acid inhibition was independent of aluminum ion concentration and occurred early in nodule development, between 12 and 96 h post inoculation with Bradyrhizobium japonicum. Biological effects were confirmed by measuring transcript numbers of known early nodulation genes. Transcripts decreased on both sides of split-root systems, where only one side was subjected to low-pH conditions. Our findings enhance the present understanding of the innate mechanisms regulating legume nodulation control under acidic conditions, which could benefit future attempts in agriculture to improve nodule development and biological nitrogen fixation in acid-stressed soils.

  3. Regulation of the Yersinia type III secretion system: traffic control

    Science.gov (United States)

    Dewoody, Rebecca S.; Merritt, Peter M.; Marketon, Melanie M.

    2013-01-01

    Yersinia species, as well as many other Gram-negative pathogens, use a type III secretion system (T3SS) to translocate effector proteins from the bacterial cytoplasm to the host cytosol. This T3SS resembles a molecular syringe, with a needle-like shaft connected to a basal body structure, which spans the inner and outer bacterial membranes. The basal body of the injectisome shares a high degree of homology with the bacterial flagellum. Extending from the T3SS basal body is the needle, which is a polymer of a single protein, YscF. The distal end of the needle serves as a platform for the assembly of a tip complex composed of LcrV. Though never directly observed, prevailing models assume that LcrV assists in the insertion of the pore-forming proteins YopB and YopD into the host cell membrane. This completes a bridge between the bacterium and host cell to provide a continuous channel through which effectors are delivered. Significant effort has gone into understanding how the T3SS is assembled, how its substrates are recognized and how substrate delivery is controlled. Arguably the latter topic is the least understood; however, recent advances have provided new insight, and therefore, this review will focus primarily on summarizing the current state of knowledge regarding the control of substrate delivery by the T3SS. Specifically, we will discuss the roles of YopK, as well as YopN and YopE, which have long been linked to regulation of translocation. We also propose models whereby the YopK regulator communicates with the basal body of the T3SS to control translocation. PMID:23390616

  4. 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... DEVICES Immunological Test Systems § 866.5900 Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation detection system. (a) Identification. The CFTR gene mutation detection system is a...

  5. New Results on the Output Regulation of the Modified Arneodo Chaotic System by State Feedback Control

    National Research Council Canada - National Science Library

    Sundarapandian Vaidyanathan

    2011-01-01

    ...).Explicitly, new state feedback control laws regulating the output of the modified Arneodo chaotic systemhave been derived so as to regulate the output of the modified Arneodo chaotic system have been...

  6. Monocytes regulate systemic coagulation and inflammation in abdominal sepsis.

    Science.gov (United States)

    Wang, Yongzhi; Braun, Oscar Ö; Zhang, Su; Norström, Eva; Thorlacius, Henrik

    2015-03-01

    Abdominal sepsis is associated with significant changes in systemic inflammation and coagulation. The purpose of the present study was to examine the role of peripheral blood monocytes for systemic coagulation, including thrombin generation and consumption of coagulation factors. Abdominal sepsis was induced by cecal ligation and puncture (CLP) in C57BL/6 mice. Plasma and lung levels of IL-6 and C-X-C motif (CXC) chemokines [chemokine CXC ligand (CXCL)1, CXCL2, and CXCL5], pulmonary activity of myeloperoxidase, thrombin generation, and coagulation factors were determined 6 h after CLP induction. Administration of clodronate liposomes decreased circulating levels of monocytes by 96%. Time to peak thrombin formation was increased and peak and total thrombin generation was decreased in plasma from CLP animals. Monocyte depletion decreased time to peak formation of thrombin and increased peak and total generation of thrombin in septic animals. In addition, monocyte depletion decreased the CLP-induced increase in the levels of thrombin-antithrombin complexes in plasma. Depletion of monocytes increased plasma levels of prothrombin, factor V, factor X, and protein C in septic mice. Moreover, depletion of monocytes decreased CLP-induced levels of IL-6 and CXC chemokines in the plasma and lung by >59% and 20%, respectively. CLP-induced myeloperoxidase activity in the lung was attenuated by 44% in animals depleted of monocytes. Taken together, our findings show, for the first time, that peripheral blood monocytes regulate systemic coagulation. The results of our study improve our understanding of the pathophysiology of sepsis and encourage further attempts to target innate immune cell functions in abdominal sepsis.

  7. Output tracking and regulation of nonlinear system based on Takagi-Sugeno fuzzy model.

    Science.gov (United States)

    Ma, X J; Sun, Z Q

    2000-01-01

    On the basis of the Takagi-Sugeno (TS) fuzzy model, this paper discusses in detail the following three problems: (1) output tracking of the nonlinear system; (2) output regulation of the nonlinear system via a state feedback; (3) output regulation of the nonlinear system via a error feedback. Numerical simulations are given to illustrate the soundness of these results and the effectiveness of the new methodology solving the output tracking and regulation problem of the nonlinear system.

  8. 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.

  9. A processed noncoding RNA regulates an altruistic bacterial antiviral system.

    Science.gov (United States)

    Blower, Tim R; Pei, Xue Y; Short, Francesca L; Fineran, Peter C; Humphreys, David P; Luisi, Ben F; Salmond, George P C

    2011-02-01

    The ≥ 10³⁰ bacteriophages on Earth relentlessly drive adaptive coevolution, forcing the generation of protective mechanisms in their bacterial hosts. One such bacterial phage-resistance system, ToxIN, consists of a protein toxin (ToxN) that is inhibited in vivo by a specific RNA antitoxin (ToxI); however, the mechanisms for this toxicity and inhibition have not been defined. Here we present the crystal structure of the ToxN-ToxI complex from Pectobacterium atrosepticum, determined to 2.75-Å resolution. ToxI is a 36-nucleotide noncoding RNA pseudoknot, and three ToxI monomers bind to three ToxN monomers to generate a trimeric ToxN-ToxI complex. Assembly of this complex is mediated entirely through extensive RNA-protein interactions. Furthermore, a 2'-3' cyclic phosphate at the 3' end of ToxI, and catalytic residues, identify ToxN as an endoRNase that processes ToxI from a repetitive precursor but is regulated by its own catalytic product.

  10. 77 FR 51783 - Federal Acquisition Regulation; Information Collection; Contractors' Purchasing Systems Reviews

    Science.gov (United States)

    2012-08-27

    ... Regulation; Information Collection; Contractors' Purchasing Systems Reviews AGENCY: Department of Defense... previously approved information collection requirement concerning contractors' purchasing systems reviews...: Submit comments identified by Information Collection 9000- 0132, Contractors' Purchasing Systems Reviews...

  11. 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.

  12. Optimal Regulation of Structural Systems with Uncertain Parameters.

    Science.gov (United States)

    1981-02-02

    0, of the associated deterministic plant regulation problem . Then, within the above restrictions, the problem is to determine a K (such that K is real...deterministic plant regulation problem we here obtain the stronger assurance of second moment stability. This is indirectly a consequence of the use of

  13. 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…

  14. 76 FR 4001 - Foreign Trade Regulations (FTR): Mandatory Automated Export System Filing for All Shipments...

    Science.gov (United States)

    2011-01-21

    ... Commerce Census Bureau 15 CFR Part 30 Foreign Trade Regulations (FTR): Mandatory Automated Export System... Foreign Trade Regulations (FTR): Mandatory Automated Export System Filing for All Shipments Requiring... Automated Export System (AES) or through AESDirect for all shipments of used self-propelled...

  15. 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.

  16. The Semiconductor Self-Excitation System of Synchronous Generator with Fuzzy Voltage Regulator

    Directory of Open Access Journals (Sweden)

    Kutsyk, А.S.

    2014-05-01

    Full Text Available The synchronous generator’s voltage control system with the synthesized fuzzy voltage regulator is described. The synthesis of the regulator is carried out with the use of mathematical model taking into account the nonlinearity of synchronous machines and semiconductor converters in the e xcitation system. This distinguishes it from traditional excitation regulators, whose synthesis is based on the use of simplified linearized models. The mathematical modeling results allow to compare the control characteristics in the system with the proposed fuzzy voltage regulator and in the system with a traditional voltage controller.

  17. Regulation and controlled synchronization for complex dynamical systems

    NARCIS (Netherlands)

    Huijberts, H.J.C.; Nijmeijer, Henk; Willems, R.M.A.

    2000-01-01

    In this paper we investigate the problem of controlled synchronization as a regulator problem. In controlled synchronization one is given autonomous transmitter dynamics and controlled receiver dynamics. The question is to find a (output) feedback controller that achieves matching between

  18. [Role of histaminergic system in the regulation of nutrition].

    Science.gov (United States)

    Khanfer'ian, R A; Mil'chenko, N O; Solntseva, T N; Gabueva, Zh V; Radzhabkadiev, R M

    2013-01-01

    In the review modern data on a role of various humoral factors (neuromediators, hormones, adipocytokines etc.) in regulation of appetite, food consumption and obesity are presented. The special attention is paid to the role of histamine and histamine receptors of H3-type in processes of regulation of a food intake. Interaction of various humoral factors is discussed at obesity and other alimentary-dependent diseases.

  19. 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.

  20. 75 FR 32635 - Defense Acquisition Regulations System; Defense Federal Acquisition Regulation Supplement...

    Science.gov (United States)

    2010-06-08

    ... Regulation Supplement; Balance of Payments Program Exemption for Commercial Information Technology... implement in the clauses at 252.225-7044, Balance of Payments Program--Construction Material, and 252.225-7045, Balance of Payments Program--Construction Material under Trade Agreements, the exemption from...

  1. Output Regulation in Discrete-Time Switched Bimodal Systems Based on Youla Parameterized Stabilizing Controllers

    Directory of Open Access Journals (Sweden)

    Zhizheng Wu

    2012-01-01

    Full Text Available Motivated by a class of contact vibration control problems in mechanical systems, this paper considers a regulation problem for discrete-time switched bimodal linear systems where it is desired to achieve output regulation against partially known deterministic and unknown random exogenous signals. First, a set of observer-based Youla parameterized stabilizing controllers is constructed, based on which the regulation conditions for the switched system against the deterministic signals along with an H2 performance constraint against the unknown random signals are derived. Then a corresponding regulator synthesis algorithm is developed based on solving properly formulated linear matrix inequalities. The proposed regulator is successfully evaluated on an experimental setup involving a switched bimodal mechanical system subject to contact vibrations, hence, demonstrating the effectiveness of the proposed regulation approach.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  3. Methods, systems and apparatus for synchronous current regulation of a five-phase machine

    Science.gov (United States)

    Gallegos-Lopez, Gabriel; Perisic, Milun

    2012-10-09

    Methods, systems and apparatus are provided for controlling operation of and regulating current provided to a five-phase machine when one or more phases has experienced a fault or has failed. In one implementation, the disclosed embodiments can be used to synchronously regulate current in a vector controlled motor drive system that includes a five-phase AC machine, a five-phase inverter module coupled to the five-phase AC machine, and a synchronous current regulator.

  4. System and method for regulating EGR cooling using a Rankine cycle

    Energy Technology Data Exchange (ETDEWEB)

    Ernst, Timothy C.; Morris, Dave

    2017-08-29

    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.

  5. Self-regulating control of parasitic loads in a fuel cell power system

    Science.gov (United States)

    Vasquez, Arturo (Inventor)

    2011-01-01

    A fuel cell power system comprises an internal or self-regulating control of a system or device requiring a parasitic load. The internal or self-regulating control utilizes certain components and an interconnection scheme to produce a desirable, variable voltage potential (i.e., power) to a system or device requiring parasitic load in response to varying operating conditions or requirements of an external load that is connected to a primary fuel cell stack of the system. Other embodiments comprise a method of designing such a self-regulated control scheme and a method of operating such a fuel cell power system.

  6. Therapeutic regulation of systemic inflammation in xenograft recipients.

    Science.gov (United States)

    Iwase, Hayato; Liu, Hong; Li, Tao; Zhang, Zhongquiang; Gao, Bingsi; Hara, Hidetaka; Wijkstrom, Martin; Long, Cassandra; Saari, Ryan; Ayares, David; Cooper, David K C; Ezzelarab, Mohamed B

    2017-03-01

    . After AAT, IL-8 was elevated. sCD40L became elevated intermittently in most recipients irrespective of the administered anti-inflammatory agent. In Group2, IL-6 was transiently elevated, particularly after IL-6RA administration. MCP-1 gradually increased by 2 months in Group2 recipients. sCD40L generally remained low except in one recipient. In Group1 and Group2 recipients, C-RP levels were elevated except after IL-6RA administration, while D-dimers were elevated regardless of administration of anti-inflammatory agent. In Group2, pig TF mRNA levels were increased in heart xenografts compared to naive pig hearts, irrespective of IL-6 receptor antagonist administration. Additionally, baboon TF mRNA levels were detectable in heart xenografts, but not in naive pig hearts. Some pro-inflammatory cytokines and chemokines are elevated in xenograft recipients, even with efficient T cell-directed immunosuppressive therapy. Persistent elevation of D-dimers, and individual cytokines and chemokines suggest a continuous inflammatory response, despite administration of anti-inflammatory agents. Systemic administration of combined anti-inflammatory agents as well as complement regulation may be essential to prevent SIXR after xenotransplantation. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. The research of power saving frequency conversion speed regulation experiment system

    Institute of Scientific and Technical Information of China (English)

    ZHONG Wei-tang

    2008-01-01

    A power saving frequency difference controlling method was introduced by the double inverter and motor experiment system. The characters of the system under differ-ent loads were investigated. The theoretical analysis and experiment results show the frequency difference method is a ideal power saving speed regulation method for the dou-ble inverter and motor system. The experiment system is simply structured, convenient to operate and provides a new way of character testing for frequency conversion speed regulation.

  8. 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.

  9. 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.

  10. 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.

  11. Regulation of Neurotransmitter Responses in the Central Nervous System

    Science.gov (United States)

    1990-02-05

    accordance with DoD 5200.1 -R, Information Security Program Regulation. Chapter V1 Section 2, V"-apaph 4-200. clasification markings are to be stamped...through pharmacologically distinct reports. Finally, the augmenting response does not appear to be mediated through protein kinase C. However, BAC...may facilitate second messenger production by altering the coupling of catecholamine receptor to C- proteins involved in the cAMP cascade. (( ( CONTRACT

  12. The Cpx System Regulates Virulence Gene Expression in Vibrio cholerae

    Science.gov (United States)

    Acosta, Nicole; Pukatzki, Stefan

    2015-01-01

    Bacteria possess signal transduction pathways capable of sensing and responding to a wide variety of signals. The Cpx envelope stress response, composed of the sensor histidine kinase CpxA and the response regulator CpxR, senses and mediates adaptation to insults to the bacterial envelope. The Cpx response has been implicated in the regulation of a number of envelope-localized virulence determinants across bacterial species. Here, we show that activation of the Cpx pathway in Vibrio cholerae El Tor strain C6706 leads to a decrease in expression of the major virulence factors in this organism, cholera toxin (CT) and the toxin-coregulated pilus (TCP). Our results indicate that this occurs through the repression of production of the ToxT regulator and an additional upstream transcription factor, TcpP. The effect of the Cpx response on CT and TCP expression is mostly abrogated in a cyclic AMP receptor protein (CRP) mutant, although expression of the crp gene is unaltered. Since TcpP production is controlled by CRP, our data suggest a model whereby the Cpx response affects CRP function, which leads to diminished TcpP, ToxT, CT, and TCP production. PMID:25824837

  13. Gene regulation in the magnocellular hypothalamo-neurohypophysial system

    NARCIS (Netherlands)

    Burbach, JPH; Luckman, SM; Murphy, D; Gainer, H

    2001-01-01

    The hypothalamo-neurohypophysial system (HNS) is the major peptidergic neurosecretory system through which the brain controls peripheral physiology. The hormones vasopressin and oxytocin released from the HNS at the neurohypophysis serve homeostatic functions of water balance and reproduction. From

  14. NF1 Is an Effector and Regulator of the GPCR Signaling in the Nervous System

    Science.gov (United States)

    2015-04-01

    1 AD______________ AWARD NUMBER: W81XWH-14-1-0074 TITLE: “NF1 Is an Effector and Regulator of the GPCR Signaling in the Nervous System ...NF1 Is an Effector and Regulator of the GPCR Signaling in the Nervous System 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Kirill Martemyanov, Ph.D...strategies. 15. SUBJECT TERMS neurofibromatosis, nervous system disorders, receptor signaling mechanisms, NF1 16. SECURITY CLASSIFICATION OF: 17

  15. 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.

  16. Neural-network-based approximate output regulation of discrete-time nonlinear systems.

    Science.gov (United States)

    Lan, Weiyao; Huang, Jie

    2007-07-01

    The existing approaches to the discrete-time nonlinear output regulation problem rely on the offline solution of a set of mixed nonlinear functional equations known as discrete regulator equations. For complex nonlinear systems, it is difficult to solve the discrete regulator equations even approximately. Moreover, for systems with uncertainty, these approaches cannot offer a reliable solution. By combining the approximation capability of the feedforward neural networks (NNs) with an online parameter optimization mechanism, we develop an approach to solving the discrete nonlinear output regulation problem without solving the discrete regulator equations explicitly. The approach of this paper can be viewed as a discrete counterpart of our previous paper on approximately solving the continuous-time nonlinear output regulation problem.

  17. Power fluctuations smoothing and regulations in wind turbine generator systems

    Science.gov (United States)

    Babazadehrokni, Hamed

    Wind is one of the most popular renewable energy sources and it has the potential to become the biggest energy source in future. Since the wind does not always blow constantly, the output wind power is not constant which may make some problem for the power grid. According to the grid code which is set by independent system operator, ISO, wind turbine generator systems need to follow some standards such as the predetermined acceptable power fluctuations. In order to smooth the output powers, the energy storage system and some power electronics modules are employed. The utilized power electronics modules in the wind turbine system can pursue many different goals, such as maintaining the voltage stability, frequency stability, providing the available and predetermined output active and reactive power. On the other side, the energy storage system can help achieving some of these goals but its main job is to store the extra energy when not needed and release the stored energy when needed. The energy storage system can be designed in different sizes, material and also combination of different energy storage systems (hybrid designs). Combination of power electronics devises and also energy storage system helps the wind turbine systems to smooth the output power according to the provided standards. In addition prediction of wind speed may improve the performance of wind turbine generator systems. In this research study all these three topics are studied and the obtained results are written in 10 papers which 7 of them are published and three of them are under process.

  18. The spleen in local and systemic regulation of immunity.

    Science.gov (United States)

    Bronte, Vincenzo; Pittet, Mikael J

    2013-11-14

    The spleen is the main filter for blood-borne pathogens and antigens, as well as a key organ for iron metabolism and erythrocyte homeostasis. Also, immune and hematopoietic functions have been recently unveiled for the mouse spleen, suggesting additional roles for this secondary lymphoid organ. Here we discuss the integration of the spleen in the regulation of immune responses locally and in the whole body and present the relevance of findings for our understanding of inflammatory and degenerative diseases and their treatments. We consider whether equivalent activities in humans are known, as well as initial therapeutic attempts to target the spleen for modulating innate and adaptive immunity.

  19. 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.

  20. GABA Regulates Stem Cell Proliferation before Nervous System Formation.

    OpenAIRE

    Wang, Doris,; Kriegstein, Arnold; Ben-Ari, Yehezkel

    2008-01-01

    International audience; HISTONE H2AX-DEPENDENT GABAA RECEPTOR REGULATION OF STEM CELL PROLIFERATION: Andäng M, Hjerling-Leffler J, Moliner A, Lundgren TK, Castelo-Branco G, Nanou E, Pozas E, Bryja V, Halliez S, Nishimaru H, Wilbertz J, Arenas E, Koltzenburg M, Charnay P, El Manira A, Ibañez CF, Ernfors P. Nature20084517177:460-46418185516 Stem cell self-renewal implies proliferation under continued maintenance of multipotency. Small changes in numbers of stem cells may lead to large differenc...

  1. 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.

  2. Isotopic insights into biological regulation of zinc in contaminated systems

    Science.gov (United States)

    Wanty, Richard B.; Balistrieri, Laurie S.; Wesner, Jeff S.; Walters, David; Schmidt, Travis S.; Podda, Francesca; De Giudici, G.; Stricker, Craig A.; Kraus, Johanna M.; Lattanzi, Pierfranco; Wolf, Ruth E.; Cidu, R.

    2015-01-01

    Aquatic organisms use a variety of biogeochemical reactions to regulate essential and non-essential trace metals. Many of these mechanisms can lead to isotopic fractionation, thus measurement of metal isotopes may yield insights into the processes by which organisms respond to metal exposure. We illustrate these concepts with two case studies, one involving an intra- and the other an extra-cellular mechanism of Zn sequestration. In the first study, the mayfly Neocloeon triangulifer was grown in the laboratory, and fed a diet of Zn-doped diatoms at Zn levels exceeding the requirements for normal mayfly life functions. The N. triangulifer larvae consumed the diatoms and retained their Zn isotopic signature. Upon metamorphosis, the subimago life stage lost Zn mass either in the exuvia or by excretion, and the Zn retained was isotopically enriched. Thus, Zn uptake is nonfractionating, but Zn regulation favors the lighter isotope. Thus the Zn remaining in the subimago was isotopically heavier. In the second study, Zn was adsorbed on the cell walls and exopolysaccharide secretions of cyanobacteria, which favored the heavier Zn isotope. Continued adsorption eventually resulted in nucleation and biomineralization of hydrozincite {Zn5(CO3)2(OH)6}. These case studies demonstrate the utility of Zn isotopes to provide insights into how aquatic insects respond to metal exposure.

  3. Robust decentralized output regulation for uncertain heterogeneous systems

    NARCIS (Netherlands)

    Persis, Claudio De; Liu, Hui; Cao, Ming

    2012-01-01

    We consider the problem in which N heterogeneous uncertain linear systems aim at tracking a reference signal generated by a given exosystem under the restriction that not all the systems are directly connected to the exosystem. To tackle this problem, the reference signal is reconstructed via local

  4. 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

  5. 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…

  6. 75 FR 25165 - Defense Federal Acquisition Regulation Supplement; Cost and Software Data Reporting System

    Science.gov (United States)

    2010-05-07

    ... reporting requirements that are essential for the DoD to estimate the cost of current and future weapon... and not cost allocations. The description will also show how the data from the offeror's accounting... Regulation Supplement; Cost and Software Data Reporting System AGENCY: Defense Acquisition Regulations...

  7. 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…

  8. Atrophy, hypertrophy, and hypoxemia induce transcriptional regulators of the ubiquitin proteasome system in the rat heart

    Science.gov (United States)

    In skeletal muscle, transcript levels of proteins regulating the ubiquitin proteasome system (UPS) increase with atrophy and decrease with hypertrophy. Whether the same is true for heart muscle is not known. We set out to characterize the transcriptional profile of regulators of the UPS during atrop...

  9. 75 FR 41097 - Homeland Security Acquisition Regulation; Lead System Integrators [HSAR Case 2009-003

    Science.gov (United States)

    2010-07-15

    ...The Department of Homeland Security (DHS) is issuing an interim rule amending the Homeland Security Acquisition Regulation (HSAR) to implement section 6405 of the U.S. Troop Readiness, Veterans' Care, Katrina Recovery, and Iraq Accountability Appropriations Act, 2007. This section of the Act and these implementing regulations restrict contractors from acting as lead system integrators in the......

  10. 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.

  11. [Establishment of a novel biotin-inducible eukaryotic gene regulation system].

    Science.gov (United States)

    Ye, Lingling; Hong, Liu; Li, Shichong; Wang, Qiwei; Lan, Sanchun; Chen, Zhaolie

    2014-08-01

    To establish a gene regulation system compatible with biopharmaceutical industry and gene therapy, we constructed a fusion protein of biotin ligase from Bacillus subtilis (BS-BirA) and the trans-activation domain, and used its expression vector as the regulatory vector. Meanwhile, BS-BirA-specific operators were ligated upstream of attenuated CMV promoter to obtain the response vector. In this way, a novel eukaryotic gene regulation system responsive to biotin was established and named BS-Biotin-On system. BS-Biotin-On system was further investigated with the enhancing green fluorescent protein (EGFP) as the reporter gene. The results showed that our system was superior to the current similar regulation system in its higher induction ratio, and that the expression of interest gene could be tuned in a rapid and efficient manner by changing the biotin concentrations in the cultures, Our results show that the established system may provide a new alternative for the exogenous gene modulation.

  12. 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.

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

    Science.gov (United States)

    Sagar, Devi Rani; Gaw, A Gemma; Okine, Bright N; Woodhams, Stephen G; Wong, Amy; Kendall, David A; Chapman, Victoria

    2009-10-08

    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.

  14. Regulation of systemic energy homeostasis by serotonin in adipose tissues.

    Science.gov (United States)

    Oh, Chang-Myung; Namkung, Jun; Go, Younghoon; Shong, Ko Eun; Kim, Kyuho; Kim, Hyeongseok; Park, Bo-Yoon; Lee, Ho Won; Jeon, Yong Hyun; Song, Junghan; Shong, Minho; Yadav, Vijay K; Karsenty, Gerard; Kajimura, Shingo; Lee, In-Kyu; Park, Sangkyu; Kim, Hail

    2015-04-13

    Central serotonin (5-HT) is an anorexigenic neurotransmitter in the brain. However, accumulating evidence suggests peripheral 5-HT may affect organismal energy homeostasis. Here we show 5-HT regulates white and brown adipose tissue function. Pharmacological inhibition of 5-HT synthesis leads to inhibition of lipogenesis in epididymal white adipose tissue (WAT), induction of browning in inguinal WAT and activation of adaptive thermogenesis in brown adipose tissue (BAT). Mice with inducible Tph1 KO in adipose tissues exhibit a similar phenotype as mice in which 5-HT synthesis is inhibited pharmacologically, suggesting 5-HT has localized effects on adipose tissues. In addition, Htr3a KO mice exhibit increased energy expenditure and reduced weight gain when fed a high-fat diet. Treatment with an Htr2a antagonist reduces lipid accumulation in 3T3-L1 adipocytes. These data suggest important roles for adipocyte-derived 5-HT in controlling energy homeostasis.

  15. 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...

  16. Is erythroferrone finally the long sought-after systemic erythroid regulator of iron?

    Institute of Scientific and Technical Information of China (English)

    Alfons; Lawen

    2015-01-01

    Iron metabolism is regulated on the cellular and the systemic level. Over the last decade, the liver peptide "hepcidin" has emerged as the body’s key irons store regulator. The long postulated "erythroid regulator of iron", however, remained elusive. Last year, evidence was provided, that a previously described myokine "myonectin" may also function as the long sought erythroid regulator of iron. Myonectin was therefore renamed "erythroferrone". This editorial provides a brief discussion on the two functions of erythroferrone and also briefly considers the emerging potential role of transferrin receptor 2 in erythropoiesis.

  17. Fragmentation and flow regulation of the world's large river systems.

    Science.gov (United States)

    Nilsson, Christer; Reidy, Catherine A; Dynesius, Mats; Revenga, Carmen

    2005-04-15

    A global overview of dam-based impacts on large river systems shows that over half (172 out of 292) are affected by dams, including the eight most biogeographically diverse. Dam-impacted catchments experience higher irrigation pressure and about 25 times more economic activity per unit of water than do unaffected catchments. In view of projected changes in climate and water resource use, these findings can be used to identify ecological risks associated with further impacts on large river systems.

  18. 75 FR 391 - Medical Device Quality System Regulation Educational Forum on Risk Management Through the Product...

    Science.gov (United States)

    2010-01-05

    ... Through the Product Life Cycle; Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice... System Regulation Educational Forum on Risk Management through the Product Life Cycle.'' This public...

  19. 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......The large grid integration of variable wind power adds to the imbalance of a power system. This necessitates the need for additional reserve power for regulation. In Denmark, the growing wind penetration aims for an expedited change of displacing the traditional generators which are currently...... simulations is modelled. Further, it is analysed for regulation services using the case of a typical windy day in the West Denmark power system. The power deviations with other control areas in an interconnected system are minimised by the faster up and down regulation characteristics of the EV battery...

  20. New clues on the regulation of the CRISPR-Cas immune system.

    Science.gov (United States)

    Lundgren, Magnus

    2015-01-01

    Research into the CRISPR-Cas immune system of prokaryotes is progressing at a tremendous pace given both its important biological function and its role as a source of new genetic tools. However, a few areas of the field have remained largely unaddressed. A recent report provides information on one such overlooked area: how the cell regulates the CRISPR-Cas immune system. The processes, despite their importance, have remained illusive. In Pectobacterium atrosepticum regulation is, perhaps surprisingly, based on metabolic factors responding to glucose levels in the cell. Regulators include both activators and repressors of cas gene expression. It remains an open question why and how this regulatory system have evolved, and if it is a typical example of how CRISPR-as systems are regulated or not.

  1. 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.

  2. 75 FR 6669 - Federal Acquisition Regulation; Submission for OMB Review; Contractors' Purchasing Systems Reviews

    Science.gov (United States)

    2010-02-10

    ... contractors' purchasing systems reviews. A request for public comments was published in the Federal Register....cundiff@gsa.gov . SUPPLEMENTARY INFORMATION: A. Purpose The objective of a contractor purchasing system... Regulation; Submission for OMB Review; Contractors' Purchasing Systems Reviews AGENCIES: Department of...

  3. 77 FR 11355 - Defense Federal Acquisition Regulation Supplement; Business Systems-Definition and Administration...

    Science.gov (United States)

    2012-02-24

    ... Defense Federal Acquisition Regulation Supplement; Business Systems--Definition and Administration (DFARS... proposed rule for Business Systems-- Definition and Administration (DFARS Case 2009-D038) in the Federal... contractor business systems, DoD has clarified the definition and administration of contractor...

  4. 75 FR 75549 - Defense Federal Acquisition Regulation Supplement; Business Systems-Definition and Administration...

    Science.gov (United States)

    2010-12-03

    ... Acquisition Regulation Supplement; Business Systems-- Definition and Administration (DFARS Case 2009-D038...D published a proposed rule for Business Systems--Definition and Administration (DFARS Case 2009... contractor business systems, DoD is considering a rule to clarify the definition and administration...

  5. 78 FR 28756 - Defense Federal Acquisition Regulation Supplement: System for Award Management Name Changes...

    Science.gov (United States)

    2013-05-16

    ... 0750-AH87 Defense Federal Acquisition Regulation Supplement: System for Award Management Name Changes... System (EPLS) databases into the System for Award Management (SAM) database. DATES: Effective Date: May... effort to improve the management and promotion of electronic Government services and processes. The Act...

  6. To eat or not to eat; regulation by the melanocortin system

    NARCIS (Netherlands)

    Hillebrand, Jacquelien J G; Kas, Martien J H; Adan, Roger A H

    2006-01-01

    The central melanocortin (MC) system is one of the best-characterized neuropeptidergic systems involved in the regulation of energy balance. This short review describes the role of the central MC system in feeding behavior. Pharmacological, anatomical and genetic studies show that activation of the

  7. Output regulation for a class of uncertain nonlinear systems with nonlinear exosystems and its application

    Institute of Scientific and Technical Information of China (English)

    SUN WeiJie; HUANG Jie

    2009-01-01

    In this paper,we consider the global robust output regulation problem for a class of uncertain nonlinear systems with nonlinear exosystems.By employing the internal model approach,we show that this problem boils down to a global robust stabilization problem of a time-varying nonlinear system in lower triangular form,the solution of which will lead to the solution of the global robust output regulation problem.An example shows the effectiveness of the proposed approach.

  8. Distributed output regulation for multi-agent systems with norm-bounded uncertainties

    Science.gov (United States)

    Yu, Lu; Wang, Jinzhi

    2014-11-01

    In this paper, we consider the distributed robust output regulation problem for multi-agent systems (MASs). It is involved with a group of heterogeneous high-order linear uncertain systems and an linear exosystem. The regulated output is a combination of the output of MAS and the exosystem, which is defined based on controlling demands. Distributed controllers are designed to ensure that the regulated output converges to the origin and meanwhile the closed-loop MAS is stable. The sufficient conditions for the solvability of distributed output regulation problem are given in terms of linear matrix inequalities. And algorithms are proposed to design distributed dynamic controllers with state feedback and output feedback, via the help of internal models. It is shown that, for any time-invariant norm-bounded uncertainties, the given controllers can realise the objective of output regulation.

  9. 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.

  10. 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.

  11. [Quantum processes in evolution of regulation of living system (mathematical modelling)].

    Science.gov (United States)

    Menshutkin, V V; Natochin, Iu V

    2011-01-01

    We have developed an imitation model of the appearance of regulation of physiological functions of protocell at the initial stages of evolution of living system. It is based on suggestion of the appearance of signal function in spontaneously formed products of partial hydrolysis of the protocell polypeptides, based on which there appear the regulatory molecules--quanta of regulation. For construction of the model, the mathematical apparatus of final automats and of genetic algorithm is used. The model has demonstrated the positive role of involvement of regulatory peptides in the system of regulation of protocell functions to provide its viability under the changing envelopment conditions.

  12. Position of Village Regulations and Folk Conventions in the Villager Autonomy System

    Institute of Scientific and Technical Information of China (English)

    Jiaming; ZHOU

    2014-01-01

    The Villagers’ Charter of Self-government,as a senior form of village regulations and folk conventions,is the general charter of villagers’ self-government. It is a small constitution of villagers,so it holds an important position in the villager autonomy system. Such position gives the credit to both historic and realistic objective factors. Rise of state power,vacancy of legislation,accumulation of excellent traditional resources,and democracy and contract spirit in village regulations and folk conventions will certainly accelerate development of village regulations and folk conventions and promote gradual improvement in the villager autonomy system.

  13. Constrained regulator problem for linear uncertain systems: control of a pH process

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available The regulator problem for linear uncertain continuous-time systems having control constraints is considered. Necessary and sufficient conditions of positive invariance of polyhedral domains are extended to the case of continuous-time uncertain systems. Robust constrained regulators are then derived. An application to the control of pH in a stirred tank is then presented. First, the uncertainty in the pH process is evaluated from first-principle models, then the design of a robust constrained regulator is presented. Simulation results show that this control law is easy to implement and that robust asymptotic stability and control admissibility are guaranteed.

  14. ARN: Analysis and Visualization System for Adipogenic Regulation Network Information.

    Science.gov (United States)

    Huang, Yan; Wang, Li; Zan, Lin-Sen

    2016-12-16

    Adipogenesis is the process of cell differentiation through which preadipocytes become adipocytes. Lots of research is currently ongoing to identify genes, including their gene products and microRNAs, that correlate with fat cell development. However, information fragmentation hampers the identification of key regulatory genes and pathways. Here, we present a database of literature-curated adipogenesis-related regulatory interactions, designated the Adipogenesis Regulation Network (ARN, http://210.27.80.93/arn/), which currently contains 3101 nodes (genes and microRNAs), 1863 regulatory interactions, and 33,969 expression records associated with adipogenesis, based on 1619 papers. A sentence-based text-mining approach was employed for efficient manual curation of regulatory interactions from approximately 37,000 PubMed abstracts. Additionally, we further determined 13,103 possible node relationships by searching miRGate, BioGRID, PAZAR and TRRUST. ARN also has several useful features: i) regulatory map information; ii) tests to examine the impact of a query node on adipogenesis; iii) tests for the interactions and modes of a query node; iv) prediction of interactions of a query node; and v) analysis of experimental data or the construction of hypotheses related to adipogenesis. In summary, ARN can store, retrieve and analyze adipogenesis-related information as well as support ongoing adipogenesis research and contribute to the discovery of key regulatory genes and pathways.

  15. 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.

  16. INVARIANT SYSTEM OF AUTOMATIC WATER-LEVEL REGULATING IN THE BOILER SHELL

    Directory of Open Access Journals (Sweden)

    G. T. Kulakov

    2015-01-01

    Full Text Available The quality of water-level regulation in the boiler-shells of heat-power and nuclear-power plants largely determines reliable and economical operation. The latter can be accomplished by means of massive reduction of the actuation-mechanism running time which depends directly on the regulator performance.The paper examines some foreign methods of PID-regulator adjusting in the cascade system of boiler-shell water-level automatic regulation. The authors derive an invariant cascade system of automatic regulation in which they offer not to measure external disturbance, the steam rate for instance, but to realize a concurrent model of the real inertial section of the controlled member. The disparity between the current value of the water-level in the shell and the output from the inertial section of the controlled-member model is fed to the input of the external-disturbance equivalent compensating device. This allows employing the compensating device in closed circuit, and consequently, the regulation quality improves under the influence of any external disturbances. The comparative analysis of the modeling results of the Cascade-System Automatic Regulation (CSAR with PID-regulator adjusted according to the foreign  methods  and  of  the  proposed  invariant  system  shows  considerable  improvement in regulation quality of the latter, viz. : system performance grows 2,5 times when working through the task jump, the peak value of overcorrection lowers from 42,5 to 10,0 %; while working through the internal disturbance, the regulating time reduces by 33 %, the maximum dynamic error of the regulation lowers by 65 %; the time of external combustion disturbance workout completion reduces two times, the maximum dynamic error of regulating – by 63 %; the maximum dynamic error of regulation while working through external disturbance with overheated steam rate diminishes by 71 %, the regulating time reduces by 1,5 times.

  17. Electrical system regulations of the IEA-R1 reactor

    Energy Technology Data Exchange (ETDEWEB)

    Mello, Jose Roberto de; Madi Filho, Tufic, E-mail: jrmello@ipen.br, E-mail: tmfilho@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    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)

  18. Information as a Regulative Element in Higher Education Systems

    Science.gov (United States)

    Kivisto, Jussi; Holtta, Seppo

    2008-01-01

    The existence of information asymmetry has ascended to a significant role in higher education systems. The article makes an attempt to conceptualise the interaction of universities with their environment, stakeholders, and the state by paying special attention to the role and substance of information asymmetry. The existence of information…

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

    African Journals Online (AJOL)

    user

    Keywords: Plant Growth Simulation Algorithm (PGSA), Radial Distribution Systems (RDS), ... branches as well as load distribution and time variation and handles fast as a ... 1985a, 1985b and 1985c) deals with the determination of the optimal ..... that is called the preferential growth node will take priority of growing a new ...

  20. 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.

  1. Systemic regulation of mineral homeostasis by micro RNAs

    Directory of Open Access Journals (Sweden)

    Julia eKehr

    2013-05-01

    Full Text Available Plants frequently have to cope with environments with sub-optimal mineral nutrient availability. Therefore they need to constantly sense changes of ion concentrations in their environment. Nutrient availabilities and needs have to be tightly coordinated between organs to ensure a balance between uptake and demand for metabolism, growth, reproduction, and defence reactions. To this end information about the nutrient status has to flow from cell-to-cell, but also between distant organs via the long-distance transport tubes to trigger adaptive responses. This systemic signalling between roots and shoots is required to maintain mineral nutrient homeostasis in the different organs under varying environmental conditions. Recent results begin to shed light on the molecular components of the complex long-distance signalling pathways and it has been proposed that systemic signals can be transported through the xylem as well as via the phloem. Several molecules, including nutrients, hormones, sugars, and small RNAs have been suggested to be involved in systemic communication over long distance (Liu et al. 2009. Recent research has suggested that in the case of mineral nutrients, the nutrients themselves, but also macromolecules like micro RNAs (miRNAs can act as important information transmitters. The following review will summarise the current knowledge about phloem-mediated systemic signalling by miRNAs during ion nutrient allocation and adaptation to mineral nutrient deprivation, concentrating on the well-analysed responses to a lack of potassium, sulphur, and copper.

  2. Shoot-derived cytokinins systemically regulate root nodulation

    National Research Council Canada - National Science Library

    Sasaki, Takema; Suzaki, Takuya; Soyano, Takashi; Kojima, Mikiko; Sakakibara, Hitoshi; Kawaguchi, Masayoshi

    2014-01-01

    ...) that translocates to roots and blocks further nodule development. Here we show that, CLE-RS1/2-HAR1 signalling activates the production of shoot-derived cytokinins, which have an SDI-like capacity to systemically suppress nodulation...

  3. Semi-global output regulation for linear systems with input saturation by composite nonlinear feedback control

    Science.gov (United States)

    Wang, Chongwen; Yu, Xiao; Lan, Weiyao

    2014-10-01

    To improve transient performance of output response, this paper applies composite nonlinear feedback (CNF) control technique to investigate semi-global output regulation problems for linear systems with input saturation. Based on a linear state feedback control law for a semi-global output regulation problem, a state feedback CNF control law is constructed by adding a nonlinear feedback part. The extra nonlinear feedback part can be applied to improve the transient performance of the closed-loop system. Moreover, an observer is designed to construct an output feedback CNF control law that also solves the semi-global output regulation problem. The sufficient solvability condition of the semi-global output regulation problem by CNF control is the same as that by linear control, but the CNF control technique can improve the transient performance. The effectiveness of the proposed method is illustrated by a disturbance rejection problem of a translational oscillator with rotational actuator system.

  4. The role of the endocannabinoid system in the regulation of energy expenditure.

    Science.gov (United States)

    Cavuoto, Paul; Wittert, Gary A

    2009-02-01

    Endocannabinoids, a lipid-derived signaling system, regulate appetite and motivation to eat via effects in the hypothalamus and nucleus accumbens. Not all the effects of endocannabinoids on fat mass can be explained by the regulation of food intake alone. Endocannabinoids and their receptors are located in areas of the central nervous system and multiple peripheral tissues involved in the regulation of intermediary metabolism and energy expenditure. In addition to regulating food intake by both central and peripherally mediated effects, endocannabinoids modify glucose and lipid metabolism so as to promote energy storage via lipogenesis and reduce energy expenditure. The endocannabinoid system appears to be overactive in obesity and may serve to maintain fat mass and underlies some of the metabolic consequences of obesity. Inhibition of the cannabinoid type-1 receptor ameliorates the effects of endocannabinoids on food intake and energy metabolism; lipogenesis is inhibited, lipolysis, fatty acid oxidation and glucose uptake increase.

  5. 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...

  6. Arabidopsis map kinase 4 negatively regulates systemic acquired resistance

    DEFF Research Database (Denmark)

    Brodersen, P; Johansen, Bo; Petersen, M;

    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) levels, 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....

  7. 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)

  8. Voltage Regulation and Line Loss Minimization of Loop Distribution Systems Using UPFC

    Science.gov (United States)

    Sayed, Mahmoud A.; Takeshita, Takaharu

    This paper presents a new method for achieving line loss minimization and voltage regulation in the loop distribution systems, simultaneously. First, mathematical analysis of the line loss minimum conditions in the loop distribution systems is presented. Then, load voltage regulation is applied in the loop distribution system under line loss minimum condition. Reference angle of the desired load voltage is the main factor that can be used to minimize total line loss during load voltage control. In order to achieve these two objectives simultaneously, the UPFC (unified power flow controller), a typical FACTS (flexible AC transmission systems) device, that is capable of instantaneous control of transmission and distribution power flow, is used. Also, the UPFC control scheme to regulate the load voltage under line loss minimization is presented. The effectiveness of the proposed control scheme has been verified experimentally using laboratory prototype in a 200V, 6kVA system.

  9. Coordinated regulation of virulence during systemic infection of Salmonella enterica serovar Typhimurium.

    Directory of Open Access Journals (Sweden)

    Hyunjin Yoon

    2009-02-01

    Full Text Available To cause a systemic infection, Salmonella must respond to many environmental cues during mouse infection and express specific subsets of genes in a temporal and spatial manner, but the 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 83 regulators inferred to play a role in Salmonella enteriditis Typhimurium (STM virulence and tested them in three virulence assays (intraperitoneal [i.p.], and intragastric [i.g.] infection in BALB/c mice, and persistence in 129X1/SvJ mice. Overall, 35 regulators were identified whose absence attenuated virulence in at least one assay, and of those, 14 regulators were required for systemic mouse infection, the most stringent virulence assay. As a first step towards understanding the interplay between a pathogen and its host from a systems biology standpoint, we focused on these 14 genes. Transcriptional profiles were obtained for deletions of each of these 14 regulators 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 14 regulators control the same 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 the response regulator SsrB and the MarR type regulator, SlyA, are the terminal regulators in a cascade that integrates multiple signals. Furthermore, experiments to demonstrate epistatic relationships showed that SsrB can replace SlyA and, in some cases, SlyA can replace SsrB for expression of SPI-2 encoded

  10. [Glutamatergic neurotransmitter system in regulation of the gastrointestinal tract motor activity].

    Science.gov (United States)

    Alekseeva, E V; Popova, T S; Sal'nikov, P S

    2015-01-01

    The review include actual facts, demonstrating high probability of glutamatergic neurotransmitter system role in the regulation of the gastrointestinal tract motor activity. These facts suggest significant role of the glutamatergic neurotransmitter system dysfunction in forming motor activity disorders of the digestive tract, including in patients in critical condition. The analysis is based on results of multiple experimental and clinical researches of glutamic acid and other components of the glutamatergic neurotransmitter system in central nervous system and autonomic nervous system (with the accent on the enteral nervous system) in normal conditions and with functioning changes of the glutamatergic neurotransmitter system in case of inflammation, hupoxia, stress and in critical condition.

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

    OpenAIRE

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

    2016-01-01

    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...

  12. Regulation Law of Turbine and Generator in Organic Rankine Cycle Power Generation Experimental System

    Institute of Scientific and Technical Information of China (English)

    潘利生; 王怀信; 史维秀

    2014-01-01

    In the performance experiment of organic Rankine cycle power generation experimental system, the load-resistance-regulation method is one of the most important regulation methods. However, the regulation law has not been clear enough to guide the experiment, which is unfavorable to the experimental research on organic Rankine cy-cle. In this paper the regulation law of turbine and generator by the load-resistance-regulation method is studied theo-retically and experimentally. The results show that when the thermal cycle parameters keep constant, the turbine speed increases with the increase of load resistance and there is a maximum value of transmission-generator efficiency with the variation of the turbine speed; when the turbine speed and generator speed keep constant, the transmission-generator efficiency decreases and gradually tends to zero with the increase of load resistance.

  13. Output regulation for linear singular systems using dual-observer based compensators

    Science.gov (United States)

    Deutscher, Joachim

    2013-05-01

    In this article, the output regulation problem is solved for singular systems by using dual observer-based compensators. This has the advantage that output regulation can be achieved under weak conditions. Namely, different from previous approaches, an implementable compensator can be directly determined in form of a classical state space model without a transformation into Weierstrass-Kronecker canonical form. Furthermore, the impulse controllability and observability of the singular system is not required and the output to be controlled needs not be measurable. The results of the article are demonstrated by means of a simple mechanical system.

  14. Overview of the South African mine health and safety standardization and regulation systems

    Institute of Scientific and Technical Information of China (English)

    LI Zhong-xue; LI Jia-jie; LI Cui-ping; LIU Shuang-yue

    2008-01-01

    Outlined the South African mine health and safety regulatory framework, including the roles of government, tripartite council, service agencies, mine enterprises,rescue stations and workers unions, analyzed the institutional structures of South African mine health and safety standardization, including the South African standard and specification systems and standard development processes, and characterized the South African mine health and safety standardization and regulation systems. Intended to provide some suggestions for the transformation and improvement of mine health and safety standardization and regulation systems in China or in similar situations.

  15. 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.

  16. 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

  17. 75 FR 71560 - Defense Federal Acquisition Regulation Supplement; Cost and Software Data Reporting System (DFARS...

    Science.gov (United States)

    2010-11-24

    ... is provided for contractors with accounting software that does not accommodate the additional data... Acquisition Regulation Supplement; Cost and Software Data Reporting System (DFARS Case 2008-D027) AGENCY... Cost and Software Data Reporting system requirements for Major Defense Acquisition Programs and...

  18. 77 FR 43523 - Revisions to the Unregulated Contaminant Monitoring Regulation (UCMR 3) for Public Water Systems

    Science.gov (United States)

    2012-07-25

    ... AGENCY 40 CFR Parts 141 and 142 RIN 2040-AF10 Revisions to the Unregulated Contaminant Monitoring Regulation (UCMR 3) for Public Water Systems Correction In rule document 2012-9978 appearing on pages 26072... table entitled ``EXHIBIT 1--APPLICABILITY OF UCMR 3 TO WATER UTILITIES BY SYSTEM TYPE AND SIZE'' should...

  19. 77 FR 39182 - Revisions to the Unregulated Contaminant Monitoring Regulation (UCMR 3) for Public Water Systems

    Science.gov (United States)

    2012-07-02

    ... AGENCY 40 CFR Parts 141 and 142 RIN 2040-AF10 Revisions to the Unregulated Contaminant Monitoring Regulation (UCMR 3) for Public Water Systems Correction In rule document 2012-9978 appearing on pages 26072... table entitled ``EXHIBIT 1--APPLICABILITY OF UCMR 3 TO WATER UTILITIES BY SYSTEM TYPE AND SIZE'' should...

  20. 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 ris

  1. Regulation for Switched Bimodal Systems with the Application to the Flying Height Control in Data Storage Devices

    Science.gov (United States)

    Wu, Zhizheng

    This paper considers a regulation problem for discrete-time switched bimodal linear systems where it is desired to achieve regulation against partially known disturbance or reference signals. First, a set of observer-based Q - parameterized stabilizing controllers for the switched system is constructed. Then a sufficient regulation condition for the switched system is obtained, and a regulator synthesis method is derived based on solving a set of properly formulated linear matrix inequalities. Finally, the proposed regulator design method is evaluated on an experimental setup motivated by the flying height regulation problem in data storage devices.

  2. Endoglin regulates mural cell adhesion in the circulatory system.

    Science.gov (United States)

    Rossi, Elisa; Smadja, David M; Boscolo, Elisa; Langa, Carmen; Arevalo, Miguel A; Pericacho, Miguel; Gamella-Pozuelo, Luis; Kauskot, Alexandre; Botella, Luisa M; Gaussem, Pascale; Bischoff, Joyce; Lopez-Novoa, José M; Bernabeu, Carmelo

    2016-04-01

    The circulatory system is walled off by different cell types, including vascular mural cells and podocytes. The interaction and interplay between endothelial cells (ECs) and mural cells, such as vascular smooth muscle cells or pericytes, play a pivotal role in vascular biology. Endoglin is an RGD-containing counter-receptor for β1 integrins and is highly expressed by ECs during angiogenesis. We find that the adhesion between vascular ECs and mural cells is enhanced by integrin activators and inhibited upon suppression of membrane endoglin or β1-integrin, as well as by addition of soluble endoglin (SolEng), anti-integrin α5β1 antibody or an RGD peptide. Analysis of different endoglin mutants, allowed the mapping of the endoglin RGD motif as involved in the adhesion process. In Eng (+/-) mice, a model for hereditary hemorrhagic telangectasia type 1, endoglin haploinsufficiency induces a pericyte-dependent increase in vascular permeability. Also, transgenic mice overexpressing SolEng, an animal model for preeclampsia, show podocyturia, suggesting that SolEng is responsible for podocytes detachment from glomerular capillaries. These results suggest a critical role for endoglin in integrin-mediated adhesion of mural cells and provide a better understanding on the mechanisms of vessel maturation in normal physiology as well as in pathologies such as preeclampsia or hereditary hemorrhagic telangiectasia.

  3. Prorenin receptor regulates more than the renin-angiotensin system.

    Science.gov (United States)

    Müller, Dominik N; Binger, Katrina J; Riediger, Fabian

    2012-06-01

    The (pro)renin receptor (PRR) was initially believed to be a contributor to the pathogenesis of cardiovascular diseases via the amplification of renin- or prorenin-induced angiotensin (Ang) formation. However, a recent paradigm shift suggests a new role for PRR, separate from the renin-angiotensin system (RAS), in contributing to cellular homeostasis. Specifically, PRR is thought to be essential for vacuolar H(+) -ATPase (V-ATPase) activity and acts as an adaptor between the V-ATPase and the Wnt signalling pathway. Recent PRR conditional knock-out studies have confirmed this link between V-ATPase and PRR, with deletion resulting in the accumulation of autophagic vacuoles and animal lethality. The molecular mechanism by which PRR contributes to V-ATPase activity, and whether multiple signalling pathways are affected by PRR loss, is currently unknown. Additionally, cleavage by furin at a single site within full-length PRR results in the production of a soluble form of the receptor, which is detectable in plasma. Soluble PRR is hypothesized to bind to specific ligands and receptors and mediate signal transduction pathways. Understanding the physiological function of full-length and soluble PRR will be important for establishing its role in pathology.

  4. Shoot-derived cytokinins systemically regulate root nodulation.

    Science.gov (United States)

    Sasaki, Takema; Suzaki, Takuya; Soyano, Takashi; Kojima, Mikiko; Sakakibara, Hitoshi; Kawaguchi, Masayoshi

    2014-09-19

    Legumes establish symbiotic associations with nitrogen-fixing bacteria (rhizobia) in root nodules to obtain nitrogen. Legumes control nodule number through long-distance communication between roots and shoots, maintaining the proper symbiotic balance. Rhizobial infection triggers the production of mobile CLE-RS1/2 peptides in Lotus japonicus roots; the perception of the signal by receptor kinase HAR1 in shoots presumably induces the production of an unidentified shoot-derived inhibitor (SDI) that translocates to roots and blocks further nodule development. Here we show that, CLE-RS1/2-HAR1 signalling activates the production of shoot-derived cytokinins, which have an SDI-like capacity to systemically suppress nodulation. In addition, we show that LjIPT3 is involved in nodulation-related cytokinin production in shoots. The expression of LjIPT3 is activated in an HAR1-dependent manner. We further demonstrate shoot-to-root long-distance transport of cytokinin in L. japonicus seedlings. These findings add essential components to our understanding of how legumes control nodulation to balance nutritional requirements and energy status.

  5. 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.

  6. Synchronised output regulation of leader-following heterogeneous networked systems via error feedback

    Science.gov (United States)

    Li, Yanjun; Wang, Xuejie; Xiang, Ji; Wei, Wei

    2016-03-01

    A dynamic error feedback controller is presented for the synchronised output regulation (SOR) of leader-following heterogeneous linear networked systems. The nodes in the networked systems are divided into two kinds: the leader node accessible to the regulated error and the following nodes inaccessible to the regulated error but accessible to the relative output errors with respect to their neighbouring nodes. By using the small-gain theorem, a sufficient criterion for the SOR problem is developed for more general networks. This criterion can be regarded as imposing an additional H∞ constraint on the classical output regulation problem. The synthesis problem is then addressed by means of linear matrix inequality technique. The efficacy of the analytic results is illustrated by simulation examples.

  7. Control, regulation and storage systems to optimize the integration of wind power

    Energy Technology Data Exchange (ETDEWEB)

    Gasco, Manuel [Universidad de Alicante (Spain). Area de Ingenieria Electrica; Rios, Alberto [Universidad Europea de Madrid (Spain). Area de Ingenieria Electrica

    2012-07-01

    Increasing integration of a wind energy into the power system increases the importance of its control and regulation. The new wind energy technologies and smart grid technologies substantially modify the power.system, acquiring this way a great amount of active elements. New devices in the grid become more important; power storage systems, regulation systems and control systems are described in this paper. When talking about power storage systems, nowadays the most important are pump and turbine systems which are used in the power grid and the electric vehicle connected to the grid. Regarding the power control, the systems applied are tap transformers and capacitor banks. However, FACTS devices are becoming increasingly important, whether they are connected in series or in parallel, they combine conventional systems, power electronics and microelectronics, together with modern telecommunication systems. Finally, the demand management systems enable us to determine the cost of energy for the consumers on the real time basis. This way the user can decide when and for how much money he wants to consume the energy. If different types of technologies integrated in the power grid are compared, different behaviors are observed. Therefore, it is possible to select those devices of control, regulation and management that should be applied to optimize the power grid. (orig.)

  8. Control, regulation and storage systems to optimize the integration of solar power

    Energy Technology Data Exchange (ETDEWEB)

    Gasco, Manuel [Universidad de Alicante (Spain). Area de Ingenieria Electrica; Rios, Alberto [Universidad Europea de Madrid (Spain). Area de Ingenieria Electrica

    2012-07-01

    Increasing integration of a solar energy into the power system increases the importance of its control and regulation. The new solar energy technologies and smart grid technologies substantially modify the power system, acquiring this way a great amount of active elements. New devices in the grid become more important; power storage systems, regulation systems and control systems are described in this paper. When talking about power storage systems, nowadays the most important are pump and turbine systems which are used in the power grid and the electric vehicle connected to the grid. Regarding the power control, the systems applied are tap transformers and capacitor banks. However, FACTS devices are becoming increasingly important, whether they are connected in series or in parallel, they combine conventional systems, power electronics and microelectronics, together with modern telecommunication systems. Finally, the demand management systems enable us to determine the cost of energy for the consumers on the real time basis. This way the user can decide when and for how much money he wants to consume the energy. If different types of technologies integrated in the power grid are compared, different behaviors are observed. Therefore, it is possible to select those devices of control, regulation and management that should be applied to optimize the power grid. (orig.)

  9. New Type Regulating Valve Applied in Cooling System of Blast Furnace

    Institute of Scientific and Technical Information of China (English)

    HE Sheng-ping; ZOU De-yu; XU Gang; LU De-chang

    2004-01-01

    A new type regulating valve with the cooling mode of constant temperature difference water supply, temperature difference self-operated regulating valve, was introduced into blast furnace cooling system to overcome shortcomings of the cooling mode of constant flow rate water supply. The results show that the temperature difference between inlet and outlet water of cooling wall can be decreased greatly and steadily, and the water supply for blast furnace cooling can be reduced considerably.

  10. Regulation of embryonic size in early mouse development in vitro culture system.

    Science.gov (United States)

    Hisaki, Tomoka; Kawai, Ikuma; Sugiura, Koji; Naito, Kunihiko; Kano, Kiyoshi

    2014-08-01

    Mammals self-regulate their body size throughout development. In the uterus, embryos are properly regulated to be a specific size at birth. Previously, size and cell number in aggregated embryos, which were made from two or more morulae, and half embryos, which were halved at the 2-cell stage, have been analysed in vivo in preimplantation and post-implantation development in mice. Here, we examined whether or not the mouse embryo has the capacity to self-regulate growth using an in vitro culture system. To elucidate embryonic histology, cells were counted in aggregated or half embryos in comparison with control embryos. Both double- and triple-aggregated embryos contained more cells than did control embryos during all culture periods, and the relative growth ratios showed no growth inhibition in an in vitro culture system. Meanwhile, half embryos contained fewer cells than control embryos, but the number grew throughout the culture period. Our data suggest that the growth of aggregated embryos is not affected and continues in an in vitro culture system. On the other hand, the growth of half embryos accelerates and continues in an in vitro culture system. This situation, in turn, implied that post-implantation mouse embryos might have some potential to regulate their own growth and size as seen by using an in vitro culture system without uterus factors. In conclusion, our results indicated that embryos have some ways in which to regulate their own size in mouse early development.

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

    Directory of Open Access Journals (Sweden)

    Létitia Jean

    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

  12. INVARIANT SYSTEM OF THE STEAM-DRUM BOILER FEED AUTOMATIC REGULATION

    Directory of Open Access Journals (Sweden)

    G. T. Kulakov

    2015-01-01

    Full Text Available The choice of the controlling system structure, law of control, and optimal parameters for the regulator dynamic settings exercise, under principal influences, substantial effect on quality of the transient processes of water-level change in the shell of the boiler. At the present moment, techniques of design by analysis for the optimal regulating systems allow improving quality of the transient processes. Applying the method of structural-parametrical optimization and the invariance theory render it possible to significantly improve quality of the boiler-shell water level maintaining by means of changing the system structure and optimizing the feed automatic-control system dynamic settings. However, this becomes attainable at the expense of increasing the control-action maximum magnitude with the feeding water rate. At the same time, the indicator of the latter should be less than the control-action value of the typical threeelement control of the feed-regulation system as this directly links to the boiler equipment safety, the drum metal and the feed-water economizer longevity. For removal of this shortcoming, the paper proposes to form in parallel to the real inertial region of the controlled member its dynamic simulation which allows separating the equivalent external disturbance without having to measure it. And to limit the compensation device output to the control-action value of the typical three-element control system of the automatic feed-regulation. This leads to the maximum control-action magnitude decrease, besides, the external-disturbances execution time remains unchanged. Altogether, under all the influences, the authors report of receiving substantial improvement of regulation quality as compared with the typical three-element automatic feed-regulation system

  13. The role of the histaminergic system in the central cardiovascular regulation in haemorrhagic hypotension.

    Science.gov (United States)

    Jochem, Jerzy; Kasperska-Zajac, Alicja

    2012-01-01

    The histaminergic system consists of neurons located in tuberomammillary nucleus of the posterior hypothalamus. It affects many functions of the central nervous system, including regulation of the brainstem cardiovascular center. In this paper, we present current review of the literature concerning the role of the histaminergic system in the cardiovascular regulation in haemorrhagic hypotension. Experimental studies demonstrate that in both, normotension and critical hemorrhagic hypotension, histamine, acting as a central neurotransmitter, evokes the pressor effect. Interestingly, increases in mean arterial pressure are significantly higher in hypovolaemic than in normovolaemic animals. Many lines of evidence support the hypothesis that in haemorrhagic shock, the histaminergic system is able to activate neural and humoral compensatory mechanisms involving the sympathetic nervous and renin-angiotensin systems, arginine vasopressin and proopiomelanocortin-derived peptides. We suggest that the histaminergic system could be a new target for treatment of hemorrhagic hypotension.

  14. The Two-Component Signal Transduction System VxrAB Positively Regulates Vibrio cholerae Biofilm Formation.

    Science.gov (United States)

    Teschler, Jennifer K; Cheng, Andrew T; Yildiz, Fitnat H

    2017-09-15

    Two-component signal transduction systems (TCSs), typically composed of a sensor histidine kinase (HK) and a response regulator (RR), are the primary mechanism by which pathogenic bacteria sense and respond to extracellular signals. The pathogenic bacterium Vibrio cholerae is no exception and harbors 52 RR genes. Using in-frame deletion mutants of each RR gene, we performed a systematic analysis of their role in V. cholerae biofilm formation. We determined that 7 RRs impacted the expression of an essential biofilm gene and found that the recently characterized RR, VxrB, regulates the expression of key structural and regulatory biofilm genes in V. choleraevxrB is part of a 5-gene operon, which contains the cognate HK vxrA and three genes of unknown function. Strains carrying ΔvxrA and ΔvxrB mutations are deficient in biofilm formation, while the ΔvxrC mutation enhances biofilm formation. The overexpression of VxrB led to a decrease in motility. We also observed a small but reproducible effect of the absence of VxrB on the levels of cyclic di-GMP (c-di-GMP). Our work reveals a new function for the Vxr TCS as a regulator of biofilm formation and suggests that this regulation may act through key biofilm regulators and the modulation of cellular c-di-GMP levels.IMPORTANCE Biofilms play an important role in the Vibrio cholerae life cycle, providing protection from environmental stresses and contributing to the transmission of V. cholerae to the human host. V. cholerae can utilize two-component systems (TCS), composed of a histidine kinase (HK) and a response regulator (RR), to regulate biofilm formation in response to external cues. We performed a systematic analysis of V. cholerae RRs and identified a new regulator of biofilm formation, VxrB. We demonstrated that the VxrAB TCS is essential for robust biofilm formation and that this system may regulate biofilm formation via its regulation of key biofilm regulators and cyclic di-GMP levels. This research furthers our

  15. 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.

  16. Ion channels, guidance molecules, intracellular signaling and transcription factors regulating nervous and vascular system development.

    Science.gov (United States)

    Akita, Tenpei; Kumada, Tatsuro; Yoshihara, Sei-ichi; Egea, Joaquim; Yamagishi, Satoru

    2016-03-01

    Our sophisticated thoughts and behaviors are based on the miraculous development of our complex nervous network system, in which many different types of proteins and signaling cascades are regulated in a temporally and spatially ordered manner. Here we review our recent attempts to grasp the principles of nervous system development in terms of general cellular phenomena and molecules, such as volume-regulated anion channels, intracellular Ca(2+) and cyclic nucleotide signaling, the Npas4 transcription factor and the FLRT family of axon guidance molecules. We also present an example illustrating that the same FLRT family may regulate the development of vascular networks as well. The aim of this review is to open up new vistas for understanding the intricacy of nervous and vascular system development.

  17. Radial MV networks voltage regulation with distribution management system coordinated controller

    Energy Technology Data Exchange (ETDEWEB)

    Bignucolo, Fabio; Caldon, Roberto [University of Padua, Department of Electrical Engineering, Via Gradenigo, 6/A, 35131 Padova (Italy); Prandoni, Valter [CESI Ricerca, Milan (Italy)

    2008-04-15

    The connection of a great number of distributed generation (DG) plants may cause a critical voltage regulation problem in actual medium voltage (MV) radial distribution networks. After a synthetic survey of different strategies reported in literature to solve this problem, a proposal for an active management of the distribution system which makes use of an innovative controller that coordinates the on load tap changer (OLTC) action with the regulation of reactive exchanges between DG plants and feeders, is presented. In order to test the effectiveness of the proposed regulation, the distribution management system coordinated controller (DMSCC) is applied to a realistic radial structure distribution network and its behaviour simulated in managing the MV system during its worst foreseeable working conditions. (author)

  18. STUDY ON THE AUTOMATIC REGULATION SYSTEM OF WIND RATE FUZZY CONTROL

    Institute of Scientific and Technical Information of China (English)

    李敬兆; 张崇巍; 周时欢; 王清灵

    2000-01-01

    This paper presents the solution of regulating the wind rate automatically by means of fuzzy control technology and implementing it with PLC (programmable logical controller) under the circumstance of many influence factors, which exists in the axial-flow fans wind rate regulation system during the process of mine ventilation, and has difficulty in modifying the mathematic model to obtain the satisfied result by normal control ways. According to this analysis, the intelligent and analytic treatment of fuzzy controller has been made and fuzzy control scheme involving self-regulation divisor and intelligent integral has been deeply proposed. Test result shows that this system based on the scheme above is obviously prior to others in its responsibility such as high-speed, overshoot, control precision and robustness. The system furnishes the great reliability of mine working safety and fans running efficiency.

  19. Voltage regulation and reactive power supply capability of distributed generation : applications in active distribution systems

    Energy Technology Data Exchange (ETDEWEB)

    Katiraei, F.; Yazdani, A.; Uluski, R. [Quanta Technology, New York, NY (United States); Vaziri, M. [Pacific Gas and Electric Co., San Fransisco, CA (United States)

    2009-07-01

    Problems regarding voltage regulation on distribution feeders arise when there is a large demand for reactive power. The addition of distributed generation changes the power flow and voltage profile of a power system. The current practice is to use distributed generation passively and perform voltage regulation as before. However, this may not function well with high distributed generation penetration. This presentation discussed voltage regulation and the reactive power supply capability of distributed generation. Several applications in active distribution systems were presented. Specifically, the presentation discussed distributed interconnection challenges; utility practices and limiting factors; and the real and reactive power capabilities of distributed generation. A case study was also presented. It was concluded that in order for distributed generation to actively participate in real and reactive power management of distribution systems, a change is needed in standards and utility guidelines, along with a better understanding of distributed generation technologies and controls. 1 tab., 11 figs.

  20. The parasympathetic nervous system as a regulator of mast cell function.

    Science.gov (United States)

    Forsythe, Paul

    2015-01-01

    Often considered as the archetype of neuroimmune communication, much of our understanding of the bidirectional relationship between the nervous and immune systems has come from the study of mast cell-nerve interaction. Mast cells play a role in resistance to infection and are extensively involved in inflammation and subsequent tissue repair. Thus, the relationship between mast cells and neurons enables the involvement of peripheral and central nervous systems in the regulation of host defense mechanisms and inflammation. Recently, with the identification of the cholinergic anti-inflammatory pathway, there has been increased interest in the role of the parasympathetic nervous system in regulating immune responses. Classical neurotransmitters and neuropeptides released from cholinergic and inhibitory NANC neurons can modulate mast cell activity, and there is good evidence for the existence of parasympathetic nerve-mast cell functional units in the skin, lung, and intestine that have the potential to regulate a range of physiological processes.

  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. 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....

  3. 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...

  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. 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.

  6. Cooperative linear output regulation for networked systems by dynamic measurement output feedback

    Science.gov (United States)

    Li, Shaobao; Feng, Gang; Wang, Juan; Luo, Xiaoyuan; Guan, Xinping

    2016-04-01

    This paper investigates the cooperative linear output regulation problem of a class of heterogeneous networked systems with a common reference input but with different disturbances for individual nodes. A novel distributed control law is presented based on dynamic measurement output feedback. It is shown that the overall networked closed-loop control system is asymptotically stable and the output regulation errors asymptotically approach zero as time goes to infinity under a sufficient and necessary condition. Finally, a numerical example is provided to demonstrate the effectiveness of the proposed control law.

  7. AN ALTERNATIVE APPROACH TO GLOBAL ROBUST OUTPUT REGULATION OF OUTPUT FEEDBACK SYSTEMS

    Institute of Scientific and Technical Information of China (English)

    Jie HUANG

    2007-01-01

    The global robust output regulation problem of the output feedback systems has been extensively studied under various assumptions of the complexity and uncertainty. All these approaches boil down to a stabilization problem of a so-called augmented extended system. This paper will describe an alternative approach which converts the original problem into a stabilization problem of a so-called extended augmented system. As the extended augmented system is somewhat simpler than the augmented extended system, this alternative approach is also simpler than the first approach.

  8. Global robust output regulation control for cascaded nonlinear systems using the internal model principle

    Science.gov (United States)

    Yu, Jiang-Bo; Zhao, Yan; Wu, Yu-Qiang

    2014-04-01

    This article considers the global robust output regulation problem via output feedback for a class of cascaded nonlinear systems with input-to-state stable inverse dynamics. The system uncertainties depend not only on the measured output but also all the unmeasurable states. By introducing an internal model, the output regulation problem is converted into a stabilisation problem for an appropriately augmented system. The designed dynamic controller could achieve the global asymptotic tracking control for a class of time-varying reference signals for the system output while keeping all other closed-loop signals bounded. It is of interest to note that the developed control approach can be applied to the speed tracking control of the fan speed control system. The simulation results demonstrate its effectiveness.

  9. 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.

  10. Effects of automobile steering characteristics on driver vehicle system dynamics in regulation tasks

    Science.gov (United States)

    Mcruer, D. T.; Klein, R.

    1975-01-01

    A regulation task which subjected the automobile to a random gust disturbance which is countered by driver control action is used to study the effects of various automobile steering characteristics on the driver/vehicle system. The experiments used a variable stability automobile specially configured to permit insertion of the simulated gust disturbance and the measurement of the driver/vehicle system characteristics. Driver/vehicle system dynamics were measured and interpreted as an effective open loop system describing function. Objective measures of system bandwidth, stability, and time delays were deduced and compared. These objective measures were supplemented by driver ratings. A tentative optimum range of vehicle dynamics for the directional regulation task was established.

  11. The ubiquitin–proteasome system and signal transduction pathways regulating Epithelial Mesenchymal transition of cancer

    Directory of Open Access Journals (Sweden)

    Voutsadakis Ioannis A

    2012-07-01

    Full Text Available Abstract Epithelial to Mesenchymal transition (EMT in cancer, a process permitting cancer cells to become mobile and metastatic, has a signaling hardwire forged from development. Multiple signaling pathways that regulate carcinogenesis enabling characteristics in neoplastic cells such as proliferation, resistance to apoptosis and angiogenesis are also the main players in EMT. These pathways, as almost all cellular processes, are in their turn regulated by ubiquitination and the Ubiquitin-Proteasome System (UPS. Ubiquitination is the covalent link of target proteins with the small protein ubiquitin and serves as a signal to target protein degradation by the proteasome or to other outcomes such as endocytosis, degradation by the lysosome or specification of cellular localization. This paper reviews signal transduction pathways regulating EMT and being regulated by ubiquitination.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1984-07-01

    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.

  13. Regulation and control of thermally activated building systems; Regelung und Steuerung von thermoaktiven Bauteilsystemen

    Energy Technology Data Exchange (ETDEWEB)

    Toedtli, Juerg [Consulting Juerg Toedtli, Zuerich (Switzerland); Gwerder, Markus; Renggli, Franz; Guentensperger, Werner [Siemens Building Technologies, Zug (Switzerland); Lehmann, Beat; Dorer, Viktor [EMPA, Duebendorf (Switzerland). Abt. Building Technologies; Hildebrand, Kurt [Hochschule Luzern - Technik und Architektur, Horw (Switzerland)

    2009-11-15

    Thermally activated building systems (TABS) are becoming increasingly important in terms of energy efficient cooling and heating of buildings. In practice, however, regulation and control of such systems often causes problems. Started five years ago with the aim of getting to grips with these problems, the TABS Control research project was completed in early 2009. The project yielded the following results: various models and simulation programs for TABS; performance-bound calculations for regulating zones; a range of zone regulation/control strategies for planners to choose from, including good solutions for automatic switching between heating and cooling, for pulsed operation of the zone pump and for room temperature control; the implementation of a subset of these strategies as standard solutions in a Siemens building automation system; laboratory tests on these strategies; a new procedure for the integrated planning of TABS and their regulation/control (referred to as UBB planning procedure - Unknown But Bounded); an Excel planning tool; guidelines on selecting the hydraulic switching topology; a method for operation optimization; the theoretical basis for the new integrated planning procedure and the new regulation/ control strategies; a patent application.

  14. Incremental Passivity and Incremental Passivity-Based Output Regulation for Switched Discrete-Time Systems.

    Science.gov (United States)

    Jiao Li; Jun Zhao

    2017-05-01

    This paper investigates incremental passivity and output regulation for switched discrete-time systems. We develop the results in two parts. First of all, a concept of incremental passivity is proposed to describe the overall incremental passivity property of a switched discrete-time system in the absence of the classic incremental passivity property of the subsystems. A condition for incremental passivity is given. A certain negative output feedback is designed to produce asymptotic stability. Incremental passivity is shown to be preserved under feedback interconnection. The second part of this paper is concerned with an application of the incremental passivity theory to the output regulation problem for switched discrete-time systems. The key idea is to construct a switched internal model with incremental passivity, which closely links the solvability of the output regulation problem. A characteristic of the switched internal model is that it does not necessarily switch synchronously with the controlled plant, which greatly increases the freedom of design. Once such a switched internal model is established, the output regulation problem is then solved by construction of the feedback interconnection between the controlled plant and the switched internal model. The main usefulness of the strategy is to get rid of the solvability of the output regulation problem for the subsystems.

  15. A Novel Method for Enhancement of System Regulating Capacity by using Seawater Desalination Plant in a Small Island Power System

    Science.gov (United States)

    Yoshihara, Toru; Yokoyama, Akihiko; Imanaka, Masaki; Onda, Yusuke; Baba, Jumpei; Kuniba, Yusuke; Higa, Naoto; Asato, Sadao

    Recently, more and more unstable renewable energy based generations such as photovoltaic generations and wind turbine generations have been installed into power systems. This paper focuses a small island power system operation and proposes a novel control method of power consumption of a seawater desalination plant as a controllable load in order to secure more regulating capacity of the power system considering the customer's convenience of the desalination plant. Through a frequency analysis simulation, fuel cost can be reduced and system frequency fluctuation can be suppressed for the proposed control method of seawater desalination plant.

  16. 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.

  17. A new approach on designing l1 optimal regulator with minimum order for SISO linear systems

    Institute of Scientific and Technical Information of China (English)

    Xiang LIU

    2006-01-01

    For a SISO linear discrete-time system with a specified input signal, a novel method to realize optimal l1 regulation control is presented. Utilizing the technique of converting a polynomial equation to its corresponding matrix equation, a linear programming problem to get an optimal l1 norm of the system output error map is developed which includes the first term and the last term of the map sequence in the objective function and the right vector of its constraint matrix equation, respectively. The adjustability for the width of the constraint matrix makes the trade-off between the order of the optimal regulator and the value of the minimum objective norm become possible, especially for achieving the optimal regulator with minimum order. By norm scaling rules for the constraint matrix equation, the optimal solution can be scaled directly or be obtained by solving a linear programming problem with l1 norm objective.

  18. Thoughts on Accelerating Establishment and Improvement of Guarantee System of Rules and Regulations

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Since the 6th-round railway speed-up campaign,a large number of new technologies and equipment have been applied and put into operation,and the technical conditions and work standards have changed dramatically.It has appeared that there exists quite some inadaptability with respect to the current rules and regulations.Therefore,it is necessary to speed up the establishment and improvement of the guarantee system of rules and regulations,make the rules and regulations scientific and standardized,and focus on the integrated support of the system with classified management and required details at different levels so as to realize the combination of safety,efficiency and benefit.

  19. Eag1 K+ Channel: Endogenous Regulation and Functions in Nervous System

    Science.gov (United States)

    Tokay, Tursonjan; Zhang, Guangming; Sun, Peng

    2017-01-01

    Ether-à-go-go1 (Eag1, Kv10.1, KCNH1) K+ channel is a member of the voltage-gated K+ channel family mainly distributed in the central nervous system and cancer cells. Like other types of voltage-gated K+ channels, the EAG1 channels are regulated by a variety of endogenous signals including reactive oxygen species, rendering the EAG1 to be in the redox-regulated ion channel family. The role of EAG1 channels in tumor development and its therapeutic significance have been well established. Meanwhile, the importance of hEAG1 channels in the nervous system is now increasingly appreciated. The present review will focus on the recent progress on the channel regulation by endogenous signals and the potential functions of EAG1 channels in normal neuronal signaling as well as neurological diseases.

  20. Eag1 K+ Channel: Endogenous Regulation and Functions in Nervous System

    Directory of Open Access Journals (Sweden)

    Bo Han

    2017-01-01

    Full Text Available Ether-à-go-go1 (Eag1, Kv10.1, KCNH1 K+ channel is a member of the voltage-gated K+ channel family mainly distributed in the central nervous system and cancer cells. Like other types of voltage-gated K+ channels, the EAG1 channels are regulated by a variety of endogenous signals including reactive oxygen species, rendering the EAG1 to be in the redox-regulated ion channel family. The role of EAG1 channels in tumor development and its therapeutic significance have been well established. Meanwhile, the importance of hEAG1 channels in the nervous system is now increasingly appreciated. The present review will focus on the recent progress on the channel regulation by endogenous signals and the potential functions of EAG1 channels in normal neuronal signaling as well as neurological diseases.

  1. Testosterone regulates alpha-synuclein mRNA in the avian song system.

    Science.gov (United States)

    Hartman, V N; Miller, M A; Clayton, D F; Liu, W C; Kroodsma, D E; Brenowitz, E A

    2001-04-17

    Alpha-synuclein is a small, highly conserved protein in vertebrates that has been linked to several neurodegenerative diseases. The avian song control system is one of the model systems in which the protein was independently discovered. Alpha-synuclein is dynamically regulated in the song system during song learning, a process in which sex steroids play a central role. We compared alpha-synuclein mRNA expression in the brains of 12 adult male chipping sparrows (Spizella passerina) treated with either testosterone or blank s.c. implants. We saw pronounced upregulation of alpha-synuclein mRNA in, as well as an increase in the volume of, the song control nucleus area X in response to exogenous testosterone. To our knowledge this is the first report of steroid regulation of synuclein gene expression in any model system.

  2. A linear quadratic regulator approach to the stabilization of uncertain linear systems

    Science.gov (United States)

    Shieh, L. S.; Sunkel, J. W.; Wang, Y. J.

    1990-01-01

    This paper presents a linear quadratic regulator approach to the stabilization of uncertain linear systems. The uncertain systems under consideration are described by state equations with the presence of time-varying unknown-but-bounded uncertainty matrices. The method is based on linear quadratic regulator (LQR) theory and Liapunov stability theory. The robust stabilizing control law for a given uncertain system can be easily constructed from the symmetric positive-definite solution of the associated augmented Riccati equation. The proposed approach can be applied to matched and/or mismatched systems with uncertainty matrices in which only their matrix norms are bounded by some prescribed values and/or their entries are bounded by some prescribed constraint sets. Several numerical examples are presented to illustrate the results.

  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

    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......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...

  5. Regulating Rac in the nervous system: molecular function and disease implication of Rac GEFs and GAPs.

    Science.gov (United States)

    Bai, Yanyang; Xiang, Xiaoliang; Liang, Chunmei; Shi, Lei

    2015-01-01

    Rho family GTPases, including RhoA, Rac1, and Cdc42 as the most studied members, are master regulators of actin cytoskeletal organization. Rho GTPases control various aspects of the nervous system and are associated with a number of neuropsychiatric and neurodegenerative diseases. The activity of Rho GTPases is controlled by two families of regulators, guanine nucleotide exchange factors (GEFs) as the activators and GTPase-activating proteins (GAPs) as the inhibitors. Through coordinated regulation by GEFs and GAPs, Rho GTPases act as converging signaling molecules that convey different upstream signals in the nervous system. So far, more than 70 members of either GEFs or GAPs of Rho GTPases have been identified in mammals, but only a small subset of them have well-known functions. Thus, characterization of important GEFs and GAPs in the nervous system is crucial for the understanding of spatiotemporal dynamics of Rho GTPase activity in different neuronal functions. In this review, we summarize the current understanding of GEFs and GAPs for Rac1, with emphasis on the molecular function and disease implication of these regulators in the nervous system.

  6. 77 FR 53826 - Special Regulations; Areas of the National Park System, Yellowstone National Park

    Science.gov (United States)

    2012-09-04

    ... National Park Service 36 CFR Part 7 RIN 1024-AE10 Special Regulations; Areas of the National Park System, Yellowstone National Park AGENCY: National Park Service, Interior. ACTION: Proposed rule. SUMMARY: This rule... snowmobiles operating in the park to meet certain National Park Service air and sound emissions......

  7. 76 FR 39048 - Special Regulations; Areas of the National Park System, Yellowstone National Park

    Science.gov (United States)

    2011-07-05

    ... National Park Service 36 CFR Part 7 RIN 1024-AD92 Special Regulations; Areas of the National Park System, Yellowstone National Park AGENCY: National Park Service, Interior. ACTION: Proposed rule. SUMMARY: The National Park Service (NPS) is proposing this rule to establish a management framework that allows...

  8. 77 FR 73919 - Special Regulations; Areas of the National Park System, Yellowstone National Park

    Science.gov (United States)

    2012-12-12

    ... National Park Service 36 CFR Part 7 RIN 1024-AE10 Special Regulations; Areas of the National Park System, Yellowstone National Park AGENCY: National Park Service, Interior. ACTION: Final rule. SUMMARY: This rule... governs winter visitation and certain recreational activities in Yellowstone National Park for the...

  9. 76 FR 77131 - Special Regulations; Areas of the National Park System, Yellowstone National Park

    Science.gov (United States)

    2011-12-12

    ... National Park Service 36 CFR Part 7 RIN 1024-AD92 Special Regulations; Areas of the National Park System, Yellowstone National Park AGENCY: National Park Service, Interior. ACTION: Final rule. SUMMARY: This rule... winter visitation and certain recreational activities in Yellowstone National Park for the...

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    Heffron Fred

    2011-06-01

    Full Text Available Abstract 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.

  12. [Automatic regulator of venous pressure and venous outflow in the perfusion system].

    Science.gov (United States)

    Smirnov, L M; Levinskiĭ, M M; Kharnas, S Sh; Cherniak, V A

    1976-01-01

    A scheme for automatic regulation of the venous pressure and venous blood outflow during extracorporeal circulation is proposed. The system consists of a photoelectric sensor placed on a tube led out of the major venous trunkline, a converter and an electromechanical eccentric clamp that compresses the venous trunkline, all of which secures stabilization of the controlled values.

  13. 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.

  14. 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

  15. Distributed Self-regulation Induced by Negative Feedbacks in Ecological and Economic Systems

    CERN Document Server

    Gafiychuk, V V; Ulanowicz, R E; Ulanowicz, Robert E.

    1998-01-01

    We consider an ecological system governed by Lotka-Volterra dynamics and an example of an economic system as a mesomarket with perfect competition. We propose a mechanism for cooperative self-regulation that enables the system under consideration to respond properly to changes in the environment. This mechanism is based on (1) active individual behavior of the system elements at each hierarchical level and (2) self-processing of information caused by the hierarchical organization. It is shown how the proposed mechanism suppresses nonlocal interaction of elements belonging to a particular level as mediated by higher levels.

  16. The σ(54)-dependent two-component system regulating sulfur oxidization (Sox) system in Acidithiobacillus caldus and some chemolithotrophic bacteria.

    Science.gov (United States)

    Li, Li-Feng; Fu, Luo-Jie; Lin, Jian-Qun; Pang, Xin; Liu, Xiang-Mei; Wang, Rui; Wang, Zhao-Bao; Lin, Jian-Qiang; Chen, Lin-Xu

    2017-03-01

    The sulfur oxidization (Sox) system is the central sulfur oxidization pathway of phototrophic and chemotrophic sulfur-oxidizing bacteria. Regulation and function of the Sox system in the chemotrophic Paracoccus pantotrophus has been elucidated; however, to date, no information is available on the regulation of this system in the chemolithotrophic Acidithiobacillus caldus, which is widely utilized in bioleaching. We described the novel tspSR-sox-like clusters in A. caldus and other chemolithotrophic sulfur-oxidizing bacteria containing Sox systems. The highly homologous σ(54)-dependent two-component signaling system (TspS/R), upstream of the sox operons in these novel clusters, was identified by phylogenetic analyses. A typical σ(54)-dependent promoter, P1, was identified upstream of soxX-I in the sox-I cluster of A. caldus MTH-04. The transcriptional start site (G) and the -12/-24 regions (GC/GG) of P1 were determined by rapid amplification of cDNA ends (5'RACE), and the upstream activator sequences (UASs; TGTCCCAAATGGGACA) were confirmed by electrophoretic mobility shift assays (EMSAs) in vitro and by UAS-probe-plasmids assays in vivo. Sequence analysis of promoter regions in tspSR-sox-like clusters revealed that there were similar σ(54)-dependent promoters upstream of the soxX genes. Based on our results, we proposed a TspSR-mediated signal transduction and transcriptional regulation pathway for the Sox system in A. caldus. The regulation of σ(54)-dependent two-component systems (TCSs) for Sox pathways were explained for the first time in A. caldus, A. thiooxidans, T. tepidarius, and T. denitrificans, indicating the significance of modulating the sulfur oxidization in these chemolithotrophic sulfur oxidizers.

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

    OpenAIRE

    Veriha Hanna V.

    2016-01-01

    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 ...

  18. The ubiquitin system: a critical regulator of innate immunity and pathogen–host interactions

    OpenAIRE

    Li, Jie; Chai, Qi-Yao; Liu, Cui Hua

    2016-01-01

    The ubiquitin system comprises enzymes that are responsible for ubiquitination and deubiquitination, as well as ubiquitin receptors that are capable of recognizing and deciphering the ubiquitin code, which act in coordination to regulate almost all host cellular processes, including host–pathogen interactions. In response to pathogen infection, the host innate immune system launches an array of distinct antimicrobial activities encompassing inflammatory signaling, phagosomal maturation, autop...

  19. On Output Regulation in Systems with Differential Variational Inequalities (Long Version)

    OpenAIRE

    Tanwani, Aneel; Brogliato, Bernard; Prieur, Christophe

    2014-01-01

    International audience; We consider the problem of designing state feedback control laws for output regulation in a class of dynamical systems which are described by variational inequalities and ordinary differential equations. In our setup, these variational inequalities are used to model state trajectories constrained to evolve within time-varying, closed, and convex sets, and systems with complementarity relations. We first derive conditions to study the existence and uniqueness of solutio...

  20. Effect of Heavy Ion Brain Radiation on Nerve-immune System Regulation Mechanism in Rat

    Institute of Scientific and Technical Information of China (English)

    YU; Ying-qi; WANG; Xiao; KONG; Fu-quan; SUI; Li; LEI; Run-hong; MA; Hong; DENG; Yu-lin; LI; Qiang

    2013-01-01

    High-dose ionizing irradiation can cause extensive injuries in susceptible tissues.Blood,nervous and immune systems are highly radiation-sensitive.While the nerve-immune system regulation of radiationdamage in the relevant research is rare.So the brain injury model that rats were subjected to 15 Gy of head irradiation was built.By detecting hypothalamic-pituitary-adrenal axis(HPA axis)changes,the

  1. Research on speed control of secondary regulation lifting system of parking equipment

    Science.gov (United States)

    Zang, Faye

    2005-12-01

    Hydrostatic transmission with secondary regulation is a new kind of hydrostatic transmission that can regenerate inertial and gravitational energy of load. On the basis of an in-depth analysis of the working principles and energy-saving mechanisms of the parking equipment lifting systems with, secondary regulating technology, this paper proposes a method of regenerating a lifting system's inertial energy by controlling rotational speed and reclaiming the gravitational energy by use of a constant rotational speed. Considering large changes of the parameters of lifting systems and then non-linearity, a fuzzy control was adopted to control the lifting system, and a mathematical model of the system was established. By simulation and experiment of the lifting system, the conclusion was reached a lifting system's braking achieved by controlling rotational speed is reliable and stable at a definite speed. It also permits changing the efficiency of recovery by changing the rotational speed. The design power of the lifting system can be chosen in terms of the system's average power, so the system's power can be reduced and energy savings achieved.

  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. 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.

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

    Science.gov (United States)

    Cao, Dan-Dan; Li, Lu; Chan, Wai-Yee

    2016-05-28

    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.

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

    Science.gov (United States)

    Woo, Choong-Wan; Roy, Mathieu; Buhle, Jason T; Wager, Tor D

    2015-01-01

    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.

  6. 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.

  7. Modeling and Verification of Distributed Generation and Voltage Regulation Equipment for Unbalanced Distribution Power Systems; Annual Subcontract Report, June 2007

    Energy Technology Data Exchange (ETDEWEB)

    Davis, M. W.; Broadwater, R.; Hambrick, J.

    2007-07-01

    This report summarizes the development of models for distributed generation and distribution circuit voltage regulation equipment for unbalanced power systems and their verification through actual field measurements.

  8. Two-component signal transduction pathways regulating growth and cell cycle progression in a bacterium: a system-level analysis

    National Research Council Canada - National Science Library

    Skerker, Jeffrey M; Prasol, Melanie S; Perchuk, Barrett S; Biondi, Emanuele G; Laub, Michael T

    2005-01-01

    Two-component signal transduction systems, comprised of histidine kinases and their response regulator substrates, are the predominant means by which bacteria sense and respond to extracellular signals...

  9. Genome-wide identification of genes regulated by the Rcs phosphorelay system in Erwinia amylovora.

    Science.gov (United States)

    Wang, Dongping; Qi, Mingsheng; Calla, Bernarda; Korban, Schuyler S; Clough, Steven J; Cock, Peter J A; Sundin, George W; Toth, Ian; Zhao, Youfu

    2012-01-01

    The exopolysaccharide amylovoran is one of the major pathogenicity factors in Erwinia amylovora, the causal agent of fire blight of apples and pears. We have previously demonstrated that the RcsBCD phosphorelay system is essential for virulence by controlling amylovoran biosynthesis. We have also found that the hybrid sensor kinase RcsC differentially regulates amylovoran production in vitro and in vivo. To further understand how the Rcs system regulates E. amylovora virulence gene expression, we conducted genome-wide microarray analyses to determine the regulons of RcsB and RcsC in liquid medium and on immature pear fruit. Array analyses identified a total of 648 genes differentially regulated by RcsCB in vitro and in vivo. Consistent with our previous findings, RcsB acts as a positive regulator in both conditions, while RcsC positively controls expression of amylovoran biosynthetic genes in vivo but negatively controls expression in vitro. Besides amylovoran biosynthesis and regulatory genes, cell-wall and cell-envelope (membrane) as well as regulatory genes were identified as the major components of the RcsBC regulon, including many novel genes. We have also demonstrated that transcripts of rcsA, rcsC, and rcsD genes but not the rcsB gene were up-regulated when bacterial cells were grown in minimal medium or following infection of pear fruits compared with those grown in Luria Bertani medium. Furthermore, using the genome of E. amylovora ATCC 49946, a hidden Markov model predicted 60 genes with a candidate RcsB binding site in the intergenic region, 28 of which were identified in the microarray assay. Based on these findings as well as previous reported data, a working model has been proposed to illustrate how the Rcs phosphorelay system regulates virulence gene expression in E. amylovora.

  10. Streptomyces lipmanii expresses two restriction systems that inhibit plasmid transformation and bacteriophage plaque formation.

    Science.gov (United States)

    Matsushima, P; Baltz, R H

    1989-06-01

    Bacteriophage host range studies suggested that several beta-lactam-producing streptomycetes express similar restriction-modification systems. Streptomyces lipmanii LE32 expressed two restriction-modification systems, designated SliI and SliII. A mutant strain, PM87, was defective only in SliI restriction but expressed both SliI and SliII modification. Streptomyces sp. strain A57986, a natural isolate partially deficient in the expression of SliI and SliII restriction, nevertheless modified bacteriophage DNA for both SliI and SliII specificities. Protoplasts of PM87 and A57986 were transformed by several plasmids, and the modified plasmids isolated from these strains transformed wild-type S. lipmanii efficiently.

  11. ACTIVE CONTROL OF QUARTER-CAR SUSPENSION SYSTEM USING LINEAR QUADRATIC REGULATOR

    Directory of Open Access Journals (Sweden)

    V.M. Nandedkar

    2011-06-01

    Full Text Available The automobile is composed of many systems. One of these is the suspension system. The main functions of the automotive suspension system are to provide vehicle support, stability and directional control during handling manoeuvres and to provide effective isolation from road disturbances. The suspension system has to balance the tradeoff between ride comfort and handling performance. This paper analyses the passive suspension system and active suspension system using a Linear Quadratic Regulator (LQR controller. A linear quarter-car model is used for the analysis and simulation. The performance of the LQR controller is compared with the passive suspension system. The simulation results show that the LQR controller improves vehicle ride comfort.

  12. Regulation of Copper Transport Crossing Brain Barrier Systems by Cu-ATPases: Effect of Manganese Exposure

    OpenAIRE

    Fu, Xue; Zhang, Yanshu; Jiang, Wendy; Monnot, Andrew Donald; Bates, Christopher Alexander; Zheng, Wei

    2014-01-01

    Regulation of cellular copper (Cu) homeostasis involves Cu-transporting ATPases (Cu-ATPases), i.e., ATP7A and ATP7B. The question as to how these Cu-ATPases in brain barrier systems transport Cu, i.e., toward brain parenchyma, cerebrospinal fluid (CSF), or blood, remained unanswered. This study was designed to characterize roles of Cu-ATPases in regulating Cu transport at the blood-brain barrier (BBB) and blood-CSF barrier (BCB) and to investigate how exposure to toxic manganese (Mn) altered ...

  13. Output regulation for linear multi-agent systems with unmeasurable nodes

    Science.gov (United States)

    Liang, Hong-Jing; Zhang, Hua-Guang; Wang, Zhan-Shan; Wang, Jun-Yi

    2014-01-01

    The output regulation of linear multi-agent systems with partial unmeasurable agents is investigated in this paper. All the agents except the exosystem can be classified into two groups. Agents in the first group can be measured by themselves and their neighbors. State variables are not fully accessible for direct communication and full order Luenberger observers are constructed for the unmeasurable agents. We give a state feedback control law to solve the output regulation problem under the communication topologies based on both measurable and unmeasurable agents. The heterogeneous agents' synchronization problem is a general case of our results. Finally, examples are utilized to show the effectiveness of the obtained results.

  14. Distributed formation output regulation of switching heterogeneous multi-agent systems

    Science.gov (United States)

    Wang, Xiaoli

    2013-11-01

    In this article, the distributed formation output regulation problem of linear heterogeneous multi-agent systems with uncertainty under switching topology is considered. It is a generalised framework for multi-agent coordination problems, which contains or concerns a variety of important multi-agent problems in a quite unified way. Its background includes active leader following formation for the agents to maintain desired relative distances and orientations to the leader with a predefined trajectory, and multi-agent formation with environmental inputs. With the help of canonical internal model we design a distributed dynamic output feedback to handle the distributed formation output regulation problem.

  15. Linear Modeling, Simulation and Experimental Verification of a Pressure Regulator for CNG Injection Systems

    Directory of Open Access Journals (Sweden)

    Dirk Hübner

    2008-08-01

    Full Text Available The number of motor vehicles powered by internal combustion engines keeps growing despite shrinking oil reserves. As a result, compressed natural gas (CNG is gaining currency as an emerging combustion engine fuel. To this day, CNG systems – e.g., in passenger cars – are not fully integrated into the development process as conducted by vehicle or engine manufacturers. Instead, they are usually "adapted in" at a downstream stage by small, specialized companies. The present paper initially outlines the state of the art in advanced gas injection technologies. Especially the development towards sequential injection systems is described. A pressure regulator for CNG driven combustion engines is examined in detail, given its role as a highly sensitive and critical system component. Based on a precise theoretical analysis, a linear model of this pressure regulator is derived and subjected to dynamic simulation. The analytical approach is accompanied by an experimental investigation of the device. On a test rig developed at the Trier University of Applied Sciences, the static and dynamic features of the pressure regulator can be measured with the requisite precision. The comparison of measured and simulated data yields a validation of the dynamic simulation model. With the approaches developed it is now possible for the first time to model, simulate and optimize single- or multi-stage pressure regulators for CNG driven engines with less effort and higher accuracy.

  16. The Role of Two-Component Signal Transduction Systems in Staphylococcus aureus Virulence Regulation.

    Science.gov (United States)

    Haag, Andreas F; Bagnoli, Fabio

    2016-01-05

    Staphylococcus aureus is a versatile, opportunistic human pathogen that can asymptomatically colonize a human host but can also cause a variety of cutaneous and systemic infections. The ability of S. aureus to adapt to such diverse environments is reflected in the presence of complex regulatory networks fine-tuning metabolic and virulence gene expression. One of the most widely distributed mechanisms is the two-component signal transduction system (TCS) which allows a pathogen to alter its gene expression profile in response to environmental stimuli. The simpler TCSs consist of only a transmembrane histidine kinase (HK) and a cytosolic response regulator. S. aureus encodes a total of 16 conserved pairs of TCSs that are involved in diverse signalling cascades ranging from global virulence gene regulation (e.g. quorum sensing by the Agr system), the bacterial response to antimicrobial agents, cell wall metabolism, respiration and nutrient sensing. These regulatory circuits are often interconnected and affect each other's expression, thus fine-tuning staphylococcal gene regulation. This manuscript gives an overview of the current knowledge of staphylococcal environmental sensing by TCS and its influence on virulence gene expression and virulence itself. Understanding bacterial gene regulation by TCS can give major insights into staphylococcal pathogenicity and has important implications for knowledge-based drug design and vaccine formulation.

  17. Design of Optimal Output Regulators for Dual-Rate Linear Discrete-Time Systems Based on the Lifting Technique

    Directory of Open Access Journals (Sweden)

    Yujian Guo

    2016-01-01

    Full Text Available A design strategy of optimal output regulators for dual-rate discrete-time systems, whose output sampling period is an integer multiple of the input updating period, is proposed. At first, by using the discrete lifting technique, the dual-rate discrete-time system is converted to a single-rate augmented system in form and the lifted state-space model is constructed. Correspondingly, the performance index of the original system is modified to the performance index of the single-rate augmented system. And the original problem is transformed into an output regulation problem for the augmented system. Then, according to the optimal regulator theory, an optimal output regulator for the dual-rate discrete-time system is derived. In the meantime, the existence conditions of the optimal output regulator are discussed. Finally, a numerical example is included to illustrate the effectiveness of the proposed method.

  18. Negative auto-regulation increases the input dynamic-range of the arabinose system of Escherichia coli

    Directory of Open Access Journals (Sweden)

    Bren Anat

    2011-07-01

    Full Text Available Abstract Background Gene regulation networks are made of recurring regulatory patterns, called network motifs. One of the most common network motifs is negative auto-regulation, in which a transcription factor represses its own production. Negative auto-regulation has several potential functions: it can shorten the response time (time to reach halfway to steady-state, stabilize expression against noise, and linearize the gene's input-output response curve. This latter function of negative auto-regulation, which increases the range of input signals over which downstream genes respond, has been studied by theory and synthetic gene circuits. Here we ask whether negative auto-regulation preserves this function also in the context of a natural system, where it is embedded within many additional interactions. To address this, we studied the negative auto-regulation motif in the arabinose utilization system of Escherichia coli, in which negative auto-regulation is part of a complex regulatory network. Results We find that when negative auto-regulation is disrupted by placing the regulator araC under constitutive expression, the input dynamic range of the arabinose system is reduced by 10-fold. The apparent Hill coefficient of the induction curve changes from about n = 1 with negative auto-regulation, to about n = 2 when it is disrupted. We present a mathematical model that describes how negative auto-regulation can increase input dynamic-range, by coupling the transcription factor protein level to the input signal. Conclusions Here we demonstrate that the negative auto-regulation motif in the native arabinose system of Escherichia coli increases the range of arabinose signals over which the system can respond. In this way, negative auto-regulation may help to increase the input dynamic-range while maintaining the specificity of cooperative regulatory systems. This function may contribute to explaining the common occurrence of negative auto-regulation

  19. Negative auto-regulation increases the input dynamic-range of the arabinose system of Escherichia coli.

    Science.gov (United States)

    Madar, Daniel; Dekel, Erez; Bren, Anat; Alon, Uri

    2011-07-12

    Gene regulation networks are made of recurring regulatory patterns, called network motifs. One of the most common network motifs is negative auto-regulation, in which a transcription factor represses its own production. Negative auto-regulation has several potential functions: it can shorten the response time (time to reach halfway to steady-state), stabilize expression against noise, and linearize the gene's input-output response curve. This latter function of negative auto-regulation, which increases the range of input signals over which downstream genes respond, has been studied by theory and synthetic gene circuits. Here we ask whether negative auto-regulation preserves this function also in the context of a natural system, where it is embedded within many additional interactions. To address this, we studied the negative auto-regulation motif in the arabinose utilization system of Escherichia coli, in which negative auto-regulation is part of a complex regulatory network. We find that when negative auto-regulation is disrupted by placing the regulator araC under constitutive expression, the input dynamic range of the arabinose system is reduced by 10-fold. The apparent Hill coefficient of the induction curve changes from about n = 1 with negative auto-regulation, to about n = 2 when it is disrupted. We present a mathematical model that describes how negative auto-regulation can increase input dynamic-range, by coupling the transcription factor protein level to the input signal. Here we demonstrate that the negative auto-regulation motif in the native arabinose system of Escherichia coli increases the range of arabinose signals over which the system can respond. In this way, negative auto-regulation may help to increase the input dynamic-range while maintaining the specificity of cooperative regulatory systems. This function may contribute to explaining the common occurrence of negative auto-regulation in biological systems.

  20. Real power regulation design for multi-terminal VSC-HVDC systems

    Science.gov (United States)

    Li, Guo-Jie; Ruan, Si-Ye; Lie, Tek

    2013-06-01

    A multi-terminal voltage-source-converter (VSC) based high voltage direct current (HVDC) system is concerned for its flexibility and reliability. In this study, a control strategy for multiple VSCs is proposed to auto-share the real power variation without changing control mode, which is based on "dc voltage droop" power regulation functions. With the proposed power regulation design, the multiple VSCs automatically share the real power change and the VSC-HVDC system is stable even under loss of any one converter while there is no overloading for any individual converter. Simulation results show that it is effective to balance real power for power disturbance and thus improves operation reliability for the multi-terminal VSC-HVDC system by the proposed control strategy.

  1. The adaptive immune system as a fundamental regulator of adipose tissue inflammation and insulin resistance.

    Science.gov (United States)

    Winer, Shawn; Winer, Daniel A

    2012-09-01

    Over the past decade, chronic inflammation in visceral adipose tissue (VAT) has gained acceptance as a lead promoter of insulin resistance in obesity. A great deal of evidence has pointed to the role of adipokines and innate immune cells, in particular, adipose tissue macrophages, in the regulation of fat inflammation and glucose homeostasis. However, more recently, cells of the adaptive immune system, specifically B and T lymphocytes, have emerged as unexpected promoters and controllers of insulin resistance. These adaptive immune cells infiltrate obesity expanded VAT and through cytokine secretion and macrophage modulation dictate the extent of the local inflammatory response, thereby directly impacting insulin resistance. The remarkable ability of our adaptive immune system to regulate insulin sensitivity and metabolism has unmasked a novel physiological function of this system, and promises new diagnostic and therapeutic strategies to manage the disease. This review highlights critical roles of adipose tissue lymphocytes in governing glucose homeostasis.

  2. Correlation between early-life regulation of the immune system by microbiota and allergy development.

    Science.gov (United States)

    Gensollen, Thomas; Blumberg, Richard S

    2017-04-01

    Early postnatal life is a key time for development of the immune system and colonization of the host by microbiota. Recent studies have shown that specific limbs of the immune system can be regulated by microbiota in a time-restricted period during early life. Studies in mouse models have shown that perturbations of the microbiota during early life can cause immune effects that can persist into adulthood and create increased host susceptibility to certain diseases. Here we discuss the role of early-life regulation of the immune system by the microbiota and how it can be related to allergy development. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  3. [The Integration and Regulation of Hormone-Sensitive Lipase in Reproductive System].

    Science.gov (United States)

    Wang, Wei-yi; Xu, Guo-Heng

    2015-02-01

    Hormone-sensitive lipase (HSL) has long been considered as a classical rate-limiting enzyme during lipolysis since it was first described in 1960s. HSL is regulated mainly by catecholamine, including adrenalin. Studies in recent years indicated that the substrates for HSL are not only triglycerides, but also diacylglycerol with the catalytic activity is ten times that of triglycerides, glycerol esters and cholesterol esters, which overthrow the opinion that HSL is specific to triglyceride. The scientists have generated HSL gene knockout mice and confirmed HSL is widely located in the reproductive system, which indicates that HSL may play an important role in the regulation of physiological and pathophysiological process in the reproductive system. Here, we will focus on the features of the HSL gene, mRNA and its protein, and summarize the HSL functions in the reproductive system.

  4. Role of the endocannabinoid system in energy balance regulation and obesity.

    Science.gov (United States)

    Cota, Daniela

    2008-01-01

    The endogenous cannabinoid system (ECS) is a neuromodulatory system recently recognized to have a role in the regulation of various aspects of eating behavior and energy balance through central and peripheral mechanisms. In the central nervous system, cannabinoid type 1 receptors and their endogenous ligands, the endocannabinoids, are involved in modulating food intake and motivation to consume palatable food. Moreover, the ECS is present in peripheral organs, such as liver, white adipose tissue, muscle, and pancreas, where it seems to be involved in the regulation of lipid and glucose homeostasis. Dysregulation of the ECS has been associated with the development of obesity and its sequelae, such as dyslipidemia and diabetes. Conversely, recent clinical trials have shown that cannabinoid type 1 receptor blockade may ameliorate these metabolic abnormalities. Although further investigation is needed to better define the actual mechanisms of action, pharmacologic approaches targeting the ECS may provide a novel, effective option for the management of obesity, type 2 diabetes and cardiovascular disease.

  5. A computer-based microarray experiment design-system for gene-regulation pathway discovery.

    Science.gov (United States)

    Yoo, Changwon; Cooper, Gregory F

    2003-01-01

    This paper reports the methods and evaluation of a computer-based system that recommends microarray experimental design for biologists - causal discovery in Gene Expression data using Expected Value of Experimentation (GEEVE). The GEEVE system uses causal Bayesian networks and generates a decision tree for recommendations. To evaluate the GEEVE system, we first built an expression simulation model based on a gene regulation model assessed by an expert biologist. Using the simulation model, we conducted a controlled study that involved 10 biologists, some of whom used GEEVE and some of whom did not. The results show that biologists who used GEEVE reached correct causal assessments about gene regulation more often than did those biologists who did not use GEEVE.

  6. Asymptotic regulation of cascade systems with unknown control directions and nonlinear parameterization

    Institute of Scientific and Technical Information of China (English)

    Qiangde WANG; Chunling WEI; Yuqiang WU

    2009-01-01

    A robust partial-state feedback asymptotic regulating control scheme is developed for a class of cascade systems with both nonlinear uncertainties and unknown control directions.A parameter separation technique is introduced to separate the time-varying uncertainty and the unmeasurable state from nonlinear functions.Then,the Nussbaum-type gain method together with the idea of changing supply functions is adopted in the design of a smooth partial-state regulator that can ensure all the signals of the closed-loop system are globally uniformly bounded.Especially,the system state asymptotically converges to zero.The design procedure is illustrated through an example and the simulation results show that the controller is feasible and effective.

  7. Central nervous system regulation of eating: Insights from human brain imaging.

    Science.gov (United States)

    Farr, Olivia M; Li, Chiang-Shan R; Mantzoros, Christos S

    2016-05-01

    Appetite and body weight regulation are controlled by the central nervous system (CNS) in a rather complicated manner. The human brain plays a central role in integrating internal and external inputs to modulate energy homeostasis. Although homeostatic control by the hypothalamus is currently considered to be primarily responsible for controlling appetite, most of the available evidence derives from experiments in rodents, and the role of this system in regulating appetite in states of hunger/starvation and in the pathogenesis of overeating/obesity remains to be fully elucidated in humans. Further, cognitive and affective processes have been implicated in the dysregulation of eating behavior in humans, but their exact relative contributions as well as the respective underlying mechanisms remain unclear. We briefly review each of these systems here and present the current state of research in an attempt to update clinicians and clinical researchers alike on the status and future directions of obesity research.

  8. 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.

  9. Leptin regulation of the interleukin-1 system in human endometrial cells.

    Science.gov (United States)

    Gonzalez, Ruben Rene; Leary, Kristen; Petrozza, John Christopher; Leavis, Paul Clifton

    2003-03-01

    We have previously shown that (i). leptin and leptin receptor (Ob-R) are expressed in the human endometrium, and (ii). leptin secretion is regulated in blastocyst and endometrial epithelial cell (EEC) co-cultures. Interleukin-1beta (IL-1beta) up-regulates leptin and Ob-R, and both cytokines up-regulate beta3 integrin expression in EEC. In the present investigation we examined the effect of leptin on the expression of the IL-1 system in EEC and endometrial stromal cells (ESC) cultured in a medium containing insulin, leptin or IL-1beta (0-3 nmol/l). Leptin stimulated IL-1 antagonist (IL-1Ra), IL-1beta secretion and expression of IL-1 receptor type I (IL-1R tI) in both cell types. IL-1beta and IL-1Ra secretion were down-regulated by IL-1R tI blockade using specific antibodies. Interestingly, leptin partially neutralized this effect. The blockade of Ob-R neutralized the effects of both leptin and IL-1beta on expression of the IL-1beta system and beta3 integrin and on phosphorylation of signal transducer and activator of transcription 3 (Stat3). These results suggest that leptin regulates the IL-1 system and that the blockade of functional Ob-R impairs leptin and IL-1beta functions at the endometrial level. Leptin could be an important molecule for implantation and a molecular mediator for actions of the IL-1 system. The fact that leptin, in the absence of IL-1, can trigger the expression of markers of endometrial receptivity and of the invasive trophoblast phenotype (as does IL-1), suggest that leptin could substitute for these IL-1 functions during the implantation process.

  10. Cardiomyocyte Regulation of Systemic Lipid Metabolism by the Apolipoprotein B-Containing Lipoproteins in Drosophila

    Science.gov (United States)

    Ishikawa, Zachary

    2017-01-01

    The heart has emerged as an important organ in the regulation of systemic lipid homeostasis; however, the underlying mechanism remains poorly understood. Here, we show that Drosophila cardiomyocytes regulate systemic lipid metabolism by producing apolipoprotein B-containing lipoproteins (apoB-lipoproteins), essential lipid carriers that are so far known to be generated only in the fat body. In a Drosophila genetic screen, we discovered that when haplo-insufficient, microsomal triglyceride transfer protein (mtp), required for the biosynthesis of apoB-lipoproteins, suppressed the development of diet-induced obesity. Tissue-specific inhibition of Mtp revealed that whereas knockdown of mtp only in the fat body decreases systemic triglyceride (TG) content on normal food diet (NFD) as expected, knockdown of mtp only in the cardiomyocytes also equally decreases systemic TG content on NFD, suggesting that the cardiomyocyte- and fat body-derived apoB-lipoproteins serve similarly important roles in regulating whole-body lipid metabolism. Unexpectedly, on high fat diet (HFD), knockdown of mtp in the cardiomyocytes, but not in fat body, protects against the gain in systemic TG levels. We further showed that inhibition of the Drosophila apoB homologue, apolipophorin or apoLpp, another gene essential for apoB-lipoprotein biosynthesis, affects systemic TG levels similarly to that of Mtp inhibition in the cardiomyocytes on NFD or HFD. Finally, we determined that HFD differentially alters Mtp and apoLpp expression in the cardiomyocytes versus the fat body, culminating in higher Mtp and apoLpp levels in the cardiomyocytes than in fat body and possibly underlying the predominant role of cardiomyocyte-derived apoB-lipoproteins in lipid metabolic regulation. Our findings reveal a novel and significant function of heart-mediated apoB-lipoproteins in controlling lipid homeostasis. PMID:28095410

  11. Performance limitations in the tracking and regulation problem for discrete-time systems.

    Science.gov (United States)

    Jiang, Xiao-Wei; Guan, Zhi-Hong; Yuan, Fu-Shun; Zhang, Xian-He

    2014-03-01

    In this paper, the optimal tracking and regulation performance of discrete-time, multi-input multi-output, linear time-invariant systems is investigated. The control signal is influenced by the external disturbance, and the output feedback is subjected to an additive white Gaussian noise (AWGN) corruption. The tracking error with channel input power constraint and the output regulation with control energy constraint are adopted as the measure of tracking and regulation performance respectively, which can be obtained by searching through all stabilizing two-parameter controllers. Both results demonstrate that the performance is closely related to locations and directions of the nonminimum phase zeros, unstable poles of the plant and may be badly degraded by external disturbance and AWGN.

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

    Science.gov (United States)

    Bogusz-Czerniewicz, Marta

    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.

  13. Bone remodeling in the context of cellular and systemic regulation: the role of osteocytes and the nervous system.

    Science.gov (United States)

    Niedźwiedzki, Tadeusz; Filipowska, Joanna

    2015-10-01

    Bone is a dynamic tissue that undergoes constant remodeling. The appropriate course of this process determines development and regeneration of the skeleton. Tight molecular control of bone remodeling is vital for the maintenance of appropriate physiology and microarchitecture of the bone, providing homeostasis, also at the systemic level. The process of remodeling is regulated by a rich innervation of the skeleton, being the source of various growth factors, neurotransmitters, and hormones regulating function of the bone. Although the course of bone remodeling at the cellular level is mainly associated with the activity of osteoclasts and osteoblasts, recently also osteocytes have gained a growing interest as the principal regulators of bone turnover. Osteocytes play a significant role in the regulation of osteogenesis, releasing sclerostin (SOST), an inhibitor of bone formation. The process of bone turnover, especially osteogenesis, is also modulated by extra-skeletal molecules. Proliferation and differentiation of osteoblasts are promoted by the brain-derived serotonin and hypothetically inhibited by its intestinal equivalent. The activity of SOST and serotonin is either directly or indirectly associated with the canonical Wnt/β-catenin signaling pathway, the main regulatory pathway of osteoblasts function. The impairment of bone remodeling may lead to many skeletal diseases, such as high bone mass syndrome or osteoporosis. In this paper, we review the most recent data on the cellular and molecular mechanisms of bone remodeling control, with particular emphasis on the role of osteocytes and the nervous system in this process.

  14. Surface acoustic wave regulated single photon emission from a coupled quantum dot-nanocavity system

    Science.gov (United States)

    Weiß, M.; Kapfinger, S.; Reichert, T.; Finley, J. J.; Wixforth, A.; Kaniber, M.; Krenner, H. J.

    2016-07-01

    A coupled quantum dot-nanocavity system in the weak coupling regime of cavity-quantumelectrodynamics is dynamically tuned in and out of resonance by the coherent elastic field of a fSAW ≃ 800 MHz surface acoustic wave. When the system is brought to resonance by the sound wave, light-matter interaction is strongly increased by the Purcell effect. This leads to a precisely timed single photon emission as confirmed by the second order photon correlation function, g(2). All relevant frequencies of our experiment are faithfully identified in the Fourier transform of g(2), demonstrating high fidelity regulation of the stream of single photons emitted by the system.

  15. Robust Regulation and Tracking Control of a Class of Uncertain 2DOF Underactuated Mechanical Systems

    Directory of Open Access Journals (Sweden)

    David I. Rosas Almeida

    2015-01-01

    Full Text Available A strategy to design and implement a robust controller for a class of underactuated mechanical systems, with two degrees of freedom, which solves the problems of regulation and trajectory tracking, is proposed. This control strategy considers the partial measurement of the state vector and the presence of parametric uncertainties in the plant; these conditions are common in the implementation of a control system. The strategy is based on the use of robust finite time convergence observers to estimate the unmeasured state variables, unknown disturbances, and other signals needed for the control system implementation. The performance of the control strategy is illustrated numerically and experimentally.

  16. 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.

  17. Frame for large self-regulated ecological system for space exploitation

    Science.gov (United States)

    Kondyurin, Alexey

    2016-07-01

    Future long term space activity with human crew requires self-regulated ecological system to provide water, air and food for crew. Modern theoretical and experimental investigation results show that a sustainable ecological system can be made, but it requires large enough area and volume, which cannot be provided with modern space ship and space station technologies. The large volume frame can be created with using of inflatable construction, which can be directly cured in space environment. Problems of the large constructions in space for self-ecological system are discussed.

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

    Science.gov (United States)

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

    2013-03-01

    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.

  19. [Importance of the endocannabinoid system in the regulation of energy homeostasis].

    Science.gov (United States)

    Kvasnicka, T

    2008-02-01

    The endocannabinoid system is an endogenous signaling system that plays a role in the regulation of energy homeostasis and lipid and glucose metabolism-all of which can influence cardiometabolic risk. The endocannabinoid system appears to be a promising novel mechanistic pathway that modulates important aspects afcardiovascular and metabolic function. The endocannabinoid system is normally a silent physiologic system that becomes transiently activated, that is, only when needed. Evidence suggests that the endocannabinoid system is tonically overactive in human obesity and in animal models of genetic and diet-induced obesity. However, there is evidence in studies that the ECS is tonically overactivated in obesity, although it remains unclear whether overactivation of the ECS precedes or is consequent to expression of the obese phenotype. Rimonabant, a selective cannabinoid-1 receptor (CB1) blocker, has been shown to reduce smoking, body weight and improve and improves the profile of several metabolic risk factors in high-risk patients.

  20. Semi-global and global output regulation for classes of nonlinear systems

    Science.gov (United States)

    McGregor, Nathan Kristin

    Many phenomena of interest to scientists and engineers can be modeled by nonlinear systems of ordinary differential equations with inputs and outputs. The dynamics of a rocket, for example, may have input and output variables representing thrust and velocity, respectively. The problem of output regulation entails the control of a given plant in such a way that the output of the system asymptotically tracks some reference trajectory while simultaneously rejecting disturbances, where the desired trajectory and the unwanted disturbances are both generated by an autonomous and exogenous system. Achieving this objective necessitates a dynamic nonlinear controller driven only by the regulated error, since neither the state of the plant nor the exogenous signals are assumed to be available for measurement. All trajectories of the resulting closed-loop system are required to remain bounded, and the regulated error must also decay asymptotically to zero. These conditions may need to be satisfied in spite of uncertainties regarding the plant, the exosystem, or the range of allowable initial states. If the state-space representation of the plant can be expressed with finitely many variables, the system is called finite-dimensional. When a solution is sought for every fixed, compact set of initial conditions, the problem is said to be semi-global. By contrast, if a solution is desired for the entire state-space, the problem is known as global regulation. In this dissertation, rather than addressing a particular application, such as a rocket, we present results on both semi-global and global output regulation for multiple classes of finite-dimensional, nonlinear control systems. In so doing, we generalize, in whole or in part, a number of recent papers in the literature. Among the concepts shared by all of these results are the notions of input-to-state stability with respect to compact sets, nonlinear immersion of the steady-state control, the normal form of nonlinear systems

  1. 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.

  2. Involvement of the Gut Chemosensory System in the Regulation of Colonic Anion Secretion

    Directory of Open Access Journals (Sweden)

    A. Kuwahara

    2015-01-01

    Full Text Available The primary function of the gastrointestinal (GI tract is the extraction of nutrients from the diet. Therefore, the GI tract must possess an efficient surveillance system that continuously monitors the luminal content for beneficial or harmful compounds. Recent studies have shown that specialized cells in the intestinal lining can sense changes in this content. These changes directly influence fundamental GI processes such as secretion, motility, and local blood flow via hormonal and/or neuronal pathways. Until recently, most studies examining the control of ion transport in the colon have focused on neural and hormonal regulation. However, study of the regulation of gut function by the gut chemosensory system has become increasingly important, as failure of this system causes dysfunctions in host homeostasis, as well as functional GI disorders. Furthermore, regulation of ion transport in the colon is critical for host defense and for electrolytes balance. This review discusses the role of the gut chemosensory system in epithelial transport, with a particular emphasis on the colon.

  3. Gene Regulation by the LiaSR Two-Component System in Streptococcus mutans.

    Directory of Open Access Journals (Sweden)

    Manoharan Shankar

    Full Text Available The LiaSR two-component signal transduction system regulates cellular responses to several environmental stresses, including those that induce cell envelope damages. Downstream regulons of the LiaSR system have been implicated in tolerance to acid, antibiotics and detergents. In the dental pathogen Streptococcus mutans, the LiaSR system is necessary for tolerance against acid, antibiotics, and cell wall damaging stresses during growth in the oral cavity. To understand the molecular mechanisms by which LiaSR regulates gene expression, we created a mutant LiaR in which the conserved aspartic acid residue (the phosphorylation site, was changed to alanine residue (D58A. As expected, the LiaR-D58A variant was unable to acquire the phosphate group and bind to target promoters. We also noted that the predicted LiaR-binding motif upstream of the lia operon does not appear to be well conserved. Consistent with this observation, we found that LiaR was unable to bind to the promoter region of lia; however, we showed that LiaR was able to bind to the promoters of SMU.753, SMU.2084 and SMU.1727. Based on sequence analysis and DNA binding studies we proposed a new 25-bp conserved motif essential for LiaR binding. Introducing alterations at fully conserved positions in the 25-bp motif affected LiaR binding, and the binding was dependent on the combination of positions that were altered. By scanning the S. mutans genome for the occurrence of the newly defined LiaR binding motif, we identified the promoter of hrcA (encoding a key regulator of the heat shock response that contains a LiaR binding motif, and we showed that hrcA is negatively regulated by the LiaSR system. Taken together our results suggest a putative role of the LiaSR system in heat shock responses of S. mutans.

  4. Chitinase expression in Listeria monocytogenes is positively regulated by the Agr system.

    Directory of Open Access Journals (Sweden)

    Dafni Katerina Paspaliari

    Full Text Available The food-borne pathogen Listeria monocytogenes encodes two chitinases, ChiA and ChiB, which allow the bacterium to hydrolyze chitin, the second most abundant polysaccharide in nature. Intriguingly, despite the absence of chitin in human and mammalian hosts, both of the chitinases have been deemed important for infection, through a mechanism that, at least in the case of ChiA, involves modulation of host immune responses. In this study, we show that the expression of the two chitinases is subject to regulation by the listerial agr system, a homologue of the agr quorum-sensing system of Staphylococcus aureus, that has so far been implicated in virulence and biofilm formation. We demonstrate that in addition to these roles, the listerial agr system is required for efficient chitin hydrolysis, as deletion of agrD, encoding the putative precursor of the agr autoinducer, dramatically decreased chitinolytic activity on agar plates. Agr was specifically induced in response to chitin addition in stationary phase and agrD was found to regulate the amount of chiA, but not chiB, transcripts. Although the transcript levels of chiB did not depend on agrD, the extracellular protein levels of both chitinases were reduced in the ΔagrD mutant. The regulatory effect of agr on chiA is potentially mediated through the small RNA LhrA, which we show here to be negatively regulated by agr. LhrA is in turn known to repress chiA translation by binding to the chiA transcript and interfering with ribosome recruitment. Our results highlight a previously unrecognized role of the agr system and suggest that autoinducer-based regulation of chitinolytic systems may be more commonplace than previously thought.

  5. UNDERSTANDING CONATIVE REGULATION SYSTEMS – AN EXAMINATION OF THE DIFFERENCES BETWEEN OFFENDERS AND NON-OFFENDERS

    Directory of Open Access Journals (Sweden)

    Sanja DJURDJEVIC

    2016-04-01

    Full Text Available Introduction: Numerous studies confirmed personality traits as being important predictors of criminal behavior. The aim of this research was to determine which constellation of basic personality traits incarcerated individuals and those serving alternative sanctions differ, and which traits make the difference between the criminal and the non-criminal populations. In this research, the model of personality used is a cybernetic model of conative functioning, which assumes that conative regulation systems almost completely describe the structure of personality. Methods: The study sample consisted of 391 male respondents (152 offenders serving prison sentence, 91 convicts sentenced to alternative penalties and 148 non-offenders. Examined variables were: the regulator of activity (Extroversion, the regulator of organic functions (Hysteria, the regulator of defense reactions (Anxiety, the regulator of attack reactions (Aggressiveness, the system for coordination of regulatory functions (Psychoticism and the system for integration of regulatory functions (Integration. Results: There were significant differences in all dimensions of personality between groups, except for the framework of Extraversion. The traits that contribute to the difference between individuals serving prison sentence and offenders sentenced to alternative penalties are Integration and Aggressiveness. The traits that contribute to the difference between non-offenders and offenders serving prison sentence are Psychoticism, Integration, Aggressiveness, and Anxiety. Among offenders sentenced to alternative penalties and the general population no difference in personality traits was found. Conclusion: Our findings may indicate the need for mandatory diagnostic psychological evaluation of persons who have committed minor offenses, to ensure the right decision is made when choosing between prison and an alternative method of punishment.

  6. 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

  7. 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

  8. A digital underwater video camera system for aquatic research in regulated rivers

    Science.gov (United States)

    Martin, Benjamin M.; Irwin, Elise R.

    2010-01-01

    We designed a digital underwater video camera system to monitor nesting centrarchid behavior in the Tallapoosa River, Alabama, 20 km below a peaking hydropower dam with a highly variable flow regime. Major components of the system included a digital video recorder, multiple underwater cameras, and specially fabricated substrate stakes. The innovative design of the substrate stakes allowed us to effectively observe nesting redbreast sunfish Lepomis auritus in a highly regulated river. Substrate stakes, which were constructed for the specific substratum complex (i.e., sand, gravel, and cobble) identified at our study site, were able to withstand a discharge level of approximately 300 m3/s and allowed us to simultaneously record 10 active nests before and during water releases from the dam. We believe our technique will be valuable for other researchers that work in regulated rivers to quantify behavior of aquatic fauna in response to a discharge disturbance.

  9. Cooperative Output Regulation of Nonlinear Multiagent Systems under a General Directed Graph

    Directory of Open Access Journals (Sweden)

    Dingcai Huang

    2015-01-01

    Full Text Available This paper studies the cooperative output regulation problem for a class of nonlinear multiagent systems modeled by nonlinear dynamics under a general directed communication topology. A type of distributed internal model is introduced to convert the cooperative output regulation problem into a robust stabilization problem of a so-called augmented system. Based on the Lyapunov stability theorem and M-matrix theorem, a kind of distributed output feedback controller only using the relative outputs of neighboring agents together with its stability analysis is further proposed with the aid of the backstepping technology, under which the outputs of the followers will asymptotically converge to that of the leader if, for each follower, there exists at least a directed path from the leader to the follower. Finally, a numerical example is provided to illustrate the effectiveness of the analytic results.

  10. Systems Chronobiology: Global Analysis of Gene Regulation in a 24-Hour Periodic World.

    Science.gov (United States)

    Mermet, Jérôme; Yeung, Jake; Naef, Felix

    2017-03-01

    Mammals have evolved an internal timing system, the circadian clock, which synchronizes physiology and behavior to the daily light and dark cycles of the Earth. The master clock, located in the suprachiasmatic nucleus (SCN) of the brain, takes fluctuating light input from the retina and synchronizes other tissues to the same internal rhythm. The molecular clocks that drive these circadian rhythms are ticking in nearly all cells in the body. Efforts in systems chronobiology are now being directed at understanding, on a comprehensive scale, how the circadian clock controls different layers of gene regulation to provide robust timing cues at the cellular and tissue level. In this review, we introduce some basic concepts underlying periodicity of gene regulation, and then highlight recent genome-wide investigations on the propagation of rhythms across multiple regulatory layers in mammals, all the way from chromatin conformation to protein accumulation.

  11. The Endocannabinoid System and Its Role in Regulating the Intrinsic Neural Circuitry of the Gastrointestinal Tract.

    Science.gov (United States)

    Trautmann, Samantha M; Sharkey, Keith A

    2015-01-01

    Endocannabinoids are important neuromodulators in the central nervous system. They regulate central transmission through pre- and postsynaptic actions on neurons and indirectly through effects on glial cells. Cannabinoids (CBs) also regulate neurotransmission in the enteric nervous system (ENS) of the gastrointestinal (GI) tract. The ENS consists of intrinsic primary afferent neurons, interneurons, and motor neurons arranged in two ganglionated plexuses which control all the functions of the gut. Increasing evidence suggests that endocannabinoids are potent neuromodulators in the ENS. In this review, we will highlight key observations on the localization of CB receptors and molecules involved in the synthesis and degradation of endocannabinoids in the ENS. We will discuss endocannabinoid signaling mechanisms, endocannabinoid tone and concepts of CB receptor metaplasticity in the ENS. We will also touch on some examples of enteric neural signaling in relation neuromuscular, secretomotor, and enteroendocrine transmission in the ENS. Finally, we will briefly discuss some key future directions.

  12. Systems and methods for regulating pressure of a filled-in gas

    Energy Technology Data Exchange (ETDEWEB)

    Stautner, Ernst Wolfgang; Michael, Joseph Darryl

    2016-05-03

    A system for regulating a pressure of a filled-in gas is presented. The system includes a reservoir that stores a reservoir gas adsorbed in a sorbent material at a storage temperature, a gas-filled tube containing the filled-in gas, a controller configured to determine a pressure change required in the filled-in gas based upon signals representative of a pressure of the filled-in gas inside the gas-filled tube and a required pressure threshold, determine an updated temperature of the sorbent material based upon the pressure change required in the filled-in gas, and regulate the pressure of the filled-in gas by controlling the reservoir to change the storage temperature of the sorbent material to reach the updated temperature of the sorbent material.

  13. 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.

  14. Two-component signal transduction system SaeRS positively regulates Staphylococcus epidermidis glucose metabolism.

    Science.gov (United States)

    Lou, Qiang; Qi, Yijun; Ma, Yuanfang; Qu, Di

    2014-01-01

    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.

  15. Complement System Part I – Molecular Mechanisms of Activation and Regulation

    Science.gov (United States)

    Merle, Nicolas S.; Church, Sarah Elizabeth; Fremeaux-Bacchi, Veronique; Roumenina, Lubka T.

    2015-01-01

    Complement is a complex innate immune surveillance system, playing a key role in defense against pathogens and in host homeostasis. The complement system is initiated by conformational changes in recognition molecular complexes upon sensing danger signals. The subsequent cascade of enzymatic reactions is tightly regulated to assure that complement is activated only at specific locations requiring defense against pathogens, thus avoiding host tissue damage. Here, we discuss the recent advances describing the molecular and structural basis of activation and regulation of the complement pathways and their implication on physiology and pathology. This article will review the mechanisms of activation of alternative, classical, and lectin pathways, the formation of C3 and C5 convertases, the action of anaphylatoxins, and the membrane-attack-complex. We will also discuss the importance of structure–function relationships using the example of atypical hemolytic uremic syndrome. Lastly, we will discuss the development and benefits of therapies using complement inhibitors. PMID:26082779

  16. [Progress of studies on mechanisms of acupuncture underlying regulation of cardiac function via autonomic nervous system].

    Science.gov (United States)

    Wang, Ya-Li; Yu, Zhi; Xu, Bin

    2014-02-01

    Acupuncture therapy has been confirmed to be effective in treating cardiovascular diseases in clinical practice. Acupuncture-induced balance of the autonomic nervous system activities is one of its key mechanisms. In the present paper, the authors review progress of studies on acupuncture treatment of cardiovascular diseases from 1) regulating cardiac sympathetic-beta-adrenergic receptor activity and myocardial intracellular GTP-binding protein (Gs)-adenylylcyclase (AC)-cyclic adenosine monophosphate (cAMP)-protein kinase (PKA) signaling, and 2) balancing cardiac sympathetic and vagal nerve activities. Due to limited experimental conditions, in-depth studies about the mechanisms of acupuncture intervention underlying improvement of cardiovascular functions are relatively fewer up to now. Along with the further development of modern biology, the mechanism of acupuncture intervention underlying regulation of cardiac function via autonomic nerve system will be revealed in detail.

  17. Value of Battery Storage System in the Ferequency Regulation Markets of PJM and CAISO

    Science.gov (United States)

    Khorsand, Shervin

    With an increasingly urgent need to decrease our utilization of fossil fuels, renewable power sources such as wind and solar are being incorporated in the electricity grid. However, these sources lack the conventional reliability that fossil fuels, such as natural gas, and oil have previously provided. The solution lies in energy storage, and exactly why battery storage systems are the means for renewable energy sources to become truly transformative and revolutionize the energy market. In the first part of this paper, a comprehensive summary of the different types of energy storage technologies have been provided along with their features, which make each technology suitable for different applications. Next, a detailed chapter focused on battery storage systems and their properties is provided along with the ancillary services they offer as sustenance and support sources integrated in the electric grid. These service are integral to the continuous transmission of power to consumers, and necessary for the supply to meet end-user demands. Among these service include frequency regulation as well as spinning reserve services, the latter being important under emergency condition following a power disruption. Regulation services however, are constantly required for grid stability and reliability, which is why this service was selected for further market analysis. For this market analysis, the California Independent Systems Operator (CAISO), and PJM Interconnection (PJM) were selected as both have extensive regulation markets and two of the major power suppliers nationwide. The main question in conducting this analysis was to determine which market would be more attractive and profitable for a potential regulation provider to invest using a Lithium ion battery. The Regulation Market Clearing Price (RMCP) for each market was extracted from the operators' annual reports over the last six years and used as measure of investor revenue. The Levelized Cost of Energy Storage

  18. 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...

  19. Deployment of low-voltage regulator considering existing voltage control in medium-voltage distribution systems

    Directory of Open Access Journals (Sweden)

    Hiroshi Kikusato

    2016-01-01

    Full Text Available Many photovoltaic (PV systems have been installed in distribution systems. This installation complicates the maintenance of all voltages within the appropriate range in all low-voltage distribution systems (LVDSs because the trends in voltage fluctuation differ in each LVDS. The installation of a low-voltage regulator (LVR that can accordingly control the voltage in each LVDS has been studied as a solution to this problem. Voltage control in a medium-voltage distribution system must be considered to study the deployment of LVRs. In this study, we installed LVRs in the LVDSs in which the existing voltage-control scheme cannot prevent voltage deviation and performed a numerical simulation by using a distribution system model with PV to evaluate the deployment of the LVRs.

  20. 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.

  1. 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

    and improving the predictability of the intermittent renewables but also of providing the ancillary services in the future energy markets. However, this is currently difficult to achieve due to high prices of the energy storage systems and difficulties with accurate prediction of the energy storage systems......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...... 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...

  2. Central nervous system: a conductor orchestrating metabolic regulations harmed by both hyperglycaemia and hypoglycaemia.

    OpenAIRE

    Scheen, André

    2010-01-01

    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 maintenanc...

  3. Guaranteed control performance robust LQG regulator for discrete-time Markovian jump systems with uncertain noise

    Institute of Scientific and Technical Information of China (English)

    Zhu Jin; Xi Hongsheng; Xiao Xiaobo; Ji Haibo

    2007-01-01

    Robust LQG problems of discrete-time Markovian jump systems with uncertain noises are investigated.The problem addressed is the construction of perturbation upper bounds on the uncertain noise covariances so as to guarantee that the deviation of the control performance remains within the precision prescribed in actual problems.Furthermore, this regulator is capable of minimizing the worst performance in an uncertain case. A numerical example is exploited to show the validity of the method.

  4. Positive regulation of the Hrp type III secretion system in Pseudomonas syringae pv. phaseolicola.

    Science.gov (United States)

    Ortiz-Martín, Inmaculada; Thwaites, Richard; Macho, Alberto P; Mansfield, John W; Beuzón, Carmen R

    2010-05-01

    Disease in compatible hosts and induction of the hypersensitive response in resistant plants by most plant-pathogenic bacteria require a functional type III secretion system (T3SS). Expression of T3SS genes responds to host and environmental factors and is induced within the plant. In Pseudomonas syringae, expression of the T3SS requires HrpL, which is transcriptionally upregulated by HrpR and HrpS. In some pathovars, expression of the hrpRS genes is upregulated by the GacA/S two-component system. Additionally, HrpA, the major component of the T3SS pilus, has also been linked to the regulation of the hrpRS gene expression. Previous studies concerning regulation of hypersensitive response and pathogenesis/hypersensitive response conserved (hrp/hrc) gene expression have used mostly in vitro inducing conditions, different pathovars, and methodology. Here, we analyze the roles of HrpL, GacA, and HrpA in the bean pathogen, using single, double, and triple mutants as well as strains ectopically expressing the regulators. We use real-time polymerase chain reaction analysis in vitro and in planta to quantify gene expression and competitive indices and other assays to assess bacterial fitness. Our results indicate that i) HrpL acts as a general virulence regulator that upregulates non-T3SS virulence determinants and downregulates flagellar function; ii) GacA modulates the expression of hrpL, and its contribution to virulence is entirely HrpL dependent; iii) there is a basal HrpL-independent expression of the T3SS genes in rich medium that is important for full activation of the system, maybe by keeping the system primed for rapid activation upon contact with the plant; and iv) HrpA upregulates expression of the T3SS genes and is essential to activate expression of the hrpZ operon upon contact with the plant.

  5. Quantitative Population Epigenetics in Screening and Development of Regulator-Active Factors of the Farming System

    OpenAIRE

    Stauss, R.

    2013-01-01

    Likewise, index selection based on statistical genetic theory in plant and animal breeding the methodology "Quantitative Population Epigenetics" can be appropriated to improve efficiency in screening and development of regulator-active factors of the farming system for potential to enhance quantitative characters such as yield, standability and resistance to unfavorable environmental influences (e.g., water stress, cold temperatures, disease resistance). For example, as was shown for an ef...

  6. Evidence for regulation of gluconeogenesis by the fructose phosphotransferase system in Salmonella typhimurium.

    OpenAIRE

    Chin, A M; Feucht, B U; Saier, M H

    1987-01-01

    A genetic locus designated fruR, previously mapped to min 3 on the Salmonella typhimurium chromosome, gave rise to constitutive expression of the fructose (fru) regulon and pleiotropically prevented growth on all Krebs cycle intermediates. Regulatory effects of fruR were independent of cyclic AMP and its receptor protein and did not prevent uptake of Krebs cycle intermediates. Instead, the phosphotransferase system appeared to regulate gluconeogenesis by controlling the activities of phosphoe...

  7. Evidence for regulation of gluconeogenesis by the fructose phosphotransferase system in Salmonella typhimurium.

    OpenAIRE

    Chin, A M; Feucht, B U; Saier, M.H.

    1987-01-01

    A genetic locus designated fruR, previously mapped to min 3 on the Salmonella typhimurium chromosome, gave rise to constitutive expression of the fructose (fru) regulon and pleiotropically prevented growth on all Krebs cycle intermediates. Regulatory effects of fruR were independent of cyclic AMP and its receptor protein and did not prevent uptake of Krebs cycle intermediates. Instead, the phosphotransferase system appeared to regulate gluconeogenesis by controlling the activities of phosphoe...

  8. 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.

  9. 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. PMID:27621697

  10. 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.

  11. The SLIT-ROBO pathway: a regulator of cell function with implications for the reproductive system.

    Science.gov (United States)

    Dickinson, Rachel E; Duncan, W Colin

    2010-04-01

    The secreted SLIT glycoproteins and their Roundabout (ROBO) receptors were originally identified as important axon guidance molecules. They function as a repulsive cue with an evolutionarily conserved role in preventing axons from migrating to inappropriate locations during the assembly of the nervous system. In addition the SLIT-ROBO interaction is involved in the regulation of cell migration, cell death and angiogenesis and, as such, has a pivotal role during the development of other tissues such as the lung, kidney, liver and breast. The cellular functions that the SLIT/ROBO pathway controls during tissue morphogenesis are processes that are dysregulated during cancer development. Therefore inactivation of certain SLITs and ROBOs is associated with advanced tumour formation and progression in disparate tissues. Recent research has indicated that the SLIT/ROBO pathway could also have important functions in the reproductive system. The fetal ovary expresses most members of the SLIT and ROBO families. The SLITs and ROBOs also appear to be regulated by steroid hormones and regulate physiological cell functions in adult reproductive tissues such as the ovary and endometrium. Furthermore several SLITs and ROBOs are aberrantly expressed during the development of ovarian, endometrial, cervical and prostate cancer. This review will examine the roles this pathway could have in the development, physiology and pathology of the reproductive system and highlight areas for future research that could further dissect the influence of the SLIT/ROBO pathway in reproduction.

  12. Heme sensing in Bacillus thuringiensis: a supplementary HssRS-regulated heme resistance system.

    Science.gov (United States)

    Schmidt, Rachel M; Carter, Micaela M; Chu, Michelle L; Latario, Casey J; Stadler, Sarah K; Stauff, Devin L

    2016-05-01

    Several Gram-positive pathogens scavenge host-derived heme to satisfy their nutritional iron requirement. However, heme is a toxic molecule capable of damaging the bacterial cell. Gram-positive pathogens within the phylum Firmicutes overcome heme toxicity by sensing heme through HssRS, a two-component system that regulates the heme detoxification transporter HrtAB. Here we show that heme sensing by HssRS and heme detoxification by HrtAB occur in the insect pathogen Bacillus thuringiensis We find that in B. thuringiensis, HssRS directly regulates an operon, hrmXY, encoding hypothetical membrane proteins that are not found in other Firmicutes with characterized HssRS and HrtAB systems. This novel HssRS-regulated operon or its orthologs BMB171_c3178 and BMB171_c3330 are required for maximal heme resistance. Furthermore, the activity of HrmXY is not dependent on expression of HrtAB. These results suggest that B. thuringiensis senses heme through HssRS and induces expression of separate membrane-localized systems capable of overcoming different aspects of heme toxicity.

  13. 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.

  14. Regulating critical period plasticity: insight from the visual system to fear circuitry for therapeutic interventions.

    Science.gov (United States)

    Nabel, Elisa M; Morishita, Hirofumi

    2013-01-01

    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. 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.

  16. 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.

  17. The Realization of a Discrete-Time Deterministic Regulator for Energy Renewable Multivariable Systems

    Directory of Open Access Journals (Sweden)

    OBINABO, EDWIN CHUKWUDI

    2010-12-01

    Full Text Available This study proposes an optimal control law for a linear constant energy renewal multivariable system supplying power to protection and signaling circuits for switchgears and substation operations. The energy storage mechanism creates a control source that dictates the frequency of the pow er supply voltage. The entire analysis was based essentially on the use of a vector of inputs and outputs, and a matrix of operations characterizing the storage mechanism, assuming the system is both controllable and observable under arbitrary state feedback. The property of the output regulator which was desirable from the view point of feedback control design was clarified.

  18. An integrated modelling framework for regulated river systems in Land Surface Hydrological Models

    Science.gov (United States)

    Rehan Anis, Muhammad; razavi, Saman; Wheater, Howard

    2017-04-01

    Many of the large river systems around the world are highly regulated with numerous physical flow control and storage structures as well as a range of water abstraction rules and regulations. Most existing Land Surface Models (LSM) do not represent the modifications to the hydrological regimes introduced by water management (reservoirs, irrigation diversions, etc.). The interactions between natural hydrological processes and changes in water and energy fluxes and storage due to human interventions are important to the understanding of how these systems may respond to climate change amongst other drivers for change as well as to the assessment of their feedbacks to the climate system at regional and global scales. This study presents an integrated modelling approach to include human interventions within natural hydrological systems using a fully coupled modelling platform. The Bow River Basin in Alberta (26,200 km2), one of the most managed Canadian rivers, is used to demonstrate the approach. We have dynamically linked the MESH modelling system, which embeds the Canadian Land Surface Scheme (CLASS), with the MODSIM-DSS water management modelling tool. MESH models the natural hydrology while MODSIM optimizes the reservoir operation of 4 simulated reservoirs to satisfy demands within the study basin. MESH was calibrated for the catchments upstream the reservoirs and gave good performance (NSE = 0.81) while BIAS was only 2.3% at the catchment outlet. Without coupling with MODSIM (i.e. no regulation), simulated hydrographs at the catchment outlet were in complete disagreement with observations (NSE = 0.28). The coupled model simulated the optimization introduced by the operation of the multi-reservoir system in the Bow river basin and shows excellent agreement between observed and simulated hourly flows (NSE = 0.98). Irrigation demands are fully satisfied during summer, however, there are some shortages in winter demand from industries, which can be rectified by

  19. A Boolean model of the Pseudomonas syringae hrp regulon predicts a tightly regulated system.

    Directory of Open Access Journals (Sweden)

    Daniel MacLean

    Full Text Available The Type III secretion system (TTSS is a protein secretion machinery used by certain gram-negative bacterial pathogens of plants and animals to deliver effector molecules to the host and is at the core of the ability to cause disease. Extensive molecular and biochemical study has revealed the components and their interactions within this system but reductive approaches do not consider the dynamical properties of the system as a whole. In order to gain a better understanding of these dynamical behaviours and to create a basis for the refinement of the experimentally derived knowledge we created a Boolean model of the regulatory interactions within the hrp regulon of Pseudomonas syringae pathovar tomato strain DC3000 Pseudomonas syringae. We compared simulations of the model with experimental data and found them to be largely in accordance, though the hrpV node shows some differences in state changes to that expected. Our simulations also revealed interesting dynamical properties not previously predicted. The model predicts that the hrp regulon is a biologically stable two-state system, with each of the stable states being strongly attractive, a feature indicative of selection for a tightly regulated and responsive system. The model predicts that the state of the GacS/GacA node confers control, a prediction that is consistent with experimental observations that the protein has a role as master regulator. Simulated gene "knock out" experiments with the model predict that HrpL is a central information processing point within the network.

  20. [Understanding of immune system by visualization of spatiotemporal regulation of immune cells in the entire body].

    Science.gov (United States)

    Tomura, Michio

    2013-01-01

    Immune system is high-dimensional integrated system distributed in the whole body. Many kinds of, total 10(11) of immune cells are regulated by receiving appropriate signals in appropriate places. We have been attempting to understand immune system by revealing spatiotemporal regulation of immune cells at the whole body level by "Visualization of immune response in vivo". Photoconvertible protein, "Kaede"-Tg mice allowed us to monitor cell-replacement and cell-movement in the whole body by marking cells with color of Kaede from green to red with exposure to violet light. It is applicable to small cell number populations in both lymphoid organs and also peripheral tissues under both normal and pathophysiological conditions. By using this system, we have demonstrated novel findings that "Naive CD4(+) T cell recirculation is an active process that they recirculate through lymphoid organs to seek limited niche for interacting with endogenous antigens and upregulate their function." and "Activated regulatory T cells emigrating from cutaneous immune response is responsible for termination of immune reponse." I will introduce these new tools of us and would like to discuss what is needed to understand immune system in the entire body.

  1. 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®.

  2. Midazolam inhibits the hypoxia-induced up-regulation of erythropoietin in the central nervous system.

    Science.gov (United States)

    Matsuyama, Tomonori; Tanaka, Tomoharu; Tatsumi, Kenichiro; Daijo, Hiroki; Kai, Shinichi; Harada, Hiroshi; Fukuda, Kazuhiko

    2015-08-15

    Erythropoietin (EPO), a regulator of red blood cell production, is endogenously expressed in the central nervous system. It is mainly produced by astrocytes under hypoxic conditions and has proven to have neuroprotective and neurotrophic effects. In the present study, we investigated the effect of midazolam on EPO expression in primary cultured astrocytes and the mouse brain. Midazolam was administered to 6-week-old BALB/c male mice under hypoxic conditions and pregnant C57BL/6N mice under normoxic conditions. Primary cultured astrocytes were also treated with midazolam under hypoxic conditions. The expression of EPO mRNA in mice brains and cultured astrocytes was studied. In addition, the expression of hypoxia-inducible factor (HIF), known as the main regulator of EPO, was evaluated. Midazolam significantly reduced the hypoxia-induced up-regulation of EPO in BALB/c mice brains and primary cultured astrocytes and suppressed EPO expression in the fetal brain. Midazolam did not affect the total amount of HIF proteins but significantly inhibited the nuclear expression of HIF-1α and HIF-2α proteins. These results demonstrated the suppressive effects of midazolam on the hypoxia-induced up-regulation of EPO both in vivo and in vitro.

  3. The maintenance and regeneration of the planarian excretory system are regulated by EGFR signaling.

    Science.gov (United States)

    Rink, Jochen C; Vu, Hanh Thi-Kim; Sánchez Alvarado, Alejandro

    2011-09-01

    The maintenance of organs and their regeneration in case of injury are crucial to the survival of all animals. High rates of tissue turnover and nearly unlimited regenerative capabilities make planarian flatworms an ideal system with which to investigate these important processes, yet little is known about the cell biology and anatomy of their organs. Here we focus on the planarian excretory system, which consists of internal protonephridial tubules. We find that these assemble into complex branching patterns with a stereotyped succession of cell types along their length. Organ regeneration is likely to originate from a precursor structure arising in the blastema, which undergoes extensive branching morphogenesis. In an RNAi screen of signaling molecules, we identified an EGF receptor (Smed-EGFR-5) as a crucial regulator of branching morphogenesis and maintenance. Overall, our characterization of the planarian protonephridial system establishes a new paradigm for regenerative organogenesis and provides a platform for exploring its functional and evolutionary homologies with vertebrate excretory systems.

  4. Surface acoustic wave regulated single photon emission from a coupled quantum dot-nanocavity system

    CERN Document Server

    Weiß, Matthias; Reichert, Thorsten; Finley, Jonathan J; Wixforth, Achim; Kaniber, Michael; Krenner, Hubert J

    2016-01-01

    A coupled quantum dot--nanocavity system in the weak coupling regime of cavity quantumelectrodynamics is dynamically tuned in and out of resonance by the coherent elastic field of a $f_{\\rm SAW}\\simeq800\\,\\mathrm{MHz}$ surface acoustic wave. When the system is brought to resonance by the sound wave, light-matter interaction is strongly increased by the Purcell effect. This leads to a precisely timed single photon emission as confirmed by the second order photon correlation function $g^{(2)}$. All relevant frequencies of our experiment are faithfully identified in the Fourier transform of $g^{(2)}$, demonstrating high fidelity regulation of the stream of single photons emitted by the system. The implemented scheme can be directly extended to strongly coupled systems and acoustically drives non-adiabatic entangling quantum gates based on Landau-Zener transitions.

  5. Distributed event-triggered output regulation of multi-agent systems

    Science.gov (United States)

    Wang, Xiaoli; Ni, Wei; Ma, Zhibin

    2015-03-01

    Motivated by the future use of embedded microprocessors with limited resources and limited computational resources, the distributed output regulation with event-driven strategies problem of linear multi-agent systems is considered in this paper. The main task is to design distributed feedback by employing event-triggered technique for multi-agent systems such that all agents can track an active leader, and/or distributed disturbance rejection. Both leader and disturbance are generated by some external system (exosystem). Both distributed static and dynamic feedback with event-triggered strategy are constructed here. Then, the input-to-state stability of the closed-loop multi-agent system is analysed. Finally, a numerical example is given to validate the proposed control.

  6. Systems Genetics as a Tool to Identify Master Genetic Regulators in Complex Disease.

    Science.gov (United States)

    Moreno-Moral, Aida; Pesce, Francesco; Behmoaras, Jacques; Petretto, Enrico

    2017-01-01

    Systems genetics stems from systems biology and similarly employs integrative modeling approaches to describe the perturbations and phenotypic effects observed in a complex system. However, in the case of systems genetics the main source of perturbation is naturally occurring genetic variation, which can be analyzed at the systems-level to explain the observed variation in phenotypic traits. In contrast with conventional single-variant association approaches, the success of systems genetics has been in the identification of gene networks and molecular pathways that underlie complex disease. In addition, systems genetics has proven useful in the discovery of master trans-acting genetic regulators of functional networks and pathways, which in many cases revealed unexpected gene targets for disease. Here we detail the central components of a fully integrated systems genetics approach to complex disease, starting from assessment of genetic and gene expression variation, linking DNA sequence variation to mRNA (expression QTL mapping), gene regulatory network analysis and mapping the genetic control of regulatory networks. By summarizing a few illustrative (and successful) examples, we highlight how different data-modeling strategies can be effectively integrated in a systems genetics study.

  7. MicroRNA-regulated networks: the perfect storm for classical molecular biology, the ideal scenario for systems biology.

    Science.gov (United States)

    Vera, Julio; Lai, Xin; Schmitz, Ulf; Wolkenhauer, Olaf

    2013-01-01

    MicroRNAs (miRNAs) are involved in many regulatory pathways some of which are complex networks enriched in regulatory motifs like positive or negative feedback loops or coherent and incoherent feedforward loops. Their complexity makes the understanding of their regulation difficult and the interpretation of experimental data cumbersome. In this book chapter we claim that systems biology is the appropriate approach to investigate the regulation of these miRNA-regulated networks. Systems biology is an interdisciplinary approach by which biomedical questions on biochemical networks are addressed by integrating experiments with mathematical modelling and simulation. We here introduce the foundations of the systems biology approach, the basic theoretical and computational tools used to perform model-based analyses of miRNA-regulated networks and review the scientific literature in systems biology of miRNA regulation, with a focus on cancer.

  8. Redox regulation and antioxidative defence in Arabidopsis leaves viewed from a systems biology perspective.

    Science.gov (United States)

    Wormuth, Dennis; Heiber, Isabelle; Shaikali, Jehad; Kandlbinder, Andrea; Baier, Margarete; Dietz, Karl-Josef

    2007-04-30

    Redox regulation is a central control element in cell metabolism. It is employed to adjust photosynthesis and the antioxidant defence system of leaves to the prevailing environment. During recent years progress has been made in describing the redox-dependent alterations in metabolism, the thiol/disulfide proteome, the redox-dependent and cross-talking signalling pathways and the target genes of redox regulation. Some transcription factors have been identified as proteins that perform thiol/disulfide transitions linked to the redox-regulation of specific plant promoters. In addition first mathematical models have been designed to simulate antioxidant defence and predict its response. Taken together, a profound experimental data set has been generated which allows to approach a systems biology type of understanding of antioxidant defence in photosynthesising cells in the near future. Since oxidative stress is likely to limit plant growth under stress, such a systematic understanding of antioxidant defence will help to define novel targets for breeding stress-tolerant plants.

  9. PreImplantation factor (PIF*) regulates systemic immunity and targets protective regulatory and cytoskeleton proteins.

    Science.gov (United States)

    Barnea, Eytan R; Hayrabedyan, Soren; Todorova, Krassimira; Almogi-Hazan, Osnat; Or, Reuven; Guingab, Joy; McElhinney, James; Fernandez, Nelson; Barder, Timothy

    2016-07-01

    Secreted by viable embryos, PIF is expressed by the placenta and found in maternal circulation. It promotes implantation and trophoblast invasion, achieving systemic immune homeostasis. Synthetic PIF successfully transposes endogenous PIF features to non-pregnant immune and transplant models. PIF affects innate and activated PBMC cytokines and genes expression. We report that PIF targets similar proteins in CD14+, CD4+ and CD8+ cells instigating integrated immune regulation. PIF-affinity chromatography followed by mass-spectrometry, pathway and heatmap analysis reveals that SET-apoptosis inhibitor, vimentin, myosin-9 and calmodulin are pivotal for immune regulation. PIF acts on macrophages down-stream of LPS (lipopolysaccharide-bacterial antigen) CD14/TLR4/MD2 complex, targeting myosin-9, thymosin-α1 and 14-3-3eta. PIF mainly targets platelet aggregation in CD4+, and skeletal proteins in CD8+ cells. Pathway analysis demonstrates that PIF targets and regulates SET, tubulin, actin-b, and S100 genes expression. PIF targets systemic immunity and has a short circulating half-life. Collectively, PIF targets identified; protective, immune regulatory and cytoskeleton proteins reveal mechanisms involved in the observed efficacy against immune disorders. Copyright © 2016 Elsevier GmbH. All rights reserved.

  10. 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

    Even though induction of seizures by electroconvulsive stimulation (ECS) is a treatment widely used for major depression in humans, the working mechanism of ECS remains uncertain. The antiepileptic effect of ECS has been suggested to be involved in mediating the therapeutic effect of ECS. The neu......Even though induction of seizures by electroconvulsive stimulation (ECS) is a treatment widely used for major depression in humans, the working mechanism of ECS remains uncertain. The antiepileptic effect of ECS has been suggested to be involved in mediating the therapeutic effect of ECS....... The neuropeptide galanin exerts antiepileptic and antidepressant-like effects and has also been implicated in the pathophysiology of depression. To explore a potential role of galanin in working mechanisms of ECS, the present study examined effects of repeated ECS on the galanin system using QRT-PCR, in situ......]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...

  11. 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.

  12. Ginseng ginsenoside pharmacology in nervous systems: involvement of the regulations of ion channels and receptors

    Directory of Open Access Journals (Sweden)

    Seung-Yeol eNah

    2014-03-01

    Full Text Available Ginseng, the root of Panax ginseng C.A. Meyer, is one of the oldest traditional medicines and is thought to be a tonic. It has been claimed that ginseng may improve vitality and health. Recent studies have advanced ginseng pharmacology and shown that ginseng has various pharmacological effects in the nervous system. Ginsenosides, steroid glycosides extracted from ginseng, were one of the first class of biologically active plant glycosides identified. The diverse pharmacological effects of ginsenosides have been investigated through the regulation of various types of ion channels and receptors in neuronal cells and heterologous expression systems. Ginsenoside Rg3 regulates voltage-gated ion channels such as Ca2+, K+, and Na+ channels, and ligand-gated ion channels such as GABAA, 5-HT3, nicotinic acetylcholine, and N-methyl-D-aspartate (NMDA receptors through interactions with various sites including channel blocker binding sites, toxin-binding sites, channel gating regions, and allosteric channel regulator binding sites when the respective ion channels or receptors are stimulated with depolarization or ligand treatment. Treatment with ginsenoside Rg3 has been found to stabilize excitable cells by blocking influxes of cations such as Ca2+ and Na+, or by enhancing Cl- influx. The aim of this review is to present recent findings on the pharmacological functions of the ginsenosides through the interactions with ion channels and receptors. This review will detail the pharmacological applications of ginsenosides as neuroprotective drugs that target ion channels and ligand-gated ion channels.

  13. The metabolic flux regulation of Klebsiella pneumoniae based on quorum sensing system

    Science.gov (United States)

    Sun, Shujing; Zhang, Haiyang; Lu, Shuyi; Lai, Chunfen; Liu, Huijun; Zhu, Hu

    2016-01-01

    Quorum-sensing (QS) systems exist universally in bacteria to regulate multiple biological functions. Klebsiella pneumoniae, an industrially important bacterium that produces bio-based chemicals such as 2,3-butanediol and acetoin, can secrete a furanosyl borate diester (AI-2) as the signalling molecule mediating a QS system, which plays a key regulatory role in the biosynthesis of secondary metabolites. In this study, the molecular regulation and metabolic functions of a QS system in K. pneumoniae were investigated. The results showed that after the disruption of AI-2-mediated QS by the knockout of luxS, the production of acetoin, ethanol and acetic acid were relatively lower in the K. pneumoniae mutant than in the wild type bacteria. However, 2,3-butanediol production was increased by 23.8% and reached 54.93 g/L. The observed enhancement may be attributed to the improvement of the catalytic activity of 2,3-butanediol dehydrogenase (BDH) in transforming acetoin to 2,3-butanediol. This possibility is consistent with the RT-PCR-verified increase in the transcriptional level of budC, which encodes BDH. These results also demonstrated that the physiological metabolism of K. pneumoniae was adversely affected by a QS system. This effect was reversed through the addition of synthetic AI-2. This study provides the basis for a QS-modulated metabolic engineering study of K. pneumoniae. PMID:27924940

  14. High-density cell systems incorporating polymer microspheres as microenvironmental regulators in engineered cartilage tissues.

    Science.gov (United States)

    Solorio, Loran D; Vieregge, Eran L; Dhami, Chirag D; Alsberg, Eben

    2013-06-01

    To address the significant clinical need for tissue-engineered therapies for the repair and regeneration of articular cartilage, many systems have recently been developed using bioactive polymer microspheres as regulators of the chondrogenic microenvironment within high-density cell cultures. In this review, we highlight various densely cellular systems utilizing polymer microspheres as three-dimensional (3D) structural elements within developing engineered cartilage tissue, carriers for cell expansion and delivery, vehicles for spatiotemporally controlled growth factor delivery, and directors of cell behavior via regulation of cell-biomaterial interactions. The diverse systems described herein represent a shift from the more traditional tissue engineering approach of combining cells and growth factors within a biomaterial scaffold, to the design of modular systems that rely on the assembly of cells and bioactive polymer microspheres as building blocks to guide the creation of articular cartilage. Cell-based assembly of 3D microsphere-incorporated structures represents a promising avenue for the future of tissue engineering.

  15. Neural reflex regulation of systemic inflammation: potential new targets for sepsis therapy.

    Science.gov (United States)

    Fernandez, Ricardo; Nardocci, Gino; Navarro, Cristina; Reyes, Edison P; Acuña-Castillo, Claudio; Cortes, Paula P

    2014-01-01

    Sepsis progresses to multiple organ dysfunction due to the uncontrolled release of inflammatory mediators, and a growing body of evidence shows that neural signals play a significant role in modulating the immune response. Thus, similar toall other physiological systems, the immune system is both connected to and regulated by the central nervous system. The efferent arc consists of the activation of the hypothalamic-pituitary-adrenal axis, sympathetic activation, the cholinergic anti-inflammatory reflex, and the local release of physiological neuromodulators. Immunosensory activity is centered on the production of pro-inflammatory cytokines, signals that are conveyed to the brain through different pathways. The activation of peripheral sensory nerves, i.e., vagal paraganglia by the vagus nerve, and carotid body (CB) chemoreceptors by the carotid/sinus nerve are broadly discussed here. Despite cytokine receptor expression in vagal afferent fibers, pro-inflammatory cytokines have no significant effect on vagus nerve activity. Thus, the CB may be the source of immunosensory inputs and incoming neural signals and, in fact, sense inflammatory mediators, playing a protective role during sepsis. Considering that CB stimulation increases sympathetic activity and adrenal glucocorticoids release, the electrical stimulation of arterial chemoreceptors may be suitable therapeutic approach for regulating systemic inflammation.

  16. Identification of a two-component signal transduction system that regulates maltose genes in Clostridium perfringens.

    Science.gov (United States)

    Hiscox, Thomas J; Ohtani, Kaori; Shimizu, Tohru; Cheung, Jackie K; Rood, Julian I

    2014-12-01

    Clostridium perfringens is a Gram-positive rod that is widely distributed in nature and is the etiological agent of several human and animal diseases. The complete genome sequence of C. perfringens strain 13 has been determined and multiple two-component signal transduction systems identified. One of these systems, designated here as the MalNO system, was analyzed in this study. Microarray analysis was used to carry out functional analysis of a malO mutant. The results, which were confirmed by quantitative reverse-transcriptase PCR, indicated that genes putatively involved in the uptake and metabolism of maltose were up-regulated in the malO mutant. These effects were reversed by complementation with the wild-type malO gene. Growth of these isogenic strains in medium with and without maltose showed that the malO mutant recovered more quickly from maltose deprivation when compared to the wild-type and complemented strains, leading to the conclusion that the MalNO system regulates maltose utilization in C. perfringens. It is postulated that this regulatory network may allow this soil bacterium and opportunistic pathogen to respond to environmental conditions where there are higher concentrations of maltose or maltodextrins, such as in the presence of decaying plant material in rich soil. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Mechanisms regulating the development of oligodendrocytes and central nervous system myelin.

    Science.gov (United States)

    Mitew, S; Hay, C M; Peckham, H; Xiao, J; Koenning, M; Emery, B

    2014-09-12

    Oligodendrocytes and the myelin they produce are a remarkable vertebrate specialization that enables rapid and efficient nerve conduction within the central nervous system. The generation of myelin during development involves a finely-tuned pathway of oligodendrocyte precursor specification, proliferation and migration followed by differentiation and the subsequent myelination of appropriate axons. In this review we summarize the molecular mechanisms known to regulate each of these processes, including the extracellular ligands that promote or inhibit development of the oligodendrocyte lineage, the intracellular pathways they signal through and the key transcription factors that mediate their effects. Many of these regulatory mechanisms have recurring roles in regulating several transitions during oligodendrocyte development, highlighting their importance. It is also highly likely that many of these developmental mechanisms will also be involved in myelin repair in human neurological disease.

  18. A novel domain regulating degradation of the glomerular slit diaphragm protein podocin in cell culture systems.

    Directory of Open Access Journals (Sweden)

    Markus Gödel

    Full Text Available Mutations in the gene NPHS2 are the most common cause of hereditary steroid-resistant nephrotic syndrome. Its gene product, the stomatin family member protein podocin represents a core component of the slit diaphragm, a unique structure that bridges the space between adjacent podocyte foot processes in the kidney glomerulus. Dislocation and misexpression of slit diaphragm components have been described in the pathogenesis of acquired and hereditary nephrotic syndrome. However, little is known about mechanisms regulating cellular trafficking and turnover of podocin. Here, we discover a three amino acids-comprising motif regulating intracellular localization of podocin in cell culture systems. Mutations of this motif led to markedly reduced degradation of podocin. These findings give novel insight into the molecular biology of the slit diaphragm protein podocin, enabling future research to establish the biological relevance of podocin turnover and localization.

  19. Systems Level Regulation of Rhythmic Growth Rate and Biomass Accumulation in Grasses

    Energy Technology Data Exchange (ETDEWEB)

    Kay, Steve A. [University of California San Diego

    2013-05-02

    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.

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

    Directory of Open Access Journals (Sweden)

    Viola Nordström

    Full Text Available 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.

  1. 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.

  2. Hypoxic preconditioning involves system Xc- regulation in mouse neural stem cells.

    Science.gov (United States)

    Sims, Brian; Clarke, Melinda; Francillion, Ludwig; Kindred, Elijah; Hopkins, Elana Shuford; Sontheimer, Harald

    2012-03-01

    In animals, hypoxic preconditioning has been used as a form of neuroprotection. The exact mechanism involved in neuroprotective hypoxic preconditioning has not been described, yet could be valuable for possible neuroprotective strategies. The overexpression of the cystine-glutamate exchanger, system Xc-, has been demonstrated as being neuroprotective (Shih, Erb et al. 2006). Here, using immunohistochemistry, we demonstrate that C57BL/6 mice exposed to hypoxia showed an increase in system Xc- expression, with the highest level of intensity in the hippocampus. Western Blot analysis also showed an almost 2-fold increase in system Xc- protein in hypoxia-exposed versus control mice. The mRNA for the regulatory subunit of system Xc-, xCT, and the xCT/actin ratio were also increased under hypoxic conditions. Experiments using hypoxia-inducible factor (HIF-1α) siRNA showed a statistically significant decrease in HIF-1α and system Xc- expression. Under hypoxic conditions, system Xc- activity, as determined by cystine uptake, increased 2-fold. Importantly, hypoxic preconditioning was attenuated in neural stem cells by pharmacological inhibition of system Xc- activity with S4-carboxyphenylglycine. These data provide the first evidence of hypoxic regulation of the cystine glutamate exchanger system Xc-.

  3. Manipulation of the carbon storage regulator system for metabolite remodeling and biofuel production in Escherichia coli

    Science.gov (United States)

    2012-01-01

    Background Microbial engineering strategies that elicit global metabolic perturbations have the capacity to increase organism robustness for targeted metabolite production. In particular, perturbations to regulators of cellular systems that impact glycolysis and amino acid production while simultaneously decreasing fermentation by-products such as acetate and CO2 make ideal targets. Intriguingly, perturbation of the Carbon Storage Regulator (Csr) system has been previously implicated in large changes in central carbon metabolism in E. coli. Therefore, we hypothesized that perturbation of the Csr system through the CsrA-CsrB ribonucleoprotein complex might increase production of biofuels and their intermediates from heterologous pathways. Results We engaged the CsrA-CsrB ribonucleoprotein complex of E. coli via overexpression of CsrB. CsrB is a 350-nucleotide non-coding RNA that antagonizes CsrA, an RNA-binding protein that regulates translation of specific mRNA targets. By using shotgun proteomics and targeted metabolomics we established that elevation of CsrB levels leads to alterations in metabolite and protein levels in glycolysis, the TCA cycle and amino acid levels. Consequently, we show that such changes can be suitably applied to improve the production of desired compounds through the native fatty acid and heterologous n-butanol and isoprenoid pathways by up to two-fold. We also observed concomitant decreases in undesirable fermentation by-products such as acetate and CO2. Conclusions We have demonstrated that simple engineering of the RNA-based Csr global regulatory system constitutes a novel approach to obtaining pathway-independent improvements within engineered hosts. Additionally, since Csr is conserved across most prokaryotic species, this approach may also be amenable to a wide variety of production hosts. PMID:22694848

  4. 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.

  5. 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

    2010-05-01

    Multiple virulence systems in the opportunistic pathogen Pseudomonas aeruginosa are regulated by the second messenger signalling 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.

  6. Regulation and control of thermally activated building systems (TABS); Regelung und Steuerung von thermoaktiven Bauteilsystemen (TABS)

    Energy Technology Data Exchange (ETDEWEB)

    Toedtli, Juerg [Consulting Juerg Toedtli, Zuerich (Switzerland); Gwerder, Markus; Renggli, Franz; Guentensperger, Werner [Siemens Building Technologies, Zug (Switzerland); Lehmann, Beat; Dorer, Viktor [Empa, Abt. Building Technologies, Duebendorf (Switzerland); Hildebrand, Kurt [Hochschule Luzern - Technik and Architektur, Horw (Switzerland)

    2009-10-15

    Thermally activated building systems (TABS) are becoming increasingly important in terms of energy efficient cooling and heating of buildings. In practice, however, regulation and control of such systems often causes problems. Started five years ago with the aim of getting to grips with these problems, the TABS Control research project was completed in early 2009. The project yielded the following results: various models and simulation programs for TABS; performance-bound calculations for regulating zones; a range of zone regulation/control strategies for planners to choose from, including good solutions for automatic switching between heating and cooling, for pulsed operation of the zone pump and for room temperature control; the implementation of a subset of these strategies as standard solutions in a Siemens building automation system; laboratory tests on these strategies; a new procedure for the integrated planning of TABS and their regulation/control (referred to as UBB planning procedure - Unknown But Bounded); an Excel planning tool; guidelines on selecting the hydraulic switching topology; a method for operation optimization; the theoretical basis for the new integrated planning procedure and the new regulation/ control strategies; a patent application. [German] Thermoaktive Bauteilsysteme (TABS) haben eine zunehmende Bedeutung bei der energieeffizienten Kuehlung und Heizung von Gebaeuden, doch ihre Regelung/Steuerung fuehrt in der Praxis oft zu Problemen. Mit dem Ziel, diese Probleme in den Griff zu bekommen, wurde vor fuenf Jahren das Forschungsprojekt TABS-Control gestartet, das zu Beginnd des Jahres 2009 abgeschlossen wurde. Es wurden folgende wesentliche Resultate erarbeitet: Modelle und Simulationsprogramme fuer TABS; Performance-Bound-Berechnungen fuer die Zonenregelung; eine Auswahl von Regel-/ Steuer-Strategien fuer die Zonenregelung, u. a. mit Loesungen fuer das automatische Umschalten zwischen Heizen und Kuehlen, fuer den Taktbetrieb der

  7. [Advances in the study of histaminergic systems and sleep-wake regulation].

    Science.gov (United States)

    Liu, Tian-Ya; Hong, Zong-Yuan; Qu, Wei-Min; Huang, Zhi-Li

    2011-03-01

    Histaminergic neurons solely originate from the tuberomammillary nucleus (TMN) in the posterior hypothalamus and send widespread projections to the whole brain. Experiments in rats show that histamine release in the central nervous system is positively correlated with wakefulness and the histamine released is 4 times higher during wake episodes than during sleep episodes. Endogeneous prostaglandin E2 and orexin activate histaminergic neurons in the TMN to release histamine and promote wakefulness. Conversely, prostaglandin D2 and adenosine inhibit histamine release by increasing GABA release in the TMN to induce sleep. This paper reviews the effects and mechanisms of action of the histaminergic system on sleep-wake regulation, and briefly discusses the possibility of developing novel sedative-hypnotics and wakefulness-promoting drugs related to the histaminergic system.

  8. Development of a waste heat recovery system onboard LNG carrier to meet IMO regulations

    Directory of Open Access Journals (Sweden)

    Khaled Senary

    2016-09-01

    Full Text Available Problems resulting from gas emissions lead to increase the concern about safety and health issues with the demand to reduce the emissions from marine shipping. Marine power plants are considered as one of the greatest contributors in the pollutants around the world. Waste heat recovery systems when implemented with ship propulsion system can reduce emissions, fuel consumption and improve the overall efficiency of power generation and utilization. The present article describes the waste heat recovery technology and the potential for ship operators to lower the fuel costs, exhaust emissions, and the effect on the EEDI of the ship. The main research target is to improve the propulsion machinery efficiency of liquefied natural gas carrier using WHRS. The proposed system leads to meet the requirements and regulations set by the IMO for TIER III.

  9. 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.

  10. New insights on the role of the endocannabinoid system in the regulation of energy balance.

    Science.gov (United States)

    Gatta-Cherifi, B; Cota, D

    2016-02-01

    Within the past 15 years, the endocannabinoid system (ECS) has emerged as a lipid signaling system critically involved in the regulation of energy balance, as it exerts a regulatory control on every aspect related to the search, the intake, the metabolism and the storage of calories. An overactive endocannabinoid cannabinoid type 1 (CB1) receptor signaling promotes the development of obesity, insulin resistance and dyslipidemia, representing a valuable pharmacotherapeutic target for obesity and metabolic disorders. However, because of the psychiatric side effects, the first generation of brain-penetrant CB1 receptor blockers developed as antiobesity treatment were removed from the European market in late 2008. Since then, recent studies have identified new mechanisms of action of the ECS in energy balance and metabolism, as well as novel ways of targeting the system that may be efficacious for the treatment of obesity and metabolic disorders. These aspects will be especially highlighted in this review.

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

    Energy Technology Data Exchange (ETDEWEB)

    Corcoran, W.P.; Nielsen, K.S.; Kelly, D.G.; Weir, R.D. [Royal Military College of Canada (RMCC), Kingston, Ontario (Canada)

    2013-07-01

    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)

  12. MANUALS OF POSTMODERN LIFE: THE REGULATION OF LIVING BY THE JUSTICE SYSTEM

    Directory of Open Access Journals (Sweden)

    Camilla Felix Barbosa de Oliveira

    2016-11-01

    Full Text Available We live, today, the growing intervention of the Justice system in different areas through policies that would give further effect to the management of relational conflicts and the protection of individual rights. Considering this scenario, this article sought to analyze such a move life adjustment through three productions of the Brazilian Justice system: the Parents’ Divorce Booklet; the Family Booklet - No to parental alienation; and the class guide Count to 10 in schools. From the analysis of contents of such materials was possible to develop a discussion on the ways of life in the context of Postmodernity, particularly with regard to the so-called crisis of authority figures, especially those more directly linked to education and socialization of children and adolescents. It was concluded that the booklets examined, and the Justice system have contributed to the weakening of those positions of authority and consequently with the regulation of living.

  13. Adaptive Output-feedback Regulation for Nonlinear Delayed Systems Using Neural Network

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    A novel adaptive neural network (NN) output-feedback regulation algorithm for a class of nonlinear time-varying time-delay systems is proposed. Both the designed observer and controller are independent of time delay. Different from the existing results,where the upper bounding functions of time-delay terms are assumed to be known, we only use an NN to compensate for all unknown upper bounding functions without that assumption. The proposed design method is proved to be able to guarantee semi-global uniform ultimate boundedness of all the signals in the closed system, and the system output is proved to converge to a small neighborhood of the origin. The simulation results verify the effectiveness of the control scheme.

  14. Voltage-Sensitive Load Controllers for Voltage Regulation and Increased Load Factor in Distribution Systems

    DEFF Research Database (Denmark)

    Douglass, Philip James; Garcia-Valle, Rodrigo; Østergaard, Jacob

    2014-01-01

    consumption which can be mapped to temperature setpoint offsets of thermostat controlled loads. In networks where a lower voltage level corresponds to high system load (and vice versa), this controller acts to regulate voltage and increase the load factor. Simulations are conducted on low- and medium-voltage......This paper presents a novel controller design for controlling appliances based on local measurements of voltage. The controller finds the normalized voltage deviation accounting for the sensitivity of voltage measurements to appliance state. The controller produces a signal indicating desired power...... distribution systems with residential loads including voltage-sensitive water heaters. In low-voltage systems, the results of the simulations show the controller to be effective at reducing the extremes of voltage and increasing the load factor while respecting end-use temperature constraints. In medium-voltage...

  15. Systemic Sclerosis Patients Present Alterations in the Expression of Molecules Involved in B-Cell Regulation.

    Science.gov (United States)

    Soto, Lilian; Ferrier, Ashley; Aravena, Octavio; Fonseca, Elianet; Berendsen, Jorge; Biere, Andrea; Bueno, Daniel; Ramos, Verónica; Aguillón, Juan Carlos; Catalán, Diego

    2015-01-01

    The activation threshold of B cells is tightly regulated by an array of inhibitory and activator receptors in such a way that disturbances in their expression can lead to the appearance of autoimmunity. The aim of this study was to evaluate the expression of activating and inhibitory molecules involved in the modulation of B cell functions in transitional, naive, and memory B-cell subpopulations from systemic sclerosis patients. To achieve this, blood samples were drawn from 31 systemic sclerosis patients and 53 healthy individuals. Surface expression of CD86, MHC II, CD19, CD21, CD40, CD22, Siglec 10, CD35, and FcγRIIB was determined by flow cytometry. IL-10 production was evaluated by intracellular flow cytometry from isolated B cells. Soluble IL-6 and IL-10 levels were measured by ELISA from supernatants of stimulated B cells. Systemic sclerosis patients exhibit an increased frequency of transitional and naive B cells related to memory B cells compared with healthy controls. Transitional and naive B cells from patients express higher levels of CD86 and FcγRIIB than healthy donors. Also, B cells from patients show high expression of CD19 and CD40, whereas memory cells from systemic sclerosis patients show reduced expression of CD35. CD19 and CD35 expression levels associate with different autoantibody profiles. IL-10(+) B cells and secreted levels of IL-10 were markedly reduced in patients. In conclusion, systemic sclerosis patients show alterations in the expression of molecules involved in B-cell regulation. These abnormalities may be determinant in the B-cell hyperactivation observed in systemic sclerosis.

  16. Systemic sclerosis patients present alterations in the expression of molecules involved in B cell regulation

    Directory of Open Access Journals (Sweden)

    Lilian eSoto

    2015-09-01

    Full Text Available The activation threshold of B cells is tightly regulated by an array of inhibitory and activator receptors, in such a way that disturbances in their expression can lead to the appearance of autoimmunity. The aim of this study was to evaluate the expression of activating and inhibitory molecules involved in the modulation of B cell functions in transitional, naïve and memory B cell sub-populations from systemic sclerosis patients. To achieve this, blood samples were drawn from thirty one systemic sclerosis patients and fifty three healthy individuals. Surface expression of CD86, MHC II, CD19, CD21, CD40, CD22, Siglec 10, CD35, and FcgammaRIIB was determined by flow cytometry. IL-10 production was evaluated by intracellular flow cytometry from isolated B cells. Soluble IL-6 and IL-10 levels were measured by ELISA from supernatants of stimulated B cells. Systemic sclerosis patients exhibit an increased frequency of transitional and naïve B cells related to memory B cells, compared to healthy controls. Transitional and naïve B cells from patients express higher levels of CD86 and FcgammaRIIB than healthy donors. Also, B cells from patients show high expression of CD19 and CD40, while memory cells from systemic sclerosis patients show reduced expression of CD35. CD19 and CD35 expression levels associate to different autoantibody profiles. IL-10+ B cells and secreted levels of IL-10 were markedly reduced in patients. In conclusion, systemic sclerosis patients show alterations in the expression of molecules involved in B cell regulation. These abnormalities may be determinant in the B cell hyperactivation observed in systemic sclerosis.

  17. 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.

  18. 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.

  19. Essential roles for the splicing regulator nSR100/SRRM4 during nervous system development.

    Science.gov (United States)

    Quesnel-Vallières, Mathieu; Irimia, Manuel; Cordes, Sabine P; Blencowe, Benjamin J

    2015-04-01

    Alternative splicing (AS) generates vast transcriptomic complexity in the vertebrate nervous system. However, the extent to which trans-acting splicing regulators and their target AS regulatory networks contribute to nervous system development is not well understood. To address these questions, we generated mice lacking the vertebrate- and neural-specific Ser/Arg repeat-related protein of 100 kDa (nSR100/SRRM4). Loss of nSR100 impairs development of the central and peripheral nervous systems in part by disrupting neurite outgrowth, cortical layering in the forebrain, and axon guidance in the corpus callosum. Accompanying these developmental defects are widespread changes in AS that primarily result in shifts to nonneural patterns for different classes of splicing events. The main component of the altered AS program comprises 3- to 27-nucleotide (nt) neural microexons, an emerging class of highly conserved AS events associated with the regulation of protein interaction networks in developing neurons and neurological disorders. Remarkably, inclusion of a 6-nt, nSR100-activated microexon in Unc13b transcripts is sufficient to rescue a neuritogenesis defect in nSR100 mutant primary neurons. These results thus reveal critical in vivo neurodevelopmental functions of nSR100 and further link these functions to a conserved program of neuronal microexon splicing.

  20. 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.

  1. Defective regulation of the ubiquitin/proteasome system in the hypothalamus of obese male mice.

    Science.gov (United States)

    Ignacio-Souza, Leticia M; Bombassaro, Bruna; Pascoal, Livia B; Portovedo, Mariana A; Razolli, Daniela S; Coope, Andressa; Victorio, Sheila C; de Moura, Rodrigo F; Nascimento, Lucas F; Arruda, Ana P; Anhe, Gabriel F; Milanski, Marciane; Velloso, Licio A

    2014-08-01

    In both human and experimental obesity, inflammatory damage to the hypothalamus plays an important role in the loss of the coordinated control of food intake and energy expenditure. Upon prolonged maintenance of increased body mass, the brain changes the defended set point of adiposity, and returning to normal weight becomes extremely difficult. Here we show that in prolonged but not in short-term obesity, the ubiquitin/proteasome system in the hypothalamus fails to maintain an adequate rate of protein recycling, leading to the accumulation of ubiquitinated proteins. This is accompanied by an increased colocalization of ubiquitin and p62 in the arcuate nucleus and reduced expression of autophagy markers in the hypothalamus. Genetic protection from obesity is accompanied by the normal regulation of the ubiquitin/proteasome system in the hypothalamus, whereas the inhibition of proteasome or p62 results in the acceleration of body mass gain in mice exposed for a short period to a high-fat diet. Thus, the defective regulation of the ubiquitin/proteasome system in the hypothalamus may be an important mechanism involved in the progression and autoperpetuation of obesity.

  2. 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.

  3. Up-regulation of the adrenomedullin system mediates hypotension and hypoaldosteronism induced by simulated microgravity.

    Science.gov (United States)

    Andreis, Paola G; Rossi, Gian Paolo; Bova, Sergio; Neri, Giuliano; Nussdorfer, Gastone G; Mazzocchi, Giuseppina

    2004-04-01

    We recently demonstrated that prolonged simulated microgravity (SMG) induced hypotension and hypoaldosteronism in rats, and gathered preliminary evidence for an involvement of circulating adrenomedullin (AM). Thus, we aimed to investigate whether short-term SMG elicits the same effects, and whether up-regulation of adrenal AM system plays a relevant role. Rats were exposed for 8 days to SMG in the form of hindlimb unweighting, and then, along with control animals, were given an intraperitoneal injection of AM22-52 and/or angiotensin-II (Ang-II) (100 nmoles/kg) or the saline vehicle. Systolic blood pressure (SBP) was measured by tail-cuff sphygmomanometry. The adrenal expression of AM was assayed by semiquantitative RT-PCR. The plasma concentrations of aldosterone (PAC) and AM, and adrenal AM content were measured by RIA. Short-term SMG induced significant decreases in SBP and PAC. Conversely, both the plasma and adrenal levels of AM, and adrenal AM mRNA were enhanced in SMG-exposed animals. The SMG-induced hypotension and hypoaldosteronism were reversed by AM22-52, an AM-receptor antagonist, thereby demonstrating a causal link between these effects and the up-regulation of AM system. SMG hampered SBP and PAC responses to Ang-II; the co-administration of AM22-52 restored these responses. These findings accord well with the known ability of AM to counteract the effects of Ang-II on both blood vessels and adrenocortical cells. Taken together, our findings allow us to conclude that up-regulation of the adrenal AM system i) occurs early and takes part in the adaptative changes occurring during SMG conditions; and ii) may account for both hypotension and hypoaldosteronism on returning to the normogravitational environment.

  4. PrhN, a putative marR family transcriptional regulator, is involved in positive regulation of type III secretion system and full virulence of Ralstonia solanacearum

    Directory of Open Access Journals (Sweden)

    Zhang eYong

    2015-04-01

    Full Text Available The MarR-family of transcriptional regulators are involved in various cellular processes, including resistance to multiple antibiotics and other toxic chemicals, adaptation to different environments and pathogenesis in many plant and animal pathogens. Here, we reported a new MarR regulator PrhN, which was involved in the pathogenesis of Ralstonia solanacearum. prhN mutant exhibited significantly reduced virulence and stem colonization compared to that of wild type in tomato plants. prhN mutant caused identical hypersensitive response (HR on resistant plants to the wild type. Deletion of prhN gene substantially reduced the expression of type III secretion system (T3SS in vitro and in planta (mainly in tomato plants, which is essential for pathogenicity of R. solanacearum, and the complemented PrhN could restore its virulence and T3SS expression to that of wild type. T3SS is directly controlled by AraC-type transcriptional regulator HrpB, and the transcription of hrpB is activated by HrpG and PrhG. HrpG and PrhG are homologues but are regulated by the PhcA positively and negatively respectively. Deletion of prhN gene also abolished the expression of hrpB and prhG, but didn't change the expression of hrpG and phcA. Together, these results indicated that PrhN positively regulates T3SS expression through PrhG and HrpB. PrhN and PhcA should regulate prhG expression in a parallel way. This is the first report on the pathogenesis of MarR regulator in R. solanacearum, and this new finding will improve our understanding on the various biological functions of MarR regulator and the complex regulatory network on hrp regulon in R. solanacearum.

  5. Simplification of heating systems by omitting circulating pumps and differential pressure regulating valves. Balancing; Vereinfachung durch Einsparung von Umwaelzpumpen und Differenzdruckregler. Hydraulischer Abgleich

    Energy Technology Data Exchange (ETDEWEB)

    Gebauer, Marc [Baelz W. und Sohn GmbH und Co., Berlin (Germany)

    2011-07-01

    Balancing of heating systems today is possible without differential pressure regulating valves. Only the design basis volume flow is adjusted at the sectioning valve of the heating section, while the part-load behaviour is regulated accurately via thermal power regulation. This simplifies balancing, and the total efficiency of systems will be better than with the commonly used differential pressure regulating valves.

  6. The cholinergic system is involved in regulation of the development of the hematopoietic system.

    Science.gov (United States)

    Serobyan, Naira; Jagannathan, Suchitra; Orlovskaya, Irina; Schraufstatter, Ingrid; Skok, Marina; Loring, Jeanne; Khaldoyanidi, Sophia

    2007-05-30

    Gene expression profiling demonstrated that components of the cholinergic system, including choline acetyltransferase, acetylcholinesterase and nicotinic acetylcholine receptors (nAChRs), are expressed in embryonic stem cells and differentiating embryoid bodies (EBs). Triggering of nAChRs expressed in EBs by nicotine resulted in activation of MAPK and shifts of spontaneous differentiation toward hemangioblast. In vivo, non-neural nAChRs are detected early during development in fetal sites of hematopoiesis. Similarly, in vivo exposure of the developing embryo to nicotine resulted in higher numbers of hematopoietic progenitors in fetal liver. However postpartum, the number of hematopoietic stem/progenitor cells (HSPC) was decreased, suggesting an impaired colonization of the fetal bone marrow with HSPCs. This correlated with increased number of circulating HSPC and decreased expression of CXCR4 that mediates migration of circulating cells into the bone marrow regulatory niche. In addition, protein microarrays demonstrated that nicotine changed the profile of cytokines produced in the niche. While the levels of IL1alpha, IL1beta, IL2, IL9 and IL10 were not changed, the production of hematopoiesis-supportive cytokines including G-CSF, GM-CSF, IL3, IL6 and IGFBP-3 was decreased. This correlated with the decreased repopulating ability of HSPC in vivo and diminished hematopoietic activity in bone marrow cultures treated with nicotine. Interestingly, nicotine stimulated the production of IL4 and IL5, implying a possible role of the cholinergic system in pathogenesis of allergic diseases. Our data provide evidence that the nicotine-induced imbalance of the cholinergic system during gestation interferes with normal development and provides the basis for negative health outcomes postpartum in active and passive smokers.

  7. 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.

  8. Role of K(ATP)(+) channels in regulation of systemic, pulmonary, and coronary vasomotor tone in exercising swine

    NARCIS (Netherlands)

    D.J.G.M. Duncker (Dirk); H.H. Oei (Hok-Hay); F. Hu; R. Stubenitsky (René); P.D. Verdouw (Pieter)

    2001-01-01

    textabstractThe role of ATP-sensitive K(+) (K(ATP)(+)) channels in vasomotor tone regulation during metabolic stimulation is incompletely understood. Consequently, we studied the contribution of K(ATP)(+) channels to vasomotor tone regulation in the systemic, pulmonary,

  9. 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

    of the hypothalamus. Adult mice were treated with ECS once daily for 14 consecutive days, a paradigm previously shown to exert antidepressant-like effects. Significant increases in galanin transcription were found in the locus coeruleus and dorsomedial nuclei of the hypothalamus. In addition, GalR2 mRNA levels...... in the ventro- and dorsomedial nuclei of the hypothalamus were upregulated whereas no GalR1 mRNA upregulation was observed. [(125)I]-galanin receptor binding was downregulated in the ventromedial nuclei of the hypothalamus and dorsal raphe. These data show that the galanin system is regulated by repeated ECS...

  10. COMPLEMENT REGULATOR FHR-3 IS ELEVATED EITHER LOCALLY OR SYSTEMICALLY IN A SELECTION OF AUTOIMMUNE DISEASES

    OpenAIRE

    Nicole Schäfer; Antje Grosche; Joerg Reinders; Stefanie Hauck; Pouw, Richard B.; Taco W Kuijpers; Diana Wouters; Boris Ehrenstein; Volker Enzmann; Peter Zipfel; Christine Skerka; Diana Pauly

    2016-01-01

    The human complement factor H-related protein-3 (FHR-3) is a soluble regulator of the complement system. Homozygous cfhr3/1 deletion is a genetic risk factor for the autoimmune form of atypical hemolytic-uremic syndrome (aHUS), while also found to be protective in age-related macular degeneration (AMD). The precise function of FHR-3 remains to be fully characterized. We generated four mouse monoclonal antibodies (mAbs) for FHR-3 (RETC) without cross-reactivity to the complement factor H (FH)-...

  11. 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.

  12. 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.

  13. Malta; Financial System Stability Assessment, including Reports on the Observance of Standards and Codes on the following topics: Monetary and Financial Policy Transparency, Banking Supervision, Securities Regulation, Insurance Regulation, Corporate Governance, and Payment Systems

    OpenAIRE

    International Monetary Fund

    2003-01-01

    The report provides the details of the Malta Financial Stability Assessment (MFSA). It defines its roles, responsibilities, and objectives for financial policies. It reviews the reports on the observance of standards and codes on monetary and financial policy transparency, banking supervision, securities regulation, insurance regulation, corporate governance, and payment systems. It assesses the macroeconomic environment and risks, soundness and vulnerabilities of the financial system, and al...

  14. Cystic fibrosis transmembrane conductance regulator protein expression in the male excretory duct system during development.

    Science.gov (United States)

    Marcorelles, Pascale; Gillet, Danièle; Friocourt, Gaëlle; Ledé, Françoise; Samaison, Laura; Huguen, Geneviève; Ferec, Claude

    2012-03-01

    Sterility due to bilateral destruction in utero or in early infancy resulting in congenital absence of the vas deferens is the rule in male patients with cystic fibrosis. To understand the developmental pattern of this anomaly, the microscopic morphology of the male excretory system was analyzed during development and the expression of the cystic fibrosis transmembrane conductance regulator protein was explored by immunohistochemistry. We observed that cystic fibrosis fetuses had no excretory ducts agenesis or obstruction until 22 weeks of gestation. However, a focal inflammatory pattern and mucinous plugs in the oldest cystic fibrosis case suggested a disruptive mechanism. Immunolabeling of cytoplasmic epithelial cystic fibrosis transmembrane conductance regulator protein was demonstrated in all cystic fibrosis and control cases with a similar pattern of expression of the protein between age-matched controls and cystic fibrosis cases. At midgestation, an apical intensification appeared in both cystic fibrosis and control cases and was stable during the remainder of fetal life. No gradient of intensity could be detected between the different segments of the excretory tract. These findings are different from those reported in adults. The absence of any morphologic anomaly until 22 weeks of gestation, the focal destruction of the epithelial structures during the second trimester, and the chronological pattern of expression of cystic fibrosis transmembrane conductance regulator are of interest for a better understanding of the pathophysiology of this disease.

  15. Functional Characterization of Gibberellin-Regulated Genes in Rice Using Microarray System

    Institute of Scientific and Technical Information of China (English)

    Asad Jan; Setsuko Komatsu

    2006-01-01

    Gibberellin (GA) is collectively referred to a group of diterpenoid acids, some of which act as plant hormones and are essential for normal plant growth and development. DNA microarray technology has become the standard tool for the parallel quantification of large numbers of messenger RNA transcripts. The power of this approach has been demonstrated in dissecting plant physiology and development, and in unraveling the underlying cellular signaling pathways. To understand the molecular mechanism by which GA regulates the growth and development of plants, with reference to the monocot model plant-rice, it is essential to identify and analyze more genes and their products at the transcription and translation levels that are regulated by GA. With the availability of draft sequences of two major rice types, indica and japonica rice, it has become possible to analyze global expression profiles of genes on a genome scale. In this review, the progress made in finding new genes in rice leaf sheath using microarray system and their characterization is discussed. It is believed that the findings made in this regard have important implications for understanding the mechanism by which GA regulates the growth and development of rice.

  16. 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.

  17. Performance Evaluation of Antlion Optimizer Based Regulator in Automatic Generation Control of Interconnected Power System

    Directory of Open Access Journals (Sweden)

    Esha Gupta

    2016-01-01

    Full Text Available This paper presents an application of the recently introduced Antlion Optimizer (ALO to find the parameters of primary governor loop of thermal generators for successful Automatic Generation Control (AGC of two-area interconnected power system. Two standard objective functions, Integral Square Error (ISE and Integral Time Absolute Error (ITAE, have been employed to carry out this parameter estimation process. The problem is transformed in optimization problem to obtain integral gains, speed regulation, and frequency sensitivity coefficient for both areas. The comparison of the regulator performance obtained from ALO is carried out with Genetic Algorithm (GA, Particle Swarm Optimization (PSO, and Gravitational Search Algorithm (GSA based regulators. Different types of perturbations and load changes are incorporated to establish the efficacy of the obtained design. It is observed that ALO outperforms all three optimization methods for this real problem. The optimization performance of ALO is compared with other algorithms on the basis of standard deviations in the values of parameters and objective functions.

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

    Science.gov (United States)

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

    2015-01-01

    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. PMID:25560704

  19. 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.

  20. 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.

  1. [Legal aspects of the REACH regulation. The control system of the REACH regulation--new approaches in the EU chemical legislation].

    Science.gov (United States)

    Pache, Eckhard

    2008-12-01

    The REACH regulation from 2006 shall overcome the deficiencies of the previously existing inconsistent legal system of chemicals and build an efficient and innovative regulation for industrial chemicals in the EU. For this purpose, the REACH regulation is not inventing a completely new legislation for chemical substances, but refers to the existing rules, regulates and structures them in a new manner and complements them. With REACH a consistent control system for chemicals in Europe has been created, which basically is managed and coordinated by the newly established European Chemicals Agency (ECHA). In the first phases of the REACH system, information about chemicals is generated and afterwards evaluated. Then this information is used in a process of authorization and restriction, to ensure adequate proliferation and safe exposure to chemical substances. Numerous duties to furnish information complement the readjustment's procedural steps, particularly with regard to the supply chain and down to the consumer. It is mainly affected by the abrogation of the determination between new and existing substances, the principle of substitution and is based on the idea that industry itself is best suited to ensure that the substances it manufactures and places on the market in the EU do not adversely affect human health or the environment.

  2. 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.

  3. K+ uptake in plant roots. The systems involved, their regulation and parallels in other organisms.

    Science.gov (United States)

    Nieves-Cordones, Manuel; Alemán, Fernando; Martínez, Vicente; Rubio, Francisco

    2014-05-15

    Potassium (K(+)) is an essential macronutrient for plants. It is taken into the plant by the transport systems present in the plasma membranes of root epidermal and cortical cells. The identity of these systems and their regulation is beginning to be understood and the systems of K(+) transport in the model species Arabidopsis thaliana remain far better characterized than in any other plant species. Roots can activate different K(+) uptake systems to adapt to their environment, important to a sessile organism that needs to cope with a highly variable environment. The mechanisms of K(+) acquisition in the model species A. thaliana are the best characterized at the molecular level so far. According to the current model, non-selective channels are probably the main pathways for K(+) uptake at high concentrations (>10mM), while at intermediate concentrations (1mM), the inward rectifying channel AKT1 dominates K(+) uptake. Under lower concentrations of external K(+) (100μM), AKT1 channels, together with the high-affinity K(+) uptake system HAK5 contribute to K(+) acquisition, and at extremely low concentrations (root K(+) uptake are shared by other organisms, whilst others are specific to plants. This indicates that some crucial properties of the ancestral of K(+) transport systems have been conserved through evolution while others have diverged among different kingdoms.

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

    Science.gov (United States)

    2014-01-01

    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

  5. 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

  6. 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.

  7. Regulation of STIM1 and SOCE by the ubiquitin-proteasome system (UPS.

    Directory of Open Access Journals (Sweden)

    Jeffrey M Keil

    Full Text Available The ubiquitin proteasome system (UPS mediates the majority of protein degradation in eukaryotic cells. The UPS has recently emerged as a key degradation pathway involved in synapse development and function. In order to better understand the function of the UPS at synapses we utilized a genetic and proteomic approach to isolate and identify novel candidate UPS substrates from biochemically purified synaptic membrane preparations. Using these methods, we have identified Stromal interacting molecule 1 (STIM1. STIM1 is as an endoplasmic reticulum (ER calcium sensor that has been shown to regulate store-operated Ca(2+ entry (SOCE. We have characterized STIM1 in neurons, finding STIM1 is expressed throughout development with stable, high expression in mature neurons. As in non-excitable cells, STIM1 is distributed in a membranous and punctate fashion in hippocampal neurons. In addition, a population of STIM1 was found to exist at synapses. Furthermore, using surface biotinylation and live-cell labeling methods, we detect a subpopulation of STIM1 on the surface of hippocampal neurons. The role of STIM1 as a regulator of SOCE has typically been examined in non-excitable cell types. Therefore, we examined the role of the UPS in STIM1 and SOCE function in HEK293 cells. While we find that STIM1 is ubiquitinated, its stability is not altered by proteasome inhibitors in cells under basal conditions or conditions that activate SOCE. However, we find that surface STIM1 levels and thapsigargin (TG-induced SOCE are significantly increased in cells treated with proteasome inhibitors. Additionally, we find that the overexpression of POSH (Plenty of SH3's, an E3 ubiquitin ligase recently shown to be involved in the regulation of Ca(2+ homeostasis, leads to decreased STIM1 surface levels. Together, these results provide evidence for previously undescribed roles of the UPS in the regulation of STIM1 and SOCE function.

  8. Rapid systemic up-regulation of genes after heat-wounding and electrical stimulation

    Science.gov (United States)

    Davies, E.; Vian, A.; Vian, C.; Stankovic, B.

    1997-01-01

    When one leaf of a tomato plant is electrically-stimulated or heat-wounded, proteinase inhibitor genes are rapidly up-regulated in distant leaves. The identity of the systemic wound signal(s) is not yet known, but major candidates include hormones transmitted via the phloem or the xylem, the electrically-stimulated self-propagating electrical signal in the phloem (the action potential, AP), or the heat-wound-induced surge in hydraulic pressure in the xylem evoking a local change in membrane potential in adjacent living cells (the variation potential, VP). In order to discriminate between these signals we have adopted two approaches. The first approach involves applying stimuli that evoke known signals and determining whether these signals have similar effects on the "model" transcripts for proteinase inhibitors (pin) and calmodulin (cal). Here we show that a heat wound almost invariably evokes a VP, while an electrical stimulation occasionally evokes an AP, and both of these signals induce accumulation of transcripts encoding proteinase inhibitors. The second approach involves identifying the array of genes turned on by heat-wounding. To this end, we have constructed a subtractive library for heat-wounded tissue, isolated over 800 putatively up-regulated clones, and shown that all but two of the fifty that we have analyzed by Northern hybridization are, indeed, up-regulated. Here we show the early kinetics of up-regulation of three of these transcripts in the terminal (4th) leaf in response to heat-wounding the 3rd leaf, about 5 cm away. Even though these transcripts show somewhat different time courses of induction, with one peaking at 30 min, another at 15 min, and another at 5 min after flaming of a distant leaf, they all exhibit a similar pattern, i.e., a transient period of transcript accumulation preceding a period of transcript decrease, followed by a second period of transcript accumulation.

  9. The development and characterization of an exogenous green-light-regulated gene expression system in marine cyanobacteria.

    Science.gov (United States)

    Badary, Amr; Abe, Koichi; Ferri, Stefano; Kojima, Katsuhiro; Sode, Koji

    2015-06-01

    A green-light-regulated gene expression system derived from Synechocystis sp. PCC 6803 was constructed and introduced into the marine cyanobacterial strain Synechococcus sp. NKBG 15041c. The regulation system was evaluated using gfp uv as a reporter gene under red-light illumination and under simultaneous red- and green-light illumination. Expression of the reporter gene was effectively repressed under red-light illumination and increased over 10-fold by illuminating with green light. Control vectors missing either the ccaS sensor histidine kinase gene or the ccaR response regulator gene showed no detectable induction of GFPuv expression. Green-light induction of gfp uv expression was further confirmed by quantitative reverse transcription PCR. The constructed system was effective at regulating the recombinant expression of a target gene using green light in a marine cyanobacterial strain that does not naturally possess such a green-light regulation system. Thus, constructed green-light-regulated gene expression system may be used as a core platform technology for the development of marine cyanobacterial strains in which bioprocesses will be regulated by light.

  10. 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

  11. Dynamic stereotype and vegetative regulation corection in childrens with effects of organic lesion of nervous system

    Directory of Open Access Journals (Sweden)

    Наталія Юріївна Гришуніна

    2015-08-01

    Full Text Available Aim of research. An assessment of the CNS state, neuropsychological indicators and influence of the modern methods of physical rehabilitation on the dynamics of vegetative adaptive and compensatory brain systems in patients with effects of an early organic lesion of nervous system.Materials and methods of research. There were examined and treated 20 children 7-11 years old. An assessment of vegetative homeostasis was carried out using cardiointervalography (CIG, neuropsychic functions and deficiency of statomotor development – the method of Luriya neuropsychological testing. The children of the first group (10 persons underwent massage and therapeutic physical training with special attention to the dynamic stereotype in complex with generally developmental, breathing, special passive and active, static and dynamic exercises, postisometric relaxation, massotherapy. The patients of the second group (10 persons underwent traditional therapeutic physical training and massage.Results of research. It was observed an inhibition of the humoral control of heart rate in examined children and at the same time an activation of sympathetic system. As a result it was detected an increase of the stress index of compensatory reactions of organism (stress index SI — 124 un. at the norm 65,0 ud.. Neuropsychological features of these patients indicated the presence of the left hemispheric and less right hemispheric deficiency, dysfunction of subcortical and stem structures.The use of the complex methodology of rehabilitation with special attention to the dynamic stereotype and manual therapy according to the aspects of genesis of myofascial dysfunction favored an optimization of the stress of compensatory mechanisms of organism (SI — 51,0 un.. In the second group it was observed a stable activity of sympathetic regulation of the heart rate compared with indicators before treatment and an insignificant decrease of the stress index of vegetative balance (SI

  12. 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

    2015-09-14

    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.

  13. A Simple Auxin Transcriptional Response System Regulates Multiple Morphogenetic Processes in the Liverwort Marchantia polymorpha.

    Science.gov (United States)

    Flores-Sandoval, Eduardo; Eklund, D Magnus; Bowman, John L

    2015-05-01

    In land plants comparative genomics has revealed that members of basal lineages share a common set of transcription factors with the derived flowering plants, despite sharing few homologous structures. The plant hormone auxin has been implicated in many facets of development in both basal and derived lineages of land plants. We functionally characterized the auxin transcriptional response machinery in the liverwort Marchantia polymorpha, a member of the basal lineage of extant land plants. All components known from flowering plant systems are present in M. polymorpha, but they exist as single orthologs: a single MpTOPLESS (TPL) corepressor, a single MpTRANSPORT inhibitor response 1 auxin receptor, single orthologs of each class of auxin response factor (ARF; MpARF1, MpARF2, MpARF3), and a single negative regulator auxin/indole-3-acetic acid (MpIAA). Phylogenetic analyses suggest this simple system is the ancestral condition for land plants. We experimentally demonstrate that these genes act in an auxin response pathway--chimeric fusions of the MpTPL corepressor with heterodimerization domains of MpARF1, MpARF2, or their negative regulator, MpIAA, generate auxin insensitive plants that lack the capacity to pattern and transition into mature stages of development. Our results indicate auxin mediated transcriptional regulation acts as a facilitator of branching, differentiation and growth, rather than acting to determine or specify tissues during the haploid stage of the M. polymorpha life cycle. We hypothesize that the ancestral role of auxin is to modulate a balance of differentiated and pluri- or totipotent cell states, whose fates are determined by interactions with combinations of unrelated transcription factors.

  14. Global output regulation of a class of lower triangular nonlinear systems with unknown control direction via output feedback

    Science.gov (United States)

    Li, Ranran

    2016-05-01

    In this paper, we study the global output regulation problem of a class of lower triangular systems under measurement output feedback. A novel high-gain filter is proposed to estimate the unmeasured states of the systems. Furthermore, we integrate the robust stabilisation technique and Nussbaumgain technique to achieve asymptotic regulation when the control direction is unknown. The simulation results illustrate the effectiveness of the proposed method.

  15. Anti-crisis Regulation, Banking Supervision and Monetary Policy in the Mechanism of Ensuring Financial Stability of the Banking System

    OpenAIRE

    Dovgan Zhanna N.

    2013-01-01

    The article develops a scheme of correlations of subjects of anti-crisis regulation and tools of support of financial stability of the banking system of Ukraine (FSBS). It analyses instruments of influence of the bodies of state regulation on financial stability of the banking system of Ukraine. It develops proposals with respect to improvement of the banking supervision in the context of ensuring FSBS of Ukraine. It studies interdependence between the type of the mode of national regulatory ...

  16. Output Consensus Regulation for State-Unmeasurable Discrete-Time Multiagent Systems with External Disturbances

    Directory of Open Access Journals (Sweden)

    He Jiang

    2015-01-01

    Full Text Available This paper deals with the output consensus regulation problem for discrete-time multiagent systems with state-unmeasurable agents and external disturbances under directed communication network topologies. Firstly, the mathematical model for the output consensus problem of discrete-time multiagent systems is deduced and formulated via making matrix transformation. Then, based on state observers, a novel output consensus protocol with dynamic compensator which is used as observer for the exosystem is proposed to solve this problem. Some knowledge of matrix theory and graph theory is introduced to design protocol parameters and the convergence of output consensus errors is proved. Finally, a numerical simulation example is shown to verify the effectiveness of the proposed protocol design.

  17. Neural regulation of gastrointestinal inflammation: role of the sympathetic nervous system.

    Science.gov (United States)

    Cervi, Andrea L; Lukewich, Mark K; Lomax, Alan E

    2014-05-01

    The sympathetic innervation of the gastrointestinal (GI) tract regulates motility, secretion and blood flow by inhibiting the activity of the enteric nervous system (ENS) and direct vasoconstrictor innervation of the gut microvasculature. In addition to these well-established roles, there is evidence that the sympathetic nervous system (SNS) can modulate GI inflammation. Postganglionic sympathetic neurons innervate lymphoid tissues and immune cells within the GI tract. Furthermore, innate and adaptive immune cells express receptors for sympathetic neurotransmitters. Activation of these receptors can affect a variety of important immune cell functions, including cytokine release and differentiation of helper T lymphocyte subsets. This review will consider the neuroanatomical evidence of GI immune cell innervation by sympathetic axons, the effects of blocking or enhancing SNS activity on GI inflammation, and the converse modulation of sympathetic neuroanatomy and function by GI inflammation.

  18. 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...... on marginal production costs, the latter aiming at finding the match between production and consumption satisfying the constraints set by the EMS level about the energy production in each time slot. Neglecting the efficiency of the different energy generation systems as well as that of the infrastructure...... for electrical energy distribution, the problem dealt with by the EMS sub-level is linear and can be solved by well known Linear Programming optimization procedures. The tertiary sub-level, below the EMS, optimizes mainly technical objectives and requires the solution of the Optimal Power Flow problem. After...

  19. Cooperative Adaptive Output Regulation for Second-Order Nonlinear Multiagent Systems With Jointly Connected Switching Networks.

    Science.gov (United States)

    Liu, Wei; Huang, Jie

    2017-01-11

    This paper studies the cooperative global robust output regulation problem for a class of heterogeneous second-order nonlinear uncertain multiagent systems with jointly connected switching networks. The main contributions consist of the following three aspects. First, we generalize the result of the adaptive distributed observer from undirected jointly connected switching networks to directed jointly connected switching networks. Second, by performing a new coordinate and input transformation, we convert our problem into the cooperative global robust stabilization problem of a more complex augmented system via the distributed internal model principle. Third, we solve the stabilization problem by a distributed state feedback control law. Our result is illustrated by the leader-following consensus problem for a group of Van der Pol oscillators.

  20. Composite nonlinear feedback control for output regulation problem of linear discrete-time systems with input saturation

    Institute of Scientific and Technical Information of China (English)

    Chongwen Wang; Xing Chu; Weiyao Lan

    2014-01-01

    Transient performance for output regulation problems of linear discrete-time systems with input saturation is addressed by using the composite nonlinear feedback (CNF) control tech-nique. The regulator is designed to be an additive combination of a linear regulator part and a nonlinear feedback part. The linear regulator part solves the regulation problem independently which produces a quick output response but large oscil ations. The non-linear feedback part with wel-tuned parameters is introduced to improve the transient performance by smoothing the oscil atory convergence. It is shown that the introduction of the nonlinear feedback part does not change the solvability conditions of the linear discrete-time output regulation problem. The effectiveness of transient improvement is il ustrated by a numeric example.

  1. From Rat to Human: Regulation of Renin-Angiotensin System Genes by Sry

    Directory of Open Access Journals (Sweden)

    Jeremy W. Prokop

    2012-01-01

    Full Text Available The testis determining protein, Sry, has functions outside of testis determination. Multiple Sry loci are found on the Y-chromosome. Proteins from these loci have differential activity on promoters of renin-angiotensin system genes, possibly contributing to elevation of blood pressure. Variation at amino acid 76 accounts for the majority of differential effects by rat proteins Sry1 and Sry3. Human SRY regulated rat promoters in the same manner as rat Sry, elevating Agt, Ren, and Ace promoter activity while downregulating Ace 2. Human SRY significantly regulated human promoters of AGT, REN, ACE2, AT2, and MAS compared to control levels, elevating AGT and REN promoter activity while decreasing ACE2, AT2, and MAS. While the effect of human SRY on individual genes is often modest, we show that many different genes participating in the renin-angiotensin system can be affected by SRY, apparently in coordinated fashion, to produce more Ang II and less Ang-(1–7.

  2. 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.

  3. Cancer metabolism meets systems biology: Pyruvate kinase isoform PKM2 is a metabolic master regulator

    Directory of Open Access Journals (Sweden)

    Fabian V Filipp

    2013-01-01

    Full Text Available Pyruvate kinase activity is controlled by a tightly woven regulatory network. The oncofetal isoform of pyruvate kinase (PKM2 is a master regulator of cancer metabolism. PKM2 engages in parallel, feed-forward, positive and negative feedback control contributing to cancer progression. Besides its metabolic role, non-metabolic functions of PKM2 as protein kinase and transcriptional coactivator for c-MYC and hypoxia-inducible factor 1-alpha are essential for epidermal growth factor receptor activation-induced tumorigenesis. These biochemical activities are controlled by a shift in the oligomeric state of PKM2 that includes acetylation, oxidation, phosphorylation, prolyl hydroxylation and sumoylation. Metabolically active PKM2 tetramer is allosterically regulated and responds to nutritional and stress signals. Metabolically inactive PKM2 dimer is imported into the nucleus and can function as protein kinase stimulating transcription. A systems biology approach to PKM2 at the genome, transcriptome, proteome, metabolome and fluxome level reveals how differences in biomolecular structure translate into a global rewiring of cancer metabolism. Cancer systems biology takes us beyond the Warburg effect, opening unprecedented therapeutic opportunities.

  4. [The role of the pineal-thymus system in the regulation of autoimmunity, aging and lifespan].

    Science.gov (United States)

    Csaba, György

    2016-07-03

    Thymus is an immunoendocrine organ, the hormones of which mainly influence its own lymphatic elements. It has a central role in the immune system, the neonatal removal causes the collapse of immune system and the whole organism. The thymic nurse cells select the bone marrow originated lymphocytes and destroy the autoreactive ones, while thymus originated Treg cells suppress the autoreactive cells in the periphery. The involution of the organ starts after birth, however, this truly happens in the end of puberty only, as before this it is overcompensated by developmental processes. From the end of adolescence the involution allows the life, proliferation and enhanced functioning of some autoreactive cells, which gradually wear down the cells and intercellular materials, causing the aging. The enhanced and mass function of autoreactive cells lead to the autoimmune diseases and natural death. This means that the involution of thymus is not a part of the organismic involution, but an originator of it, which is manifested in the lifespan-pacemaker function. Thus, aging can be conceptualized as a thymus-commanded slow autoimmune process. The neonatal removal of pineal gland leads to the complete destruction of the thymus and the crashing down of the immune system, as well as to wasting disease. The involution of the pineal and thymus runs parallel, because the two organs form a functional unit. It is probable that the pineal gland is responsible for the involution of thymus and also regulates its lifespan determining role. However, the data reviewed here do not prove the exclusive role of the pineal-thymus system in the regulation of aging and lifespan, but only call attention to such possibility.

  5. Regulation of acid resistance by connectors of two-component signal transduction systems in Escherichia coli.

    Science.gov (United States)

    Eguchi, Yoko; Ishii, Eiji; Hata, Kensuke; Utsumi, Ryutaro

    2011-03-01

    Two-component signal transduction systems (TCSs), utilized extensively by bacteria and archaea, are involved in the rapid adaptation of the organisms to fluctuating environments. A typical TCS transduces the signal by a phosphorelay between the sensor histidine kinase and its cognate response regulator. Recently, small-sized proteins that link TCSs have been reported and are called "connectors." Their physiological roles, however, have remained elusive. SafA (sensor associating factor A) (formerly B1500), a small (65-amino-acid [65-aa]) membrane protein, is among such connectors and links Escherichia coli TCSs EvgS/EvgA and PhoQ/PhoP. Since the activation of the EvgS/EvgA system induces acid resistance, we examined whether the SafA-activated PhoQ/PhoP system is also involved in the acid resistance induced by EvgS/EvgA. Using a constitutively active evgS1 mutant for the activation of EvgS/EvgA, we found that SafA, PhoQ, and PhoP all contributed to the acid resistance phenotype. Moreover, EvgS/EvgA activation resulted in the accumulation of cellular RpoS in the exponential-phase cells in a SafA-, PhoQ-, and PhoP-dependent manner. This RpoS accumulation was caused by another connector, IraM, expression of which was induced by the activation of the PhoQ/PhoP system, thus preventing RpoS degradation by trapping response regulator RssB. Acid resistance assays demonstrated that IraM also participated in the EvgS/EvgA-induced acid resistance. Therefore, we propose a model of a signal transduction cascade proceeding from EvgS/EvgA to PhoQ/PhoP and then to RssB (connected by SafA and IraM) and discuss its contribution to the acid resistance phenotype.

  6. 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.; Czyz, Daniel M.; Babnigg, Gyorgy; Kim, Youngchang; Crosson, Sean

    2017-03-01

    Brucella abortus sigma(E1) is 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 sigma(E1) regulon. 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 of yehZYXW is activated by the general stress sigma factor sigma(S) in Enterobacteriaceae, which suggests a functional role for this transport system in bacterial stress response across the classes Alphaproteobacteria and Gammaproteobacteria. We present evidence that B. abortus YehZYXW does not function as an importer of known compatible solutes under physiological conditions and does not contribute to the virulence defect of a sigma(E1)- null strain. The sole in vitro phenotype associated with genetic disruption of this putative transport system is reduced growth in the presence of high Li+ ion concentrations. A crystal structure of B. abortus YehZ revealed a class II periplasmic binding protein fold with significant structural homology to Archaeoglobus fulgidus ProX, which binds glycine betaine. However, the structure of the YehZ ligand-binding pocket is incompatible with high-affinity binding to glycine betaine. This is consistent with weak measured binding of YehZ to glycine betaine and related compatible solutes. We conclude that YehZYXW is a conserved, stress-regulated transport system that is phylogenetically and functionally distinct from quaternary ammonium-compatible solute importers

  7. 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.

  8. HDAC Inhibitors as Epigenetic Regulators of the Immune System: Impacts on Cancer Therapy and Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Elizabeth E. Hull

    2016-01-01

    Full Text Available Histone deacetylase (HDAC inhibitors are powerful epigenetic regulators that have enormous therapeutic potential and have pleiotropic effects at the cellular and systemic levels. To date, HDAC inhibitors are used clinically for a wide variety of disorders ranging from hematopoietic malignancies to psychiatric disorders, are known to have anti-inflammatory properties, and are in clinical trials for several other diseases. In addition to influencing gene expression, HDAC enzymes also function as part of large, multisubunit complexes which have many nonhistone targets, alter signaling at the cellular and systemic levels, and result in divergent and cell-type specific effects. Thus, the effects of HDAC inhibitor treatment are too intricate to completely understand with current knowledge but the ability of HDAC inhibitors to modulate the immune system presents intriguing therapeutic possibilities. This review will explore the complexity of HDAC inhibitor treatment at the cellular and systemic levels and suggest strategies for effective use of HDAC inhibitors in biomedical research, focusing on the ability of HDAC inhibitors to modulate the immune system. The possibility of combining the documented anticancer effects and newly emerging immunomodulatory effects of HDAC inhibitors represents a promising new combinatorial therapeutic approach for HDAC inhibitor treatments.

  9. System identification: a multi-signal approach for probing neural cardiovascular regulation.

    Science.gov (United States)

    Xiao, Xinshu; Mullen, Thomas J; Mukkamala, Ramakrishna

    2005-06-01

    Short-term, beat-to-beat cardiovascular variability reflects the dynamic interplay between ongoing perturbations to the circulation and the compensatory response of neurally mediated regulatory mechanisms. This physiologic information may be deciphered from the subtle, beat-to-beat variations by using digital signal processing techniques. While single signal analysis techniques (e.g., power spectral analysis) may be employed to quantify the variability itself, the multi-signal approach of system identification permits the dynamic characterization of the neural regulatory mechanisms responsible for coupling the variability between signals. In this review, we provide an overview of applications of system identification to beat-to-beat variability for the quantitative characterization of cardiovascular regulatory mechanisms. After briefly summarizing the history of the field and basic principles, we take a didactic approach to describe the practice of system identification in the context of probing neural cardiovascular regulation. We then review studies in the literature over the past two decades that have applied system identification for characterizing the dynamical properties of the sinoatrial node, respiratory sinus arrhythmia, and the baroreflex control of sympathetic nerve activity, heart rate and total peripheral resistance. Based on this literature review, we conclude by advocating specific methods of practice and that future research should focus on nonlinear and time-varying behaviors, validation of identification methods, and less understood neural regulatory mechanisms. Ultimately, we hope that this review stimulates such future investigations by both new and experienced system identification researchers.

  10. 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.

  11. 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.

  12. Bifurcation analysis of hydro-turbine regulating system with saturation nonlinearity for hydropower station with upstream and downstream surge chambers

    Science.gov (United States)

    Chen, J. P.; Yang, J. D.; Guo, W. C.

    2016-11-01

    A nonlinear mathematical model of hydraulic turbine regulating system is applied to describe hydropower stations with upstream and downstream surge chambers. This model features saturation nonlinearity including pipeline system and turbine regulating system used in stability analysis. First, the existence conditions and direction of Hopf bifurcation are obtained. Second, based on the algebraic criteria for the occurrence of Hopf bifurcation, the stability domain is drawn in a coordinate system, where the proportional gain Kp is the abscissa and the integral gain Ki is the ordinate. Third, the nonlinear dynamic behaviour of a regulating system with different state parameters are analyzed, and the variations of the system stability around the two sides of the bifurcation point are numerically calculated. Based on this work we conclude that the Hopf bifurcation of system is supercritical. The bifurcation parameters that are far from the bifurcation point would be advantageous to the rapid system regulation needed to sustain equilibrium. Furthermore, it is established that using a PID controller is more conducive to stability than a PI controller. The unit stability regulation gets worse by taking into account the saturation nonlinearity.

  13. 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.

  14. Mutual regulation of growth hormone and bone morphogenetic protein system in steroidogenesis by rat granulosa cells.

    Science.gov (United States)

    Nakamura, Eri; Otsuka, Fumio; Inagaki, Kenichi; Miyoshi, Tomoko; Matsumoto, Yoshinori; Ogura, Kanako; Tsukamoto, Naoko; Takeda, Masaya; Makino, Hirofumi

    2012-01-01

    GH induces preantral follicle growth and differentiation with oocyte maturation. However, the effects of GH on ovarian steroidogenesis and the mechanisms underlying its effects have yet to be elucidated. In this study, we investigated the actions of GH on steroidogenesis by rat granulosa cells isolated from early antral follicles by focusing on the ovarian bone morphogenetic protein (BMP) system. We found that GH suppressed FSH-induced estradiol production with reduction in aromatase expression and, in contrast, GH increased FSH-induced progesterone level with induction of steroidogenic acute regulatory protein, side chain cleavage cytochrome P450, and 3β-hydroxysteroid dehydrogenase. The effects of GH on steroidogenesis by granulosa cells were enhanced in the presence of the BMP antagonist noggin. Coculture of GH with oocytes did not alter GH regulation of steroidogenesis. Steroid production induced by cAMP donors was not affected by GH treatment and the GH effects on FSH-induced steroid production were not accompanied by changes in cAMP synthesis, suggesting that GH actions were not directly mediated by the cAMP-protein kinase A pathway. GH exerted synergistic effects on MAPK activation elicited by FSH, which regulated FSH-induced steroidogenesis. In addition, GH-induced signal transducer and activator of transcription phosphorylation was involved in the induction of IGF-I expression. GH increased IGF-I, IGF-I receptor, and FSH receptor expression in granulosa cells, and inhibition of IGF-I signaling restored GH stimulation of FSH-induced progesterone production, suggesting that endogenous IGF-I is functionally involved in GH effects on progesterone induction. BMP inhibited IGF-I effects that increased FSH-induced estradiol production with suppression of expression of the GH/IGF-I system, whereas GH/IGF-I actions impaired BMP-Sma and Mad related protein 1/5/8 signaling through down-regulation of the expression of BMP receptors. Thus, GH acts to modulate estrogen

  15. 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.

  16. Phylogenetic footprint of the plant clock system in angiosperms: evolutionary processes of Pseudo-Response Regulators

    Science.gov (United States)

    2010-01-01

    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. PMID:20433765

  17. Phylogenetic footprint of the plant clock system in angiosperms: evolutionary processes of pseudo-response regulators.

    Science.gov (United States)

    Takata, Naoki; Saito, Shigeru; Saito, Claire Tanaka; Uemura, Matsuo

    2010-05-01

    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. 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. 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.

  18. A fixed by-pass for the regulation of low temperature space heating systems; Un bipasse fixe pour la regulation des systemes de chauffage a basse temperature

    Energy Technology Data Exchange (ETDEWEB)

    Didier, G.

    2003-06-01

    A fixed by-pass is an important element of the regulation of a water space heating installation. It allows to stabilize the temperature, to reduce the diameter of the regulation valves and to improve their operation. This technical article makes a numerical comparison between different space heating loops involving a three-way mixing valve or a two-way mixing valve with or without a fixed by-pass. (J.S.)

  19. 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.; Czyż, Daniel M.; Babnigg, Gyorgy; Kim, Youngchang; Crosson, Sean; Stock, Ann M.

    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

  20. 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...... 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...... for the BPA and California ISO systems by using a large energy storage facility. The paper evaluates several utility-scale energy storage technology options for their usage as regulation resources. The regulation service requires a participating resource to quickly vary its power output following the rapidly...