Sample records for sigma factor network

  1. Reconstruction and topological characterization of the sigma factor regulatory network of Mycobacterium tuberculosis

    PubMed Central

    Chauhan, Rinki; Ravi, Janani; Datta, Pratik; Chen, Tianlong; Schnappinger, Dirk; Bassler, Kevin E.; Balázsi, Gábor; Gennaro, Maria Laura

    2016-01-01

    Accessory sigma factors, which reprogram RNA polymerase to transcribe specific gene sets, activate bacterial adaptive responses to noxious environments. Here we reconstruct the complete sigma factor regulatory network of the human pathogen Mycobacterium tuberculosis by an integrated approach. The approach combines identification of direct regulatory interactions between M. tuberculosis sigma factors in an E. coli model system, validation of selected links in M. tuberculosis, and extensive literature review. The resulting network comprises 41 direct interactions among all 13 sigma factors. Analysis of network topology reveals (i) a three-tiered hierarchy initiating at master regulators, (ii) high connectivity and (iii) distinct communities containing multiple sigma factors. These topological features are likely associated with multi-layer signal processing and specialized stress responses involving multiple sigma factors. Moreover, the identification of overrepresented network motifs, such as autoregulation and coregulation of sigma and anti-sigma factor pairs, provides structural information that is relevant for studies of network dynamics. PMID:27029515

  2. Elucidation of Sigma Factor-Associated Networks in Pseudomonas aeruginosa Reveals a Modular Architecture with Limited and Function-Specific Crosstalk

    PubMed Central

    Schulz, Sebastian; Eckweiler, Denitsa; Bielecka, Agata; Nicolai, Tanja; Franke, Raimo; Dötsch, Andreas; Hornischer, Klaus; Bruchmann, Sebastian; Düvel, Juliane; Häussler, Susanne

    2015-01-01

    Sigma factors are essential global regulators of transcription initiation in bacteria which confer promoter recognition specificity to the RNA polymerase core enzyme. They provide effective mechanisms for simultaneously regulating expression of large numbers of genes in response to challenging conditions, and their presence has been linked to bacterial virulence and pathogenicity. In this study, we constructed nine his-tagged sigma factor expressing and/or deletion mutant strains in the opportunistic pathogen Pseudomonas aeruginosa. To uncover the direct and indirect sigma factor regulons, we performed mRNA profiling, as well as chromatin immunoprecipitation coupled to high-throughput sequencing. We furthermore elucidated the de novo binding motif of each sigma factor, and validated the RNA- and ChIP-seq results by global motif searches in the proximity of transcriptional start sites (TSS). Our integrated approach revealed a highly modular network architecture which is composed of insulated functional sigma factor modules. Analysis of the interconnectivity of the various sigma factor networks uncovered a limited, but highly function-specific, crosstalk which orchestrates complex cellular processes. Our data indicate that the modular structure of sigma factor networks enables P. aeruginosa to function adequately in its environment and at the same time is exploited to build up higher-level functions by specific interconnections that are dominated by a participation of RpoN. PMID:25780925

  3. Functional modules of sigma factor regulons guarantee adaptability and evolvability

    PubMed Central

    Binder, Sebastian C.; Eckweiler, Denitsa; Schulz, Sebastian; Bielecka, Agata; Nicolai, Tanja; Franke, Raimo; Häussler, Susanne; Meyer-Hermann, Michael

    2016-01-01

    The focus of modern molecular biology turns from assigning functions to individual genes towards understanding the expression and regulation of complex sets of molecules. Here, we provide evidence that alternative sigma factor regulons in the pathogen Pseudomonas aeruginosa largely represent insulated functional modules which provide a critical level of biological organization involved in general adaptation and survival processes. Analysis of the operational state of the sigma factor network revealed that transcription factors functionally couple the sigma factor regulons and significantly modulate the transcription levels in the face of challenging environments. The threshold quality of newly evolved transcription factors was reached faster and more robustly in in silico testing when the structural organization of sigma factor networks was taken into account. These results indicate that the modular structures of alternative sigma factor regulons provide P. aeruginosa with a robust framework to function adequately in its environment and at the same time facilitate evolutionary change. Our data support the view that widespread modularity guarantees robustness of biological networks and is a key driver of evolvability. PMID:26915971

  4. Inference of sigma factor controlled networks by using numerical modeling applied to microarray time series data of the germinating prokaryote.

    PubMed

    Strakova, Eva; Zikova, Alice; Vohradsky, Jiri

    2014-01-01

    A computational model of gene expression was applied to a novel test set of microarray time series measurements to reveal regulatory interactions between transcriptional regulators represented by 45 sigma factors and the genes expressed during germination of a prokaryote Streptomyces coelicolor. Using microarrays, the first 5.5 h of the process was recorded in 13 time points, which provided a database of gene expression time series on genome-wide scale. The computational modeling of the kinetic relations between the sigma factors, individual genes and genes clustered according to the similarity of their expression kinetics identified kinetically plausible sigma factor-controlled networks. Using genome sequence annotations, functional groups of genes that were predominantly controlled by specific sigma factors were identified. Using external binding data complementing the modeling approach, specific genes involved in the control of the studied process were identified and their function suggested.

  5. Whole-genome phylogenies of the family Bacillaceae and expansion of the sigma factor gene family in the Bacillus cereus species-group

    PubMed Central

    2011-01-01

    Background The Bacillus cereus sensu lato group consists of six species (B. anthracis, B. cereus, B. mycoides, B. pseudomycoides, B. thuringiensis, and B. weihenstephanensis). While classical microbial taxonomy proposed these organisms as distinct species, newer molecular phylogenies and comparative genome sequencing suggests that these organisms should be classified as a single species (thus, we will refer to these organisms collectively as the Bc species-group). How do we account for the underlying similarity of these phenotypically diverse microbes? It has been established for some time that the most rapidly evolving and evolutionarily flexible portions of the bacterial genome are regulatory sequences and transcriptional networks. Other studies have suggested that the sigma factor gene family of these organisms has diverged and expanded significantly relative to their ancestors; sigma factors are those portions of the bacterial transcriptional apparatus that control RNA polymerase recognition for promoter selection. Thus, examining sigma factor divergence in these organisms would concurrently examine both regulatory sequences and transcriptional networks important for divergence. We began this examination by comparison to the sigma factor gene set of B. subtilis. Results Phylogenetic analysis of the Bc species-group utilizing 157 single-copy genes of the family Bacillaceae suggests that several taxonomic revisions of the genus Bacillus should be considered. Within the Bc species-group there is little indication that the currently recognized species form related sub-groupings, suggesting that they are members of the same species. The sigma factor gene family encoded by the Bc species-group appears to be the result of a dynamic gene-duplication and gene-loss process that in previous analyses underestimated the true heterogeneity of the sigma factor content in the Bc species-group. Conclusions Expansion of the sigma factor gene family appears to have preferentially occurred within the extracytoplasmic function (ECF) sigma factor genes, while the primary alternative (PA) sigma factor genes are, in general, highly conserved with those found in B. subtilis. Divergence of the sigma-controlled transcriptional regulons among various members of the Bc species-group likely has a major role in explaining the diversity of phenotypic characteristics seen in members of the Bc species-group. PMID:21864360

  6. Crystal structure of the Escherichia coli regulator of sigma70, Rsd, in complex with sigma70 domain 4.

    PubMed

    Patikoglou, Georgia A; Westblade, Lars F; Campbell, Elizabeth A; Lamour, Valérie; Lane, William J; Darst, Seth A

    2007-09-21

    The Escherichia coli Rsd protein binds tightly and specifically to the RNA polymerase (RNAP) sigma(70) factor. Rsd plays a role in alternative sigma factor-dependent transcription by biasing the competition between sigma(70) and alternative sigma factors for the available core RNAP. Here, we determined the 2.6 A-resolution X-ray crystal structure of Rsd bound to sigma(70) domain 4 (sigma(70)(4)), the primary determinant for Rsd binding within sigma(70). The structure reveals that Rsd binding interferes with the two primary functions of sigma(70)(4), core RNAP binding and promoter -35 element binding. Interestingly, the most highly conserved Rsd residues form a network of interactions through the middle of the Rsd structure that connect the sigma(70)(4)-binding surface with three cavities exposed on distant surfaces of Rsd, suggesting functional coupling between sigma(70)(4) binding and other binding surfaces of Rsd, either for other proteins or for as yet unknown small molecule effectors. These results provide a structural basis for understanding the role of Rsd, as well as its ortholog, AlgQ, a positive regulator of Pseudomonas aeruginosa virulence, in transcription regulation.

  7. Genexpi: a toolset for identifying regulons and validating gene regulatory networks using time-course expression data.

    PubMed

    Modrák, Martin; Vohradský, Jiří

    2018-04-13

    Identifying regulons of sigma factors is a vital subtask of gene network inference. Integrating multiple sources of data is essential for correct identification of regulons and complete gene regulatory networks. Time series of expression data measured with microarrays or RNA-seq combined with static binding experiments (e.g., ChIP-seq) or literature mining may be used for inference of sigma factor regulatory networks. We introduce Genexpi: a tool to identify sigma factors by combining candidates obtained from ChIP experiments or literature mining with time-course gene expression data. While Genexpi can be used to infer other types of regulatory interactions, it was designed and validated on real biological data from bacterial regulons. In this paper, we put primary focus on CyGenexpi: a plugin integrating Genexpi with the Cytoscape software for ease of use. As a part of this effort, a plugin for handling time series data in Cytoscape called CyDataseries has been developed and made available. Genexpi is also available as a standalone command line tool and an R package. Genexpi is a useful part of gene network inference toolbox. It provides meaningful information about the composition of regulons and delivers biologically interpretable results.

  8. Role of extracytoplasmic function sigma factor PG1660 (RpoE) in the oxidative stress resistance regulatory network of Porphyromonas gingivalis

    PubMed Central

    Dou, Y.; Rutanhira, H.; Chen, X.; Mishra, A.; Wang, C.; Fletcher, H.M.

    2018-01-01

    Summary In Porphyromonas gingivalis, the protein PG1660, composed of 174 amino acids, is annotated as an extracytoplasmic function (ECF) sigma factor (RpoE homologue-σ24). Because PG1660 can modulate several virulence factors and responds to environmental signals in P. gingivalis, its genetic properties were evaluated. PG1660 is co-transcribed with its downstream gene PG1659, and the transcription start site was identified as adenine residue 54-nucleotides upstream of the ATG translation start codon. In addition to binding its own promoter, using the purified rPG1660 and RNAP core enzyme from Escherichia coli with the PG1660 promoter DNA as template, the function of PG1660 as a sigma factor was demonstrated in an in vitro transcription assay. Transcriptome analyses of a P. gingivalis PG1660-defective isogenic mutant revealed that under oxidative stress conditions 176 genes including genes involved in secondary metabolism were downregulated more than two-fold compared with the parental strain. The rPG1660 protein also showed the ability to bind to the promoters of the highly downregulated genes in the PG1660-deficient mutant. As the ECF sigma factor PG0162 has a 29% identity with PG1660 and can modulate its expression, the cross-talk between their regulatory networks was explored. The expression profile of the PG0162PG1660-deficient mutant (P. gingivalis FLL356) revealed that the type IX secretion system genes and several virulence genes were downregulated under hydrogen peroxide stress conditions. Taken together, we have confirmed that PG1660 can function as a sigma factor, and plays an important regulatory role in the oxidative stress and virulence regulatory network of P. gingivalis. PMID:29059500

  9. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Patikoglou,G.; Westblade, L.; Campbell, E.

    The Escherichia coli Rsd protein binds tightly and specifically to the RNA polymerase (RNAP) {sigma}{sup 70} factor. Rsd plays a role in alternative {sigma} factor-dependent transcription by biasing the competition between {sigma}{sup 70} and alternative {sigma} factors for the available core RNAP. Here, we determined the 2.6 {angstrom}-resolution X-ray crystal structure of Rsd bound to {sigma}{sup 70} domain 4 ({sigma}{sup 70}{sub 4}), the primary determinant for Rsd binding within {sigma}{sup 70}. The structure reveals that Rsd binding interferes with the two primary functions of {sigma}{sup 70}{sub 4}, core RNAP binding and promoter -35 element binding. Interestingly, the most highly conservedmore » Rsd residues form a network of interactions through the middle of the Rsd structure that connect the {sigma}{sup 70}{sub 4}-binding surface with three cavities exposed on distant surfaces of Rsd, suggesting functional coupling between {sigma}{sup 70}{sub 4} binding and other binding surfaces of Rsd, either for other proteins or for as yet unknown small molecule effectors. These results provide a structural basis for understanding the role of Rsd, as well as its ortholog, AlgQ, a positive regulator of Pseudomonas aeruginosa virulence, in transcription regulation.« less

  10. Carotenoid Biosynthetic Pathways Are Regulated by a Network of Multiple Cascades of Alternative Sigma Factors in Azospirillum brasilense Sp7.

    PubMed

    Rai, Ashutosh Kumar; Dubey, Ashutosh Prakash; Kumar, Santosh; Dutta, Debashis; Mishra, Mukti Nath; Singh, Bhupendra Narain; Tripathi, Anil Kumar

    2016-11-01

    Carotenoids constitute an important component of the defense system against photooxidative stress in bacteria. In Azospirillum brasilense Sp7, a nonphotosynthetic rhizobacterium, carotenoid synthesis is controlled by a pair of extracytoplasmic function sigma factors (RpoEs) and their cognate zinc-binding anti-sigma factors (ChrRs). Its genome harbors two copies of the gene encoding geranylgeranyl pyrophosphate synthase (CrtE), the first critical step in the carotenoid biosynthetic pathway in bacteria. Inactivation of each of two crtE paralogs found in A. brasilense caused reduction in carotenoid content, suggesting their involvement in carotenoid synthesis. However, the effect of crtE1 deletion was more pronounced than that of crtE2 deletion. Out of the five paralogs of rpoH in A. brasilense, overexpression of rpoH1 and rpoH2 enhanced carotenoid synthesis. Promoters of crtE2 and rpoH2 were found to be dependent on RpoH2 and RpoE1, respectively. Using a two-plasmid system in Escherichia coli, we have shown that the crtE2 gene of A. brasilense Sp7 is regulated by two cascades of sigma factors: one consisting of RpoE1and RpoH2 and the other consisting of RpoE2 and RpoH1. In addition, expression of crtE1 was upregulated indirectly by RpoE1 and RpoE2. This study shows, for the first time in any carotenoid-producing bacterium, that the regulation of carotenoid biosynthetic pathway involves a network of multiple cascades of alternative sigma factors. Carotenoids play a very important role in coping with photooxidative stress in prokaryotes and eukaryotes. Although extracytoplasmic function (ECF) sigma factors are known to directly regulate the expression of carotenoid biosynthetic genes in bacteria, regulation of carotenoid biosynthesis by one or multiple cascades of sigma factors had not been reported. This study provides the first evidence of the involvement of multiple cascades of sigma factors in the regulation of carotenoid synthesis in any bacterium by showing the regulation of a gene encoding geranylgeranyl pyrophosphate synthase (crtE2) by RpoE1→RpoH2→CrtE2 and RpoE2→RpoH1→CrtE2 cascades in A. brasilense It also provides an insight into existence of an additional cascade or cascades regulating expression of another paralog of crtE. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  11. Carotenoid Biosynthetic Pathways Are Regulated by a Network of Multiple Cascades of Alternative Sigma Factors in Azospirillum brasilense Sp7

    PubMed Central

    Rai, Ashutosh Kumar; Dubey, Ashutosh Prakash; Kumar, Santosh; Dutta, Debashis; Mishra, Mukti Nath; Singh, Bhupendra Narain

    2016-01-01

    ABSTRACT Carotenoids constitute an important component of the defense system against photooxidative stress in bacteria. In Azospirillum brasilense Sp7, a nonphotosynthetic rhizobacterium, carotenoid synthesis is controlled by a pair of extracytoplasmic function sigma factors (RpoEs) and their cognate zinc-binding anti-sigma factors (ChrRs). Its genome harbors two copies of the gene encoding geranylgeranyl pyrophosphate synthase (CrtE), the first critical step in the carotenoid biosynthetic pathway in bacteria. Inactivation of each of two crtE paralogs found in A. brasilense caused reduction in carotenoid content, suggesting their involvement in carotenoid synthesis. However, the effect of crtE1 deletion was more pronounced than that of crtE2 deletion. Out of the five paralogs of rpoH in A. brasilense, overexpression of rpoH1 and rpoH2 enhanced carotenoid synthesis. Promoters of crtE2 and rpoH2 were found to be dependent on RpoH2 and RpoE1, respectively. Using a two-plasmid system in Escherichia coli, we have shown that the crtE2 gene of A. brasilense Sp7 is regulated by two cascades of sigma factors: one consisting of RpoE1and RpoH2 and the other consisting of RpoE2 and RpoH1. In addition, expression of crtE1 was upregulated indirectly by RpoE1 and RpoE2. This study shows, for the first time in any carotenoid-producing bacterium, that the regulation of carotenoid biosynthetic pathway involves a network of multiple cascades of alternative sigma factors. IMPORTANCE Carotenoids play a very important role in coping with photooxidative stress in prokaryotes and eukaryotes. Although extracytoplasmic function (ECF) sigma factors are known to directly regulate the expression of carotenoid biosynthetic genes in bacteria, regulation of carotenoid biosynthesis by one or multiple cascades of sigma factors had not been reported. This study provides the first evidence of the involvement of multiple cascades of sigma factors in the regulation of carotenoid synthesis in any bacterium by showing the regulation of a gene encoding geranylgeranyl pyrophosphate synthase (crtE2) by RpoE1→RpoH2→CrtE2 and RpoE2→RpoH1→CrtE2 cascades in A. brasilense. It also provides an insight into existence of an additional cascade or cascades regulating expression of another paralog of crtE. PMID:27551017

  12. Connecting Metabolic Pathways: Sigma Factors in Streptomyces spp.

    PubMed Central

    Sun, Di; Liu, Cong; Zhu, Jingrong; Liu, Weijie

    2017-01-01

    The gram-positive filamentous bacterium Streptomyces is one of the largest resources for bioactive metabolites, particularly antibiotics. Antibiotic production and other metabolic processes are tightly regulated at the transcriptional level. Sigma (σ) factors are components of bacterial RNA polymerases that determine promoter specificity. In Streptomyces, σ factors also play essential roles in signal transduction and in regulatory networks, thereby assisting in their survival in complex environments. However, our current understanding of σ factors in Streptomyces is still limited. In this mini-review, we demonstrate the roles of Streptomyces σ factors, illustrating that these serve as linkers of different metabolic pathways. Further investigations on σ factors may improve our knowledge of Streptomyces physiology and benefit exploitation of Streptomyces resources. PMID:29312231

  13. The Spore Differentiation Pathway in the Enteric Pathogen Clostridium difficile

    PubMed Central

    Pereira, Fátima C.; Saujet, Laure; Tomé, Ana R.; Serrano, Mónica; Monot, Marc; Couture-Tosi, Evelyne; Martin-Verstraete, Isabelle; Dupuy, Bruno; Henriques, Adriano O.

    2013-01-01

    Endosporulation is an ancient bacterial developmental program that culminates with the differentiation of a highly resistant endospore. In the model organism Bacillus subtilis, gene expression in the forespore and in the mother cell, the two cells that participate in endospore development, is governed by cell type-specific RNA polymerase sigma subunits. σF in the forespore, and σE in the mother cell control early stages of development and are replaced, at later stages, by σG and σK, respectively. Starting with σF, the activation of the sigma factors is sequential, requires the preceding factor, and involves cell-cell signaling pathways that operate at key morphological stages. Here, we have studied the function and regulation of the sporulation sigma factors in the intestinal pathogen Clostridium difficile, an obligate anaerobe in which the endospores are central to the infectious cycle. The morphological characterization of mutants for the sporulation sigma factors, in parallel with use of a fluorescence reporter for single cell analysis of gene expression, unraveled important deviations from the B. subtilis paradigm. While the main periods of activity of the sigma factors are conserved, we show that the activity of σE is partially independent of σF, that σG activity is not dependent on σE, and that the activity of σK does not require σG. We also show that σK is not strictly required for heat resistant spore formation. In all, our results indicate reduced temporal segregation between the activities of the early and late sigma factors, and reduced requirement for the σF-to-σE, σE-to-σG, and σG-to-σK cell-cell signaling pathways. Nevertheless, our results support the view that the top level of the endosporulation network is conserved in evolution, with the sigma factors acting as the key regulators of the pathway, established some 2.5 billion years ago upon its emergence at the base of the Firmicutes Phylum. PMID:24098139

  14. Integration of light and circadian signals that regulate chloroplast transcription by a nuclear-encoded sigma factor.

    PubMed

    Belbin, Fiona E; Noordally, Zeenat B; Wetherill, Sarah J; Atkins, Kelly A; Franklin, Keara A; Dodd, Antony N

    2017-01-01

    We investigated the signalling pathways that regulate chloroplast transcription in response to environmental signals. One mechanism controlling plastid transcription involves nuclear-encoded sigma subunits of plastid-encoded plastid RNA polymerase. Transcripts encoding the sigma factor SIG5 are regulated by light and the circadian clock. However, the extent to which a chloroplast target of SIG5 is regulated by light-induced changes in SIG5 expression is unknown. Moreover, the photoreceptor signalling pathways underlying the circadian regulation of chloroplast transcription by SIG5 are unidentified. We monitored the regulation of chloroplast transcription in photoreceptor and sigma factor mutants under controlled light regimes in Arabidopsis thaliana. We established that a chloroplast transcriptional response to light intensity was mediated by SIG5; a chloroplast transcriptional response to the relative proportions of red and far red light was regulated by SIG5 through phytochrome and photosynthetic signals; and the circadian regulation of chloroplast transcription by SIG5 was predominantly dependent on blue light and cryptochrome. Our experiments reveal the extensive integration of signals concerning the light environment by a single sigma factor to regulate chloroplast transcription. This may originate from an evolutionarily ancient mechanism that protects photosynthetic bacteria from high light stress, which subsequently became integrated with higher plant phototransduction networks. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  15. Transcriptional regulation of the operon encoding stress-responsive ECF sigma factor SigH and its anti-sigma factor RshA, and control of its regulatory network in Corynebacterium glutamicum

    PubMed Central

    2012-01-01

    Background The expression of genes in Corynebacterium glutamicum, a Gram-positive non-pathogenic bacterium used mainly for the industrial production of amino acids, is regulated by seven different sigma factors of RNA polymerase, including the stress-responsive ECF-sigma factor SigH. The sigH gene is located in a gene cluster together with the rshA gene, putatively encoding an anti-sigma factor. The aim of this study was to analyze the transcriptional regulation of the sigH and rshA gene cluster and the effects of RshA on the SigH regulon, in order to refine the model describing the role of SigH and RshA during stress response. Results Transcription analyses revealed that the sigH gene and rshA gene are cotranscribed from four sigH housekeeping promoters in C. glutamicum. In addition, a SigH-controlled rshA promoter was found to only drive the transcription of the rshA gene. To test the role of the putative anti-sigma factor gene rshA under normal growth conditions, a C. glutamicum rshA deletion strain was constructed and used for genome-wide transcription profiling with DNA microarrays. In total, 83 genes organized in 61 putative transcriptional units, including those previously detected using sigH mutant strains, exhibited increased transcript levels in the rshA deletion mutant compared to its parental strain. The genes encoding proteins related to disulphide stress response, heat stress proteins, components of the SOS-response to DNA damage and proteasome components were the most markedly upregulated gene groups. Altogether six SigH-dependent promoters upstream of the identified genes were determined by primer extension and a refined consensus promoter consisting of 45 original promoter sequences was constructed. Conclusions The rshA gene codes for an anti-sigma factor controlling the function of the stress-responsive sigma factor SigH in C. glutamicum. Transcription of rshA from a SigH-dependent promoter may serve to quickly shutdown the SigH-dependent stress response after the cells have overcome the stress condition. Here we propose a model of the regulation of oxidative and heat stress response including redox homeostasis by SigH, RshA and the thioredoxin system. PMID:22943411

  16. Transcriptional regulation of the operon encoding stress-responsive ECF sigma factor SigH and its anti-sigma factor RshA, and control of its regulatory network in Corynebacterium glutamicum.

    PubMed

    Busche, Tobias; Silar, Radoslav; Pičmanová, Martina; Pátek, Miroslav; Kalinowski, Jörn

    2012-09-03

    The expression of genes in Corynebacterium glutamicum, a Gram-positive non-pathogenic bacterium used mainly for the industrial production of amino acids, is regulated by seven different sigma factors of RNA polymerase, including the stress-responsive ECF-sigma factor SigH. The sigH gene is located in a gene cluster together with the rshA gene, putatively encoding an anti-sigma factor. The aim of this study was to analyze the transcriptional regulation of the sigH and rshA gene cluster and the effects of RshA on the SigH regulon, in order to refine the model describing the role of SigH and RshA during stress response. Transcription analyses revealed that the sigH gene and rshA gene are cotranscribed from four sigH housekeeping promoters in C. glutamicum. In addition, a SigH-controlled rshA promoter was found to only drive the transcription of the rshA gene. To test the role of the putative anti-sigma factor gene rshA under normal growth conditions, a C. glutamicum rshA deletion strain was constructed and used for genome-wide transcription profiling with DNA microarrays. In total, 83 genes organized in 61 putative transcriptional units, including those previously detected using sigH mutant strains, exhibited increased transcript levels in the rshA deletion mutant compared to its parental strain. The genes encoding proteins related to disulphide stress response, heat stress proteins, components of the SOS-response to DNA damage and proteasome components were the most markedly upregulated gene groups. Altogether six SigH-dependent promoters upstream of the identified genes were determined by primer extension and a refined consensus promoter consisting of 45 original promoter sequences was constructed. The rshA gene codes for an anti-sigma factor controlling the function of the stress-responsive sigma factor SigH in C. glutamicum. Transcription of rshA from a SigH-dependent promoter may serve to quickly shutdown the SigH-dependent stress response after the cells have overcome the stress condition. Here we propose a model of the regulation of oxidative and heat stress response including redox homeostasis by SigH, RshA and the thioredoxin system.

  17. Dynamical systems approach to the study of a sociophysics agent-based model

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Timpanaro, Andre M.; Prado, Carmen P. C.

    2011-03-24

    The Sznajd model is a Potts-like model that has been studied in the context of sociophysics [1,2](where spins are interpreted as opinions). In a recent work [3], we generalized the Sznajd model to include assymetric interactions between the spins (interpreted as biases towards opinions) and used dynamical systems techniques to tackle its mean-field version, given by the flow: {eta}{sub {sigma}} = {Sigma}{sub {sigma}}'{sup M} = 1{eta}{sub {sigma}}{eta}{sigma}'({eta}{sub {sigma}}{rho}{sigma}'{yields}{sigma}-{sigma}'{rho}{sigma}{yields}{sigma}').Where hs is the proportion of agents with opinion (spin){sigma}', M is the number of opinions and {sigma}'{yields}{sigma}' is the probability weight for an agent with opinion {sigma} being convinced by another agentmore » with opinion {sigma}'. We made Monte Carlo simulations of the model in a complex network (using Barabasi-Albert networks [4]) and they displayed the same attractors than the mean-field. Using linear stability analysis, we were able to determine the mean-field attractor structure analytically and to show that it has connections with well known graph theory problems (maximal independent sets and positive fluxes in directed graphs). Our dynamical systems approach is quite simple and can be used also in other models, like the voter model.« less

  18. The sigma factors of Bacillus subtilis.

    PubMed Central

    Haldenwang, W G

    1995-01-01

    The specificity of DNA-dependent RNA polymerase for target promotes is largely due to the replaceable sigma subunit that it carries. Multiple sigma proteins, each conferring a unique promoter preference on RNA polymerase, are likely to be present in all bacteria; however, their abundance and diversity have been best characterized in Bacillus subtilis, the bacterium in which multiple sigma factors were first discovered. The 10 sigma factors thus far identified in B. subtilis directly contribute to the bacterium's ability to control gene expression. These proteins are not merely necessary for the expression of those operons whose promoters they recognize; in many instances, their appearance within the cell is sufficient to activate these operons. This review describes the discovery of each of the known B. subtilis sigma factors, their characteristics, the regulons they direct, and the complex restrictions placed on their synthesis and activities. These controls include the anticipated transcriptional regulation that modulates the expression of the sigma factor structural genes but, in the case of several of the B. subtilis sigma factors, go beyond this, adding novel posttranslational restraints on sigma factor activity. Two of the sigma factors (sigma E and sigma K) are, for example, synthesized as inactive precursor proteins. Their activities are kept in check by "pro-protein" sequences which are cleaved from the precursor molecules in response to intercellular cues. Other sigma factors (sigma B, sigma F, and sigma G) are inhibited by "anti-sigma factor" proteins that sequester them into complexes which block their ability to form RNA polymerase holoenzymes. The anti-sigma factors are, in turn, opposed by additional proteins which participate in the sigma factors' release. The devices used to control sigma factor activity in B, subtilis may prove to be as widespread as multiple sigma factors themselves, providing ways of coupling sigma factor activation to environmental or physiological signals that cannot be readily joined to other regulatory mechanisms. PMID:7708009

  19. Alternative sigma factor RpoN and its modulation protein YhbH are indispensable for Erwinia amylovora virulence.

    PubMed

    Ancona, Veronica; Li, Wenting; Zhao, Youfu

    2014-01-01

    In Erwinia amylovora, ECF (extracytoplasmic functions) alternative sigma factor HrpL regulates the transcription of hrp (hypersensitive response and pathogenicity)-type III secretion system (T3SS) genes by binding to a consensus sequence known as the hrp box in hrp gene promoters. In turn, the expression of hrpL has been proposed to be positively controlled by alternative sigma factor 54 (σ(54)) (RpoN) and HrpS, a member of the σ(54) enhancer-binding proteins (EBPs). However, the function of RpoN has not been characterized genetically in E. amylovora. In this study, we investigated the role of RpoN, a nitrogen limitation sigma factor, and its modulation protein YhbH, a novel ribosome-associated protein, in E. amylovora virulence. Our results showed that mutations in hrpS, hrpL, rpoN and yhbH, but not yfiA and rmf3, resulted in a nonpathogenic phenotype on immature pear fruits and apple shoots. Consistently, the expression of T3SS genes, including hrpL, dspE, hrpN and hrpA, was barely detected in hrpS, hrpL, rpoN and yhbH mutants. These mutants were also not capable of eliciting a hypersensitive response (HR) on tobacco; however, the overexpression of hrpL using an inducible promoter rescued the HR-eliciting abilities of these mutants. These results suggest that a sigma factor cascade exists in the regulatory networks of E. amylovora and regulates important virulence factors. On the basis of this study and previously reported data, a model is proposed for the regulation of T3SS in E. amylovora. © 2013 BSPP AND JOHN WILEY & SONS LTD.

  20. Rsd family proteins make simultaneous interactions with regions 2 and 4 of the primary sigma factor.

    PubMed

    Yuan, Andy H; Gregory, Brian D; Sharp, Josh S; McCleary, Katherine D; Dove, Simon L; Hochschild, Ann

    2008-12-01

    Bacterial anti-sigma factors typically regulate sigma factor function by restricting the access of their cognate sigma factors to the RNA polymerase (RNAP) core enzyme. The Escherichia coli Rsd protein forms a complex with the primary sigma factor, sigma(70), inhibits sigma(70)-dependent transcription in vitro, and has been proposed to function as a sigma(70)-specific anti-sigma factor, thereby facilitating the utilization of alternative sigma factors. In prior work, Rsd has been shown to interact with conserved region 4 of sigma(70), but it is not known whether this interaction suffices to account for the regulatory functions of Rsd. Here we show that Rsd and the Rsd orthologue AlgQ, a global regulator of gene expression in Pseudomonas aeruginosa, interact with conserved region 2 of sigma(70). We show further that Rsd and AlgQ can interact simultaneously with regions 2 and 4 of sigma(70). Our findings establish that the abilities of Rsd and AlgQ to interact with sigma(70) region 2 are important determinants of their in vitro and in vivo activities.

  1. Bacterial Sigma Factors and Anti-Sigma Factors: Structure, Function and Distribution

    PubMed Central

    Paget, Mark S.

    2015-01-01

    Sigma factors are multi-domain subunits of bacterial RNA polymerase (RNAP) that play critical roles in transcription initiation, including the recognition and opening of promoters as well as the initial steps in RNA synthesis. This review focuses on the structure and function of the major sigma-70 class that includes the housekeeping sigma factor (Group 1) that directs the bulk of transcription during active growth, and structurally-related alternative sigma factors (Groups 2–4) that control a wide variety of adaptive responses such as morphological development and the management of stress. A recurring theme in sigma factor control is their sequestration by anti-sigma factors that occlude their RNAP-binding determinants. Sigma factors are then released through a wide variety of mechanisms, often involving branched signal transduction pathways that allow the integration of distinct signals. Three major strategies for sigma release are discussed: regulated proteolysis, partner-switching, and direct sensing by the anti-sigma factor. PMID:26131973

  2. Regulation of antimicrobial resistance by extracytoplasmic function (ECF) sigma factors

    PubMed Central

    Woods, Emily C.; McBride, Shonna M.

    2017-01-01

    Extracytoplasmic function (ECF) sigma factors are a subfamily of σ70 sigma factors that activate genes involved in stress-response functions. In many bacteria, ECF sigma factors regulate resistance to antimicrobial compounds. This review will summarize the ECF sigma factors that regulate antimicrobial resistance in model organisms and clinically relevant pathogens. PMID:28153747

  3. How the early sporulation sigma factor sigmaF delays the switch to late development in Bacillus subtilis.

    PubMed

    Karmazyn-Campelli, Céline; Rhayat, Lamya; Carballido-López, Rut; Duperrier, Sandra; Frandsen, Niels; Stragier, Patrick

    2008-03-01

    Sporulation in Bacillus subtilis is a primitive differentiation process involving two cell types, the forespore and the mother cell. Each cell implements two successive transcription programmes controlled by specific sigma factors. We report that activity of sigma(G), the late forespore sigma factor, is kept in check by Gin, the product of csfB, a gene controlled by sigma(F), the early forespore sigma factor. Gin abolishes sigma(G) transcriptional activity when sigma(G) is artificially synthesized during growth, but has no effect on sigma(F). Gin interacts strongly with sigma(G) but not with sigma(F) in a yeast two-hybrid experiment. The absence of Gin allows sigma(G) to be active during sporulation independently of the mother-cell development to which it is normally coupled. Premature sigma(G) activity leads to the formation of slow-germinating spores, and complete deregulation of sigma(G) synthesis is lethal when combined with gin inactivation. Gin allows sigma(F) to delay the switch to the late forespore transcription programme by preventing sigma(G) to take over before the cell has reached a critical stage of development. A similar strategy, following a completely unrelated route, is used by the mother cell.

  4. Insulation of the σF Regulatory System in Bacillus subtilis

    PubMed Central

    Carniol, Karen; Kim, Tae-Jong; Price, Chester W.; Losick, Richard

    2004-01-01

    The transcription factors σF and σB are related RNA polymerase sigma factors that govern dissimilar networks of adaptation to stress conditions in Bacillus subtilis. The two factors are controlled by closely related regulatory pathways, involving protein kinases and phosphatases. We report that insulation of the σF pathway from the σB pathway involves the integrated action of both the cognate kinase and the cognate phosphatase. PMID:15205443

  5. Genome-scale reconstruction of the sigma factor network in Escherichia coli: topology and functional states

    PubMed Central

    2014-01-01

    Background At the beginning of the transcription process, the RNA polymerase (RNAP) core enzyme requires a σ-factor to recognize the genomic location at which the process initiates. Although the crucial role of σ-factors has long been appreciated and characterized for many individual promoters, we do not yet have a genome-scale assessment of their function. Results Using multiple genome-scale measurements, we elucidated the network of σ-factor and promoter interactions in Escherichia coli. The reconstructed network includes 4,724 σ-factor-specific promoters corresponding to transcription units (TUs), representing an increase of more than 300% over what has been previously reported. The reconstructed network was used to investigate competition between alternative σ-factors (the σ70 and σ38 regulons), confirming the competition model of σ substitution and negative regulation by alternative σ-factors. Comparison with σ-factor binding in Klebsiella pneumoniae showed that transcriptional regulation of conserved genes in closely related species is unexpectedly divergent. Conclusions The reconstructed network reveals the regulatory complexity of the promoter architecture in prokaryotic genomes, and opens a path to the direct determination of the systems biology of their transcriptional regulatory networks. PMID:24461193

  6. Use of In Vitro Transcription System for Analysis of Corynebacterium glutamicum Promoters Recognized by Two Sigma Factors.

    PubMed

    Šilar, Radoslav; Holátko, Jiří; Rucká, Lenka; Rapoport, Andrey; Dostálová, Hana; Kadeřábková, Pavla; Nešvera, Jan; Pátek, Miroslav

    2016-09-01

    Promoter activities in Corynebacterium glutamicum strains with deletions of genes encoding sigma factors of RNA polymerase suggested that transcription from some promoters is controlled by two sigma factors. To prove that different sigma factors are involved in the recognition of selected Corynebacterium glutamicum promoters, in vitro transcription system was applied. It was found that a typical housekeeping promoter Pper interacts with the alternative sigma factor σ(B) in addition to the primary sigma factor σ(A). On the other way round, the σ(B)-dependent promoter of the pqo gene that is expressed mainly in the stationary growth phase was active also with σ(A). Some promoters of genes involved in stress responses (P1clgR, P2dnaK, and P2dnaJ2) were found to be recognized by two stress-responding sigma factors, σ(H) and σ(E). In vitro transcription system thus proved to be a useful direct technique for demonstrating the overlap of different sigma factors in recognition of individual promoters in C. glutamicum.

  7. L(p) approximation capabilities of sum-of-product and sigma-pi-sigma neural networks.

    PubMed

    Long, Jinling; Wu, Wei; Nan, Dong

    2007-10-01

    This paper studies the L(p) approximation capabilities of sum-of-product (SOPNN) and sigma-pi-sigma (SPSNN) neural networks. It is proved that the set of functions that are generated by the SOPNN with its activation function in $L_{loc};p(\\mathcal{R})$ is dense in $L;p(\\mathcal{K})$ for any compact set $\\mathcal{K}\\subset \\mathcal{R};N$, if and only if the activation function is not a polynomial almost everywhere. It is also shown that if the activation function of the SPSNN is in ${L_{loc};\\infty(\\mathcal{R})}$, then the functions generated by the SPSNN are dense in $L;p(\\mathcal{K})$ if and only if the activation function is not a constant (a.e.).

  8. The Rsb Phosphoregulatory Network Controls Availability of the Primary Sigma Factor in Chlamydia trachomatis and Influences the Kinetics of Growth and Development

    PubMed Central

    Thompson, Christopher C.; Griffiths, Cherry; Nicod, Sophie S.; Lowden, Nicole M.; Wigneshweraraj, Sivaramesh; Fisher, Derek J.; McClure, Myra O.

    2015-01-01

    Chlamydia trachomatis is an obligate intracellular human pathogen that exhibits stage-specific gene transcription throughout a biphasic developmental cycle. The mechanisms that control modulation in transcription and associated phenotypic changes are poorly understood. This study provides evidence that a switch-protein kinase regulatory network controls availability of σ66 , the main sigma subunit for transcription in Chlamydia. In vitro analysis revealed that a putative switch-protein kinase regulator, RsbW, is capable of interacting directly with σ66, as well as phosphorylating its own antagonist, RsbV1, rendering it inactive. Conversely, the putative PP2C-like phosphatase domain of chlamydial RsbU was capable of reverting RsbV1 into its active state. Recent advances in genetic manipulation of Chlamydia were employed to inactivate rsbV1, as well as to increase the expression levels of rsbW or rsbV1, in vivo. Representative σ66-dependent gene transcription was repressed in the absence of rsbV1 or upon increased expression of RsbW, and increased upon elevated expression of RsbV1. These effects on housekeeping transcription were also correlated to several measures of growth and development. A model is proposed where the relative levels of active antagonist (RsbV1) and switch-protein anti-sigma factor (RsbW) control the availability of σ66 and subsequently act as a molecular 'throttle' for Chlamydia growth and development. PMID:26313645

  9. Six sigma critical success factors in manufacturing industries

    NASA Astrophysics Data System (ADS)

    Mustafa, Zainol; Jamaluddin, Z.

    2017-04-01

    The success of Six Sigma implementation is known to depend on a number of contributing factors. The purpose of this paper is to explore Six Sigma critical success factors (CSFs) in the context of Malaysian manufacturing organizations. Although Six Sigma success factors have been abundantly researched in the global context, in this paper, a maiden attempt is made to identify, through an extensive literature review, the CSFs for Six Sigma implementation followed by their validation using primary data collection from Malaysian manufacturing companies. A total of 33 indicators have thus been compiled through an extensive literature review which then been grouped into 6 contributing factors. These contributing success factors are then validated through an empirical research of selected Malaysian manufacturing companies at various stages of implementation of the Six Sigma process improvement methodology. There has been an overemphasis on the role and commitment of the management in the success of a Six Sigma program. Though it is undoubted, certain other factors also play an equally important role in ensuring that the Six Sigma programs are successful. The factor analysis of CSFs of the Malaysian manufacturing organizations selected in this study demonstrates that the top factor is a composite factor showing combination of the ability of the project teams to use the process management on quality initiative and a training using a proper analysis in problem solving. The CSFs extracted through the factor analysis could provide a basis for manufacturing organizations embarking on the Six Sigma journey to look beyond just management involvement. Thus, one can develop an integrated framework of other factors as outlined and give them appropriate priority and focus.

  10. Mutational analysis of RsrA, a zinc-binding anti-sigma factor with a thiol-disulphide redox switch.

    PubMed

    Paget, M S; Bae, J B; Hahn, M Y; Li, W; Kleanthous, C; Roe, J H; Buttner, M J

    2001-02-01

    In the Gram-positive bacterium, Streptomyces coelicolor A3(2), expression of the thioredoxin system is modulated by a sigma factor called sigmaR in response to changes in the cytoplasmic thiol-disulphide status, and the activity of sigmaR is controlled post-translationally by an anti-sigma factor, RsrA. In vitro, the anti-sigma factor activity of RsrA, which contains seven cysteines, correlates with its thiol-disulphide redox status. Here, we investigate the function of RsrA in vivo. A constructed rsrA null mutant had very high constitutive levels of disulphide reductase activity and sigmaR-dependent transcription, confirming that RsrA is a negative regulator of sigmaR and a key sensor of thiol-disulphide status. Targeted mutagenesis revealed that three of the seven cysteines in RsrA (C11, C41 and C44) were essential for anti-sigma factor activity and that a mutant RsrA protein containing only these three cysteines was active and still redox sensitive in vivo. We also show that RsrA is a metalloprotein, containing near-stoichiometric amounts of zinc. On the basis of these data, we propose that a thiol-disulphide redox switch is formed between two of C11, C41 and C44, and that all three residues play an essential role in anti-sigma factor activity in their reduced state, perhaps by acting as ligands for zinc. Unexpectedly, rsrA null mutants were blocked in sporulation, probably as a consequence of an increase in the level of free sigmaR.

  11. Photocurrent polarization anisotropy of randomly oriented nanowire networks.

    PubMed

    Yu, Yanghai; Protasenko, Vladimir; Jena, Debdeep; Xing, Huili Grace; Kuno, Masaru

    2008-05-01

    While the polarization sensitivity of single or aligned NW ensembles is well-known, this article reports on the existence of residual photocurrent polarization sensitivities in random NW networks. In these studies, CdSe and CdTe NWs were deposited onto glass substrates and contacted with Au electrodes separated by 30-110 microm gaps. SEM and AFM images of resulting devices show isotropically distributed NWs between the electrodes. Complementary high resolution TEM micrographs reveal component NWs to be highly crystalline with diameters between 10 and 20 nm and with lengths ranging from 1 to 10 microm. When illuminated with visible (linearly polarized) light, such random NW networks exhibit significant photocurrent anisotropies rho = 0.25 (sigma = 0.04) [rho = 0.22 (sigma = 0.04)] for CdSe (CdTe) NWs. Corresponding bandwidth measurements yield device polarization sensitivities up to 100 Hz. Additional studies have investigated the effects of varying the electrode potential, gap width, and spatial excitation profile. These experiments suggest electrode orientation as the determining factor behind the polarization sensitivity of NW devices. A simple geometric model has been developed to qualitatively explain the phenomenon. The main conclusion from these studies, however, is that polarization sensitive devices can be made from random NW networks without the need to align component wires.

  12. Positive and negative feedback regulatory loops of thiol-oxidative stress response mediated by an unstable isoform of sigmaR in actinomycetes.

    PubMed

    Kim, Min-Sik; Hahn, Mi-Young; Cho, Yoobok; Cho, Sang-Nae; Roe, Jung-Hye

    2009-09-01

    Alternate sigma factors provide an effective way of diversifying bacterial gene expression in response to environmental changes. In Streptomyces coelicolor where more than 65 sigma factors are predicted, sigma(R) is the major regulator for response to thiol-oxidative stresses. sigma(R) becomes available when its bound anti-sigma factor RsrA is oxidized at sensitive cysteine thiols to form disulphide bonds. sigma(R) regulon includes genes for itself and multiple thiol-reducing systems, which constitute positive and negative feedback loops respectively. We found that the positive amplification loop involves an isoform of sigma(R) (sigma(R')) with an N-terminal extension of 55 amino acids, produced from an upstream start codon. A major difference between constitutive sigma(R) and inducible sigma(R') is that the latter is markedly unstable (t(1/2) approximately 10 min) compared with the former (> 70 min). The rapid turnover of sigma(R') is partly due to induced ClpP1/P2 proteases from the sigma(R) regulon. This represents a novel way of elaborating positive and negative feedback loops in a control circuit. Similar phenomenon may occur in other actinomycetes that harbour multiple start codons in the sigR homologous gene. We observed that sigH gene, the sigR orthologue in Mycobacterium smegmatis, produces an unstable larger isoform of sigma(H) upon induction by thiol-oxidative stress.

  13. The Escherichia coli regulator of sigma 70 protein, Rsd, can up-regulate some stress-dependent promoters by sequestering sigma 70.

    PubMed

    Mitchell, Jennie E; Oshima, Taku; Piper, Sarah E; Webster, Christine L; Westblade, Lars F; Karimova, Gouzel; Ladant, Daniel; Kolb, Annie; Hobman, Jon L; Busby, Stephen J W; Lee, David J

    2007-05-01

    The Escherichia coli Rsd protein forms complexes with the RNA polymerase sigma(70) factor, but its biological role is not understood. Transcriptome analysis shows that overexpression of Rsd causes increased expression from some promoters whose expression depends on the alternative sigma(38) factor, and this was confirmed by experiments with lac fusions at selected promoters. The LP18 substitution in Rsd increases the Rsd-dependent stimulation of these promoter-lac fusions. Analysis with a bacterial two-hybrid system shows that the LP18 substitution in Rsd increases its interaction with sigma(70). Our experiments support a model in which the role of Rsd is primarily to sequester sigma(70), thereby increasing the levels of RNA polymerase containing the alternative sigma(38) factor.

  14. Switching between nitrogen and glucose limitation: Unraveling transcriptional dynamics in Escherichia coli.

    PubMed

    Löffler, Michael; Simen, Joana Danica; Müller, Jan; Jäger, Günter; Laghrami, Salaheddine; Schäferhoff, Karin; Freund, Andreas; Takors, Ralf

    2017-09-20

    Transcriptional control under nitrogen and carbon-limitation conditions have been well analyzed for Escherichia coli. However, the transcriptional dynamics that underlie the shift in regulatory programs from nitrogen to carbon limitation is not well studied. In the present study, cells were cultivated at steady state under nitrogen (ammonia)-limited conditions then shifted to carbon (glucose) limitation to monitor changes in transcriptional dynamics. Nitrogen limitation was found to be dominated by sigma 54 (RpoN) and sigma 38 (RpoS), whereas the "housekeeping" sigma factor 70 (RpoD) and sigma 38 regulate cellular status under glucose limitation. During the transition, nitrogen-mediated control was rapidly redeemed and mRNAs that encode active uptake systems, such as ptsG and manXYZ, were quickly amplified. Next, genes encoding facilitators such as lamB were overexpressed, followed by high affinity uptake systems such as mglABC and non-specific porins such as ompF. These regulatory programs are complex and require well-equilibrated and superior control. At the metabolome level, 2-oxoglutarate is the likely component that links carbon- and nitrogen-mediated regulation by interacting with major regulatory elements. In the case of dual glucose and ammonia limitation, sigma 24 (RpoE) appears to play a key role in orchestrating these complex regulatory networks. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. A structural model of anti-anti-[sigma] inhibition by a two-component receiver domain: the PhyR stress response regulator

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Herrou, Julien; Foreman, Robert; Fiebig, Aretha

    2012-05-09

    PhyR is a hybrid stress regulator conserved in {alpha}-proteobacteria that contains an N-terminal {sigma}-like (SL) domain and a C-terminal receiver domain. Phosphorylation of the receiver domain is known to promote binding of the SL domain to an anti-{sigma} factor. PhyR thus functions as an anti-anti-{sigma} factor in its phosphorylated state. We present genetic evidence that Caulobacter crescentus PhyR is a phosphorylation-dependent stress regulator that functions in the same pathway as {sigma}{sup T} and its anti-{sigma} factor, NepR. Additionally, we report the X-ray crystal structure of PhyR at 1.25 {angstrom} resolution, which provides insight into the mechanism of anti-anti-{sigma} regulation. Directmore » intramolecular contact between the PhyR receiver and SL domains spans regions {sigma}{sub 2} and {sigma}{sub 4}, likely serving to stabilize the SL domain in a closed conformation. The molecular surface of the receiver domain contacting the SL domain is the structural equivalent of {alpha}4-{beta}5-{alpha}5, which is known to undergo dynamic conformational change upon phosphorylation in a diverse range of receiver proteins. We propose a structural model of PhyR regulation in which receiver phosphorylation destabilizes the intramolecular interaction between SL and receiver domains, thereby permitting regions {sigma}{sub 2} and {sigma}{sub 4} in the SL domain to open about a flexible connector loop and bind anti-{sigma} factor.« less

  16. A structural model of anti-anti-[sigma];#963; inhibition by a two-component receiver domain: the PhyR stress response regulator

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Herrou, Julien; Foreman, Robert; Fiebig, Aretha

    2012-03-30

    PhyR is a hybrid stress regulator conserved in {alpha}-proteobacteria that contains an N-terminal {sigma}-like (SL) domain and a C-terminal receiver domain. Phosphorylation of the receiver domain is known to promote binding of the SL domain to an anti-{sigma} factor. PhyR thus functions as an anti-anti-{sigma} factor in its phosphorylated state. We present genetic evidence that Caulobacter crescentus PhyR is a phosphorylation-dependent stress regulator that functions in the same pathway as {sigma}{sup T} and its anti-{sigma} factor, NepR. Additionally, we report the X-ray crystal structure of PhyR at 1.25 {angstrom} resolution, which provides insight into the mechanism of anti-anti-{sigma} regulation. Directmore » intramolecular contact between the PhyR receiver and SL domains spans regions {sigma}{sub 2} and {sigma}{sub 4}, likely serving to stabilize the SL domain in a closed conformation. The molecular surface of the receiver domain contacting the SL domain is the structural equivalent of {alpha}4-{beta}5-{alpha}5, which is known to undergo dynamic conformational change upon phosphorylation in a diverse range of receiver proteins. We propose a structural model of PhyR regulation in which receiver phosphorylation destabilizes the intramolecular interaction between SL and receiver domains, thereby permitting regions {sigma}{sub 2} and {sigma}{sub 4} in the SL domain to open about a flexible connector loop and bind anti-{sigma} factor.« less

  17. Host control of plasmid replication: requirement for the sigma factor sigma 32 in transcription of mini-F replication initiator gene.

    PubMed Central

    Wada, C; Imai, M; Yura, T

    1987-01-01

    Replication of F factor or mini-F plasmid is strongly inhibited in the rpoH (htpR) mutants of Escherichia coli deficient in the sigma factor (sigma 32) known to be required for heat shock gene expression. Transcription of the mini-F repE gene encoding a replication initiator protein (E protein) was examined by operon fusion and by direct determination of repE mRNA. The synthesis rate and the level of repE mRNA were found to increase transiently upon temperature upshift (30 degrees C to 42 degrees C) in wild-type cells but to decrease rapidly in the rpoH mutants. Thus sigma 32 appeared to be directly involved in transcription of repE whose product, E protein, in turn activates DNA replication from the mini-F ori2 region. This scheme of host-controlled plasmid replication is further supported by the analysis of transcription in vitro: RNA synthesis can be initiated from the repE promoter by a minor form of RNA polymerase containing sigma 32 but not by the major polymerase containing the normal sigma factor sigma 70. The sigma 32-mediated transcription from the repE promoter is strongly inhibited by the E protein. We conclude that transcription of the mini-F repE gene is mediated by the host transcription factor sigma 32 and is negatively controlled by its own product. Images PMID:2447584

  18. Mapping of the Rsd contact site on the sigma 70 subunit of Escherichia coli RNA polymerase.

    PubMed

    Jishage, M; Dasgupta, D; Ishihama, A

    2001-05-01

    Rsd (regulator of sigma D) is an anti-sigma factor for the Escherichia coli RNA polymerase sigma(70) subunit. The contact site of Rsd on sigma(70) was analyzed after mapping of the contact-dependent cleavage sites by Rsd-tethered iron-p-bromoacetamidobenzyl EDTA and by analysis of the complex formation between Ala-substituted sigma(70) and Rsd. Results indicate that the Rsd contact site is located downstream of the promoter -35 recognition helix-turn-helix motif within region 4, overlapping with the regions involved in interaction with both core enzyme and sigma(70) contact transcription factors.

  19. Bacillus subtilis sporulation: regulation of gene expression and control of morphogenesis.

    PubMed Central

    Errington, J

    1993-01-01

    Bacillus subtilis sporulation is an adaptive response to nutritional stress and involves the differential development of two cells. In the last 10 years or so, virtually all of the regulatory genes controlling sporulation, and many genes directing the structural and morphological changes that accompany sporulation, have been cloned and characterized. This review describes our current knowledge of the program of gene expression during sporulation and summarizes what is known about the functions of the genes that determine the specialized biochemical and morphological properties of sporulating cells. Most steps in the genetic program are controlled by transcription factors that have been characterized in vitro. Two sporulation-specific sigma factors, sigma E and sigma F, appear to segregate at septation, effectively determining the differential development of the mother cell and prespore. Later, each sigma is replaced by a second cell-specific sigma factor, sigma K in the mother cell and sigma G in the prespore. The synthesis of each sigma factor is tightly regulated at both the transcriptional and posttranslational levels. Usually this regulation involves an intercellular interaction that coordinates the developmental programmes of the two cells. At least two other transcription factors fine tune the timing and levels of expression of genes in the sigma E and sigma K regulons. The controlled synthesis of the sigma factors and other transcription factors leads to a spatially and temporally ordered program of gene expression. The gene products made during each successive stage of sporulation help to bring about a sequence of gross morphological changes and biochemical adaptations. The formation of the asymmetric spore septum, engulfment of the prespore by the mother cell, and formation of the spore core, cortex, and coat are described. The importance of these structures in the development of the resistance, dormancy, and germination properties of the spore is assessed. Images PMID:8464402

  20. Mutational analysis of Escherichia coli heat shock transcription factor sigma 32 reveals similarities with sigma 70 in recognition of the -35 promoter element and differences in promoter DNA melting and -10 recognition.

    PubMed

    Kourennaia, Olga V; Tsujikawa, Laura; Dehaseth, Pieter L

    2005-10-01

    Upon the exposure of Escherichia coli to high temperature (heat shock), cellular levels of the transcription factor sigma32 rise greatly, resulting in the increased formation of the sigma32 holoenzyme, which is capable of transcription initiation at heat shock promoters. Higher levels of heat shock proteins render the cell better able to cope with the effects of higher temperatures. To conduct structure-function studies on sigma32 in vivo, we have carried out site-directed mutagenesis and employed a previously developed system involving sigma32 expression from one plasmid and a beta-galactosidase reporter gene driven by the sigma32-dependent groE promoter on another in order to monitor the effects of single amino acid substitutions on sigma32 activity. It was found that the recognition of the -35 region involves similar amino acid residues in regions 4.2 of E. coli sigma32 and sigma70. Three conserved amino acids in region 2.3 of sigma32 were found to be only marginally important in determining activity in vivo. Differences between sigma32 and sigma70 in the effects of mutation in region 2.4 on the activities of the two sigma factors are consistent with the pronounced differences between both the amino acid sequences in this region and the recognized promoter DNA sequences.

  1. Post-transcriptional regulation of the Streptomyces coelicolor stress responsive sigma factor, SigH, involves translational control, proteolytic processing, and an anti-sigma factor homolog.

    PubMed

    Viollier, Patrick H; Weihofen, Andreas; Folcher, Marc; Thompson, Charles J

    2003-01-24

    The sigH gene encodes a sigma factor whose transcription is controlled by stress regulatory systems and the developmental program in Streptomyces coelicolor. Here, we describe developmentally regulated post-transcriptional control systems for SigH. sigH is expressed as three primary translation products, SigH-sigma(37), SigH-sigma(51), and SigH-sigma(52). In vitro, SigH-sigma(52) was comparable to SigH-sigma(37) in its ability to associate with RNA polymerase core enzyme and specifically initiate transcription in vitro. While SigH-sigma(51/52) were the primary gene products observed throughout early phases of growth, their abundance decreased during later stages in liquid or solid phase cultures while levels of shorter, C-terminally encoded products increased. These included SigH-sigma(37), a product of the downstream translational initiation site, as well as two proteolytic derivatives of SigH-sigma(51/52) (34kDa and 38kDa). Accumulation of SigH-sigma(37) and processing of SigH-sigma(51/52) into these stable 34kDa and 38kDa derivatives correlated with morphological changes on solid medium and physiological maturation in liquid medium. SigH-sigma(51/52) processing did not occur on medium non-permissive for aerial mycelium formation or in one particular developmental mutant (brgA). The proteolytic activity could be detected in vitro using crude extracts of stationary phase cultures, but was absent from exponential phase cultures. prsH, the gene upstream of sigH having sequence similarity to known anti-sigma factors, was able to bind to, and thus presumably inactivate SigH-sigma(52), SigH-sigma(51), and SigH-sigma(37). We have shown elsewhere that prsH was conditionally required for colonial development. Thus, while at least one transcriptional regulator is known to bring about the accumulation of sigH mRNA at different times and different locations in colonies, the post-transcriptional processes described here regulate the activity of different SigH isoforms and program their temporal accumulation pattern, i.e. the elimination of SigH-sigma(51/52) and accumulation of SigH-sigma(37)-like proteins, as a function of development.

  2. Differential mechanisms of binding of anti-sigma factors Escherichia coli Rsd and bacteriophage T4 AsiA to E. coli RNA polymerase lead to diverse physiological consequences.

    PubMed

    Sharma, Umender K; Chatterji, Dipankar

    2008-05-01

    Anti-sigma factors Escherichia coli Rsd and bacteriophage T4 AsiA bind to the essential housekeeping sigma factor, sigma(70), of E. coli. Though both factors are known to interact with the C-terminal region of sigma(70), the physiological consequences of these interactions are very different. This study was undertaken for the purpose of deciphering the mechanisms by which E. coli Rsd and bacteriophage T4 AsiA inhibit or modulate the activity of E. coli RNA polymerase, which leads to the inhibition of E. coli cell growth to different amounts. It was found that AsiA is the more potent inhibitor of in vivo transcription and thus causes higher inhibition of E. coli cell growth. Measurements of affinity constants by surface plasmon resonance experiments showed that Rsd and AsiA bind to sigma(70) with similar affinity. Data obtained from in vivo and in vitro binding experiments clearly demonstrated that the major difference between AsiA and Rsd is the ability of AsiA to form a stable ternary complex with RNA polymerase. The binding patterns of AsiA and Rsd with sigma(70) studied by using the yeast two-hybrid system revealed that region 4 of sigma(70) is involved in binding to both of these anti-sigma factors; however, Rsd interacts with other regions of sigma(70) as well. Taken together, these results suggest that the higher inhibition of E. coli growth by AsiA expression is probably due to the ability of the AsiA protein to trap the holoenzyme RNA polymerase rather than its higher binding affinity to sigma(70).

  3. Information processing in network architecture of genome controlled signal transduction circuit. A proposed theoretical explanation.

    PubMed

    Chakraborty, Chiranjib; Sarkar, Bimal Kumar; Patel, Pratiksha; Agoramoorthy, Govindasamy

    2012-01-01

    In this paper, Shannon information theory has been applied to elaborate cell signaling. It is proposed that in the cellular network architecture, four components viz. source (DNA), transmitter (mRNA), receiver (protein) and destination (another protein) are involved. The message transmits from source (DNA) to transmitter (mRNA) and then passes through a noisy channel reaching finally the receiver (protein). The protein synthesis process is here considered as the noisy channel. Ultimately, signal is transmitted from receiver to destination (another protein). The genome network architecture elements were compared with genetic alphabet L = {A, C, G, T} with a biophysical model based on the popular Shannon information theory. This study found the channel capacity as maximum for zero error (sigma = 0) and at this condition, transition matrix becomes a unit matrix with rank 4. The transition matrix will be erroneous and finally at sigma = 1 channel capacity will be localized maxima with a value of 0.415 due to the increased value at sigma. On the other hand, minima exists at sigma = 0.75, where all transition probabilities become 0.25 and uncertainty will be maximum resulting in channel capacity with the minima value of zero.

  4. Control of transcription of the Bacillus subtilis spoIIIG gene, which codes for the forespore-specific transcription factor sigma G.

    PubMed

    Sun, D X; Cabrera-Martinez, R M; Setlow, P

    1991-05-01

    The Bacillus subtilis spoIIIG gene codes for a sigma factor termed sigma G which directs transcription of genes expressed only in the forespore compartment of the sporulating cell. Use of spoIIIG-lacZ transcriptional fusions showed that spoIIIG is cotranscribed with the spoIIG operon beginning at t0.5-1 of sporulation. However, this large mRNA produced little if any sigma G, and transferring the spoIIIG gene without the spoIIG promoter into the amyE locus resulted in a Spo+ phenotype. Significant translation of spoIIIG began at t2.5-3 with use of an mRNA whose 5' end is just upstream of the spoIIIG coding sequence. Synthesis of this spoIIIG-specific mRNA was not abolished by a deletion in spoIIIG itself. Similar results were obtained when a spoIIIG-lacZ translational fusion lacking the spoIIG promoter was integrated at the amyE locus. These data suggest that synthesis of sigma G is dependent neither on transcription from the spoIIG promoter nor on sigma G itself but can be due to another transcription factor. This transcription factor may be sigma F, the product of the spoIIAC locus, since a spoIIAC mutation blocked spoIIIG expression, and sequences upstream of the 5' end of the spoIIIG-specific mRNA agree well with the recognition sequence for sigma F. RNA polymerase containing sigma F (E sigma F) initiated transcription in vitro on a spoIIIG template at the 5' end found in vivo, as did E sigma G. However, E sigma F showed a greater than 20-fold preference for spoIIIG over a known sigma G-dependent gene compared with the activity of E sigma G.

  5. Sigma1 Pharmacology in the Context of Cancer.

    PubMed

    Kim, Felix J; Maher, Christina M

    2017-01-01

    Sigma1 (also known as sigma-1 receptor, Sig1R, σ1 receptor) is a unique pharmacologically regulated integral membrane chaperone or scaffolding protein. The majority of publications on the subject have focused on the neuropharmacology of Sigma1. However, a number of publications have also suggested a role for Sigma1 in cancer. Although there is currently no clinically used anti-cancer drug that targets Sigma1, a growing body of evidence supports the potential of Sigma1 ligands as therapeutic agents to treat cancer. In preclinical models, compounds with affinity for Sigma1 have been reported to inhibit cancer cell proliferation and survival, cell adhesion and migration, tumor growth, to alleviate cancer-associated pain, and to have immunomodulatory properties. This review will highlight that although the literature supports a role for Sigma1 in cancer, several fundamental questions regarding drug mechanism of action and the physiological relevance of aberrant SIGMAR1 transcript and Sigma1 protein expression in certain cancers remain unanswered or only partially answered. However, emerging lines of evidence suggest that Sigma1 is a component of the cancer cell support machinery, that it facilitates protein interaction networks, that it allosterically modulates the activity of its associated proteins, and that Sigma1 is a selectively multifunctional drug target.

  6. Application of Six Sigma methodology to a cataract surgery unit.

    PubMed

    Taner, Mehmet Tolga

    2013-01-01

    The article's aim is to focus on the application of Six Sigma to minimise intraoperative and post-operative complications rates in a Turkish public hospital cataract surgery unit. Implementing define-measure-analyse-improve and control (DMAIC) involves process mapping, fishbone diagrams and rigorous data-collection. Failure mode and effect analysis (FMEA), pareto diagrams, control charts and process capability analysis are applied to redress cataract surgery failure root causes. Inefficient skills of assistant surgeons and technicians, low quality of IOLs used, wrong IOL placement, unsystematic sterilisation of surgery rooms and devices, and the unprioritising network system are found to be the critical drivers of intraoperative-operative and post-operative complications. Sigma level was increased from 2.60 to 3.75 subsequent to extensive training of assistant surgeons, ophthalmologists and technicians, better quality IOLs, systematic sterilisation and air-filtering, and the implementation of a more sophisticated network system. This article shows that Six Sigma measurement and process improvement can become the impetus for cataract unit staff to rethink their process and reduce malpractices. Measuring, recording and reporting data regularly helps them to continuously monitor their overall process and deliver safer treatments. This is the first Six Sigma ophthalmology study in Turkey.

  7. Orbit analysis of a bright Southern sigma Sagittariids fireball

    NASA Astrophysics Data System (ADS)

    Koukal, Jakub

    2018-02-01

    During twilight on June 14, 2017, CEMeNt network cameras recorded a long and bright fireball with an absolute magnitude of -7.9 ± 0.2m, whose atmospheric path began over the northwest of Romania and ended up above southern Poland. This fireball belongs to the Southern sigma Sagittariids meteor shower and was recorded from 9 cameras of the CEMeNt network. The atmospheric path of the fireball as well as the heliocentric orbit of the meteoroid are analyzed in this article.

  8. Simultaneous inactivation of sigma factors B and D interferes with light acclimation of the cyanobacterium Synechocystis sp. strain PCC 6803.

    PubMed

    Pollari, Maija; Ruotsalainen, Virpi; Rantamäki, Susanne; Tyystjärvi, Esa; Tyystjärvi, Taina

    2009-06-01

    In cyanobacteria, gene expression is regulated mainly at the level of transcription initiation, which is mediated by the RNA polymerase holoenzyme. The RNA polymerase core is catalytically active, while the sigma factor recognizes promoter sequences. Group 2 sigma factors are similar to the principal sigma factor but are nonessential. Group 2 sigma factors SigB and SigD are structurally the most similar sigma factors in Synechocystis sp. strain PCC 6803. Under standard growth conditions, simultaneous inactivation of sigB and sigD genes did not affect the growth, but the photosynthesis and growth of the DeltasigBD strain were slower than in the control strain at double light intensity. Light-saturated electron transfer rates and the fluorescence and thermoluminescence measurements showed that photosynthetic light reactions are fully functional in the DeltasigBD strain, but absorption and 77 K emission spectra measurements suggest that the light-harvesting system of the DeltasigBD strain does not acclimate normally to higher light intensity. Furthermore, the DeltasigBD strain is more sensitive to photoinhibition under bright light because impaired upregulation of psbA genes leads to insufficient PSII repair.

  9. Faceting of {sigma}3 and {sigma}9 grain boundaries in Cu-Bi alloys

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Straumal, B.B.; Polyakov, S.A.; Max-Planck-Institut fuer Metallforschung and Institut fuer Metallkunde, Heisenbergstr. 3, 70569 Stuttgart

    2005-01-10

    The faceting of {sigma}3 and {sigma}9 tilt grain boundaries (GBs) has been studied in bicrystals of pure Cu and Cu-Bi alloys containing 2.5 x 10{sup -3}, 10 x 10{sup -3} and 16 x 10{sup -3} at.% Bi. The {sigma}3(1 0 0), {sigma}9(1 0 0), {sigma}9(-1 1 0), and {sigma}9(-1 2 0) facets and non-CSL {sigma}3 82 deg 9R facet were observed, where {sigma} is the inverse density of coincidence sites. The ratio between GB energy, {sigma}{sub GB}, and surface energy, {sigma}{sub sur}, was measured by atomic force microscopy using the GB thermal-groove method. The GB energy and thermal-groove deepening ratemore » increased slightly between 0 and 10 x 10{sup -3} at.% Bi for all facets studied. However, between 10 x 10{sup -3} and 16 x 10{sup -3} at.% Bi the GB energy increased dramatically [from a factor 2 for the {sigma}9(1 1 0) facet to 15 times larger for the {sigma}3(1 0 0) facet]. The thermal-groove deepening rate also increased by a factor of 10 in this concentration range. This change corresponds well with the GB solidus line (i.e., the formation of a stable layer of a liquid-like GB phase called GB prewetting) observed previously. Wulff diagrams were constructed using measured {sigma}{sub GB}/{sigma}{sub sur} values.« less

  10. Beta-decay rates of FP shell nuclei with A greater than 60 in massive stars at the presupernova stage

    NASA Astrophysics Data System (ADS)

    Kar, K.; Ray, A.; Sarkar, S.

    1994-10-01

    Beta decay and electron capture on a number of neutron-rich nuclei with A greater than 60 at the presupernova stage may play an important role in determining the hydrostatic core structure of massive presupernova stars and, through this, affect the subsequent evolution during the gravitational collapse and supernova explosion phases. In particular, some isotopes of cobalt and copper can make a substantial contribution to the overall changes in the lepton fraction and entropy of the stellar core during its very late stage of evolution. In the stellar evolution calculations to date, many of these nuclei could not be appropriately tracked in the reaction network, since reliable rates for these have not been available so far. We describe a model to calculate the beta-decay rates using an average beta strength function and an electron phase-space factor evaluated for typical presupernova matter density (rho = 3 x 107-3 x 109 g/cu cm) and temperature (T = (2-5) x 109 K). For the Gamnow-Teller (GT) strength function we use a sum rule calculated by the spectral distribution theory, and the centroid of the distribution is obtained from experimental data on (p, n) reactions. The width sigma of the GT strength function has two parts (sigma2 = (sigmaN exp 2 + (sigmaC exp 2, with sigmaC = 0.157ZA-1/3). The parameter sigmaN is fixed by a best fit to the observed half-lives for the free decays of a number of A greater than 60 nuclei. In the calculation of rates we include contributions from the excited states of the mother nucleus wherever they are known experimentally. For the excited states one uses the same form of the GT strength function, but shifted in energy using the extended isobaric analog state argument. The method is particularly suited for calculating contributions from the excited states important at high temperatures relevant at the presupernova stellar evolution phase. We also include the contributions to the transition rates from the Gamow-Teller resonance states (e.g., the GTR+ state) in the mother nucleus, which may be thermally populated. The beta-decay rates for nuclei having A greater than 60 reported here can be inputs for presupernova stellar evolution and nucleosynthesis calculations employing detailed nuclear reaction networks relevant in the advanced phases of hydrostatic nuclear burning.

  11. Measuring Ionospheric Irregularities Globally by the Rate of TEC Index and GNSS Networks

    NASA Technical Reports Server (NTRS)

    Pi, Xiaoqing

    2012-01-01

    Outline of presentation: Why do we use the rate of TEC index (ROTI) instead of the standard s4 and sigma-phi indices? What are the differences between S4, sigma-phi and ROTI? Examples of ROTI measurements and Development status and plan.

  12. Redox-dependent changes in RsrA, an anti-sigma factor in Streptomyces coelicolor: zinc release and disulfide bond formation.

    PubMed

    Bae, Jae-Bum; Park, Joo-Hong; Hahn, Mi-Young; Kim, Min-Sik; Roe, Jung-Hye

    2004-01-09

    sigmaR is a sigma factor for transcribing genes to defend cells against oxidative stresses in the antibiotic-producing bacterium Streptomyces coelicolor. The availability of sigmaR is regulated by RsrA, an anti-sigma factor, whose sigmaR-binding activity is regulated by redox changes in the environment, via thiol-disulfide exchange. We found that reduced RsrA contains zinc in a stoichiometric amount, whereas oxidized form has very little: 1 mol of zinc per mol of RsrA was released upon oxidation as monitored by a chromogenic Zn-chelator, 4-(2-pyridylazo)-resorcinol (PAR). Measurement of zinc bound in several RsrA mutants of various cysteine and histidine substitutions suggested that C3, H7, C41, and C44 serve as zinc-binding sites. The zinc-binding and sigmaR-binding activities of mutant proteins did not coincide, suggesting that zinc might not be absolutely required for the anti-sigma activity of RsrA. Zn-free apo-RsrA bound sigmaR and inhibited sigmaR-dependent transcription in vitro. Compared with Zn-RsrA, the anti-transcription activity of apo-RsrA was about threefold lower and its sigmaR-binding affinity decreased by about ninefold when measured by surface plasmon resonance analysis. Apo-RsrA was more sensitive to protease, suggesting that zinc allows RsrA to maintain a more compact structure, optimized for binding sigmaR. The cysteine pairs that form disulfide bonds were determined by MALDI-TOF mass spectrometry, revealing formation of the critical disulfide bond between C11 and one of the essential cysteine residues C41 or 44, most likely C44. An improved model for the mechanism of redox-modulation of RsrA was presented.

  13. The alternative sigma factor, sigmaS, affects polyhydroxyalkanoate metabolism in Pseudomonas putida.

    PubMed

    Raiger-Iustman, Laura J; Ruiz, Jimena A

    2008-07-01

    To determine whether the stationary sigma factor, sigma(S), influences polyhydroxyalkanoate metabolism in Pseudomonas putida KT2440, an rpoS-negative mutant was constructed to evaluate polyhydroxyalkanoate accumulation and expression of a translational fusion to the promoter region of the genes that code for polyhydroxyalkanoate synthase 1 (phaC1) and polyhydroxyalkanoate depolymerase (phaZ). By comparison with the wild-type, the rpoS mutant showed a higher polyhydroxyalkanoate degradation rate and increased expression of the translational fusion during the stationary growth phase. These results suggest that sigma(S) might control the genes involved in polyhydroxyalkanoate metabolism, possibly in an indirect manner. In addition, survival and oxidative stress assays performed under polyhydroxyalkanoate- and nonpolyhydroxyalkanoate- accumulating conditions demonstrated that the accumulated polyhydroxyalkanoate increased the survival and stress tolerance of the rpoS mutant. According to this, polyhydroxyalkanoate accumulation would help cells to overcome the adverse conditions encountered during the stationary phase in the strain that lacks RpoS.

  14. {sigma}({chi}{sub c1})/{sigma}({chi}{sub c2}) ratio in the k{sub t}-factorization approach

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Baranov, S. P.

    2011-02-01

    We address the puzzle of {sigma}({chi}{sub c1})/{sigma}({chi}{sub c2}) ratio at the collider and fixed-target experiments. We consider several factors that can affect the predicted ratio of the production rates. In particular, we discuss the effect of {chi}{sub cJ} polarization, the effect of including next-to-leading order contributions, and the effect of probably different {chi}{sub c1} and {chi}{sub c2} wave functions.

  15. The Role of zinc in the disulphide stress-regulated anti-sigma factor RsrA from Streptomyces coelicolor.

    PubMed

    Li, Wei; Bottrill, Andrew R; Bibb, Maureen J; Buttner, Mark J; Paget, Mark S B; Kleanthous, Colin

    2003-10-17

    The regulation of disulphide stress in actinomycetes such as Streptomyces coelicolor is known to involve the zinc-containing anti-sigma factor RsrA that binds and inactivates the redox-regulated sigma factor sigmaR. However, it is not known how RsrA senses disulphide stress nor what role the metal ion plays. Using in vitro assays, we show that while zinc is not required for sigmaR binding it is required for functional anti-sigma factor activity, and that it plays a critical role in modulating the reactivity of RsrA cysteine thiol groups towards oxidation. Apo-RsrA is easily oxidised and, while the Zn-bound form is relatively resistant, the metal ion is readily expelled when the protein is treated with strong oxidants such as diamide. We also show, using a combination of proteolysis and mass spectrometry, that the first critical disulphide to form in RsrA involves Cys11 and one of either Cys41 or Cys44, all previously implicated in metal binding. Circular dichroism spectroscopy was used to follow structural changes during oxidation of RsrA, which indicated that concomitant with formation of this critical disulphide bond is a major restructuring of the protein where its alpha-helical content increases. Our data demonstrate that RsrA can only bind sigmaR in the reduced state and that this state is stabilised by zinc. Redox stress induces disulphide bond formation amongst zinc-ligating residues, expelling the metal ion and stabilising a structure incapable of binding the sigma factor.

  16. SigmaS controls multiple pathways associated with intracellular multiplication of Legionella pneumophila.

    PubMed

    Hovel-Miner, Galadriel; Pampou, Sergey; Faucher, Sebastien P; Clarke, Margaret; Morozova, Irina; Morozov, Pavel; Russo, James J; Shuman, Howard A; Kalachikov, Sergey

    2009-04-01

    Legionella pneumophila is the causative agent of the severe and potentially fatal pneumonia Legionnaires' disease. L. pneumophila is able to replicate within macrophages and protozoa by establishing a replicative compartment in a process that requires the Icm/Dot type IVB secretion system. The signals and regulatory pathways required for Legionella infection and intracellular replication are poorly understood. Mutation of the rpoS gene, which encodes sigma(S), does not affect growth in rich medium but severely decreases L. pneumophila intracellular multiplication within protozoan hosts. To gain insight into the intracellular multiplication defect of an rpoS mutant, we examined its pattern of gene expression during exponential and postexponential growth. We found that sigma(S) affects distinct groups of genes that contribute to Legionella intracellular multiplication. We demonstrate that rpoS mutants have a functional Icm/Dot system yet are defective for the expression of many genes encoding Icm/Dot-translocated substrates. We also show that sigma(S) affects the transcription of the cpxR and pmrA genes, which encode two-component response regulators that directly affect the transcription of Icm/Dot substrates. Our characterization of the L. pneumophila small RNA csrB homologs, rsmY and rsmZ, introduces a link between sigma(S) and the posttranscriptional regulator CsrA. We analyzed the network of sigma(S)-controlled genes by mutational analysis of transcriptional regulators affected by sigma(S). One of these, encoding the L. pneumophila arginine repressor homolog gene, argR, is required for maximal intracellular growth in amoebae. These data show that sigma(S) is a key regulator of multiple pathways required for L. pneumophila intracellular multiplication.

  17. Dipole moments and transition probabilities of the i 3Pi sub g-b 3Sigma(+) sub u, c 3Pi sub u-a 3Sigma(+) sub g, and i 3Pi sub g-c 3Pi sub u systems of molecular hydrogen

    NASA Technical Reports Server (NTRS)

    Guberman, Steven L.; Dalgarno, A.

    1992-01-01

    Bonn-Oppenheimer-based ab initio calculations of dipole moments from the i 3Pi sub g-b 3Sigma(+) sub u, c 3Pi sub u-a 3Sigma(+) sub g, and i 3Pi sub g-c 3Pi sub u transitions of H2 have been conducted, to yield a tabulation of the dipole transition probabilities and Franck-Condon factors. These factors are given for transitions originating in the lowest vibrational level of the ground X 1Sigma(+) sub g state.

  18. The Bartonella quintana Extracytoplasmic Function Sigma Factor RpoE Has a Role in Bacterial Adaptation to the Arthropod Vector Environment

    PubMed Central

    Abromaitis, Stephanie

    2013-01-01

    Bartonella quintana is a vector-borne bacterial pathogen that causes fatal disease in humans. During the infectious cycle, B. quintana transitions from the hemin-restricted human bloodstream to the hemin-rich body louse vector. Because extracytoplasmic function (ECF) sigma factors often regulate adaptation to environmental changes, we hypothesized that a previously unstudied B. quintana ECF sigma factor, RpoE, is involved in the transition from the human host to the body louse vector. The genomic context of B. quintana rpoE identified it as a member of the ECF15 family of sigma factors found only in alphaproteobacteria. ECF15 sigma factors are believed to be the master regulators of the general stress response in alphaproteobacteria. In this study, we examined the B. quintana RpoE response to two stressors that are encountered in the body louse vector environment, a decreased temperature and an increased hemin concentration. We determined that the expression of rpoE is significantly upregulated at the body louse (28°C) versus the human host (37°C) temperature. rpoE expression also was upregulated when B. quintana was exposed to high hemin concentrations. In vitro and in vivo analyses demonstrated that RpoE function is regulated by a mechanism involving the anti-sigma factor NepR and the response regulator PhyR. The ΔrpoE ΔnepR mutant strain of B. quintana established that RpoE-mediated transcription is important in mediating the tolerance of B. quintana to high hemin concentrations. We present the first analysis of an ECF15 sigma factor in a vector-borne human pathogen and conclude that RpoE has a role in the adaptation of B. quintana to the hemin-rich arthropod vector environment. PMID:23564167

  19. Mechanistic Implications of the Unique Structural Features and Dimerization of the Cytoplasmic Domain of the Pseudomonas Sigma Regulator, PupR

    DOE PAGES

    Jensen, Jaime L.; Balbo, Andrea; Neau, David B.; ...

    2015-09-29

    Gram-negative bacteria tightly regulate intracellular levels of iron, an essential nutrient. To ensure this tight regulation, some outer membrane TonB-dependent transporters (TBDTs) that are responsible for iron import stimulate their own transcription in response to extracellular binding by an iron-laden siderophore. This process is mediated by an inner membrane sigma regulator protein (an anti-sigma factor) that transduces an unknown periplasmic signal from the TBDT to release an intracellular sigma factor from the inner membrane, which ultimately upregulates TBDT transcription. Here we use the Pseudomonas putida ferric-pseudobactin BN7/BN8 sigma regulator, PupR, as a model system to understand the molecular mechanism ofmore » this conserved class of sigma regulators. We have determined the X-ray crystal structure of the cytoplasmic anti-sigma domain (ASD) of PupR to 2.0 Å. Size exclusion chromatography, small angle X-ray scattering, and sedimentation velocity analytical ultracentrifugation, all indicate that in contrast to other ASDs, the PupR-ASD exists as a dimer in solution. Mutagenesis of residues at the dimer interface identified from the crystal structure disrupts dimerization and protein stability, as determined by sedimentation velocity analytical ultracentrifugation and thermal denaturation circular dichroism spectroscopy. Lastly, these combined results suggest that this type of inner membrane sigma regulator may utilize an unusual mechanism to sequester their cognate sigma factors and prevent transcription activation.« less

  20. Mechanistic Implications of the Unique Structural Features and Dimerization of the Cytoplasmic Domain of the Pseudomonas Sigma Regulator, PupR

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jensen, Jaime L.; Balbo, Andrea; Neau, David B.

    Gram-negative bacteria tightly regulate intracellular levels of iron, an essential nutrient. To ensure this tight regulation, some outer membrane TonB-dependent transporters (TBDTs) that are responsible for iron import stimulate their own transcription in response to extracellular binding by an iron-laden siderophore. This process is mediated by an inner membrane sigma regulator protein (an anti-sigma factor) that transduces an unknown periplasmic signal from the TBDT to release an intracellular sigma factor from the inner membrane, which ultimately upregulates TBDT transcription. Here we use the Pseudomonas putida ferric-pseudobactin BN7/BN8 sigma regulator, PupR, as a model system to understand the molecular mechanism ofmore » this conserved class of sigma regulators. We have determined the X-ray crystal structure of the cytoplasmic anti-sigma domain (ASD) of PupR to 2.0 Å. Size exclusion chromatography, small angle X-ray scattering, and sedimentation velocity analytical ultracentrifugation, all indicate that in contrast to other ASDs, the PupR-ASD exists as a dimer in solution. Mutagenesis of residues at the dimer interface identified from the crystal structure disrupts dimerization and protein stability, as determined by sedimentation velocity analytical ultracentrifugation and thermal denaturation circular dichroism spectroscopy. Lastly, these combined results suggest that this type of inner membrane sigma regulator may utilize an unusual mechanism to sequester their cognate sigma factors and prevent transcription activation.« less

  1. Anti-Sigma Factors in E. coli: Common Regulatory Mechanisms Controlling Sigma Factors Availability

    PubMed Central

    Treviño-Quintanilla, Luis Gerardo; Freyre-González, Julio Augusto; Martínez-Flores, Irma

    2013-01-01

    In bacteria, transcriptional regulation is a key step in cellular gene expression. All bacteria contain a core RNA polymerase that is catalytically competent but requires an additional σ factor for specific promoter recognition and correct transcriptional initiation. The RNAP core is not able to selectively bind to a given σ factor. In contrast, different σ factors have different affinities for the RNAP core. As a consequence, the concentration of alternate σ factors requires strict regulation in order to properly control the delicate interplay among them, which favors the competence for the RNAP core. This control is archived by different σ/anti-σ controlling mechanisms that shape complex regulatory networks and cascades, and enable the response to sudden environmental cues, whose global understanding is a current challenge for systems biology. Although there have been a number of excellent studies on each of these σ/anti-σ post-transcriptional regulatory systems, no comprehensive comparison of these mechanisms in a single model organism has been conducted. Here, we survey all these systems in E. coli dissecting and analyzing their inner workings and highlightin their differences. Then, following an integral approach, we identify their commonalities and outline some of the principles exploited by the cell to effectively and globally reprogram the transcriptional machinery. These principles provide guidelines for developing biological synthetic circuits enabling an efficient and robust response to sudden stimuli. PMID:24396271

  2. The alternative sigma factor sigma B of Staphylococcus aureus modulates virulence in experimental central venous catheter-related infections.

    PubMed

    Lorenz, Udo; Hüttinger, Christian; Schäfer, Tina; Ziebuhr, Wilma; Thiede, Arnulf; Hacker, Jörg; Engelmann, Susanne; Hecker, Michael; Ohlsen, Knut

    2008-03-01

    The impact of the alternative sigma factor sigma B (SigB) on pathogenesis of Staphylococcus aureus is not conclusively clarified. In this study, a central venous catheter (CVC) related model of multiorgan infection was used to investigate the role of SigB for the pathogenesis of S. aureus infections and biofilm formation in vivo. Analysis of two SigB-positive wild-type strains and their isogenic mutants revealed uniformly that the wild-type was significantly more virulent than the SigB-deficient mutant. The observed difference in virulence was apparently not linked to the capability of the strains to form biofilms in vivo since wild-type and mutant strains were able to produce biofilm layers inside of the catheter. The data strongly indicate that the alternative sigma factor SigB plays a role in CVC-associated infections caused by S. aureus.

  3. Different intracellular distribution of avian reovirus core protein sigmaA in cells of avian and mammalian origin

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Vazquez-Iglesias, Lorena; Lostale-Seijo, Irene; Martinez-Costas, Jose

    2012-10-25

    A comparative analysis of the intracellular distribution of avian reovirus (ARV) core protein sigmaA in cells of avian and mammalian origin revealed that, whereas the viral protein accumulates in the cytoplasm and nucleolus of avian cells, most sigmaA concentrates in the nucleoplasm of mammalian cells in tight association with the insoluble nuclear matrix fraction. Our results further showed that sigmaA becomes arrested in the nucleoplasm of mammalian cells via association with mammalian cell-specific factors and that this association prevents nucleolar targeting. Inhibition of RNA polymerase II activity, but not of RNA polymerase I activity, in infected mammalian cells induces nucleus-to-cytoplasmmore » sigmaA translocation through a CRM1- and RanGTP-dependent mechanism, yet a heterokaryon assay suggests that sigmaA does not shuttle between the nucleus and cytoplasm. The scarcity of sigmaA in cytoplasmic viral factories of infected mammalian cells could be one of the factors contributing to limited ARV replication in mammalian cells.« less

  4. Correlates of hepatitis B virus health-related behaviors of Korean Americans: a situation-specific nursing theory.

    PubMed

    Lee, Haeok; Fawcett, Jacqueline; Yang, Jin Hyang; Hann, Hie-Won

    2012-12-01

    The purpose of this article is to explain the evolution of a situation-specific theory developed to enhance understanding of health-related behaviors of Korean Americans (KAs) who have or are at risk for a chronic hepatitis B virus (HBV) infection. The situation-specific theory evolved from an integration of the Network Episode Model, studies of health-related behaviors of people with HBV infection, and our studies of and practice experiences with Asian American individuals with HBV infection. The major concepts of the theory are sociocultural context, social network, individual-level factors, illness experience, and health-related behaviors. The major propositions of the theory are that sociocultural context, social network, and individual-level factors influence the illness experience, and that sociocultural context, social network, individual-level factors, and the illness experience influence health-related behaviors of KAs who have or are at risk for HBV infection. This situation-specific theory represents a translation of abstract concepts into clinical reality. The theory is an explanation of correlates of health-related HBV behaviors of KAs. The next step is to develop and test the effectiveness of a nursing intervention designed to promote behaviors that will enhance the health of KAs who have or are at risk for HBV infection, and that takes into account sociocultural context, social network, individual-level factors, and illness experience. © 2012 Sigma Theta Tau International.

  5. The E. coli Anti-Sigma Factor Rsd: Studies on the Specificity and Regulation of Its Expression

    PubMed Central

    Hofmann, Nina; Wurm, Reinhild; Wagner, Rolf

    2011-01-01

    Background Among the seven different sigma factors in E. coli σ70 has the highest concentration and affinity for the core RNA polymerase. The E. coli protein Rsd is regarded as an anti-sigma factor, inhibiting σ70-dependent transcription at the onset of stationary growth. Although binding of Rsd to σ70 has been shown and numerous structural studies on Rsd have been performed the detailed mechanism of action is still unknown. Methodology/Principal Findings We have performed studies to unravel the function and regulation of Rsd expression in vitro and in vivo. Cross-linking and affinity binding revealed that Rsd is able to interact with σ70, with the core enzyme of RNA polymerase and is able to form dimers in solution. Unexpectedly, we find that Rsd does also interact with σ38, the stationary phase-specific sigma factor. This interaction was further corroborated by gel retardation and footprinting studies with different promoter fragments and σ38- or σ70-containing RNA polymerase in presence of Rsd. Under competitive in vitro transcription conditions, in presence of both sigma factors, a selective inhibition of σ70-dependent transcription was prevailing, however. Analysis of rsd expression revealed that the nucleoid-associated proteins H-NS and FIS, StpA and LRP bind to the regulatory region of the rsd promoters. Furthermore, the major promoter P2 was shown to be down-regulated in vivo by RpoS, the stationary phase-specific sigma factor and the transcription factor DksA, while induction of the stringent control enhanced rsd promoter activity. Most notably, the dam-dependent methylation of a cluster of GATC sites turned out to be important for efficient rsd transcription. Conclusions/Significance The results contribute to a better understanding of the intricate mechanism of Rsd-mediated sigma factor specificity changes during stationary phase. PMID:21573101

  6. The E. coli anti-sigma factor Rsd: studies on the specificity and regulation of its expression.

    PubMed

    Hofmann, Nina; Wurm, Reinhild; Wagner, Rolf

    2011-05-06

    Among the seven different sigma factors in E. coli σ(70) has the highest concentration and affinity for the core RNA polymerase. The E. coli protein Rsd is regarded as an anti-sigma factor, inhibiting σ(70)-dependent transcription at the onset of stationary growth. Although binding of Rsd to σ(70) has been shown and numerous structural studies on Rsd have been performed the detailed mechanism of action is still unknown. We have performed studies to unravel the function and regulation of Rsd expression in vitro and in vivo. Cross-linking and affinity binding revealed that Rsd is able to interact with σ(70), with the core enzyme of RNA polymerase and is able to form dimers in solution. Unexpectedly, we find that Rsd does also interact with σ(38), the stationary phase-specific sigma factor. This interaction was further corroborated by gel retardation and footprinting studies with different promoter fragments and σ(38)- or σ(70)-containing RNA polymerase in presence of Rsd. Under competitive in vitro transcription conditions, in presence of both sigma factors, a selective inhibition of σ(70)-dependent transcription was prevailing, however. Analysis of rsd expression revealed that the nucleoid-associated proteins H-NS and FIS, StpA and LRP bind to the regulatory region of the rsd promoters. Furthermore, the major promoter P2 was shown to be down-regulated in vivo by RpoS, the stationary phase-specific sigma factor and the transcription factor DksA, while induction of the stringent control enhanced rsd promoter activity. Most notably, the dam-dependent methylation of a cluster of GATC sites turned out to be important for efficient rsd transcription. The results contribute to a better understanding of the intricate mechanism of Rsd-mediated sigma factor specificity changes during stationary phase.

  7. Rhodopseudomonas palustris CGA010 Proteome Implicates Extracytoplasmic Function Sigma Factor in Stress Response

    DOE PAGES

    Allen, Michael S.; Hurst, Gregory B.; Lu, Tse-Yuan S.; ...

    2015-04-08

    Rhodopseudomonas palustris encodes 16 extracytoplasmic function (ECF) σ factors. In this paper, to begin to investigate the regulatory network of one of these ECF σ factors, the whole proteome of R. palustris CGA010 was quantitatively analyzed by tandem mass spectrometry from cultures episomally expressing the ECF σ RPA4225 (ecfT) versus a WT control. Among the proteins with the greatest increase in abundance were catalase KatE, trehalose synthase, a DPS-like protein, and several regulatory proteins. Alignment of the cognate promoter regions driving expression of several upregulated proteins suggested a conserved binding motif in the -35 and -10 regions with the consensusmore » sequence GGAAC-18N-TT. Additionally, the putative anti-σ factor RPA4224, whose gene is contained in the same predicted operon as RPA4225, was identified as interacting directly with the predicted response regulator RPA4223 by mass spectrometry of affinity-isolated protein complexes. Furthermore, another gene (RPA4226) coding for a protein that contains a cytoplasmic histidine kinase domain is located immediately upstream of RPA4225. The genomic organization of orthologs for these four genes is conserved in several other strains of R. palustris as well as in closely related α-Proteobacteria. Finally, taken together, these data suggest that ECF σ RPA4225 and the three additional genes make up a sigma factor mimicry system in R. palustris.« less

  8. Rhodopseudomonas palustris CGA010 Proteome Implicates Extracytoplasmic Function Sigma Factor in Stress Response

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Allen, Michael S.; Hurst, Gregory B.; Lu, Tse-Yuan S.

    Rhodopseudomonas palustris encodes 16 extracytoplasmic function (ECF) σ factors. In this paper, to begin to investigate the regulatory network of one of these ECF σ factors, the whole proteome of R. palustris CGA010 was quantitatively analyzed by tandem mass spectrometry from cultures episomally expressing the ECF σ RPA4225 (ecfT) versus a WT control. Among the proteins with the greatest increase in abundance were catalase KatE, trehalose synthase, a DPS-like protein, and several regulatory proteins. Alignment of the cognate promoter regions driving expression of several upregulated proteins suggested a conserved binding motif in the -35 and -10 regions with the consensusmore » sequence GGAAC-18N-TT. Additionally, the putative anti-σ factor RPA4224, whose gene is contained in the same predicted operon as RPA4225, was identified as interacting directly with the predicted response regulator RPA4223 by mass spectrometry of affinity-isolated protein complexes. Furthermore, another gene (RPA4226) coding for a protein that contains a cytoplasmic histidine kinase domain is located immediately upstream of RPA4225. The genomic organization of orthologs for these four genes is conserved in several other strains of R. palustris as well as in closely related α-Proteobacteria. Finally, taken together, these data suggest that ECF σ RPA4225 and the three additional genes make up a sigma factor mimicry system in R. palustris.« less

  9. A sigma factor toolbox for orthogonal gene expression in Escherichia coli

    PubMed Central

    Van Brempt, Maarten; Van Nerom, Katleen; Van Hove, Bob; Maertens, Jo; De Mey, Marjan; Charlier, Daniel

    2018-01-01

    Abstract Synthetic genetic sensors and circuits enable programmable control over timing and conditions of gene expression and, as a result, are increasingly incorporated into the control of complex and multi-gene pathways. Size and complexity of genetic circuits are growing, but stay limited by a shortage of regulatory parts that can be used without interference. Therefore, orthogonal expression and regulation systems are needed to minimize undesired crosstalk and allow for dynamic control of separate modules. This work presents a set of orthogonal expression systems for use in Escherichia coli based on heterologous sigma factors from Bacillus subtilis that recognize specific promoter sequences. Up to four of the analyzed sigma factors can be combined to function orthogonally between each other and toward the host. Additionally, the toolbox is expanded by creating promoter libraries for three sigma factors without loss of their orthogonal nature. As this set covers a wide range of transcription initiation frequencies, it enables tuning of multiple outputs of the circuit in response to different sensory signals in an orthogonal manner. This sigma factor toolbox constitutes an interesting expansion of the synthetic biology toolbox and may contribute to the assembly of more complex synthetic genetic systems in the future. PMID:29361130

  10. Timeline Resource Analysis Program (TRAP): User's manual and program document

    NASA Technical Reports Server (NTRS)

    Sessler, J. G.

    1981-01-01

    The Timeline Resource Analysis Program (TRAP), developed for scheduling and timelining problems, is described. Given an activity network, TRAP generates timeline plots, resource histograms, and tabular summaries of the network, schedules, and resource levels. It is written in ANSI FORTRAN for the Honeywell SIGMA 5 computer and operates in the interactive mode using the TEKTRONIX 4014-1 graphics terminal. The input network file may be a standard SIGMA 5 file or one generated using the Interactive Graphics Design System. The timeline plots can be displayed in two orderings: according to the sequence in which the tasks were read on input, and a waterfall sequence in which the tasks are ordered by start time. The input order is especially meaningful when the network consists of several interacting subnetworks. The waterfall sequence is helpful in assessing the project status at any point in time.

  11. Interaction of sigma 70 with Escherichia coli RNA polymerase core enzyme studied by surface plasmon resonance.

    PubMed

    Ferguson, A L; Hughes, A D; Tufail, U; Baumann, C G; Scott, D J; Hoggett, J G

    2000-09-22

    The interaction between the core form of bacterial RNA polymerases and sigma factors is essential for specific promoter recognition, and for coordinating the expression of different sets of genes in response to varying cellular needs. The interaction between Escherichia coli core RNA polymerase and sigma 70 has been investigated by surface plasmon resonance. The His-tagged form of sigma 70 factor was immobilised on a Ni2+-NTA chip for monitoring its interaction with core polymerase. The binding constant for the interaction was found to be 1.9x10(-7) M, and the dissociation rate constant for release of sigma from core, in the absence of DNA or transcription, was 4x10(-3) s(-1), corresponding to a half-life of about 200 s.

  12. Different intracellular distribution of avian reovirus core protein sigmaA in cells of avian and mammalian origin.

    PubMed

    Vázquez-Iglesias, Lorena; Lostalé-Seijo, Irene; Martínez-Costas, José; Benavente, Javier

    2012-10-25

    A comparative analysis of the intracellular distribution of avian reovirus (ARV) core protein sigmaA in cells of avian and mammalian origin revealed that, whereas the viral protein accumulates in the cytoplasm and nucleolus of avian cells, most sigmaA concentrates in the nucleoplasm of mammalian cells in tight association with the insoluble nuclear matrix fraction. Our results further showed that sigmaA becomes arrested in the nucleoplasm of mammalian cells via association with mammalian cell-specific factors and that this association prevents nucleolar targeting. Inhibition of RNA polymerase II activity, but not of RNA polymerase I activity, in infected mammalian cells induces nucleus-to-cytoplasm sigmaA translocation through a CRM1- and RanGTP-dependent mechanism, yet a heterokaryon assay suggests that sigmaA does not shuttle between the nucleus and cytoplasm. The scarcity of sigmaA in cytoplasmic viral factories of infected mammalian cells could be one of the factors contributing to limited ARV replication in mammalian cells. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. Defining the disulphide stress response in Streptomyces coelicolor A3(2): identification of the sigmaR regulon.

    PubMed

    Paget, M S; Molle, V; Cohen, G; Aharonowitz, Y; Buttner, M J

    2001-11-01

    In the Gram-positive, antibiotic-producing bacterium Streptomyces coelicolor A3(2), the thiol-disulphide status of the hyphae is controlled by a novel regulatory system consisting of a sigma factor, sigmaR, and its cognate anti-sigma factor, RsrA. Oxidative stress induces intramolecular disulphide bond formation in RsrA, which causes it to lose affinity for sigmaR, thereby releasing sigmaR to activate transcription of the thioredoxin operon, trxBA. Here, we exploit a preliminary consensus sequence for sigmaR target promoters to identify 27 new sigmaR target genes and operons, thereby defining the global response to disulphide stress in this organism. Target genes related to thiol metabolism encode a second thioredoxin (TrxC), a glutaredoxin-like protein and enzymes involved in the biosynthesis of the low-molecular-weight thiol-containing compounds cysteine and molybdopterin. In addition, the level of the major actinomycete thiol buffer, mycothiol, was fourfold lower in a sigR null mutant, although no candidate mycothiol biosynthetic genes were identified among the sigmaR targets. Three sigmaR target genes encode ribosome-associated products (ribosomal subunit L31, ppGpp synthetase and tmRNA), suggesting that the translational machinery is modified by disulphide stress. The product of another sigmaR target gene was found to be a novel RNA polymerase-associated protein, RbpA, suggesting that the transcriptional machinery may also be modified in response to disulphide stress. We present DNA sequence evidence that many of the targets identified in S. coelicolor are also under the control of the sigmaR homologue in the actinomycete pathogen Mycobacterium tuberculosis.

  14. Study of Single Top Quark Production Using Bayesian Neural Networks With D0 Detector at the Tevatron

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Joshi, Jyoti

    2012-01-01

    Top quark, the heaviest and most intriguing among the six known quarks, can be created via two independent production mechanisms in {\\pp} collisions. The primary mode, strong {\\ttbar} pair production from amore » $gtt$$ vertex, was used by the {\\d0} and CDF collaborations to establish the existence of the top quark in March 1995. The second mode is the electroweak production of a single top quark or antiquark, which has been observed recently in March 2009. Since single top quarks are produced at hadron colliders through a $$Wtb$ vertex, thereby provide a direct probe of the nature of $Wtb$ coupling and of the Cabibbo-Kobayashi-Maskawa matrix element, $$V_{tb}$$. So this mechanism provides a sensitive probe for several, standard model and beyond standard model, parameters such as anomalous $Wtb$ couplings. In this thesis, we measure the cross section of the electroweak produced top quark in three different production modes, $s+t$, $s$ and $t$-channels using a technique based on the Bayesian neural networks. This technique is applied for analysis of the 5.4 $$fb^{-1}$$ of data collected by the {\\d0} detector. From a comparison of the Bayesian neural networks discriminants between data and the signal-background model using Bayesian statistics, the cross sections of the top quark produced through the electroweak mechanism have been measured as: \\[\\sigma(p\\bar{p}→tb+X,tqb+X) = 3.11^{+0.77}_{-0.71}\\;\\rm pb\\] \\[\\sigma(p\\bar{p}→tb+X) = 0.72^{+0.44}_{-0.43}\\;\\rm pb\\] \\[\\sigma(p\\bar{p}→tqb+X) = 2.92^{+0.87}_{-0.73}\\;\\rm pb\\] % The $s+t$-channel has a gaussian significance of $$4.7\\sigma$$, the $s$-channel $$0.9\\sigma$$ and the $t$-channel~$$4.7\\sigma$$. The results are consistent with the standard model predictions within one standard deviation. By combining these results with the results for two other analyses (using different MVA techniques) improved results \\[\\sigma(p\\bar{p}→tb+X,tqb+X) = 3.43^{+0.73}_{-0.74}\\;\\rm pb\\] \\[\\sigma(p\\bar{p}→tb+X) = 0.68^{+0.38}_{-0.35}\\;\\rm pb\\] \\[\\sigma(p\\bar{p}→tqb+X) = 2.86^{+0.69}_{-0.63}\\;\\rm pb\\] % were obtained with a significance of $$5.4\\sigma$$, $$1.8\\sigma$$ and $$5.0\\sigma$$ respectively for $s+t$, $s$ and $t$-channels. Using this measured cross section and constraining $$0 \\leq |V_{tb}|^2 \\leq 1$$, the lower limit has been calculated to be $$|V_{tb}| > 0.79$$ with 95\\% confidence level (C.L.). Another measurement of $tqb$ production cross section is done using the same dataset and discriminant but without any assumption on the $tb$ production rate. From this measurement, we obtain a cross section of $$2.90^{+0.59}_{-0.59}$$~pb for $t$-channel and corresponding significance of $$5.5\\sigma$$. In addition to the above mentioned work, a search is made for the anomalous $Wtb$ couplings in single top quark production. Within the Standard Model, the $Wtb$ vertex is purely left-handed, and its amplitude is given by the $$V_{tb}$$, related to weak interaction between a top and a $b$$-quark. In a more general way, additional anomalous couplings such as right-handed vectorial couplings and left and right-handed tensorial couplings can also be considered. An analysis based on the Bayesian neural networks method is used to separate the signal from expected backgrounds. We find no evidence for anomalous couplings and set 95\\% C.L. limits on these couplings as $$|V_{tb} \\cdot f_{L_T}|^2<0.06$, $$|V_{tb} \\cdot f_{R_V}|^2<0.93$$ and $$|V_{tb} \\cdot f_{R_T}|^2<0.13$$. This result represents the most stringent direct constraints on anomalous $Wtb$ interactions. This work has been done in collaboration with \\d0 experiment but the analyses and results presented in this thesis are my contribution.« less

  15. Characterization and in vivo regulon determination of an ECF sigma factor and its cognate anti-sigma factor in Nostoc punctiforme.

    PubMed

    Bell, Nicole; Lee, Jamie J; Summers, Michael L

    2017-04-01

    Based on primary sequence comparisons and genomic context, Npun_F4153 (SigG)/Npun_F4154 (SapG) of the cyanobacterium Nostoc punctiforme were hypothesized to encode an ECF sigma factor/anti-sigma factor pair. Transcription of sigG increased in heterocysts and akinetes, and after EDTA treatment. Interaction between SigG and the predicted cytoplasmic domain of SapG was observed in vitro. A SigG-GFP translational fusion protein localized to the periphery of vegetative cells in vivo, but lost this association following heat stress. A sigG mutant was unable to survive envelope damage caused by heat or EDTA, but was able to form functional heterocysts. Akinetes in the mutant strain appeared normal, but these cultures were less resistant to lysozyme and cold treatments than those of the wild-type strain. The SigG in vivo regulon was determined before and during akinete differentiation using DNA microarray analysis, and found to include multiple genes with putative association to the cell envelope. Mapped promoters common to both arrays enabled identification of a SigG promoter-binding motif that was supported in vivo by reporter studies, and in vitro by run-off transcription experiments. These findings support SigG/SapG as a sigma/anti-sigma pair involved in repair of envelope damage resulting from exogenous sources or cellular differentiation. © 2017 John Wiley & Sons Ltd.

  16. Characterization and in vivo regulon determination of an ECF sigma factor and its cognate anti-sigma factor in Nostoc punctiforme

    PubMed Central

    Bell, Nicole; Lee, Jamie J.; Summers, Michael L.

    2017-01-01

    Summary Based on primary sequence comparisons and genomic context, Npun_F4153 (SigG)/Npun_F4154 (SapG) of the cyanobacterium Nostoc punctiforme were hypothesized to encode an ECF sigma factor/anti-sigma factor pair. Transcription of sigG increased in heterocysts and akinetes, and after EDTA treatment. Interaction between SigG and the predicted cytoplasmic domain of SapG was observed in vitro. A SigG-GFP translational fusion protein localized to the periphery of vegetative cells in vivo, but lost this association following heat stress. A sigG mutant was unable to survive envelope damage caused by heat or EDTA, but was able to form functional heterocysts. Akinetes in the mutant strain appeared normal, but these cultures were less resistant to lysozyme and cold treatments than those of the wild-type strain. The SigG in vivo regulon was determined before and during akinete differentiation using DNA microarray analysis, and found to include multiple genes with putative association to the cell envelope. Mapped promoters common to both arrays enabled identification of a SigG promoter-binding motif that was supported in vivo by reporter studies, and in vitro by run-off transcription experiments. These findings support SigG/SapG as a sigma/anti-sigma pair involved in repair of envelope damage resulting from exogenous sources or cellular differentiation. PMID:28105698

  17. Random walks on cubic lattices with bond disorder

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ernst, M.H.; van Velthoven, P.F.J.

    1986-12-01

    The authors consider diffusive systems with static disorder, such as Lorentz gases, lattice percolation, ants in a labyrinth, termite problems, random resistor networks, etc. In the case of diluted randomness the authors can apply the methods of kinetic theory to obtain systematic expansions of dc and ac transport properties in powers of the impurity concentration c. The method is applied to a hopping model on a d-dimensional cubic lattice having two types of bonds with conductivity sigma and sigma/sub 0/ = 1, with concentrations c and 1-c, respectively. For the square lattice the authors explicitly calculate the diffusion coefficient D(c,sigma)more » as a function of c, to O(c/sup 2/) terms included for different ratios of the bond conductivity sigma. The probability of return at long times is given by P/sub 0/(t) approx. (4..pi..D(c,sigma)t)/sup -d/2/, which is determined by the diffusion coefficient of the disordered system.« less

  18. A self-adaption compensation control for hysteresis nonlinearity in piezo-actuated stages based on Pi-sigma fuzzy neural network

    NASA Astrophysics Data System (ADS)

    Xu, Rui; Zhou, Miaolei

    2018-04-01

    Piezo-actuated stages are widely applied in the high-precision positioning field nowadays. However, the inherent hysteresis nonlinearity in piezo-actuated stages greatly deteriorates the positioning accuracy of piezo-actuated stages. This paper first utilizes a nonlinear autoregressive moving average with exogenous inputs (NARMAX) model based on the Pi-sigma fuzzy neural network (PSFNN) to construct an online rate-dependent hysteresis model for describing the hysteresis nonlinearity in piezo-actuated stages. In order to improve the convergence rate of PSFNN and modeling precision, we adopt the gradient descent algorithm featuring three different learning factors to update the model parameters. The convergence of the NARMAX model based on the PSFNN is analyzed effectively. To ensure that the parameters can converge to the true values, the persistent excitation condition is considered. Then, a self-adaption compensation controller is designed for eliminating the hysteresis nonlinearity in piezo-actuated stages. A merit of the proposed controller is that it can directly eliminate the complex hysteresis nonlinearity in piezo-actuated stages without any inverse dynamic models. To demonstrate the effectiveness of the proposed model and control methods, a set of comparative experiments are performed on piezo-actuated stages. Experimental results show that the proposed modeling and control methods have excellent performance.

  19. The Burkholderia cepacia rpoE gene is not involved in exopolysaccharide production and onion pathogenicity.

    PubMed

    Devescovi, Giulia; Venturi, Vittorio

    2006-03-01

    Burkholderia cepacia was originally described as the causative agent of bacterial rot of onions, and it has now emerged as an important opportunistic pathogen causing severe chronic lung infections in patients having cystic fibrosis. Burkholderia cepacia is now classified into nine very closely related species (previously designated as genomovars), all of which have been isolated from both environmental and clinical sources and are collectively known as the B. cepacia complex. The alternative extracytoplasmic function sigma factor, sigmaE, has been determined in several bacterial species as making substantial contributions to bacterial survival under stress conditions. Here, we report the identification and characterization of the rpoE gene, encoding sigmaE, of B. cepacia. It is highly similar to sigmaE of other bacteria, including Escherichia coli and Pseudomonas aeruginosa. Studies using an rpoE knockout mutant of B. cepacia revealed that many stress adaptations, including osmotic, oxidative, desiccation, carbon, and nitrogen stress, were independent of sigmaE. Similarly, biofilm formation; production of exopolysaccharides, N-acyl homoserine lactones, and several exoenzymes; and onion pathogenicity were not affected by the absence of sigmaE. In contrast, sigmaE contributed to the adaptation to heat stress and phosphate starvation.

  20. The ECF sigma factor, PSPTO_1043, in Pseudomonas syringae pv. tomato DC3000 is induced by oxidative stress and regulates genes involved in oxidative stress response

    PubMed Central

    Butcher, Bronwyn G.; Bao, Zhongmeng; Wilson, Janet; Swingle, Bryan; Filiatrault, Melanie; Schneider, David; Cartinhour, Samuel

    2017-01-01

    The bacterial plant pathogen Pseudomonas syringae adapts to changes in the environment by modifying its gene expression profile. In many cases, the response is mediated by the activation of extracytoplasmic function (ECF) sigma factors that direct RNA polymerase to transcribe specific sets of genes. In this study we focus on PSPTO_1043, one of ten ECF sigma factors in P. syringae pv. tomato DC3000 (DC3000). PSPTO_1043, together with PSPTO_1042, encode an RpoERsp/ChrR-like sigma/anti-sigma factor pair. Although this gene pair is unique to the P. syringae group among the pseudomonads, homologous genes can be found in photosynthetic genera such as Rhodospirillum, Thalassospira, Phaeospirillum and Parvibaculum. Using ChIP-Seq, we detected 137 putative PSPTO_1043 binding sites and identified a likely promoter motif. We characterized 13 promoter candidates, six of which regulate genes that appear to be found only in P. syringae. PSPTO_1043 responds to the presence of singlet oxygen (1O2) and tert-butyl hydroperoxide (tBOOH) and several of the genes regulated by PSPTO_1043 appear to be involved in response to oxidative stress. PMID:28700608

  1. The ECF sigma factor, PSPTO_1043, in Pseudomonas syringae pv. tomato DC3000 is induced by oxidative stress and regulates genes involved in oxidative stress response.

    PubMed

    Butcher, Bronwyn G; Bao, Zhongmeng; Wilson, Janet; Stodghill, Paul; Swingle, Bryan; Filiatrault, Melanie; Schneider, David; Cartinhour, Samuel

    2017-01-01

    The bacterial plant pathogen Pseudomonas syringae adapts to changes in the environment by modifying its gene expression profile. In many cases, the response is mediated by the activation of extracytoplasmic function (ECF) sigma factors that direct RNA polymerase to transcribe specific sets of genes. In this study we focus on PSPTO_1043, one of ten ECF sigma factors in P. syringae pv. tomato DC3000 (DC3000). PSPTO_1043, together with PSPTO_1042, encode an RpoERsp/ChrR-like sigma/anti-sigma factor pair. Although this gene pair is unique to the P. syringae group among the pseudomonads, homologous genes can be found in photosynthetic genera such as Rhodospirillum, Thalassospira, Phaeospirillum and Parvibaculum. Using ChIP-Seq, we detected 137 putative PSPTO_1043 binding sites and identified a likely promoter motif. We characterized 13 promoter candidates, six of which regulate genes that appear to be found only in P. syringae. PSPTO_1043 responds to the presence of singlet oxygen (1O2) and tert-butyl hydroperoxide (tBOOH) and several of the genes regulated by PSPTO_1043 appear to be involved in response to oxidative stress.

  2. An evaluation of the rate of absorption of solar radiation in the O2(X3Sigma-g - b1Sigma-g) transition

    NASA Technical Reports Server (NTRS)

    Mlynczak, Martin G.

    1993-01-01

    The rate at which molecular oxygen absorbs radiation in the O2(X3Sigma-g - b1Sigma-g) transition is calculated using a line-by-line radiative transfer model. This rate is critical to the determination of the population of the O2(b1Sigma-g) state required for studies of the O2(b1Sigma-g - X3Sigma-g) dayglow, the O2(a1Delta-g - X3Sigma-g) dayglow, and possibly the rates of oxidation of H2 and N2O. Previous evaluations of this rate (which is sometimes called the g-factor) have significantly overestimated its value. The rate is tabulated as a function of altitude, pressure, and solar zenith angle.

  3. Processing of the mother-cell sigma factor, sigma K, may depend on events occurring in the forespore during Bacillus subtilis development.

    PubMed Central

    Lu, S; Halberg, R; Kroos, L

    1990-01-01

    During sporulation of the Gram-positive bacterium Bacillus subtilis, transcription of genes encoding spore coat proteins in the mother-cell compartment of the sporangium is controlled by RNA polymerase containing the sigma subunit called sigma K. Based on comparison of the N-terminal amino acid sequence of sigma K with the nucleotide sequence of the gene encoding sigma K (sigK), the primary product of sigK was inferred to be a pro-protein (pro-sigma K) with 20 extra amino acids at the N terminus. Using antibodies generated against pro-sigma K, we have detected pro-sigma K beginning at the third hour of sporulation and sigma K beginning about 1 hr later. Even when pro-sigma K is expressed artificially during growth and throughout sporulation, sigma K appears at the normal time and expression of a sigma K-controlled gene occurs normally. These results suggest that pro-sigma K is an inactive precursor that is proteolytically processed to active sigma K in a developmentally regulated fashion. Mutations that block forespore gene expression block accumulation of sigma K but not accumulation of pro-sigma K, suggesting that pro-sigma K processing is a regulatory device that couples the programs of gene expression in the two compartments of the sporangium. We propose that this regulatory device ensures completion of forespore morphogenesis prior to the synthesis in the mother-cell of spore coat proteins that will encase the forespore. Images PMID:2124700

  4. Interaction of sigma factor sigmaN with Escherichia coli RNA polymerase core enzyme.

    PubMed

    Scott, D J; Ferguson, A L; Gallegos, M T; Pitt, M; Buck, M; Hoggett, J G

    2000-12-01

    The equilibrium binding and kinetics of assembly of the DNA-dependent RNA polymerase (RNAP) sigma(N)-holoenzyme has been investigated using biosynthetically labelled 7-azatryptophyl- (7AW)sigma(N). The spectroscopic properties of such 7AW proteins allows their absorbance and fluorescence to be monitored selectively, even in the presence of high concentrations of other tryptophan-containing proteins. The 7AWsigma(N) retained its biological activity in stimulating transcription from sigma(N)-specific promoters, and in in vitro gel electrophoresis assays of binding to core RNAP from Escherichia coli. Furthermore, five Trp-->Ala single mutants of sigma(N) were shown to support growth under conditions of nitrogen limitation, and showed comparable efficiency in activating the sigma(N)-dependent nifH promoter in vivo, indicating that none of the tryptophan residues were essential for activity. The equilibrium binding of 7AWsigma(N) to core RNAP was examined by analytical ultracentrifugation. In sedimentation equilibrium experiments, absorbance data at 315 nm (which reports selectively on the distribution of free and bound 7AWsigma(N)) established that a 1:1 complex was formed, with a dissociation constant lower than 2 microM. The kinetics of the interaction between 7AWsigma(N) and core RNAP was investigated using stopped-flow spectrofluorimetry. A biphasic decrease in fluorescence intensity was observed when samples were excited at 280 nm, whereas only the slower of the two phases was observed at 315 nm. The kinetic data were analysed in terms of a mechanism in which a fast bimolecular association of sigma(N) with core RNAP is followed by a relatively slow isomerization step. The consequences of these findings on the competition between sigma(N) and the major sigma factor, sigma(70), in Escherichia coli are discussed.

  5. Interaction of sigma factor sigmaN with Escherichia coli RNA polymerase core enzyme.

    PubMed Central

    Scott, D J; Ferguson, A L; Gallegos, M T; Pitt, M; Buck, M; Hoggett, J G

    2000-01-01

    The equilibrium binding and kinetics of assembly of the DNA-dependent RNA polymerase (RNAP) sigma(N)-holoenzyme has been investigated using biosynthetically labelled 7-azatryptophyl- (7AW)sigma(N). The spectroscopic properties of such 7AW proteins allows their absorbance and fluorescence to be monitored selectively, even in the presence of high concentrations of other tryptophan-containing proteins. The 7AWsigma(N) retained its biological activity in stimulating transcription from sigma(N)-specific promoters, and in in vitro gel electrophoresis assays of binding to core RNAP from Escherichia coli. Furthermore, five Trp-->Ala single mutants of sigma(N) were shown to support growth under conditions of nitrogen limitation, and showed comparable efficiency in activating the sigma(N)-dependent nifH promoter in vivo, indicating that none of the tryptophan residues were essential for activity. The equilibrium binding of 7AWsigma(N) to core RNAP was examined by analytical ultracentrifugation. In sedimentation equilibrium experiments, absorbance data at 315 nm (which reports selectively on the distribution of free and bound 7AWsigma(N)) established that a 1:1 complex was formed, with a dissociation constant lower than 2 microM. The kinetics of the interaction between 7AWsigma(N) and core RNAP was investigated using stopped-flow spectrofluorimetry. A biphasic decrease in fluorescence intensity was observed when samples were excited at 280 nm, whereas only the slower of the two phases was observed at 315 nm. The kinetic data were analysed in terms of a mechanism in which a fast bimolecular association of sigma(N) with core RNAP is followed by a relatively slow isomerization step. The consequences of these findings on the competition between sigma(N) and the major sigma factor, sigma(70), in Escherichia coli are discussed. PMID:11085949

  6. The sigmaR regulon of Streptomyces coelicolor A32 reveals a key role in protein quality control during disulphide stress.

    PubMed

    Kallifidas, Dimitris; Thomas, Derek; Doughty, Phillip; Paget, Mark S B

    2010-06-01

    Diamide is an artificial disulphide-generating electrophile that mimics an oxidative shift in the cellular thiol-disulphide redox state (disulphide stress). The Gram-positive bacterium Streptomyces coelicolor senses and responds to disulphide stress through the sigma(R)-RsrA system, which comprises an extracytoplasmic function (ECF) sigma factor and a redox-active anti-sigma factor. Known targets that aid in the protection and recovery from disulphide stress include the thioredoxin system and genes involved in producing the major thiol buffer mycothiol. Here we determine the global response to diamide in wild-type and sigR mutant backgrounds to understand the role of sigma(R) in this response and to reveal additional regulatory pathways that allow cells to cope with disulphide stress. In addition to thiol oxidation, diamide was found to cause protein misfolding and aggregation, which elicited the induction of the HspR heat-shock regulon. Although this response is sigma(R)-independent, sigma(R) does directly control Clp and Lon ATP-dependent AAA(+) proteases, which may partly explain the reduced ability of a sigR mutant to resolubilize protein aggregates. sigma(R) also controls msrA and msrB methionine sulphoxide reductase genes, implying that sigma(R)-RsrA is responsible for the maintenance of both cysteine and methionine residues during oxidative stress. This work shows that the sigma(R)-RsrA system plays a more significant role in protein quality control than previously realized, and emphasizes the importance of controlling the cellular thiol-disulphide redox balance.

  7. Global Analysis of the Sporulation Pathway of Clostridium difficile

    PubMed Central

    Fimlaid, Kelly A.; Bond, Jeffrey P.; Schutz, Kristin C.; Putnam, Emily E.; Leung, Jacqueline M.; Lawley, Trevor D.; Shen, Aimee

    2013-01-01

    The Gram-positive, spore-forming pathogen Clostridium difficile is the leading definable cause of healthcare-associated diarrhea worldwide. C. difficile infections are difficult to treat because of their frequent recurrence, which can cause life-threatening complications such as pseudomembranous colitis. The spores of C. difficile are responsible for these high rates of recurrence, since they are the major transmissive form of the organism and resistant to antibiotics and many disinfectants. Despite the importance of spores to the pathogenesis of C. difficile, little is known about their composition or formation. Based on studies in Bacillus subtilis and other Clostridium spp., the sigma factors σF, σE, σG, and σK are predicted to control the transcription of genes required for sporulation, although their specific functions vary depending on the organism. In order to determine the roles of σF, σE, σG, and σK in regulating C. difficile sporulation, we generated loss-of-function mutations in genes encoding these sporulation sigma factors and performed RNA-Sequencing to identify specific sigma factor-dependent genes. This analysis identified 224 genes whose expression was collectively activated by sporulation sigma factors: 183 were σF-dependent, 169 were σE-dependent, 34 were σG-dependent, and 31 were σK-dependent. In contrast with B. subtilis, C. difficile σE was dispensable for σG activation, σG was dispensable for σK activation, and σF was required for post-translationally activating σG. Collectively, these results provide the first genome-wide transcriptional analysis of genes induced by specific sporulation sigma factors in the Clostridia and highlight that diverse mechanisms regulate sporulation sigma factor activity in the Firmicutes. PMID:23950727

  8. Global analysis of the sporulation pathway of Clostridium difficile.

    PubMed

    Fimlaid, Kelly A; Bond, Jeffrey P; Schutz, Kristin C; Putnam, Emily E; Leung, Jacqueline M; Lawley, Trevor D; Shen, Aimee

    2013-01-01

    The Gram-positive, spore-forming pathogen Clostridium difficile is the leading definable cause of healthcare-associated diarrhea worldwide. C. difficile infections are difficult to treat because of their frequent recurrence, which can cause life-threatening complications such as pseudomembranous colitis. The spores of C. difficile are responsible for these high rates of recurrence, since they are the major transmissive form of the organism and resistant to antibiotics and many disinfectants. Despite the importance of spores to the pathogenesis of C. difficile, little is known about their composition or formation. Based on studies in Bacillus subtilis and other Clostridium spp., the sigma factors σ(F), σ(E), σ(G), and σ(K) are predicted to control the transcription of genes required for sporulation, although their specific functions vary depending on the organism. In order to determine the roles of σ(F), σ(E), σ(G), and σ(K) in regulating C. difficile sporulation, we generated loss-of-function mutations in genes encoding these sporulation sigma factors and performed RNA-Sequencing to identify specific sigma factor-dependent genes. This analysis identified 224 genes whose expression was collectively activated by sporulation sigma factors: 183 were σ(F)-dependent, 169 were σ(E)-dependent, 34 were σ(G)-dependent, and 31 were σ(K)-dependent. In contrast with B. subtilis, C. difficile σ(E) was dispensable for σ(G) activation, σ(G) was dispensable for σ(K) activation, and σ(F) was required for post-translationally activating σ(G). Collectively, these results provide the first genome-wide transcriptional analysis of genes induced by specific sporulation sigma factors in the Clostridia and highlight that diverse mechanisms regulate sporulation sigma factor activity in the Firmicutes.

  9. Cooperative triple-proton/hydrogen atom relay in 7-azaindole(CH3OH)2 in the gas phase: remarkable change in the reaction mechanism from vibrational-mode specific to statistical fashion with increasing internal energy.

    PubMed

    Sakota, Kenji; Inoue, Naomi; Komoto, Yusuke; Sekiya, Hiroshi

    2007-05-31

    The 7-azaindole-methanol 1:2 cluster [7AI(CH(3)OH)2] undergoes excited-state triple-proton/hydrogen atom transfer (ESTPT/HT) along the hydrogen-bonded network in the gas phase. The measurements of the resonance-enhanced multiphoton ionization (REMPI) spectra of 7AI(CH(3)OH)2-d(n) (n = 0-3), where subscript n indicates the number of deuterium, and the fluorescence excitation spectrum of 7AI(CH(3)OH)2-d(0) allowed us to investigate the ESTPT/HT dynamics. By comparing the intensity ratios of the vibronic bands between 7AI(CH(3)OH)2-d(0) and 7AI(CH(3)OH)2-d(3) in REMPI spectra, we obtained the lower limit of an acceleration factor (f(a)(low)) of 7AI(CH(3)OH)2-d(0), which is the ratio of the reaction rate for the excitation of a vibronic state to that of the zero-point state in S(1). The f(a)(low) values are 2.7 +/- 0.83 and 4.0 +/- 1.2 for an in-phase intermolecular stretching vibration (sigma(1)) and its overtone (2sigma(1)) observed at 181 cm(-1) and 359 cm(-1) in the excitation spectrum, respectively, while that of the vibration (nu(2)/sigma(1) or nu(3)/sigma(1)) at 228 cm(-1) is 1.1 +/- 0.83. Thus, vibrational-mode-specific ESTPT/HT occurs in the low-energy region (600 cm(-1)). The excitation of an intramolecular ring mode (nu(intra)) of 7AI at 744 cm(-1) substantially enhances the reaction rate (f(a)(low) = 4.4 +/- 0.98), but the increase of f(a)(low) is not prominent for the excitation of v(intra) + sigma(1) at 926 cm(-1) (f(a)(low) = 5.0 +/- 1.6), although the sigma(1) mode is excited. These results suggest that the ESTPT/HT reaction in 7AI(CH(3)OH)2-d(0) directly proceeds from the photoexcited states with the internal energy less than approximately 600 cm(-1), but it occurs from the isoenergetically vibrational-energy redistributed states when the internal energy is large. This shows a remarkable feature of ESTPT/HT in 7AI(CH(3)OH)2; the nature of the reaction mechanism changes from vibrational-mode specific to statistical fashion with increasing the internal energy. The hydrogen-bonded network in 7AI(CH(3)OH)2-d(0) is represented by a directed graph. This shows that ESTPT/HT is one of the simplest examples of cooperative phenomena.

  10. Mass spectrometry of Escherichia coli RNA polymerase: interactions of the core enzyme with sigma70 and Rsd protein.

    PubMed

    Ilag, Leopold L; Westblade, Lars F; Deshayes, Caroline; Kolb, Annie; Busby, Stephen J W; Robinson, Carol V

    2004-02-01

    The E. coli RNA polymerase core enzyme is a multisubunit complex of 388,981 Da. To initiate transcription at promoters, the core enzyme associates with a sigma subunit to form holo RNA polymerase. Here we have used nanoflow electrospray mass spectrometry, coupled with tandem mass spectrometry, to probe the interaction of the RNA polymerase core enzyme with the most abundant sigma factor, sigma70. The results show remarkably well-resolved spectra for both the core and holo RNA polymerases. The regulator of sigma70, Rsd protein, has previously been identified as a protein that binds to free sigma70. We show that Rsd also interacts with core enzyme. In addition, by adding increasing amounts of Rsd, we show that sigma70 is displaced from holo RNA polymerase, resulting in complexes of Rsd with core and sigma70. The results argue for a model in which Rsd not only sequesters sigma70, but is also an effector of core RNA polymerase.

  11. sigmaR, an RNA polymerase sigma factor that modulates expression of the thioredoxin system in response to oxidative stress in Streptomyces coelicolor A3(2).

    PubMed Central

    Paget, M S; Kang, J G; Roe, J H; Buttner, M J

    1998-01-01

    We have identified an RNA polymerase sigma factor, sigmaR, that is part of a system that senses and responds to thiol oxidation in the Gram-positive, antibiotic-producing bacterium Streptomyces coelicolor A3(2). Deletion of the gene (sigR) encoding sigmaR caused sensitivity to the thiol-specific oxidant diamide and to the redox cycling compounds menadione and plumbagin. This correlated with reduced levels of disulfide reductase activity and an inability to induce this activity on exposure to diamide. The trxBA operon, encoding thioredoxin reductase and thioredoxin, was found to be under the direct control of sigmaR. trxBA is transcribed from two promoters, trxBp1 and trxBp2, separated by 5-6 bp. trxBp1 is transiently induced at least 50-fold in response to diamide treatment in a sigR-dependent manner. Purified sigmaR directed transcription from trxBp1 in vitro, indicating that trxBp1 is a target for sigmaR. Transcription of sigR itself initiates at two promoters, sigRp1 and sigRp2, which are separated by 173 bp. The sigRp2 transcript was undetectable in a sigR-null mutant, and purified sigmaR could direct transcription from sigRp2 in vitro, indicating that sigR is positively autoregulated. Transcription from sigRp2 was also transiently induced (70-fold) following treatment with diamide. We propose a model in which sigmaR induces expression of the thioredoxin system in response to cytoplasmic disulfide bond formation. Upon reestablishment of normal thiol levels, sigmaR activity is switched off, resulting in down-regulation of trxBA and sigR. We present evidence that the sigmaR system also functions in the actinomycete pathogen Mycobacterium tuberculosis. PMID:9755177

  12. sigmaR, an RNA polymerase sigma factor that modulates expression of the thioredoxin system in response to oxidative stress in Streptomyces coelicolor A3(2).

    PubMed

    Paget, M S; Kang, J G; Roe, J H; Buttner, M J

    1998-10-01

    We have identified an RNA polymerase sigma factor, sigmaR, that is part of a system that senses and responds to thiol oxidation in the Gram-positive, antibiotic-producing bacterium Streptomyces coelicolor A3(2). Deletion of the gene (sigR) encoding sigmaR caused sensitivity to the thiol-specific oxidant diamide and to the redox cycling compounds menadione and plumbagin. This correlated with reduced levels of disulfide reductase activity and an inability to induce this activity on exposure to diamide. The trxBA operon, encoding thioredoxin reductase and thioredoxin, was found to be under the direct control of sigmaR. trxBA is transcribed from two promoters, trxBp1 and trxBp2, separated by 5-6 bp. trxBp1 is transiently induced at least 50-fold in response to diamide treatment in a sigR-dependent manner. Purified sigmaR directed transcription from trxBp1 in vitro, indicating that trxBp1 is a target for sigmaR. Transcription of sigR itself initiates at two promoters, sigRp1 and sigRp2, which are separated by 173 bp. The sigRp2 transcript was undetectable in a sigR-null mutant, and purified sigmaR could direct transcription from sigRp2 in vitro, indicating that sigR is positively autoregulated. Transcription from sigRp2 was also transiently induced (70-fold) following treatment with diamide. We propose a model in which sigmaR induces expression of the thioredoxin system in response to cytoplasmic disulfide bond formation. Upon reestablishment of normal thiol levels, sigmaR activity is switched off, resulting in down-regulation of trxBA and sigR. We present evidence that the sigmaR system also functions in the actinomycete pathogen Mycobacterium tuberculosis.

  13. A global view of Escherichia coli Rsd protein and its interactions.

    PubMed

    Piper, Sarah E; Mitchell, Jennie E; Lee, David J; Busby, Stephen J W

    2009-12-01

    The Escherichia coli Rsd protein forms 1 : 1 complexes with sigma(70) protein, which is the major factor in determining promoter recognition by RNA polymerase. Here we describe measurements of the levels of Rsd, RNA polymerase, sigma(70) and the alternative sigma(38) factor. Rsd levels are sufficient to sequester a significant proportion of sigma(70) and immunoaffinity pull-down experiments show that this occurs in stationary phase but not in exponentially growing cells. Rsd expression is controlled by two promoters, P1 and P2. Experiments with lac fusions show that the P2 promoter is stronger than P1, that P2 is active in all phases of growth, and that this accounts for the high levels of Rsd.

  14. Effects on Chronic Stress on Anterior Pituitary and Brain Corticotropin- Releasing Factor Receptors,

    DTIC Science & Technology

    1993-01-01

    test tubes, and aprotinin (Sigma A-6012, Sigma Animals Chemical Co., St. Louis, MO), a peptidase inhibitor, was Male Sprague-Dawley rats (200-225 g...Science 226:1342-1344; 49. Widerlov, E.; Bissette, G.; Nemeroff, C. B. Monoamine metabo- 1984. lites, corticotropin releasing factor and somatostatin

  15. Expression in Bacillus subtilis of the Bacillus thuringiensis cryIIIA toxin gene is not dependent on a sporulation-specific sigma factor and is increased in a spo0A mutant.

    PubMed

    Agaisse, H; Lereclus, D

    1994-08-01

    Expression of the Bacillus thuringiensis cryIIIA gene encoding a Coleoptera-specific toxin is weak during vegetative growth and is activated at the onset of the stationary phase. cryIIIA'-'lacZ fusions and primer extension analysis show that the regulation of cryIIIA expression is similar in Bacillus subtilis and in B. thuringiensis. Activation of cryIIIA expression was not altered in B. subtilis mutant strains deficient for the sigma H and sigma E sporulation-specific sigma factors or for minor sigma factors such as sigma B, sigma D, or sigma L. This result and the nucleotide sequence of the -35 and -10 regions of the cryIIIA promoter suggest that cryIIIA expression might be directed by the E sigma A form of RNA polymerase. Expression of the cryIIIA'-'lacZ fusion is shut off after t2 (2 h after time zero) of sporulation in the B. subtilis wild-type strain grown on nutrient broth sporulation medium. However, no decrease in cryIIIA-directed beta-galactosidase activity occurred in sigma H, kinA, or spo0A mutant strains. Moreover, beta-galactosidase activity was higher and remained elevated after t2 in the spo0A mutant strain. beta-Galactosidase activity was weak in abrB and spo0A abrB mutant strains, suggesting that AbrB is responsible for the higher level of cryIIIA expression observed in a spo0A mutant. However, both in spo0A and spo0A abrB mutant strains, beta-galactosidase activity remained elevated after t2, suggesting that even in the absence of AbrB, cryIIIA expression is controlled through modulation of the phosphorylated form of Spo0A. When the cryIIIA gene is expressed in a B. subtilis spo0A mutant strain or in the 168 wild-type strain, large amounts of toxins are produced and accumulate to form a flat rectangular crystal characteristic of the coleopteran-specific B. thuringiensis strains.

  16. A contrast between DEMATEL-ANP and ANP methods for six sigma project selection: a case study in healthcare industry.

    PubMed

    Ortíz, Miguel A; Felizzola, Heriberto A; Nieto Isaza, Santiago

    2015-01-01

    The project selection process is a crucial step for healthcare organizations at the moment of implementing six sigma programs in both administrative and caring processes. However, six-sigma project selection is often defined as a decision making process with interaction and feedback between criteria; so that it is necessary to explore different methods to help healthcare companies to determine the Six-sigma projects that provide the maximum benefits. This paper describes the application of both ANP (Analytic Network process) and DEMATEL (Decision Making trial and evaluation laboratory)-ANP in a public medical centre to establish the most suitable six sigma project and finally, these methods were compared to evaluate their performance in the decision making process. ANP and DEMATEL-ANP were used to evaluate 6 six sigma project alternatives under an evaluation model composed by 3 strategies, 4 criteria and 15 sub-criteria. Judgement matrixes were completed by the six sigma team whose participants worked in different departments of the medical centre. The improving of care opportunity in obstetric outpatients was elected as the most suitable six sigma project with a score of 0,117 as contribution to the organization goals. DEMATEL-ANP performed better at decision making process since it reduced the error probability due to interactions and feedback. ANP and DEMATEL-ANP effectively supported six sigma project selection processes, helping to create a complete framework that guarantees the prioritization of projects that provide maximum benefits to healthcare organizations. As DEMATEL- ANP performed better, it should be used by practitioners involved in decisions related to the implementation of six sigma programs in healthcare sector accompanied by the adequate identification of the evaluation criteria that support the decision making model. Thus, this comparative study contributes to choosing more effective approaches in this field. Suggestions of further work are also proposed so that these methods can be applied more adequate in six sigma project selection processes in healthcare.

  17. A contrast between DEMATEL-ANP and ANP methods for six sigma project selection: a case study in healthcare industry

    PubMed Central

    2015-01-01

    Background The project selection process is a crucial step for healthcare organizations at the moment of implementing six sigma programs in both administrative and caring processes. However, six-sigma project selection is often defined as a decision making process with interaction and feedback between criteria; so that it is necessary to explore different methods to help healthcare companies to determine the Six-sigma projects that provide the maximum benefits. This paper describes the application of both ANP (Analytic Network process) and DEMATEL (Decision Making trial and evaluation laboratory)-ANP in a public medical centre to establish the most suitable six sigma project and finally, these methods were compared to evaluate their performance in the decision making process. Methods ANP and DEMATEL-ANP were used to evaluate 6 six sigma project alternatives under an evaluation model composed by 3 strategies, 4 criteria and 15 sub-criteria. Judgement matrixes were completed by the six sigma team whose participants worked in different departments of the medical centre. Results The improving of care opportunity in obstetric outpatients was elected as the most suitable six sigma project with a score of 0,117 as contribution to the organization goals. DEMATEL-ANP performed better at decision making process since it reduced the error probability due to interactions and feedback. Conclusions ANP and DEMATEL-ANP effectively supported six sigma project selection processes, helping to create a complete framework that guarantees the prioritization of projects that provide maximum benefits to healthcare organizations. As DEMATEL- ANP performed better, it should be used by practitioners involved in decisions related to the implementation of six sigma programs in healthcare sector accompanied by the adequate identification of the evaluation criteria that support the decision making model. Thus, this comparative study contributes to choosing more effective approaches in this field. Suggestions of further work are also proposed so that these methods can be applied more adequate in six sigma project selection processes in healthcare. PMID:26391445

  18. Functional Analysis of the Alternative Sigma-28 Factor FliA and Its Anti-Sigma Factor FlgM of the Nonflagellated Legionella Species L. oakridgensis.

    PubMed

    Tlapák, Hana; Rydzewski, Kerstin; Schulz, Tino; Weschka, Dennis; Schunder, Eva; Heuner, Klaus

    2017-06-01

    Legionella oakridgensis causes Legionnaires' disease but is known to be less virulent than Legionella pneumophila L. oakridgensis is one of the Legionella species that is nonflagellated. The genes of the flagellar regulon are absent, except those encoding the alternative sigma-28 factor (FliA) and its anti-sigma-28 factor (FlgM). Similar to L. oakridgensis , Legionella adelaidensis and Legionella londiniensis , located in the same phylogenetic clade, have no flagellar regulon, although both are positive for fliA and flgM Here, we investigated the role and function of both genes to better understand the role of FliA, the positive regulator of flagellin expression, in nonflagellated strains. We demonstrated that the FliA gene of L. oakridgensis encodes a functional sigma-28 factor that enables the transcription start from the sigma-28-dependent promoter site. The investigations have shown that FliA is necessary for full fitness of L. oakridgensis Interestingly, expression of FliA-dependent genes depends on the growth phase and temperature, as already shown for L. pneumophila strains that are flagellated. In addition, we demonstrated that FlgM is a negative regulator of FliA-dependent gene expression. FlgM seems to be degraded in a growth-phase- and temperature-dependent manner, instead of being exported into the medium as reported for most bacteria. The degradation of FlgM leads to an increase of FliA activity. IMPORTANCE A less virulent Legionella species, L. oakridgensis , causes Legionnaires' disease and is known to not have flagella, even though L. oakridgensis has the regulator of flagellin expression (FliA). This protein has been shown to be involved in the expression of virulence factors. Thus, the strain was chosen for use in this investigation to search for FliA target genes and to identify putative virulence factors of L. oakridgensis One of the five major target genes of FliA identified here encodes the anti-FliA sigma factor FlgM. Interestingly, in contrast to most homologs in other bacteria, FlgM in L. oakridgensis seems not to be transported from the cell so that FliA gets activated. In L. oakridgensis , FlgM seems to be degraded by protease activities. Copyright © 2017 American Society for Microbiology.

  19. Can nature's design be improved upon? High strength, transparent nacre-like nanocomposites with double network of sacrificial cross links.

    PubMed

    Podsiadlo, Paul; Kaushik, Amit K; Shim, Bong Sup; Agarwal, Ashish; Tang, Zhiyong; Waas, Anthony M; Arruda, Ellen M; Kotov, Nicholas A

    2008-11-20

    The preparation of a high-strength and highly transparent nacre-like nanocomposite via layer-by-layer assembly technique from poly(vinyl alcohol) (PVA) and Na+-montmorillonite clay nanosheets is reported in this article. We show that a high density of weak bonding interactions between the polymer and the clay particles: hydrogen, dipole-induced dipole, and van der Waals undergoing break-reform deformations, can lead to high strength nanocomposites: sigmaUTS approximately 150 MPa and E' approximately 13 GPa. Further introduction of ionic bonds into the polymeric matrix creates a double network of sacrificial bonds which dramatically increases the mechanical properties: sigmaUTS approximately 320 MPa and E' approximately 60 GPa.

  20. Building Process Improvement Business Cases Using Bayesian Belief Networks and Monte Carlo Simulation

    DTIC Science & Technology

    2009-07-01

    simulation. The pilot described in this paper used this two-step approach within a Define, Measure, Analyze, Improve, and Control ( DMAIC ) framework to...networks, BBN, Monte Carlo simulation, DMAIC , Six Sigma, business case 15. NUMBER OF PAGES 35 16. PRICE CODE 17. SECURITY CLASSIFICATION OF

  1. Transcription factor-based biosensor

    DOEpatents

    Dietrich, Jeffrey A; Keasling, Jay D

    2013-10-08

    The present invention provides for a system comprising a BmoR transcription factor, a .sigma..sup.54-RNA polymerase, and a pBMO promoter operatively linked to a reporter gene, wherein the pBMO promoter is capable of expression of the reporter gene with an activated form of the BmoR and the .sigma..sup.54-RNA polymerase.

  2. Alternative Sigma Factor Over-Expression Enables Heterologous Expression of a Type II Polyketide Biosynthetic Pathway in Escherichia coli

    PubMed Central

    Stevens, David Cole; Conway, Kyle R.; Pearce, Nelson; Villegas-Peñaranda, Luis Roberto; Garza, Anthony G.; Boddy, Christopher N.

    2013-01-01

    Background Heterologous expression of bacterial biosynthetic gene clusters is currently an indispensable tool for characterizing biosynthetic pathways. Development of an effective, general heterologous expression system that can be applied to bioprospecting from metagenomic DNA will enable the discovery of a wealth of new natural products. Methodology We have developed a new Escherichia coli-based heterologous expression system for polyketide biosynthetic gene clusters. We have demonstrated the over-expression of the alternative sigma factor σ54 directly and positively regulates heterologous expression of the oxytetracycline biosynthetic gene cluster in E. coli. Bioinformatics analysis indicates that σ54 promoters are present in nearly 70% of polyketide and non-ribosomal peptide biosynthetic pathways. Conclusions We have demonstrated a new mechanism for heterologous expression of the oxytetracycline polyketide biosynthetic pathway, where high-level pleiotropic sigma factors from the heterologous host directly and positively regulate transcription of the non-native biosynthetic gene cluster. Our bioinformatics analysis is consistent with the hypothesis that heterologous expression mediated by the alternative sigma factor σ54 may be a viable method for the production of additional polyketide products. PMID:23724102

  3. Anti-sigma factor YlaD regulates transcriptional activity of sigma factor YlaC and sporulation via manganese-dependent redox-sensing molecular switch in Bacillus subtilis.

    PubMed

    Kwak, Min-Kyu; Ryu, Han-Bong; Song, Sung-Hyun; Lee, Jin-Won; Kang, Sa-Ouk

    2018-05-14

    YlaD, a membrane-anchored anti-sigma factor of Bacillus subtilis , contains a HX 3 CXXC motif that functions as a redox-sensing domain and belongs to one of the zinc-coordinated anti-sigma factor families. Despite previously showing that the YlaC transcription is controlled by YlaD, experimental evidence of how the YlaC-YlaD interaction is affected by active cysteines and/or metal ions is lacking. Here, we showed that the P yla promoter is autoregulated solely by YlaC. Moreover, reduced YlaD contained zinc and iron, while oxidized YlaD did not. Cysteine substitution in YlaD led to changes in its secondary structure; Cys3 had important structural functions in YlaD, and its mutation caused dissociation from YlaC, indicating the essential requirement of a HX 3 CXXC motif for regulating interactions of YlaC with YlaD. Analyses of the far-UV CD spectrum and metal content revealed that the addition of Mn ions to Zn-YlaD changed its secondary structure and that iron was substituted for manganese. The ylaC gene expression using βGlu activity from P yla : gusA was observed at the late-exponential and early-stationary phase and the ylaC -overexpressing mutant constitutively expressed gene transcripts of clpP and sigH , an important alternative sigma factor regulated by ClpXP. Collectively, our data demonstrated that YlaD senses redox changes and elicits increase in manganese ion concentrations and that, in turn, YlaD-mediated transcriptional activity of YlaC regulates sporulation initiation under oxidative stress and manganese-substituted conditions by regulating clpP gene transcripts. This is the first report of the involvement of oxidative stress-responsive B. subtilis extracytoplasmic function sigma factors during sporulation via a manganese-dependent redox-sensing molecular switch. ©2018 The Author(s).

  4. Bacterial two-hybrid analysis of interactions between region 4 of the sigma(70) subunit of RNA polymerase and the transcriptional regulators Rsd from Escherichia coli and AlgQ from Pseudomonas aeruginosa.

    PubMed

    Dove, S L; Hochschild, A

    2001-11-01

    A number of transcriptional regulators mediate their effects through direct contact with the sigma(70) subunit of Escherichia coli RNA polymerase (RNAP). In particular, several regulators have been shown to contact a C-terminal portion of sigma(70) that harbors conserved region 4. This region of sigma contains a putative helix-turn-helix DNA-binding motif that contacts the -35 element of sigma(70)-dependent promoters directly. Here we report the use of a recently developed bacterial two-hybrid system to study the interaction between the putative anti-sigma factor Rsd and the sigma(70) subunit of E. coli RNAP. Using this system, we found that Rsd can interact with an 86-amino-acid C-terminal fragment of sigma(70) and also that amino acid substitution R596H, within region 4 of sigma(70), weakens this interaction. We demonstrated the specificity of this effect by showing that substitution R596H does not weaken the interaction between sigma and two other regulators shown previously to contact region 4 of sigma(70). We also demonstrated that AlgQ, a homolog of Rsd that positively regulates virulence gene expression in Pseudomonas aeruginosa, can contact the C-terminal region of the sigma(70) subunit of RNAP from this organism. We found that amino acid substitution R600H in sigma(70) from P. aeruginosa, corresponding to the R596H substitution in E. coli sigma(70), specifically weakens the interaction between AlgQ and sigma(70). Taken together, our findings suggest that Rsd and AlgQ contact similar surfaces of RNAP present in region 4 of sigma(70) and probably regulate gene expression through this contact.

  5. Does living near a Superfund site contribute to higher polychlorinated biphenyl (PCB) exposure?

    PubMed

    Choi, Anna L; Levy, Jonathan I; Dockery, Douglas W; Ryan, Louise M; Tolbert, Paige E; Altshul, Larisa M; Korrick, Susan A

    2006-07-01

    We assessed determinants of cord serum polychlorinated biphenyl (PCB) levels among 720 infants born between 1993 and 1998 to mothers living near a PCB-contaminated Superfund site in Massachusetts, measuring the sum of 51 PCB congeners (capital sigmaPCB) and ascertaining maternal address, diet, sociodemographics, and exposure risk factors. Addresses were geocoded to obtain distance to the Superfund site and neighborhood characteristics. We modeled log10(capital sigmaPCB) as a function of potential individual and neighborhood risk factors, mapping model residuals to assess spatial correlates of PCB exposure. Similar analyses were performed for light (mono-tetra) and heavy (penta-deca) PCBs to assess potential differences in exposure pathways as a function of relative volatility. PCB-118 (relatively prevalent in site sediments and cord serum) was assessed separately. The geometric mean of capital sigmaPCB levels was 0.40 (range, 0.068-18.14) ng/g serum. Maternal age and birthplace were the strongest predictors of capital sigmaPCB levels. Maternal consumption of organ meat and local dairy products was associated with higher and smoking and previous lactation with lower capital sigmaPCB levels. Infants born later in the study had lower capital sigmaPCB levels, likely due to temporal declines in exposure and site remediation in 1994-1995. No association was found between capital sigmaPCB levels and residential distance from the Superfund site. Similar results were found with light and heavy PCBs and PCB-118. Previously reported demographic (age) and other (lactation, smoking, diet) correlates of PCB exposure, as well as local factors (consumption of local dairy products and Superfund site dredging) but not residential proximity to the site, were important determinants of cord serum PCB levels in the study community.

  6. Biosynthetic burden and plasmid burden limit expression of chromosomally integrated heterologous genes (pdc, adhB) in Escherichia coli

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Martinez, A.; York, S.W.; Yomano, L.P.

    1999-10-01

    Previous studies have shown an unexpectedly high nutrient requirement for efficient ethanol production by ethanologenic recombinants of Escherichia coli B such as LY01 which contain chromosomally integrated Zymomonas mobilis genes (pdc, adhB) encoding the ethanol pathway. The basis for this requirement has been identified as a media-dependent effect on the expression of the Z. mobilis genes rather than a nutritional limitation. Ethanol production was substantially increased without additional nutrients simply by increasing the level of pyruvate decarboxylase activity. This was accomplished by adding a multicopy plasmid containing pdc alone (but not adhB alone) to strain LY01, and by adding multicopymore » plasmids which express pdc and adhB from strong promoters. New strong promoters were isolated from random fragments of Z. mobilis DNA and characterized but were not used to construct integrated biocatalysts. These promoters contained regions resembling recognition sites for 3 different E. coli sigma factors: {sigma}{sup 70}, {sigma}{sup 38}, and {sigma}{sup 28}. The most effective plasmid-based promoters for fermentation were recognized by multiple sigma factors, expressed both pdc and adhB at high levels, and produced ethanol efficiently while allowing up to 80% reduction in complex nutrients as compared to LY01. The ability to utilize multiple sigma factors may be advantageous to maintain the high levels of PDC and ADH needed for efficient ethanol production throughout batch fermentation.« less

  7. Chlorinated hydrocarbon contaminants in polar bears from eastern Russia, North America, Greenland, and Svalbard: Biomonitoring of Arctic pollution

    USGS Publications Warehouse

    Norstrom, R.J.; Belikov, Stanislav; Born, E.W.; Garner, G.W.; Malone, B.; Olpinski, S.; Ramsay, M.A.; Schliebe, S.; Stirling, I.; Sitshov, M.S.; Taylor, M.K.; Wiig, Øystein

    1998-01-01

    Adipose tissue samples from polar bears (Ursus maritimus) were obtained by necropsy or biopsy between the spring of 1989 to the spring of 1993 from Wrangel Island in Russia, most of the range of the bear in North America, eastern Greenland, and Svalbard. Samples were divided into 16 regions corresponding as much as possible to known stocks or management zones. Concentrations of dieldrin (DIEL), 4,4'-DDE (DDE), sum of 16 polychlorinated biphenyl congeners (sigma PCB), and sum of 11 chlordane-related compounds and metabolites (sigma CHL) were determined. In order to minimize the effect of age, only data for adults (320 bears age 5 years and older) was used to compare concentrations among regions. Concentrations of sigma PCB were 46% higher in adult males than females, and there was no significant trend with age. Concentrations of sigma CHL were 30% lower in adult males than females. Concentrations of sigma PCB, sigma CHL, and DDE in individual adult female bears were standardized to adult males using factors derived from the least-square means of each sex category, and geometric means of the standardized concentrations on a lipid weight basis were compared among regions. Median geometric mean standardized concentrations (lipid weight basis) and ranges among regions were as follows: sigma PCB, 5,942 (2,763-24,316) micrograms/kg; sigma CHL, 1,952 (727-4,632) micrograms/kg; DDE, 219 (52-560) micrograms/kg; DIEL, 157 (31-335) micrograms/kg. Geometric mean sigma PCB concentrations in bears from Svalbard, East Greenland, and the Arctic Ocean near Prince Patrick Island in Canada were similar (20,256-24,316 micrograms/kg) and significantly higher than most other areas. Atmospheric, oceanic, and ice transport, as well as ecological factors may contribute to these high concentrations of sigma PCB. sigma CHL was more uniformly distributed among regions than the other CHCs. Highest sigma CHL concentrations were found in southeastern Hudson Bay, which also had the highest DDE and DIEL concentrations. In general, concentrations of sigma CHL, DDE, and DIEL were higher in eastern than western regions, suggesting an influence of North American sources. Average sigma PCB concentrations in bears from the Canadian Arctic were similar to those in 1982-84, while average sigma CHL and DDE concentrations were 35-44% lower and DIEL was 90% lower. However, the significance of these temporal trends during the 1980s is not conclusive because of the problems of comparability of data.

  8. Contribution of partner switching and SpoIIAA cycling to regulation of sigmaF activity in sporulating Bacillus subtilis.

    PubMed

    Magnin, T; Lord, M; Yudkin, M D

    1997-06-01

    sigmaF, the first compartment-specific transcription factor in sporulating Bacillus subtilis, is negatively regulated by an anti-sigma factor, SpoIIAB. SpoIIAB has an alternative binding partner, SpoIIAA. To see whether (as has been proposed) SpoIIAB's binding preference for SpoIIAA or sigmaF depends on the nature of the adenine nucleotide present, we used surface plasmon resonance to measure the dissociation constants of the three complexes SpoIIAA-SpoIIAB-ADP, sigmaF-SpoIIAB-ADP, and sigmaF-SpoIIAB-ATP. The results suggested that SpoIIAB's choice of binding partner is unlikely to depend on the ATP/ADP ratio in the cell. The intracellular concentrations of sigmaF, SpoIIAB, SpoIIAA, and SpoIIAA-phosphate (SpoIIAA-P) were measured by quantitative immunoblotting between 0 and 3 h after the beginning of sporulation (t0 to t3). sigmaF and SpoIIAB were barely detectable at t0, but their concentrations increased in parallel to reach maxima at about t1.5. SpoIIAA-P increased steadily to a maximum at t3, but nonphosphorylated SpoIIAA was detectable only from t1.5, reached a maximum at t2.5, and then declined. Kinetic studies of the phosphorylation of SpoIIAA catalyzed by SpoIIAB suggested that the reaction was limited by a very slow release of one of the products (SpoIIAA-P or ADP) from SpoIIAB, with a turnover of about once per 20 min. This remarkable kinetic property provides an unexpected mechanism for the regulation of sigmaF. We propose that when SpoIIE (which dephosphorylates SpoIIAA-P) is active at the same time as SpoIIAB, SpoIIAA cycles repeatedly between the phosphorylated and nonphosphorylated forms. This cycling sequesters SpoIIAB in a long-lived complex and prevents it from inhibiting sigmaF.

  9. Building a complete image of genome regulation in the model organism Escherichia coli.

    PubMed

    Ishihama, Akira

    2018-01-15

    The model organism, Escherichia coli, contains a total of more than 4,500 genes, but the total number of RNA polymerase (RNAP) core enzyme or the transcriptase is only about 2,000 molecules per genome. The regulatory targets of RNAP are, however, modulated by changing its promoter selectivity through two-steps of protein-protein interplay with 7 species of the sigma factor in the first step, and then 300 species of the transcription factor (TF) in the second step. Scientists working in the field of prokaryotic transcription in Japan have made considerable contributions to the elucidation of genetic frameworks and regulatory modes of the genome transcription in E. coli K-12. This review summarizes the findings by this group, first focusing on three sigma factors, the stationary-phase sigma RpoS, the heat-shock sigma RpoH, and the flagellar-chemotaxis sigma RpoF, as examples. It also presents an overview of the current state of the systematic research being carried out to identify the regulatory functions of all TFs from a single and the same bacterium E. coli K-12, using the genomic SELEX and PS-TF screening systems. All these studies have been undertaken with the aim of understanding the genome regulation in E. coli K-12 as a whole.

  10. Design and implementation of quadrature bandpass sigma-delta modulator used in low-IF RF receiver

    NASA Astrophysics Data System (ADS)

    Ge, Binjie; Li, Yan; Yu, Hang; Feng, Xiaoxing

    2018-05-01

    This paper presents the design and implementation of quadrature bandpass sigma-delta modulator. A pole movement method for transforming real sigma-delta modulator to a quadrature one is proposed by detailed study of the relationship of noise-shaping center frequency and integrator pole position in sigma-delta modulator. The proposed modulator uses sampling capacitor sharing switched capacitor integrator, and achieves a very small feedback coefficient by a series capacitor network, and those two techniques can dramatically reduce capacitor area. Quantizer output-dependent dummy capacitor load for reference voltage buffer can compensate signal-dependent noise that is caused by load variation. This paper designs a quadrature bandpass Sigma-Delta modulator for 2.4 GHz low IF receivers that achieve 69 dB SNDR at 1 MHz BW and -1 MHz IF with 48 MHz clock. The chip is fabricated with SMIC 0.18 μm CMOS technology, it achieves a total power current of 2.1 mA, and the chip area is 0.48 mm2. Project supported by the National Natural Science Foundation of China (Nos. 61471245, U1201256), the Guangdong Province Foundation (No. 2014B090901031), and the Shenzhen Foundation (Nos. JCYJ20160308095019383, JSGG20150529160945187).

  11. A comparison of back propagation and Generalized Regression Neural Networks performance in neutron spectrometry.

    PubMed

    Martínez-Blanco, Ma Del Rosario; Ornelas-Vargas, Gerardo; Solís-Sánchez, Luis Octavio; Castañeda-Miranada, Rodrigo; Vega-Carrillo, Héctor René; Celaya-Padilla, José M; Garza-Veloz, Idalia; Martínez-Fierro, Margarita; Ortiz-Rodríguez, José Manuel

    2016-11-01

    The process of unfolding the neutron energy spectrum has been subject of research for many years. Monte Carlo, iterative methods, the bayesian theory, the principle of maximum entropy are some of the methods used. The drawbacks associated with traditional unfolding procedures have motivated the research of complementary approaches. Back Propagation Neural Networks (BPNN), have been applied with success in neutron spectrometry and dosimetry domains, however, the structure and learning parameters are factors that highly impact in the networks performance. In ANN domain, Generalized Regression Neural Network (GRNN) is one of the simplest neural networks in term of network architecture and learning algorithm. The learning is instantaneous, requiring no time for training. Opposite to BPNN, a GRNN would be formed instantly with just a 1-pass training on the development data. In the network development phase, the only hurdle is to optimize the hyper-parameter, which is known as sigma, governing the smoothness of the network. The aim of this work was to compare the performance of BPNN and GRNN in the solution of the neutron spectrometry problem. From results obtained it can be observed that despite the very similar results, GRNN performs better than BPNN. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. New Insights into the Regulation of Cell-Surface Signaling Activity Acquired from a Mutagenesis Screen of the Pseudomonas putida IutY Sigma/Anti-Sigma Factor

    PubMed Central

    Bastiaansen, Karlijn C.; Civantos, Cristina; Bitter, Wilbert; Llamas, María A.

    2017-01-01

    Cell-surface signaling (CSS) is a signal transfer system that allows Gram-negative bacteria to detect environmental signals and generate a cytosolic response. These systems are composed of an outer membrane receptor that senses the inducing signal, an extracytoplasmic function sigma factor (σECF) that targets the cytosolic response by modifying gene expression and a cytoplasmic membrane anti-sigma factor that keeps the σECF in an inactive state in the absence of the signal and transduces its presence from the outer membrane to the cytosol. Although CSS systems regulate bacterial processes as crucial as stress response, iron scavenging and virulence, the exact mechanisms that drive CSS are still not completely understood. Binding of the signal to the CSS receptor is known to trigger a signaling cascade that results in the regulated proteolysis of the anti-sigma factor and the activation of the σECF in the cytosol. This study was carried out to generate new insights in the proteolytic activation of CSS σECF. We performed a random mutagenesis screen of the unique IutY protein of Pseudomonas putida, a protein that combines a cytosolic σECF domain and a periplasmic anti-sigma factor domain in a single polypeptide. In response to the presence of an iron carrier, the siderophore aerobactin, in the extracellular medium, IutY is processed by two different proteases, Prc and RseP, which results in the release and activation of the σIutY domain. Our experiments show that all IutY mutant proteins that contain periplasmic residues depend on RseP for activation. In contrast, Prc is only required for mutant variants with a periplasmic domain longer than 50 amino acids, which indicates that the periplasmic region of IutY is trimmed down to ~50 amino acids creating the RseP substrate. Moreover, we have identified several conserved residues in the CSS anti-sigma factor family of which mutation leads to constitutive activation of their cognate σECF. These findings advance our knowledge on how CSS activity is regulated by the consecutive action of two proteases. Elucidation of the exact mechanism behind CSS activation will enable the development of strategies to block CSS in pathogenic bacteria. PMID:28512454

  13. Mapping of the Rsd Contact Site on the Sigma 70 Subunit of Escherichia coli RNA Polymerase

    PubMed Central

    Jishage, Miki; Dasgupta, Dipak; Ishihama, Akira

    2001-01-01

    Rsd (regulator of sigma D) is an anti-sigma factor for the Escherichia coli RNA polymerase ς70 subunit. The contact site of Rsd on ς70 was analyzed after mapping of the contact-dependent cleavage sites by Rsd-tethered iron-p-bromoacetamidobenzyl EDTA and by analysis of the complex formation between Ala-substituted ς70 and Rsd. Results indicate that the Rsd contact site is located downstream of the promoter −35 recognition helix-turn-helix motif within region 4, overlapping with the regions involved in interaction with both core enzyme and ς70 contact transcription factors. PMID:11292818

  14. LINE ABSORPTION OSCILLATOR STRENGTHS FOR THE c'{sub 4}{sup 1}{Sigma}{sup +}{sub u}(3)-X{sup 1}{Sigma}{sup +}{sub g}(0-5) BANDS IN N{sub 2}

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lavin, C.; Velasco, A. M., E-mail: clavin@qf.uva.es

    Theoretical absorption oscillator strengths and emission branching ratios for rotational lines of the c'{sub 4}{sup 1}{Sigma}{sup +}{sub u}(3)-X{sup 1}{Sigma}{sup +}{sub g}(0-5) bands of molecular nitrogen are reported. The calculations have been performed with the molecular quantum defect orbital method, which has proved to be reliable in previous studies of rovibronic transitions in diatomic molecules. The strong interaction between c'{sub 4}{sup 1}{Sigma}{sup +}{sub u}(3) and b' {sup 1}{Sigma}{sup +}{sub u}(10) states has been analyzed through an interaction matrix that includes rotational terms. Owing to the perturbation, the c'{sub 4}{sup 1}{Sigma}{sup +}{sub u}(3)-X{sup 1}{Sigma}{sup +}{sub g}(0), c'{sub 4}{sup 1}{Sigma}{sup +}{sub u}(3)-X{sup 1}{Sigma}{supmore » +}{sub g}(1), and c'{sub 4}{sup 1}{Sigma}{sup +}{sub u}(3)-X{sup 1}{Sigma}{sup +}{sub g}(5) bands are not weak, in contrast to what would be expected on the basis of the Franck-Condon principle. Moreover, the intensity distribution of the rotational lines within each of the vibronic bands deviates from considerations based on Hoenl-London factors. In this work, we provide data that may be useful to interpret spectra from atmospheres of the Earth, Titan, and Triton, in which transitions from the c'{sub 4}{sup 1}{Sigma}{sup +}{sub u}(3) level have been detected.« less

  15. Bioaccumulation of organochlorine contaminants in bowhead whales (Balaena mysticetus) from Barrow, Alaska.

    PubMed

    Hoekstra, P F; O'Hara, T M; Pallant, S J; Solomon, K R; Muir, D C G

    2002-05-01

    Bowhead whale (Balaena mysticetus) blubber (n = 72) and liver (n = 23) samples were collected during seven consecutive subsistence harvests (1997-2000) at Barrow, Alaska, to investigate the bioaccumulation of organochlorine contaminants (OCs) by this long-lived mysticete. The rank order of OC group concentrations (geometric mean, wet weight) in bowhead blubber samples were toxaphene (TOX; 455 ng/g) > polychlorinated biphenyls (SigmaPCBs; 410 ng/g) > dichlorodiphenyltrichloroethane-related compounds (SigmaDDT; 331 ng/g) >or= hexachlorocyclohexane isomers (SigmaHCHs; 203 ng/g) >or= chlordanes and related isomers (SigmaCHLOR; 183 ng/g) > chlorobenzenes (SigmaCIBz; 106 ng/g). In liver, SigmaHCH (9.5 ng/g; wet weight) was the most abundant SigmaOC group, followed by SigmaPCBs (9.1 ng/g) >or= TOX (8.8 ng/g) > SigmaCHLOR (5.5 ng/g) > SigmaCIBz (4.2 ng/g) >or= SigmaDDT (3.7 ng/g). The dominant analyte in blubber and liver was p,p'-DDE and alpha-HCH, respectively. Total TOX, SigmaPCBs, SigmaDDT, and SigmaCHLOR concentrations in blubber generally increased with age of male whales (as interpreted by body length), but this relationship was not significant for adult female whales. Biomagnification factor (BMF) values (0.1-45.5) for OCs from zooplankton (Calanus sp.) to bowhead whale were consistent with findings for other mysticetes. Tissue-specific differences in OC patterns in blubber and liver may be attributed to variation of tissue composition and the relatively low capacity of this species to biotransform various OCs. Principal component analysis of contaminants levels in bowhead blubber samples suggest that proportions of OCs, such as beta-HCH, fluctuate with seasonal migration of this species between the Bering, Chukchi, and Beaufort Seas.

  16. Partially pre-calculated weights for the backpropagation learning regime and high accuracy function mapping using continuous input RAM-based sigma-pi nets.

    PubMed

    Neville, R S; Stonham, T J; Glover, R J

    2000-01-01

    In this article we present a methodology that partially pre-calculates the weight updates of the backpropagation learning regime and obtains high accuracy function mapping. The paper shows how to implement neural units in a digital formulation which enables the weights to be quantised to 8-bits and the activations to 9-bits. A novel methodology is introduced to enable the accuracy of sigma-pi units to be increased by expanding their internal state space. We, also, introduce a novel means of implementing bit-streams in ring memories instead of utilising shift registers. The investigation utilises digital "Higher Order" sigma-pi nodes and studies continuous input RAM-based sigma-pi units. The units are trained with the backpropagation learning regime to learn functions to a high accuracy. The neural model is the sigma-pi units which can be implemented in digital microelectronic technology. The ability to perform tasks that require the input of real-valued information, is one of the central requirements of any cognitive system that utilises artificial neural network methodologies. In this article we present recent research which investigates a technique that can be used for mapping accurate real-valued functions to RAM-nets. One of our goals was to achieve accuracies of better than 1% for target output functions in the range Y epsilon [0,1], this is equivalent to an average Mean Square Error (MSE) over all training vectors of 0.0001 or an error modulus of 0.01. We present a development of the sigma-pi node which enables the provision of high accuracy outputs. The sigma-pi neural model was initially developed by Gurney (Learning in nets of structured hypercubes. PhD Thesis, Department of Electrical Engineering, Brunel University, Middlessex, UK, 1989; available as Technical Memo CN/R/144). Gurney's neuron models, the Time Integration Node (TIN), utilises an activation that was derived from a bit-stream. In this article we present a new methodology for storing sigma-pi node's activations as single values which are averages. In the course of the article we state what we define as a real number; how we represent real numbers and input of continuous values in our neural system. We show how to utilise the bounded quantised site-values (weights) of sigma-pi nodes to make training of these neurocomputing systems simple, using pre-calculated look-up tables to train the nets. In order to meet our accuracy goal, we introduce a means of increasing the bandwidth capability of sigma-pi units by expanding their internal state-space. In our implementation we utilise bit-streams when we calculate the real-valued outputs of the net. To simplify the hardware implementation of bit-streams we present a method of mapping them to RAM-based hardware using 'ring memories'. Finally, we study the sigma-pi units' ability to generalise once they are trained to map real-valued, high accuracy, continuous functions. We use sigma-pi units as they have been shown to have shorter training times than their analogue counterparts and can also overcome some of the drawbacks of semi-linear units (Gurney, 1992. Neural Networks, 5, 289-303).

  17. Shewregdb: Database and visualization environment for experimental and predicted regulatory information in Shewanella oneidensis mr-1

    PubMed Central

    Syed, Mustafa H; Karpinets, Tatiana V; Leuze, Michael R; Kora, Guruprasad H; Romine, Margaret R; Uberbacher, Edward C

    2009-01-01

    Shewanella oneidensis MR-1 is an important model organism for environmental research as it has an exceptional metabolic and respiratory versatility regulated by a complex regulatory network. We have developed a database to collect experimental and computational data relating to regulation of gene and protein expression, and, a visualization environment that enables integration of these data types. The regulatory information in the database includes predictions of DNA regulator binding sites, sigma factor binding sites, transcription units, operons, promoters, and RNA regulators including non-coding RNAs, riboswitches, and different types of terminators. Availability http://shewanella-knowledgebase.org:8080/Shewanella/gbrowserLanding.jsp PMID:20198195

  18. Lagrange constraint neural network for audio varying BSS

    NASA Astrophysics Data System (ADS)

    Szu, Harold H.; Hsu, Charles C.

    2002-03-01

    Lagrange Constraint Neural Network (LCNN) is a statistical-mechanical ab-initio model without assuming the artificial neural network (ANN) model at all but derived it from the first principle of Hamilton and Lagrange Methodology: H(S,A)= f(S)- (lambda) C(s,A(x,t)) that incorporates measurement constraint C(S,A(x,t))= (lambda) ([A]S-X)+((lambda) 0-1)((Sigma) isi -1) using the vector Lagrange multiplier-(lambda) and a- priori Shannon Entropy f(S) = -(Sigma) i si log si as the Contrast function of unknown number of independent sources si. Szu et al. have first solved in 1997 the general Blind Source Separation (BSS) problem for spatial-temporal varying mixing matrix for the real world remote sensing where a large pixel footprint implies the mixing matrix [A(x,t)] necessarily fill with diurnal and seasonal variations. Because the ground truth is difficult to be ascertained in the remote sensing, we have thus illustrated in this paper, each step of the LCNN algorithm for the simulated spatial-temporal varying BSS in speech, music audio mixing. We review and compare LCNN with other popular a-posteriori Maximum Entropy methodologies defined by ANN weight matrix-[W] sigmoid-(sigma) post processing H(Y=(sigma) ([W]X)) by Bell-Sejnowski, Amari and Oja (BSAO) called Independent Component Analysis (ICA). Both are mirror symmetric of the MaxEnt methodologies and work for a constant unknown mixing matrix [A], but the major difference is whether the ensemble average is taken at neighborhood pixel data X's in BASO or at the a priori sources S variables in LCNN that dictates which method works for spatial-temporal varying [A(x,t)] that would not allow the neighborhood pixel average. We expected the success of sharper de-mixing by the LCNN method in terms of a controlled ground truth experiment in the simulation of variant mixture of two music of similar Kurtosis (15 seconds composed of Saint-Saens Swan and Rachmaninov cello concerto).

  19. State selected ion--molecule reactions by a TESICO technique. IV. Relative importance of the two spin-orbit states of Ar/sup +/ in the charge transfer reactions with N/sub 2/ and CO

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kato, T.; Tanaka, K.; Koyano, I.

    1982-07-01

    Charge transfer reactions Ar/sup +/ (/sup 2/P/sub J/)+N/sub 2/..-->..N/sup +//sub 2/+Ar (1) and Ar/sup +/(/sup 2/P/sub J/)+CO..-->..CO/sup +/+Ar (2) have been studied for the two spin-orbit states (J = 3/2 and 1/2) separately using the threshold electron-secondary ion coincidence (TESICO) technique. Relative cross sections for the two states sigma(3/2) and sigma(1/2) have been determined at three collision energies 0.2, 1.4, and 5.8 eV. It has been found that in Reaction (1), sigma(3/2) is larger than sigma (1/2) with ratio sigma(1/2)/sigma(3/2) ranging from 0.5 to 0.8 depending on the collision energy, whereas in Reaction (2), sigma(1/2) is larger than sigma(3/2) withmore » the ratio ranging from 1.2 to 1.6. The implications of these results are discussed with regard to the roles of energy resonance and Franck--Condon factors in charge transfer processes.« less

  20. Effective Radius of Ice Cloud Particle Populations Derived from Aircraft Probes

    NASA Technical Reports Server (NTRS)

    Heymsfield, Andrew J.; Schmitt, Carl; Bansemer, Aaron; vanZadelhoff, Gerd-Jan; McGill, Matthew J.; Twohy, Cynthia

    2005-01-01

    The effective radius(r(sub e)) is a crucial variable in representing the radiative properties of cloud layers in general circulation models. This parameter is proportional to the condensed water content (CWC) divided by the extinction (sigma). For ice cloud layers, parameterizations for r(sub e), have been developed from aircraft in-situ measurements 1) indirectly, using data obtained from particle spectrometer probes and assumptions or observations about particle shape and mass to get the ice water content (IWC) and area to get sigma, and recently 2) from probes that measure IWC and sigma directly. This study compares [IWC/sigma] derived from the two methods using data sets acquired from comparable instruments on two aircraft, one sampling clouds at mid-levels and the other at upper-levels during the CRYSTAL-FACE field program in Florida in 2002. The sigma and IWC derived by each method are compared and evaluated in different ways for each aircraft data set. Direct measurements of sigma exceed those derived indirectly by a factor of two to two and a half. The IWC probes, relying on ice sublimation, appear to measure accurately except when the IWC is high or the particles too large to sublimate completely during the short transit time through the probe. The IWC estimated from the particle probes are accurate when direct measurements are available to provide constraints and useful information in high IWC/large particle situations. Because of the discrepancy in sigma estimates between the direct and indirect approaches, there is a factor of 2 to 3 difference in [IWC/sigma] between them. Although there are significant uncertainties involved in its use, comparisons with several independent data sources suggest that the indirect method is the more accurate of the two approaches. However, experiments are needed to resolve the source of the discrepancy in sigma.

  1. The electromagnetic Sigma-to-Lambda hyperon transition form factors at low energies

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Granados, Carlos; Leupold, Stefan; Perotti, Elisabetta

    Using dispersion theory the low-energy electromagnetic form factors for the transition of a Sigma to a Lambda hyperon are related to the pion vector form factor. The additionally required input, i.e. the two-pion-Sigma-Lambda amplitudes are determined from relativistic next-to-leading-order (NLO) baryon chiral perturbation theory including the baryons from the octet and optionally from the decuplet. Pion rescattering is again taken into account by dispersion theory. It turns out that the inclusion of decuplet baryons is not an option but a necessity to obtain reasonable results. The electric transition form factor remains very small in the whole low-energy region. The magneticmore » transition form factor depends strongly on one not very well determined low-energy constant of the NLO Lagrangian. Furthermore, one obtains reasonable predictive power if this low-energy constant is determined from a measurement of the magnetic transition radius. Such a measurement can be performed at the future Facility for Antiproton and Ion Research (FAIR).« less

  2. The electromagnetic Sigma-to-Lambda hyperon transition form factors at low energies

    DOE PAGES

    Granados, Carlos; Leupold, Stefan; Perotti, Elisabetta

    2017-06-09

    Using dispersion theory the low-energy electromagnetic form factors for the transition of a Sigma to a Lambda hyperon are related to the pion vector form factor. The additionally required input, i.e. the two-pion-Sigma-Lambda amplitudes are determined from relativistic next-to-leading-order (NLO) baryon chiral perturbation theory including the baryons from the octet and optionally from the decuplet. Pion rescattering is again taken into account by dispersion theory. It turns out that the inclusion of decuplet baryons is not an option but a necessity to obtain reasonable results. The electric transition form factor remains very small in the whole low-energy region. The magneticmore » transition form factor depends strongly on one not very well determined low-energy constant of the NLO Lagrangian. Furthermore, one obtains reasonable predictive power if this low-energy constant is determined from a measurement of the magnetic transition radius. Such a measurement can be performed at the future Facility for Antiproton and Ion Research (FAIR).« less

  3. Global repression of host-associated genes of the Lyme disease spirochete through post-transcriptional modulation of the alternative sigma factor RpoS.

    PubMed

    Dulebohn, Daniel P; Hayes, Beth M; Rosa, Patricia A

    2014-01-01

    Borrelia burgdorferi, the agent of Lyme disease, is a vector-borne pathogen that transits between Ixodes ticks and vertebrate hosts. During the natural infectious cycle, spirochetes must globally adjust their transcriptome to survive in these dissimilar environments. One way B. burgdorferi accomplishes this is through the use of alternative sigma factors to direct transcription of specific genes. RpoS, one of only three sigma factors in B. burgdorferi, controls expression of genes required during tick-transmission and infection of the mammalian host. How spirochetes switch between different sigma factors during the infectious cycle has remained elusive. Here we establish a role for a novel protein, BBD18, in the regulation of the virulence-associated sigma factor RpoS. Constitutive expression of BBD18 repressed transcription of RpoS-dependent genes to levels equivalent to those observed in an rpoS mutant. Consistent with the global loss of RpoS-dependent transcripts, we were unable to detect RpoS protein. However, constitutive expression of BBD18 did not diminish the amount of rpoS transcript, indicating post-transcriptional regulation of RpoS by BBD18. Interestingly, BBD18-mediated repression of RpoS is independent of both the rpoS promoter and the 5' untranslated region, suggesting a mechanism of protein destabilization rather than translational control. We propose that BBD18 is a novel regulator of RpoS and its activity likely represents a first step in the transition from an RpoS-ON to an RpoS-OFF state, when spirochetes transition from the host to the tick vector.

  4. Interest and limits of the six sigma methodology in medical laboratory.

    PubMed

    Scherrer, Florian; Bouilloux, Jean-Pierre; Calendini, Ors'Anton; Chamard, Didier; Cornu, François

    2017-02-01

    The mandatory accreditation of clinical laboratories in France provides an incentive to develop real tools to measure performance management methods and to optimize the management of internal quality controls. Six sigma methodology is an approach commonly applied to software quality management and discussed in numerous publications. This paper discusses the primary factors that influence the sigma index (the choice of the total allowable error, the approach used to address bias) and compares the performance of different analyzers on the basis of the sigma index. Six sigma strategy can be applied to the policy management of internal quality control in a laboratory and demonstrates through a comparison of four analyzers that there is no single superior analyzer in clinical chemistry. Similar sigma results are obtained using approaches toward bias based on the EQAS or the IQC. The main difficulty in using the six sigma methodology lies in the absence of official guidelines for the definition of the total error acceptable. Despite this drawback, our comparison study suggests that difficulties with defined analytes do not vary with the analyzer used.

  5. Sigma Routing Metric for RPL Protocol.

    PubMed

    Sanmartin, Paul; Rojas, Aldo; Fernandez, Luis; Avila, Karen; Jabba, Daladier; Valle, Sebastian

    2018-04-21

    This paper presents the adaptation of a specific metric for the RPL protocol in the objective function MRHOF. Among the functions standardized by IETF, we find OF0, which is based on the minimum hop count, as well as MRHOF, which is based on the Expected Transmission Count (ETX). However, when the network becomes denser or the number of nodes increases, both OF0 and MRHOF introduce long hops, which can generate a bottleneck that restricts the network. The adaptation is proposed to optimize both OFs through a new routing metric. To solve the above problem, the metrics of the minimum number of hops and the ETX are combined by designing a new routing metric called SIGMA-ETX, in which the best route is calculated using the standard deviation of ETX values between each node, as opposed to working with the ETX average along the route. This method ensures a better routing performance in dense sensor networks. The simulations are done through the Cooja simulator, based on the Contiki operating system. The simulations showed that the proposed optimization outperforms at a high margin in both OF0 and MRHOF, in terms of network latency, packet delivery ratio, lifetime, and power consumption.

  6. Sigma Routing Metric for RPL Protocol

    PubMed Central

    Rojas, Aldo; Fernandez, Luis

    2018-01-01

    This paper presents the adaptation of a specific metric for the RPL protocol in the objective function MRHOF. Among the functions standardized by IETF, we find OF0, which is based on the minimum hop count, as well as MRHOF, which is based on the Expected Transmission Count (ETX). However, when the network becomes denser or the number of nodes increases, both OF0 and MRHOF introduce long hops, which can generate a bottleneck that restricts the network. The adaptation is proposed to optimize both OFs through a new routing metric. To solve the above problem, the metrics of the minimum number of hops and the ETX are combined by designing a new routing metric called SIGMA-ETX, in which the best route is calculated using the standard deviation of ETX values between each node, as opposed to working with the ETX average along the route. This method ensures a better routing performance in dense sensor networks. The simulations are done through the Cooja simulator, based on the Contiki operating system. The simulations showed that the proposed optimization outperforms at a high margin in both OF0 and MRHOF, in terms of network latency, packet delivery ratio, lifetime, and power consumption. PMID:29690524

  7. Identification of Disulphide Stress-responsive Extracytoplasmic Function Sigma Factors in Rothia mucilaginosa

    DTIC Science & Technology

    2013-01-01

    GC) content of deoxyribonucleic acid (DNA).1 This organism belongs to the actinobacteria , which includes the genera Actinomyces, Corynebacterium...however, it still remains unclear how Rothia species respond to environmental stress. The responsiveness and adaptation of a few actinobacteria to various... actinobacteria , the number of sigma factors in R. mucilaginosa is relatively small (microbial signal transduction (MiST2) database, http://mistdb.com/); however

  8. Structural basis for the sequestration of the anti-σ(70) factor Rsd from σ(70) by the histidine-containing phosphocarrier protein HPr.

    PubMed

    Park, Young Ha; Um, Si Hyeon; Song, Saemee; Seok, Yeong Jae; Ha, Nam Chul

    2015-10-01

    Histidine-containing phosphocarrier protein (HPr) is a general component of the bacterial phosphoenolpyruvate:sugar phosphotransferase system (PTS) involved in the phosphorylation-coupled transport of numerous sugars called PTS sugars. HPr mainly exists in a dephosphorylated form in the presence of PTS sugars in the medium, while its phosphorylation increases in the absence of PTS sugars. A recent study revealed that the dephosphorylated form of HPr binds and antagonizes the function of the antisigma factor Rsd. This anti-sigma factor sequesters the housekeeping sigma factor σ(70) to facilitate switching of the sigma subunit on RNA polymerase from σ(70) to the stress-responsive sigma factor σ(S) in stationary-phase cells. In this study, the structure of the complex of Rsd and HPr was determined at 2.1 Å resolution and revealed that the binding site for HPr on the surface of Rsd partly overlaps with that for σ(70). The localization of the phosphorylation site on HPr at the binding interface for Rsd explains why phosphorylation of HPr abolishes its binding to Rsd. The mutation of crucial residues involved in the HPr-Rsd interaction significantly influenced the competition between HPr and σ(70) for binding to Rsd both in vitro and in vivo. The results provide a structural basis for the linkage of global gene regulation to nutrient availability in the external environment.

  9. Selection bias in dynamically-measured super-massive black hole samples: its consequences and the quest for the most fundamental relation

    NASA Astrophysics Data System (ADS)

    Shankar, Francesco; Bernardi, M.; Sheth, R. K.; Weinberg, D. H.; Miralda-Escudé, J.; Ferrarese, L.; Graham, A.; Sesana, A.; Lapi, A.; Marconi, A.; Allevato, V.; Savorgnan, G.; Laesker, R.

    2016-08-01

    We compare the set of local galaxies having dynamically measured black holes with a large, unbiased sample of galaxies extracted from the Sloan Digital Sky Survey. We confirm earlier work showing that the majority of black hole hosts have significantly higher velocity dispersions sigma than local galaxies of similar stellar mass. We use Monte-Carlo simulations to illustrate the effect on black hole scaling relations if this bias arises from the requirement that the black hole sphere of influence must be resolved to measure black hole masses with spatially resolved kinematics. We find that this selection effect artificially increases the normalization of the Mbh-sigma relation by a factor of at least ~3; the bias for the Mbh-Mstar relation is even larger. Our Monte Carlo simulations and analysis of the residuals from scaling relations both indicate that sigma is more fundamental than Mstar or effective radius. In particular, the Mbh-Mstar relation is mostly a consequence of the Mbh-sigma and sigma-Mstar relations, and is heavily biased by up to a factor of 50 at small masses. This helps resolve the discrepancy between dynamically-based black hole-galaxy scaling relations versus those of active galaxies. Our simulations also disfavour broad distributions of black hole masses at fixed sigma. Correcting for this bias suggests that the calibration factor used to estimate black hole masses in active galaxies should be reduced to values of fvir~1. Black hole mass densities should also be proportionally smaller, perhaps implying significantly higher radiative efficiencies/black hole spins. Reducing black hole masses also reduces the gravitational wave signal expected from black hole mergers.

  10. Ground Motion Uncertainty and Variability (single-station sigma): Insights from Euroseistest, Greece

    NASA Astrophysics Data System (ADS)

    Ktenidou, O. J.; Roumelioti, Z.; Abrahamson, N. A.; Cotton, F.; Pitilakis, K.

    2014-12-01

    Despite recent improvements in networks and data, the global aleatory uncertainty (sigma) in GMPEs is still large. One reason is the ergodic approach, where we combine data in space to make up for lack of data in time. By estimating the systematic site response, we can make site-specific GMPEs and use a lower, site-specific uncertainty: single-station sigma. In this study we use the EUROSEISTEST database (http://euroseisdb.civil.auth.gr), which has two distinct advantages: good existing knowledge of site conditions at all stations, and careful relocation of the recorded events. Constraining the site and source parameters as best we can, we minimise the within- and between-events components of the global, ergodic sigma. Following that, knowledge of the site response from empirical and theoretical approaches permits us to move on to single-station sigma. The variability per site is not clearly correlated to the site class. We show that in some cases knowledge of Vs30 is not sufficient, and that site-specific data are needed to capture the response, possibly due to 2D/3D effects from complex geometry. Our values of single-station sigma are low compared to the literature. This may be due to the good ray coverage we have in all directions for small, nearby records. Indeed, our single-station sigma values are similar to published single-path values, which means that they may correspond to a fully -rather than partially- non-ergodic approach. We find larger ground motion variability for short distances and small magnitudes. This may be related to the uncertainty in the depth affecting nearby records more, or to stress drop and causing trade-offs between the source and site terms for small magnitudes.

  11. Determination of the geophysical model function of the ERS-1 scatterometer by the use of neural networks

    NASA Astrophysics Data System (ADS)

    Mejia, Carlos; Thiria, Sylvie; Tran, Ngan; CréPon, Michel; Badran, Fouad

    1998-06-01

    We present a geophysical model function (GMF) for the ERS-1 scatterometer computed by the use of neural networks. The neural networks GMF (NN GMF) is calibrated with ERS-1 scatterometer sigma 0 collocated with European Center for Medium-Range Weather Forecasts (ECMWF) analyzed wind vectors. Four different NN GMFs have been computed: one for each antenna and an average NN GMF. These NN GMFs do not present any significant differences which means that the three antenna are quasi-identical. The NN GMFs exhibit a biharmonic dependence on the wind azimuth with a small upwind-downwind modulation as found on previous GMFs. In order to check the validity of the NN GMF systematic comparisons with the European Space Agency (ESA) C band model (CMOD4) GMF (version 2 of March 25, 1993) and the Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER) CMOD213 GMF are done. It is found that the NN GMFs are highly accurate and relevant functions to model the ERS-1 scatterometer sigma 0.

  12. Stoichiometric network theory for nonequilibrium biochemical systems.

    PubMed

    Qian, Hong; Beard, Daniel A; Liang, Shou-dan

    2003-02-01

    We introduce the basic concepts and develop a theory for nonequilibrium steady-state biochemical systems applicable to analyzing large-scale complex isothermal reaction networks. In terms of the stoichiometric matrix, we demonstrate both Kirchhoff's flux law sigma(l)J(l)=0 over a biochemical species, and potential law sigma(l) mu(l)=0 over a reaction loop. They reflect mass and energy conservation, respectively. For each reaction, its steady-state flux J can be decomposed into forward and backward one-way fluxes J = J+ - J-, with chemical potential difference deltamu = RT ln(J-/J+). The product -Jdeltamu gives the isothermal heat dissipation rate, which is necessarily non-negative according to the second law of thermodynamics. The stoichiometric network theory (SNT) embodies all of the relevant fundamental physics. Knowing J and deltamu of a biochemical reaction, a conductance can be computed which directly reflects the level of gene expression for the particular enzyme. For sufficiently small flux a linear relationship between J and deltamu can be established as the linear flux-force relation in irreversible thermodynamics, analogous to Ohm's law in electrical circuits.

  13. Annual Meeting of International Neural Network Society

    DTIC Science & Technology

    1990-07-31

    presentations, tutorials, commercial and publishing exhibits, government agency presentations, and social events. - Join us in Boston September 6-10, 1988! iii...Merrill, John and Port, Robert India;ia University Towards A Connectionist Model of Italian Morphology Arbitrio, Aiessandro Istituto Psicologia CNR & AI Lab...Connectionist Network Nolfi Stefano Fondazione Sigma Tau Parisi, Domenico Instituto di Psicologia C.N.R., Roma Decision Rules for Perception of Species

  14. Immunocytochemical assessment of sigma-1 receptor and human sterol isomerase in breast cancer and their relationship with a series of prognostic factors

    PubMed Central

    Simony-Lafontaine, J; Esslimani, M; Bribes, E; Gourgou, S; Lequeux, N; Lavail, R; Grenier, J; Kramar, A; Casellas, P

    2000-01-01

    The purpose of this study was to immunocytochemically investigate two new markers, the sigma-1 receptor and the human sterol isomerase (hSI), in comparison with a series of clinicopathological and immunocytochemical prognostic factors in a trial including 95 patients with operable primary breast cancers. Our results showed no statistically significant relationship between these two markers and the age of the patients, their menopausal status, the tumour size and its histological grade, the nodal status and the expression of the Ki-67 proliferative marker. However, we evidenced a close correlation between the sigma-1 receptor expression and the hormonal receptor positivity (P = 0.008), essentially due to a link with the progesterone receptor status (P = 0.01). By contrast there was an inverse relationship between hSI expression and the oestrogen receptor and/or progesterone receptor positivity (P = 0.098). A significant relationship was shown between both the sigma-1 receptor, hSI expressions and Bcl2 expression, with P = 0.017 and 0.035 respectively. We also assessed whether the expression of the sigma-1 receptor or hSI might be linked with disease-free survival (DFS) and found that the presence of hSI and the absence of sigma-1 receptor expression were associated with a poorer disease-free survival (P = 0.007). Altogether these results suggest that in primary breast carcinomas in association with the evaluation of the steroid receptor status, the sigma-1 receptor and hSI may be interesting new markers useful to identify those patients who might be able to benefit from an adjuvant therapy. © 2000 Cancer Research Campaign PMID:10864204

  15. Rivited panel surface measurement using photogrammetry

    NASA Technical Reports Server (NTRS)

    Merrick, W. D.; Lobb, V. B.; Lansing, F. L.; Stoller, F. W.

    1986-01-01

    Two riveted antenna panels on rings number 3 and 9 were removed from the 34m antenna at DSS-15, fixed in the leveled position and the surface was photographed indoors. The results from this pilot photogrammetric demonstration and diagnostics of panel surface contours, are presented. The photogrammetric network for each panel incorporated eight photographs, two from each of four camera stations and observed over 200 targets. The accuracy (1 sigma) of the XYZ coordinates for the error ellipsoids was + or - 0.013 mm (0.0005 inch). This level of precision relative to the object size corresponds roughly to 1 part in 250,000 which is superior to conventional dial sweep-arm template techniques by at least a factor of 4.

  16. State selected ion--molecule reactions by a TESICO technique. V. N/sub 2//sup +/(v)+Ar. -->. N/sub 2/+Ar/sup +/

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kato, T.; Tanaka, K.; Koyano, I.

    1982-07-15

    Charge transfer reactions N/sub 2//sup +/(v)+Ar..-->..Ar/sup +/+N/sub 2/ (1) have been studied by selecting the vibrational states of N/sub 2//sup +/ using the threshold electron--secondary ion coincidence (TESICO) technique. Relative cross sections sigma(v) for the individual vibrational states v = 0--3 have been determined at three collision energies, 0.3, 1.5, and 11.8 eV. Results show that Reaction (1), which is endoergic for v = 0, is considerably enhanced by the vibrational excitation of N/sub 2//sup +/ at all collision energies. While excitation of one vibrational quantum enhances the cross section substantially, excitation of additional quanta further increases the cross sectionmore » up to v = 3. The ratios sigma(2)/sigma(1) and sigma(3)/sigma(2) are, however, much smaller than sigma(1)/sigma(0) and are significantly larger at the highest collision energy than at the other two collision energies. These results are discussed in conjunction with the calculated results based on the simple two-state theory of Rapp and Francis and the Franck--Condon factors.« less

  17. Fluoro-Phenyl-Styrene-Sulfonamide, a Novel Inhibitor of σB Activity, Prevents the Activation of σB by Environmental and Energy Stresses in Bacillus subtilis

    PubMed Central

    Ringus, Daina L.; Gaballa, Ahmed; Helmann, John D.; Wiedmann, Martin

    2013-01-01

    Sigma B (σB) is an alternative sigma factor that regulates the general stress response in Bacillus subtilis and in many other Gram-positive organisms. σB activity in B. subtilis is tightly regulated via at least three distinct pathways within a complex signal transduction cascade in response to a variety of stresses, including environmental stress, energy stress, and growth at high or low temperatures. We probed the ability of fluoro-phenyl-styrene-sulfonamide (FPSS), a small-molecule inhibitor of σB activity in Listeria monocytogenes, to inhibit σB activity in B. subtilis through perturbation of signal transduction cascades under various stress conditions. FPSS inhibited the activation of σB in response to multiple categories of stress known to induce σB activity in B. subtilis. Specifically, FPSS prevented the induction of σB activity in response to energy stress, including entry into stationary phase, phosphate limitation, and azide stress. FPSS also inhibited chill induction of σB activity in a ΔrsbV strain, suggesting that FPSS does not exclusively target the RsbU and RsbP phosphatases or the anti–anti-sigma factor RsbV, all of which contribute to posttranslational regulation of σB activity. Genetic and biochemical experiments, including artificial induction of σB, analysis of the phosphorylation state of the anti–anti-sigma factor RsbV, and in vitro transcription assays, indicate that while FPSS does not bind directly to σB to inhibit activity, it appears to prevent the release of B. subtilis σB from its anti-sigma factor RsbW. PMID:23524614

  18. Sigma-1 receptor chaperone and brain-derived neurotrophic factor: emerging links between cardiovascular disease and depression.

    PubMed

    Hashimoto, Kenji

    2013-01-01

    Epidemiological studies have demonstrated a close relationship between depression and cardiovascular disease (CVD). Although it is known that the central nervous system (CNS) contributes to this relationship, the detailed mechanisms involved in this process remain unclear. Recent studies suggest that the endoplasmic reticulum (ER) molecular chaperone sigma-1 receptor and brain-derived neurotrophic factor (BDNF) play a role in the pathophysiology of CVD and depression. Several meta-analysis studies have showed that levels of BDNF in the blood of patients with major depressive disorder (MDD) are lower than normal controls, indicating that blood BDNF might be a biomarker for depression. Furthermore, blood levels of BDNF in patients with CVD are also lower than normal controls. A recent study using conditional BDNF knock-out mice in animal models of myocardial infarction highlighted the role of CNS-mediated mechanisms in the cardioprotective effects of BDNF. In addition, a recent study shows that decreased levels of sigma-1 receptor in the mouse brain contribute to the association between heart failure and depression. Moreover, sigma-1 receptor agonists, including the endogenous neurosteroid dehydroepiandosterone (DHEA) and the selective serotonin reuptake inhibitor (SSRI) fluvoxamine, show potent cardioprotective and antidepressive effects in rodents, via sigma-1 receptor stimulation. Interestingly, agonist activation of sigma-1 receptors increased the secretion of mature BDNF from its precursor proBDNF via chaperone activity in the ER. Given the role of ER stress in the pathophysiology of CVD and MDD, the author will discuss the potential link between sigma-1 receptors and BDNF-TrkB pathway in the pathophysiology of these two diseases. Finally, the author will make a case for potent sigma-1 receptor agonists and TrkB agonists as new potential therapeutic drugs for depressive patients with CVD. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Combating the Military’s Escalating Pharmacy Costs: A Lean Six Sigma Approach

    DTIC Science & Technology

    2008-12-01

    without illustrating anything that can essentially go wrong. Not surprisingly, not everyone shares the belief that Lean Six Sigma is a cure all for cost...or absenteeism ; however, these factors are discussed in the conclusion found in Chapter VIII. The resources are also only available during

  20. Sequence information gain based motif analysis.

    PubMed

    Maynou, Joan; Pairó, Erola; Marco, Santiago; Perera, Alexandre

    2015-11-09

    The detection of regulatory regions in candidate sequences is essential for the understanding of the regulation of a particular gene and the mechanisms involved. This paper proposes a novel methodology based on information theoretic metrics for finding regulatory sequences in promoter regions. This methodology (SIGMA) has been tested on genomic sequence data for Homo sapiens and Mus musculus. SIGMA has been compared with different publicly available alternatives for motif detection, such as MEME/MAST, Biostrings (Bioconductor package), MotifRegressor, and previous work such Qresiduals projections or information theoretic based detectors. Comparative results, in the form of Receiver Operating Characteristic curves, show how, in 70% of the studied Transcription Factor Binding Sites, the SIGMA detector has a better performance and behaves more robustly than the methods compared, while having a similar computational time. The performance of SIGMA can be explained by its parametric simplicity in the modelling of the non-linear co-variability in the binding motif positions. Sequence Information Gain based Motif Analysis is a generalisation of a non-linear model of the cis-regulatory sequences detection based on Information Theory. This generalisation allows us to detect transcription factor binding sites with maximum performance disregarding the covariability observed in the positions of the training set of sequences. SIGMA is freely available to the public at http://b2slab.upc.edu.

  1. In depth analysis of the mechanism of action of metal-dependent sigma factors: characterization of CorE2 from Myxococcus xanthus

    PubMed Central

    Marcos-Torres, Francisco Javier; Pérez, Juana; Gómez-Santos, Nuria; Moraleda-Muñoz, Aurelio; Muñoz-Dorado, José

    2016-01-01

    Extracytoplasmic function sigma factors represent the third pillar of signal-transduction mechanisms in bacteria. The variety of stimuli they recognize and mechanisms of action they use have allowed their classification into more than 50 groups. We have characterized CorE2 from Myxococcus xanthus, which belongs to group ECF44 and upregulates the expression of two genes when it is activated by cadmium and zinc. Sigma factors of this group contain a Cys-rich domain (CRD) at the C terminus which is essential for detecting metals. Point mutations at the six Cys residues of the CRD have revealed the contribution of each residue to CorE2 activity. Some of them are essential, while others are either dispensable or their mutations only slightly affect the activity of the protein. However, importantly, mutation of Cys174 completely shifts the specificity of CorE2 from cadmium to copper, indicating that the Cys arrangement of the CRD determines the metal specificity. Moreover, the conserved CxC motif located between the σ2 domain and the σ4.2 region has also been found to be essential for activity. The results presented here contribute to our understanding of the mechanism of action of metal-dependent sigma factors and help to define new common features of the members of this group of regulators. PMID:26951374

  2. Intracellular concentrations of 65 species of transcription factors with known regulatory functions in Escherichia coli.

    PubMed

    Ishihama, Akira; Kori, Ayako; Koshio, Etsuko; Yamada, Kayoko; Maeda, Hiroto; Shimada, Tomohiro; Makinoshima, Hideki; Iwata, Akira; Fujita, Nobuyuki

    2014-08-01

    The expression pattern of the Escherichia coli genome is controlled in part by regulating the utilization of a limited number of RNA polymerases among a total of its approximately 4,600 genes. The distribution pattern of RNA polymerase changes from modulation of two types of protein-protein interactions: the interaction of core RNA polymerase with seven species of the sigma subunit for differential promoter recognition and the interaction of RNA polymerase holoenzyme with about 300 different species of transcription factors (TFs) with regulatory functions. We have been involved in the systematic search for the target promoters recognized by each sigma factor and each TF using the newly developed Genomic SELEX system. In parallel, we developed the promoter-specific (PS)-TF screening system for identification of the whole set of TFs involved in regulation of each promoter. Understanding the regulation of genome transcription also requires knowing the intracellular concentrations of the sigma subunits and TFs under various growth conditions. This report describes the intracellular levels of 65 species of TF with known function in E. coli K-12 W3110 at various phases of cell growth and at various temperatures. The list of intracellular concentrations of the sigma factors and TFs provides a community resource for understanding the transcription regulation of E. coli under various stressful conditions in nature. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  3. SP10 Infectivity Is Aborted after Bacteriophage SP10 Infection Induces nonA Transcription on the Prophage SPβ Region of the Bacillus subtilis Genome

    PubMed Central

    Yamamoto, Tatsuya; Obana, Nozomu; Yee, Lii Mien; Asai, Kei; Nomura, Nobuhiko

    2014-01-01

    Bacteria have developed various strategies for phage resistance. Infection with phage induces the transcription of part of the phage resistance gene, but the regulatory mechanisms of such transcription remain largely unknown. The phage resistance gene nonA is located on the SPβ prophage region of the Bacillus subtilis Marburg strain genome. The nonA transcript was detected at the late stage of SP10 infection but is undetectable in noninfected cells. The nonA transcript was detected after the induction of the sigma factor Orf199-Orf200 (σOrf199-200), when sigma factors encoded in the SP10 genome were expressed from a xylose-inducible plasmid. Thus, the SP10 sigma factor is an activator of a set of SP10 genes and nonA. The nonA gene encodes a 72-amino-acid protein with a transmembrane motif and has no significant homology with any protein in any database. NonA overexpression halted cell growth and reduced the efficiency of B. subtilis colony formation and respiration activity. In addition, SP10 virion protein synthesis was inhibited in the nonA+ strain, and SP10 virion particles were scarce in it. These results indicate that NonA is a novel protein that can abort SP10 infection, and its transcription was regulated by SP10 sigma factor. PMID:24272782

  4. Stress tensor and focal mechanisms in the Dead Sea basin

    NASA Astrophysics Data System (ADS)

    Hofstetter, A.; Dorbath, C.; Dorbath, L.; Braeuer, B.; Weber, M. H.

    2015-12-01

    We use the recorded seismicity, confined to the Dead Sea basin and its boundaries, by the Dead Sea Integrated Research (DESIRE) portable seismic network and the Israel and Jordan permanent seismic networks for studying the mechanisms of earthquakes that occurred in the Dead Sea basin. The observed seismicity in the Dead Sea basin was divided into 9 regions according to the spatial distribution of the earthquakes and the known tectonic features. The large number of recording stations and the good station distribution allowed the reliable determinations of 494 earthquake focal mechanisms. For each region, based on the inversion of the observed polarities of the earthquakes, we determine the focal mechanisms and the associated stress tensor. For 159 earthquakes out of the 494 mechanisms we could determine compatible fault planes. On the eastern side, the focal mechanisms are mainly strike-slip mechanism with nodal planes in the N-S and E-W directions. The azimuths of the stress axes are well constrained presenting minimal variability in the inversion of the data, which is in good agreement with the Arava fault on the eastern side of the Dead Sea basin and what we had expected from the regional geodynamics. However, larger variabilities of the azimuthal and dip angles are observed on the western side of the basin. Due to the wider range of azimuths of the fault planes, we observe the switching of sigma1 and sigma2 or the switching of sigma2 and sigma3as major horizontal stress directions. This observed switching of stress axes allows having dip-slip and normal mechanisms in a region that is dominated by strike-slip motion.

  5. Microscopic study of spin cut-off factors of nuclear level densities

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gholami, M.; Kildir, M.; Behkami, A. N.

    Level densities and spin cut-off factors have been investigated within the microscopic approach based on the BCS Hamiltonian. In particular, the spin cut-off parameters have been calculated at neutron binding energies over a large range of nuclear mass using the BCS theory. The spin cut-off parameters {sigma}{sup 2}(E) have also been obtained from the Gilbert and Cameron expression and from rigid body calculations. The results were compared with their corresponding macroscopic values. It was found that the values of {sigma}{sup 2}(E) did not increase smoothly with A as expected based on macroscopic theory. Instead, the values of {sigma}{sup 2}(E) showmore » structure reflecting the angular momentum of the shell model orbitals near the Fermi energy.« less

  6. Correcting Velocity Dispersion Measurements for Inclination and Implications for the M-Sigma Relation

    NASA Astrophysics Data System (ADS)

    Bellovary, Jillian M.; Holley-Bockelmann, Kelly; Gultekin, Kayhan; Christensen, Charlotte; Governato, Fabio

    2015-01-01

    The relation between central black hole mass and stellar spheroid velocity dispersion (the M-Sigma relation) is one of the best-known correlations linking black holes and their host galaxies. However, there is a large amount of scatter at the low-mass end, indicating that the processes that relate black holes to lower-mass hosts are not straightforward. Some of this scatter can be explained by inclination effects; contamination from disk stars along the line of sight can artificially boost velocity dispersion measurements by 30%. Using state of the art simulations, we have developed a correction factor for inclination effects based on purely observational quantities. We present the results of applying these factors to observed samples of galaxies and discuss the effects on the M-Sigma relation.

  7. On the direct and dissociative excitation of the O(3s 3S0) state by electron impact on atomic and molecular oxygen

    NASA Technical Reports Server (NTRS)

    Zipf, E. C.

    1986-01-01

    The ratio of the cross sections for the direct and dissociative excitation of the OI(3s 3S0-2p 3P; 1304 A wavelength) transition, sigma A/sigma D, are accurately determined, and the sigma A/sigma D ratio is directly normalized to the ratio of the O(+) and O2(+) ionization cross sections using a high-density diffuse gas source, an electrostatically focused electron gun, a vacuum-ultraviolet monochromater, and a quadrupole mass spectrometer for simultaneous optical and composition measurements. Using revised sigma A(1304 A) values calculated with new calibration standards, the shape of the cross section for the excitation of the O(3s 3S0) state agrees well with previous results, though the absolute magnitude of sigma A(1304 A) is smaller than the results of Stone and Zipf (1974) by a factor of 2.8. The revised cross sections agree well with recent quantum calculations when cascade excitation of the 3s 3S0 state is taken into account.

  8. Microwave Conductivity of Laser Ablated YBa2Cu3O7-delta Superconducting Films and Its Relation to Microstrip Transmission Line Performance

    NASA Technical Reports Server (NTRS)

    Bhasin, K. B.; Warner, J. D.; Chorey, C. M.; Ebihara, B. T.; Romanofsky, R. R.; Heinen, V. O.

    1990-01-01

    We report on the values of the microwave conductivity in the normal (sigma(subN)) and superconducting (sigma*=sigma(sub1)-j sigma(sub2)) states of two laser ablated YBa2CU3O7(sigma) thin films at 35 GHz, in the temperature range from 20 to 300 K. The films 0.7 and 0.4 micrometers) were deposited on LaA10(sub3) by laser ablation. The conductivity was obtained from the microwave power transmitted through the films and assuming a two-fluid model. Values of sigma(subN) approximately 2.3 X 10(exp5) S/m at room temperature for both films, and of sigma(sub1) approximately 6.3 X 10(exp5) and 4.6 X 10(exp5) S/m at temperatures around 80 K were obtained for the 0.7 and 0.4 micrometer films respectively. For sigma(sub2) values of 4.9 X 10(exp6) and 5.4 X 10(exp6) S/m were obtained for the 0.7 and 0.4 micrometer films at 80 K. The expected conductor losses and Q-factor of a superconducting ring resonator were calculated using these conductivity values. The theoretical values were then compared with the experimental results obtained for a resonator fabricated from one of these films.

  9. Region 4 of Rhizobium etli Primary Sigma Factor (SigA) Confers Transcriptional Laxity in Escherichia coli.

    PubMed

    Santillán, Orlando; Ramírez-Romero, Miguel A; Lozano, Luis; Checa, Alberto; Encarnación, Sergio M; Dávila, Guillermo

    2016-01-01

    Sigma factors are RNA polymerase subunits engaged in promoter recognition and DNA strand separation during transcription initiation in bacteria. Primary sigma factors are responsible for the expression of housekeeping genes and are essential for survival. RpoD, the primary sigma factor of Escherichia coli, a γ-proteobacteria, recognizes consensus promoter sequences highly similar to those of some α-proteobacteria species. Despite this resemblance, RpoD is unable to sustain transcription from most of the α-proteobacterial promoters tested so far. In contrast, we have found that SigA, the primary sigma factor of Rhizobium etli, an α-proteobacteria, is able to transcribe E. coli promoters, although it exhibits only 48% identity (98% coverage) to RpoD. We have called this the transcriptional laxity phenomenon. Here, we show that SigA partially complements the thermo-sensitive deficiency of RpoD285 from E. coli strain UQ285 and that the SigA region σ4 is responsible for this phenotype. Sixteen out of 74 residues (21.6%) within region σ4 are variable between RpoD and SigA. Mutating these residues significantly improves SigA ability to complement E. coli UQ285. Only six of these residues fall into positions already known to interact with promoter DNA and to comprise a helix-turn-helix motif. The remaining variable positions are located on previously unexplored sites inside region σ4, specifically into the first two α-helices of the region. Neither of the variable positions confined to these helices seem to interact directly with promoter sequence; instead, we adduce that these residues participate allosterically by contributing to correct region folding and/or positioning of the HTH motif. We propose that transcriptional laxity is a mechanism for ensuring transcription in spite of naturally occurring mutations from endogenous promoters and/or horizontally transferred DNA sequences, allowing survival and fast environmental adaptation of α-proteobacteria.

  10. Region 4 of Rhizobium etli Primary Sigma Factor (SigA) Confers Transcriptional Laxity in Escherichia coli

    PubMed Central

    Santillán, Orlando; Ramírez-Romero, Miguel A.; Lozano, Luis; Checa, Alberto; Encarnación, Sergio M.; Dávila, Guillermo

    2016-01-01

    Sigma factors are RNA polymerase subunits engaged in promoter recognition and DNA strand separation during transcription initiation in bacteria. Primary sigma factors are responsible for the expression of housekeeping genes and are essential for survival. RpoD, the primary sigma factor of Escherichia coli, a γ-proteobacteria, recognizes consensus promoter sequences highly similar to those of some α-proteobacteria species. Despite this resemblance, RpoD is unable to sustain transcription from most of the α-proteobacterial promoters tested so far. In contrast, we have found that SigA, the primary sigma factor of Rhizobium etli, an α-proteobacteria, is able to transcribe E. coli promoters, although it exhibits only 48% identity (98% coverage) to RpoD. We have called this the transcriptional laxity phenomenon. Here, we show that SigA partially complements the thermo-sensitive deficiency of RpoD285 from E. coli strain UQ285 and that the SigA region σ4 is responsible for this phenotype. Sixteen out of 74 residues (21.6%) within region σ4 are variable between RpoD and SigA. Mutating these residues significantly improves SigA ability to complement E. coli UQ285. Only six of these residues fall into positions already known to interact with promoter DNA and to comprise a helix-turn-helix motif. The remaining variable positions are located on previously unexplored sites inside region σ4, specifically into the first two α-helices of the region. Neither of the variable positions confined to these helices seem to interact directly with promoter sequence; instead, we adduce that these residues participate allosterically by contributing to correct region folding and/or positioning of the HTH motif. We propose that transcriptional laxity is a mechanism for ensuring transcription in spite of naturally occurring mutations from endogenous promoters and/or horizontally transferred DNA sequences, allowing survival and fast environmental adaptation of α-proteobacteria. PMID:27468278

  11. The transcriptional regulator pool of the marine bacterium Rhodopirellula baltica SH 1T as revealed by whole genome comparisons.

    PubMed

    Lombardot, Thierry; Bauer, Margarete; Teeling, Hanno; Amann, Rudolf; Glöckner, Frank Oliver

    2005-01-01

    Rhodopirellula baltica (strain SH 1T) is a free-living marine representative of the phylogenetically independent and environmentally relevant phylum Planctomycetes. Little is known about the regulatory strategies of free-living bacteria with large (7.15 Mb) genomes. Therefore, a consistent, quantitative and qualitative description was produced by comparing R. baltica's transcriptional regulator pool with that of 123 publicly available bacterial genomes. The overall results are congruous with earlier observations that in Bacteria, the proportion of genes encoding transcriptional regulators generally increases with genome size. However, R. baltica distinctly stands out from this trend with only 2.4% (174) of all genes predicted to encode transcriptional regulators. The qualitative investigation of R. baltica's transcriptional regulators revealed a clear shift towards high numbers of two-component systems (66) as well as high numbers of sigma factors (49), with more than 76% (37) belonging to the extra-cytoplasmic function subfamily of sigma-70. Only one predicted sigma factor showed a relatively close phylogenetic relationship to that of another bacterium, the sigma factor SigZ of Bacillus subtilis. In summary, analysis of the R. baltica genome revealed disparate regulatory mechanisms and a clear bias towards direct environmental sensing. This strategy might provide a selective advantage for organisms living in habitats with frequently changing environmental conditions.

  12. The transcriptional response of Escherichia coli to recombinant protein insolubility.

    PubMed

    Smith, Harold E

    2007-03-01

    Bacterial production of recombinant proteins offers several advantages over alternative expression methods and remains the system of choice for many structural genomics projects. However, a large percentage of targets accumulate as insoluble inclusion bodies rather than soluble protein, creating a significant bottleneck in the protein production pipeline. Numerous strategies have been reported that can improve in vivo protein solubility, but most do not scale easily for high-throughput expression screening. To understand better the host cell response to the accumulation of insoluble protein, we determined genome-wide changes in bacterial gene expression upon induction of either soluble or insoluble target proteins. By comparing transcriptional profiles for multiple examples from the soluble or insoluble class, we identified a pattern of gene expression that correlates strongly with protein solubility. Direct targets of the sigma32 heat shock sigma factor, which includes genes involved in protein folding and degradation, were highly expressed in response to induction of insoluble protein. This same group of genes was also upregulated by insoluble protein accumulation under a different growth regime, indicating that sigma32-mediated gene expression is a general response to protein insolubility. This knowledge provides a starting point for the rational design of growth parameters and host strains with improved protein solubility characteristics. Summary Problems with protein solubility are frequently encountered when recombinant proteins are expressed in E. coli. The bacterial host responds to this problem by increasing expression of the protein folding machinery via the heat shock sigma factor sigma32. Manipulation of the sigma32 regulon might provide a general mechanism for improving recombinant protein solubility.

  13. ClpC regulates the fate of a sporulation initiation sigma factor, sigmaH protein, in Bacillus subtilis at elevated temperatures.

    PubMed

    Nanamiya, H; Ohashi, Y; Asai, K; Moriya, S; Ogasawara, N; Fujita, M; Sadaie, Y; Kawamura, F

    1998-07-01

    Using a strain carrying a clpC-bgaB transcriptional fusion at the amyE locus, we found that the expression of a clpC operon was induced at the end of exponential growth in a sigmaB-independent manner and ceased around T3.5 in the wild type but not in a spo0H mutant. This suggests that some gene product(s) whose expression is dependent on sigmaH function is required for the turn-off of clpC transcription during an early stage of sporulation. A clpC deletion mutant showed a temperature-sensitive sporulation phenotype and exhibited an abnormally large accumulation of sigmaH in the cell at 45 degrees C after T2, at which time the sigmaH level in the wild type had begun to decrease. These results, together with the fact that spo0H transcription in the clpC deletion mutant was similar to that of the wild type, suggested that ClpC may be responsible for the degradation of sigmaH after the accomplishment of its role in sporulation. Moreover, as expected from these results, overproduction of Spo0A was also observed after the initiation of sporulation in the clpC deletion mutant at 45 degrees C.

  14. The carbon isotope biogeochemistry of (epsilon)CO2 production in a methanogenic marine sediment

    NASA Technical Reports Server (NTRS)

    Boehme, Susan E.

    1993-01-01

    To investigate the relationship between sigma(CO2) delta(C-13) values and rates of the dominant remineralization processes at the organic-rich field site of Cape Lookout Bight, NC, the isotopic composition of porewater sigma(CO2) was measured on a seasonal basis. The sigma(CO2) delta(C-13) values varies seasonally in response to changes in rates of sulfate reduction and methanogenesis, the dominant remineralization processes at this site. A tube incubation experiment was also performed to determine the isotopic signature of the sigma(CO2) produced by sulfate reduction and methanogenesis. The delta(C-13) of the sigma(CO2) produced in the sulfate reduction zone determined from the tube incubation was -14.3 plus or minus 1.9, a value enriched in C-13 relative to the labile organic fraction. The C-13-enrichment may be caused by low rates of methanogenesis occurring in the sulfate reduction zone. The delta(C-13) of the sigma(CO2) produced in the methanogenic zone was estimated to be +44 per mil, whereas the co-produced methane was -65 per mil. The fractionation factor for CO2 reduction was calculated to be 1.055, a value in agreement with previous estimates at this site. The measured concentration and delta(C-13) of the sigma(CO2) at Cape Lookout was closely reproduced by a diagenetic model using the measured rates of sulfate reduction and sigma(CO2) production, and the isotopic signature of the sigma(CO2) production in the two biogeochemical zones.

  15. Role and regulation of sigma S in general resistance conferred by low-shear simulated microgravity in Escherichia coli.

    PubMed

    Lynch, S V; Brodie, E L; Matin, A

    2004-12-01

    Life on Earth evolved in the presence of gravity, and thus it is of interest from the perspective of space exploration to determine if diminished gravity affects biological processes. Cultivation of Escherichia coli under low-shear simulated microgravity (SMG) conditions resulted in enhanced stress resistance in both exponential- and stationary-phase cells, making the latter superresistant. Given that microgravity of space and SMG also compromise human immune response, this phenomenon constitutes a potential threat to astronauts. As low-shear environments are encountered by pathogens on Earth as well, SMG-conferred resistance is also relevant to controlling infectious disease on this planet. The SMG effect resembles the general stress response on Earth, which makes bacteria resistant to multiple stresses; this response is sigma s dependent, irrespective of the growth phase. However, SMG-induced increased resistance was dependent on sigma s only in stationary phase, being independent of this sigma factor in exponential phase. sigma s concentration was some 30% lower in exponential-phase SMG cells than in normal gravity cells but was twofold higher in stationary-phase SMG cells. While SMG affected sigma s synthesis at all levels of control, the main reasons for the differential effect of this gravity condition on sigma s levels were that it rendered the sigma protein less stable in exponential phase and increased rpoS mRNA translational efficiency. Since sigma s regulatory processes are influenced by mRNA and protein-folding patterns, the data suggest that SMG may affect these configurations.

  16. DO QUIESCENT AND ACTIVE GALAXIES HAVE DIFFERENT M{sub BH}-{sigma}{sub *} RELATIONS?

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Woo, Jong-Hak; Park, Daeseong; Kang, Wol-Rang

    To investigate the validity of the assumption that quiescent galaxies and active galaxies follow the same black hole mass (M{sub BH})-stellar velocity dispersion ({sigma}{sub *}) relation, as required for the calibration of M{sub BH} estimators for broad line active galactic nuclei (AGNs), we determine and compare the M{sub BH}-{sigma}{sub *} relations, respectively, for quiescent and active galaxies. For the quiescent galaxy sample, composed of 72 dynamical M{sub BH} measurements, we update {sigma}{sub *} for 28 galaxies using homogeneous H-band measurements that are corrected for galaxy rotation. For active galaxies, we collect 25 reverberation-mapped AGNs and improve {sigma}{sub *} measurement formore » two objects. Combining the two samples, we determine the virial factor f, first by scaling the active galaxy sample to the M{sub BH}-{sigma}{sub *} relation of quiescent galaxies, and second by simultaneously fitting the quiescent and active galaxy samples, as f=5.1{sub -1.1}{sup +1.5} and f=5.9{sub -1.5}{sup +2.1}, respectively. The M{sub BH}-{sigma}{sub *} relation of active galaxies appears to be shallower than that of quiescent galaxies. However, the discrepancy is caused by a difference in the accessible M{sub BH} distribution at given {sigma}{sub *}, primarily due to the difficulty of measuring reliable stellar velocity dispersion for the host galaxies of luminous AGNs. Accounting for the selection effects, we find that active and quiescent galaxies are consistent with following intrinsically the same M{sub BH}-{sigma}{sub *} relation.« less

  17. The anti-sigma factor RsrA responds to oxidative stress by reburying its hydrophobic core

    PubMed Central

    Rajasekar, Karthik V.; Zdanowski, Konrad; Yan, Jun; Hopper, Jonathan T. S.; Francis, Marie-Louise R.; Seepersad, Colin; Sharp, Connor; Pecqueur, Ludovic; Werner, Jörn M.; Robinson, Carol V.; Mohammed, Shabaz; Potts, Jennifer R.; Kleanthous, Colin

    2016-01-01

    Redox-regulated effector systems that counteract oxidative stress are essential for all forms of life. Here we uncover a new paradigm for sensing oxidative stress centred on the hydrophobic core of a sensor protein. RsrA is an archetypal zinc-binding anti-sigma factor that responds to disulfide stress in the cytoplasm of Actinobacteria. We show that RsrA utilizes its hydrophobic core to bind the sigma factor σR preventing its association with RNA polymerase, and that zinc plays a central role in maintaining this high-affinity complex. Oxidation of RsrA is limited by the rate of zinc release, which weakens the RsrA–σR complex by accelerating its dissociation. The subsequent trigger disulfide, formed between specific combinations of RsrA's three zinc-binding cysteines, precipitates structural collapse to a compact state where all σR-binding residues are sequestered back into its hydrophobic core, releasing σR to activate transcription of anti-oxidant genes. PMID:27432510

  18. Optimal design of stimulus experiments for robust discrimination of biochemical reaction networks.

    PubMed

    Flassig, R J; Sundmacher, K

    2012-12-01

    Biochemical reaction networks in the form of coupled ordinary differential equations (ODEs) provide a powerful modeling tool for understanding the dynamics of biochemical processes. During the early phase of modeling, scientists have to deal with a large pool of competing nonlinear models. At this point, discrimination experiments can be designed and conducted to obtain optimal data for selecting the most plausible model. Since biological ODE models have widely distributed parameters due to, e.g. biologic variability or experimental variations, model responses become distributed. Therefore, a robust optimal experimental design (OED) for model discrimination can be used to discriminate models based on their response probability distribution functions (PDFs). In this work, we present an optimal control-based methodology for designing optimal stimulus experiments aimed at robust model discrimination. For estimating the time-varying model response PDF, which results from the nonlinear propagation of the parameter PDF under the ODE dynamics, we suggest using the sigma-point approach. Using the model overlap (expected likelihood) as a robust discrimination criterion to measure dissimilarities between expected model response PDFs, we benchmark the proposed nonlinear design approach against linearization with respect to prediction accuracy and design quality for two nonlinear biological reaction networks. As shown, the sigma-point outperforms the linearization approach in the case of widely distributed parameter sets and/or existing multiple steady states. Since the sigma-point approach scales linearly with the number of model parameter, it can be applied to large systems for robust experimental planning. An implementation of the method in MATLAB/AMPL is available at http://www.uni-magdeburg.de/ivt/svt/person/rf/roed.html. flassig@mpi-magdeburg.mpg.de Supplementary data are are available at Bioinformatics online.

  19. Captodiamine, a putative antidepressant, enhances hypothalamic BDNF expression in vivo by synergistic 5-HT2c receptor antagonism and sigma-1 receptor agonism.

    PubMed

    Ring, Rebecca M; Regan, Ciaran M

    2013-10-01

    The putative antidepressant captodiamine is a 5-HT2c receptor antagonist and agonist at sigma-1 and D3 dopamine receptors, exerts an anti-immobility action in the forced swim paradigm, and enhances dopamine turnover in the frontal cortex. Captodiamine has also been found to ameliorate stress-induced anhedonia, reduce the associated elevations of hypothalamic corticotrophin-releasing factor (CRF) and restore the reductions in hypothalamic BDNF expression. Here we demonstrate chronic administration of captodiamine to have no significant effect on hypothalamic CRF expression through sigma-1 receptor agonism; however, both sigma-1 receptor agonism or 5-HT2c receptor antagonism were necessary to enhance BDNF expression. Regulation of BDNF expression by captodiamine was associated with increased phosphorylation of transcription factor CREB and mediated through sigma-1 receptor agonism but blocked by 5-HT2c receptor antagonism. The existence of two separate signalling pathways was confirmed by immunolocalisation of each receptor to distinct cell populations in the paraventricular nucleus of the hypothalamus. Increased BDNF induced by captodiamine was also associated with enhanced expression of synapsin, but not PSD-95, suggesting induction of long-term structural plasticity between hypothalamic synapses. These unique features of captodiamine may contribute to its ability to ameliorate stress-induced anhedonia as the hypothalamus plays a prominent role in regulating HPA axis activity.

  20. The response regulator expM is essential for the virulence of Erwinia carotovora subsp. carotovora and acts negatively on the sigma factor RpoS (sigma s).

    PubMed

    Andersson, R A; Palva, E T; Pirhonen, M

    1999-07-01

    The main virulence factors of Erwinia carotovora subsp. carotovora, the secreted, extracellular cell-wall-degrading enzymes, are controlled by several regulatory mechanisms. We have isolated transposon mutants with reduced virulence on tobacco. One of these mutants, with a mutation in a gene designated expM, was characterized in this study. This mutant produces slightly reduced amounts of extracellular enzymes in vitro and the secretion of the enzymes is also affected. The expM wild-type allele was cloned together with an upstream gene, designated expL, that has an unknown function. The expM gene was sequenced and found to encode a protein with similarity to the RssB/SprE protein of Escherichia coli and the MviA protein of Salmonella typhimurium. These proteins belong to a new type of two-component response regulators that negatively regulate the stability of the Sigma factor RpoS (sigma s) at the protein level. The results of this study suggest that ExpM has a similar function in E. carotovora subsp. carotovora. We also provide evidence that the overproduction of RpoS in the expM mutant is an important factor for the reduced virulence phenotype and that it partly causes the observed phenotype seen in vitro. However, an expM/rpoS double mutant is still affected in secretion of extracellular enzymes, suggesting that ExpM in addition to RpoS also acts on other targets.

  1. AtSIG6 and other members of the sigma gene family jointly but differentially determine plastid target gene expression in Arabidopsis thaliana

    PubMed Central

    Bock, Sylvia; Ortelt, Jennifer; Link, Gerhard

    2014-01-01

    Plants contain a nuclear gene family for plastid sigma factors, i.e., proteins that associate with the “bacterial-type” organellar RNA polymerase and confer the ability for correct promoter binding and transcription initiation. Questions that are still unresolved relate to the “division of labor” among members of the sigma family, both in terms of their range of target genes and their temporal and spatial activity during development. Clues to the in vivo role of individual sigma genes have mainly come from studies of sigma knockout lines. Despite its obvious strengths, however, this strategy does not necessarily trace-down causal relationships between mutant phenotype and a single sigma gene, if other family members act in a redundant and/or compensatory manner. We made efforts to reduce the complexity by genetic crosses of Arabidopsis single mutants (with focus on a chlorophyll-deficient sig6 line) to generate double knockout lines. The latter typically had a similar visible phenotype as the parental lines, but tended to be more strongly affected in the transcript patterns of both plastid and sigma genes. Because triple mutants were lethal under our growth conditions, we exploited a strategy of transformation of single and double mutants with RNAi constructs that contained sequences from the unconserved sigma region (UCR). These RNAi/knockout lines phenotypically resembled their parental lines, but were even more strongly affected in their plastid transcript patterns. Expression patterns of sigma genes revealed both similarities and differences compared to the parental lines, with transcripts at reduced or unchanged amounts and others that were found to be present in higher (perhaps compensatory) amounts. Together, our results reveal considerable flexibility of gene activity at the levels of both sigma and plastid gene expression. A (still viable) “basal state” seems to be reached, if 2–3 of the 6 Arabidopsis sigma genes are functionally compromised. PMID:25505479

  2. Thermo-labile stability of sigmaH (Spo0H) in temperature-sensitive spo0H mutants of Bacillus subtilis can be suppressed by mutations in RNA polymerase beta subunit.

    PubMed

    Ohashi, Y; Sugimaru, K; Nanamiya, H; Sebata, T; Asai, K; Yoshikawa, H; Kawamura, F

    1999-03-18

    We isolated novel temperature-sensitive mutants of spo0H, spo0H1 and spo0H5, having E61K and G30E amino-acid substitutions within the sigmaH protein, respectively, and located in the highly conserved region, "2", among prokaryotic sigma factors that participates in binding to core enzyme of RNA polymerase. These mutants showed a sporulation-deficient phenotype at 43 degrees C. Moreover, we successfully isolated suppressor mutants that were spontaneously generated from the spo0H mutants. Our genetic analysis of these suppressor mutations revealed that the suppressor mutations are within the rpoB gene coding for the beta subunit of RNA polymerase. The mutations caused single amino-acid substitutions, E857A and P1055S, in rpoB18 and rpoB532 mutants that were generated from spo0H1 and spo0H5, respectively. Whereas the sigmaH-dependent expression of a spo0A-bgaB fusion was greatly reduced in both spo0H mutants, their expression was partially restored in the suppressor mutants at 43 degrees C. Western blot analysis showed that the level of sigmaH protein in the wild type increased between T0 and T2 and decreased after T3, while the level of sigmaH protein in spo0H mutants was greatly reduced throughout growth, indicating that the mutant sigmaH proteins were rapidly degraded by some unknown proteolytic enzyme(s). The analysis of the half-life of sigmaH protein showed that the short life of sigmaH in spo0H mutants is prolonged in the suppressor mutants. These findings suggest that, at least to some extent, the process of E-sigmaH formation may be involved in stabilization of sigmaH at the onset of sporulation.

  3. [Improvement of medical processes with Six Sigma - practicable zero-defect quality in preparation for surgery].

    PubMed

    Sobottka, Stephan B; Töpfer, Armin; Eberlein-Gonska, Maria; Schackert, Gabriele; Albrecht, D Michael

    2010-01-01

    Six Sigma is an innovative management- approach to reach practicable zero- defect quality in medical service processes. The Six Sigma principle utilizes strategies, which are based on quantitative measurements and which seek to optimize processes, limit deviations or dispersion from the target process. Hence, Six Sigma aims to eliminate errors or quality problems of all kinds. A pilot project to optimize the preparation for neurosurgery could now show that the Six Sigma method enhanced patient safety in medical care, while at the same time disturbances in the hospital processes and failure costs could be avoided. All six defined safety relevant quality indicators were significantly improved by changes in the workflow by using a standardized process- and patient- oriented approach. Certain defined quality standards such as a 100% complete surgical preparation at start of surgery and the required initial contact of the surgeon with the patient/ surgical record on the eve of surgery could be fulfilled within the range of practical zero- defect quality. Likewise, the degree of completion of the surgical record by 4 p.m. on the eve of surgery and their quality could be improved by a factor of 170 and 16, respectively, at sigma values of 4.43 and 4.38. The other two safety quality indicators "non-communicated changes in the OR- schedule" and the "completeness of the OR- schedule by 12:30 a.m. on the day before surgery" also show an impressive improvement by a factor of 2.8 and 7.7, respectively, corresponding with sigma values of 3.34 and 3.51. The results of this pilot project demonstrate that the Six Sigma method is eminently suitable for improving quality of medical processes. In our experience this methodology is suitable, even for complex clinical processes with a variety of stakeholders. In particular, in processes in which patient safety plays a key role, the objective of achieving a zero- defect quality is reasonable and should definitely be aspirated. Copyright © 2010. Published by Elsevier GmbH.

  4. A UNIVERSAL NEUTRAL GAS PROFILE FOR NEARBY DISK GALAXIES

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bigiel, F.; Blitz, L., E-mail: bigiel@uni-heidelberg.de

    2012-09-10

    Based on sensitive CO measurements from HERACLES and H I data from THINGS, we show that the azimuthally averaged radial distribution of the neutral gas surface density ({Sigma}{sub HI}+ {Sigma}{sub H2}) in 33 nearby spiral galaxies exhibits a well-constrained universal exponential distribution beyond 0.2 Multiplication-Sign r{sub 25} (inside of which the scatter is large) with less than a factor of two scatter out to two optical radii r{sub 25}. Scaling the radius to r{sub 25} and the total gas surface density to the surface density at the transition radius, i.e., where {Sigma}{sub HI} and {Sigma}{sub H2} are equal, as wellmore » as removing galaxies that are interacting with their environment, yields a tightly constrained exponential fit with average scale length 0.61 {+-} 0.06 r{sub 25}. In this case, the scatter reduces to less than 40% across the optical disks (and remains below a factor of two at larger radii). We show that the tight exponential distribution of neutral gas implies that the total neutral gas mass of nearby disk galaxies depends primarily on the size of the stellar disk (influenced to some degree by the great variability of {Sigma}{sub H2} inside 0.2 Multiplication-Sign r{sub 25}). The derived prescription predicts the total gas mass in our sub-sample of 17 non-interacting disk galaxies to within a factor of two. Given the short timescale over which star formation depletes the H{sub 2} content of these galaxies and the large range of r{sub 25} in our sample, there appears to be some mechanism leading to these largely self-similar radial gas distributions in nearby disk galaxies.« less

  5. Assignment of the zinc ligands in RsrA, a redox-sensing ZAS protein from Streptomyces coelicolor.

    PubMed

    Zdanowski, Konrad; Doughty, Phillip; Jakimowicz, Piotr; O'Hara, Liisa; Buttner, Mark J; Paget, Mark S B; Kleanthous, Colin

    2006-07-11

    ZAS proteins are widespread bacterial zinc-containing anti-sigma factors that regulate the activity of sigma factors in response to diverse cues. One of the best characterized ZAS proteins is RsrA from Streptomyces coelicolor, which responds to disulfide stress. Zn-RsrA binds and represses the transcriptional activity of sigmaR in the reducing environment of the cytoplasm but undergoes reversible, intramolecular disulfide bond formation during oxidative stress. This expels the single metal ion and causes dramatic structural changes in RsrA that result in its dissociation from sigmaR, leaving the sigma factor free to activate the transcription of antioxidant genes. We showed recently that Zn2+ serves a critical role in modulating the redox activity of RsrA thiols but uncertainty remains as to how the metal ion is coordinated in RsrA and related ZAS proteins. Using a combination of random and site-specific mutagenesis with zinc K-edge extended X-ray absorption fine structure (EXAFS) spectroscopy, we have assigned unambiguously the metal ligands in RsrA, thereby distinguishing between the different ligation models that have been proposed. The data show that the zinc site in RsrA is comprised of Cys11, His37, Cys41, and Cys44. Three of these residues are part of a conserved ZAS-specific sequence motif (H37xxxC41xxC44), with the fourth ligand, Cys11, found in a subset of ZAS proteins. Cys11 and Cys44 form the trigger disulfide in RsrA, explaining why the metal ion is expelled during oxidation. We discuss these data in the context of redox sensing by RsrA and the sensory mechanisms of other ZAS proteins.

  6. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Shaing, K.C.

    The poloidal flow damping rate in the vicinity of the magnetic axis in tokamaks is calculated using the time-dependent plasma viscosity. It is found that the damping rate is of the order of {nu}{sub ii}/f{sub t}{sup 2}, where {nu}{sub ii} is the ion-ion collision frequency, and f{sub t} is the fraction of the trapped potatoes. The corresponding neoclassical polarization or inertia enhancement factor is [1+({sigma}{sub p}q{sup 2}/f{sub t})], where {sigma}{sub p} is a numerical number of the order of unity, and q is the safety factor.

  7. 14-3-3 sigma and 14-3-3 zeta plays an opposite role in cell growth inhibition mediated by transforming growth factor-beta 1.

    PubMed

    Hong, Hye-Young; Jeon, Woo-Kwang; Bae, Eun-Jin; Kim, Shin-Tae; Lee, Ho-Jae; Kim, Seong-Jin; Kim, Byung-Chul

    2010-03-01

    The expression of 14-3-3 proteins is dysregulated in various types of cancer. This study was undertaken to investigate the effects of 14-3-3 zeta and 14-3-3 sigma on cell growth inhibition mediated by transforming growth factor-beta 1 (TGF-beta1). Mouse mammary epithelial cells (Eph4) that are transformed with oncogenic c-H-Ras (EpRas) and no longer sensitive to TGF-beta1-mediated growth inhibition displayed increased expression of 14-3-3 zeta and decreased expression of 14-3-3 sigma compared with parental Eph4 cells. Using small interfering RNA-mediated knockdown and overexpression of 14-3-3 sigma or 14-3-3 zeta, we showed that 14-3-3 sigma is required for TGF-beta1-mediated growth inhibition whereas 14-3-3 zeta negatively modulates this growth inhibitory response. Notably, overexpression of 14-3-3 zeta increased the level of Smad3 protein that is phosphorylated at linker regions and cannot mediate the TGF-beta1 growth inhibitory response. Consistent with this finding, mutation of the 14-3-3 zeta phosphorylation sites in Smad3 markedly reduced the 14-3-3 zeta-mediated inhibition of TGF-beta1-induced p15 promoter-reporter activity and cell cycle arrest, suggesting that these residues are critical targets of 14-3-3 zeta in the suppression of TGF-beta1-mediated growth. Taken together, our findings indicate that dysregulation of 14-3-3 sigma or 14-3-3 zeta contributes to TGF-beta1 resistance in cancer cells.

  8. THE STAR FORMATION LAWS OF EDDINGTON-LIMITED STAR-FORMING DISKS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ballantyne, D. R.; Armour, J. N.; Indergaard, J., E-mail: david.ballantyne@physics.gatech.edu

    2013-03-10

    Two important avenues into understanding the formation and evolution of galaxies are the Kennicutt-Schmidt (K-S) and Elmegreen-Silk (E-S) laws. These relations connect the surface densities of gas and star formation ({Sigma}{sub gas} and {Sigma}-dot{sub *}, respectively) in a galaxy. To elucidate the K-S and E-S laws for disks where {Sigma}{sub gas} {approx}> 10{sup 4} M{sub Sun} pc{sup -2}, we compute 132 Eddington-limited star-forming disk models with radii spanning tens to hundreds of parsecs. The theoretically expected slopes ( Almost-Equal-To 1 for the K-S law and Almost-Equal-To 0.5 for the E-S relation) are relatively robust to spatial averaging over the disks.more » However, the star formation laws exhibit a strong dependence on opacity that separates the models by the dust-to-gas ratio that may lead to the appearance of a erroneously large slope. The total infrared luminosity (L{sub TIR}) and multiple carbon monoxide (CO) line intensities were computed for each model. While L{sub TIR} can yield an estimate of the average {Sigma}-dot{sub *} that is correct to within a factor of two, the velocity-integrated CO line intensity is a poor proxy for the average {Sigma}{sub gas} for these warm and dense disks, making the CO conversion factor ({alpha}{sub CO}) all but useless. Thus, observationally derived K-S and E-S laws at these values of {Sigma}{sub gas} that uses any transition of CO will provide a poor measurement of the underlying star formation relation. Studies of the star formation laws of Eddington-limited disks will require a high-J transition of a high density molecular tracer, as well as a sample of galaxies with known metallicity estimates.« less

  9. Responsibility Factors of Reducing Inefficiencies in Information System Processes and Their Role on Intention to Acquire Six Sigma Certification

    ERIC Educational Resources Information Center

    Hejazi, Sara

    2009-01-01

    Organizations worldwide have been turning to Six Sigma program (SSP) to eliminate the defects in their products or drive out the variability in their processes to attain a competitive advantage in their marketplace. An effective certification program has been touted as a major contributor to successful implementation of SSP. An effective…

  10. The Clostridium sporulation programs: diversity and preservation of endospore differentiation.

    PubMed

    Al-Hinai, Mohab A; Jones, Shawn W; Papoutsakis, Eleftherios T

    2015-03-01

    Bacillus and Clostridium organisms initiate the sporulation process when unfavorable conditions are detected. The sporulation process is a carefully orchestrated cascade of events at both the transcriptional and posttranslational levels involving a multitude of sigma factors, transcription factors, proteases, and phosphatases. Like Bacillus genomes, sequenced Clostridium genomes contain genes for all major sporulation-specific transcription and sigma factors (spo0A, sigH, sigF, sigE, sigG, and sigK) that orchestrate the sporulation program. However, recent studies have shown that there are substantial differences in the sporulation programs between the two genera as well as among different Clostridium species. First, in the absence of a Bacillus-like phosphorelay system, activation of Spo0A in Clostridium organisms is carried out by a number of orphan histidine kinases. Second, downstream of Spo0A, the transcriptional and posttranslational regulation of the canonical set of four sporulation-specific sigma factors (σ(F), σ(E), σ(G), and σ(K)) display different patterns, not only compared to Bacillus but also among Clostridium organisms. Finally, recent studies demonstrated that σ(K), the last sigma factor to be activated according to the Bacillus subtilis model, is involved in the very early stages of sporulation in Clostridium acetobutylicum, C. perfringens, and C. botulinum as well as in the very late stages of spore maturation in C. acetobutylicum. Despite profound differences in initiation, propagation, and orchestration of expression of spore morphogenetic components, these findings demonstrate not only the robustness of the endospore sporulation program but also the plasticity of the program to generate different complex phenotypes, some apparently regulated at the epigenetic level. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  11. The Clostridium Sporulation Programs: Diversity and Preservation of Endospore Differentiation

    PubMed Central

    Al-Hinai, Mohab A.; Jones, Shawn W.

    2015-01-01

    SUMMARY Bacillus and Clostridium organisms initiate the sporulation process when unfavorable conditions are detected. The sporulation process is a carefully orchestrated cascade of events at both the transcriptional and posttranslational levels involving a multitude of sigma factors, transcription factors, proteases, and phosphatases. Like Bacillus genomes, sequenced Clostridium genomes contain genes for all major sporulation-specific transcription and sigma factors (spo0A, sigH, sigF, sigE, sigG, and sigK) that orchestrate the sporulation program. However, recent studies have shown that there are substantial differences in the sporulation programs between the two genera as well as among different Clostridium species. First, in the absence of a Bacillus-like phosphorelay system, activation of Spo0A in Clostridium organisms is carried out by a number of orphan histidine kinases. Second, downstream of Spo0A, the transcriptional and posttranslational regulation of the canonical set of four sporulation-specific sigma factors (σF, σE, σG, and σK) display different patterns, not only compared to Bacillus but also among Clostridium organisms. Finally, recent studies demonstrated that σK, the last sigma factor to be activated according to the Bacillus subtilis model, is involved in the very early stages of sporulation in Clostridium acetobutylicum, C. perfringens, and C. botulinum as well as in the very late stages of spore maturation in C. acetobutylicum. Despite profound differences in initiation, propagation, and orchestration of expression of spore morphogenetic components, these findings demonstrate not only the robustness of the endospore sporulation program but also the plasticity of the program to generate different complex phenotypes, some apparently regulated at the epigenetic level. PMID:25631287

  12. The Clostridium Sporulation Programs: Diversity and Preservation of Endospore Differentiation

    DOE PAGES

    Al-Hinai, Mohab A.; Jones, Shawn W.; Papoutsakis, Eleftherios T.

    2015-01-28

    Bacillus and Clostridium organisms initiate the sporulation process when unfavorable conditions are detected. The sporulation process is a carefully orchestrated cascade of events at both the transcriptional and posttranslational levels involving a multitude of sigma factors, transcription factors, proteases, and phosphatases. Like Bacillus genomes, sequenced Clostridium genomes contain genes for all major sporulation-specific transcription and sigma factors (spo0A, sigH, sigF, sigE, sigG, and sigK) that orchestrate the sporulation program. However, recent studies have shown that there are substantial differences in the sporulation programs between the two genera as well as among different Clostridium species. First, in the absence of amore » Bacillus-like phosphorelay system, activation of Spo0A in Clostridium organisms is carried out by a number of orphan histidine kinases. Second, downstream of Spo0A, the transcriptional and posttranslational regulation of the canonical set of four sporulation-specific sigma factors (σF, σE, σG, and σK) display different patterns, not only compared to Bacillus but also among Clostridium organisms. Finally, recent studies demonstrated that σK, the last sigma factor to be activated according to the Bacillus subtilis model, is involved in the very early stages of sporulation in Clostridium acetobutylicum, C. perfringens, and C. botulinum as well as in the very late stages of spore maturation in C. acetobutylicum. Despite profound differences in initiation, propagation, and orchestration of expression of spore morphogenetic components, these findings demonstrate not only the robustness of the endospore sporulation program but also the plasticity of the program to generate different complex phenotypes, some apparently regulated at the epigenetic level.« less

  13. Differential Mechanisms of Binding of Anti-Sigma Factors Escherichia coli Rsd and Bacteriophage T4 AsiA to E. coli RNA Polymerase Lead to Diverse Physiological Consequences▿

    PubMed Central

    Sharma, Umender K.; Chatterji, Dipankar

    2008-01-01

    Anti-sigma factors Escherichia coli Rsd and bacteriophage T4 AsiA bind to the essential housekeeping sigma factor, σ70, of E. coli. Though both factors are known to interact with the C-terminal region of σ70, the physiological consequences of these interactions are very different. This study was undertaken for the purpose of deciphering the mechanisms by which E. coli Rsd and bacteriophage T4 AsiA inhibit or modulate the activity of E. coli RNA polymerase, which leads to the inhibition of E. coli cell growth to different amounts. It was found that AsiA is the more potent inhibitor of in vivo transcription and thus causes higher inhibition of E. coli cell growth. Measurements of affinity constants by surface plasmon resonance experiments showed that Rsd and AsiA bind to σ70 with similar affinity. Data obtained from in vivo and in vitro binding experiments clearly demonstrated that the major difference between AsiA and Rsd is the ability of AsiA to form a stable ternary complex with RNA polymerase. The binding patterns of AsiA and Rsd with σ70 studied by using the yeast two-hybrid system revealed that region 4 of σ70 is involved in binding to both of these anti-sigma factors; however, Rsd interacts with other regions of σ70 as well. Taken together, these results suggest that the higher inhibition of E. coli growth by AsiA expression is probably due to the ability of the AsiA protein to trap the holoenzyme RNA polymerase rather than its higher binding affinity to σ70. PMID:18359804

  14. Comparative analyses imply that the enigmatic sigma factor 54 is a central controller of the bacterial exterior

    PubMed Central

    2011-01-01

    Background Sigma-54 is a central regulator in many pathogenic bacteria and has been linked to a multitude of cellular processes like nitrogen assimilation and important functional traits such as motility, virulence, and biofilm formation. Until now it has remained obscure whether these phenomena and the control by Sigma-54 share an underlying theme. Results We have uncovered the commonality by performing a range of comparative genome analyses. A) The presence of Sigma-54 and its associated activators was determined for all sequenced prokaryotes. We observed a phylum-dependent distribution that is suggestive of an evolutionary relationship between Sigma-54 and lipopolysaccharide and flagellar biosynthesis. B) All Sigma-54 activators were identified and annotated. The relation with phosphotransfer-mediated signaling (TCS and PTS) and the transport and assimilation of carboxylates and nitrogen containing metabolites was substantiated. C) The function annotations, that were represented within the genomic context of all genes encoding Sigma-54, its activators and its promoters, were analyzed for intra-phylum representation and inter-phylum conservation. Promoters were localized using a straightforward scoring strategy that was formulated to identify similar motifs. We found clear highly-represented and conserved genetic associations with genes that concern the transport and biosynthesis of the metabolic intermediates of exopolysaccharides, flagella, lipids, lipopolysaccharides, lipoproteins and peptidoglycan. Conclusion Our analyses directly implicate Sigma-54 as a central player in the control over the processes that involve the physical interaction of an organism with its environment like in the colonization of a host (virulence) or the formation of biofilm. PMID:21806785

  15. Calculated hydroxyl A2 sigma --> X2 pi (0, 0) band emission rate factors applicable to atmospheric spectroscopy

    NASA Technical Reports Server (NTRS)

    Cageao, R. P.; Ha, Y. L.; Jiang, Y.; Morgan, M. F.; Yung, Y. L.; Sander, S. P.

    1997-01-01

    A calculation of the A2 sigma --> X2 pi (0, 0) band emission rate factors and line center absorption cross sections of OH applicable to its measurement using solar resonant fluorescence in the terrestrial atmosphere is presented in this paper. The most accurate available line parameters have been used. Special consideration has been given to the solar input flux because of its highly structured Fraunhofer spectrum. The calculation for the OH atmospheric emission rate factor in the solar resonant fluorescent case is described in detail with examples and intermediate results. Results of this calculation of OH emission rate factors for individual rotational lines are on average 30% lower than the values obtained in an earlier work.

  16. A Mutation in the Bacillus subtilis rsbU Gene That Limits RNA Synthesis during Sporulation.

    PubMed

    Rothstein, David M; Lazinski, David; Osburne, Marcia S; Sonenshein, Abraham L

    2017-07-15

    Mutants of Bacillis subtilis that are temperature sensitive for RNA synthesis during sporulation were isolated after selection with a 32 P suicide agent. Whole-genome sequencing revealed that two of the mutants carried an identical lesion in the rsbU gene, which encodes a phosphatase that indirectly activates SigB, the stress-responsive RNA polymerase sigma factor. The mutation appeared to cause RsbU to be hyperactive, because the mutants were more resistant than the parent strain to ethanol stress. In support of this hypothesis, pseudorevertants that regained wild-type levels of sporulation at high temperature had secondary mutations that prevented expression of the mutant rsbU gene. The properties of these RsbU mutants support the idea that activation of SigB diminishes the bacterium's ability to sporulate. IMPORTANCE Most bacterial species encode multiple RNA polymerase promoter recognition subunits (sigma factors). Each sigma factor directs RNA polymerase to different sets of genes; each gene set typically encodes proteins important for responses to specific environmental conditions, such as changes in temperature, salt concentration, and nutrient availability. A selection for mutants of Bacillus subtilis that are temperature sensitive for RNA synthesis during sporulation unexpectedly yielded strains with a point mutation in rsbU , a gene that encodes a protein that normally activates sigma factor B (SigB) under conditions of salt stress. The mutation appears to cause RsbU, and therefore SigB, to be active inappropriately, thereby inhibiting, directly or indirectly, the ability of the cells to transcribe sporulation genes. Copyright © 2017 American Society for Microbiology.

  17. 76 FR 35476 - Notice of Determinations Regarding Eligibility To Apply for Worker Adjustment Assistance and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-17

    ...' industry (i.e., conditions within the industry are adverse). Affirmative Determinations for Worker...' industry are not adverse. None. Negative Determinations for Worker Adjustment Assistance and Alternative...,095; 6ixSigma Apparel Network, LLC, New York, NY. The investigation revealed that criteria of Section...

  18. B-jet and c-jet identification with Neural Networks as well as combination of multivariate analyses for the search for of multivariate analyses for the search for single top-quark production

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Renz, Manuel; /Karlsruhe U., EKP

    2008-06-01

    In the first part of this diploma thesis, the current version of the KIT Flavor Separator, a neural network which is able to distinguish between tagged b-quark jets and tagged c/light-quark jets, is presented. In comparison with previous versions four new input variables are utilized and new Monte Carlo samples with a larger number of simulated events are used for the training of the neural network. It is illustrated that the output of the neural network is continuously distributed between 1 and -1, whereas b-quark jets accumulate at 1, however, c-quark jets and light-quark jets have outputs next to -1.more » To ensure that the network output describes observed events correctly, the shapes of all input variables are compared in simulation and data. Thus the mismodelling of any input variable is excluded. Moreover, the b jet and light jet output distributions are compared with the output of samples of observed events, which are enhanced in the particular flavor. In contrast to previous versions, no b-jet output correction function has to be calculated, because the agreement between simulation and collision data is excellent for b-quark jets. For the light-jet output, correction functions are developed. Different applications of the KIT Flavor Separator are mentioned. For example it provides a precious input to all three CDF single top quark analyses. Furthermore, it is shown that the KIT Flavor Separator is a universal tool, which can be used in every high-p{sub T} analysis that requires the identification of b-quark jets with high efficiency. As it is pointed out, a further application is the estimation of the flavor composition of a given sample of observed events. In addition a neural network, which is able to separate c-quark jets from light-quark jets, is trained. It is shown, that all three flavors can be separated in the c-net-Flavor Separator plane. As a result, the uncertainties on the estimation of the flavor composition in events with one tagged jet are cut into half. In the second part of this diploma thesis, a method for the combination of three multivariate single-top analyses using an integrated luminosity of 2.2 fb{sup -1} is presented. For this purpose the discriminants of the Likelihood Function analysis, the Matrix Element method and the Neural Network analysis are used as input variables to a neural network. Overall four different networks are trained, one for events with two or three jets and one or two SecVtx tags, respectively. Using a binned likelihood function, the outputs of these networks are fitted to the output distribution of observed events. A single top-quark production cross section of {sigma}{sub single-top} = 2.2{sub -0.7}{sup +0.8} pb is measured. Ensemble tests are performed for the calculation of the sensitivity and observed significance, which are found to be 4.8{sigma} and 3.9{sigma}, respectively. Hence the improvement of this combination is roughly 8% in comparison with sensitivities found by the individual analyses. Due to the proportionality of {sigma}{sub single-top} and |V{sub tb}|{sup 2} and under the assumption V{sub tb} >> V{sub ts}, V{sub td}, a value for |V{sub tb}| is quoted: |V{sub tb}| = 0.88{sub -0.12}{sup +0.14}(exp.) {+-} 0.07(theo.). It can be seen, that the given uncertainties are too large for a verification or falsification of the unitarity assumption of the CKM-matrix. Parallel to this combination a further combination method (NEAT-combination) has been developed. This combination uses a neural network trained with a neuroevolution technique, which optimizes the neural network architecture and weights through the use of genetic algorithms. In this analysis an improvement of roughly 12% could be reached. In figure 7.1 the current situation for the measurement of the single top-quark production cross section is summarized. After collecting more data, CDF will be able to observe single top-quark production with a significance larger than 5.0{sigma}. Nevertheless, the cross section measurement will still have large uncertainties on the level of 20%. Precise measurements on the few percent level will only be possible at the LHC. Recent studies for the CMS detector showed, that the t-channel cross section can be measured with an accuracy of 7% in 1 fb{sup -1} of LHC data.« less

  19. Strong leadership: the case for global connections.

    PubMed

    Rosser, Elizabeth A; Scammell, Janet; Bevan, Ann; Hundley, Vanora A

    2017-04-01

    To identify how nurse leaders view and experience the opportunities offered by one of the largest global nursing organisations Sigma Theta Tau International. Worldwide, nursing leadership is challenged with addressing the complex issues impacting on care delivery. International nursing organisations are a means to bring together individuals to promote leadership and scholarship for nursing practice to promote patient safety and quality care. The newly established all-England chapter of Sigma Theta Tau International is a recent addition to the society in terms of nurse leadership in Europe, as such faces challenges as it establishes its identity and seeks to interpret the organisational vision: to advance world health through nursing leadership and scholarship. Moving forward, members views were sought on the goals of the chapter and how they may be enacted. In July 2013, all chapter members at that time had been nominated on the basis of achievement in nurse leadership; all were invited to participate in an online survey. The online questionnaire contained a series of closed and open questions. Most respondents joined because they believed in the vision and networking opportunities Sigma Theta Tau International provides. Three themes were extracted from the data: the value of networking and communication, leadership and the development of culturally sensitive organisations and the need for shared scholarship for nursing practice. Findings indicate the growth of effective leadership at all levels of nursing could be harnessed through successful collaboration and keen support for robust connections between practice and education to promote quality care. Whilst challenging, globalisation presents an opportunity for a nursing society such as Sigma Theta Tau International to work collaboratively to address healthcare issues. A nursing society that explores and resolves its own complex issues by actively promoting leadership and collaborative scholarship reveals a potential to empower the profession to share our collective solutions towards enhancing clinical practice. © 2016 John Wiley & Sons Ltd.

  20. The Measurement of Strong-Interaction Effects in High-Z Sigma Hyperonic Atoms.

    NASA Astrophysics Data System (ADS)

    Phillips, William Clarke

    Strong-interaction effects have been observed in the X-ray spectra of atoms formed with Sigma ^- in lead and tungsten. In the experiment, performed at the Alternating Gradient Synchrotron of Brookhaven National Laboratory, negative kaons were brought to rest in a novel laminar target consisting of thin sheets of high-Z material in a liquid hydrogen bath. The geometry of the target was designed to optimize the production of high-Z Sigma^- atoms and the detection of their subsequent de-excitation X rays. A method of identifying the energetic pi^+ from the production reaction K^-+ p toSigma^- +pi^+ resulted in a factor of 15 improvement in the signal-to -noise ratio of the Sigma^- atom X-rays over that of previous experiments. The X-ray spectra were recorded by three high-resolution intrinsic Ge detectors and analyzed for shifts, broadenings, and yield reductions of the final X-ray transitions before absorption of the Sigma^- into the nucleus. A lineshape function which reflected the non-Gaussian response of the X-ray spectroscopy system was developed for this analysis. The results are(UNFORMATTED TABLE OR EQUATION FOLLOWS)eqalign {Sigma^- - W (10to9): varepsilon = 650 +/- 30 eV,&quadGamma = 380 +/- 70 eV,quad %Y = .98 +/- .04cr Sigma^- - Pb (10to9): varepsilon = 510 +/- 50 eV,&quadGamma = 290 +/- 140 eV, quad %Y = .53 +/- .04cr} (TABLE/EQUATION ENDS)where varepsilon = E_{rm meds} - E_{rm calc }, Gamma is the Lorentzian FWHM, and %Y is the ratio (measured yield)/(yield calculated with no strong interaction). Optical model calculations with a = (0.928 + i0.022) fm are able to reproduce all observed effects in the Sigma^--W spectra. Such calculations with a = (0.247 + i0.039) fm reproduce the observed shift and width of the (10to9) transition in Sigma^--Pb, but fail to reproduce the observed yield reduction. It is doubtful if the current status of the theory of Sigma ^--N interactions can explain this discrepancy.

  1. Genome-wide dynamics of a bacterial response to antibiotics that target the cell envelope

    PubMed Central

    2011-01-01

    Background A decline in the discovery of new antibacterial drugs, coupled with a persistent rise in the occurrence of drug-resistant bacteria, has highlighted antibiotics as a diminishing resource. The future development of new drugs with novel antibacterial activities requires a detailed understanding of adaptive responses to existing compounds. This study uses Streptomyces coelicolor A3(2) as a model system to determine the genome-wide transcriptional response following exposure to three antibiotics (vancomycin, moenomycin A and bacitracin) that target distinct stages of cell wall biosynthesis. Results A generalised response to all three antibiotics was identified which involves activation of transcription of the cell envelope stress sigma factor σE, together with elements of the stringent response, and of the heat, osmotic and oxidative stress regulons. Attenuation of this system by deletion of genes encoding the osmotic stress sigma factor σB or the ppGpp synthetase RelA reduced resistance to both vancomycin and bacitracin. Many antibiotic-specific transcriptional changes were identified, representing cellular processes potentially important for tolerance to each antibiotic. Sensitivity studies using mutants constructed on the basis of the transcriptome profiling confirmed a role for several such genes in antibiotic resistance, validating the usefulness of the approach. Conclusions Antibiotic inhibition of bacterial cell wall biosynthesis induces both common and compound-specific transcriptional responses. Both can be exploited to increase antibiotic susceptibility. Regulatory networks known to govern responses to environmental and nutritional stresses are also at the core of the common antibiotic response, and likely help cells survive until any specific resistance mechanisms are fully functional. PMID:21569315

  2. MOLECULAR GAS AND STAR FORMATION IN NEARBY DISK GALAXIES

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Leroy, Adam K.; Munoz-Mateos, Juan-Carlos; Walter, Fabian

    2013-08-01

    We compare molecular gas traced by {sup 12}CO (2-1) maps from the HERACLES survey, with tracers of the recent star formation rate (SFR) across 30 nearby disk galaxies. We demonstrate a first-order linear correspondence between {Sigma}{sub mol} and {Sigma}{sub SFR} but also find important second-order systematic variations in the apparent molecular gas depletion time, {tau}{sub dep}{sup mol}={Sigma}{sub mol}/{Sigma}{sub SFR}. At the 1 kpc common resolution of HERACLES, CO emission correlates closely with many tracers of the recent SFR. Weighting each line of sight equally, using a fixed {alpha}{sub CO} equivalent to the Milky Way value, our data yield a molecularmore » gas depletion time, {tau}{sub dep}{sup mol}={Sigma}{sub mol}/{Sigma}{sub SFR}{approx}2.2 Gyr with 0.3 dex 1{sigma} scatter, in very good agreement with recent literature data. We apply a forward-modeling approach to constrain the power-law index, N, that relates the SFR surface density and the molecular gas surface density, {Sigma}{sub SFR}{proportional_to}{Sigma}{sub mol}{sup N}. We find N = 1 {+-} 0.15 for our full data set with some scatter from galaxy to galaxy. This also agrees with recent work, but we caution that a power-law treatment oversimplifies the topic given that we observe correlations between {tau}{sub dep}{sup mol} and other local and global quantities. The strongest of these are a decreased {tau}{sub dep}{sup mol} in low-mass, low-metallicity galaxies and a correlation of the kpc-scale {tau}{sub dep}{sup mol} with dust-to-gas ratio, D/G. These correlations can be explained by a CO-to-H{sub 2} conversion factor ({alpha}{sub CO}) that depends on dust shielding, and thus D/G, in the theoretically expected way. This is not a unique interpretation, but external evidence of conversion factor variations makes this the most conservative explanation of the strongest observed {tau}{sub dep}{sup mol} trends. After applying a D/G-dependent {alpha}{sub CO}, some weak correlations between {tau}{sub dep}{sup mol} and local conditions persist. In particular, we observe lower {tau}{sub dep}{sup mol} and enhanced CO excitation associated with nuclear gas concentrations in a subset of our targets. These appear to reflect real enhancements in the rate of star formation per unit gas, and although the distribution of {tau}{sub dep} does not appear bimodal in galaxy centers, {tau}{sub dep} does appear multivalued at fixed {Sigma}{sub H2}, supporting the idea of ''disk'' and ''starburst'' modes driven by other environmental parameters.« less

  3. Site term from single-station sigma analysis of S-waves in western Turkey

    NASA Astrophysics Data System (ADS)

    Akyol, Nihal

    2018-05-01

    The main aim of this study is to obtain site terms from single-station sigma analysis and to compare them with the site functions resulting from different techniques. The dataset consists of 1764 records from 322 micro- and moderate-size local earthquakes recorded by 29 stations in western Turkey. Median models were derived from S-wave Fourier amplitude spectra for selected 22 frequencies, by utilizing the MLR procedure which performs the maximum likelihood (ML) estimation of mixed models where the fixed effects are treated as random (R) effects with infinite variance. At this stage, b (geometrical spreading coefficient) and Q (quality factor) values were decomposed, simultaneously. The residuals of the median models were examined by utilizing the single-station sigma analysis to obtain the site terms of 29 stations. Sigma for the median models is about 0.422 log10 units and decreases to about 0.308, when the site terms from the single-station sigma analysis were considered (27% reduction). The event-corrected within-event standard deviations for each frequency are rather stable, in the range 0.19-0.23 log10 units with an average value of 0.20 (± 0.01). The site terms from single-station sigma analysis were compared with the site function estimates from the horizontal-to-vertical-spectral-ratio (HVSR) and generalized inversion (INV) techniques by Akyol et al. (2013) and Kurtulmuş and Akyol (2015), respectively. Consistency was observed between the single-station sigma site terms and the INV site transfer functions. The results imply that the single-station sigma analysis could separate the site terms with respect to the median models.

  4. Providing critical laboratory results on time, every time to help reduce emergency department length of stay: how our laboratory achieved a Six Sigma level of performance.

    PubMed

    Blick, Kenneth E

    2013-08-01

    To develop a fully automated core laboratory, handling samples on a "first in, first out" real-time basis with Lean/Six Sigma management tools. Our primary goal was to provide services to critical care areas, eliminating turnaround time outlier percentage (TAT-OP) as a factor in patient length of stay (LOS). A secondary goal was to achieve a better laboratory return on investment. In 2011, we reached our primary goal when we calculated the TAT-OP distribution and found we had achieved a Six Sigma level of performance, ensuring that our laboratory service can be essentially eliminated as a factor in emergency department patient LOS. We also measured return on investment, showing a productivity improvement of 35%, keeping pace with our increased testing volume. As a result of our Lean process improvements and Six Sigma initiatives, in part through (1) strategic deployment of point-of-care testing and (2) core laboratory total automation with robotics, middleware, and expert system technology, physicians and nurses at the Oklahoma University Medical Center can more effectively deliver lifesaving health care using evidence-based protocols that depend heavily on "on time, every time" laboratory services.

  5. Genome-wide inference of regulatory networks in Streptomyces coelicolor.

    PubMed

    Castro-Melchor, Marlene; Charaniya, Salim; Karypis, George; Takano, Eriko; Hu, Wei-Shou

    2010-10-18

    The onset of antibiotics production in Streptomyces species is co-ordinated with differentiation events. An understanding of the genetic circuits that regulate these coupled biological phenomena is essential to discover and engineer the pharmacologically important natural products made by these species. The availability of genomic tools and access to a large warehouse of transcriptome data for the model organism, Streptomyces coelicolor, provides incentive to decipher the intricacies of the regulatory cascades and develop biologically meaningful hypotheses. In this study, more than 500 samples of genome-wide temporal transcriptome data, comprising wild-type and more than 25 regulatory gene mutants of Streptomyces coelicolor probed across multiple stress and medium conditions, were investigated. Information based on transcript and functional similarity was used to update a previously-predicted whole-genome operon map and further applied to predict transcriptional networks constituting modules enriched in diverse functions such as secondary metabolism, and sigma factor. The predicted network displays a scale-free architecture with a small-world property observed in many biological networks. The networks were further investigated to identify functionally-relevant modules that exhibit functional coherence and a consensus motif in the promoter elements indicative of DNA-binding elements. Despite the enormous experimental as well as computational challenges, a systems approach for integrating diverse genome-scale datasets to elucidate complex regulatory networks is beginning to emerge. We present an integrated analysis of transcriptome data and genomic features to refine a whole-genome operon map and to construct regulatory networks at the cistron level in Streptomyces coelicolor. The functionally-relevant modules identified in this study pose as potential targets for further studies and verification.

  6. The Flagellar Regulon of Legionella—A Review

    PubMed Central

    Appelt, Sandra; Heuner, Klaus

    2017-01-01

    The Legionella genus comprises more than 60 species. In particular, Legionella pneumophila is known to cause severe illnesses in humans. Legionellaceae are ubiquitous inhabitants of aquatic environments. Some Legionellaceae are motile and their motility is important to move around in habitats. Motility can be considered as a potential virulence factor as already shown for various human pathogens. The genes of the flagellar system, regulator and structural genes, are structured in hierarchical levels described as the flagellar regulon. Their expression is modulated by various environmental factors. For L. pneumophila it was shown that the expression of genes of the flagellar regulon is modulated by the actual growth phase and temperature. Especially, flagellated Legionella are known to express genes during the transmissive phase of growth that are involved in the expression of virulence traits. It has been demonstrated that the alternative sigma-28 factor is part of the link between virulence expression and motility. In the following review, the structure of the flagellar regulon of L. pneumophila is discussed and compared to other flagellar systems of different Legionella species. Recently, it has been described that Legionella micdadei and Legionella fallonii contain a second putative partial flagellar system. Hence, the report will focus on flagellated and non-flagellated Legionella strains, phylogenetic relationships, the role and function of the alternative sigma factor (FliA) and its anti-sigma-28 factor (FlgM). PMID:29104863

  7. The Flagellar Regulon of Legionella-A Review.

    PubMed

    Appelt, Sandra; Heuner, Klaus

    2017-01-01

    The Legionella genus comprises more than 60 species. In particular, Legionella pneumophila is known to cause severe illnesses in humans. Legionellaceae are ubiquitous inhabitants of aquatic environments. Some Legionellaceae are motile and their motility is important to move around in habitats. Motility can be considered as a potential virulence factor as already shown for various human pathogens. The genes of the flagellar system, regulator and structural genes, are structured in hierarchical levels described as the flagellar regulon. Their expression is modulated by various environmental factors. For L. pneumophila it was shown that the expression of genes of the flagellar regulon is modulated by the actual growth phase and temperature. Especially, flagellated Legionella are known to express genes during the transmissive phase of growth that are involved in the expression of virulence traits. It has been demonstrated that the alternative sigma-28 factor is part of the link between virulence expression and motility. In the following review, the structure of the flagellar regulon of L. pneumophila is discussed and compared to other flagellar systems of different Legionella species. Recently, it has been described that Legionella micdadei and Legionella fallonii contain a second putative partial flagellar system. Hence, the report will focus on flagellated and non-flagellated Legionella strains, phylogenetic relationships, the role and function of the alternative sigma factor (FliA) and its anti-sigma-28 factor (FlgM).

  8. Differential cross sections for the electron impact excitation of the A {sup 3}{sigma}{sub u}{sup +}, B {sup 3}{pi}{sub g}, W {sup 3}{delta}{sub u}, B{sup '} {sup 3}{sigma}{sub u}{sup -}, a{sup '} {sup 1}{sigma}{sub u}{sup -}, a {sup 1}{pi}{sub g}, w {sup 1}{delta}{sub u}, and C {sup 3}{pi}{sub u} states of N{sub 2}

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Khakoo, M.A.; Ozkay, I.; Johnson, P.V.

    2005-06-15

    Measurements of differential cross sections for the electron-impact excitation of molecular nitrogen from the ground X {sup 1}{sigma}{sub g}{sup +}(v{sup ''}=0) level to the A {sup 3}{sigma}{sub u}{sup +}(v{sup '}), B {sup 3}{pi}{sub g}(v{sup '}), W {sup 3}{delta}{sub u}(v{sup '}), B{sup '} {sup 3}{sigma}{sub u}{sup -}(v{sup '}), a{sup '} {sup 1}{sigma}{sub u}{sup -}(v{sup '}), a {sup 1}{pi}{sub g}(v{sup '}), w {sup 1}{delta}{sub u}(v{sup '}), and C {sup 3}{pi}{sub u}(v{sup '}) levels are presented. The data are obtained at the incident energies of 10, 12.5, 15, 17.5, 20, 30, 50, and 100 eV over the angular range of 5 deg. -130more » deg. in 5 deg. intervals. The individual electronic state excitation differential cross sections are obtained by unfolding electron energy-loss spectra of molecular nitrogen using available semiempirical Frank-Condon factors. The data are compared to previous measurements and to available theory. We also make several important suggestions regarding future work that, like the present, relies on the unfolding of electron energy-loss spectra for obtaining differential cross sections.« less

  9. Factors of Resilience in Emergency Department Nurses Who Have Experienced Workplace Violence in Taiwan.

    PubMed

    Hsieh, Hsiu-Fen; Hung, Yu-Tung; Wang, Hsiu-Hung; Ma, Shu-Ching; Chang, Shu-Chen

    2016-01-01

    This study investigated the relationship among personality traits, social network integration (SNI), and resilience in emergency department (ED) nurses who had suffered from physical or verbal violence by patients or their families. A cross-sectional study with convenience sampling was conducted for exploring the related factors of resilience on abused nurses. A total of 187 participants met our inclusion criteria and completed all questionnaires. Higher degrees of extraversion and peer support were associated with greater resilience among all abused nurses, whereas neuroticism was inversely associated with their resilience. Among all forms of SNI, only peer support was shown to enhance an individual's resilience. In addition, personality traits were associated with resilience, and religions did not play an important role in enhancing resilience among our participants. Through a clearer understanding of the role of peer support in resilience among ED nurses, healthcare managers should provide and enhance their peer support to intensify their resilience for prevention of consequences of workplace violence. © 2015 Sigma Theta Tau International.

  10. Interactions of 13. 6-GeV/nucleon [sup 16]O and [sup 28]Si with carbon, aluminum, and copper

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cumming, J.B.; Chu, Y.Y.; Haustein, P.E.

    1993-10-01

    Cross sections for forming [sup 24]Na and [sup 18]F by the interactions of 13.6-GeV/nucleon [sup 16]O and [sup 28]Si ions with Al and for forming [sup 24]Na in [sup 16]O interactions with Cu have been measured relative to the cross section for forming [sup 11]C from carbon. The results are generally consistent with energy-independent inclusive cross sections (limiting fragmentation) for heavy ions between [similar to]2 and 13.6 GeV/nucleon. However, comparison of the heavy-ion data with those for high-energy protons indicates a significantly weaker dependence on projectile size than that predicted by the factorization hypothesis for [sigma][sub C]([sup 11]C), [sigma][sub Al]([supmore » 18]F), and [sigma][sub Al]([sup 24]Na). The dependence is slightly stronger in the case of [sigma][sub Cu]([sup 24]Na).« less

  11. An application of Six Sigma methodology to turnover intentions in health care.

    PubMed

    Taner, Mehmet

    2009-01-01

    The purpose of this study is to show how the principles of Six Sigma can be applied to the high turnover problem of doctors in medical emergency services and paramedic backup. Six Sigma's define-measure-analyse-improve-control (DMAIC) is applied for reducing the turnover rate of doctors in an organisation operating in emergency services. Variables of the model are determined. Explanatory factor analysis, multiple regression, analysis of variance (ANOVA) and Gage R&R are employed for the analysis. Personal burnout/stress and dissatisfaction from salary were found to be the "vital few" variables. The organisation took a new approach by improving its initiatives to doctors' working conditions. Sigma level of the process is increased. New policy and process changes have been found to effectively decrease the incidence of turnover intentions. The improved process is gained, standardised and institutionalised. This study is one of the few papers in the literature that elaborates the turnover problem of doctors working in the emergency and paramedic backup services.

  12. Collisional dark matter and the origin of massive black holes

    PubMed

    Ostriker

    2000-06-05

    If the cosmological dark matter is primarily in the form of an elementary particle which has mass m(p) and cross section for self-interaction sigma, then seed black holes (formed in stellar collapse) will grow in a Hubble time t(H) due to accretion of the dark matter to a mass, M(H) = sqrt[IC(9)(A)t(H)(sigma/G(3)m(p)c(2))] = 7.1x10(6)(sigma/m(p))(1/2)V(9/2)(c)t(1/2)(H,15) solar masses. Here I is a numerical factor, C(A) the galactic velocity dispersion, and V(c) its rotation velocity. For the same values of ( sigma/m(p)) that are attractive with respect to other cosmological desiderata, this produces massive black holes in the (10(6)-10(9))M( middle dot in circle) range observed, with the same dependence on a V(c) seen, and with a time dependence consistent with observations. Other astrophysical consequences of collisional dark matter and tests of the idea are noted.

  13. The rpoE operon regulates heat stress response in Burkholderia pseudomallei.

    PubMed

    Vanaporn, Muthita; Vattanaviboon, Paiboon; Thongboonkerd, Visith; Korbsrisate, Sunee

    2008-07-01

    Burkholderia pseudomallei is a gram-negative bacterium and the causative agent of melioidosis, one of the important lethal diseases in tropical regions. In this article, we demonstrate the crucial role of the B. pseudomallei rpoE locus in the response to heat stress. The rpoE operon knockout mutant exhibited growth retardation and reduced survival when exposed to a high temperature. Expression analysis using rpoH promoter-lacZ fusion revealed that heat stress induction of rpoH, which encodes heat shock sigma factor (sigma(H)), was abolished in the B. pseudomallei rpoE mutant. Analysis of the rpoH promoter region revealed sequences sharing high homology to the consensus sequence of sigma(E)-dependent promoters. Moreover, the putative heat-induced sigma(H)-regulated heat shock proteins (i.e. GroEL and HtpG) were also absent in the rpoE operon mutant. Altogether, our data suggest that the rpoE operon regulates B. pseudomallei heat stress response through the function of rpoH.

  14. Theoretical study of photoacidity of HCN: the effect of complexation with water.

    PubMed

    Muchová, Eva; Spirko, Vladimir; Hobza, Pavel; Nachtigallová, Dana

    2006-11-14

    The character of the hydrogen bonding and the excited state proton transfer (ESPT) in the model system HCN...H(2)O is investigated. The PES of the two lowest excited states of the H(2)O...HCN complex was calculated using the CASPT2 method. The nonadiabatic coupling of the two states of the (pi-->pi*) and (pi-->sigma*) character is responsible for the excited state proton/hydrogen transfer. Compared to the ground state, the barrier for this process is significantly smaller. An increased number of water molecules in the complex with cyclic hydrogen-bonded network causes a large blue shift of the state of the (pi-->sigma*) character. The question of the dissociation of the complex in its excited state is also addressed.

  15. The whole set of the constitutive promoters recognized by four minor sigma subunits of Escherichia coli RNA polymerase

    PubMed Central

    Shimada, Tomohiro; Tanaka, Kan

    2017-01-01

    The promoter selectivity of Escherichia coli RNA polymerase (RNAP) is determined by the sigma subunit. The model prokaryote Escherichia coli K-12 contains seven species of the sigma subunit, each recognizing a specific set of promoters. For identification of the “constitutive promoters” that are recognized by each RNAP holoenzyme alone in the absence of other supporting factors, we have performed the genomic SELEX screening in vitro for their binding sites along the E. coli K-12 W3110 genome using each of the reconstituted RNAP holoenzymes and a collection of genome DNA segments of E. coli K-12. The whole set of constitutive promoters for each RNAP holoenzyme was then estimated based on the location of RNAP-binding sites. The first successful screening of the constitutive promoters was achieved for RpoD (σ70), the principal sigma for transcription of growth-related genes. As an extension, we performed in this study the screening of constitutive promoters for four minor sigma subunits, stationary-phase specific RpoS (σ38), heat-shock specific RpoH (σ32), flagellar-chemotaxis specific RpoF (σ28) and extra-cytoplasmic stress-response RpoE (σ24). The total number of constitutive promoters were: 129~179 for RpoS; 101~142 for RpoH; 34~41 for RpoF; and 77~106 for RpoE. The list of constitutive promoters were compared with that of known promoters identified in vivo under various conditions and using varieties of E. coli strains, altogether allowing the estimation of “inducible promoters” in the presence of additional supporting factors. PMID:28666008

  16. Differential Cross Sections for the Electron Impact Excitation of the A(sup 3)(Sigma)(sub u)(sup +), B(sup 3)Pi(sub g), W(sup 3)(Delta)(sub u), B'(sup 3)(Sigma)(sub u)(sup -), a'(sup 1)Sigma(sub u)(sup -), a(sup 1)Pi(sub g), w(sup 1)Delta(sub u), and C(sup 3)Pi(sub u) States of N(sub 2)

    NASA Technical Reports Server (NTRS)

    Khakoo, M. A.; Johnson, P. V.; Ozkay, I.; Yan, P.; Trajmar, S.; Kanik, I.

    2005-01-01

    Measurements of differential cross sections for the electron-impact excitation of molecular nitrogen from the ground X(sup 1)(Sigma)(sub g)(sup +)(v''=0)level to the A(sup 3)(Sigma)(sub u)(sup +)(v'), B(sup 3)Pi(sub g)(v'), W(sup 3)(Delta)(sub u)(v'),B'(sup 3)(Sigma)(sub u)(sup -)(v'), a(sup 1)(Pi)(sub g)(v'), w(sup 1)(Delta)(sub u)(v'), and C(sup 3)(Pi)(sub u)(v') levels are presented. The data are obtained at the incident energies of 10, 12.5, 15, 17.5, 20, 30, 50, and 100 eV over the angular range of 5(deg)-130(deg) in 5(deg) intervals. The individual electronic state excitation differential cross sections are obtained by unfolding electron energy-loss spectra of molecular nitrogen using available semiempirical Frank-Condon factors. The data are compared to previous measurements and to available theory. We also make several important suggestions regarding future work that, like the present, relies on the unfolding of electron energy-loss spectra for obtaining differential cross sections.

  17. Levitation effect: Distinguishing anomalous from linear regime of guests sorbed in zeolites through the decay of intermediate scattering function and wavevector dependence of self-diffusivity.

    PubMed

    Ghorai, Pradip Kr; Yashonath, S

    2005-03-10

    Previous work investigating the dependence of self-diffusivity, D, on the size of the guest diffusing within the porous solid such as zeolite has reported the existence of an anomalous maximum in the diffusion coefficient (J. Phys. Chem. 1994, 98, 6368). Two distinct regimes of dependence of D on sigma(gg), diameter of the guest were reported. D proportional to 1/sigma(gg)2, often referred to as linear regime (LR), is found when sigma(gg) is smaller than sigma(v), the diameter of the void. A maximum in D has been observed when sigma(gg) is comparable to sigma(v) and this regime is referred to as anomalous regime (AR). Here we report the intermediate scattering function for a particle from LR and AR in zeolite faujasite. A particle from LR exhibits a biexponential decay while a particle from AR exhibits a single-exponential decay at small k. Variation with k of the full width at half-maximum of the self-part of the dynamic structure factor is nonmonotonic for a particle in the linear regime. In contrast, this variation is monotonic for a particle in the anomalous regime. These results can be understood in terms of the existence of energetic barrier at the bottleneck, the 12-ring window, in the path of diffusion. They provide additional signatures for the linear regime and anomalous regimes and therefore for levitation effect (LE).

  18. RpoH2 sigma factor controls the photooxidative stress response in a non-photosynthetic rhizobacterium, Azospirillum brasilense Sp7.

    PubMed

    Kumar, Santosh; Rai, Ashutosh Kumar; Mishra, Mukti Nath; Shukla, Mansi; Singh, Pradhyumna Kumar; Tripathi, Anil Kumar

    2012-12-01

    Bacteria belonging to the Alphaproteobacteria normally harbour multiple copies of the heat shock sigma factor (known as σ(32), σ(H) or RpoH). Azospirillum brasilense, a non-photosynthetic rhizobacterium, harbours five copies of rpoH genes, one of which is an rpoH2 homologue. The genes around the rpoH2 locus in A. brasilense show synteny with that found in rhizobia. The rpoH2 of A. brasilense was able to complement the temperature-sensitive phenotype of the Escherichia coli rpoH mutant. Inactivation of rpoH2 in A. brasilense results in increased sensitivity to methylene blue and to triphenyl tetrazolium chloride (TTC). Exposure of A. brasilense to TTC and the singlet oxygen-generating agent methylene blue induced several-fold higher expression of rpoH2. Comparison of the proteome of A. brasilense with its rpoH2 deletion mutant and with an A. brasilense strain overexpressing rpoH2 revealed chaperone GroEL, elongation factors (Ef-Tu and EF-G), peptidyl prolyl isomerase, and peptide methionine sulfoxide reductase as the major proteins whose expression was controlled by RpoH2. Here, we show that the RpoH2 sigma factor-controlled photooxidative stress response in A. brasilense is similar to that in the photosynthetic bacterium Rhodobacter sphaeroides, but that RpoH2 is not involved in the detoxification of methylglyoxal in A. brasilense.

  19. Competence for Genetic Transformation in Streptococcus pneumoniae: Mutations in σA Bypass the comW Requirement

    PubMed Central

    Tovpeko, Yanina

    2014-01-01

    Competence for genetic transformation in the genus Streptococcus depends on an alternative sigma factor, σX, for coordinated synthesis of 23 proteins, which together establish the X state by permitting lysis of incompetent streptococci, uptake of DNA fragments, and integration of strands of that DNA into the resident genome. Initiation of transient accumulation of high levels of σX is coordinated between cells by transcription factors linked to peptide pheromone signals. In Streptococcus pneumoniae, elevated σX is insufficient for development of full competence without coexpression of a second competence-specific protein, ComW. ComW, shared by eight species in the Streptococcus mitis and Streptococcus anginosus groups, is regulated by the same pheromone circuit that controls σX, but its role in expression of the σX regulon is unknown. Using the strong, but not absolute, dependence of transformation on comW as a selective tool, we collected 27 independent comW bypass mutations and mapped them to 10 single-base transitions, all within rpoD, encoding the primary sigma factor subunit of RNA polymerase, σA. Eight mapped to sites in rpoD region 4 that are implicated in interaction with the core β subunit, indicating that ComW may act to facilitate competition of the alternative sigma factor σX for access to core polymerase. PMID:25112479

  20. Response of Desulfovibrio vulgaris to Alkaline Stress

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Stolyar, S.; He, Q.; He, Z.

    2007-11-30

    The response of exponentially growing Desulfovibrio vulgarisHildenborough to pH 10 stress was studied using oligonucleotidemicroarrays and a study set of mutants with genes suggested by microarraydata to be involved in the alkaline stress response deleted. The datashowed that the response of D. vulgaris to increased pH is generallysimilar to that of Escherichia coli but is apparently controlled byunique regulatory circuits since the alternative sigma factors (sigma Sand sigma E) contributing to this stress response in E. coli appear to beabsent in D. vulgaris. Genes previously reported to be up-regulated in E.coli were up-regulated in D. vulgaris; these genes included threemore » ATPasegenes and a tryptophan synthase gene. Transcription of chaperone andprotease genes (encoding ATP-dependent Clp and La proteases and DnaK) wasalso elevated in D. vulgaris. As in E. coli, genes involved in flagellumsynthesis were down-regulated. The transcriptional data also identifiedregulators, distinct from sigma S and sigma E, that are likely part of aD. vulgaris Hildenborough-specific stress response system.Characterization of a study set of mutants with genes implicated inalkaline stress response deleted confirmed that there was protectiveinvolvement of the sodium/proton antiporter NhaC-2, tryptophanase A, andtwo putative regulators/histidine kinases (DVU0331 andDVU2580).« less

  1. Chemical origin of blue- and redshifted hydrogen bonds: intramolecular hyperconjugation and its coupling with intermolecular hyperconjugation.

    PubMed

    Li, An Yong

    2007-04-21

    Upon formation of a H bond Y...H-XZ, intramolecular hyperconjugation n(Z)-->sigma*(X-H) of the proton donor plays a key role in red- and blueshift characters of H bonds and must be introduced in the concepts of hyperconjugation and rehybridization. Intermolecular hyperconjugation transfers electron density from Y to sigma*(X-H) and causes elongation and stretch frequency redshift of the X-H bond; intramolecular hyperconjugation couples with intermolecular hyperconjugation and can adjust electron density in sigma*(X-H); rehybridization causes contraction and stretch frequency blueshift of the X-H bond on complexation. The three factors--intra- and intermolecular hyperconjugations and rehybridization--determine commonly red- or blueshift of the formed H bond. A proton donor that has strong intramolecular hyperconjugation often forms blueshifted H bonds.

  2. The Role of Margin in Link Design and Optimization

    NASA Technical Reports Server (NTRS)

    Cheung, K.

    2015-01-01

    Link analysis is a system engineering process in the design, development, and operation of communication systems and networks. Link models that are mathematical abstractions representing the useful signal power and the undesirable noise and attenuation effects (including weather effects if the signal path transverses through the atmosphere) that are integrated into the link budget calculation that provides the estimates of signal power and noise power at the receiver. Then the link margin is applied which attempts to counteract the fluctuations of the signal and noise power to ensure reliable data delivery from transmitter to receiver. (Link margin is dictated by the link margin policy or requirements.) A simple link budgeting approach assumes link parameters to be deterministic values typically adopted a rule-of-thumb policy of 3 dB link margin. This policy works for most S- and X-band links due to their insensitivity to weather effects. But for higher frequency links like Ka-band, Ku-band, and optical communication links, it is unclear if a 3 dB link margin would guarantee link closure. Statistical link analysis that adopted the 2-sigma or 3-sigma link margin incorporates link uncertainties in the sigma calculation. (The Deep Space Network (DSN) link margin policies are 2-sigma for downlink and 3-sigma for uplink.) The link reliability can therefore be quantified statistically even for higher frequency links. However in the current statistical link analysis approach, link reliability is only expressed as the likelihood of exceeding the signal-to-noise ratio (SNR) threshold that corresponds to a given bit-error-rate (BER) or frame-error-rate (FER) requirement. The method does not provide the true BER or FER estimate of the link with margin, or the required signalto-noise ratio (SNR) that would meet the BER or FER requirement in the statistical sense. In this paper, we perform in-depth analysis on the relationship between BER/FER requirement, operating SNR, and coding performance curve, in the case when the channel coherence time of link fluctuation is comparable or larger than the time duration of a codeword. We compute the "true" SNR design point that would meet the BER/FER requirement by taking into account the fluctuation of signal power and noise power at the receiver, and the shape of the coding performance curve. This analysis yields a number of valuable insights on the design choices of coding scheme and link margin for the reliable data delivery of a communication system - space and ground. We illustrate the aforementioned analysis using a number of standard NASA error-correcting codes.

  3. Neural network-based model reference adaptive control system.

    PubMed

    Patino, H D; Liu, D

    2000-01-01

    In this paper, an approach to model reference adaptive control based on neural networks is proposed and analyzed for a class of first-order continuous-time nonlinear dynamical systems. The controller structure can employ either a radial basis function network or a feedforward neural network to compensate adaptively the nonlinearities in the plant. A stable controller-parameter adjustment mechanism, which is determined using the Lyapunov theory, is constructed using a sigma-modification-type updating law. The evaluation of control error in terms of the neural network learning error is performed. That is, the control error converges asymptotically to a neighborhood of zero, whose size is evaluated and depends on the approximation error of the neural network. In the design and analysis of neural network-based control systems, it is important to take into account the neural network learning error and its influence on the control error of the plant. Simulation results showing the feasibility and performance of the proposed approach are given.

  4. An Extracytoplasmic Function Sigma Factor-Mediated Cell Surface Signaling System in Pseudomonas syringae pv. tomato DC3000 Regulates Gene Expression in Response to Heterologous Siderophores ▿ †

    PubMed Central

    Markel, Eric; Maciak, Charlene; Butcher, Bronwyn G.; Myers, Christopher R.; Stodghill, Paul; Bao, Zhongmeng; Cartinhour, Sam; Swingle, Bryan

    2011-01-01

    The diversity of regulatory systems encoded by bacteria provides an indication of the variety of stresses and interactions that these organisms encounter in nature. We have been investigating how the plant pathogen Pseudomonas syringae pv. tomato DC3000 responds to iron limitation and have focused on the iron starvation (IS) sigma factors to identify regulon members and to explore the mechanistic details of genetic control for this class of regulators. In the study described in this report, we used chromatin immunoprecipitation paired with high-throughput sequencing (ChIP-Seq) to screen the genome for locations associated with binding of the P. syringae IS sigma factor PSPTO_1203. We used multiple methods to demonstrate differential regulation of two genes identified in the ChIP-Seq screen and characterize the promoter elements that facilitate PSPTO_1203-dependent regulation. The genes regulated by PSPTO_1203 encode a TonB-dependent transducer (PSPTO_1206) and a cytoplasmic membrane protein (PSPTO_2145), which is located in the P. syringae pyoverdine cluster. Additionally, we identified siderophores that induce the activity of PSPTO_1203 and used this information to investigate the functional components of the signal transduction cascade. PMID:21840980

  5. An extracytoplasmic function sigma factor cotranscribed with its cognate anti-sigma factor confers tolerance to NaCl, ethanol and methylene blue in Azospirillum brasilense Sp7.

    PubMed

    Mishra, Mukti Nath; Kumar, Santosh; Gupta, Namrata; Kaur, Simarjot; Gupta, Ankush; Tripathi, Anil K

    2011-04-01

    Azospirillum brasilense, a plant-growth-promoting rhizobacterium, is exposed to changes in its abiotic environment, including fluctuations in temperature, salinity, osmolarity, oxygen concentration and nutrient concentration, in the rhizosphere and in the soil. Since extra-cytoplasmic function (ECF) sigma factors play an important role in stress adaptation, we analysed the role of ECF sigma factor (also known as RpoE or σ(E)) in abiotic stress tolerance in A. brasilense. An in-frame rpoE deletion mutant of A. brasilense Sp7 was carotenoidless and slow-growing, and was sensitive to salt, ethanol and methylene blue stress. Expression of rpoE in the rpoE deletion mutant complemented the defects in growth, carotenoid biosynthesis and sensitivity to different stresses. Based on data from reverse transcriptase-PCR, a two-hybrid assay and a pull-down assay, we present evidence that rpoE is cotranscribed with chrR and the proteins synthesized from these two overlapping genes interact with each other. Identification of the transcription start site by 5' rapid amplification of cDNA ends showed that the rpoE-chrR operon was transcribed by two promoters. The proximal promoter was less active than the distal promoter, whose consensus sequence was characteristic of RpoE-dependent promoters found in alphaproteobacteria. Whereas the proximal promoter was RpoE-independent and constitutively expressed, the distal promoter was RpoE-dependent and strongly induced in response to stationary phase and elevated levels of ethanol, salt, heat and methylene blue. This study shows the involvement of RpoE in controlling carotenoid synthesis as well as in tolerance to some abiotic stresses in A. brasilense, which might be critical in the adaptation, survival and proliferation of this rhizobacterium in the soil and rhizosphere under stressful conditions.

  6. SigCH, an extracytoplasmic function sigma factor of Porphyromonas gingivalis regulates the expression of cdhR and hmuYR.

    PubMed

    Ota, Koki; Kikuchi, Yuichiro; Imamura, Kentaro; Kita, Daichi; Yoshikawa, Kouki; Saito, Atsushi; Ishihara, Kazuyuki

    2017-02-01

    Extracytoplasmic function (ECF) sigma factors play an important role in the bacterial response to various environmental stresses. Porphyromonas gingivalis, a prominent etiological agent in human periodontitis, possesses six putative ECF sigma factors. So far, information is limited on the ECF sigma factor, PGN_0319. The aim of this study was to investigate the role of PGN_0319 (SigCH) of P. gingivalis, focusing on the regulation of hmuY and hmuR, which encode outer-membrane proteins involved in hemin utilization, and cdhR, a transcriptional regulator of hmuYR. First, we evaluated the gene expression profile of the sigCH mutant by DNA microarray. Among the genes with altered expression levels, those involved in hemin utilization were downregulated in the sigCH mutant. To verify the microarray data, quantitative reverse transcription PCR analysis was performed. The RNA samples used were obtained from bacterial cells grown to early-log phase, in which sigCH expression in the wild type was significantly higher than that in mid-log and late-log phases. The expression levels of hmuY, hmuR, and cdhR were significantly decreased in the sigCH mutant compared to wild type. Transcription of these genes was restored in a sigCH complemented strain. Compared to the wild type, the sigCH mutant showed reduced growth in log phase under hemin-limiting conditions. Electrophoretic mobility shift assays showed that recombinant SigCH protein bound to the promoter region of hmuY and cdhR. These results suggest that SigCH plays an important role in the early growth of P. gingivalis, and directly regulates cdhR and hmuYR, thereby playing a potential role in the mechanisms of hemin utilization by P. gingivalis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. [Accumulative levels of organochlorine pesticides of HCHs, DDTs in breast milk and risk factors analysis in Shenzhen].

    PubMed

    Shi, Rongjie; Zhong, Yuetong; Lei, Yixiong; Zhang, Jianqing; Li, Shengnong; Jiang, Yousheng; Zhou, Jian; Lu, Shaoyou

    2013-03-01

    To first investigate the accumulative levels of DDTs and HCHs in human breast milk of primipara in Shenzhen area, analyze influencing factors and assess exposure risk of infant in Shenzhen. From April in 2011 to April in 2012, 85 primiparas who have lived in Shenzhen over 3 years after parturition 4 - 6 weeks were recruited, and their breast milk were collected and questionnaires were filled out simultaneously. The samples were extracted five times with hexane, cleaned up by gel permeation chromatograph (GPC) and SPE, and quantified by gas chromatography-election capture detection (GC-ECD). Correlations between DDTs, HCHs and maternal age, weight, dietary, living time as well as infant birth weight and length were also analyzed with the SPSS 13.0 statistical software respectively. Among the several groups of DDTs and HCHs metabolites, p,p'-DDE were detected in total 85 samples and beta-HCH were detected in 58 samples, which accounted for 68.2% of the breast milk. The median levels of sigmaHCHs and sigma DDTs were 2.980 ng/g whole weight (80.200 ng/g fat) and 9.610 ng/g whole weight (268.390 ng/g fat). Both levels of sigmaHCHs and sigmaDDTs in the human milk had a positive association with maternal age among the demographic characteristics of primiparas. Furthermore, levels of sigma HCHs were positively correlated with freshwater fish consumption. However, sigma DDTs levels which were calculated in fat had a positive association only with the amount of poultry meat intake. Beta-HCH and p,p'-DDE were detected in human breast milk, and correlated with age and dietary intake. The average estimated daily intakes of HCHs and DDTs by infants are 0.468, 1.842 microg/(kg x BW x d) respectively, lower than acceptable daily intakes (ADI) proposed by the Ministry of Health of China and (the WHO/FAO) Joint Meeting of Pesticide Residues (JMPR). The average levels of HCHs, DDTs in the breast milk in Shenzhen general population are lower than those of Chinese average level.

  8. The Escherichia coli Regulator of Sigma 70 Protein, Rsd, Can Up-Regulate Some Stress-Dependent Promoters by Sequestering Sigma 70▿

    PubMed Central

    Mitchell, Jennie E.; Oshima, Taku; Piper, Sarah E.; Webster, Christine L.; Westblade, Lars F.; Karimova, Gouzel; Ladant, Daniel; Kolb, Annie; Hobman, Jon L.; Busby, Stephen J. W.; Lee, David J.

    2007-01-01

    The Escherichia coli Rsd protein forms complexes with the RNA polymerase σ70 factor, but its biological role is not understood. Transcriptome analysis shows that overexpression of Rsd causes increased expression from some promoters whose expression depends on the alternative σ38 factor, and this was confirmed by experiments with lac fusions at selected promoters. The LP18 substitution in Rsd increases the Rsd-dependent stimulation of these promoter-lac fusions. Analysis with a bacterial two-hybrid system shows that the LP18 substitution in Rsd increases its interaction with σ70. Our experiments support a model in which the role of Rsd is primarily to sequester σ70, thereby increasing the levels of RNA polymerase containing the alternative σ38 factor. PMID:17351046

  9. The Listeria monocytogenes strain 10403S BioCyc database

    PubMed Central

    Orsi, Renato H.; Bergholz, Teresa M.; Wiedmann, Martin; Boor, Kathryn J.

    2015-01-01

    Listeria monocytogenes is a food-borne pathogen of humans and other animals. The striking ability to survive several stresses usually used for food preservation makes L. monocytogenes one of the biggest concerns to the food industry, while the high mortality of listeriosis in specific groups of humans makes it a great concern for public health. Previous studies have shown that a regulatory network involving alternative sigma (σ) factors and transcription factors is pivotal to stress survival. However, few studies have evaluated at the metabolic networks controlled by these regulatory mechanisms. The L. monocytogenes BioCyc database uses the strain 10403S as a model. Computer-generated initial annotation for all genes also allowed for identification, annotation and display of predicted reactions and pathways carried out by a single cell. Further ongoing manual curation based on published data as well as database mining for selected genes allowed the more refined annotation of functions, which, in turn, allowed for annotation of new pathways and fine-tuning of previously defined pathways to more L. monocytogenes-specific pathways. Using RNA-Seq data, several transcription start sites and promoter regions were mapped to the 10403S genome and annotated within the database. Additionally, the identification of promoter regions and a comprehensive review of available literature allowed the annotation of several regulatory interactions involving σ factors and transcription factors. The L. monocytogenes 10403S BioCyc database is a new resource for researchers studying Listeria and related organisms. It allows users to (i) have a comprehensive view of all reactions and pathways predicted to take place within the cell in the cellular overview, as well as to (ii) upload their own data, such as differential expression data, to visualize the data in the scope of predicted pathways and regulatory networks and to carry on enrichment analyses using several different annotations available within the database. Database URL: http://biocyc.org/organism-summary?object=10403S_RAST PMID:25819074

  10. The Listeria monocytogenes strain 10403S BioCyc database.

    PubMed

    Orsi, Renato H; Bergholz, Teresa M; Wiedmann, Martin; Boor, Kathryn J

    2015-01-01

    Listeria monocytogenes is a food-borne pathogen of humans and other animals. The striking ability to survive several stresses usually used for food preservation makes L. monocytogenes one of the biggest concerns to the food industry, while the high mortality of listeriosis in specific groups of humans makes it a great concern for public health. Previous studies have shown that a regulatory network involving alternative sigma (σ) factors and transcription factors is pivotal to stress survival. However, few studies have evaluated at the metabolic networks controlled by these regulatory mechanisms. The L. monocytogenes BioCyc database uses the strain 10403S as a model. Computer-generated initial annotation for all genes also allowed for identification, annotation and display of predicted reactions and pathways carried out by a single cell. Further ongoing manual curation based on published data as well as database mining for selected genes allowed the more refined annotation of functions, which, in turn, allowed for annotation of new pathways and fine-tuning of previously defined pathways to more L. monocytogenes-specific pathways. Using RNA-Seq data, several transcription start sites and promoter regions were mapped to the 10403S genome and annotated within the database. Additionally, the identification of promoter regions and a comprehensive review of available literature allowed the annotation of several regulatory interactions involving σ factors and transcription factors. The L. monocytogenes 10403S BioCyc database is a new resource for researchers studying Listeria and related organisms. It allows users to (i) have a comprehensive view of all reactions and pathways predicted to take place within the cell in the cellular overview, as well as to (ii) upload their own data, such as differential expression data, to visualize the data in the scope of predicted pathways and regulatory networks and to carry on enrichment analyses using several different annotations available within the database. © The Author(s) 2015. Published by Oxford University Press.

  11. Transcriptional organization and in vivo role of the Escherichia coli rsd gene, encoding the regulator of RNA polymerase sigma D.

    PubMed

    Jishage, M; Ishihama, A

    1999-06-01

    The regulator of sigma D (Rsd) was identified as an RNA polymerase sigma70-associated protein in stationary-phase Escherichia coli with the inhibitory activity of sigma70-dependent transcription in vitro (M. Jishage and A. Ishihama, Proc. Natl. Acad. Sci. USA 95:4953-4958, 1998). Primer extension analysis of rsd mRNA indicated the presence of two promoters, sigmaS-dependent P1 and sigma70-dependent P2 with the gearbox sequence. To get insight into the in vivo role of Rsd, the expression of a reporter gene fused to either the sigma70- or sigmaS-dependent promoter was analyzed in the absence of Rsd or the presence of overexpressed Rsd. In the rsd null mutant, the sigma70- and sigmaS-dependent gene expression was increased or decreased, respectively. On the other hand, the sigma70- or sigmaS-dependent transcription was reduced or enhanced, respectively, after overexpression of Rsd. The repression of the sigmaS-dependent transcription in the rsd mutant is overcome by increased production of the sigmaS subunit. Together these observations support the prediction that Rsd is involved in replacement of the RNA polymerase sigma subunit from sigma70 to sigmaS during the transition from exponential growth to the stationary phase.

  12. Assurance of Myeloid Growth Factor Administration in an Infusion Center: Pilot Quality Improvement Initiative.

    PubMed

    Ramirez, Pamela Maree; Peterson, Barry; Holtshopple, Christine; Borja, Kristina; Torres, Vincent; Valdivia-Peppers, Lucille; Harriague, Julio; Joe, Melanie D

    2017-12-01

    Four incident reports involving missed doses of myeloid growth factors (MGFs) triggered the need for an outcome-driven initiative. From March 1, 2015, to February 29, 2016, at University of California Irvine Health Chao Infusion Center, 116 of 3,300 MGF doses were missed (3.52%), including pegfilgrastim, filgrastim, and sargramostim. We hypothesized that with the application of Lean Six Sigma methodology, we would achieve our primary objective of reducing the number of missed MGF doses to < 0.5%. This quality improvement initiative was conducted at Chao Infusion Center as part of a Lean Six Sigma Green Belt Certification Program. Therefore, Lean Six Sigma principles and tools were used throughout each phase of the project. Retrospective and prospective medical record reviews and data analyses were performed to evaluate the extent of the identified problem and impact of the process changes. Improvements included systems applications, practice changes, process modifications, and safety-net procedures. Preintervention, 24 missed doses (20.7%) required patient supportive care measures, resulting in increased hospital costs and decreased quality of care. Postintervention, from June 8, 2016, to August 7, 2016, zero of 489 MGF doses were missed after 2 months of intervention ( P < .001). Chao Infusion Center reduced missed doses from 3.52% to 0%, reaching the goal of < 0.5%. The establishment of simplified and standardized processes with safety checks for error prevention increased quality of care. Lean Six Sigma methodology can be applied by other institutions to produce positive outcomes and implement similar practice changes.

  13. Radio Galaxy Zoo: compact and extended radio source classification with deep learning

    NASA Astrophysics Data System (ADS)

    Lukic, V.; Brüggen, M.; Banfield, J. K.; Wong, O. I.; Rudnick, L.; Norris, R. P.; Simmons, B.

    2018-05-01

    Machine learning techniques have been increasingly useful in astronomical applications over the last few years, for example in the morphological classification of galaxies. Convolutional neural networks have proven to be highly effective in classifying objects in image data. In the context of radio-interferometric imaging in astronomy, we looked for ways to identify multiple components of individual sources. To this effect, we design a convolutional neural network to differentiate between different morphology classes using sources from the Radio Galaxy Zoo (RGZ) citizen science project. In this first step, we focus on exploring the factors that affect the performance of such neural networks, such as the amount of training data, number and nature of layers, and the hyperparameters. We begin with a simple experiment in which we only differentiate between two extreme morphologies, using compact and multiple-component extended sources. We found that a three-convolutional layer architecture yielded very good results, achieving a classification accuracy of 97.4 per cent on a test data set. The same architecture was then tested on a four-class problem where we let the network classify sources into compact and three classes of extended sources, achieving a test accuracy of 93.5 per cent. The best-performing convolutional neural network set-up has been verified against RGZ Data Release 1 where a final test accuracy of 94.8 per cent was obtained, using both original and augmented images. The use of sigma clipping does not offer a significant benefit overall, except in cases with a small number of training images.

  14. Ward Identity and Scattering Amplitudes for Nonlinear Sigma Models

    NASA Astrophysics Data System (ADS)

    Low, Ian; Yin, Zhewei

    2018-02-01

    We present a Ward identity for nonlinear sigma models using generalized nonlinear shift symmetries, without introducing current algebra or coset space. The Ward identity constrains correlation functions of the sigma model such that the Adler's zero is guaranteed for S -matrix elements, and gives rise to a subleading single soft theorem that is valid at the quantum level and to all orders in the Goldstone decay constant. For tree amplitudes, the Ward identity leads to a novel Berends-Giele recursion relation as well as an explicit form of the subleading single soft factor. Furthermore, interactions of the cubic biadjoint scalar theory associated with the single soft limit, which was previously discovered using the Cachazo-He-Yuan representation of tree amplitudes, can be seen to emerge from matrix elements of conserved currents corresponding to the generalized shift symmetry.

  15. Assessing and Ensuring GOES-R Magnetometer Accuracy

    NASA Technical Reports Server (NTRS)

    Carter, Delano R.; Todirita, Monica; Kronenwetter, Jeffrey; Chu, Donald

    2016-01-01

    The GOES-R magnetometer subsystem accuracy requirement is 1.7 nanoteslas (nT). During quiet times (100 nT), accuracy is defined as absolute mean plus 3 sigma. During storms (300 nT), accuracy is defined as absolute mean plus 2 sigma. Error comes both from outside the magnetometers, e.g. spacecraft fields and misalignments, as well as inside, e.g. zero offset and scale factor errors. Because zero offset and scale factor drift over time, it will be necessary to perform annual calibration maneuvers. To predict performance before launch, we have used Monte Carlo simulations and covariance analysis. Both behave as expected, and their accuracy predictions agree within 30%. With the proposed calibration regimen, both suggest that the GOES-R magnetometer subsystem will meet its accuracy requirements.

  16. Experimental Study of the NaK 3(1)Pi State.

    PubMed

    Laub; Mazsa; Webb; La Civita J; Prodan; Jabbour; Namiotka; Huennekens

    1999-02-01

    We report the results of an optical-optical double resonance experiment to determine the NaK 3(1)Pi state potential energy curve. In the first step, a narrow band cw dye laser (PUMP) is tuned to line center of a particular 2(A)1Sigma+(v', J') <-- 1(X)1Sigma+(v", J") transition, and its frequency is then fixed. A second narrowband tunable cw Ti:Sapphirelaser (PROBE) is then scanned, while 3(1)Pi --> 1(X)1Sigma+ violet fluorescence is monitored. The Doppler-free signals accurately map the 3(1)Pi(v, J) ro-vibrational energy levels. These energy levels are then fit to a Dunham expansion to provide a set of molecular constants. The Dunham constants, in turn, are used to construct an RKR potential curve. Resolved 3(1)Pi(v, J) --> 1(X)1Sigma+(v", J") fluorescence scans are also recorded with both PUMP and PROBE laser frequencies fixed. Comparison between observed and calculated Franck-Condon factors is used to determine the absolute vibrational numbering of the 3(1)Pi state levels and to determine the variation of the 3(1)Pi --> 1(X)1Sigma+ transitiondipole moment with internuclear separation. The recent theoretical calculation of the NaK 3(1)Pi state potential reported by Magnier and Millié (1996, Phys. Rev. A 54, 204) is in excellent agreement with the present experimental RKR curve. Copyright 1999 Academic Press.

  17. Response of Desulfovibrio vulgaris to Alkaline Stress▿ †

    PubMed Central

    Stolyar, Sergey; He, Qiang; Joachimiak, Marcin P.; He, Zhili; Yang, Zamin Koo; Borglin, Sharon E.; Joyner, Dominique C.; Huang, Katherine; Alm, Eric; Hazen, Terry C.; Zhou, Jizhong; Wall, Judy D.; Arkin, Adam P.; Stahl, David A.

    2007-01-01

    The response of exponentially growing Desulfovibrio vulgaris Hildenborough to pH 10 stress was studied using oligonucleotide microarrays and a study set of mutants with genes suggested by microarray data to be involved in the alkaline stress response deleted. The data showed that the response of D. vulgaris to increased pH is generally similar to that of Escherichia coli but is apparently controlled by unique regulatory circuits since the alternative sigma factors (sigma S and sigma E) contributing to this stress response in E. coli appear to be absent in D. vulgaris. Genes previously reported to be up-regulated in E. coli were up-regulated in D. vulgaris; these genes included three ATPase genes and a tryptophan synthase gene. Transcription of chaperone and protease genes (encoding ATP-dependent Clp and La proteases and DnaK) was also elevated in D. vulgaris. As in E. coli, genes involved in flagellum synthesis were down-regulated. The transcriptional data also identified regulators, distinct from sigma S and sigma E, that are likely part of a D. vulgaris Hildenborough-specific stress response system. Characterization of a study set of mutants with genes implicated in alkaline stress response deleted confirmed that there was protective involvement of the sodium/proton antiporter NhaC-2, tryptophanase A, and two putative regulators/histidine kinases (DVU0331 and DVU2580). PMID:17921288

  18. ELECTRON IMPACT DISSOCIATION X {sup 1}{Sigma}{sup +} {sub g} {yields} b {sup 3}{Sigma} {sub u} {sup +} AND EXCITATIONS X {sup 1}{Sigma}{sup +} {sub g} {yields} a {sup 3}{Sigma} {sub g} {sup +} AND X {sup 1}{Sigma}{sup +} {sub g} {yields} B {sup 1}{Sigma} {sub u} {sup +} OF MOLECULAR HYDROGEN IN NONTHERMAL ASTROPHYSICAL PLASMAS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ki, Dae-Han; Jung, Young-Dae, E-mail: ydjung@hanyang.ac.kr

    We investigate the electronic transitions X {sup 1}{Sigma}{sup +} {sub g} {yields} b {sup 3}{Sigma} {sub u} {sup +}, X {sup 1}{Sigma}{sup +} {sub g} {yields} a {sup 3}{Sigma} {sub g} {sup +}, and X {sup 1}{Sigma}{sup +} {sub g} {yields} B {sup 1}{Sigma} {sub u} {sup +} of molecular hydrogen by studying electron impacts in astrophysical Lorentzian plasmas. Useful fitting formulae for the X {sup 1}{Sigma}{sup +} {sub g} {yields} b {sup 3}{Sigma} {sub u} {sup +}, X {sup 1}{Sigma}{sup +} {sub g} {yields} a {sup 3}{Sigma} {sub g} {sup +}, and X {sup 1}{Sigma}{sup +} {sub g} {yields}more » B {sup 1}{Sigma} {sub u} {sup +} excitation cross sections are employed in order to obtain the electronic excitation rate coefficients of H{sub 2} as functions of the spectral index and temperature. In low-temperature regions, it is found that the excitation rate coefficients R{sub b{sup 3}{Sigma}{sub u{sup {sub +}}}}, R{sub a{sup 3}{Sigma}{sub g{sup {sub +}}}}, and R{sub B{sub {sup 1}{Sigma}{sub u{sup {sub +}}}}} of H{sub 2} in non-Maxwellian plasmas are smaller than those in Maxwellian plasmas. However, in high-temperature regions, the excitation rate coefficients of H{sub 2} in non-Maxwellian plasmas are greater than those in Maxwellian plasmas. It is also shown that the X {sup 1}{Sigma}{sup +} {sub g} {yields} b {sup 3}{Sigma} {sub u} {sup +} excitation rate coefficient is the main contributor in low-temperature regions. In contrast, it is found that the X {sup 1}{Sigma}{sup +} {sub g} {yields} B {sup 1}{Sigma} {sub u} {sup +} electronic excitation is dominant in high-temperature regions.« less

  19. High solar activity predictions through an artificial neural network

    NASA Astrophysics Data System (ADS)

    Orozco-Del-Castillo, M. G.; Ortiz-Alemán, J. C.; Couder-Castañeda, C.; Hernández-Gómez, J. J.; Solís-Santomé, A.

    The effects of high-energy particles coming from the Sun on human health as well as in the integrity of outer space electronics make the prediction of periods of high solar activity (HSA) a task of significant importance. Since periodicities in solar indexes have been identified, long-term predictions can be achieved. In this paper, we present a method based on an artificial neural network to find a pattern in some harmonics which represent such periodicities. We used data from 1973 to 2010 to train the neural network, and different historical data for its validation. We also used the neural network along with a statistical analysis of its performance with known data to predict periods of HSA with different confidence intervals according to the three-sigma rule associated with solar cycles 24-26, which we found to occur before 2040.

  20. The role of pressure in rubber elasticity.

    PubMed

    Bower, A F; Weiner, J H

    2004-06-22

    We describe a series of molecular dynamics computations that reveal an intimate connection at the atomic scale between difference stress (which resists stretches) and pressure (which resists volume changes) in an idealized elastomer, in contrast to the classical theory of rubber elasticity. Our simulations idealize the elastomer as a "pearl necklace," in which the covalent bonds are stiff linear springs, while nonbonded atoms interact through a Lennard-Jones potential with energy epsilon(LJ) and radius sigma(LJ). We calculate the difference stress t(11)-(t(22)+t(33))/2 and mean stress (t(11)+t(22)+t(33))/3 induced by a constant volume extension in the x(1) direction, as a function of temperature T and reduced density rho(*)=Nsigma(IJ) (3)/nu. Here, N is the number of atoms in the simulation cell and nu is the cell volume. Results show that for rho(*)<1, the difference stress is purely entropic and is in good agreement with the classical affine network model of rubber elasticity, which neglects nonbonded interactions. However, data presented by van Krevelen [Properties of Polymers, 3rd ed. (Elsevier, Amsterdam, 1990), p. 79] indicate that rubber at standard conditions corresponds to rho(*)=1.2. For rho(*)>1, the system is entropic for kT/epsilon(LJ)>2, but at lower temperatures the difference stress contains an additional energy component, which increases as rho(*) increases and temperature decreases. Finally, the model exhibits a glass transition for rho(*)=1.2 and kT/epsilon(LJ) approximately 2. The atomic-scale processes responsible for generating stress are explored in detail. Simulations demonstrate that the repulsive portion of the Lennard-Jones potential provides a contribution sigma(nbr)>0 to the difference stress, the attractive portion provides sigma(nba) approximately 0, while the covalent bonds provide sigma(b)<0. In contrast, their respective contributions to the mean stress satisfy Pi(nbr)<0, Pi(nba)>0, and Pi(b)<0. Analytical calculations, together with simulations, demonstrate that mean and difference stresses are related by sigma(nbr)=-APi(nbr)P(2)(theta(b)), sigma(b)=BPi(b)P(2)(theta(b)), where P(2)(theta(b)) is a measure of the anisotropy of the orientation of the covalent bonds, and A and B are coefficients that depend weakly on rho(*) and temperature. For high values of rho(*), we find that [sigma(nbr)]>[sigma(b)], and in this regime our model predicts behavior that is in good agreement with experimental data of D.L. Quested et al. [J. Appl. Phys. 52, 5977 (1981)] for the influence of pressure on the difference stress induced by stretching solithane. (c) 2004 American Institute of Physics.

  1. Optical characterization of the oceanic unicellular cyanobacterium Synechococcus grown under a day-night cycle in natural irradiance

    NASA Technical Reports Server (NTRS)

    Stramski, Dariusz; Shalapyonok, Alexi; Reynolds, Rick A.

    1995-01-01

    The optical properties of the ocenanic cyanobacterium Synechococcus (clone WH8103) were examined in a nutrient-replete laboratory culture grown under a day-night cycle in natural irradiance. Measurements of the spectral absorption and beam attenuation coefficients, the size distribution of cells in suspension, and microscopic analysis of samples were made at intervals of 2-4 hours for 2 days. These measurements were used to calculate the optical properties at the level of a single 'mean' cell representative of the acutal population, specifically, the optical cross sections for spectral absorption bar-(sigma(sub a)), scattering bar-sigma(sub b))(lambda), and attentuation bar-(sigma(sub c))(lambda). In addition, concurrent determinations of chlorophyll a and particulate organic carbon allowed calculation of the Chl a- and C-specific optical coefficients. The refractive index of cells was derived from the observed data using a theory of light absorption and scattering by homogeneous spheres. Low irradiance because of cloudy skies resulted in slow division rates of cells in the culture. The percentage of dividing cells was unusually high (greater than 30%) throughout the experiment. The optical cross sections varied greatly over a day-night cycle, with a minimum near dawn or midmorning and maximum near dusk. During daylight hours, bar-(sigma(sub b)) and bar-(sigma(sub c)) can increase more than twofold and bar-(sigma(sub a) by as much as 45%. The real part of the refractive index n increaed during the day; changes in n had equal or greater effect than the varying size distribution on changes in bar-(sigma(sub c)) and bar-(sigma(sub b)). The contribution of changes in n to the increase of bar-(sigma(sub c))(660) during daylight hours was 65.7% and 45.1% on day 1 and 2, respectively. During the dark period, when bar-(sigma(sub c))(660) decreased by a factor of 2.9, the effect of decreasing n was dominant (86.3%). With the exception of a few hours during the second light period, the imaginary part of the refractive index n' showed little variation over a day-night cycle, and bar-(sigma(sub a)) was largely controlled by variations in cell size. The real part of the refractive index at lambda = 660 nm was correlated with the intracellular C concentration and the imaginary part at lambda = 678 nm with the intracellular Chl a concentration. The C-specfic attenuation coefficient showed significant diel variability, which has implications for the estimation of oceanic primary production from measurements of diel variability in beam attenuation. This study provides strong evidence that diel variability is an important component of the optical characterization of marine phytoplankton.

  2. CHARACTERIZATION OF A SAMPLE OF INTERMEDIATE-TYPE ACTIVE GALACTIC NUCLEI. II. HOST BULGE PROPERTIES AND BLACK HOLE MASS ESTIMATES

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Benitez, Erika; Cruz-Gonzalez, Irene; Martinez, Benoni

    2013-02-15

    We present a study of the host bulge properties and their relations with the black hole mass for a sample of 10 intermediate-type active galactic nuclei (AGNs). Our sample consists mainly of early-type spirals, four of them hosting a bar. For 70{sup +10} {sub -17}% of the galaxies, we have been able to determine the type of the bulge, and find that these objects probably harbor a pseudobulge or a combination of classical bulge/pseudobulge, suggesting that pseudobulges might be frequent in intermediate-type AGNs. In our sample, 50% {+-} 14% of the objects show double-peaked emission lines. Therefore, narrow double-peaked emissionmore » lines seem to be frequent in galaxies harboring a pseudobulge or a combination of classical bulge/pseudobulge. Depending on the bulge type, we estimated the black hole mass using the corresponding M {sub BH}-{sigma}* relation and found them within a range of 5.69 {+-} 0.21 < log M {sup {sigma}}*{sub BH} < 8.09 {+-} 0.24. Comparing these M {sup {sigma}}*{sub BH} values with masses derived from the FWHM of H{beta} and the continuum luminosity at 5100 A from their SDSS-DR7 spectra (M {sub BH}), we find that 8 out of 10 (80{sup +7} {sub -17}%) galaxies have black hole masses that are compatible within a factor of 3. This result would support that M {sub BH} and M {sup {sigma}}*{sub BH} are the same for intermediate-type AGNs, as has been found for type 1 AGNs. However, when the type of the bulge is taken into account, only three out of the seven (43{sup +18} {sub -15}%) objects of the sample have their M {sup {sigma}}*{sub BH} and M {sub BH} compatible within 3{sigma} errors. We also find that estimations based on the M {sub BH}-{sigma}* relation for pseudobulges are not compatible in 50% {+-} 20% of the objects.« less

  3. Carotenoid production and phenotypic variation in Azospirillum brasilense.

    PubMed

    Brenholtz, Gal Reem; Tamir-Ariel, Dafna; Okon, Yaacov; Burdman, Saul

    2017-06-01

    We assessed the occurrence of phenotypic variation in Azospirillum brasilense strains Sp7, Cd, Sp245, Az39 and phv2 during growth in rich media, screening for variants altered in colony pigmentation or extracellular polysaccharide (EPS) production. Previous studies showed that EPS-overproducing variants of Sp7 appear frequently following starvation or growth in minimal medium. In contrast, no such variants were detected during growth in rich media in the tested strains except for few variants of phv2. Regarding alteration in colony pigmentation (from pink to white in strain Cd and from white to pink in the others), strain Sp7 showed a relatively high frequency of variation (0.009-0.026%). Strain Cd showed a lower frequency of alteration in pigmentation (0-0.008%), and this type of variation was not detected in the other strains. In A. brasilense, carotenoid synthesis is controlled by two RpoE sigma factors and their cognate ChrR anti-sigma factors, the latter acting as negative regulators of carotenoid synthesis. Here, all tested (n = 28) pink variants of Sp7 carried mutations in one of the anti-sigma factor genes, chrR1. Our findings indicate that, in A. brasilense, phenotypic variation is strain- and environment-dependent and support the central role of ChrR1 in regulation of carotenoid production. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  4. Cross-talk between cognate and noncognate RpoE sigma factors and Zn(2+)-binding anti-sigma factors regulates photooxidative stress response in Azospirillum brasilense.

    PubMed

    Gupta, Namrata; Gupta, Ankush; Kumar, Santosh; Mishra, Rajeev; Singh, Chhaya; Tripathi, Anil Kumar

    2014-01-01

    Azospirillum brasilense harbors two redox-sensitive Zinc-binding anti-sigma (ZAS) factors (ChrR1 and ChrR2), which negatively regulate the activity of their cognate extra-cytoplasmic function (ECF) σ factors (RpoE1 and RpoE2) by occluding their binding to the core enzyme. Both pairs of RpoE-ChrR control responses to photooxidative stress. The aim of this study was to investigate whether the two RpoE-ChrR pairs cross-talk while responding to the stress. In silico analysis showed a high sequence similarity between ChrR1 and ChrR2 proteins, but differences in redox sensitivity. Using in silico and in vitro methods of protein-protein interaction, we have shown that both ChrR1 and ChrR2 proteins physically bind to their noncognate RpoE proteins. Restoration of the phenotypes of chrR1::Tn5 and chrR2::Km mutants related to carotenoid biosynthesis and photooxidative stress tolerance by expressing chrR1 or chrR2 provided in vivo evidence for the cross-talk. In addition, up- or down-regulation of several identical proteins by expressing chrR1 or chrR2 in the chrR1::Tn5 mutant provided another in vivo evidence for the cross-talk. Although multiple redox-sensitive ZAS anti-σ factors occur in some Gram-positive bacteria, no cross-talk is reported among them. We report here, for the first time, that the two ZAS anti-σ factors of A. brasilense also interact with their noncognate σ factors and affect gene expression. The two redox-sensitive ZAS anti-σ factors in A. brasilense may interact with their cognate as well as noncognate ECF σ factors to play an important role in redox homeostasis by facilitating recovery from the oxidative stress.

  5. Production Time Loss Reduction in Sauce Production Line by Lean Six Sigma Approach

    NASA Astrophysics Data System (ADS)

    Ritprasertsri, Thitima; Chutima, Parames

    2017-06-01

    In all industries, time losses, which are incurred in processing are very important. As a result, losses are incurred in productivity and cost. This research aimed to reduce lost time that occurs in sauce production line by using the lean six sigma approach. The main objective was to reduce the time for heating sauce which causes a lot of time lost in the production line which affects productivity. The methodology was comprised of the five-phase improvement model of Six Sigma. This approach begins with defining phase, measuring phase, analysing phase, improving phase and controlling phase. Cause-and-effect matrix and failure mode and effect analysis (FMEA) were adopted to screen the factors which affect production time loss. The results showed that the percentage of lost time from heating sauce reduced by 47.76%. This increased productivity to meet the plan.

  6. Change of Precipitation Behavior and Impact Toughness with Depths in Quenched Thick SAF 2507 Super Duplex Stainless Steel

    NASA Astrophysics Data System (ADS)

    Ahiale, Godwin Kwame; Kim, Doo-Hyun; Yang, Won-Jon; Lee, Jong-Hoon; Oh, Yong-Jun

    2018-03-01

    We investigated the change of precipitation behavior and impact resistance as a function of depth from the surface of thick block of SAF 2507 super duplex stainless steel with the thickness (T) of 200 mm after water quenching from 1050 °C. The amount of detrimental sigma phase increased smoothly until the depth of 0.25T, followed by a rapid increase from 0.25T to the center. However, the impact strength decreased significantly with only 1.3% of area fraction of sigma phase as the depth increased past 0.1T. Based on fractography analysis for the samples at such small depth ranges, the distance between the sigma phase particles affected the relative amount of initiating brittle cracks in front of the notch and was one of the crucial factors that dramatically reduced impact resistance with depth.

  7. Acceleration and collimation of relativistic plasmas ejected by fast rotators

    NASA Astrophysics Data System (ADS)

    Bogovalov, S. V.

    2001-06-01

    A stationary self-consistent outflow of a magnetised relativistic plasma from a rotating object with an initially monopole-like magnetic field is investigated in the ideal MHD approximation under the condition sigma U02 > 1, where sigma is the ratio of the Poynting flux over the mass energy flux at the equator and the surface of the star, with U0=gamma 0v0/c and gamma0 the initial four-velocity and Lorentz factor of the plasma. The mechanism of the magnetocentrifugal acceleration and self-collimation of the relativistic plasma is investigated. A jet-like relativistic flow along the axis of rotation is found in the steady-state solution under the condition sigma U02 > 1 with properties predicted analytically. The amount of the collimated matter in the jet is rather small in comparison to the total mass flux in the wind. An explanation for the weak self-collimation of relativistic winds is given.

  8. Operating and environmental characteristics of Sigma Tau hydrogen masers used in the Very Long Baseline Array (VLBA)

    NASA Technical Reports Server (NTRS)

    Tucker, T. K.

    1989-01-01

    Presented here are the results obtained from performance evaluation of a pair of Sigma Tau Standards Corporation Model VLBA-112 active hydrogen maser frequency standards. These masers were manufactured for the National Radio Astronomy Observatory (NRAO) for use on the Very Long Baseline Array (VLBA) project and were furnished to the Jet Propulsion Laboratory (JPL) for the purpose of these tests. Tests on the two masers were performed in the JPL Frequency Standards Laboratory (FSL) and included the characterization of output frequency stability versus environmental factors such as temperature, humidity, magnetic field, and barometric pressure. The performance tests also included the determination of phase noise and Allan variance using both FSL and Sigma Tau masers as references. All tests were conducted under controlled laboratory conditions, with only the desired environmental and operational parameters varied to determine sensitivity to external environment.

  9. Introduction to Sigma Proteins: Evolution of the Concept of Sigma Receptors.

    PubMed

    Kim, Felix J

    2017-01-01

    For over 40 years, scientists have endeavored to understand the so-called sigma receptors. During this time, the concept of sigma receptors has continuously and significantly evolved. With thousands of publications on the subject, these proteins have been implicated in various diseases, disorders, and physiological processes. Nevertheless, we are just beginning to understand what sigma proteins do and how they work. Two subtypes have been identified, Sigma1 and Sigma2. Whereas Sigma1 (also known as sigma-1 receptor, Sig1R, σ1 receptor, and several other names) was cloned over 20 years ago, Sigma2 (sigma-2 receptor, σ2 receptor) was cloned very recently and had remained a pharmacologically defined entity. In this volume, we will focus primarily on Sigma1. We will highlight several key subject areas in which Sigma1 has been well characterized as well as (re)emerging areas of interest. Despite the large number of publications regarding Sigma1, several fundamental questions remain unanswered or only partially answered. Most of what we know about Sigma1 comes from pharmacological studies; however, a clearly defined molecular mechanism of action remains elusive. One concept has become clear; Sigma1 is not a traditional receptor. Sigma1 is now considered a unique pharmacologically regulated integral membrane chaperone or scaffolding protein. A number of landmark discoveries over the past decade have begun to reshape the concept of sigma receptors. With the rapid emergence of new information, development of new tools, and changing conceptual frameworks, the field is poised for a period of accelerated progress.

  10. Facilitating process changes in meal delivery and radiological testing to improve inpatient insulin timing using six sigma method.

    PubMed

    Yamamoto, J Jay; Malatestinic, Bill; Lehman, Angela; Juneja, Rattan

    2010-01-01

    The objective of this project was to improve the timing of inpatient insulin administration related to meal delivery and the scheduling of radiology tests by Lean Six Sigma method. A multidisciplinary hospital team and a Six Sigma team from a pharmaceutical manufacturer collaborated to evaluate food delivery and radiology scheduling processes related to the timing of insulin administration. Key factors leading to problems within each system were addressed to improve the efficiency of each process while improving the timeliness of glucose testing and insulin administration. Standardizing the food delivery schedule and utilizing scorecards to track on-time meal deliveries to the floor enabled nursing to more accurately administer insulin in coordination with the delivery of meals. Increasing communication and restricting the scheduling of inpatient procedures during mealtimes reduced disruptions to insulin administration. Data at 6 months postimplementation demonstrated that the institution met goals for most primary outcome metrics including increasing on-time meal delivery and the proportion of patients taking insulin scheduled for radiology tests during appropriate times. By implementing the recommendations identified via Lean Six Sigma, this collaborative effort improved the timing of inpatient insulin administration related to meal delivery and radiology testing.

  11. Orbital Evolution of Jupiter-Family Comets

    NASA Technical Reports Server (NTRS)

    Ipatov, S. I.; Mather, J. S.; Oegerle, William R. (Technical Monitor)

    2002-01-01

    We investigated the evolution for periods of at least 5-10 Myr of 2500 Jupiter-crossing objects (JCOs) under the gravitational influence of all planets, except for Mercury and Pluto (without dissipative factors). In the first series we considered N=2000 orbits near the orbits of 30 real Jupiter-family comets with period less than 10 yr, and in the second series we took 500 orbits close to the orbit of Comet 10P Tempel 2. We calculated the probabilities of collisions of objects with the terrestrial planets, using orbital elements obtained with a step equal to 500 yr and then summarized the results for all time intervals and all bodies, obtaining the total probability P(sub sigma) of collisions with a planet and the total time interval T(sub sigma) during which perihelion distance of bodies was less than a semimajor axis of the planet. The values of P = 10(exp 6)P(sub sigma)/N and T = T(sub sigma)/1000 yr are presented in Table together with the ratio r of the total time interval when orbits were of Apollo type (at e less than 0.999) to that of Amor type.

  12. Simplified Daylight Spectrum Approximation by Blending Two Light Emitting Diode Sources

    DTIC Science & Technology

    2012-03-01

    Iota Epsilon (SIE). Michael E. Miller, PhD is an Assistant Professor of Human Systems Integration at the Air Force Institute of Technology. His...USA. Dr Grimaila’s research interests include mission assurance, network management 49 and security , quantum information warfare, and systems...Engineers (SAME) and Sigma Iota Epsilon (SIE). John Colombi, Ph.D. is an Assistant Professor of Systems Engineering at the Air Force Institute of

  13. KINETIC ENERGY DISTRIBUTION OF H(1s) FROM H{sub 2} X {sup 1}{Sigma}{sup +} {sub g}-a {sup 3}{Sigma}{sup +} {sub g} EXCITATION AND LIFETIMES AND TRANSITION PROBABILITIES OF a {sup 3}{Sigma}{sup +} {sub g}(v, J)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liu Xianming; Johnson, Paul V.; Malone, Charles P.

    Dissociative excitation of molecular hydrogen plays an important role in the heating of outer planet upper thermospheres. This paper addresses the role of one of the triplet states involved in the process. H{sub 2} excited to the a {sup 3}{Sigma}{sup +} {sub g} state, or higher triplet-ungerade states, is dissociated via the a {sup 3}{Sigma}{sup +} {sub g}-b {sup 3}{Sigma}{sup +} {sub u} continuum. The kinetic energy distribution of H(1s) produced from direct X {sup 1}{Sigma}{sup +} {sub g}-a {sup 3}{Sigma}{sup +} {sub g}(v, J) excitation by electrons is investigated by an accurate theoretical evaluation of spontaneous transition probabilities ofmore » the a {sup 3}{Sigma}{sup +} {sub g}(v, J)-b {sup 3}{Sigma}{sup +} {sub u} continuum transition. It is shown that the X {sup 1}{Sigma}{sup +} {sub g}(0)-a {sup 3}{Sigma}{sup +} {sub g}(v, J) excitation primarily produces H(1s) atoms with kinetic energies lower than 2 eV. In addition to the continuum a {sup 3}{Sigma}{sup +} {sub g}(v, J)-b {sup 3}{Sigma}{sup +} {sub u} transition probabilities, spontaneous emission lifetimes of the a {sup 3}{Sigma}{sup +} {sub g}(v, J) (v = 0-20, J {<=} 14) levels have been calculated by considering both the a {sup 3}{Sigma}{sup +} {sub g}-b {sup 3}{Sigma}{sup +} {sub u} and a {sup 3}{Sigma}{sup +} {sub g}-c {sup 3}{Pi} {sub u} transitions. The calculated lifetimes show a moderately strong rotational dependence, and the lifetimes for the J = 0 rotational level of the low v levels agree well with previous calculations and experimental measurements. Calculations of the a {sup 3}{Sigma}{sup +} {sub g}-b {sup 3}{Sigma}{sup +} {sub u} continuum emission spectra from electron impact X {sup 1}{Sigma}{sup +} {sub g}-a {sup 3}{Sigma}{sup +} {sub g} excitation are included.« less

  14. Bacillus subtilis extracytoplasmic function (ECF) sigma factors and defense of the cell envelope

    PubMed Central

    Helmann, John D.

    2016-01-01

    Summary Bacillus subtilis provides a model for investigation of the bacterial cell envelope, the first line of defense against environmental threats. Extracytoplasmic function (ECF) sigma factors activate genes that confer resistance to agents that threaten the integrity of the envelope. Although their individual regulons overlap, σW is most closely associated with membrane-active agents, σX with cationic antimicrobial peptide resistance, and σV with resistance to lysozyme. Here, I highlight the role of the σM regulon, which is strongly induced by conditions that impair peptidoglycan synthesis and includes the core pathways of envelope synthesis and cell division, as well as stress-inducible alternative enzymes. Studies of these cell envelope stress responses provide insights into how bacteria acclimate to the presence of antibiotics. PMID:26901131

  15. Evolution of the transcription complex during sporulation of Bacillus subtilis.

    PubMed

    Brevet, J

    1976-01-01

    Ribonucleic acid polymerase activity in partially purified extract of cells of Bacillus subtilis harvested at different times (t-1, to, t1, and t2) was studied by zone centrifugation. During the course of sporulation, vegetative sigma-factor activity decreased and the transcription complex lost some of its affinity for active sigma factor. The complex underwent a two-stage change in sedimentation value, from 14.5S in vegetative growth phase to a 13S species very early in sporulation to a 16S species at later times. Two SpoO mutants have been studied by zone centrifugation. One strain, a rifampin-resistant (RfmR) mutant, failed to show any modification of the transcription complex, whereas the other, a Rfms strain, underwent a partial evolution of the transcription complex after to.

  16. Integer Flows and Circuit Covers of Graphs and Signed Graphs

    NASA Astrophysics Data System (ADS)

    Cheng, Jian

    The work in Chapter 2 is motivated by Tutte and Jaeger's pioneering work on converting modulo flows into integer-valued flows for ordinary graphs. For a signed graphs (G, sigma), we first prove that for each k ∈ {2, 3}, if (G, sigma) is (k - 1)-edge-connected and contains an even number of negative edges when k = 2, then every modulo k-flow of (G, sigma) can be converted into an integer-valued ( k + 1)-ow with a larger or the same support. We also prove that if (G, sigma) is odd-(2p+1)-edge-connected, then (G, sigma) admits a modulo circular (2 + 1/ p)-flows if and only if it admits an integer-valued circular (2 + 1/p)-flows, which improves all previous result by Xu and Zhang (DM2005), Schubert and Steffen (EJC2015), and Zhu (JCTB2015). Shortest circuit cover conjecture is one of the major open problems in graph theory. It states that every bridgeless graph G contains a set of circuits F such that each edge is contained in at least one member of F and the length of F is at most 7/5∥E(G)∥. This concept was recently generalized to signed graphs by Macajova et al. (JGT2015). In Chapter 3, we improve their upper bound from 11∥E( G)∥ to 14/3 ∥E(G)∥, and if G is 2-edgeconnected and has even negativeness, then it can be further reduced to 11/3 ∥E(G)∥. Tutte's 3-flow conjecture has been studied by many graph theorists in the last several decades. As a new approach to this conjecture, DeVos and Thomassen considered the vectors as ow values and found that there is a close relation between vector S1-flows and integer 3-NZFs. Motivated by their observation, in Chapter 4, we prove that if a graph G admits a vector S1-flow with rank at most two, then G admits an integer 3-NZF. The concept of even factors is highly related to the famous Four Color Theorem. We conclude this dissertation in Chapter 5 with an improvement of a recent result by Chen and Fan (JCTB2016) on the upperbound of even factors. We show that if a graph G contains an even factor, then it contains an even factor H with. ∥E(H)∥ ≥ 4/7 (∥ E(G)∥+1)+ 1/7 ∥V2 (G)∥, where V2( G) is the set of vertices of degree two.

  17. Utilizing NASA EOS Data for Fire Management in el Departmento del Valle del Cauco, Colombia

    NASA Astrophysics Data System (ADS)

    Brenton, J. C.; Bledsoe, N.; Alabdouli, K.

    2012-12-01

    In the last few years, fire incidence in Colombian wild areas has increased, damaging pristine forests into savannas and sterile lands. Fire poses a significant threat to biodiversity, rural communities and established infrastructure. These events issue an urgent need to address this problem. NASA Earth Observing System (EOS) can play a significant role in the monitoring fires and natural disasters. SERVIR, the Regional Visualization and Monitoring Network, constitutes a platform for the observation, forecasting and modeling of environmental processes in Central America. A project called "The GIS for fire management in Guatemala (SIGMA-I)" has been already conducted to address the same problem in another Latin American country, Guatemala. SIGMA-I was developed by the Inter-agency work among the National protected areas council (CONAP), National Forestry Institution (INAB), the National Coordinator for Disaster Reduction / National Forest Fire Prevention and Control System (CONRED/SIPECIF), and the Ministry of the Environment and National Resources (MARN) in Guatemala under the guidance and assistance of SERVIR. With SIGMA-I as an example, we proposed to conduct a similar project for the country of Colombia. First, a pilot study in the area of the watershed of the Cali River, Colombia was conducted to ensure that the data was available and that the maps and models were accurate. The proposed study will investigate the technical resources required: 1.) A fire map with a compilation of ignition data (hot spots) utilizing Fire Information for Resource Management System (FIRMS) derived from MODIS (Moderate Resolution Imaging Spectroradiometer) products MOD14 and MYD14 2.) A map of fire scars derived from medium resolution satellite data (ASTER) during the period 2003-2011 for the entire country, and a map of fire scar recurrence and statistics derived from the datasets produced. 3.) A pattern analysis and ignition cause model derived from a matrix of variables statistically exploring the demographic and environmental factors of fire risk, such as land surface temperature, precipitation, and NDVI .4.) A dynamic fire risk evaluation able to generate a dynamic map of ignition risk based on statistical analysis factors. This study aims to research integrating MODIS, Landsat and ASTER data along with in-situ data on environmental parameters from the Corporation of the Cauca Valley River (CVC) along with other data on social, economical and cultural variables obtained by researchers of the Wild Fire Observatory (OCIF) from the "Universidad Autónoma de Occidente" in order to create an ignition cause model, dynamic fire risk evaluation system and compile any and all geospatial data generated for the region. In this way the research will help predict and forecast fire vulnerabilities in the region. The team undertook this project through SERVIR with the guidance of the scientist, Victor Hugo Ramos, who was the leader and principal investigator on the SIGMA-I.

  18. Procedures for estimating confidence intervals for selected method performance parameters.

    PubMed

    McClure, F D; Lee, J K

    2001-01-01

    Procedures for estimating confidence intervals (CIs) for the repeatability variance (sigmar2), reproducibility variance (sigmaR2 = sigmaL2 + sigmar2), laboratory component (sigmaL2), and their corresponding standard deviations sigmar, sigmaR, and sigmaL, respectively, are presented. In addition, CIs for the ratio of the repeatability component to the reproducibility variance (sigmar2/sigmaR2) and the ratio of the laboratory component to the reproducibility variance (sigmaL2/sigmaR2) are also presented.

  19. Widely different luminescence lifetimes of the [Delta]RRR, [Lambda]SSS and the [Delta]RRS, [Lambda]SSR diastereomers of fac-tris[(8-quinolyl)phenylmethylsily] iridium(III): Exciplex formation with solvents by distinct [sigma]-donor and [pi]-acceptor binding mechanisms

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Djurovich, P.I.; Cook, W.; Joshi, R.

    1994-01-13

    Luminescence lifetimes ([tau][sub m]) of the [sigma]-bond-to-ligand charge-transfer (SBLCT) excited states of two diastereomers of fac-tris[(8-quinolyl)phenylmethylsilyl]iridium(III) differ by about a factor of 2 and are strongly solvent dependent. The [tau][sub m] values of the more symmetric [Delta]RRR, [Lambda]SSS diastereomer (A) are generally longer than those of the less symmetric [Delta]RRS, [Lambda]SSR diastereomer (B); [tau][sub m]'s of both diastereomers are substantially shortened relative to their values in aliphatic hydrocarbons by exciplex formation with a variety of weakly coordinating solvents including aromatic hydrocarbons, olefins, ethers, ketones, alcohols, and nitriles. Quenching constants (k[sub q]) due to exciplex formation are found to be muchmore » larger for B than they are for A in the [sigma]-donor solvents (cyclic ethers, ketones, alcohols, and nitriles); however, k[sub q] values of B are slightly smaller than those of A in [pi]-acceptor solvents (aromatic hydrocarbons, olefins). The results suggest that [sigma]-donor solvents form exciplexes by binding at the metal center, whereas [pi]-acceptor solvents bind at a quinolyl radical anion ligand site. A and B may prove useful as luminescent environmental probes which can distinguish between [sigma]-donor and [pi]-acceptor binding sites. 19 refs., 1 fig., 1 tab.« less

  20. Classification and pose estimation of objects using nonlinear features

    NASA Astrophysics Data System (ADS)

    Talukder, Ashit; Casasent, David P.

    1998-03-01

    A new nonlinear feature extraction method called the maximum representation and discrimination feature (MRDF) method is presented for extraction of features from input image data. It implements transformations similar to the Sigma-Pi neural network. However, the weights of the MRDF are obtained in closed form, and offer advantages compared to nonlinear neural network implementations. The features extracted are useful for both object discrimination (classification) and object representation (pose estimation). We show its use in estimating the class and pose of images of real objects and rendered solid CAD models of machine parts from single views using a feature-space trajectory (FST) neural network classifier. We show more accurate classification and pose estimation results than are achieved by standard principal component analysis (PCA) and Fukunaga-Koontz (FK) feature extraction methods.

  1. Conservation of σ28-Dependent Non-Coding RNA Paralogs and Predicted σ54-Dependent Targets in Thermophilic Campylobacter Species

    PubMed Central

    Le, My Thanh; van Veldhuizen, Mart; Porcelli, Ida; Bongaerts, Roy J.; Gaskin, Duncan J. H.; Pearson, Bruce M.; van Vliet, Arnoud H. M.

    2015-01-01

    Assembly of flagella requires strict hierarchical and temporal control via flagellar sigma and anti-sigma factors, regulatory proteins and the assembly complex itself, but to date non-coding RNAs (ncRNAs) have not been described to regulate genes directly involved in flagellar assembly. In this study we have investigated the possible role of two ncRNA paralogs (CjNC1, CjNC4) in flagellar assembly and gene regulation of the diarrhoeal pathogen Campylobacter jejuni. CjNC1 and CjNC4 are 37/44 nt identical and predicted to target the 5' untranslated region (5' UTR) of genes transcribed from the flagellar sigma factor σ54. Orthologs of the σ54-dependent 5' UTRs and ncRNAs are present in the genomes of other thermophilic Campylobacter species, and transcription of CjNC1 and CNC4 is dependent on the flagellar sigma factor σ28. Surprisingly, inactivation and overexpression of CjNC1 and CjNC4 did not affect growth, motility or flagella-associated phenotypes such as autoagglutination. However, CjNC1 and CjNC4 were able to mediate sequence-dependent, but Hfq-independent, partial repression of fluorescence of predicted target 5' UTRs in an Escherichia coli-based GFP reporter gene system. This hints towards a subtle role for the CjNC1 and CjNC4 ncRNAs in post-transcriptional gene regulation in thermophilic Campylobacter species, and suggests that the currently used phenotypic methodologies are insufficiently sensitive to detect such subtle phenotypes. The lack of a role of Hfq in the E. coli GFP-based system indicates that the CjNC1 and CjNC4 ncRNAs may mediate post-transcriptional gene regulation in ways that do not conform to the paradigms obtained from the Enterobacteriaceae. PMID:26512728

  2. Strategic Assessment of Lean Six Sigma Practicality in the Turkish Army

    DTIC Science & Technology

    2015-12-01

    quo is not responding to the current problem that the organization should create a need to overcome resistance and mobilize commitment. The second...we think this factor has a small effect on LSS aplication in an organization since questions in this factor focus on individual employees’ perceptions

  3. ςBldN, an Extracytoplasmic Function RNA Polymerase Sigma Factor Required for Aerial Mycelium Formation in Streptomyces coelicolor A3(2)

    PubMed Central

    Bibb, Maureen J.; Molle, Virginie; Buttner, Mark J.

    2000-01-01

    Sporulation mutants of Streptomyces coelicolor appear white because they are defective in the synthesis of the gray polyketide spore pigment, and such white (whi) mutants have been used to define 13 sporulation loci. whiN, one of five new whi loci identified in a recent screen of NTG (N-methyl-N′-nitro-N-nitrosoguanidine)-induced whi strains (N. J. Ryding et al., J. Bacteriol. 181:5419–5425, 1999), was defined by two mutants, R112 and R650. R650 produced frequent spores that were longer than those of the wild type. In contrast, R112 produced long, straight, undifferentiated hyphae, although rare spore chains were observed, sometimes showing highly irregular septum placement. Subcloning and sequencing showed that whiN encodes a member of the extracytoplasmic function subfamily of RNA polymerase sigma factors and that the sigma factor has an unusual N-terminal extension of approximately 86 residues that is not present in other sigma factors. A constructed whiN null mutant failed to form aerial mycelium (the “bald” phenotype) and, as a consequence, whiN was renamed bldN. This observation was not totally unexpected because, on some media, the R112 point mutant produced substantially less aerial mycelium than its parent, M145. The bldN null mutant did not fit simply into the extracellular signaling cascade proposed for S. coelicolor bld mutants. Expression of bldN was analyzed during colony development in wild-type and aerial mycelium-deficient bld strains. bldN was transcribed from a single promoter, bldNp. bldN transcription was developmentally regulated, commencing approximately at the time of aerial mycelium formation, and depended on bldG and bldH, but not on bldA, bldB, bldC, bldF, bldK, or bldJ or on bldN itself. Transcription from the p1 promoter of the response-regulator gene bldM depended on bldN in vivo, and the bldMp1 promoter was shown to be a direct biochemical target for ςBldN holoenzyme in vitro. PMID:10913095

  4. A Study of the X(sup 2) Sigma(sup +) and A(sup 2) Pi States of MgAr(sup +) and MgKr(sup +)

    NASA Technical Reports Server (NTRS)

    Bauschlicher, Charles W., Jr.; Partridge, Harry; Langhoff, Stephen R. (Technical Monitor)

    1995-01-01

    The ground (sup 2)Sigma(sup +) and lowest excited (sup 2)Pi states of MgAr(sup +) and MgKr(sup +) are studied using the singles and doubles configuration interaction (SDCI) approach, in conjunction with large basis sets. The effect of Mg core correlation and core polarization are accounted for using the core-polarization potential (CPP) approach. Franck-Condon factors, oscillator strengths, radiative lifetimes, dissociation energies, bond lengths, and excitation energies are reported. The computed results are in good agreement with the available experimental data.

  5. Practical recursive solution of degenerate Rayleigh-Schroedinger perturbation theory and application to high-order calculations of the Zeeman effect in hydrogen

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Silverstone, H.J.; Moats, R.K.

    1981-04-01

    With the aim of high-order calculations, a new recursive solution for the degenerate Rayleigh-Schroedinger perturbation-theory wave function and energy has been derived. The final formulas, chi/sup (N/)/sub sigma/ = R/sup () -sigma/summation/sup N/-1/sub k/ = 0 H/sup (sigma+1+k/)/sub sigma+1/chi/sup (N/-1-k), E/sup (N/+sigma) = <0Vertical BarH/sup (N/+sigma)/sub sigma+1/Vertical Bar0> + < 0Vertical Barsummation/sup N/-2/sub k/ = 0H/sup (sigma+1+k/)/sub sigma+1/ Vertical Barchi/sup (N/-1-k)>,which involve new Hamiltonian-related operators H/sup (sigma+k/)/sub sigma/ and H/sup( sigma+k/)/sub sigma/, strongly resemble the standard nondegenerate recursive formulas. As an illustration, the perturbed energy coefficients for the 3s-3d/sub 0/ states of hydrogen in the Zeeman effect have been calculatedmore » recursively through 87th order in the square of the magnetic field. Our treatment is compared with that of Hirschfelder and Certain (J. Chem. Phys. 60, 1118 (1974)), and some relative advantages of each are pointed out.« less

  6. Short communication; Formula for the calculation of ground temperature at 1 M depth in Turkey

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tezcan, A.K.

    1992-06-01

    This paper reports that the formula has been found by using the yearly averages of the temperatures at 1 m depth measured in 193 meteorological stations, distributed all over Turkey. It has thus become possible to determine the regional temperature value at 1 m depth at any point in Turkey, if the latitude, longitude and elevation are known. The values, calculated by the formula, can contribute to geothermal exploration in Turkey by providing values that can be compared with the observed ones, and, by becoming second values for the calculation of geothermal gradients where only single downhole temperatures are available.more » The formula has been evolved by expressing the temperatures as the linear function of latitude (La), longitude (Lo) and elevation (H): T = a + b [center dot] La + c [center dot] Lo + d [center dot] H. The derived four least square equations are a [center dot] n + b [center dot] [Sigma](La) + c [center dot] [Sigma](lo) + d [center dot] [Sigma]H = [Sigma]T a [center dot] [Sigma](La) + b [center dot] [Sigma](La)[sup 2] + c [center dot] [Sigma](La)(Lo) + d [center dot] [Sigma]H(La) =[Sigma]T(La) a [center dot] [Sigma](Lo) + b [center dot] [Sigma](La)(Lo) + c [center dot] [Sigma](Lo)[sup 2] + d [center dot] [Sigma]H(Lo) = [Sigma]T(Lo) a[center dot] [Sigma]H + b [center dot] [Sigma]H(La) + c [center dot] [Sigma](Lo) + d [center dot] [Sigma]H[sup 2] = [Sigma]TH where n is the number of data sets. The calculation of sigma values and the solution of the set of equations have been performed by means of a personal computer. The resulting formula is: T = 57.487 [minus] 1.078 La + 0.102 Lo [minus] 0.00488H where latitude and longitude are expressed in degrees, and elevation in meters. The regional value at Ankara (latitude 39.9[degrees], longitude 32.9[degrees], elevation 894 m) is calculated as 13.5[degrees]C (the measured value at 1 m depth is 14.6[degrees]C) and at Adana.« less

  7. Application of Sigma Metrics Analysis for the Assessment and Modification of Quality Control Program in the Clinical Chemistry Laboratory of a Tertiary Care Hospital.

    PubMed

    Iqbal, Sahar; Mustansar, Tazeen

    2017-03-01

    Sigma is a metric that quantifies the performance of a process as a rate of Defects-Per-Million opportunities. In clinical laboratories, sigma metric analysis is used to assess the performance of laboratory process system. Sigma metric is also used as a quality management strategy for a laboratory process to improve the quality by addressing the errors after identification. The aim of this study is to evaluate the errors in quality control of analytical phase of laboratory system by sigma metric. For this purpose sigma metric analysis was done for analytes using the internal and external quality control as quality indicators. Results of sigma metric analysis were used to identify the gaps and need for modification in the strategy of laboratory quality control procedure. Sigma metric was calculated for quality control program of ten clinical chemistry analytes including glucose, chloride, cholesterol, triglyceride, HDL, albumin, direct bilirubin, total bilirubin, protein and creatinine, at two control levels. To calculate the sigma metric imprecision and bias was calculated with internal and external quality control data, respectively. The minimum acceptable performance was considered as 3 sigma. Westgard sigma rules were applied to customize the quality control procedure. Sigma level was found acceptable (≥3) for glucose (L2), cholesterol, triglyceride, HDL, direct bilirubin and creatinine at both levels of control. For rest of the analytes sigma metric was found <3. The lowest value for sigma was found for chloride (1.1) at L2. The highest value of sigma was found for creatinine (10.1) at L3. HDL was found with the highest sigma values at both control levels (8.8 and 8.0 at L2 and L3, respectively). We conclude that analytes with the sigma value <3 are required strict monitoring and modification in quality control procedure. In this study application of sigma rules provided us the practical solution for improved and focused design of QC procedure.

  8. Information Technology. DOD Needs to Strengthen Management of Its Statutorily Mandated Software and System Process Improvement Efforts

    DTIC Science & Technology

    2009-09-01

    NII)/CIO Assistant Secretary of Defense for Networks and Information Integration/Chief Information Officer CMMI Capability Maturity Model...a Web-based portal to share knowledge about software process-related methodologies, such as the SEI’s Capability Maturity Model Integration ( CMMI ...19 SEI’s IDEALSM model, and Lean Six Sigma.20 For example, the portal features content areas such as software acquisition management, the SEI CMMI

  9. Expression of sigma receptor 1 mRNA and protein in rat retina.

    PubMed

    Liu, L L; Wang, L; Zhong, Y M; Yang, X L

    2010-06-02

    Sigma receptor (sigmaR), known as a unique nonopiate, nonphencyclidine brain receptor, can bind diverse classes of psychotropic drugs, neurosteroids and other synthetic compounds, such as (+)pentazocine, etc. Two types of sigmaRs have been identified: sigmaR1 and sigmaR2. In this work, we examined the expression of sigmaR1 in rat retina by reverse transcription-polymerase chain reactive (RT-PCR) analysis and immunofluorescence double labeling. RT-PCR analysis showed that sigmaR1 mRNA was present in rat retina. Furthermore, labeling for sigmaR1 was diffusely distributed in the outer and inner plexiform layers. The sigmaR1-immunoreactivity (IR) was also observed in many cells in the inner nuclear layer and the ganglion cell layer. In the outer retina sigmaR1 was expressed in all horizontal cells labeled by calbindin. In contrast, no sigmaR1-IR was detected in several subtypes of bipolar cells, including rod-dominant ON-type bipolar cells, types 2, 3, 5 and 8 bipolar cells, labeled by protein kinase C (PKC), recoverin and hyperpolarization-activated cyclic nucleotide-gated potassium channel 4 (HCN4) respectively. In the inner retina, most of GABAergic amacrine cells, including dopaminergic and cholinergic ones, stained by tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT) respectively, expressed sigmaR1. Some glycinergic amacrine cells were also labeled by sigmaR1, but glycinergic AII amacrine cells were not labeled. In addition, sigmaR1-IR was seen in almost all somata of the ganglion cells retrogradely labeled by fluorogold. These results suggest that sigmaR1 may have neuromodulatory and neuroprotective roles in the retina. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. Monte Carlo analysis of uncertainty propagation in a stratospheric model. 2: Uncertainties due to reaction rates

    NASA Technical Reports Server (NTRS)

    Stolarski, R. S.; Butler, D. M.; Rundel, R. D.

    1977-01-01

    A concise stratospheric model was used in a Monte-Carlo analysis of the propagation of reaction rate uncertainties through the calculation of an ozone perturbation due to the addition of chlorine. Two thousand Monte-Carlo cases were run with 55 reaction rates being varied. Excellent convergence was obtained in the output distributions because the model is sensitive to the uncertainties in only about 10 reactions. For a 1 ppby chlorine perturbation added to a 1.5 ppby chlorine background, the resultant 1 sigma uncertainty on the ozone perturbation is a factor of 1.69 on the high side and 1.80 on the low side. The corresponding 2 sigma factors are 2.86 and 3.23. Results are also given for the uncertainties, due to reaction rates, in the ambient concentrations of stratospheric species.

  11. Bacillus subtilis extracytoplasmic function (ECF) sigma factors and defense of the cell envelope.

    PubMed

    Helmann, John D

    2016-04-01

    Bacillus subtilis provides a model for investigation of the bacterial cell envelope, the first line of defense against environmental threats. Extracytoplasmic function (ECF) sigma factors activate genes that confer resistance to agents that threaten the integrity of the envelope. Although their individual regulons overlap, σ(W) is most closely associated with membrane-active agents, σ(X) with cationic antimicrobial peptide resistance, and σ(V) with resistance to lysozyme. Here, I highlight the role of the σ(M) regulon, which is strongly induced by conditions that impair peptidoglycan synthesis and includes the core pathways of envelope synthesis and cell division, as well as stress-inducible alternative enzymes. Studies of these cell envelope stress responses provide insights into how bacteria acclimate to the presence of antibiotics. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Multi-level evaluation of Escherichia coli polyphosphate related mutants using global transcriptomic, proteomic and phenomic analyses.

    PubMed

    Varas, Macarena; Valdivieso, Camilo; Mauriaca, Cecilia; Ortíz-Severín, Javiera; Paradela, Alberto; Poblete-Castro, Ignacio; Cabrera, Ricardo; Chávez, Francisco P

    2017-04-01

    Polyphosphate (polyP) is a linear biopolymer found in all living cells. In bacteria, mutants lacking polyphosphate kinase 1 (PPK1), the enzyme responsible for synthesis of most polyP, have many structural and functional defects. However, little is known about the causes of these pleiotropic alterations. The link between ppk1 deletion and those numerous phenotypes observed can be the result of complex molecular interactions that can be elucidated via a systems biology approach. By integrating different omics levels (transcriptome, proteome and phenome), we described the functioning of various metabolic pathways among Escherichia coli polyphosphate mutant strains (Δppk1, Δppx, and ΔpolyP). Bioinformatic analyses reveal the complex metabolic and regulatory bases of the phenotypes unique to polyP mutants. Our results suggest that during polyP deficiency (Δppk1 mutant), metabolic pathways needed for energy supply are up-regulated, including fermentation, aerobic and anaerobic respiration. Transcriptomic and q-proteomic contrasting changes between Δppk1 and Δppx mutant strains were observed in those central metabolic pathways and confirmed by using Phenotypic microarrays. In addition, our results suggest a regulatory connection between polyP, second messenger metabolism, alternative Sigma/Anti-Sigma factors and type-II toxin-antitoxin (TA) systems. We suggest a broader role for polyP via regulation of ATP-dependent proteolysis of type II toxin-antitoxin system and alternative Sigma/Anti-Sigma factors, that could explain the multiple structural and functional deficiencies described due to alteration of polyP metabolism. Understanding the interplay of polyP in bacterial metabolism using a systems biology approach can help to improve design of novel antimicrobials toward pathogens. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. THE VIRUS-P EXPLORATION OF NEARBY GALAXIES (VENGA): THE X {sub CO} GRADIENT IN NGC 628

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Blanc, Guillermo A.; Schruba, Andreas; Evans, Neal J. II

    2013-02-20

    We measure the radial profile of the {sup 12}CO(1-0) to H{sub 2} conversion factor (X {sub CO}) in NGC 628. The H{alpha} emission from the VENGA integral field spectroscopy is used to map the star formation rate (SFR) surface density ({Sigma}{sub SFR}). We estimate the molecular gas surface density ({Sigma}{sub H2}) from {Sigma}{sub SFR} by inverting the molecular star formation law (SFL), and compare it to the CO intensity to measure X {sub CO}. We study the impact of systematic uncertainties by changing the slope of the SFL, using different SFR tracers (H{alpha} versus far-UV plus 24 {mu}m), and COmore » maps from different telescopes (single-dish and interferometers). The observed X {sub CO} profile is robust against these systematics, drops by a factor of two from R {approx} 7 kpc to the center of the galaxy, and is well fit by a gradient {Delta}log(X {sub CO}) = 0.06 {+-} 0.02 dex kpc{sup -1}. We study how changes in X {sub CO} follow changes in metallicity, gas density, and ionization parameter. Theoretical models show that the gradient in X {sub CO} can be explained by a combination of decreasing metallicity, and decreasing {Sigma}{sub H2} with radius. Photoelectric heating from the local UV radiation field appears to contribute to the decrease of X {sub CO} in higher density regions. Our results show that galactic environment plays an important role at setting the physical conditions in star-forming regions, in particular the chemistry of carbon in molecular complexes, and the radiative transfer of CO emission. We caution against adopting a single X {sub CO} value when large changes in gas surface density or metallicity are present.« less

  14. Expression, subcellular localization, and regulation of sigma receptor in retinal muller cells.

    PubMed

    Jiang, Guoliang; Mysona, Barbara; Dun, Ying; Gnana-Prakasam, Jaya P; Pabla, Navjotsin; Li, Weiguo; Dong, Zheng; Ganapathy, Vadivel; Smith, Sylvia B

    2006-12-01

    Sigma receptors (sigmaRs) are nonopioid, nonphencyclidine binding sites with robust neuroprotective properties. Type 1 sigmaR1 (sigmaR1) is expressed in brain oligodendrocytes, but its expression and binding capacity have not been analyzed in retinal glial cells. This study examined the expression, subcellular localization, binding activity, and regulation of sigmaR1 in retinal Müller cells. Primary mouse Müller cells (MCs) were analyzed by RT-PCR, immunoblotting, and immunocytochemistry for the expression of sigmaR1, and data were compared with those of the rat Müller cell line (rMC-1) and the rat ganglion cell line (RGC-5). Confocal microscopy was used to determine the subcellular sigmaR1 location in primary mouse MCs. Membranes prepared from these cells were used for binding assays with [3H]-pentazocine (PTZ). The kinetics of binding, the ability of various sigmaR1 ligands to compete with sigmaR1 binding, and the effects of donated nitric oxide (NO) and reactive oxygen species (ROS) on binding were examined. sigmaR1 is expressed in primary mouse MCs and is localized to the nuclear and endoplasmic reticulum membranes. Binding assays showed that in primary mouse MCs, rMC-1, and RGC-5, the binding of PTZ was saturable. [3H]-PTZ bound with high affinity in RGC-5 and rMC-1 cells, and the binding was similarly robust in primary mouse MCs. Competition studies showed marked inhibition of [3H]-PTZ binding in the presence of sigmaR1-specific ligands. Incubation of cells with NO and ROS donors markedly increased sigmaR1 binding activity. MCs express sigmaR1 and demonstrate robust sigmaR1 binding activity, which is inhibited by sigmaR1 ligands and is stimulated during oxidative stress. The potential of Müller cells to bind sigmaR1 ligands may prove beneficial in retinal degenerative diseases such as diabetic retinopathy.

  15. Reducing the risk of healthcare-associated infections through Lean Six Sigma: The case of the medicine areas at the Federico II University Hospital in Naples (Italy).

    PubMed

    Improta, Giovanni; Cesarelli, Mario; Montuori, Paolo; Santillo, Liberatina Carmela; Triassi, Maria

    2018-04-01

    Lean Six Sigma (LSS) has been recognized as an effective management tool for improving healthcare performance. Here, LSS was adopted to reduce the risk of healthcare-associated infections (HAIs), a critical quality parameter in the healthcare sector. Lean Six Sigma was applied to the areas of clinical medicine (including general medicine, pulmonology, oncology, nephrology, cardiology, neurology, gastroenterology, rheumatology, and diabetology), and data regarding HAIs were collected for 28,000 patients hospitalized between January 2011 and December 2016. Following the LSS define, measure, analyse, improve, and control cycle, the factors influencing the risk of HAI were identified by using typical LSS tools (statistical analyses, brainstorming sessions, and cause-effect diagrams). Finally, corrective measures to prevent HAIs were implemented and monitored for 1 year after implementation. Lean Six Sigma proved to be a useful tool for identifying variables affecting the risk of HAIs and implementing corrective actions to improve the performance of the care process. A reduction in the number of patients colonized by sentinel bacteria was achieved after the improvement phase. The implementation of an LSS approach could significantly decrease the percentage of patients with HAIs. © 2017 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley & Sons Ltd.

  16. Zinc-responsive regulation of alternative ribosomal protein genes in Streptomyces coelicolor involves zur and sigmaR.

    PubMed

    Owen, Gillian A; Pascoe, Ben; Kallifidas, Dimitris; Paget, Mark S B

    2007-06-01

    Streptomyces coelicolor contains paralogous versions of seven ribosomal proteins (S14, S18, L28, L31, L32, L33, and L36), which differ in their potential to bind structural zinc. The paralogues are termed C(+) or C(-) on the basis of the presence or absence of putative cysteine ligands. Here, mutational studies suggest that the C(-) version of L31 can functionally replace its C(+) paralogue only when expressed at an artificially elevated level. We show that the level of expression of four transcriptional units encoding C(-) proteins is elevated under conditions of zinc deprivation. Zur controls the expression of three transcriptional units (including rpmG2, rpmE2, rpmB2, rpsN2, rpmF2, and possibly rpsR2). Zur also controls the expression of the znuACB operon, which is predicted to encode a high-affinity zinc transport system. Surprisingly, the zinc-responsive control of the rpmG3-rpmJ2 operon is dictated by sigma(R), a sigma factor that was previously shown to control the response to disulfide stress in S. coelicolor. The induction of sigma(R) activity during zinc limitation establishes an important link between thiol-disulfide metabolism and zinc homeostasis.

  17. Physicochemical properties/descriptors governing the solubility and partitioning of chemicals in water-solvent-gas systems. Part 1. Partitioning between octanol and air.

    PubMed

    Raevsky, O A; Grigor'ev, V J; Raevskaja, O E; Schaper, K-J

    2006-06-01

    QSPR analyses of a data set containing experimental partition coefficients in the three systems octanol-water, water-gas, and octanol-gas for 98 chemicals have shown that it is possible to calculate any partition coefficient in the system 'gas phase/octanol/water' by three different approaches: (1) from experimental partition coefficients obtained in the corresponding two other subsystems. However, in many cases these data may not be available. Therefore, a solution may be approached (2), a traditional QSPR analysis based on e.g. HYBOT descriptors (hydrogen bond acceptor and donor factors, SigmaCa and SigmaCd, together with polarisability alpha, a steric bulk effect descriptor) and supplemented with substructural indicator variables. (3) A very promising approach which is a combination of the similarity concept and QSPR based on HYBOT descriptors. In this approach observed partition coefficients of structurally nearest neighbours of a compound-of-interest are used. In addition, contributions arising from differences in alpha, SigmaCa, and SigmaCd values between the compound-of-interest and its nearest neighbour(s), respectively, are considered. In this investigation highly significant relationships were obtained by approaches (1) and (3) for the octanol/gas phase partition coefficient (log Log).

  18. Reducing the risk of healthcare‐associated infections through Lean Six Sigma: The case of the medicine areas at the Federico II University Hospital in Naples (Italy)

    PubMed Central

    Cesarelli, Mario; Montuori, Paolo; Santillo, Liberatina Carmela; Triassi, Maria

    2017-01-01

    Abstract Rationale, aims, and objectives Lean Six Sigma (LSS) has been recognized as an effective management tool for improving healthcare performance. Here, LSS was adopted to reduce the risk of healthcare‐associated infections (HAIs), a critical quality parameter in the healthcare sector. Methods Lean Six Sigma was applied to the areas of clinical medicine (including general medicine, pulmonology, oncology, nephrology, cardiology, neurology, gastroenterology, rheumatology, and diabetology), and data regarding HAIs were collected for 28,000 patients hospitalized between January 2011 and December 2016. Following the LSS define, measure, analyse, improve, and control cycle, the factors influencing the risk of HAI were identified by using typical LSS tools (statistical analyses, brainstorming sessions, and cause‐effect diagrams). Finally, corrective measures to prevent HAIs were implemented and monitored for 1 year after implementation. Results Lean Six Sigma proved to be a useful tool for identifying variables affecting the risk of HAIs and implementing corrective actions to improve the performance of the care process. A reduction in the number of patients colonized by sentinel bacteria was achieved after the improvement phase. Conclusions The implementation of an LSS approach could significantly decrease the percentage of patients with HAIs. PMID:29098756

  19. Enhancing the management of the noise level using six sigma method: a case study on the machining industry

    NASA Astrophysics Data System (ADS)

    Rimantho, D.; Hanantya, M. W.

    2017-12-01

    The hearing disorder is caused by noises in the workplace, it has been a concern for numerous researchers. This study aims to improve the performance of the management of the noise level by applying the six sigma method. Data collection is done directly by using a sound level meter. In addition, several key informants also used in order to gather information related to the problem. The results showed the values of Cp and Cpk on the entire department are still below the recommended value. Moreover, the results also showed the potential failure (DPMO) approximately 115,260.6 and equivalent to the Sigma value is approximately 2.70. Furthermore, the highest value of the RPN in FMEA analysis is the workers not wear factor of earplug which is about 56. Thus, it is necessary to make enhancements to the process of managing the noise level in the framework of continuous improvement.

  20. Sigma receptor type 1 gene variation in a group of Polish patients with Alzheimer's disease and mild cognitive impairment.

    PubMed

    Maruszak, Aleksandra; Safranow, Krzysztof; Gacia, Magdalena; Gabryelewicz, Tomasz; Słowik, Agnieszka; Styczyńska, Maria; Pepłońska, Beata; Golan, Maciej P; Zekanowski, Cezary; Barcikowska, Maria

    2007-01-01

    The sigma-1 receptor (SIGMAR1) is a subtype of a nonopioid sigma receptor family and is implicated in numerous functions connected with Alzheimer's disease (AD). Two common genetic variants were identified in SIGMAR1: GC-241 -240TT and Q2P (A61C). It was suggested that the TT-C haplotype is a protective factor for AD. We decided to investigate a putative link between the variants of SIGMAR1 and AD in a group of Polish patients with late-onset AD, in patients with mild cognitive impairment, and in a control group. We observed no significant differences for the SIGMAR1 allele, genotype, haplotype, and diplotype distributions between the studied groups. Multivariate logistic regression analysis showed no interaction between the APOE4 and SIGMAR1 polymorphisms. Further studies using data from different populations are required to elucidate the effect of SIGMAR1 polymorphisms on AD.

  1. Persistent organic pollutants and stable isotopes in biopsy samples (2004/2006) from Southern Resident killer whales.

    PubMed

    Krahn, Margaret M; Hanson, M Bradley; Baird, Robin W; Boyer, Richard H; Burrows, Douglas G; Emmons, Candice K; Ford, John K B; Jones, Linda L; Noren, Dawn P; Ross, Peter S; Schorr, Gregory S; Collier, Tracy K

    2007-12-01

    "Southern Resident" killer whales include three "pods" (J, K and L) that reside primarily in Puget Sound/Georgia Basin during the spring, summer and fall. This population was listed as "endangered" in the US and Canada following a 20% decline between 1996 and 2001. The current study, using blubber/epidermis biopsy samples, contributes contemporary information about potential factors (i.e., levels of pollutants or changes in diet) that could adversely affect Southern Residents. Carbon and nitrogen stable isotopes indicated J- and L-pod consumed prey from similar trophic levels in 2004/2006 and also showed no evidence for a large shift in the trophic level of prey consumed by L-pod between 1996 and 2004/2006. Sigma PCBs decreased for Southern Residents biopsied in 2004/2006 compared to 1993-1995. Surprisingly, however, a three-year-old male whale (J39) had the highest concentrations of Sigma PBDEs, Sigma HCHs and HCB. POP ratio differences between J- and L-pod suggested that they occupy different ranges in winter.

  2. Environmental fate and biodegradability of benzene derivatives as studied in a model aquatic ecosystem.

    PubMed Central

    Lu, P Y; Metcalf, R L

    1975-01-01

    A model aquatic ecosystem is devised for studying relatively volatile organic compounds and simulating direct discharge of chemical wastes into aquatic ecosystems. Six simple benzene derivatives (aniline, anisole, benzoic acid, chlorobenzene, nitrobenzene, and phthalic anhydride) and other important specialty chemicals: hexachlorobenzene, pentachlorophenol, 2,6-diethylaniline, and 3,5,6-trichloro-2-pyridinol were also chosen for study of environmental behavior and fate in the model aquatic ecosystem. Quantitative relationships of the intrinsic molecular properties of the environmental micropollutants with biological responses are established, e.g., water solubility, partition coefficient, pi constant, sigma constant, ecological magnification, biodegradability index, and comparative detoxication mechanisms, respectively. Water solubility, pi constant, and sigma constant are the most significant factors and control the biological responses of the food chain members. Water solubility and pi constant control the degree of bioaccumulation, and sigma constant limits the metabolism of the xenobiotics via microsomal detoxication enzymes. These highly significant correlations should be useful for predicting environmental fate of organic chemicals. PMID:1157796

  3. Grain boundary character, and carbide size and spatial distribution in a ternary nickel alloy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liu, H.; Gao, M.; Harlow, D.G.

    1995-06-01

    A preliminary investigation of the grain boundary character and its relationship to carbide distribution in a Ni-18Cr-18Fe ternary alloy was conducted. The results showed that there was a strong preference for the formation of {Sigma}3 (44.6%) and twin-related {Sigma}9 and {Sigma}27 CSL boundaries. If the coherent {Sigma}3{sub c} twin and the twin-related boundaries are excluded, then the distribution would consist of nearly 80% random (high angle) boundaries and about 20% CSL (with {Sigma} {<=} 49) boundaries. The size and spacing of grain boundary carbides were influenced by grain boundary {Sigma}; the carbides being smaller and more closely spaced on themore » {Sigma}1, {Sigma}9 and {Sigma}27 boundaries, and none could be resolved on the coherent {Sigma}3 twin boundaries. The results could be understood, in part, in terms of the influence of grain boundary energy, but the understanding is incomplete. Further studies are in progress and will be reported.« less

  4. Development and initial test of the University of Wisconsin global isentropic-sigma model

    NASA Technical Reports Server (NTRS)

    Zapotocny, Tom H.; Johnson, Donald R.; Reames, Fred M.

    1994-01-01

    The description of a global version of the University of Wisconsin (UW) hybrid isentropic-sigma (theta-sigma) model and the results from an initial numerical weather prediction experiment are presented in this paper. The main objectives of this initial test are to (1) discuss theta-sigma model development and computer requirements, (2) demonstrate the ability of the UW theta-sigma model for global numerical weather prediction using realistic orography and parameterized physical processes, and (3) compare the transport of an inert trace constituent against a nominally 'identical' sigma coordinate model. Initial and verifying data for the 5-day simulations presented in this work were supplied by the Goddard Earth Observing System (GEOS-1) data assimilation system. The time period studied is 1-6 February 1985. This validation experiment demonstrates that the global UW theta-sigma model produces a realistic 5-day simulation of the mass and momentum distributions when compared to both the identical sigma model and GEOS-1 verification. Root-mean-square errors demonstrate that the theta-sigma model is slightly more accurate than the nominally identical sigma model with respect to standard synoptic variables. Of particular importance, the UW theta-sigma model displays a distinct advantage over the conventional sigma model with respect to the prognostic simulation of inert trace constituent transport in amplifying baroclinic waves of the extratropics. This is especially true in the upper troposphere and stratosphere where the spatial integrity and conservation of an inert trace constituent is severely compromised in the sigma model compared to the theta-sigma model.

  5. Mechanical and structural model of fractal networks of fat crystals at low deformations.

    PubMed

    Narine, S S; Marangoni, A G

    1999-12-01

    Fat-crystal networks demonstrate viscoelastic behavior at very small deformations. A structural model of these networks is described and supported by polarized light and atomic-force microscopy. A mechanical model is described which allows the shear elastic modulus (G') of the system to be correlated with forces acting within the network. The fractal arrangement of the network at certain length scales is taken into consideration. It is assumed that the forces acting are due to van der Waals forces. The final expression for G' is related to the volume fraction of solid fat (Phi) via the mass fractal dimension (D) of the network, which agrees with the experimental verification of the scaling behavior of fat-crystal networks [S. S. Narine and A. G. Marangoni, Phys. Rev. E 59, 1908 (1999)]. G' was also found to be inversely proportional to the diameter of the primary particles (sigma approximately equal to 6 microm) within the network (microstructural elements) as well as to the diameter of the microstructures (xi approximately equal to 100 microm) and inversely proportional to the cube of the intermicrostructural element distance (d(0)). This formulation of the elastic modulus agrees well with experimental observations.

  6. THE L{proportional_to}{sigma}{sup 8} CORRELATION FOR ELLIPTICAL GALAXIES WITH CORES: RELATION WITH BLACK HOLE MASS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kormendy, John; Bender, Ralf, E-mail: kormendy@astro.as.utexas.edu, E-mail: bender@mpe.mpg.de

    We construct the Faber-Jackson correlation between velocity dispersion {sigma} and total galaxy luminosity L{sub V} separately for elliptical galaxies with and without cores. The coreless ellipticals show the well-known, steep relationship dlog {sigma}/dlog L{sub V} = 0.268 or L{sub V} {proportional_to}{sigma}{sup 3.74}. This corresponds to dlog {sigma}/dlog M = 0.203, where M is the stellar mass and we use M/L{proportional_to}L {sup 0.32}. In contrast, the velocity dispersions of core ellipticals increase much more slowly with L{sub V} and M: dlog {sigma}/dlog L{sub V} = 0.120, L{sub V} {proportional_to}{sigma}{sup 8.33}, and dlog {sigma}/dlog M = 0.091. Dissipationless major galaxy mergers aremore » expected to preserve {sigma} according to the simplest virial-theorem arguments. However, numerical simulations show that {sigma} increases slowly in dry major mergers, with dlog {sigma}/dlog M {approx_equal} +0.15. In contrast, minor mergers cause {sigma} to decrease, with dlog {sigma}/dlog M {approx_equal} -0.05. Thus, the observed relation argues for dry major mergers as the dominant growth mode of the most massive ellipticals. This is consistent with what we know about the formation of cores. We know no viable way to explain galaxy cores except through dissipationless mergers of approximately equal-mass galaxies followed by core scouring by binary supermassive black holes. The observed, shallow {sigma}{proportional_to}L{sub V}{sup +0.12} relation for core ellipticals provides further evidence that they formed in dissipationless and predominantly major mergers. Also, it explains the observation that the correlation of supermassive black hole mass with velocity dispersion, M{sub .}{proportional_to}{sigma}{sup 4}, ''saturates'' at high M{sub .} such that M{sub .} becomes almost independent of {sigma}.« less

  7. Complex regulation of AprA metalloprotease in Pseudomonas fluorescens M114: evidence for the involvement of iron, the ECF sigma factor, PbrA and pseudobactin M114 siderophore.

    PubMed

    Maunsell, Bláithín; Adams, Claire; O'Gara, Fergal

    2006-01-01

    In the soil bacterium Pseudomonas fluorescens M114, extracellular proteolytic activity and fluorescent siderophore (pseudobactin M114) production were previously shown to be co-ordinately negatively regulated in response to environmental iron levels. An iron-starvation extracytoplasmic function sigma factor, PbrA, required for the transcription of siderophore biosynthetic genes, was also implicated in M114 protease regulation. The current study centred on the characterization and genetic regulation of the gene(s) responsible for protease production in M114. A serralysin-type metalloprotease gene, aprA, was identified and found to encode the major, if not only, extracellular protease produced by this strain. The expression of aprA and its protein product were found to be subject to complex regulation. Transcription analysis confirmed that PbrA was required for full aprA transcription under low iron conditions, while the ferric uptake regulator, Fur, was implicated in aprA repression under high iron conditions. Interestingly, the iron regulation of AprA was dependent on culture conditions, with PbrA-independent AprA-mediated proteolytic activity observed on skim milk agar supplemented with yeast extract, when supplied with iron or purified pseudobactin M114. These effects were not observed on skim milk agar without yeast extract. PbrA-independent aprA expression was also observed from a truncated transcriptional fusion when grown in sucrose asparagine tryptone broth supplied with iron or purified pseudobactin M114. Thus, experimental evidence suggested that iron mediated its effects via transcriptional activation by PbrA under low iron conditions, while an as-yet-unidentified sigma factor(s) may be required for the PbrA-independent aprA expression and AprA proteolytic activity induced by siderophore and iron.

  8. A modified integrated NDVI for improving estimates of terrestrial net primary production

    NASA Technical Reports Server (NTRS)

    Running, Steven W.

    1990-01-01

    Logic is presented for a time-integrated NDVI that is modified by an AVHRR derived surface evaporation resistance factor sigma, and truncated by temperatures that cause plant dormancy, to improve environmental sensitivity. With this approach, NDVI observed during subfreezing temperatures is not integrated. Water stress-related impairment in plant activity is incorporated by reducing the effective NDVI at each integration with sigma, which is derived from the slope of the surface temperature to NDVI ratio for climatically similar zones of the scene. A comparison of surface resistance before and after an extended drought period for a 1200 sq km region of coniferous forest in Montana is presented.

  9. Direct Comparison of Brookhaven Reflectivity Measurements with Free-Electron Theory

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bane, Karl L.F.

    2010-12-13

    The reflectivity at normal incidence of copper and aluminum samples was recently measured over a large frequency range at Brookhaven by one of us (JT). Then using the Kramers-Kroning integrals, and assuming the free-electron model of conductivity, the dependence of conductivity on frequency was obtained. The results seemed to suggest, for example, that the dc conductivities of the copper and evaporated aluminum samples are a factor of 3 lower than expected. We propose in this report, instead, directly fitting the free-electron model to the low frequency end of the reflectivity data. This fitting does not depend on the higher frequencymore » results and on Kramers-Kronig integrations, but it does assume that the data at the low frequency end is sufficiently accurate. Note that for our LCLS wakefield studies, it is only over these (relatively) low frequencies that we need to know the electrical properties of the metals. The equations that relate reflectivity R with the free electron parameters dc conductivity {sigma} and relaxation time {tau} are: (1) {tilde {sigma}} = {sigma}/1-ikc{tau}; (2) {tilde n} = {radical} {tilde {epsilon}} = {radical}(1+4{pi}i{tilde k}c/{omega}); and (3) R = |{tilde n}-1/{tilde n} + 1|{sup 2}. The parameters are ac conductivity {tilde {sigma}}, index of refraction {tilde n}, dielectric constant {tilde {epsilon}}, and wave number k = {omega}/c, with {omega} frequency and c the speed of light. In Fig. 1 we show the ideal behavior of R for a reasonably good conducting metal, where {sigma} = 0.12 x 10{sup 17}/s and {tau} = 0.55 x 10{sup -14} s (solid line); these parameters are, respectively, 2% ({sigma}) and 20% ({tau}) of the nominal values for copper. The parameters were chosen so that the important features of R(k) could be seen easily in one plot. We see 3 distinct regions: (1) for low frequencies, k {approx}< 1/c{tau}, R continually decreases, with positive curvature, and with a low frequency asymptote of (1 - {radical}2kc/{pi}{sigma}); (2) for intermediate frequencies the reflectivity is nearly constant, R {approx} (1 - {radical}1/{pi}{sigma}{tau}); (3) for k {approx}> k{sub p} = {radical}4{pi}{sigma}/c{sup 2}{tau}, the plasma frequency of the metal, R quickly drops to zero. The dashed lines in Fig. 1 give the analytic guideposts for the 3 regions. Note that it is only in the first and part of the second region that we can expect the free electron model to have validity in real metals; at higher frequencies the effects of absorption bands and other physics will distort the R(k) curve. In principle, knowing R accurately in the entire 1st region suffices for obtaining the free-electron parameters {sigma} and {tau}; in practice, however, knowing it also in the 2nd region gives us more confidence in the model and especially in the value of {tau}.« less

  10. Cost-effective bidirectional digitized radio-over-fiber systems employing sigma delta modulation

    NASA Astrophysics Data System (ADS)

    Lee, Kyung Woon; Jung, HyunDo; Park, Jung Ho

    2016-11-01

    We propose a cost effective digitized radio-over-fiber (D-RoF) system employing a sigma delta modulation (SDM) and a bidirectional transmission technique using phase modulated downlink and intensity modulated uplink. SDM is transparent to different radio access technologies and modulation formats, and more suitable for a downlink of wireless system because a digital to analog converter (DAC) can be avoided at the base station (BS). Also, Central station and BS share the same light source by using a phase modulation for the downlink and an intensity modulation for the uplink transmission. Avoiding DACs and light sources have advantages in terms of cost reduction, power consumption, and compatibility with conventional wireless network structure. We have designed a cost effective bidirectional D-RoF system using a low pass SDM and measured the downlink and uplink transmission performance in terms of error vector magnitude, signal spectra, and constellations, which are based on the 10MHz LTE 64-QAM standard.

  11. Contribution of X/Ka VLBI to Multi-Wavelength Celestial Frame Studies

    NASA Technical Reports Server (NTRS)

    Jacobs, C. S.; Clark, J. E.; Garcia-Miro, C.; Horiuchi, S.; Sotuela, I.

    2011-01-01

    This paper is an update of Sotuela et al. (2011) which improves their simulated Gaia frame tie precision by approximately 10% by adding three additional VLBI observing sessions. Astrometry at X/Ka-band (8.4/32 GHz) using NASAs Deep Space Network has detected 466 quasars with accuracies of 200-300 micro-arc seconds. A program is underway to reduce errors by a factor of 2-3. From our sample, 245 sources have optical magnitudes V less than 20 and should also be detectable by Gaia. A covariance study using existing X/Ka data and simulated Gaia uncertainties for the 345 objects yields a frame tie precision of 10-15 micro-arc seconds (1 - sigma). The characterization of wavelength dependent systematic from extended source morphology and core shift should benefit greatly from adding X/Ka-band measurements to S/X-band (2.3/8.4 GHz) measurements thus helping to constrain astrophysical models of the wavelength dependence of positions.

  12. Genome amplification and promoter mutation expand the range of csgD-dependent biofilm responses in an STEC population.

    PubMed

    Uhlich, Gaylen A; Chen, Chin-Yi; Cottrell, Bryan J; Andreozzi, Elisa; Irwin, Peter L; Nguyen, Ly-Huong

    2017-04-01

    Expression of the major biofilm components of E. coli, curli fimbriae and cellulose, requires the CsgD transcription factor. A complex regulatory network allows environmental control of csgD transcription and biofilm formation. However, most clinical serotype O157 : H7 strains contain prophage insertions in the csgD regulator, mlrA, or mutations in other regulators that restrict csgD expression. These barriers can be circumvented by certain compensating mutations that restore higher csgD expression. One mechanism is via csgD promoter mutations that switch sigma factor utilization. Biofilm-forming variants utilizing RpoD rather than RpoS have been identified in glycerol freezer stocks of the non-biofilm-forming food-borne outbreak strain, ATCC 43894. In this study we used whole genome sequencing and RNA-seq to study genotypic and transcriptomic differences between those strains. In addition to defining the consequences of the csgD promoter switch and identifying new csgD-controlled genes, we discovered a region of genome amplification in our laboratory stock of 43894 (designated 43894OW) that contributed to the regulation of csgD-dependent properties.

  13. Temporal regulation and forespore-specific expression of the spore photoproduct lyase gene by sigma-G RNA polymerase during Bacillus subtilis sporulation.

    PubMed Central

    Pedraza-Reyes, M; Gutiérrez-Corona, F; Nicholson, W L

    1994-01-01

    Bacterial spores are highly resistant to killing by UV radiation and exhibit unique DNA photochemistry. UV irradiation of spore DNA results in formation of spore photoproduct (SP), the thymine dimer 5-thyminyl-5,6-dihydrothymine. Repair of SP occurs during germination of Bacillus subtilis spores by two distinct routes, either by the general nucleotide excision repair (uvr) pathway or by a novel SP-specific monomerization reaction mediated by the enzyme SP lyase, which is encoded by the spl gene. Repair of SP occurs early in spore germination and is independent of de novo protein synthesis, suggesting that the SP repair enzymes are synthesized during sporulation and are packaged in the dormant spore. To test this hypothesis, the expression of a translational spl-lacZ fusion integrated at the spl locus was monitored during B. subtilis growth and sporulation. beta-Galactosidase expression from the spl-lacZ fusion was silent during vegetative growth and was not DNA damage inducible, but it was activated at morphological stage III of sporulation specifically in the forespore compartment, coincident with activation of expression of the stage III marker enzyme glucose dehydrogenase. Expression of the spl-lacZ fusion was shown to be dependent upon the sporulation-specific RNA polymerase containing the sigma-G factor (E sigma G), as spl-lacZ expression was abolished in a mutant harboring a deletion in the sigG gene and restored by expression of the sigG gene in trans. Primer extension analysis of spl mRNA revealed a major extension product initiating upstream from a small open reading frame of unknown function which precedes spl, and it revealed two other shorter minor extension products. All three extension products were present in higher quantities during sporulation and after sigG induction. The three putative transcripts are all preceded by sequences which share homology with the consensus sigma-G factor-type promoter sequence, but in vitro transcription by purified sigma-G RNA polymerase was detected only from the promoter corresponding to the major extension product. The open reading frame-spl operon therefore appears to be an additional member of the sigma-G regulon, which also includes as members the small, acid-soluble spore proteins which are in large part responsible for spore DNA photochemistry. Therefore, sporulating bacteria appear to coordinately regulate genes whose products not only alter spore DNA photochemistry but also repair the major spore-specific photoproduct during germination Images PMID:8021181

  14. Characterization of 4-Nitrophenylpropyl-N-alkylamine Interactions with Sigma Receptors

    PubMed Central

    Chu, Uyen B.; Hajipour, Abdol R.; Ramachandran, Subramaniam; Ruoho, Arnold E.

    2011-01-01

    Sigma receptors are small membrane proteins implicated in a number of pathophysiological conditions including drug addiction, psychosis and cancer; thus, small molecule inhibitors of sigma receptors have been proposed as potential pharmacotherapeutics for these diseases. We previously discovered that endogenous monochain N-alkyl sphingolipids including D-erythro-sphingosine, sphinganine, and N,N-dimethyl sphingosine bind to the sigma-1 receptor at physiologically relevant concentrations [Ramachandran et al. 2009 Eur J Pharmacol. 609(1–3):19–26]. Here, we investigated several N-alkylamines of varying chain lengths as sigma receptor ligands. Although the KI values for N-alkylamines were found to be in the micromolar range, when N-3-phenylpropyl and N-3-(4-nitrophenyl)propyl derivatives of butyl- (1a and 1b), heptyl- (2a and 2b), dodecyl- (3a and 3b), and octadecyl-amine (4a and 4b) were evaluated as sigma receptor ligands we found that these compounds exhibited nanomolar affinities with both sigma-1 and sigma-2 receptors. A screen of the high affinity ligands 2a, 2b, 3a and 3b against a variety of other receptors/transporters confirmed these four compounds to be highly selective mixed sigma-1 and sigma-2 ligands. Additionally, in HEK293 cells reconstituted with Kv1.4 potassium channel and the sigma-1 receptor, these derivatives were able to inhibit the outward current from the channel – consistent with sigma receptor modulation. Finally, cytotoxicity assays showed that 2a, 2b, 3a and 3b were highly potent against a number of cancer cell lines, demonstrating their potential utility as mixed sigma-1 and sigma-2 receptor anti-cancer agents. PMID:21790129

  15. Studies of the Escherichia coli Rsd-sigma70 complex.

    PubMed

    Westblade, Lars F; Ilag, Leopold L; Powell, Andrew K; Kolb, Annie; Robinson, Carol V; Busby, Stephen J W

    2004-01-16

    Escherichia coli Rsd protein was previously identified on the basis of its binding to the RNA polymerase sigma(70) subunit. The Rsd-sigma(70) complex has been studied using different methods. Our data show that Rsd associates with sigma(70) to form a complex with a stoichiometry of 1:1. Alanine scanning and deletion mutagenesis were used to locate regions of sigma(70) that are required for the formation of the Rsd-sigma(70) complex.

  16. The Local Supercluster as a test of cosmological models

    NASA Technical Reports Server (NTRS)

    Cen, Renyue

    1994-01-01

    The Local Supercluster kinematic properties (the Local Group infall toward the Virgo Cluster and galaxy density distribution about the Virgo Cluster) in various cosmological models are examined utilizing large-scale N-body (PM) simulations 500(exp 3) cells, 250(exp 3) particles, and box size of 400 h(exp -1) Mpc) and are compared to observations. Five models are investigated: (1) the standard, Cosmic Background Explorer Satellite (COBE)-normalized cold dark matter (CDM) model with omega = 1, h = 0.5, and sigma(sub 8) = 1.05; (2) the standard Hot Dark Matter (HDM) model with omega = 1, h = 0.75, and sigma(sub 8) = 1; (3) the tilted CDM model with omega = 1, h = 0.5, n = 0.7, and sigma(sub 8) = 0.5; (4) a CDM + lambda model with omega = 0.3, lambda = 0.7, h = 2/3, and sigma(sub 8) = 2/3; (5) the PBI model with omega = 0.2, h = 0.8, x = 0.1, m = -0.5, and sigma(sub 8) = 0.9. Comparison of the five models with the presently available observational measurements v(sub LG) = 85 - 305 km/s (with mean of 250 km/s), delta(n(sub g))/(n(sub g)-bar) = 1.40 + or - 0.35) suggests that an open universe with omega approximately 0.5 (with or without lambda) and sigma(sub 8) approximately 0.8 is preferred, with omega = 0.3-1.0 (with or without lambda) and sigma(sub 8) = 0.7-1.0 being the acceptable range. At variance with some previous claims based on either direct N-body or spherical nonlinear approaches, we find that a flat model with sigma(sub 8) approximately 0.7-1.0 seems to be reasonably consistent with observations. However, if one favors the low limit of v(sub LG) = 85 km/s, then an omega approximately 0.2-0.3 universe seems to provide a better fit, and flat (omega = 1) models are ruled out at approximately 95% confidence level. On the other hand, if the high limit of v(sub LG) = 350 km/s is closer to the truth, then it appears that omega approximately 0.7-0.8 is more consistent. This test is insensitive to the shape of the power spectrum, but rather sensitive to the normalization of the perturbation amplitude on the relevant scale (e.g., sigma(sub 8)) and omega. We find that neither linear nor nonlinear relations (with spherical symmetry) are good approximations for the relation between radial peculiar velocity and density perturbation, i.e., nonspherical effects and gravitational tidal field are important. The derived omega using either of the two relations is underestimated. In some cases, this error is as large as a factor of 2-4.

  17. An accuracy assessment of different rigid body image registration methods and robotic couch positional corrections using a novel phantom

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Arumugam, Sankar; Xing Aitang; Jameson, Michael G.

    2013-03-15

    Purpose: Image guided radiotherapy (IGRT) using cone beam computed tomography (CBCT) images greatly reduces interfractional patient positional uncertainties. An understanding of uncertainties in the IGRT process itself is essential to ensure appropriate use of this technology. The purpose of this study was to develop a phantom capable of assessing the accuracy of IGRT hardware and software including a 6 degrees of freedom patient positioning system and to investigate the accuracy of the Elekta XVI system in combination with the HexaPOD robotic treatment couch top. Methods: The constructed phantom enabled verification of the three automatic rigid body registrations (gray value, bone,more » seed) available in the Elekta XVI software and includes an adjustable mount that introduces known rotational offsets to the phantom from its reference position. Repeated positioning of the phantom was undertaken to assess phantom rotational accuracy. Using this phantom the accuracy of the XVI registration algorithms was assessed considering CBCT hardware factors and image resolution together with the residual error in the overall image guidance process when positional corrections were performed through the HexaPOD couch system. Results: The phantom positioning was found to be within 0.04 ({sigma}= 0.12) Degree-Sign , 0.02 ({sigma}= 0.13) Degree-Sign , and -0.03 ({sigma}= 0.06) Degree-Sign in X, Y, and Z directions, respectively, enabling assessment of IGRT with a 6 degrees of freedom patient positioning system. The gray value registration algorithm showed the least error in calculated offsets with maximum mean difference of -0.2({sigma}= 0.4) mm in translational and -0.1({sigma}= 0.1) Degree-Sign in rotational directions for all image resolutions. Bone and seed registration were found to be sensitive to CBCT image resolution. Seed registration was found to be most sensitive demonstrating a maximum mean error of -0.3({sigma}= 0.9) mm and -1.4({sigma}= 1.7) Degree-Sign in translational and rotational directions over low resolution images, and this is reduced to -0.1({sigma}= 0.2) mm and -0.1({sigma}= 0.79) Degree-Sign using high resolution images. Conclusions: The phantom, capable of rotating independently about three orthogonal axes was successfully used to assess the accuracy of an IGRT system considering 6 degrees of freedom. The overall residual error in the image guidance process of XVI in combination with the HexaPOD couch was demonstrated to be less than 0.3 mm and 0.3 Degree-Sign in translational and rotational directions when using the gray value registration with high resolution CBCT images. However, the residual error, especially in rotational directions, may increase when the seed registration is used with low resolution images.« less

  18. Running Head: Implementing Six Sigma Efforts

    ERIC Educational Resources Information Center

    Lindsay, Jamie Eleaitia Mae

    2005-01-01

    Six Sigma is an organization wide program that provides common set of goals, language, and methodology for improving the overall quality of the processes within the organization (Davis & Heineke 2004). Six Sigma main concern is for the customer. What will the customers want? Need? Six Sigma has a model that helps Sigma get implemented DMAIC model…

  19. Radiometric errors in complex Fourier transform spectrometry.

    PubMed

    Sromovsky, Lawrence A

    2003-04-01

    A complex spectrum arises from the Fourier transform of an asymmetric interferogram. A rigorous derivation shows that the rms noise in the real part of that spectrum is indeed given by the commonly used relation sigmaR = 2X x NEP/(etaAomega square root(tauN)), where NEP is the delay-independent and uncorrelated detector noise-equivalent power per unit bandwidth, +/- X is the delay range measured with N samples averaging for a time tau per sample, eta is the system optical efficiency, and Aomega is the system throughput. A real spectrum produced by complex calibration with two complex reference spectra [Appl. Opt. 27, 3210 (1988)] has a variance sigmaL2 = sigmaR2 + sigma(c)2 (Lh - Ls)2/(Lh - Lc)2 + sigma(h)2 (Ls - Lc)2/(Lh - Lc)2, valid for sigmaR, sigma(c), and sigma(h) small compared with Lh - Lc, where Ls, Lh, and Lc are scene, hot reference, and cold reference spectra, respectively, and sigma(c) and sigma(h) are the respective combined uncertainties in knowledge and measurement of the hot and cold reference spectra.

  20. Experimental and Coupled-channels Investigation of the Radiative Properties of the N2 c4 (sup 1)Sigma+(sub u) - X (sup 1)Sigma+(sub g) Band System

    NASA Technical Reports Server (NTRS)

    Liu, Xianming; Shemansky, Donald E.; Malone, Charles P.; Johnson, Paul V.; Ajello, Joseph M.; Kanik, Isik; Heays, Alan N.; Lewis, Brenton R.; Gibson, Stephen T.; Stark, Glenn

    2008-01-01

    The emission properties of the N2 c(sup prime)(sub 4) (sup 1)Sigma+(sub u) - Chi (sup 1)Sigma+(sub g) band system have been investigated in a joint experimental and coupled-channels theoretical study. Relative intensities of the c(sup prime)(sub 4) (sup 1)Sigma+(sub u)(0) - Chi (sup 1)Sigma+(sub g)(v(sub i)) transitions, measured via electron-impact-induced emission spectroscopy, are combined with a coupled-channel Schroedinger equation (CSE) model of the N2 molecule, enabling determination of the diabatic electronic transition moment for the c(sup prime)(sub 4) (sup 1)Sigma+(sub u) - Chi (sup 1)Sigma+(sub g) system as a function of internuclear distance. The CSE probabilities are further verified by comparison with a high-resolution experimental spectrum. Spontaneous transition probabilities of the c(sup prime)(sub 4) (sup 1)Sigma+(sub u) - Chi (sup 1)Sigma+(sub g) modeling atmospheric emission, can now be calculated reliably.

  1. Close encounters of the third-body kind. [intruding bodies in binary star systems

    NASA Technical Reports Server (NTRS)

    Davies, M. B.; Benz, W.; Hills, J. G.

    1994-01-01

    We simulated encounters involving binaries of two eccentricities: e = 0 (i.e., circular binaries) and e = 0.5. In both cases the binary contained a point mass of 1.4 solar masses (i.e., a neutron star) and a 0.8 solar masses main-sequence star modeled as a polytrope. The semimajor axes of both binaries were set to 60 solar radii (0.28 AU). We considered intruders of three masses: 1.4 solar masses (a neutron star), 0.8 solar masses (a main-sequence star or a higher mass white dwarf), and 0.64 solar masses (a more typical mass white dwarf). Our strategy was to perform a large number (40,000) of encounters using a three-body code, then to rerun a small number of cases with a three-dimensional smoothed particle hydrodynamics (SPH) code to determine the importance of hydrodynamical effects. Using the results of the three-body runs, we computed the exchange across sections, sigma(sub ex). From the results of the SPH runs, we computed the cross sections for clean exchange, denoted by sigma(sub cx); the formation of a triple system, denoted by sigma(sub trp); and the formation of a merged binary with an object formed from the merger of two of the stars left in orbit around the third star, denoted by sigma(sub mb). For encounters between either binary and a 1.4 solar masses neutron star, sigma(sub cx) approx. 0.7 sigma(sub ex) and sigma(sub mb) + sigma(sub trp) approx. 0.3 sigma(sub ex). For encounters between either binary and the 0.8 solar masses main-sequence star, sigma(sub cx) approx. 0.50 sigma(sub ex) and sigma(sub mb) + sigma(sub trp) approx. 1.0 sigma(sub ex). If the main sequence star is replaced by a main-sequence star of the same mass, we have sigma(sub cx) approx. 0.5 sigma(sub ex) and sigma(sub mb) + sigma(sub trp) approx. 1.6 sigma(sub ex). Although the exchange cross section is a sensitive function of intruder mass, we see that the cross section to produce merged binaries is roughly independent of intruder mass. The merged binaries produced have semi-major axes much larger than either those of the original binaries or those of binaries produced in clean exchanges. Coupled with their lower kick velocities, received from the encounters, their larger size will enhance their cross section, shortening the waiting time to a subsequent encounter with another single star.

  2. Analysis of sigma receptor (sigmaR1) expression in retinal ganglion cells cultured under hyperglycemic conditions and in diabetic mice.

    PubMed

    Ola, M Shamsul; Moore, Pamela; Maddox, Dennis; El-Sherbeny, Amira; Huang, Wei; Roon, Penny; Agarwal, Neeraj; Ganapathy, Vadivel; Smith, Sylvia B

    2002-11-15

    The type 1 sigma receptor (sigmaR1) is a nonopiate and nonphencyclidine binding site that has numerous pharmacological and physiological functions. In some studies, agonists for sigmaR1 have been shown to afford neuroprotection against overstimulation of the NMDA receptor. sigmaR1 expression has been demonstrated recently in retinal ganglion cells (RGC). RGCs undergo apoptosis early in diabetic retinopathy via NMDA receptor overstimulation. In the present study we asked whether RGCs cultured under hyperglycemic conditions and RGCs of diabetic mice continue to express sigmaR1. RGCs were cultured 48 h in RPMI medium containing either 45 mM glucose or 11 mM glucose plus 34 mM mannitol (osmolar control). C57BL/6 mice were made diabetic using streptozotocin. The retina was dissected from normal and streptozotocin-induced diabetic mice 3, 6 and 12 weeks post-onset of diabetes. sigmaR1 was analyzed in cells using semiquantitative RT-PCR and in tissues by semiquantitative RT-PCR, in situ hybridization, Western blot analysis and immunolocalization. The RT-PCR analysis of cultured RGCs showed that sigmaR1 mRNA is expressed under hyperglycemic conditions at levels similar to control cells. Similarly, analysis of retinas of diabetic mice showed no difference in levels of mRNA encoding sigmaR1 compared to retinas of control mice. In situ hybridization analysis showed that expression patterns of sigmaR1 mRNA in the ganglion cell layer were similar between diabetic and control mice. Western blot analysis suggested that levels of sigmaR1 in retina were similar between diabetic and control retinas. Immunohistochemical analysis of sigmaR1 showed a similar pattern of sigmaR1 protein expression between control and diabetic retina. These studies demonstrate that sigmaR1 is expressed under hyperglycemic conditions in vitro and in vivo.

  3. SEVEN-YEAR WILKINSON MICROWAVE ANISOTROPY PROBE (WMAP ) OBSERVATIONS: POWER SPECTRA AND WMAP-DERIVED PARAMETERS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Larson, D.; Bennett, C. L.; Gold, B.

    2011-02-01

    The WMAP mission has produced sky maps from seven years of observations at L2. We present the angular power spectra derived from the seven-year maps and discuss the cosmological conclusions that can be inferred from WMAP data alone. With the seven-year data, the temperature (TT) spectrum measurement has a signal-to-noise ratio per multipole that exceeds unity for l < 919; and in band powers of width {Delta}l = 10, the signal-to-noise ratio exceeds unity up to l = 1060. The third acoustic peak in the TT spectrum is now well measured by WMAP. In the context of a flat {Lambda}CDMmore » model, this improvement allows us to place tighter constraints on the matter density from WMAP data alone, {Omega}{sub m} h {sup 2} = 0.1334{sup +0.0056}{sub -0.0055}, and on the epoch of matter-radiation equality, z{sub eq} = 3196{sup +134}{sub -133}. The temperature-polarization (TE) spectrum is detected in the seven-year data with a significance of 20{sigma}, compared to 13{sigma} with the five-year data. We now detect the second dip in the TE spectrum near l {approx} 450 with high confidence. The TB and EB spectra remain consistent with zero, thus demonstrating low systematic errors and foreground residuals in the data. The low-l EE spectrum, a measure of the optical depth due to reionization, is detected at 5.5{sigma} significance when averaged over l = 2-7: l(l + 1)C {sup EE}{sub l}/(2{pi}) = 0.074{sup +0.034}{sub -0.025} {mu}K{sup 2} (68% CL). We now detect the high-l, 24 {<=} l {<=} 800, EE spectrum at over 8{sigma}. The BB spectrum, an important probe of gravitational waves from inflation, remains consistent with zero; when averaged over l = 2-7, l(l + 1)C {sup BB}{sub l}/(2{pi}) < 0.055 {mu}K{sup 2} (95% CL). The upper limit on tensor modes from polarization data alone is a factor of two lower with the seven-year data than it was using the five-year data. The data remain consistent with the simple {Lambda}CDM model: the best-fit TT spectrum has an effective {chi}{sup 2} of 1227 for 1170 degrees of freedom, with a probability to exceed of 9.6%. The allowable volume in the six-dimensional space of {Lambda}CDM parameters has been reduced by a factor of 1.5 relative to the five-year volume, while the {Lambda}CDM model that allows for tensor modes and a running scalar spectral index has a factor of three lower volume when fit to the seven-year data. We test the parameter recovery process for bias and find that the scalar spectral index, n{sub s} , is biased high, but only by 0.09{sigma}, while the remaining parameters are biased by <0.15{sigma}. The improvement in the third peak measurement leads to tighter lower limits from WMAP on the number of relativistic degrees of freedom (e.g., neutrinos) in the early universe: N{sub eff}>2.7(95%CL). Also, using WMAP data alone, the primordial helium mass fraction is found to be Y{sub He} = 0.28{sup +0.14}{sub -0.15}, and with data from higher-resolution cosmic microwave background experiments included, we now establish the existence of pre-stellar helium at >3{sigma}. These new WMAP measurements provide important tests of big bang cosmology.« less

  4. The low-lying {pi}{sigma}* state and its role in the intramolecular charge transfer of aminobenzonitriles and aminobenzethyne

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, Jae-Kwang; Fujiwara, Takashige; Kofron, William G.

    2008-04-28

    Electronic absorption spectra of the low-lying {pi}{pi}* and {pi}{sigma}* states of several aminobenzonitriles and 4-dimethylaminobenzethyne have been studied by time-resolved transient absorption and time-dependent density functional theory calculation. In acetonitrile, the lifetime of the {pi}{sigma}*-state absorption is very short (picoseconds or subpicosecond) for molecules that exhibit intramolecular charge transfer (ICT), and very long (nanoseconds) for those that do not. Where direct comparison of the temporal characteristics of the {pi}{sigma}*-state and the ICT-state transients could be made, the formation rate of the ICT state is identical to the decay rate of the {pi}{sigma}* state within the experimental uncertainty. These results aremore » consistent with the {pi}{sigma}*-mediated ICT mechanism, L{sub a} ({pi}{pi}*){yields}{pi}{sigma}*{yields}ICT, in which the decay rate of the {pi}{sigma}* state is determined by the rate of the solvent-controlled {pi}{sigma}*{yields}ICT charge-shift reaction. The {pi}{pi}*{yields}{pi}{sigma}* state crossing does not occur in 3-dimethylaminobenzonitrile or 2-dimethylaminobenzonitrile, as predicted by the calculation, and 4-aminobenzonitrile and 4-dimethylaminobenzethyne does not exhibit the ICT reaction, consistent with the higher energy of the ICT state relative to the {pi}{sigma}* state.« less

  5. Quantitative application of sigma metrics in medical biochemistry.

    PubMed

    Nanda, Sunil Kumar; Ray, Lopamudra

    2013-12-01

    Laboratory errors are result of a poorly designed quality system in the laboratory. Six Sigma is an error reduction methodology that has been successfully applied at Motorola and General Electric. Sigma (σ) is the mathematical symbol for standard deviation (SD). Sigma methodology can be applied wherever an outcome of a process has to be measured. A poor outcome is counted as an error or defect. This is quantified as defects per million (DPM). A six sigma process is one in which 99.999666% of the products manufactured are statistically expected to be free of defects. Six sigma concentrates, on regulating a process to 6 SDs, represents 3.4 DPM (defects per million) opportunities. It can be inferred that as sigma increases, the consistency and steadiness of the test improves, thereby reducing the operating costs. We aimed to gauge performance of our laboratory parameters by sigma metrics. Evaluation of sigma metrics in interpretation of parameter performance in clinical biochemistry. The six month internal QC (October 2012 to march 2013) and EQAS (external quality assurance scheme) were extracted for the parameters-Glucose, Urea, Creatinine, Total Bilirubin, Total Protein, Albumin, Uric acid, Total Cholesterol, Triglycerides, Chloride, SGOT, SGPT and ALP. Coefficient of variance (CV) were calculated from internal QC for these parameters. Percentage bias for these parameters was calculated from the EQAS. Total allowable errors were followed as per Clinical Laboratory Improvement Amendments (CLIA) guidelines. Sigma metrics were calculated from CV, percentage bias and total allowable error for the above mentioned parameters. For parameters - Total bilirubin, uric acid, SGOT, SGPT and ALP, the sigma values were found to be more than 6. For parameters - glucose, Creatinine, triglycerides, urea, the sigma values were found to be between 3 to 6. For parameters - total protein, albumin, cholesterol and chloride, the sigma values were found to be less than 3. ALP was the best performer when it was gauzed on the sigma scale, with a sigma metrics value of 8.4 and chloride had the least sigma metrics value of 1.4.

  6. Probability of fixation under weak selection: a branching process unifying approach.

    PubMed

    Lambert, Amaury

    2006-06-01

    We link two-allele population models by Haldane and Fisher with Kimura's diffusion approximations of the Wright-Fisher model, by considering continuous-state branching (CB) processes which are either independent (model I) or conditioned to have constant sum (model II). Recent works by the author allow us to further include logistic density-dependence (model III), which is ubiquitous in ecology. In all models, each allele (mutant or resident) is then characterized by a triple demographic trait: intrinsic growth rate r, reproduction variance sigma and competition sensitivity c. Generally, the fixation probability u of the mutant depends on its initial proportion p, the total initial population size z, and the six demographic traits. Under weak selection, we can linearize u in all models thanks to the same master formula u = p + p(1 - p)[g(r)s(r) + g(sigma)s(sigma) + g(c)s(c)] + o(s(r),s(sigma),s(c), where s(r) = r' - r, s(sigma) = sigma-sigma' and s(c) = c - c' are selection coefficients, and g(r), g(sigma), g(c) are invasibility coefficients (' refers to the mutant traits), which are positive and do not depend on p. In particular, increased reproduction variance is always deleterious. We prove that in all three models g(sigma) = 1/sigma and g(r) = z/sigma for small initial population sizes z. In model II, g(r) = z/sigma for all z, and we display invasion isoclines of the 'mean vs variance' type. A slight departure from the isocline is shown to be more beneficial to alleles with low sigma than with high r. In model III, g(c) increases with z like ln(z)/c, and g(r)(z) converges to a finite limit L > K/sigma, where K = r/c is the carrying capacity. For r > 0 the growth invasibility is above z/sigma when z < K, and below z/sigma when z > K, showing that classical models I and II underestimate the fixation probabilities in growing populations, and overestimate them in declining populations.

  7. HOW UNIVERSAL IS THE {Sigma}{sub SFR}-{Sigma}{sub H{sub 2}} RELATION?

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Feldmann, R.; Gnedin, N. Y.; Kravtsov, A. V., E-mail: feldmann@fnal.gov

    It is a well-established empirical fact that the surface density of the star formation rate, {Sigma}{sub SFR}, strongly correlates with the surface density of molecular hydrogen, {Sigma}{sub H{sub 2}}, at least when averaged over large ({approx}kpc) scales. Much less is known, however, about whether (and how) the {Sigma}{sub SFR}-{Sigma}{sub H{sub 2}} relation depends on environmental parameters, such as the metallicity or the UV radiation field in the interstellar medium (ISM). Furthermore, observations indicate that the scatter in the {Sigma}{sub SFR}-{Sigma}{sub H{sub 2}} relation increases rapidly with decreasing averaging scale. How the scale-dependent scatter is generated and how one recovers amore » tight {approx} kpc scale {Sigma}{sub SFR}-{Sigma}{sub 2} relation in the first place is still largely debated. Here, these questions are explored with hydrodynamical simulations that follow the formation and destruction of H{sub 2}, include radiative transfer of UV radiation, and resolve the ISM on {approx}60 pc scales. We find that within the considered range of H{sub 2} surface densities (10-100 M{sub sun} pc{sup -2}), the {Sigma}{sub SFR}-{Sigma}{sub H{sub 2}} relation is steeper in environments of low-metallicity and/or high-radiation fields (compared to the Galaxy), that the star formation rate (SFR) at a given H{sub 2} surface density is larger, and the scatter is increased. Deviations from a 'universal' {Sigma}{sub SFR}-{Sigma}{sub H{sub 2}} relation should be particularly relevant for high-redshift galaxies or for low-metallicity dwarfs at z {approx} 0. We also find that the use of time-averaged SFRs produces a large, scale-dependent scatter in the {Sigma}{sub SFR}-{Sigma}{sub H{sub 2}} relation. Given the plethora of observational data expected from upcoming surveys such as ALMA, the scale-scatter relation may indeed become a valuable tool for determining the physical mechanisms connecting star formation and H{sub 2} formation.« less

  8. Immunogenicity and protection induced by a Mycobacterium tuberculosis sigE mutant in a BALB/c mouse model of progressive pulmonary tuberculosis.

    PubMed

    Hernandez Pando, Rogelio; Aguilar, Leon Diana; Smith, Issar; Manganelli, Riccardo

    2010-07-01

    Tuberculosis is still one of the main challenges to human global health, leading to about two million deaths every year. One of the reasons for its success is the lack of efficacy of the widely used vaccine Mycobacterium bovis BCG. In this article, we analyze the potential use of an attenuated mutant of Mycobacterium tuberculosis H37Rv lacking the sigma factor sigma(E) as a live vaccine. We have demonstrated that BALB/c mice infected by the intratracheal route with this mutant strain showed significantly higher survival rates and less tissue damage than animals infected with the parental or complemented mutant strain. Although animals infected with the sigE mutant had low bacillary loads, their lungs showed significantly higher production of the protective factors gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), inducible nitric oxide synthase (iNOS), and beta-defensins than those of animals infected with the parental or complemented mutant strain. Moreover, we demonstrate that the sigE mutant, when inoculated subcutaneously, was more attenuated than BCG in immunodeficient nude mice, thus representing a good candidate for a novel attenuated live vaccine strain. Finally, when we used the sigE mutant as a subcutaneous vaccine, it was able to induce a higher level of protection than did BCG with both H37Rv and a highly virulent strain of M. tuberculosis (Beijing code 9501000). Taken together, our findings suggest that the sigE mutant is a very promising strain for the development of a new vaccine against tuberculosis.

  9. Bioaccumulation and biotransformation of brominated and chlorinated contaminants and their metabolites in ringed seals (Pusa hispida) and polar bears (Ursus maritimus) from East Greenland.

    PubMed

    Letcher, Robert J; Gebbink, Wouter A; Sonne, Christian; Born, Erik W; McKinney, Melissa A; Dietz, Rune

    2009-11-01

    We report on the comparative bioaccumulation, biotransformation and/or biomagnification from East Greenland ringed seal (Pusa hispida) blubber to polar bear (Ursus maritimus) tissues (adipose, liver and brain) of various classes and congeners of persistent chlorinated and brominated contaminants and metabolic by-products: polychlorinated biphenyls (PCBs), chlordanes (CHLs), hydroxyl (OH-) and methylsulfonyl (MeSO(2)-) PCBs, polybrominated biphenyls (PBBs), OH-PBBs, polybrominated diphenyl ether (PBDE) and hexabromocyclododecane (HBCD) flame retardants and OH- and methoxyl (MeO-) PBDEs, 2,2-dichloro-bis(4-chlorophenyl)ethene (p,p'-DDE), 3-MeSO(2)-p,p'-DDE, pentachlorophenol (PCP) and 4-OH-heptachlorostyrene (4-OH-HpCS). We detected all of the investigated contaminants in ringed seal blubber with high frequency, the main diet of East Greenland bears, with the exception of OH-PCBs and 4-OH-HpCS, which indicated that these phenolic contaminants were likely of metabolic origin and formed in the bears from accumulated PCBs and octachlorostyrene (OCS), respectively, rather than being bioaccumulated from a seal blubber diet. For all of the detectable sum of classes or individual organohalogens, in general, the ringed seal to polar bear mean BMFs for SigmaPCBs, p,p'-DDE, SigmaCHLs, SigmaMeSO(2)-PCBs, 3-MeSO(2)-p,p'-DDE, PCP, SigmaPBDEs, total-(alpha)-HBCD, SigmaOH-PBDEs, SigmaMeO-PBDEs and SigmaOH-PBBs indicated that these organohalogens bioaccumulate, and in some cases there was tissue-specific biomagnification, e.g., BMFs for bear adipose and liver ranged from 2 to 570. The blood-brain barrier appeared to be effective in minimizing brain accumulation as BMFs were

  10. Application of Artificial Neural Network to Optical Fluid Analyzer

    NASA Astrophysics Data System (ADS)

    Kimura, Makoto; Nishida, Katsuhiko

    1994-04-01

    A three-layer artificial neural network has been applied to the presentation of optical fluid analyzer (OFA) raw data, and the accuracy of oil fraction determination has been significantly improved compared to previous approaches. To apply the artificial neural network approach to solving a problem, the first step is training to determine the appropriate weight set for calculating the target values. This involves using a series of data sets (each comprising a set of input values and an associated set of output values that the artificial neural network is required to determine) to tune artificial neural network weighting parameters so that the output of the neural network to the given set of input values is as close as possible to the required output. The physical model used to generate the series of learning data sets was the effective flow stream model, developed for OFA data presentation. The effectiveness of the training was verified by reprocessing the same input data as were used to determine the weighting parameters and then by comparing the results of the artificial neural network to the expected output values. The standard deviation of the expected and obtained values was approximately 10% (two sigma).

  11. Small-Molecule Sigma1 Modulator Induces Autophagic Degradation of PD-L1.

    PubMed

    Maher, Christina M; Thomas, Jeffrey D; Haas, Derick A; Longen, Charles G; Oyer, Halley M; Tong, Jane Y; Kim, Felix J

    2018-02-01

    Emerging evidence suggests that Sigma1 ( SIGMAR1 , also known as sigma-1 receptor) is a unique ligand-regulated integral membrane scaffolding protein that contributes to cellular protein and lipid homeostasis. Previously, we demonstrated that some small-molecule modulators of Sigma1 alter endoplasmic reticulum (ER)-associated protein homeostasis pathways in cancer cells, including the unfolded protein response and autophagy. Programmed death-ligand 1 (PD-L1) is a type I integral membrane glycoprotein that is cotranslationally inserted into the ER and is processed and transported through the secretory pathway. Once at the surface of cancer cells, PD-L1 acts as a T-cell inhibitory checkpoint molecule and suppresses antitumor immunity. Here, we demonstrate that in Sigma1-expressing triple-negative breast and androgen-independent prostate cancer cells, PD-L1 protein levels were suppressed by RNAi knockdown of Sigma1 and by small-molecule inhibition of Sigma1. Sigma1-mediated action was confirmed by pharmacologic competition between Sigma1-selective inhibitor and activator ligands. When administered alone, the Sigma1 inhibitor decreased cell surface PD-L1 expression and suppressed functional interaction of PD-1 and PD-L1 in a coculture of T cells and cancer cells. Conversely, the Sigma1 activator increased PD-L1 cell surface expression, demonstrating the ability to positively and negatively modulate Sigma1 associated PD-L1 processing. We discovered that the Sigma1 inhibitor induced degradation of PD-L1 via autophagy, by a mechanism distinct from bulk macroautophagy or general ER stress-associated autophagy. Finally, the Sigma1 inhibitor suppressed IFNγ-induced PD-L1. Our data demonstrate that small-molecule Sigma1 modulators can be used to regulate PD-L1 in cancer cells and trigger its degradation by selective autophagy. Implications: Sigma1 modulators sequester and eliminate PD-L1 by autophagy, thus preventing functional PD-L1 expression at the cell surface. This posits Sigma1 modulators as novel therapeutic agents in PD-L1/PD-1 blockade strategies that regulate the tumor immune microenvironment. Visual Overview: http://mcr.aacrjournals.org/content/molcanres/16/2/243/F1.large.jpg Mol Cancer Res; 16(2); 243-55. ©2017 AACR . ©2017 American Association for Cancer Research.

  12. VizieR Online Data Catalog: H2 d3{Pi}u excitation by elec

    NASA Astrophysics Data System (ADS)

    Liu, X.; Shemansky, D. E.; Yoshii, J.; Johnson, P. V.; Malone, C. P.; Ajello, J. M.

    2016-05-01

    Electron-impact excitation of H2 triplet states plays an imp role in the heating of outer planet upper thermospheres. The d3{Pi}u state is the third ungerade triplet state, and the d3{Pi}u-a3{Sigma}g+ emission is the largest cascade channel for the a3{Sigma}g+ state. Accurate energies of the d3{Pi}u-(v, J) levels are calculated from an ab initio potential energy curve. Radiative lifetimes of the d3{Pi}u(v,J) levels are obtained by an accurate evaluation of the d3{Pi}u-a3{Sigma}g+ transition probabilities. The emission yields are determined from experimental lifetimes and calculated radiative lifetimes and are further verified by comparing experimental and synthetic d3{Pi}u-a3{Sigma}g+ spectra at 20eV impact energy. Spectral analysis revealed that multipolar components beyond the dipolar term are required to model the X1{Sigma}g+-d3{Pi}u excitation, and significant cascade excitation occurs at the d3{Pi}u (v=0,1) levels. Kinetic energy (Ek) distributions of H atoms produced via predissociation of the 3{Pi}u state and the d3{Pi}u-a3{Sigma}g+-b3{Sigma}u+ cascade dissociative emission are obtained. Predissociation of the d3{Pi}u state produces H atoms with an average Ek of 2.3+/-0.4 eV/atom, while the Ekdistribution of the d3{Pi}u-a3{Sigma}g+-b3{Sigma}u+ channel is similar to that of the X1{Sigma}g+-a3{Sigma}g+-b3{Sigma}u+ channel and produces H(1s) atoms with an average Ek of 1.15+/-0.05eV/atom. On average, each H2 excited to the d3{Pi}u state in an H2-dominated atmosphere deposits 3.3+/-0.4eV into the atmosphere, while each H2directly excited to the a3{Sigma}g+ state gives 2.2-2.3eV to the atmosphere. The spectral distribution of the calculated a3{Sigma}g+-b3{Sigma}u+ continuum emission due to the X1{Sigma}g+-d3{Pi}u excitation is significantly different from that of direct a3{Sigma}g+ excitation. (2 data files).

  13. Theoretical Study of the B(sup 3) Sigma(sup -, sub u) - X(sup3)Sigma(sub g, sup -) and B"(sup 3)Pi(sub u) - X(sup 3)Sigma(sub g, sup -) Band Systems of S(sub 2)

    NASA Technical Reports Server (NTRS)

    Pradhan, Atul D.; Partridge, Harry; Langhoff, Stephen R. (Technical Monitor)

    1995-01-01

    Multireference configuration-interaction (MRCI) wavefunctions and potential energy curves have been calculated for the X(sup 3)Sigma(sub g,sup -), B(sup 3)Sigma(sub u, Sup -) and B"(sup 3)Pi((sub u) states of S(sub 2) using correlation consistent Gaussian basis sets. These wavefunctions are utilized to compute the the transition dipole moments of the B(sup 3)Sigma(sub g, sup -) - X(sup 3) Sigma(sub g, sup -) and B"(sup 3)Pi(sub u) - X(sup 3)Sigma(sub g, sup -) systems. Oscillator strengths, transition probabilities, and radiative lifetimes are computed for the X-B system and comparison is made with experimental data.

  14. The Hallucinogen N,N-Dimethyltryptamine (DMT) Is an Endogenous Sigma-1 Receptor Regulator

    PubMed Central

    Fontanilla, Dominique; Johannessen, Molly; Hajipour, Abdol R.; Cozzi, Nicholas V.; Jackson, Meyer B.; Ruoho, Arnold E.

    2010-01-01

    The sigma-1 receptor is widely distributed in the central nervous system and periphery. Originally mischaracterized as an opioid receptor, the sigma-1 receptor binds a vast number of synthetic compounds but does not bind opioid peptides; it is currently considered an orphan receptor. The sigma-1 receptor pharmacophore includes an alkylamine core, also found in the endogenous compound N,N-dimethyltryptamine (DMT). DMT acts as a hallucinogen, but its receptor target has been unclear. DMT bound to sigma-1 receptors and inhibited voltage-gated sodium ion (Na+) channels in both native cardiac myocytes and heterologous cells that express sigma-1 receptors. DMT induced hypermobility in wild-type mice but not in sigma-1 receptor knockout mice. These biochemical, physiological, and behavioral experiments indicate that DMT is an endogenous agonist for the sigma-1 receptor. PMID:19213917

  15. The hallucinogen N,N-dimethyltryptamine (DMT) is an endogenous sigma-1 receptor regulator.

    PubMed

    Fontanilla, Dominique; Johannessen, Molly; Hajipour, Abdol R; Cozzi, Nicholas V; Jackson, Meyer B; Ruoho, Arnold E

    2009-02-13

    The sigma-1 receptor is widely distributed in the central nervous system and periphery. Originally mischaracterized as an opioid receptor, the sigma-1 receptor binds a vast number of synthetic compounds but does not bind opioid peptides; it is currently considered an orphan receptor. The sigma-1 receptor pharmacophore includes an alkylamine core, also found in the endogenous compound N,N-dimethyltryptamine (DMT). DMT acts as a hallucinogen, but its receptor target has been unclear. DMT bound to sigma-1 receptors and inhibited voltage-gated sodium ion (Na+) channels in both native cardiac myocytes and heterologous cells that express sigma-1 receptors. DMT induced hypermobility in wild-type mice but not in sigma-1 receptor knockout mice. These biochemical, physiological, and behavioral experiments indicate that DMT is an endogenous agonist for the sigma-1 receptor.

  16. Agronomic and chemical evaluation of smooth sumac, Rhus glabra

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Campbell, T.A.

    Smooth sumac (Rhus glabra) is a potential whole-plant source of polyphenol and oil. In a 2-yr evaluation of progenies from 14 Maryland, 1 northern Virginia, and 2 Georgia populations, highly significant variation (1% level) in vigor, number of plants surviving the seeding year, dry matter yield the seeding year, and number of tillers produced the second year was observed. In 15 entries, highly significant variation (1% level) in polyphenol + oil and in gallotannins was observed. Dry matter yields, extrapolated to Mg ha/sup -1/, ranged from 0.02 to 1.4 (for a single harvest), % polyphenol + oil from 19.4-31.1, andmore » % gallotannins (a class of polyphenols) from 9.8 to 15.7. It is suggested that significantly improved lines could be developed through breeding. Based on estimated ratios of sigma/sup 2//sub Entries//sigma/sup 2//sub Entries/ + sigma/sup 2/, genetic variation for most agronomic traits could be estimated with fair precision whereas variation for chemical traits could be affected substantially by nongenetic factors. Factor analysis indicated plants that would perform reasonably well over a 2-yr period could be selected on the basis of early seeding-year vigor scores. Selection for high amount of polyphenol + oil and gallotannins would have to be done independently of agronomic selection. Cutting frequencies should not exceed 2 x yr/sup -1/ or serious stand loss would occur.« less

  17. RNA Initiation with Dinucleoside Monophosphates during Transcription of Bacteriophage T4 DNA with RNA Polymerase of Escherichia coli

    PubMed Central

    Hoffman, David J.; Niyogi, Salil K.

    1973-01-01

    The effects of dinucleoside monophosphates on the transcription of phage T4 DNA by E. coli RNA polymerase have been examined at various concentrations of the sigma subunit and extremely low concentration of ribonucleoside triphosphate. The following conclusions were reached: (i) Labeled specific dinucleoside monophosphates are incorporated as chain initiators. (ii) When the ratio of sigma factor to core enzyme is small, there is a general stimulation by most 5′-guanosyl dinucleoside monophosphates. (iii) When the ratio is increased or holoenzyme is present, ApU, CpA, UpA, and GpU are the most effective stimulators. (iv) At high concentrations of sigma factor, only certain adenosine-containing dinucleoside monophosphates (ApU, CpA, UpA, and ApA) stimulate the reaction. (v) Competition hybridization studies indicate that the RNAs stimulated by dinucleoside monophosphates (ApU, CpA, UpA, and GpU) are of the T4 “early” type. (vi) Studies involving both combinations of stimulatory dinucleoside monophosphates and competitive effects of these compounds on chain initiation by ATP and GTP suggest that the stimulatory dinucleoside monophosphates act as chain initiators and may recognize part of a continuous sequence in a promoter region. Studies based on the incorporation of 3H-labeled stimulatory dinucleoside monophosphates support the above conclusions. PMID:4568732

  18. Towards Resolving the Crab Sigma-Problem: A Linear Accelerator?

    NASA Technical Reports Server (NTRS)

    Contopoulos, Ioannis; Kazanas, Demosthenes; White, Nicholas E. (Technical Monitor)

    2002-01-01

    Using the exact solution of the axisymmetric pulsar magnetosphere derived in a previous publication and the conservation laws of the associated MHD flow, we show that the Lorentz factor of the outflowing plasma increases linearly with distance from the light cylinder. Therefore, the ratio of the Poynting to particle energy flux, generically referred to as sigma, decreases inversely proportional to distance, from a large value (typically approx. greater than 10(exp 4)) near the light cylinder to sigma approx. = 1 at a transition distance R(sub trans). Beyond this distance the inertial effects of the outflowing plasma become important and the magnetic field geometry must deviate from the almost monopolar form it attains between R(sub lc), and R(sub trans). We anticipate that this is achieved by collimation of the poloidal field lines toward the rotation axis, ensuring that the magnetic field pressure in the equatorial region will fall-off faster than 1/R(sup 2) (R being the cylindrical radius). This leads both to a value sigma = a(sub s) much less than 1 at the nebular reverse shock at distance R(sub s) (R(sub s) much greater than R(sub trans)) and to a component of the flow perpendicular to the equatorial component, as required by observation. The presence of the strong shock at R = R(sub s) allows for the efficient conversion of kinetic energy into radiation. We speculate that the Crab pulsar is unique in requiring sigma(sub s) approx. = 3 x 10(exp -3) because of its small translational velocity, which allowed for the shock distance R(sub s) to grow to values much greater than R(sub trans).

  19. Factorial-based response-surface modeling with confidence intervals for optimizing thermal-optical transmission analysis of atmospheric black carbon.

    PubMed

    Conny, J M; Norris, G A; Gould, T R

    2009-03-09

    Thermal-optical transmission (TOT) analysis measures black carbon (BC) in atmospheric aerosol on a fibrous filter. The method pyrolyzes organic carbon (OC) and employs laser light absorption to distinguish BC from the pyrolyzed OC; however, the instrument does not necessarily separate the two physically. In addition, a comprehensive temperature protocol for the analysis based on the Beer-Lambert Law remains elusive. Here, empirical response-surface modeling was used to show how the temperature protocol in TOT analysis can be modified to distinguish pyrolyzed OC from BC based on the Beer-Lambert Law. We determined the apparent specific absorption cross sections for pyrolyzed OC (sigma(Char)) and BC (sigma(BC)), which accounted for individual absorption enhancement effects within the filter. Response-surface models of these cross sections were derived from a three-factor central-composite factorial experimental design: temperature and duration of the high-temperature step in the helium phase, and the heating increase in the helium-oxygen phase. The response surface for sigma(BC), which varied with instrument conditions, revealed a ridge indicating the correct conditions for OC pyrolysis in helium. The intersection of the sigma(BC) and sigma(Char) surfaces indicated the conditions where the cross sections were equivalent, satisfying an important assumption upon which the method relies. 95% confidence interval surfaces defined a confidence region for a range of pyrolysis conditions. Analyses of wintertime samples from Seattle, WA revealed a temperature between 830 degrees C and 850 degrees C as most suitable for the helium high-temperature step lasting 150s. However, a temperature as low as 750 degrees C could not be rejected statistically.

  20. The nature of the bonding in XCO for X = Fe, Ni, and Cu

    NASA Technical Reports Server (NTRS)

    Bauschlicher, C. W., Jr.; Bagus, P. S.; Nelin, C. J.; Roos, B. O.

    1986-01-01

    The bonding in the (5,3)Sigma - and 3Delta states of FeCO, the (3,1)Sigma + , 3Delta, and 3Pi states of NiCO, and the 2Sigma + state of CuCO are analyzed using the constrained-space orbital-variation (CSOV) technique for both (CASSCF) and SCF wave functions. The bonding is discussed in terms of sigma repulsion between the metals 4s and the CO 5-sigma and CO-to-metal sigma donation when there is an empty or partly occupied d-sigma orbital and metal-to-CO 2pi(asterisk) backdonation. The bonding is compared for the different metals and between the different states.

  1. On the Longitudinal Morphology of Zonal Irregularity Drift Measured using Networks of GPS Scintillation Monitors

    NASA Astrophysics Data System (ADS)

    Carrano, C. S.; Groves, K. M.; Valladares, C. E.; Delay, S. H.

    2014-12-01

    A complete characterization of field-aligned ionospheric irregularities responsible for the scintillation of satellite signals includes not only their spectral properties (power spectral strength, spectral index, anisotropy ratio, and outer-scale) but also their horizontal drift velocity. From a system impacts perspective, the horizontal drift velocity is important in that it dictates the rate of signal fading and also, to an extent, the level of phase fluctuations encountered by the receiver. From a physics perspective, studying the longitudinal morphology of zonal irregularity may lead to an improved understanding of the F region dynamo and regional electrodynamics at low latitudes. The irregularity drift at low latitudes is predominantly zonal and is most commonly measured by cross-correlating observations of satellite signals made by a pair of closely-spaced antennas. The AFRL-SCINDA network operates a small number of VHF spaced-antenna systems at low latitude stations for this purpose. A far greater number of GPS scintillation monitors are operated by AFRL-SCINDA (25-30) and the Low Latitude Ionospheric Sensor Network (35-50), but the receivers are situated too far apart to monitor the drift using cross-correlation techniques. In this paper, we present an alternative approach that leverages the weak scatter scintillation theory (Rino, Radio Sci., 1979) to infer the zonal irregularity drift from single-station GPS measurements of S4, sigma-phi, and the propagation geometry alone. Unlike the spaced-receiver technique, this technique requires assumptions for the height of the scattering layer (which introduces a bias in the drift estimates) and the spectral index of the irregularities (which affects the spread of the drift estimates about the mean). Nevertheless, theory and experiment show that the ratio of sigma-phi to S4 is less sensitive to these parameters than it is to the zonal drift, and hence the zonal drift can be estimated with reasonable accuracy. In this talk, we first validate the technique using spaced VHF-antenna measurements of zonal irregularity drift from the AFRL-SCINDA network. Next, we discuss preliminary results from our investigation into the longitudinal morphology of zonal irregularity drift using the AFRL-SCINDA and LISN networks of GPS scintillation monitors.

  2. Description and properties of a resistive network applied to emission tomography detector readouts

    NASA Astrophysics Data System (ADS)

    Boisson, F.; Bekaert, V.; Sahr, J.; Brasse, D.

    2017-11-01

    Over the last twenty years, PET systems have used discrete crystal detector modules coupled to multi-channel photodetectors, mostly to improve the spatial resolution. Although reading each readout channels individually would be of great interest, costs associated with the electronics would, in most cases, be too expensive. It is therefore essential to propose lower-cost solutions that do not degrade the overall system's performance. One possible solution to reduce the development costs of a PET system without degrading performance is the use of a resistive network which reduces the total number of readout channels. In this study, we present a symmetric charge division resistive network and associated software methods to assess the performance of a PET detector. Our approach consists in keeping the n lines and n columns information provided by a symmetric charge division circuit (SCD). We provided equations relative to output currents of the network, which enable estimation of the charge. We propose a novel approach to reconstruct the charge distribution from the lines and columns projection using a maximum likelihood expectation maximization (MLEM) approach which takes the non-uniformity of the photodetector channel gains into account. We also introduce a mathematical proof of the relation between the sigma of the reconstructed charge distribution and the Ratio between the line of interest (maximum value) and the background signal charges. To the best of our knowledge, this is the first study reporting these equations. Preliminary results obtained with a resistive network used in readout of a monolithic 50 × 50 × 8mm3 LYSO crystal coupled to a H9500 PMT validated the effectiveness of the reconstructed charge distribution to optimize both the x and y spatial resolution and the energy resolution. We obtained a mean x and y spatial resolution of 1.10 mm FWHM and a 14.7% energy resolution by calculating the integral of the reconstructed charge distribution. Finally, the relation between the ratio and the sigma of the reconstructed charge distribution may provide new opportunities in terms of Depth-of-Interaction estimation when using a monolithic crystal coupled to a multi-channel photodetector.

  3. Integrating Six Sigma with total quality management: a case example for measuring medication errors.

    PubMed

    Revere, Lee; Black, Ken

    2003-01-01

    Six Sigma is a new management philosophy that seeks a nonexistent error rate. It is ripe for healthcare because many healthcare processes require a near-zero tolerance for mistakes. For most organizations, establishing a Six Sigma program requires significant resources and produces considerable stress. However, in healthcare, management can piggyback Six Sigma onto current total quality management (TQM) efforts so that minimal disruption occurs in the organization. Six Sigma is an extension of the Failure Mode and Effects Analysis that is required by JCAHO; it can easily be integrated into existing quality management efforts. Integrating Six Sigma into the existing TQM program facilitates process improvement through detailed data analysis. A drilled-down approach to root-cause analysis greatly enhances the existing TQM approach. Using the Six Sigma metrics, internal project comparisons facilitate resource allocation while external project comparisons allow for benchmarking. Thus, the application of Six Sigma makes TQM efforts more successful. This article presents a framework for including Six Sigma in an organization's TQM plan while providing a concrete example using medication errors. Using the process defined in this article, healthcare executives can integrate Six Sigma into all of their TQM projects.

  4. Mucosal vaccination by adenoviruses displaying reovirus sigma 1

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Weaver, Eric A.; Camacho, Zenaido T.; Hillestad, Matthew L.

    We developed adenovirus serotype 5 (Ad5) vectors displaying the sigma 1 protein from reovirus as mucosal vaccines. Ad5-sigma retargets to JAM-1 and sialic acid, but has 40-fold reduced gene delivery when compared to Ad5. While weaker at transduction, Ad5-sigma generates stronger T cell responses than Ad5 when used for mucosal immunization. In this work, new Ad5-fiber-sigma vectors were generated by varying the number of fiber β-spiral shaft repeats (R) between the fiber tail and sigma. Increasing chimera length led to decreasing insertion of these proteinsAd5 virions. Ad-R3 and R14 vectors effectively targeted JAM-1 in vitro while R20 did not. Whenmore » wereused to immunize mice by the intranasal route, Ad5-R3-sigma produced higher serum and vaginal antibody responses than Ad5. These data suggest optimized Ad-sigma vectors may be useful vectors for mucosal vaccination. - Highlights: • Constructed adenoviruses (Ads) displaying different reovirus sigma 1 fusion proteins. • Progressively longer chimeras were more poorly encapsidated onto Ad virions. • Ad5-R3-sigma mediated better systemic and mucosal immune responses than Ad5.« less

  5. Sigma metrics as a tool for evaluating the performance of internal quality control in a clinical chemistry laboratory.

    PubMed

    Kumar, B Vinodh; Mohan, Thuthi

    2018-01-01

    Six Sigma is one of the most popular quality management system tools employed for process improvement. The Six Sigma methods are usually applied when the outcome of the process can be measured. This study was done to assess the performance of individual biochemical parameters on a Sigma Scale by calculating the sigma metrics for individual parameters and to follow the Westgard guidelines for appropriate Westgard rules and levels of internal quality control (IQC) that needs to be processed to improve target analyte performance based on the sigma metrics. This is a retrospective study, and data required for the study were extracted between July 2015 and June 2016 from a Secondary Care Government Hospital, Chennai. The data obtained for the study are IQC - coefficient of variation percentage and External Quality Assurance Scheme (EQAS) - Bias% for 16 biochemical parameters. For the level 1 IQC, four analytes (alkaline phosphatase, magnesium, triglyceride, and high-density lipoprotein-cholesterol) showed an ideal performance of ≥6 sigma level, five analytes (urea, total bilirubin, albumin, cholesterol, and potassium) showed an average performance of <3 sigma level and for level 2 IQCs, same four analytes of level 1 showed a performance of ≥6 sigma level, and four analytes (urea, albumin, cholesterol, and potassium) showed an average performance of <3 sigma level. For all analytes <6 sigma level, the quality goal index (QGI) was <0.8 indicating the area requiring improvement to be imprecision except cholesterol whose QGI >1.2 indicated inaccuracy. This study shows that sigma metrics is a good quality tool to assess the analytical performance of a clinical chemistry laboratory. Thus, sigma metric analysis provides a benchmark for the laboratory to design a protocol for IQC, address poor assay performance, and assess the efficiency of existing laboratory processes.

  6. Proton Form Factor Puzzle and the CEBAF Large Acceptance Spectrometer (CLAS) two-photon exchange experiment

    NASA Astrophysics Data System (ADS)

    Rimal, Dipak

    The electromagnetic form factors are the most fundamental observables that encode information about the internal structure of the nucleon. The electric (GE) and the magnetic ( GM) form factors contain information about the spatial distribution of the charge and magnetization inside the nucleon. A significant discrepancy exists between the Rosenbluth and the polarization transfer measurements of the electromagnetic form factors of the proton. One possible explanation for the discrepancy is the contributions of two-photon exchange (TPE) effects. Theoretical calculations estimating the magnitude of the TPE effect are highly model dependent, and limited experimental evidence for such effects exists. Experimentally, the TPE effect can be measured by comparing the ratio of positron-proton elastic scattering cross section to that of the electron-proton [R = sigma(e +p)/sigma(e+p)]. The ratio R was measured over a wide range of kinematics, utilizing a 5.6 GeV primary electron beam produced by the Continuous Electron Beam Accelerator Facility (CEBAF) at Jefferson Lab. This dissertation explored dependence of R on kinematic variables such as squared four-momentum transfer (Q2) and the virtual photon polarization parameter (epsilon). A mixed electron-positron beam was produced from the primary electron beam in experimental Hall B. The mixed beam was scattered from a liquid hydrogen (LH2) target. Both the scattered lepton and the recoil proton were detected by the CEBAF Large Acceptance Spectrometer (CLAS). The elastic events were then identified by using elastic scattering kinematics. This work extracted the Q2 dependence of R at high epsilon(epsilon > 0.8) and the $epsilon dependence of R at approx 0.85 GeV2. In these kinematics, our data confirm the validity of the hadronic calculations of the TPE effect by Blunden, Melnitchouk, and Tjon. This hadronic TPE effect, with additional corrections contributed by higher excitations of the intermediate state nucleon, largely reconciles the Rosenbluth and the polarization transfer measurements of the electromagnetic form factors.

  7. Reducing liver transplant length of stay: a Lean Six Sigma approach.

    PubMed

    Toledo, Alexander H; Carroll, Tracy; Arnold, Emily; Tulu, Zeynep; Caffey, Tom; Kearns, Lauren E; Gerber, David A

    2013-12-01

    Organ transplant centers are under increasing scrutiny to maintain outcomes while controlling cost in a challenging population of patients. Throughout health care and transplant specifically, length of stay is used as a benchmark for both quality and resource utilization. To decrease our length of stay for liver transplant by using Lean Six Sigma methods. The Six Sigma DMAIC (Define, Measure, Analyze, Improve, Control) method was used to systematically analyze our process from transplant listing to hospital discharge after transplant, identifying many factors affecting length of stay. Adult, single-organ, primary liver transplant recipients between July 2008 and June 2012 were included in the study. Recipients with living donors or fulminant liver failure were excluded. Multiple interventions, including a clinical pathway and enhanced communication, were implemented. Length of stay after liver transplant and readmission after liver transplant.R ESULTS: Median length of stay decreased significantly from 11 days before the intervention to 8 days after the intervention. Readmission rate did not change throughout the study. The improved length of stay was maintained for 24 months after the study. Using a Lean Six Sigma approach, we were able to significantly decrease the length of stay of liver transplant patients. These results brought our center's outcomes in accordance with our goal and industry benchmark of 8 days. Clear expectations, improved teamwork, and a multidisciplinary clinical pathway were key elements in achieving and maintaining these gains.

  8. An on-line pre-concentration system for determination of cadmium in drinking water using FAAS.

    PubMed

    dos Santos, Walter N L; Costa, Jorge L O; Araujo, Rennan G O; de Jesus, Djane S; Costa, Antônio C S

    2006-10-11

    In the present paper, a minicolumn of polyurethane foam loaded with 4-(2-pyridylazo)-resorcinol (PAR) is proposed as pre-concentration system for cadmium determination in drinking water samples by flame atomic absorption spectrometry. The optimization step was performed using two-level full factorial design and Doehlert matrix, involving the variables: sampling flow rate, elution concentration, buffer concentration and pH. Using the established experimental conditions in the optimization step of: pH 8.2, sampling flow rate 8.5 mL min(-1), buffer concentration 0.05 mol L(-1) and elution concentration of 1.0 mol L(-1), this system allows the determination of cadmium with detection limit (LD) (3sigma/S) of 20.0 ng L(-1) and quantification limit (LQ) (10sigma/S) of 64 ng L(-1), precision expressed as relative standard deviation (R.S.D.) of 5.0 and 4.7% for cadmium concentration of 5.0 and 40.0 microg L(-1), respectively, and a pre-concentration factor of 158 for a sample volume of 20.0 mL. The accuracy was confirmed by cadmium determination in the standard reference material, NIST SRM 1643d trace elements in natural water. This procedure was applied for cadmium determination in drinking water samples collected from Salvador City, Bahia, Brazil. For five samples analyzed, the achieved concentrations varied from 0.31 to 0.86 microg L(-1).

  9. On the Statistical Analysis of X-ray Polarization Measurements

    NASA Technical Reports Server (NTRS)

    Strohmayer, T. E.; Kallman, T. R.

    2013-01-01

    In many polarimetry applications, including observations in the X-ray band, the measurement of a polarization signal can be reduced to the detection and quantification of a deviation from uniformity of a distribution of measured angles of the form alpha plus beta cosine (exp 2)(phi - phi(sub 0) (0 (is) less than phi is less than pi). We explore the statistics of such polarization measurements using both Monte Carlo simulations as well as analytic calculations based on the appropriate probability distributions. We derive relations for the number of counts required to reach a given detection level (parameterized by beta the "number of sigma's" of the measurement) appropriate for measuring the modulation amplitude alpha by itself (single interesting parameter case) or jointly with the position angle phi (two interesting parameters case). We show that for the former case when the intrinsic amplitude is equal to the well known minimum detectable polarization (MDP) it is, on average, detected at the 3sigma level. For the latter case, when one requires a joint measurement at the same confidence level, then more counts are needed, by a factor of approximately equal to 2.2, than that required to achieve the MDP level. We find that the position angle uncertainty at 1sigma confidence is well described by the relation sigma(sub pi) equals 28.5(degrees) divided by beta.

  10. ABSOLUTE INTEGRAL CROSS SECTIONS AND PRODUCT BRANCHING RATIOS FOR THE VIBRATIONALLY SELECTED ION-MOLECULE REACTIONS: N{sub 2}{sup +}(X {sup 2}{Sigma}{sub g}{sup +}; v {sup +} = 0-2) + CH{sub 4}

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xu Yuntao; Chang, Yih Chung; Lu Zhou

    Absolute vibrationally selected integral cross sections ({sigma}{sub v+}'s) for the ion-molecule reaction N{sub 2}{sup +}(X {sup 2}{Sigma}{sub g}{sup +}; v {sup +} = 0-2) + CH{sub 4} have been measured by using the newly developed vacuum ultraviolet (VUV) laser pulsed field ionization-photoion (PFI-PI) double-quadrupole-double-octopole ion guide apparatus. By employing a novel electric field pulsing scheme to the VUV laser PFI-PI source, we have been able to prepare reactant N{sub 2}{sup +} ions in single-vibrational quantum states with not only high intensity and high purity but also high kinetic energy resolution, allowing integral cross section measurements to be conducted in themore » center-of-mass kinetic energies (E{sub cm}'s) from 0.05 to 10.00 eV. Three primary product channels corresponding to the formations of CH{sub 3}{sup +}, CH{sub 2}{sup +}, and N{sub 2}H{sup +} were identified. After correcting for the secondary reactions involving CH{sub 3}{sup +} and CH{sub 2}{sup +}, we have determined the {sigma}{sub v+} values of the formation of these primary product ions, {sigma}{sub v+}(CH{sub 3}{sup +}), {sigma}{sub v+}(CH{sub 2}{sup +}), and {sigma}{sub v+}(N{sub 2}H{sup +}), and their branching ratios, [{sigma}{sub v+}(CH{sub 3}{sup +}): {sigma}{sub v+}(CH{sub 2}{sup +}): {sigma}{sub v+}(N{sub 2}H{sup +})]/{sigma}{sub v+}(CH{sub 3}{sup +} + CH{sub 2}{sup +} + N{sub 2}H{sup +}), v {sup +} = 0-2, in the E{sub cm} range of 0.05-10.00 eV, where {sigma}{sub v+}(CH{sub 3}{sup +} + CH{sub 2}{sup +} + N{sub 2}H{sup +}) = {sigma}{sub v+}(CH{sub 3}{sup +}) + {sigma}{sub v+}(CH{sub 2}{sup +}) + {sigma}{sub v+}(N{sub 2}H{sup +}). The branching ratios are found to be nearly independent of the v {sup +} state and E{sub cm}. Complex v {sup +}-state and E{sub cm} dependences for {sigma}{sub v+}(CH{sub 3}{sup +}), {sigma}{sub v+}(CH{sub 2}{sup +}), and {sigma}{sub v+}(N{sub 2}H{sup +}) along with vibrational inhibition for the formation of these product ions are observed. The vibrational effects on the {sigma}{sub v+} values are sufficiently large to warrant the inclusion of the vibrationally excited reactions N{sub 2}{sup +}(X {sup 2}{Sigma}{sub g}{sup +}; v {sup +} {>=} 1) + CH{sub 4} for a more realistic modeling of the ion and neutral densities observed in the atmosphere of Titan. The cross-sectional data obtained in the present study are also useful for benchmarking theoretical calculations on ion-neutral collision dynamics.« less

  11. Methionine-141 directly influences the binding of 4-methylpyrazole in human sigma sigma alcohol dehydrogenase.

    PubMed Central

    Xie, P. T.; Hurley, T. D.

    1999-01-01

    Pyrazole and its 4-alkyl substituted derivatives are potent inhibitors for many alcohol dehydrogenases. However, the human sigma sigma isoenzyme exhibits a 580-fold lower affinity for 4-methylpyrazole than does the human beta1beta1 isoenzyme, with which it shares 69% sequence identity. In this study, structural and kinetic studies were utilized in an effort to identify key structural features that affect the binding of 4-methylpyrazole in human alcohol dehydrogenase isoenzymes. We have extended the resolution of the human sigma sigma alcohol dehydrogenase (ADH) isoenzyme to 2.5 A resolution. Comparison of this structure to the human beta1beta1 isoenzyme structure indicated that the side-chain position for Met141 in sigma sigma ADH might interfere with 4-methylpyrazole binding. Mutation of Met141 in sigma sigma ADH to Leu (sigma141L) lowers the Ki for 4-methylpyrazole from 350 to 10 microM, while having a much smaller effect on the Ki for pyrazole. Thus, the mutagenesis results show that the residue at position 141, which lines the substrate-binding pocket at a position close to the methyl group of 4-methylpyrazole, directly affects the binding of the inhibitor. To rule out nonspecific structural changes due to the mutation, the X-ray structure of the sigma141L mutant enzyme was determined to 2.4 A resolution. The three-dimensional structure of the mutant enzyme is identical to the wild-type enzyme, with the exception of the residue at position 141. Thus, the differences in 4-methylpyrazole binding between the mutant and wild-type sigma sigma ADH isoenzymes can be completely ascribed to the local changes in the topology of the substrate binding site, and provides an explanation for the class-specific differences in 4-methylpyrazole binding to the human ADH isoenzymes. PMID:10631979

  12. Ab initio calculation of the electronic structures of the (7)Sigma+ ground and A (7)Pi and a (5)Sigma+ excited states of MnH.

    PubMed

    Tomonari, Mutsumi; Nagashima, Umpei; Hirano, Tsuneo

    2009-04-21

    Electronic structures and molecular constants of the ground (7)Sigma(+) and low-lying A (7)Pi and a (5)Sigma(+) electronic excited states of the MnH molecule were studied by multireference single and double excitation configuration interaction (MR-SDCI) with Davidson's correction (+Q) calculations under exact C(infinity v) symmetry using Slater-type basis sets. To correctly describe the (7)Sigma(+) electronic ground state, X (7)Sigma(+), at the MR-SDCI+Q calculation, we employed a large number of reference configurations in terms of the state-averaged complete active space self-consistent field (CASSCF) orbitals, taking into account the contribution from the B (7)Sigma(+) excited state. The A (7)Pi and a (5)Sigma(+) states can well be described by the MR-SDCI wave functions based on the CASSCF orbitals obtained for the lowest state only. In the MR-SDCI+Q, calculations of the X (7)Sigma(+), A (7)Pi, and a (5)Sigma(+) states required 16, 7, and 17 reference configurations, respectively. Molecular constants, i.e., r(e) and omega(e) of these states and excitation energy from the X (7)Sigma(+) state, obtained at the MR-SDCI+Q level, showed a good agreement with experimental values. The small remaining differences may be accounted for by taking relativistic effects into account.

  13. Short-term prediction of chaotic time series by using RBF network with regression weights.

    PubMed

    Rojas, I; Gonzalez, J; Cañas, A; Diaz, A F; Rojas, F J; Rodriguez, M

    2000-10-01

    We propose a framework for constructing and training a radial basis function (RBF) neural network. The structure of the gaussian functions is modified using a pseudo-gaussian function (PG) in which two scaling parameters sigma are introduced, which eliminates the symmetry restriction and provides the neurons in the hidden layer with greater flexibility with respect to function approximation. We propose a modified PG-BF (pseudo-gaussian basis function) network in which the regression weights are used to replace the constant weights in the output layer. For this purpose, a sequential learning algorithm is presented to adapt the structure of the network, in which it is possible to create a new hidden unit and also to detect and remove inactive units. A salient feature of the network systems is that the method used for calculating the overall output is the weighted average of the output associated with each receptive field. The superior performance of the proposed PG-BF system over the standard RBF are illustrated using the problem of short-term prediction of chaotic time series.

  14. Einstein coefficients for rotational lines of the (0,0) band of the NO A2sigma(+)-X2Pi system

    NASA Technical Reports Server (NTRS)

    Reisel, John R.; Carter, Campbell D.; Laurendeau, Normand M.

    1992-01-01

    A summary of the spectroscopic equations necessary for prediction of the molecular transition energies and the Einstein A and B coefficients for rovibronic lines of the gamma(0,0) band of nitric oxide (NO) is presented. The calculated molecular transition energies are all within 0.57/cm of published experimental values; in addition, over 95 percent of the calculated energies give agreement with measured results within 0.25/cm. Einstein coefficients are calculated from the band A00 value and the known Hoenl-London factors and are tabulated for individual rovibronic transitions in the NO A2sigma(+)-X2Pi(0,0) band.

  15. Absolute Rovibrational Intensities, Self-Broadening and Self-Shift Coefficients for the X(sup 1) Sigma(+) V=3 (left arrow) V=0 Band (C-12)(O-16)

    NASA Technical Reports Server (NTRS)

    Chackerian, Charles, Jr.; Freedman, R.; Giver, L. P.; Brown, L. R.

    2001-01-01

    The rotationless transition moment squared for the x(sup 1) sigma (sup +) v=3 (left arrow) v=0 band of CO is measured to be the absolute value of R (sub 3-0) squared = 1.7127(25)x 10(exp -7) Debye squared. This value is about 8.6 percent smaller than the value assumed for HITRAN 2000. The Herman-Wallis intensity factor of this band is F=1+0.01168(11)m+0.0001065(79)m squared. The determination of self-broadening coefficients is improved with the inclusion of line narrowing; self-shifts are also reported.

  16. Assessing and Ensuring GOES-R Magnetometer Accuracy

    NASA Technical Reports Server (NTRS)

    Kronenwetter, Jeffrey; Carter, Delano R.; Todirita, Monica; Chu, Donald

    2016-01-01

    The GOES-R magnetometer accuracy requirement is 1.7 nanoteslas (nT). During quiet times (100 nT), accuracy is defined as absolute mean plus 3 sigma. During storms (300 nT), accuracy is defined as absolute mean plus 2 sigma. To achieve this, the sensor itself has better than 1 nT accuracy. Because zero offset and scale factor drift over time, it is also necessary to perform annual calibration maneuvers. To predict performance, we used covariance analysis and attempted to corroborate it with simulations. Although not perfect, the two generally agree and show the expected behaviors. With the annual calibration regimen, these predictions suggest that the magnetometers will meet their accuracy requirements.

  17. Reinforcing effects of sigma-receptor agonists in rats trained to self-administer cocaine.

    PubMed

    Hiranita, Takato; Soto, Paul L; Tanda, Gianluigi; Katz, Jonathan L

    2010-02-01

    sigma-Receptor (sigmaR) antagonists have been reported to block certain effects of psychostimulant drugs. The present study examined the effects of sigmaR ligands in rats trained to self-administer cocaine (0.032-1.0 mg/kg/inj i.v.) under fixed-ratio 5-response schedules of reinforcement. Maximal rates of responding were maintained by 0.32 mg/kg/inj cocaine, or by the sigmaR agonists, 1,3-di-(2-tolyl)guanidine (DTG; 1.0 mg/kg/inj) or 2-(4-morpholinethyl) 1-phenylcyclohexane-1-carboxylate hydrochloride (PRE-084; 0.32 mg/kg/inj), when substituted for cocaine. Lower response rates were maintained at higher and lower doses of the compounds. No dose of the sigmaR antagonists [N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (BD 1008), N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino)ethylamine (BD 1047), N-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine (BD 1063)] maintained responding appreciably above levels obtained when responding had no consequences. Presession treatment with sigmaR agonists dose-dependently shifted the cocaine self-administration dose-effect curve leftward. The dopamine-uptake inhibitor, (-)-2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane (WIN 35,428), dose-dependently shifted the DTG and PRE-084 self-administration dose-effect curves leftward. Treatment with the sigmaR antagonists dose-dependently decreased response rates maintained by DTG or PRE-084, but did not affect cocaine self-administration. Response rates maintained by maximally effective DTG or PRE-084 doses were decreased by sigmaR antagonists at lower doses than those that decreased response rates maintained by food reinforcement. Although sigmaR antagonists block some cocaine-induced effects, the lack of effect on cocaine self-administration suggests that the primary reinforcing effects of cocaine do not involve direct effects at sigmaRs. However, the self-administration of sigmaR agonists in cocaine-trained subjects, facilitation of cocaine self-administration by sigmaR-agonist pretreatment, and the facilitation of sigmaR-agonist self-administration by WIN 35,428, together suggest enhanced abuse-related effects resulting from concomitant dopaminergically mediated actions and sigmaR-mediated actions of the drugs.

  18. Coulomb Scattering in the Massless Nelson Model III: Ground State Wave Functions and Non-commutative Recurrence Relations

    NASA Astrophysics Data System (ADS)

    Dybalski, Wojciech; Pizzo, Alessandro

    2018-02-01

    Let $H_{P,\\sigma}$ be the single-electron fiber Hamiltonians of the massless Nelson model at total momentum $P$ and infrared cut-off $\\sigma>0$. We establish detailed regularity properties of the corresponding $n$-particle ground state wave functions $f^n_{P,\\sigma}$ as functions of $P$ and $\\sigma$. In particular, we show that \\[ |\\partial_{P^j}f^{n}_{P,\\sigma}(k_1,\\ldots, k_n)|, \\ \\ |\\partial_{P^j} \\partial_{P^{j'}} f^{n}_{P,\\sigma}(k_1,\\ldots, k_n)| \\leq \\frac{1}{\\sqrt{n!}} \\frac{(c\\lambda_0)^n}{\\sigma^{\\delta_{\\lambda_0}}} \\prod_{i=1}^n\\frac{ \\chi_{[\\sigma,\\kappa)}(k_i)}{|k_i|^{3/2}}, \\] where $c$ is a numerical constant, $\\lambda_0\\mapsto \\delta_{\\lambda_0}$ is a positive function of the maximal admissible coupling constant which satisfies $\\lim_{\\lambda_0\\to 0}\\delta_{\\lambda_0}=0$ and $\\chi_{[\\sigma,\\kappa)}$ is the (approximate) characteristic function of the energy region between the infrared cut-off $\\sigma$ and the ultraviolet cut-off $\\kappa$. While the analysis of the first derivative is relatively straightforward, the second derivative requires a new strategy. By solving a non-commutative recurrence relation we derive a novel formula for $f^n_{P,\\sigma}$ with improved infrared properties. In this representation $\\partial_{P^{j'}}\\partial_{P^{j}}f^n_{P,\\sigma}$ is amenable to sharp estimates obtained by iterative analytic perturbation theory in part II of this series of papers. The bounds stated above are instrumental for scattering theory of two electrons in the Nelson model, as explained in part I of this series.

  19. Observation of the Heavy Baryons Sigma b and Sigma b*.

    PubMed

    Aaltonen, T; Abulencia, A; Adelman, J; Affolder, T; Akimoto, T; Albrow, M G; Amerio, S; Amidei, D; Anastassov, A; Anikeev, K; Annovi, A; Antos, J; Aoki, M; Apollinari, G; Arisawa, T; Artikov, A; Ashmanskas, W; Attal, A; Aurisano, A; Azfar, F; Azzi-Bacchetta, P; Azzurri, P; Bacchetta, N; Badgett, W; Barbaro-Galtieri, A; Barnes, V E; Barnett, B A; Baroiant, S; Bartsch, V; Bauer, G; Beauchemin, P-H; Bedeschi, F; Behari, S; Bellettini, G; Bellinger, J; Belloni, A; Benjamin, D; Beretvas, A; Beringer, J; Berry, T; Bhatti, A; Binkley, M; Bisello, D; Bizjak, I; Blair, R E; Blocker, C; Blumenfeld, B; Bocci, A; Bodek, A; Boisvert, V; Bolla, G; Bolshov, A; Bortoletto, D; Boudreau, J; Boveia, A; Brau, B; Brigliadori, L; Bromberg, C; Brubaker, E; Budagov, J; Budd, H S; Budd, S; Burkett, K; Busetto, G; Bussey, P; Buzatu, A; Byrum, K L; Cabrera, S; Campanelli, M; Campbell, M; Canelli, F; Canepa, A; Carillo, S; Carlsmith, D; Carosi, R; Carron, S; Casal, B; Casarsa, M; Castro, A; Catastini, P; Cauz, D; Cavalli-Sforza, M; Cerri, A; Cerrito, L; Chang, S H; Chen, Y C; Chertok, M; Chiarelli, G; Chlachidze, G; Chlebana, F; Cho, I; Cho, K; Chokheli, D; Chou, J P; Choudalakis, G; Chuang, S H; Chung, K; Chung, W H; Chung, Y S; Cilijak, M; Ciobanu, C I; Ciocci, M A; Clark, A; Clark, D; Coca, M; Compostella, G; Convery, M E; Conway, J; Cooper, B; Copic, K; Cordelli, M; Cortiana, G; Crescioli, F; Cuenca Almenar, C; Cuevas, J; Culbertson, R; Cully, J C; DaRonco, S; Datta, M; D'Auria, S; Davies, T; Dagenhart, D; de Barbaro, P; De Cecco, S; Deisher, A; De Lentdecker, G; De Lorenzo, G; Dell'Orso, M; Delli Paoli, F; Demortier, L; Deng, J; Deninno, M; De Pedis, D; Derwent, P F; Di Giovanni, G P; Dionisi, C; Di Ruzza, B; Dittmann, J R; D'Onofrio, M; Dörr, C; Donati, S; Dong, P; Donini, J; Dorigo, T; Dube, S; Efron, J; Erbacher, R; Errede, D; Errede, S; Eusebi, R; Fang, H C; Farrington, S; Fedorko, I; Fedorko, W T; Feild, R G; Feindt, M; Fernandez, J P; Field, R; Flanagan, G; Forrest, R; Forrester, S; Franklin, M; Freeman, J C; Furic, I; Gallinaro, M; Galyardt, J; Garcia, J E; Garberson, F; Garfinkel, A F; Gay, C; Gerberich, H; Gerdes, D; Giagu, S; Giannetti, P; Gibson, K; Gimmell, J L; Ginsburg, C; Giokaris, N; Giordani, M; Giromini, P; Giunta, M; Giurgiu, G; Glagolev, V; Glenzinski, D; Gold, M; Goldschmidt, N; Goldstein, J; Golossanov, A; Gomez, G; Gomez-Ceballos, G; Goncharov, M; González, O; Gorelov, I; Goshaw, A T; Goulianos, K; Gresele, A; Grinstein, S; Grosso-Pilcher, C; Grundler, U; Guimaraes da Costa, J; Gunay-Unalan, Z; Haber, C; Hahn, K; Hahn, S R; Halkiadakis, E; Hamilton, A; Han, B-Y; Han, J Y; Handler, R; Happacher, F; Hara, K; Hare, D; Hare, M; Harper, S; Harr, R F; Harris, R M; Hartz, M; Hatakeyama, K; Hauser, J; Hays, C; Heck, M; Heijboer, A; Heinemann, B; Heinrich, J; Henderson, C; Herndon, M; Heuser, J; Hidas, D; Hill, C S; Hirschbuehl, D; Hocker, A; Holloway, A; Hou, S; Houlden, M; Hsu, S-C; Huffman, B T; Hughes, R E; Husemann, U; Huston, J; Incandela, J; Introzzi, G; Iori, M; Ivanov, A; Iyutin, B; James, E; Jang, D; Jayatilaka, B; Jeans, D; Jeon, E J; Jindariani, S; Johnson, W; Jones, M; Joo, K K; Jun, S Y; Jung, J E; Junk, T R; Kamon, T; Karchin, P E; Kato, Y; Kemp, Y; Kephart, R; Kerzel, U; Khotilovich, V; Kilminster, B; Kim, D H; Kim, H S; Kim, J E; Kim, M J; Kim, S B; Kim, S H; Kim, Y K; Kimura, N; Kirsch, L; Klimenko, S; Klute, M; Knuteson, B; Ko, B R; Kondo, K; Kong, D J; Konigsberg, J; Korytov, A; Kotwal, A V; Kraan, A C; Kraus, J; Kreps, M; Kroll, J; Krumnack, N; Kruse, M; Krutelyov, V; Kubo, T; Kuhlmann, S E; Kuhr, T; Kulkarni, N P; Kusakabe, Y; Kwang, S; Laasanen, A T; Lai, S; Lami, S; Lammel, S; Lancaster, M; Lander, R L; Lannon, K; Lath, A; Latino, G; Lazzizzera, I; LeCompte, T; Lee, J; Lee, J; Lee, Y J; Lee, S W; Lefèvre, R; Leonardo, N; Leone, S; Levy, S; Lewis, J D; Lin, C; Lin, C S; Lindgren, M; Lipeles, E; Lister, A; Litvintsev, D O; Liu, T; Lockyer, N S; Loginov, A; Loreti, M; Lu, R-S; Lucchesi, D; Lujan, P; Lukens, P; Lungu, G; Lyons, L; Lys, J; Lysak, R; Lytken, E; Mack, P; MacQueen, D; Madrak, R; Maeshima, K; Makhoul, K; Maki, T; Maksimovic, P; Malde, S; Malik, S; Manca, G; Manousakis, A; Margaroli, F; Marginean, R; Marino, C; Marino, C P; Martin, A; Martin, M; Martin, V; Martínez, M; Martínez-Ballarín, R; Maruyama, T; Mastrandrea, P; Masubuchi, T; Matsunaga, H; Mattson, M E; Mazini, R; Mazzanti, P; McFarland, K S; McIntyre, P; McNulty, R; Mehta, A; Mehtala, P; Menzemer, S; Menzione, A; Merkel, P; Mesropian, C; Messina, A; Miao, T; Miladinovic, N; Miles, J; Miller, R; Mills, C; Milnik, M; Mitra, A; Mitselmakher, G; Miyamoto, A; Moed, S; Moggi, N; Mohr, B; Moon, C S; Moore, R; Morello, M; Movilla Fernandez, P; Mülmenstädt, J; Mukherjee, A; Muller, Th; Mumford, R; Murat, P; Mussini, M; Nachtman, J; Nagano, A; Naganoma, J; Nakamura, K; Nakano, I; Napier, A; Necula, V; Neu, C; Neubauer, M S; Nielsen, J; Nodulman, L; Norniella, O; Nurse, E; Oh, S H; Oh, Y D; Oksuzian, I; Okusawa, T; Oldeman, R; Orava, R; Osterberg, K; Pagliarone, C; Palencia, E; Papadimitriou, V; Papaikonomou, A; Paramonov, A A; Parks, B; Pashapour, S; Patrick, J; Pauletta, G; Paulini, M; Paus, C; Pellett, D E; Penzo, A; Phillips, T J; Piacentino, G; Piedra, J; Pinera, L; Pitts, K; Plager, C; Pondrom, L; Portell, X; Poukhov, O; Pounder, N; Prakoshyn, F; Pronko, A; Proudfoot, J; Ptohos, F; Punzi, G; Pursley, J; Rademacker, J; Rahaman, A; Ramakrishnan, V; Ranjan, N; Redondo, I; Reisert, B; Rekovic, V; Renton, P; Rescigno, M; Richter, S; Rimondi, F; Ristori, L; Robson, A; Rodrigo, T; Rogers, E; Rolli, S; Roser, R; Rossi, M; Rossin, R; Roy, P; Ruiz, A; Russ, J; Rusu, V; Saarikko, H; Safonov, A; Sakumoto, W K; Salamanna, G; Saltó, O; Santi, L; Sarkar, S; Sartori, L; Sato, K; Savard, P; Savoy-Navarro, A; Scheidle, T; Schlabach, P; Schmidt, E E; Schmidt, M A; Schmidt, M P; Schmitt, M; Schwarz, T; Scodellaro, L; Scott, A L; Scribano, A; Scuri, F; Sedov, A; Seidel, S; Seiya, Y; Semenov, A; Sexton-Kennedy, L; Sfyrla, A; Shalhout, S Z; Shapiro, M D; Shears, T; Shepard, P F; Sherman, D; Shimojima, M; Shochet, M; Shon, Y; Shreyber, I; Sidoti, A; Sinervo, P; Sisakyan, A; Slaughter, A J; Slaunwhite, J; Sliwa, K; Smith, J R; Snider, F D; Snihur, R; Soderberg, M; Soha, A; Somalwar, S; Sorin, V; Spalding, J; Spinella, F; Spreitzer, T; Squillacioti, P; Stanitzki, M; Staveris-Polykalas, A; St Denis, R; Stelzer, B; Stelzer-Chilton, O; Stentz, D; Strologas, J; Stuart, D; Suh, J S; Sukhanov, A; Sun, H; Suslov, I; Suzuki, T; Taffard, A; Takashima, R; Takeuchi, Y; Tanaka, R; Tecchio, M; Teng, P K; Terashi, K; Tesarek, R J; Thom, J; Thompson, A S; Thomson, E; Tipton, P; Tiwari, V; Tkaczyk, S; Toback, D; Tokar, S; Tollefson, K; Tomura, T; Tonelli, D; Torre, S; Torretta, D; Tourneur, S; Trischuk, W; Tsuno, S; Tu, Y; Turini, N; Ukegawa, F; Uozumi, S; Vallecorsa, S; van Remortel, N; Varganov, A; Vataga, E; Vazquez, F; Velev, G; Vellidis, C; Veramendi, G; Veszpremi, V; Vidal, M; Vidal, R; Vila, I; Vilar, R; Vine, T; Vogel, M; Vollrath, I; Volobouev, I; Volpi, G; Würthwein, F; Wagner, P; Wagner, R G; Wagner, R L; Wagner, J; Wagner, W; Wallny, R; Wang, S M; Warburton, A; Waters, D; Weinberger, M; Wester, W C; Whitehouse, B; Whiteson, D; Wicklund, A B; Wicklund, E; Williams, G; Williams, H H; Wilson, P; Winer, B L; Wittich, P; Wolbers, S; Wolfe, C; Wright, T; Wu, X; Wynne, S M; Yagil, A; Yamamoto, K; Yamaoka, J; Yamashita, T; Yang, C; Yang, U K; Yang, Y C; Yao, W M; Yeh, G P; Yoh, J; Yorita, K; Yoshida, T; Yu, G B; Yu, I; Yu, S S; Yun, J C; Zanello, L; Zanetti, A; Zaw, I; Zhang, X; Zhou, J; Zucchelli, S

    2007-11-16

    We report an observation of new bottom baryons produced in pp collisions at the Tevatron. Using 1.1 fb(-1) of data collected by the CDF II detector, we observe four Lambda b 0 pi+/- resonances in the fully reconstructed decay mode Lambda b 0-->Lambda c + pi-, where Lambda c+-->pK* pi+. We interpret these states as the Sigma b(*)+/- baryons and measure the following masses: m Sigma b+=5807.8 -2.2 +2.0(stat.)+/-1.7(syst.) MeV/c2, m Sigma b- =5815.2+/-1.0(stat.)+/-1.7(syst.) MeV/c2, and m(Sigma b*)-m(Sigma b)=21.2-1.9 +2.0(stat.)-0.3+0.4(syst.) MeV/c2.

  20. Mended chiral symmetry and the linear sigma model in one-loop order

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Scadron, M.D.

    1992-02-28

    In this paper it is shown that the linear {sigma}-model in one loop order in the chiral limit recovers meson masses m{sub {pi}} = 0, m{sub {sigma}} = 2m{sub qk} (NJL), m {sub {rho}} = {radical}2 g{sub {rho}}f{pi} (KSRF), along with couplings g{sigma}{pi}{pi} = m{sup 2}{sub {sigma}}/2f{pi}, g{rho}{pi}{pi} = g{sub {rho}} (VMD universality) and Weinberg's mended chiral symmetry decay width relation {Gamma}{sub {sigma}} = (9/2){Gamma}{sub {rho}}. The linear {sigma}-model combined quark and meson loops also properly predict the radiative decays {pi}{sup 0} {yields} 2{gamma} {yields} e{nu}{gamma} and {delta}{sup 0} (983) {yields} 2{gamma}.

  1. Effects of sigma-phase formation on some mechanical properties of a wrought nickel-base superalloy (IN-100)

    NASA Technical Reports Server (NTRS)

    Dreshfield, R. L.; Ashbrook, R. L.

    1974-01-01

    The effect of sigma phase formation on an extruded and forged nickel base superalloy with the composition of the casting alloy IN-100 was studied. By adding only aluminum and titanium to remelt stock, three compositions were produced which had varying propensities for sigma formation. These compositions were given a four step heat treatment and were stress-ruptured or tensile tested. The very sigma prone composition had a shorter rupture life than the sigma-free or moderately sigma prone compositions when tested at 843 and 885 C. Elongation in room temperature tensile tests was considerably lower for the very sigma prone composition than for the other two wrought compositions after prolonged exposure at 732 or 843 C.

  2. Mutations in the rpoS gene are the major limiting factor for biofilm formation in Escherichia coli serotype O157:H7 clinical isolates

    USDA-ARS?s Scientific Manuscript database

    Background: Biofilm formation is a complex process that is highly regulated through a battery of transcriptional regulators, small regulatory RNAs, and environmental conditions. RpoS sigma factor along with MlrA protein directly regulate the expression of the curli key regulator CsgD. In most serot...

  3. Stress Sensors and Signal Transducers in Cyanobacteria

    PubMed Central

    Los, Dmitry A.; Zorina, Anna; Sinetova, Maria; Kryazhov, Sergey; Mironov, Kirill; Zinchenko, Vladislav V.

    2010-01-01

    In living cells, the perception of environmental stress and the subsequent transduction of stress signals are primary events in the acclimation to changes in the environment. Some molecular sensors and transducers of environmental stress cannot be identified by traditional and conventional methods. Based on genomic information, a systematic approach has been applied to the solution of this problem in cyanobacteria, involving mutagenesis of potential sensors and signal transducers in combination with DNA microarray analyses for the genome-wide expression of genes. Forty-five genes for the histidine kinases (Hiks), 12 genes for serine-threonine protein kinases (Spks), 42 genes for response regulators (Rres), seven genes for RNA polymerase sigma factors, and nearly 70 genes for transcription factors have been successfully inactivated by targeted mutagenesis in the unicellular cyanobacterium Synechocystis sp. PCC 6803. Screening of mutant libraries by genome-wide DNA microarray analysis under various stress and non-stress conditions has allowed identification of proteins that perceive and transduce signals of environmental stress. Here we summarize recent progress in the identification of sensory and regulatory systems, including Hiks, Rres, Spks, sigma factors, transcription factors, and the role of genomic DNA supercoiling in the regulation of the responses of cyanobacterial cells to various types of stress. PMID:22294932

  4. [Multilevel model analysis on the relevant factors influencing the total amount of drinking water consumed daily by Beijing residents].

    PubMed

    Zhao, Jinhui; Wei, Jianrong; Chen, Huajie; Liu, Yumin; Li, Tiantian; Sun, Qinghua; Liu, Qiaolan

    2012-09-01

    To investigate the influencing factors for daily water intake of Beijing residents. A multi-stage sampling method was constructed to interview 270 Beijing residents in the winter of 2009 and in the summer of 2010 by using a questionnaire to collect data on daily drinking water consumption. Multilevel models were used to analyze the variation and influencing factors for the amount of water intake. Multilevel model results showed that the average daily water intake of residents living in different villages or neighborhood committees was statistically significant (sigma2 mu0 = = 0.030 (0.009), P < 0.05). The individual variation in the same village or neighborhood committee was also significant (sigma2 e0 = 0.157 (0.010), P < 0.05). Season, gender, and body weight affected the daily water intake (P < 0.05). There were interaction between season and source of water supply. The average daily water intake of residents was affected by several factors. In the health risk assessment of drinking water, it needs considering not only the individual characteristics but also the differences of villages/neighborhood committees and the seasonal variation.

  5. Organohalogen concentrations in blood and adipose tissue of Southern Beaufort Sea polar bears.

    PubMed

    Bentzen, T W; Muir, D C G; Amstrup, S C; O'Hara, T M

    2008-11-15

    We analyzed 151 organohalogen chemicals (OHCs) in whole blood and subcutaneous fat of 57 polar bears sampled along the Alaskan Beaufort Sea coast in spring, 2003. All major organochlorine pesticides, PCBs, PBDEs and their congeners were assessed. Concentrations of most OHCs continue to be lower among Southern Beaufort Sea polar bears than reported for other populations. Additionally, toxaphenes and related compounds were assessed in adipose tissue, and 8 perflourinated compounds (PFCs) were examined in blood. Perfluorooctane sulfonate (PFOS) concentrations exceeded those of any other contaminant measured in blood. SigmaChlordane concentrations were higher in females, and both SigmaPCBs and SigmaChlordane concentrations in adipose tissue decreased significantly with age. The rank order of OHC mean concentrations; SigmaPCB>Sigma10PCB>PCB153>SigmaChlordane>Oxychlordane>PCB180>SigmaHCH>beta-HCH>SigmaDDT>p,p-DDE>SigmaPBDE>HCB>Toxaphene was similar for compounds above detection limits in both fat and blood. Although correlation between OHC concentrations in blood and adipose tissue was examined, the predictability of concentrations in one matrix for the other was limited.

  6. Regulation of Global Transcription in Escherichia coli by Rsd and 6S RNA

    PubMed Central

    Lal, Avantika; Krishna, Sandeep; Seshasayee, Aswin Sai Narain

    2018-01-01

    In Escherichia coli, the sigma factor σ70 directs RNA polymerase to transcribe growth-related genes, while σ38 directs transcription of stress response genes during stationary phase. Two molecules hypothesized to regulate RNA polymerase are the protein Rsd, which binds to σ70, and the non-coding 6S RNA which binds to the RNA polymerase-σ70 holoenzyme. Despite multiple studies, the functions of Rsd and 6S RNA remain controversial. Here we use RNA-Seq in five phases of growth to elucidate their function on a genome-wide scale. We show that Rsd and 6S RNA facilitate σ38 activity throughout bacterial growth, while 6S RNA also regulates widely different genes depending upon growth phase. We discover novel interactions between 6S RNA and Rsd and show widespread expression changes in a strain lacking both regulators. Finally, we present a mathematical model of transcription which highlights the crosstalk between Rsd and 6S RNA as a crucial factor in controlling sigma factor competition and global gene expression. PMID:29686109

  7. Regulation of Global Transcription in Escherichia coli by Rsd and 6S RNA.

    PubMed

    Lal, Avantika; Krishna, Sandeep; Seshasayee, Aswin Sai Narain

    2018-05-31

    In Escherichia coli , the sigma factor σ 70 directs RNA polymerase to transcribe growth-related genes, while σ 38 directs transcription of stress response genes during stationary phase. Two molecules hypothesized to regulate RNA polymerase are the protein Rsd, which binds to σ 70 , and the non-coding 6S RNA which binds to the RNA polymerase-σ 70 holoenzyme. Despite multiple studies, the functions of Rsd and 6S RNA remain controversial. Here we use RNA-Seq in five phases of growth to elucidate their function on a genome-wide scale. We show that Rsd and 6S RNA facilitate σ 38 activity throughout bacterial growth, while 6S RNA also regulates widely different genes depending upon growth phase. We discover novel interactions between 6S RNA and Rsd and show widespread expression changes in a strain lacking both regulators. Finally, we present a mathematical model of transcription which highlights the crosstalk between Rsd and 6S RNA as a crucial factor in controlling sigma factor competition and global gene expression. Copyright © 2018 Lal et al.

  8. Under the knife: a national survey of six sigma programs in US healthcare organizations.

    PubMed

    Feng, Qianmei; Manuel, Chris M

    2008-01-01

    Medical and policy literature reports many six sigma applications at specific healthcare organizations. However, there is a lack of studies that investigate the broader status of six sigma in US healthcare systems. The purpose of this paper is to present the results from a national survey of six sigma programs in US healthcare organizations. Through the design, distribution, and analysis of a nationwide survey, this paper assesses the implementation of six sigma in healthcare facilities. Two sets of surveys were designed based on whether an organization has adopted six sigma or not. Findings from this paper indicate the common six sigma projects implemented in healthcare organizations, typical implementation durations, cost benefits, and major barriers in implementation, and so on. This paper is limited by the low-response rate owing to time and budget constraints. Through the dissemination of this paper, it is hoped that more organizations will become interested in this subject and participate in future studies. This work is the first study to investigate the implementation status of six sigma in US healthcare systems. It will share experiences amongst six sigma institutions and promote its application in many institutions. The findings will provide instructive information to six sigma practitioners and researchers, and particularly to health care management.

  9. Effect of tree structure on X-band microwave signature of conifers

    NASA Technical Reports Server (NTRS)

    Mougin, Eric; Lopes, Armand; Karam, Mostafa A.; Fung, Adrian K.

    1993-01-01

    Experimental studies are performed on some coniferous trees (Austrian pine, Nordmann spruce, and Norway spruce) to investigate the relation between the tree architecture and radar signal at X-band. For a single tree, the RCS is measured as a function of the scatterer location at 90 deg incidence. It is found that the main scatterers are the leafy branches and the difference between sigma(vv) and sigma(hh) is significant at the upper portion of the tree. At the lower portion of the tree, sigma(vv) and sigma(hh) have almost the same level. For a group of trees the angular trends of sigma(vv) and sigma(hh) are measured. It is found that the levels of sigma(vv) and sigma(hh) are of the same order, but their angular trends vary from one tree species to the other depending on the tree species structure. The interpretation of these experimental results is carried out with the help of a theoretical model which accounts for the structure of the tree. According to this theoretical study, the major scattering trend is due to the leaves, while the perturbation to the angular trend and the level difference between sigma(vv) and sigma(hh) are due to the branch orientation distributions (i.e., the tree architecture).

  10. Aβ mediates Sigma receptor degradation via CaN/NFAT pathway

    PubMed Central

    Fang, Min; Zhang, Pei; Zhao, Yanxin; Jin, Aiping; Liu, Xueyuan

    2016-01-01

    Sigma receptor is an endoplasmic reticulum protein and belongs to non-opioid receptor. Increasing evidence shows that Sigma receptor activation can significantly attenuate AD induced neurological dysfunction and the functional deficiency of Sigma receptor plays an important role in the Aβ induced neuronal loss. This study aimed to investigate the influence of extracellular accumulation of Aβ on the Sigma receptor expression. Our results showed the increase in extracellular Aβ had little influence on the mRNA expression of Sigma receptor, but gradually reduced its protein expression. Co-immunoprecipitation was employed to evaluate the interaction of Sigma receptor with other proteins. Results showed BIP could bind to Sigma receptor to affect the ubiquitination of Sigma receptor. Further investigation showed there was a NFAT binding site at the promoter of BIP. Then, Western blot assay was performed to detect NFAT expression. Results showed extracellular Aβ affected the nuclear translocation of NFAT and the CaN activity of NFAT also increased with the accumulation of extracellular Aβ. In this study, NFAT-BIP luciferase reporter gene system was constructed. Results showed NFAT was able to regulate the transcription of BIP. Thus, we speculate that extracellular Aβ accumulation may activate CaN/NFAT signaling pathway to induce chaperone BIP expression, which results in Sigma receptor ubiquitination and its degradation. PMID:27648137

  11. Atmospheric PCB concentrations at Terra Nova Bay, Antarctica.

    PubMed

    Gambaro, Andrea; Manodori, Laura; Zangrando, Roberta; Cincinelli, Alessandra; Capodaglio, Gabriele; Cescon, Paolo

    2005-12-15

    Concentrations of gas-phase polychlorobiphenyls (PCBs) were studied over an austral summer at a site in Terra Nova Bay, Antarctica. Gas-phase concentrations of individual PCB congeners in the atmosphere of Terra Nova Bay ranged from below the detection limit to 0.25 pg m(-3), with a mean concentration of sigmaPCB of 1.06 pg m(-3). The PCB profile was dominated by lower-chlorinated PCB congeners; in fact >78% of the total PCB content was due to congeners with 1-4 chlorine atoms and only about 10% with 5-7 chlorines, whereas higher-chlorinated PCB congeners were below detection limits. The mean sigmaPCB concentration obtained in this study were lower than those reported in previous Antarctic studies. Temporal concentration profiles of sigmaPCB do not correspond to seasonal temperature changes. In consideration of the low PCB concentrations observed, the studies with the wind roses, the regression between In P(PCB) and T(-1), and the distribution of congeners, we can hypothesize that PCB local source contributions are not very important, whereas long-distance transport is the prevalent factor bringing PCBs to Terra Nova Bay.

  12. Improving Quality of Seal Leak Test Product using Six Sigma

    NASA Astrophysics Data System (ADS)

    Luthfi Malik, Abdullah; Akbar, Muhammad; Irianto, Dradjad

    2016-02-01

    Seal leak test part is a polyurethane material-based product. Based on past data, defect level of this product was 8%, higher than the target of 5%. Quality improvement effort was done using six sigma method that included phases of define, measure, analyse, improve, and control. In the design phase, a Delphi method was used to identify factors that were critical to quality. In the measure phase, stability and process capability was measured. Fault tree analysis (FTA) and failure mode and effect analysis (FMEA) were used in the next phase to analize the root cause and to determine the priority issues. Improve phase was done by compiling, selecting, and designing alternative repair. Some improvement efforts were identified, i.e. (i) making a checklist for maintenance schedules, (ii) making written reminder form, (iii) modifying the SOP more detail, and (iv) performing a major service to the vacuum machine. To ensure the continuity of improvement efforts, some control activities were executed, i.e. (i) controlling, monitoring, documenting, and setting target frequently, (ii) implementing reward and punishment system, (iii) adding cleaning tool, and (iv) building six sigma organizational structure.

  13. Volcanic Signatures in Estimates of Stratospheric Aerosol Size, Distribution Width, Surface Area, and Volume Deduced from Global Satellite-Based Observations

    NASA Technical Reports Server (NTRS)

    Bauman, J. J.; Russell, P. B.

    2000-01-01

    Volcanic signatures in the stratospheric aerosol layer are revealed by two independent techniques which retrieve aerosol information from global satellite-based observations of particulate extinction. Both techniques combine the 4-wavelength Stratospheric Aerosol and Gas Experiment (SAGE) II extinction measurements (0.385 <= lambda <= 1.02 microns) with the 7.96 micron and 12.82 micron extinction measurements from the Cryogenic Limb Array Etalon Spectrometer (CLAES) instrument. The algorithms use the SAGE II/CLAES composite extinction spectra in month-latitude-altitude bins to retrieve values and uncertainties of particle effective radius R(sub eff), surface area S, volume V and size distribution width sigma(sub R). The first technique is a multi-wavelength Look-Up-Table (LUT) algorithm which retrieves values and uncertainties of R(sub eff) by comparing ratios of extinctions from SAGE II and CLAES (e.g., E(sub lambda)/E(sub 1.02) to pre-computed extinction ratios which are based on a range of unimodal lognormal size distributions. The pre-computed ratios are presented as a function of R(sub eff) for a given sigma(sub g); thus the comparisons establish the range of R(sub eff) consistent with the measured spectra for that sigma(sub g). The fact that no solutions are found for certain sigma(sub g) values provides information on the acceptable range of sigma(sub g), which is found to evolve in response to volcanic injections and removal periods. Analogous comparisons using absolute extinction spectra and error bars establish the range of S and V. The second technique is a Parameter Search Technique (PST) which estimates R(sub eff) and sigma(sub g) within a month-latitude-altitude bin by minimizing the chi-squared values obtained by comparing the SAGE II/CLAES extinction spectra and error bars with spectra calculated by varying the lognormal fitting parameters: R(sub eff), sigma(sub g), and the total number of particles N(sub 0). For both techniques, possible biases in retrieved-parameters caused by assuming a unimodal functional form are removed using correction factors computed from representative in situ measurements of bimodal size distributions. Some interesting features revealed by the LUT and PST retrievals include: (1) Increases in S and V (but not R(sub eff)) after the Ruiz and Kelut injections, (2) Increases in S, V, R(sub eff) after Pinatubo, (3) Post-Pinatubo increases in S, V, and R(sub eff) that are more rapid in the tropics than elsewhere, (4) Mid-latitude post-Pinatubo increases in R(sub eff) that lag increases in S and V, (5) S and V returning to pre-Pinatubo values sooner than R(sub eff) does, (6) Sharp increases in sigma(sub g), after Pinatubo and slight increases in sigma(sub g) after Ruiz, Etna, Kelut, Spurr and Rabaul, and (7) Gradual declines in the heights at which R(sub eff), S and V peak after Pinatubo.

  14. Active participation of Hsp90 in the biogenesis of the trimeric reovirus cell attachment protein sigma1.

    PubMed

    Gilmore, R; Coffey, M C; Lee, P W

    1998-06-12

    The reovirus cell attachment protein, sigma1, is a lollipop-shaped homotrimer with an N-terminal fibrous tail and a C-terminal globular head. Biogenesis of this protein involves two trimerization events: N-terminal trimerization, which occurs cotranslationally and is Hsp70/ATP-independent, and C-terminal trimerization, which occurs posttranslationally and is Hsp70/ATP-dependent. To determine if Hsp90 also plays a role in sigma1 biogenesis, we analyzed sigma1 synthesized in rabbit reticulocyte lysate. Coprecipitation experiments using anti-Hsp90 antibodies revealed that Hsp90 was associated with immature sigma1 trimers (hydra-like intermediates with assembled N termini and unassembled C termini) but not with mature trimers. The use of truncated sigma1 further demonstrated that only the C-terminal half of sigma1 associated with Hsp90. In the presence of the Hsp90 binding drug geldanamycin, N-terminal trimerization proceeded normally, but C-terminal trimerization was blocked. Geldanamycin did not inhibit the association of Hsp90 with sigma 1 but prevented the subsequent release of Hsp90 from the immature sigma1 complex. We also examined the status of p23, an Hsp90-associated cochaperone. Like Hsp90, p23 only associated with immature sigma1 trimers, and this association was mapped to the C-terminal half of sigma1. However, unlike Hsp90, p23 was released from the sigma1 complex upon the addition of geldanamycin. These results highlight an all-or-none concept of chaperone involvement in different oligomerization domains within a single protein and suggest a possible common usage of chaperones in the regulation of general protein folding and of steroid receptor activation.

  15. Lean and Six Sigma in acute care: a systematic review of reviews.

    PubMed

    Deblois, Simon; Lepanto, Luigi

    2016-01-01

    The purpose of this paper is to present a systematic review of literature reviews, summarizing how Lean and Six Sigma management techniques have been implemented in acute care settings to date, and assessing their impact. To aid decision makers who wish to use these techniques by identifying the sectors of activity most often targeted, the main results of the interventions, as well as barriers and facilitators involved. To identify areas of future research. A literature search was conducted, using eight databases. The methodological quality of the selected reviews was appraised with AMSTAR. A narrative synthesis was performed according to the guidelines proposed by Popay et al. (2006). Data were reported according to PRISMA. The literature search identified 149 publications published from 1999 to January 2015. Seven literature reviews were included into the systematic review, upon appraisal. The overall quality of the evidence was poor to fair. The clinical settings most described were specialized health care services, including operating suites, intensive care units and emergency departments. The outcomes most often appraised related to processes and quality. The evidence suggests that Lean and Six Sigma are better adapted to settings where processes involve a linear sequence of events. There is a need for more studies of high methodological quality to better understand the effects of these approaches as well as the factors of success and barriers to their implementation. Field studies comparing the effects of Lean and Six Sigma to those of other process redesign or quality improvement efforts would bring a significant contribution to the body of knowledge. Lean and Six Sigma can be considered valuable process optimization approaches in acute health care settings. The success of their implementation requires significant participation of clinical personnel from the frontline as well as clinical leaders and managers. More research is needed to better understand the factors of success and the barriers to their implementation, as well as their long-term impact. This is the first broad systematic review of reviews, synthesizing data pertaining to implementation issues and results in acute care settings, to be published. It will benefit health care managers assessing the potential of these approaches and the potential drawbacks associated with their implementation. Moreover, it identifies directions for future research.

  16. Modulation of serotonergic neurotransmission by short- and long-term treatments with sigma ligands

    PubMed Central

    Bermack, J E; Debonnel, G

    2001-01-01

    Sigma receptors were first described in 1976 as opiate receptors but were later determined to be a distinct class of receptors with two subtypes, sigma1 and sigma2. Although the endogenous ligand is yet to be elucidated, the sigma1 receptor has recently been cloned. Behavioural models used to test potential antidepressants have shown sigma ligands to produce antidepressant effects but their mechanism of action is unknown. The goal of the present study was to assess the effects of various sigma1 ligands on the firing activity of serotonin (5-HT) neurons of the dorsal raphe nucleus (DRN) using extracellular in vivo recordings in anaesthetized rats. The sigma1 ligands (+)-pentazocine and 4-(N-benzylpiperidin-4-yl)-4-iodobenzamide (4-IBP) (2 mg kg−1 day−1) increased markedly 5-HT firing activity after 2 days of treatment and maintained the same increased firing rate after long-term (21 days) treatments. Furthermore, the increased firing rate produced by 2 and 21 day treatments with (+)-pentazocine was prevented by the co-administration of N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)-thylamine (NE-100) (10 mg kg−1 day−1) a selective sigma1 antagonist, confirming the sigma1 receptor's modulation of these effects. In contrast, the sigma1 ligands (+)-N-cyclopropylmethyl-N-methyl-1,4-diphenyl-1-1-ethyl-but-3-en-1-ylamine hydrochloride (JO-1784) and 2-(4-morpholinoethyl 1-phenyl-cyclohexane-1-carboxylate hydrochloride (PRE-084) had no effect. Following a 21-day treatment with (+)-pentazocine there was a marked reduction in the number of neurons found per track. This decrease was not seen after chronic treatment with 4-IBP and may represent a depolarization block. These results suggest a modulation of serotonergic neurotransmission by some sigma receptors and provide a potential mechanism for the ‘antidepressant effects' reported and provide evidence toward sigma1 ligands as potential antidepressants with a rapid onset of action. PMID:11588125

  17. Modulation of serotonergic neurotransmission by short- and long-term treatments with sigma ligands.

    PubMed

    Bermack, J E; Debonnel, G

    2001-10-01

    1. Sigma receptors were first described in 1976 as opiate receptors but were later determined to be a distinct class of receptors with two subtypes, sigma(1) and sigma(2). Although the endogenous ligand is yet to be elucidated, the sigma(1) receptor has recently been cloned. 2. Behavioural models used to test potential antidepressants have shown sigma ligands to produce antidepressant effects but their mechanism of action is unknown. 3. The goal of the present study was to assess the effects of various sigma(1) ligands on the firing activity of serotonin (5-HT) neurons of the dorsal raphe nucleus (DRN) using extracellular in vivo recordings in anaesthetized rats. 4. The sigma(1) ligands (+)-pentazocine and 4-(N-benzylpiperidin-4-yl)-4-iodobenzamide (4-IBP) (2 mg kg(-1) day(-1)) increased markedly 5-HT firing activity after 2 days of treatment and maintained the same increased firing rate after long-term (21 days) treatments. Furthermore, the increased firing rate produced by 2 and 21 day treatments with (+)-pentazocine was prevented by the co-administration of N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)-thylamine (NE-100) (10 mg kg(-1) day(-1)) a selective sigma(1) antagonist, confirming the sigma(1) receptor's modulation of these effects. In contrast, the sigma(1) ligands (+)-N-cyclopropylmethyl-N-methyl-1,4-diphenyl-1-1-ethyl-but-3-en-1-ylamine hydrochloride (JO-1784) and 2-(4-morpholinoethyl 1-phenyl-cyclohexane-1-carboxylate hydrochloride (PRE-084) had no effect. 5. Following a 21-day treatment with (+)-pentazocine there was a marked reduction in the number of neurons found per track. This decrease was not seen after chronic treatment with 4-IBP and may represent a depolarization block. 6. These results suggest a modulation of serotonergic neurotransmission by some sigma receptors and provide a potential mechanism for the 'antidepressant effects' reported and provide evidence toward sigma(1) ligands as potential antidepressants with a rapid onset of action.

  18. Sigma metrics as a tool for evaluating the performance of internal quality control in a clinical chemistry laboratory

    PubMed Central

    Kumar, B. Vinodh; Mohan, Thuthi

    2018-01-01

    OBJECTIVE: Six Sigma is one of the most popular quality management system tools employed for process improvement. The Six Sigma methods are usually applied when the outcome of the process can be measured. This study was done to assess the performance of individual biochemical parameters on a Sigma Scale by calculating the sigma metrics for individual parameters and to follow the Westgard guidelines for appropriate Westgard rules and levels of internal quality control (IQC) that needs to be processed to improve target analyte performance based on the sigma metrics. MATERIALS AND METHODS: This is a retrospective study, and data required for the study were extracted between July 2015 and June 2016 from a Secondary Care Government Hospital, Chennai. The data obtained for the study are IQC - coefficient of variation percentage and External Quality Assurance Scheme (EQAS) - Bias% for 16 biochemical parameters. RESULTS: For the level 1 IQC, four analytes (alkaline phosphatase, magnesium, triglyceride, and high-density lipoprotein-cholesterol) showed an ideal performance of ≥6 sigma level, five analytes (urea, total bilirubin, albumin, cholesterol, and potassium) showed an average performance of <3 sigma level and for level 2 IQCs, same four analytes of level 1 showed a performance of ≥6 sigma level, and four analytes (urea, albumin, cholesterol, and potassium) showed an average performance of <3 sigma level. For all analytes <6 sigma level, the quality goal index (QGI) was <0.8 indicating the area requiring improvement to be imprecision except cholesterol whose QGI >1.2 indicated inaccuracy. CONCLUSION: This study shows that sigma metrics is a good quality tool to assess the analytical performance of a clinical chemistry laboratory. Thus, sigma metric analysis provides a benchmark for the laboratory to design a protocol for IQC, address poor assay performance, and assess the efficiency of existing laboratory processes. PMID:29692587

  19. 76 FR 13515 - Medicare Program; Revisions to the Reductions and Increases to Hospitals' FTE Resident Caps for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-14

    ..., [Sigma] line 3.08 minus [Sigma] (lines 3.04 + 3.05-applicable section 422 reduction amount). For direct GME, [Sigma] line 3.05 minus [Sigma] (lines 3.01 + 3.02-applicable section 422 reduction amount). (5...

  20. Sigma receptors as potential therapeutic targets for neuroprotection.

    PubMed

    Nguyen, Linda; Kaushal, Nidhi; Robson, Matthew J; Matsumoto, Rae R

    2014-11-15

    Sigma receptors comprise a unique family of proteins that have been implicated in the pathophysiology and treatment of many central nervous system disorders, consistent with their high level of expression in the brain and spinal cord. Mounting evidence indicate that targeting sigma receptors may be particularly beneficial in a number of neurodegenerative conditions including Alzheimer׳s disease, Parkinson׳s disease, stroke, methamphetamine neurotoxicity, Huntington׳s disease, amyotrophic lateral sclerosis, and retinal degeneration. In this perspective, a brief overview is given on sigma receptors, followed by a focus on common mechanisms of neurodegeneration that appear amenable to modulation by sigma receptor ligands to convey neuroprotective effects and/or restorative functions. Within each of the major mechanisms discussed herein, the neuroprotective effects of sigma ligands are summarized, and when known, the specific sigma receptor subtype(s) involved are identified. Together, the literature suggests sigma receptors may provide a novel target for combatting neurodegenerative diseases through both neuronal and glial mechanisms. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Sigma: Strain-level inference of genomes from metagenomic analysis for biosurveillance

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ahn, Tae-Hyuk; Chai, Juanjuan; Pan, Chongle

    Motivation: Metagenomic sequencing of clinical samples provides a promising technique for direct pathogen detection and characterization in biosurveillance. Taxonomic analysis at the strain level can be used to resolve serotypes of a pathogen in biosurveillance. Sigma was developed for strain-level identification and quantification of pathogens using their reference genomes based on metagenomic analysis. Results: Sigma provides not only accurate strain-level inferences, but also three unique capabilities: (i) Sigma quantifies the statistical uncertainty of its inferences, which includes hypothesis testing of identified genomes and confidence interval estimation of their relative abundances; (ii) Sigma enables strain variant calling by assigning metagenomic readsmore » to their most likely reference genomes; and (iii) Sigma supports parallel computing for fast analysis of large datasets. In conclusion, the algorithm performance was evaluated using simulated mock communities and fecal samples with spike-in pathogen strains. Availability and Implementation: Sigma was implemented in C++ with source codes and binaries freely available at http://sigma.omicsbio.org.« less

  2. Sigma: Strain-level inference of genomes from metagenomic analysis for biosurveillance

    DOE PAGES

    Ahn, Tae-Hyuk; Chai, Juanjuan; Pan, Chongle

    2014-09-29

    Motivation: Metagenomic sequencing of clinical samples provides a promising technique for direct pathogen detection and characterization in biosurveillance. Taxonomic analysis at the strain level can be used to resolve serotypes of a pathogen in biosurveillance. Sigma was developed for strain-level identification and quantification of pathogens using their reference genomes based on metagenomic analysis. Results: Sigma provides not only accurate strain-level inferences, but also three unique capabilities: (i) Sigma quantifies the statistical uncertainty of its inferences, which includes hypothesis testing of identified genomes and confidence interval estimation of their relative abundances; (ii) Sigma enables strain variant calling by assigning metagenomic readsmore » to their most likely reference genomes; and (iii) Sigma supports parallel computing for fast analysis of large datasets. In conclusion, the algorithm performance was evaluated using simulated mock communities and fecal samples with spike-in pathogen strains. Availability and Implementation: Sigma was implemented in C++ with source codes and binaries freely available at http://sigma.omicsbio.org.« less

  3. Observations of Global and Regional Ionospheric Irregularities and Scintillation Using GNSS Tracking Networks

    NASA Technical Reports Server (NTRS)

    Pi, Xiaoqing; Mannucci, Anthony J.; Valant-Spaight, Bonnie; Bar-Sever, Yoaz; Romans, Larry J.; Skone, Susan; Sparks, Lawrence; Hall, G. Martin

    2013-01-01

    The rate of TEC index (ROTI) is a measurement that characterizes ionospheric irregularities. It can be obtained from standard GNSS dual-frequency phase data collected using a geodetic type of GNSS receiver. By processing GPS data from ground-based networks of International GNSS Service and Continuously Operating Reference Station (CORS), ROTI maps have been produced to observe global and regional scintillation activities. A major mid-latitude scintillation event in the contiguous United States is reported here that was captured in ROTI maps produced using CORS GPS data collected during a space weather storm. The analyses conducted in this work and previously by another group indicate that ROTI is a good occurrence indicator of both amplitude and phase scintillations of GPS L-band signals, even though the magnitudes of ROTI, S4, and sigma(sub phi) can be different. For example, our analysis indicates that prominent ROTI and the L1 phase scintillation (sigma(sub phi)) are well correlated temporally in the polar region while L1 amplitude scintillation rarely occurs. The differences are partially attributed to physics processes in different latitude regions, such as high-speed plasma convection in the polar region that can suppress the amplitude scintillation. An analysis of the impact of ionospheric scintillation on precise positioning, which requires use of dual-frequency phase data, is also conducted. The results indicate that significant (more than an order of magnitude) positioning errors can occur under phase scintillation conditions.

  4. Tracking Data Certification for the Lunar Reconnaissance Orbiter

    NASA Technical Reports Server (NTRS)

    Morinelli, Patrick J.; Socoby, Joseph; Hendry, Steve; Campion, Richard

    2010-01-01

    This paper details the National Aeronautics and Space Administration (NASA) Goddard Space Flight Center (GSFC) Flight Dynamics Facility (FDF) tracking data certification effort of the Lunar Reconnaissance Orbiter (LRO) Space Communications Network (SCN) complement of tracking stations consisting of the NASA White Sands 1 antenna (WS1), and the commercial provider Universal Space Network (USN) antennas at South Point, Hawaii; Dongara Australia; Weilheim, Germany; and Kiruna, Sweden. Certification assessment required the cooperation and coordination of parties not under the control of either the LRO project or ground stations as uplinks on cooperating spacecraft were necessary. The LRO range-tracking requirement of 10m 1 sigma could be satisfactorily demonstrated using any typical spacecraft capable of range tracking. Though typical Low Earth Orbiting (LEO) or Geosynchronous Earth Orbiting (GEO) spacecraft may be adequate for range certification, their measurement dynamics and noise would be unacceptable for proper Doppler certification of 1-3mm/sec 1 sigma. As LRO will orbit the Moon, it was imperative that a suitable target spacecraft be utilized which can closely mimic the expected lunar orbital Doppler dynamics of +/-1.6km/sec and +/-1.5m/sq sec to +/-0.15m/sq sec, is in view of the ground stations, supports coherent S-Band Doppler tracking measurements, and can be modeled by the FDF. In order to meet the LRO metric tracking data specifications, the SCN ground stations employed previously uncertified numerically controlled tracking receivers. Initial certification testing revealed certain characteristics of the units that required resolution before being granted certification.

  5. The sigma-2 receptor as a therapeutic target for drug delivery in triple negative breast cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Makvandi, Mehran; Tilahun, Estifanos D.; Lieberman, Brian P.

    Background: Triple-negative breast cancer (TNBC) is associated with high relapse rates and increased mortality when compared with other breast cancer subtypes. In contrast to receptor positive breast cancers, there are no approved targeted therapies for TNBC. Identifying biomarkers for TNBC is of high importance for the advancement of patient care. The sigma-2 receptor has been shown to be overexpressed in triple negative breast cancer in vivo and has been characterized as a marker of proliferation. The aim of the present study was to define the sigma-2 receptor as a target for therapeutic drug delivery and biomarker in TNBC. Methods: Three TNBCmore » cell lines were evaluated: MDA-MB-231, HCC1937 and HCC1806. Sigma-2 compounds were tested for pharmacological properties specific to the sigma-2 receptor through competitive inhibition assays. Sigma-2 receptor expression was measured through radioligand receptor saturation studies. Drug sensitivity for taxol was compared to a sigma-2 targeting compound conjugated to a cytotoxic payload, SW IV-134. Cell viability was assessed after treatments for 2 or 48 h. Sigma-2 blockade was assessed to define sigma-2 mediated cytotoxicity of SW IV-134. Caspase 3/7 activation induced by SW IV-134 was measured at corresponding treatment time points. Results: SW IV-134 was the most potent compound tested in two of the three cell lines and was similarly effective in all three. MDA-MB-231 displayed a statistically significant higher sigma-2 receptor expression and also was the most sensitive cell line evaluated to SW IV-134. Conclusion: Targeting the sigma-2 receptor with a cytotoxic payload was effective in all the three cell lines evaluated and provides the proof of concept for future development of a therapeutic platform for the treatment of TNBC. - Highlights: • TNBC cells are sensitive to sigma-2 receptor targeted drug conjugate SW IV-134. • MDA-MB-231 displayed the highest amount of sigma-2 receptors and corresponded well with sensitivity. • The sigma-2 receptor is a potential biomarker in TNBC for prognosis and therapy.« less

  6. Sigma-1 receptor: the novel intracellular target of neuropsychotherapeutic drugs.

    PubMed

    Hayashi, Teruo

    2015-01-01

    Sigma-1 receptor ligands have been long expected to serve as drugs for treatment of human diseases such as neurodegenerative disorders, depression, idiopathic pain, drug abuse, and cancer. Recent research exploring the molecular function of the sigma-1 receptor started unveiling underlying mechanisms of the therapeutic activity of those ligands. Via the molecular chaperone activity, the sigma-1 receptor regulates protein folding/degradation, ER/oxidative stress, and cell survival. The chaperone activity is activated or inhibited by synthetic sigma-1 receptor ligands in an agonist-antagonist manner. Sigma-1 receptors are localized at the endoplasmic reticulum (ER) membranes that are physically associated with the mitochondria (MAM: mitochondria-associated ER membrane). In specific types of neurons (e.g., those at the spinal cord), sigma-1 receptors are also clustered at ER membranes that juxtapose postsynaptic plasma membranes. Recent studies indicate that sigma-1 receptors, partly in sake of its unique subcellular localization, regulate the mitochondria function that involves bioenergetics and free radical generation. The sigma-1 receptor may thus provide an intracellular drug target that enables controlling ER stress and free radical generation under pathological conditions. Copyright © 2014 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.

  7. The transcriptional regulatory network of Corynebacterium jeikeium K411 and its interaction with metabolic routes contributing to human body odor formation.

    PubMed

    Barzantny, Helena; Schröder, Jasmin; Strotmeier, Jasmin; Fredrich, Eugenie; Brune, Iris; Tauch, Andreas

    2012-06-15

    Lipophilic corynebacteria are involved in the generation of volatile odorous products in the process of human body odor formation by degrading skin lipids and specific odor precursors. Therefore, these bacteria represent appropriate model systems for the cosmetic industry to examine axillary malodor formation on the molecular level. To understand the transcriptional control of metabolic pathways involved in this process, the transcriptional regulatory network of the lipophilic axilla isolate Corynebacterium jeikeium K411 was reconstructed from the complete genome sequence. This bioinformatic approach detected a gene-regulatory repertoire of 83 candidate proteins, including 56 DNA-binding transcriptional regulators, nine two-component systems, nine sigma factors, and nine regulators with diverse physiological functions. Furthermore, a cross-genome comparison among selected corynebacterial species of the taxonomic cluster 3 revealed a common gene-regulatory repertoire of 44 transcriptional regulators, including the MarR-like regulator Jk0257, which is exclusively encoded in the genomes of this taxonomical subline. The current network reconstruction comprises 48 transcriptional regulators and 674 gene-regulatory interactions that were assigned to five interconnected functional modules. Most genes involved in lipid degradation are under the combined control of the global cAMP-sensing transcriptional regulator GlxR and the LuxR-family regulator RamA, probably reflecting the essential role of lipid degradation in C. jeikeium. This study provides the first genome-scale in silico analysis of the transcriptional regulation of metabolism in a lipophilic bacterium involved in the formation of human body odor. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xu, J.; Bugaris, D. E.; Xiao, Z. L.

    We report the occurrence of reentrantmetallic behavior in theWeyl semimetal NbP. When the appliedmagnetic field H is above a critical value H-c, a reentrance appears as a peak in the temperature-dependent resistivity rho(xx) (T) at T = T-p, similar to that observed in graphite where it was attributed to local superconductivity. The Tp(H) relationship follows a power-law dependence T-p similar to (H-H-c)(1/nu) where. can be derived from the temperature dependence of the zero-field resistivity rho(0)(T) similar to T-nu. From concurrent measurements of the transverse rho(xx) (T) and Hall rho(xy)(T) magnetoresistivities, we reveal a clear correlation between the rapidly increasing rho(xy)more » (T) and the occurrence of a peak in the rho(xx) (T) curve. Quantitative analysis indicates that the reentrantmetallic behavior arises from the competition of the magnetoconductivity sigma(xx) (T) with an additional component Delta sigma(xx) (T) = kappa(H)sigma(xx)(T) where kappa(H) = [rho(xy)(T)/rho(xx)(T)](2) is the Hall factor. We find that the Hall factor (kappa(H) approximate to 0.4) at peak temperature T-p is nearly field independent, leading to the observed T-p (H) relationship. Furthermore, the reentrant metallic behavior in rho(xx) (T) also is reflected in the behavior of rho(xx) (H) that ranges from nonsaturating at T > 70K to saturation at liquid-helium temperatures. The latter can be explained with the magnetic field dependence of the Hall factor kappa(H) (H). Our paper demonstrates that a semiclassical theory can account for the "anomalies" in the magnetotransport phenomena of NbP without invoking an exotic mechanism.« less

  9. The SigF Regulon in Mycobacterium smegmatis Reveals Roles in Adaptation to Stationary Phase, Heat, and Oxidative Stress▿ ‡

    PubMed Central

    Hümpel, Anja; Gebhard, Susanne; Cook, Gregory M.; Berney, Michael

    2010-01-01

    SigF is an alternative sigma factor that is highly conserved among species of the genus Mycobacterium. In this study we identified the SigF regulon in Mycobacterium smegmatis using whole-genome microarray and promoter consensus analyses. In total, 64 genes in exponential phase and 124 genes in stationary phase are SigF dependent (P < 0.01, >2-fold expression change). Our experimental data reveal the SigF-dependent promoter consensus GTTT-N(15-17)-GGGTA for M. smegmatis, and we propose 130 potential genes under direct control of SigF, of which more than 50% exhibited reduced expression in a ΔsigF strain. We previously reported an increased susceptibility of the ΔsigF strain to heat and oxidative stress, and our expression data indicate a molecular basis for these phenotypes. We observed SigF-dependent expression of several genes purportedly involved in oxidative stress defense, namely, a heme-containing catalase, a manganese-containing catalase, a superoxide dismutase, the starvation-induced DNA-protecting protein MsDps1, and the biosynthesis genes for the carotenoid isorenieratene. Our data suggest that SigF regulates the biosynthesis of the thermoprotectant trehalose, as well as an uptake system for osmoregulatory compounds, and this may explain the increased heat susceptibility of the ΔsigF strain. We identified the regulatory proteins SigH3, PhoP, WhiB1, and WhiB4 as possible genes under direct control of SigF and propose four novel anti-sigma factor antagonists that could be involved in the posttranslational regulation of SigF in M. smegmatis. This study emphasizes the importance of this sigma factor for stationary-phase adaptation and stress response in mycobacteria. PMID:20233930

  10. A two scale analysis of tight sandstones

    NASA Astrophysics Data System (ADS)

    Adler, P. M.; Davy, C. A.; Song, Y.; Troadec, D.; Hauss, G.; Skoczylas, F.

    2015-12-01

    Tight sandstones have a low porosity and a very small permeability K. Available models for K do not compare well with measurements. These sandstones are made of SiO_2 grains, with a typical size of several hundreds of micron. These grains are separated by a network of micro-cracks, with sizes ranging between microns down to tens of nm. Therefore, the structure can be schematized by Voronoi polyhedra separated by plane and permeable polygonal micro-cracks. Our goal is to estimate K based on a two scale analysis and to compare the results to measurements. For a particular sample [2], local measurements on several scales include FIB/SEM [3], CMT and 2D SEM. FIB/SEM is selected because the peak pore size given by Mercury Intrusion Porosimetry is of 350nm. FIB/SEM imaging (with 50 nm voxel size) identifies an individual crack of 180nm average opening, whereas CMT provides a connected porosity (individual crack) for 60 nm voxel size, of 4 micron average opening. Numerical modelling is performed by combining the micro-crack network scale (given by 2D SEM) and the 3D micro-crack scale (given by either FIB/SEM or CMT). Estimates of the micro-crack density are derived from 2D SEM trace maps by counting the intersections with scanlines, the surface density of traces, and the number of fracture intersections. K is deduced by using a semi empirical formula valid for identical, isotropic and uniformly distributed fractures [1]. This value is proportional to the micro-crack transmissivity sigma. Sigma is determined by solving the Stokes equation in the micro-cracks measured by FIB/SEM or CMT. K is obtained by combining the two previous results. Good correlation with measured values on centimetric plugs is found when using sigma from CMT data. The results are discussed and further research is proposed. [1] Adler et al, Fractured porous media, Oxford Univ. Press, 2012. [2] Duan et al, Int. J. Rock Mech. Mining Sci., 65, p75, 2014. [3] Song et al, Marine and Petroleum Eng., 65, p63, 2015.

  11. Variance and covariance estimates for weaning weight of Senepol cattle.

    PubMed

    Wright, D W; Johnson, Z B; Brown, C J; Wildeus, S

    1991-10-01

    Variance and covariance components were estimated for weaning weight from Senepol field data for use in the reduced animal model for a maternally influenced trait. The 4,634 weaning records were used to evaluate 113 sires and 1,406 dams on the island of St. Croix. Estimates of direct additive genetic variance (sigma 2A), maternal additive genetic variance (sigma 2M), covariance between direct and maternal additive genetic effects (sigma AM), permanent maternal environmental variance (sigma 2PE), and residual variance (sigma 2 epsilon) were calculated by equating variances estimated from a sire-dam model and a sire-maternal grandsire model, with and without the inverse of the numerator relationship matrix (A-1), to their expectations. Estimates were sigma 2A, 139.05 and 138.14 kg2; sigma 2M, 307.04 and 288.90 kg2; sigma AM, -117.57 and -103.76 kg2; sigma 2PE, -258.35 and -243.40 kg2; and sigma 2 epsilon, 588.18 and 577.72 kg2 with and without A-1, respectively. Heritability estimates for direct additive (h2A) were .211 and .210 with and without A-1, respectively. Heritability estimates for maternal additive (h2M) were .47 and .44 with and without A-1, respectively. Correlations between direct and maternal (IAM) effects were -.57 and -.52 with and without A-1, respectively.

  12. Model representations for systems of selfadjoint operators satisfying commutation relations

    NASA Astrophysics Data System (ADS)

    Zolotarev, Vladimir A.

    2010-12-01

    Model representations are constructed for a system \\{B_k\\}_1^n of bounded linear selfadjoint operators in a Hilbert space H such that \\displaystyle \\lbrack B_k,B_s \\rbrack =\\frac i2\\varphi^*R_{k,s}^-\\varphi, \\qquad\\sigma_k\\varphi B_s-\\sigma_s\\varphi B_k=R_{k,s}^+\\varphi, \\displaystyle \\sigma_k\\varphi\\varphi^*\\sigma_s-\\sigma_s\\varphi\\varphi^*\\sigma_k=2iR_{k,s}^-,\\qquad1\\le k, s\\le n, where \\varphi is a linear operator from H into a Hilbert space E and \\{\\sigma_k,R_{k,s}^+/-\\}_1^n are some selfadjoint operators in E. A realization of these models in function spaces on a Riemann surface is found and a full set of invariants for \\{B_k\\}_1^n is described. Bibliography: 11 titles.

  13. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Widesott, Lamberto; Lomax, Antony J.; Schwarz, Marco

    Purpose: To assess the quality of dose distributions in real clinical cases for different dimensions of scanned proton pencil beams. The distance between spots (i.e., the grid of delivery) is optimized for each dimension of the pencil beam. Methods: The authors vary the {sigma} of the initial Gaussian size of the spot, from {sigma}{sub x} = {sigma}{sub y} = 3 mm to {sigma}{sub x} = {sigma}{sub y} = 8 mm, to evaluate the impact of the proton beam size on the quality of intensity modulated proton therapy (IMPT) plans. The distance between spots, {Delta}x and {Delta}y, is optimized on themore » spot plane, ranging from 4 to 12 mm (i.e., each spot size is coupled with the best spot grid resolution). In our Hyperion treatment planning system (TPS), constrained optimization is applied with respect to the organs at risk (OARs), i.e., the optimization tries to satisfy the dose objectives in the planning target volume (PTV) as long as all planning objectives for the OARs are met. Three-field plans for a nasopharynx case, two-field plans for a prostate case, and two-field plans for a malignant pleural mesothelioma case are considered in our analysis. Results: For the head and neck tumor, the best grids (i.e., distance between spots) are 5, 4, 6, 6, and 8 mm for {sigma} = 3, 4, 5, 6, and 8 mm, respectively. {sigma} {<=} 5 mm is required for tumor volumes with low dose and {sigma}{<=} 4 mm for tumor volumes with high dose. For the prostate patient, the best grid is 4, 4, 5, 5, and 5 mm for {sigma} = 3, 4, 5, 6, and 8 mm, respectively. Beams with {sigma} > 3 mm did not satisfy our first clinical requirement that 95% of the prescribed dose is delivered to more than 95% of prostate and proximal seminal vesicles PTV. Our second clinical requirement, to cover the distal seminal vesicles PTV, is satisfied for beams as wide as {sigma} = 6 mm. For the mesothelioma case, the low dose PTV prescription is well respected for all values of {sigma}, while there is loss of high dose PTV coverage for {sigma} > 5 mm. The best grids have a spacing of 6, 7, 8, 9, and 12 mm for {sigma} = 3, 4, 5, 6, and 8 mm, respectively. Conclusions: The maximum acceptable proton pencil beam {sigma} depends on the volume treated, the protocol of delivery, and optimization of the plan. For the clinical cases, protocol and optimization used in this analysis, acceptable {sigma}s are {<=} 4 mm for the head and neck tumor, {<=} 3 mm for the prostate tumor and {<=} 6 mm for the malignant pleural mesothelioma. One can apply the same procedure used in this analysis when given a ''class'' of patients, a {sigma} and a clinical protocol to determine the optimal grid spacing.« less

  14. Sigma metrics used to assess analytical quality of clinical chemistry assays: importance of the allowable total error (TEa) target.

    PubMed

    Hens, Koen; Berth, Mario; Armbruster, Dave; Westgard, Sten

    2014-07-01

    Six Sigma metrics were used to assess the analytical quality of automated clinical chemistry and immunoassay tests in a large Belgian clinical laboratory and to explore the importance of the source used for estimation of the allowable total error. Clinical laboratories are continually challenged to maintain analytical quality. However, it is difficult to measure assay quality objectively and quantitatively. The Sigma metric is a single number that estimates quality based on the traditional parameters used in the clinical laboratory: allowable total error (TEa), precision and bias. In this study, Sigma metrics were calculated for 41 clinical chemistry assays for serum and urine on five ARCHITECT c16000 chemistry analyzers. Controls at two analyte concentrations were tested and Sigma metrics were calculated using three different TEa targets (Ricos biological variability, CLIA, and RiliBÄK). Sigma metrics varied with analyte concentration, the TEa target, and between/among analyzers. Sigma values identified those assays that are analytically robust and require minimal quality control rules and those that exhibit more variability and require more complex rules. The analyzer to analyzer variability was assessed on the basis of Sigma metrics. Six Sigma is a more efficient way to control quality, but the lack of TEa targets for many analytes and the sometimes inconsistent TEa targets from different sources are important variables for the interpretation and the application of Sigma metrics in a routine clinical laboratory. Sigma metrics are a valuable means of comparing the analytical quality of two or more analyzers to ensure the comparability of patient test results.

  15. Efficiencies of Rotational Raman, and Rayleigh Techniques for Laser Remote Sensing of the Atmospheric Temperature

    NASA Technical Reports Server (NTRS)

    Ivanova, I. D.; Gurdev, L. L.; Mitev, V. M.

    1992-01-01

    Various lidar methods have been developed for measuring the atmospheric temperature, making use of the temperature dependant characteristics of rotational Raman scattering (RRS) from nitrogen and oxygen, and Rayleigh or Rayleigh-Brillowin scattering (RS or RBS). These methods have various advantages and disadvantages as compared to each other but their potential accuracies are principal characteristics of their efficiency. No systematic attempt has been undertaken so far to compare the efficiences, in the above meaning, of different temperature lidar methods. Two RRS techniques have been compared. Here, we do such a comparison using two methods based on the detection and analysis of RS (RBS) spectra. Four methods are considered here for measuring the atmospheric temperature. One of them (Schwiesow and Lading, 1981) is based on an analysis of the RS linewidth with two Michelson interferometers (MI) in parallel. The second method (Shimisu et al., 1986) employs a high-resolution analysis of the RBS line shape. The third method (Cooney, 1972) employs the temperature dependance of the RRS spectrum envelope. The fourth method (Armstrong, 1974) makes use of a scanning Fabry-Perot interferometer (FPI) as a comb filter for processing the periodic RRS spectrum of the nitrogen. Let us denote the corresponding errors in measuring the temperature by sigma(sub MI), sigma(sub HR), sigma(sub ENV), and sigma(sub FPI). Let us also define the ratios chi(sub 1) = sigma(sub MI)/sigma(sub ENV), chi(sub 2) = sigma(sub HR)/sigma(sub ENV), and chi(sub 3) = sigma(sub FPI)/sigma(sub ENV) interpreted as relative errors with respect to sigma(sub ENV).

  16. Incorporating Six Sigma Methodology Training into Chemical Engineering Education

    ERIC Educational Resources Information Center

    Dai, Lenore L.

    2007-01-01

    Six Sigma is a buzz term in today's technology and business world and there has been increasing interest to initiate Six Sigma training in college education. We have successfully incorporated Six Sigma methodology training into a traditional chemical engineering course, Engineering Experimentation, at Texas Tech University. The students have…

  17. Mapping the CgrA regulon of Rhodospirillum centenum reveals a hierarchal network controlling Gram-negative cyst development.

    PubMed

    Dong, Qian; Fang, Mingxu; Roychowdhury, Sugata; Bauer, Carl E

    2015-12-16

    Several Gram-negative species undergo development leading to the formation of metabolically dormant desiccation resistant cysts. Recent analysis of cyst development has revealed that ~20 % of the Rhodospirillum centenum transcriptome undergo temporal changes in expression as cells transition from vegetative to cyst forms. It has also been established that one trigger for cyst formation is the synthesis of the signaling nucleotide 3', 5'- cyclic guanosine monophosphate (cGMP) that is sensed by a homolog of the catabolite repressor protein called CgrA. CgrA in the presence of cGMP initiate a cascade of gene expression leading to the development of cysts. In this study, we have used RNA-seq and chromatin immunoprecipitation (ChIP-Seq) techniques to define the CgrA-cGMP regulon. Our results indicate that disruption of CgrA leads to altered expression of 258 genes, 131 of which have been previously reported to be involved in cyst development. ChIP-seq analysis combined with transcriptome data also demonstrates that CgrA directly regulates the expression of numerous sigma factors and transcription factors several of which are known to be involved in cyst cell development. This analysis reveals the presence of CgrA binding sites upstream of many developmentally regulated genes including many transcription factors and signal transduction components. CgrA thus functions as master controller of the cyst development by initiating a hierarchal cascade of downstream transcription factors that induces temporal expression of encystment genes.

  18. Switches from pi- to sigma-bonding complexes controlled by gate voltages.

    PubMed

    Matsui, Eriko; Harnack, Oliver; Matsuzawa, Nobuyuki N; Yasuda, Akio

    2005-10-01

    A conjugated polymer/metal ion/liquid-crystal molecular system was set between source and drain electrodes with a 100 nm gap. When gate voltage (Vg) increases, the current between source and drain electrodes increases. Infrared spectra show this system to be composed of pi and sigma complexes. At Vg = 0, the pi complex dominates the sigma complex, whereas the sigma complex becomes dominant when Vg is switched on. Calculations found that the pi complex has lower conductivity than the sigma complex.

  19. The Alternative Sigma Factors SigE and SigB Are Involved in Tolerance and Persistence to Antitubercular Drugs

    PubMed Central

    Pisu, Davide; Provvedi, Roberta; Espinosa, Dulce Mata; Payan, Jorge Barrios; Boldrin, Francesca; Palù, Giorgio; Hernandez-Pando, Rogelio

    2017-01-01

    ABSTRACT The emergence and spread of drug-resistant Mycobacterium tuberculosis strains possibly threaten our ability to treat this disease in the future. Even though two new antitubercular drugs have recently been introduced, there is still the need to design new molecules whose mechanisms of action could reduce the length of treatment. We show that two alternative sigma factors of M. tuberculosis (SigE and SigB) have a major role in determining the level of basal resistance to several drugs and the amount of persisters surviving long-duration drug treatment. We also demonstrate that ethambutol, a bacteriostatic drug, is highly bactericidal for M. tuberculosis mutants missing either SigE or SigB. We suggest that molecules able to interfere with the activity of SigE or SigB not only could reduce M. tuberculosis virulence in vivo but also could boost the effect of other drugs by increasing the sensitivity of the organism and reducing the number of persisters able to escape killing. PMID:28993339

  20. Improving furfural tolerance of Zymomonas mobilis by rewiring a sigma factor RpoD protein.

    PubMed

    Tan, Fu-Rong; Dai, Li-Chun; Wu, Bo; Qin, Han; Shui, Zong-Xia; Wang, Jing-Li; Zhu, Qi-Li; Hu, Qi-Chun; Ruan, Zhi-Yong; He, Ming-Xiong

    2015-06-01

    Furfural from lignocellulosic hydrolysates is the key inhibitor for bio-ethanol fermentation. In this study, we report a strategy of improving the furfural tolerance in Zymomonas mobilis on the transcriptional level by engineering its global transcription sigma factor (σ(70), RpoD) protein. Three furfural tolerance RpoD mutants (ZM4-MF1, ZM4-MF2, and ZM4-MF3) were identified from error-prone PCR libraries. The best furfural-tolerance strain ZM4-MF2 reached to the maximal cell density (OD600) about 2.0 after approximately 30 h, while control strain ZM4-rpoD reached its highest cell density of about 1.3 under the same conditions. ZM4-MF2 also consumed glucose faster and yield higher ethanol; expression levels and key Entner-Doudoroff (ED) pathway enzymatic activities were also compared to control strain under furfural stress condition. Our results suggest that global transcription machinery engineering could potentially be used to improve stress tolerance and ethanol production in Z. mobilis.

  1. Six Sigma methods applied to cryogenic coolers assembly line

    NASA Astrophysics Data System (ADS)

    Ventre, Jean-Marc; Germain-Lacour, Michel; Martin, Jean-Yves; Cauquil, Jean-Marc; Benschop, Tonny; Griot, René

    2009-05-01

    Six Sigma method have been applied to manufacturing process of a rotary Stirling cooler: RM2. Name of the project is NoVa as main goal of the Six Sigma approach is to reduce variability (No Variability). Project has been based on the DMAIC guideline following five stages: Define, Measure, Analyse, Improve, Control. Objective has been set on the rate of coolers succeeding performance at first attempt with a goal value of 95%. A team has been gathered involving people and skills acting on the RM2 manufacturing line. Measurement System Analysis (MSA) has been applied to test bench and results after R&R gage show that measurement is one of the root cause for variability in RM2 process. Two more root causes have been identified by the team after process mapping analysis: regenerator filling factor and cleaning procedure. Causes for measurement variability have been identified and eradicated as shown by new results from R&R gage. Experimental results show that regenerator filling factor impacts process variability and affects yield. Improved process haven been set after new calibration process for test bench, new filling procedure for regenerator and an additional cleaning stage have been implemented. The objective for 95% coolers succeeding performance test at first attempt has been reached and kept for a significant period. RM2 manufacturing process is now managed according to Statistical Process Control based on control charts. Improvement in process capability have enabled introduction of sample testing procedure before delivery.

  2. A computational analysis of the impact of the transient genetic imbalance on compartmentalized gene expression during sporulation in Bacillus subtilis.

    PubMed

    Iber, Dagmar

    2006-06-30

    Sporulation in Bacillus subtilis serves as paradigm for the development of two different cell types (mother cell and prespore) from a single cell. Differential gene expression is achieved by restricting the activation of the key transcription factor sigmaF to the smaller prespore. By use of a combination of mathematical and experimental techniques we have recently shown that the volume difference determines cell fate and that the accumulation of the phosphatase SpoIIE on the asymmetrically placed septum is sufficient for prespore-specific sigmaF activation. Since compartmentalized gene expression is still obtained when SpoIIE cannot accumulate on the septum a number of alternative mechanisms have been proposed. These mechanisms focus on the difference in gene content between mother cell and prespore immediately after septation. Here the computational model is employed to show that under physiological conditions the transient genetic imbalance is unlikely to affect the septation-dependent release of sigmaF. The duration of the transient genetic imbalance is too short for the degradation of SpoIIAB to have an impact on the release of sigmaF. Moreover, the existence of an elusive IIE inhibitor, which has been proposed to become depleted in the prespore because of the transient genetic imbalance, is shown to be inconsistent with available experimental data. We conclude that the volume difference between the two compartments is the main determinant of cell fate.

  3. Adjustable Nyquist-rate System for Single-Bit Sigma-Delta ADC with Alternative FIR Architecture

    NASA Astrophysics Data System (ADS)

    Frick, Vincent; Dadouche, Foudil; Berviller, Hervé

    2016-09-01

    This paper presents a new smart and compact system dedicated to control the output sampling frequency of an analogue-to-digital converters (ADC) based on single-bit sigma-delta (ΣΔ) modulator. This system dramatically improves the spectral analysis capabilities of power network analysers (power meters) by adjusting the ADC's sampling frequency to the input signal's fundamental frequency with a few parts per million accuracy. The trade-off between straightforwardness and performance that motivated the choice of the ADC's architecture are preliminary discussed. It particularly comes along with design considerations of an ultra-steep direct-form FIR that is optimised in terms of size and operating speed. Thanks to compact standard VHDL language description, the architecture of the proposed system is particularly suitable for application-specific integrated circuit (ASIC) implementation-oriented low-power and low-cost power meter applications. Field programmable gate array (FPGA) prototyping and experimental results validate the adjustable sampling frequency concept. They also show that the system can perform better in terms of implementation and power capabilities compared to dedicated IP resources.

  4. The sigma-1 receptor chaperone as an inter-organelle signaling modulator

    PubMed Central

    Su, Tsung-Ping; Hayashi, Teruo; Maurice, Tangui; Buch, Shilpa; Ruoho, Arnold E.

    2010-01-01

    Inter-organelle signaling plays important roles in many physiological functions. Endoplasmic reticulum (ER)-mitochondrion signaling affects intra-mitochondrial calcium (Ca2+) homeostasis and cellular bioenergetics. ER-nucleus signaling attenuates ER stress. ER-plasma membrane signaling regulates cytosolic Ca2+ homeostasis, and ER-mitochondrion-plasma membrane signaling regulates hippocampal dendritic spine formation. Here we propose that the sigma-1 receptor (Sig-1R), an ER chaperone protein, acts as an inter-organelle signaling modulator. Sig-1Rs normally reside at the ER-mitochondrion contact called the MAM (mitochondrion-associated ER membrane), where Sig-1Rs regulate ER-mitochondrion signaling and the ER-nucleus cross-talk. When cells are stimulated by ligands or undergo prolonged stress, Sig-1Rs translocate from the MAM to the ER reticular network and plasmalemma/plasma membrane to regulate a variety of functional proteins, including ion channels, receptors, and kinases. Thus, the Sig-1R serves as an inter-organelle signaling modulator locally at the MAM and remotely at the plasmalemma/plasma membrane. Many pharmacological/physiological effects of Sig-1Rs may relate to this unique action of Sig-1Rs. PMID:20869780

  5. First measurements of J/{psi} decays into {sigma}{sup +}{sigma}{sup -} and {xi}{sup 0}{xi}{sup 0}

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ablikim, M.; Bai, J. Z.; Bai, Y.

    Based on 58x10{sup 6} J/{psi} events collected with the BESII detector at the Beijing Electron-Positron Collider, the baryon pair processes J/{psi}{yields}{sigma}{sup +}{sigma}{sup -} and J/{psi}{yields}{xi}{sup 0}{xi}{sup 0} are observed for the first time. The branching fractions are measured to be B(J/{psi}{yields}{sigma}{sup +}{sigma}{sup -})=(1.50{+-}0.10{+-}0.22)x10{sup -3} and B(J/{psi}{yields}{xi}{sup 0}{xi}{sup 0})=(1.20{+-}0.12{+-}0.21)x10{sup -3}, where the first errors are statistical and the second ones are systematic.

  6. Sigma meson in vacuum and nuclear matter

    NASA Astrophysics Data System (ADS)

    Menchaca-Maciel, M. C.; Morones-Ibarra, J. R.

    2013-04-01

    We have obtained the value of the interaction constant g σππ that adjusts the values obtained in the E791 Collaboration at Fermilab and BES Collaboration at the Beijing Electron Positron Collider experiments. To get this we have used the concept of critical width to make compatible the parameters obtained from the Breit-Wigner formula and those obtained from the density function. Also, the total width and effective mass modification of the sigma meson in nuclear matter has been studied in the Walecka model, assuming that the sigma couples to a pair of nucleon-antinucleon states and to particle-hole states, including the in-medium effect of sigma-omega mixing. We have considered, for completeness, the coupling of sigma to two virtual pions. We have found that the sigma meson mass decreases with respect to its value in vacuum and that the contribution of the sigma-omega mixing effect on the mass shift is relevant.

  7. Baryon masses and σ terms in SU(3) BChPT×1/N c

    DOE PAGES

    Fernando, Ishara P.; Alarcon-Soriano, Jose-Manuel; Goity, Jose Luis

    2018-04-27

    Baryon masses and nucleonmore » $$\\sigma$$ terms are studied with the effective theory that combines the chiral and $$1/N_c$$ expansions for three flavors. In particular the connection between the deviation of the Gell-Mann-Okubo relation and the $$\\sigma$$ term associated with the scalar density $$\\bar u u+\\bar d d-2\\bar s s$$ is emphasized. The latter is at lowest order related to a mass combination whose low value has given rise to a $$\\sigma$$ term puzzle. It is shown that while the nucleon $$\\sigma$$ terms have a well behaved low energy expansion, that mass combination is affected by large higher order corrections non-analytic in quark masses. Lastly, adding to the analysis lattice QCD baryon masses, it is found that $$\\sigma_{\\pi N}=69(10)$$~MeV and $$\\sigma_s$$ has natural magnitude within its relative large uncertainty.« less

  8. The sigma-1 receptor modulates NMDA receptor synaptic transmission and plasticity via SK channels in rat hippocampus.

    PubMed

    Martina, Marzia; Turcotte, Marie-Eve B; Halman, Samantha; Bergeron, Richard

    2007-01-01

    The sigma receptor (sigmaR), once considered a subtype of the opioid receptor, is now described as a distinct pharmacological entity. Modulation of N-methyl-D-aspartate receptor (NMDAR) functions by sigmaR-1 ligands is well documented; however, its mechanism is not fully understood. Using patch-clamp whole-cell recordings in CA1 pyramidal cells of rat hippocampus and (+)pentazocine, a high-affinity sigmaR-1 agonist, we found that sigmaR-1 activation potentiates NMDAR responses and long-term potentiation (LTP) by preventing a small conductance Ca2+-activated K+ current (SK channels), known to shunt NMDAR responses, to open. Therefore, the block of SK channels and the resulting increased Ca2+ influx through the NMDAR enhances NMDAR responses and LTP. These results emphasize the importance of the sigmaR-1 as postsynaptic regulator of synaptic transmission.

  9. Regions of attraction and ultimate boundedness for linear quadratic regulators with nonlinearities

    NASA Technical Reports Server (NTRS)

    Joshi, S. M.

    1984-01-01

    The closed-loop stability of multivariable linear time-invariant systems controlled by optimal linear quadratic (LQ) regulators is investigated for the case when the feedback loops have nonlinearities N(sigma) that violate the standard stability condition, sigma N(sigma) or = 0.5 sigma(2). The violations of the condition are assumed to occur either (1) for values of sigma away from the origin (sigma = 0) or (2) for values of sigma in a neighborhood of the origin. It is proved that there exists a region of attraction for case (1) and a region of ultimate boundedness for case (2), and estimates are obtained for these regions. The results provide methods for selecting the performance function parameters to design LQ regulators with better tolerance to nonlinearities. The results are demonstrated by application to the problem of attitude and vibration control of a large, flexible space antenna in the presence of actuator nonlinearities.

  10. Baryon masses and σ terms in SU(3) BChPT×1/N c

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fernando, Ishara P.; Alarcon-Soriano, Jose-Manuel; Goity, Jose Luis

    Baryon masses and nucleonmore » $$\\sigma$$ terms are studied with the effective theory that combines the chiral and $$1/N_c$$ expansions for three flavors. In particular the connection between the deviation of the Gell-Mann-Okubo relation and the $$\\sigma$$ term associated with the scalar density $$\\bar u u+\\bar d d-2\\bar s s$$ is emphasized. The latter is at lowest order related to a mass combination whose low value has given rise to a $$\\sigma$$ term puzzle. It is shown that while the nucleon $$\\sigma$$ terms have a well behaved low energy expansion, that mass combination is affected by large higher order corrections non-analytic in quark masses. Lastly, adding to the analysis lattice QCD baryon masses, it is found that $$\\sigma_{\\pi N}=69(10)$$~MeV and $$\\sigma_s$$ has natural magnitude within its relative large uncertainty.« less

  11. Evaluation of normalization reference genes for RT-qPCR analysis of spo0A and four sporulation sigma factor genes in Clostridium botulinum Group I strain ATCC 3502.

    PubMed

    Kirk, David G; Palonen, Eveliina; Korkeala, Hannu; Lindström, Miia

    2014-04-01

    Heat-resistant spores of Clostridium botulinum can withstand the pasteurization processes in modern food processing. This poses a risk to food safety as spores may germinate into botulinum neurotoxin-producing vegetative cells. Sporulation in Bacillus subtilis, the model organism for sporulation, is regulated by the transcription factor Spo0A and four alternative sigma factors, SigF, SigE, SigG, and SigK. While the corresponding regulators are found in available genomes of C. botulinum, little is known about their expression. To accurately measure the expression of these genes using quantitative reverse-transcriptase PCR (RT-qPCR) during the exponential and stationary growth phases, a suitable normalization reference gene is required. 16S rrn, adK, alaS, era, gluD, gyrA, rpoC, and rpsJ were selected as the candidate reference genes. The most stable candidate reference gene was 16S ribosomal RNA gene (rrn), based on its low coefficient of variation (1.81%) measured during the 18-h study time. Using 16S rrn as the normalization reference gene, the relative expression levels of spo0A, sigF, sigE, sigG, and sigK were measured over 18h. The pattern of expression showed spo0A expression during the logarithmic growth phase, followed by a drop in expression upon entry to the stationary phase. Expression levels of sigF, sigE, and sigG peaked simultaneously at the end of the exponential growth phase. Peak expression of sigK occurred at 18h, however low levels of expression were detected during the exponential phase. These findings suggest these sigma factors play a role in C. botulinum sporulation that is similar, but not equal, to their role in the B. subtilis model. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Relative intensity calculations for nitrous oxide.

    NASA Technical Reports Server (NTRS)

    Young, L. D. G.

    1972-01-01

    A tabulation of calculated rotational line intensities, relative to the integrated intensity of a vibration-rotation band, is given for Sigma-Sigma, Pi-Sigma, Sigma-Pi, Pi-Pi, and Delta-Pi transitions of nitrous oxide. These calculations were made for temperatures of 250 K and 300 K. A summary of band-intensity measurements is also presented.

  13. 77 FR 1491 - Sigma Corporation; Analysis of Proposed Consent Order To Aid Public Comment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-10

    ... FEDERAL TRADE COMMISSION [File No. 101 0080] Sigma Corporation; Analysis of Proposed Consent Order... instructions in the Request for Comment part of the SUPPLEMENTARY INFORMATION section below. Write ``Sigma.... Write ``Sigma, File No. 101 0080'' on your comment. Your comment--including your name and your state...

  14. Reflection coefficients of permeant molecules in human red cell suspensions.

    PubMed

    Owen, J D; Eyring, E M

    1975-08-01

    The Staverman reflection coefficient, sigma for several permeant molecules was determined in human red cell suspensions with a Durrum stopped-flow spectrophotometer. This procedure was first used with dog, cat, and beef red cells and with human red cells. The stopped-flow technique used was similar to the rapid-flow method used by those who originally reported sigma measurements in human red cells for molecules which rapidly penetrate the red cell membrane. The sigma values we obtained agreed with those previously reported for most of the slow penetrants, except malonamide, but disagreed with all the sigma values previously reported for the rapid penetrants. We were unable to calculate an "equivalent pore radius" with our sigma data. The advantages of our equipment and our experimental procedure are discussed. Our sigma data suggest that sigma is indirectly proportional to the log of the nonelectrolyte permeability coefficient, omega. Since a similar trend has been previously shown for log omega and molar volume of the permeant molecules, a correlatioo was shown between sigma and molar volume suggesting the membrane acts as a sieve.

  15. An exploratory analysis for Lean and Six Sigma implementation in hospitals: Together is better?

    PubMed

    Lee, Jung Young; McFadden, Kathleen L; Gowen, Charles R

    Despite the increasing interest for Lean and Six Sigma implementations in hospitals, there has been little empirical evidence that goes beyond descriptive case studies to address the current status and the effectiveness of the implementations. The aim of this study was to explore existing patterns of Lean and Six Sigma implementation in U.S. hospitals and compare the performance of the different patterns. We collected data from 215 U.S. hospitals via a survey that includes measurement items developed from related literature. Using the cross-sectional data, we conducted a cluster analysis, followed by t tests, chi-square tests, and regression analyses for cluster verification. The cluster analysis identifies two clusters, a Moderate Six Sigma group and a Lean Six Sigma group. Results show that the Lean Six Sigma group outperforms the Moderate Six Sigma group across many performance dimensions: responsiveness capability, patient safety, and possibly cost saving. In addition, the Lean Six Sigma group tends to be composed of larger, private teaching hospitals located in more urban areas, and they employ more resources for quality improvement. Our research contributes to the quality management literature by supporting the possible complementary relationship between Lean and Six Sigma in hospitals. Our study encourages practitioners and managers to pay more attention to Lean implementation. Although Lean seems to be conducted in a limited fashion in many hospitals, it should be expanded and combined with Six Sigma for better results.

  16. Inverse regulatory coordination of motility and curli-mediated adhesion in Escherichia coli.

    PubMed

    Pesavento, Christina; Becker, Gisela; Sommerfeldt, Nicole; Possling, Alexandra; Tschowri, Natalia; Mehlis, Anika; Hengge, Regine

    2008-09-01

    During the transition from post-exponential to stationary phase, Escherichia coli changes from the motile-planktonic to the adhesive-sedentary "lifestyle." We demonstrate this transition to be controlled by mutual inhibition of the FlhDC/motility and sigma(S)/adhesion control cascades at two distinct hierarchical levels. At the top level, motility gene expression and the general stress response are inversely coordinated by sigma(70)/sigma(FliA)/sigma(S) competition for core RNA polymerase and the FlhDC-controlled FliZ protein acting as a sigma(S) inhibitor. At a lower level, the signaling molecule bis-(3'-5')-cyclic-diguanosine monophosphate (c-di-GMP) reduces flagellar activity and stimulates transcription of csgD, which encodes an essential activator of adhesive curli fimbriae expression. This c-di-GMP is antagonistically controlled by sigma(S)-regulated GGDEF proteins (mainly YegE) and YhjH, an EAL protein and c-di-GMP phosphodiesterase under FlhDC/FliA control. The switch from motility-based foraging to the general stress response and curli expression requires sigma(S)-modulated down-regulation of expression of the flagellar regulatory cascade as well as proteolysis of the flagellar master regulator FlhDC. Control of YhjH by FlhDC and of YegE by sigma(S) produces a fine-tuned checkpoint system that "unlocks" curli expression only after down-regulation of flagellar gene expression. In summary, these data reveal the logic and sequence of molecular events underlying the motile-to-adhesive "lifestyle" switch in E. coli.

  17. A Direct Interaction between the Sigma-1 Receptor and the hERG Voltage-gated K+ Channel Revealed by Atomic Force Microscopy and Homogeneous Time-resolved Fluorescence (HTRF®)*

    PubMed Central

    Balasuriya, Dilshan; D'Sa, Lauren; Talker, Ronel; Dupuis, Elodie; Maurin, Fabrice; Martin, Patrick; Borgese, Franck; Soriani, Olivier; Edwardson, J. Michael

    2014-01-01

    The sigma-1 receptor is an endoplasmic reticulum chaperone protein, widely expressed in central and peripheral tissues, which can translocate to the plasma membrane and modulate the function of various ion channels. The human ether-à-go-go-related gene encodes hERG, a cardiac voltage-gated K+ channel that is abnormally expressed in many human cancers and is known to interact functionally with the sigma-1 receptor. Our aim was to investigate the nature of the interaction between the sigma-1 receptor and hERG. We show that the two proteins can be co-isolated from a detergent extract of stably transfected HEK-293 cells, consistent with a direct interaction between them. Atomic force microscopy imaging of the isolated protein confirmed the direct binding of the sigma-1 receptor to hERG monomers, dimers, and tetramers. hERG dimers and tetramers became both singly and doubly decorated by sigma-1 receptors; however, hERG monomers were only singly decorated. The distribution of angles between pairs of sigma-1 receptors bound to hERG tetramers had two peaks, at ∼90 and ∼180° in a ratio of ∼2:1, indicating that the sigma-1 receptor interacts with hERG with 4-fold symmetry. Homogeneous time-resolved fluorescence (HTRF®) allowed the detection of the interaction between the sigma-1 receptor and hERG within the plane of the plasma membrane. This interaction was resistant to sigma ligands, but was decreased in response to cholesterol depletion of the membrane. We suggest that the sigma-1 receptor may bind to hERG in the endoplasmic reticulum, aiding its assembly and trafficking to the plasma membrane. PMID:25266722

  18. Application of sigma metrics for the assessment of quality control in clinical chemistry laboratory in Ghana: A pilot study.

    PubMed

    Afrifa, Justice; Gyekye, Seth A; Owiredu, William K B A; Ephraim, Richard K D; Essien-Baidoo, Samuel; Amoah, Samuel; Simpong, David L; Arthur, Aaron R

    2015-01-01

    Sigma metrics provide a uniquely defined scale with which we can assess the performance of a laboratory. The objective of this study was to assess the internal quality control (QC) in the clinical chemistry laboratory of the University of Cape Cost Hospital (UCC) using the six sigma metrics application. We used commercial control serum [normal (L1) and pathological (L2)] for validation of quality control. Metabolites (glucose, urea, and creatinine), lipids [triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-C)], enzymes [alkaline phosphatase (ALP), alanine aminotransferase (AST)], electrolytes (sodium, potassium, chloride) and total protein were assessed. Between-day imprecision (CVs), inaccuracy (Bias) and sigma values were calculated for each control level. Apart from sodium (2.40%, 3.83%), chloride (2.52% and 2.51%) for both L1 and L2 respectively, and glucose (4.82%), cholesterol (4.86%) for L2, CVs for all other parameters (both L1 and L2) were >5%. Four parameters (HDL-C, urea, creatinine and potassium) achieved sigma levels >1 for both controls. Chloride and sodium achieved sigma levels >1 for L1 but <1 for L2. In contrast, cholesterol, total protein and AST achieved sigma levels <1 for L1 but >1 for L2. Glucose and ALP achieved a sigma level >1 for both control levels whereas TG achieved a sigma level >2 for both control levels. Unsatisfactory sigma levels (<3) where achieved for all parameters using both control levels, this shows instability and low consistency of results. There is the need for detailed assessment of the analytical procedures and the strengthening of the laboratory control systems in order to achieve effective six sigma levels for the laboratory.

  19. Organochlorine contaminant and stable isotope profiles in Arctic fox (Alopex lagopus) from the Alaskan and Canadian Arctic.

    PubMed

    Hoekstra, P F; Braune, B M; O'Hara, T M; Elkin, B; Solomon, K R; Muir, D C G

    2003-01-01

    Arctic fox (Alopex lagopus) is a circumpolar species distributed across northern Canada and Alaska. Arctic fox muscle and liver were collected at Barrow, AK, USA (n=18), Holman, NT, Canada (n=20), and Arviat, NU, Canada (n=20) to elucidate the feeding ecology of this species and relate these findings to body residue patterns of organochlorine contaminants (OCs). Stable carbon (delta 13C) and nitrogen (delta 15N) isotope analyses of Arctic fox muscle indicated that trophic position (estimated by delta 15N) is positively correlated with increasing delta 13C values, suggesting that Arctic fox with a predominantly marine-based foraging strategy occupy a higher trophic level than individuals mostly feeding from a terrestrial-based carbon source. At all sites, the rank order for OC groups in muscle was polychlorinated biphenyls (Sigma PCB) > chlordane-related compounds (Sigma CHLOR) > hexachlorocyclohexane (Sigma HCH) > total toxaphene (TOX) > or = chlorobenzenes (Sigma ClBz) > DDT-related isomers (Sigma DDT). In liver, Sigma CHLOR was the most abundant OC group, followed by Sigma PCB > TOX > Sigma HCH > Sigma ClBz > Sigma DDT. The most abundant OC analytes detected from Arctic fox muscle and liver were oxychlordane, PCB-153, and PCB-180. The comparison of delta 15N with OC concentrations indicated that relative trophic position might not accurately predict OC bioaccumulation in Arctic fox. The bioaccumulation pattern of OCs in the Arctic fox is similar to the polar bear. While Sigma PCB concentrations were highly variable, concentrations in the Arctic fox were generally below those associated with the toxicological endpoints for adverse effects on mammalian reproduction. Further research is required to properly elucidate the potential health impacts to this species from exposure to OCs.

  20. Application of sigma metrics for the assessment of quality control in clinical chemistry laboratory in Ghana: A pilot study

    PubMed Central

    Afrifa, Justice; Gyekye, Seth A.; Owiredu, William K. B. A.; Ephraim, Richard K. D.; Essien-Baidoo, Samuel; Amoah, Samuel; Simpong, David L.; Arthur, Aaron R.

    2015-01-01

    Background: Sigma metrics provide a uniquely defined scale with which we can assess the performance of a laboratory. The objective of this study was to assess the internal quality control (QC) in the clinical chemistry laboratory of the University of Cape Cost Hospital (UCC) using the six sigma metrics application. Materials and Methods: We used commercial control serum [normal (L1) and pathological (L2)] for validation of quality control. Metabolites (glucose, urea, and creatinine), lipids [triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-C)], enzymes [alkaline phosphatase (ALP), alanine aminotransferase (AST)], electrolytes (sodium, potassium, chloride) and total protein were assessed. Between-day imprecision (CVs), inaccuracy (Bias) and sigma values were calculated for each control level. Results: Apart from sodium (2.40%, 3.83%), chloride (2.52% and 2.51%) for both L1 and L2 respectively, and glucose (4.82%), cholesterol (4.86%) for L2, CVs for all other parameters (both L1 and L2) were >5%. Four parameters (HDL-C, urea, creatinine and potassium) achieved sigma levels >1 for both controls. Chloride and sodium achieved sigma levels >1 for L1 but <1 for L2. In contrast, cholesterol, total protein and AST achieved sigma levels <1 for L1 but >1 for L2. Glucose and ALP achieved a sigma level >1 for both control levels whereas TG achieved a sigma level >2 for both control levels. Conclusion: Unsatisfactory sigma levels (<3) where achieved for all parameters using both control levels, this shows instability and low consistency of results. There is the need for detailed assessment of the analytical procedures and the strengthening of the laboratory control systems in order to achieve effective six sigma levels for the laboratory. PMID:25657495

  1. High occupancy of sigma-1 receptors in the human brain after single oral administration of fluvoxamine: a positron emission tomography study using [11C]SA4503.

    PubMed

    Ishikawa, Masatomo; Ishiwata, Kiichi; Ishii, Kenji; Kimura, Yuichi; Sakata, Muneyuki; Naganawa, Mika; Oda, Keiichi; Miyatake, Ryousuke; Fujisaki, Mihisa; Shimizu, Eiji; Shirayama, Yukihiko; Iyo, Masaomi; Hashimoto, Kenji

    2007-10-15

    Sigma-1 receptors might be implicated in the pathophysiology of psychiatric diseases, as well as in the mechanisms of action of some selective serotonin reuptake inhibitors (SSRIs). Among the several SSRIs, fluvoxamine has the highest affinity for sigma-1 receptors (Ki = 36 nM), whereas paroxetine shows low affinity (Ki = 1893 nM). The present study was undertaken to examine whether fluvoxamine binds to sigma-1 receptors in living human brain. A dynamic positron emission tomography (PET) data acquisition using the selective sigma-1 receptor ligand [(11)C]SA4503 was performed with arterial blood sampling to evaluate quantitatively the binding of [(11)C]SA4503 to sigma-1 receptors in 15 healthy male volunteers. Each subject had two PET scans before and after randomly receiving a single dose of either fluvoxamine (50, 100, 150, or 200 mg) or paroxetine (20 mg). The binding potential of [(11)C]SA4503 in 9 regions of the brain was calculated by a 2-tissue 3-compartment model. In addition, we examined the effects of functional polymorphisms of the sigma-1 receptor (SIGMAR1) gene on the binding potential of [(11)C]SA4503. Fluvoxamine bound to sigma-1 receptors in all brain regions in a dose-dependent manner, whereas paroxetine did not bind to sigma-1 receptors. However, there was no association between the SIGMAR1 gene polymorphism GC-241-240TT and binding potential. The study demonstrated that fluvoxamine bound to sigma-1 receptors in living human brain at therapeutic doses. These findings suggest that sigma-1 receptors may play an important role in the mechanism of action of fluvoxamine.

  2. Guiding inpatient quality improvement: a systematic review of Lean and Six Sigma.

    PubMed

    Glasgow, Justin M; Scott-Caziewell, Jill R; Kaboli, Peter J

    2010-12-01

    Two popular quality improvement (QI) approaches in health care are Lean and Six Sigma. Hospitals continue to adopt these QI approaches-or the hybrid Lean Sigma approach-with little knowledge on how well they produce sustainable improvements. A systematic literature review was conducted to determine whether Lean, Six Sigma, or Lean Sigma have been effectively used to create and sustain improvements in the acute care setting. Databases were searched for articles published in the health care, business, and engineering literatures. Study inclusion criteria required identification of a Six Sigma, Lean, or Lean Sigma project; QI efforts focused on hospitalized patients; descriptions of project improvements; and reported results. Depending on the quality of data reported, articles were classified as summary reports, pre-post observational studies, or time-series reports. Database searches identified 539 potential articles. After review of titles, abstracts, and full text, 47 articles met inclusion criteria--10 articles summarized multiple projects, 12 reported Lean projects, 20 reported Six Sigma projects, and 5 reported Lean Sigma projects. Generally, the studies provided limited data, with only 15 articles providing any sort of follow-up data; of the 15, only 3 report a follow-up period greater than two years. Lean, Six Sigma, and Lean Sigma as QI approaches can aid institutions in tackling a wide variety of problems encountered in acute care. However, the true impact of these approaches is difficult to judge, given that the lack of rigorous evaluation or clearly sustained improvements provides little evidence supporting broad adoption. There is still a need for future work that will improve the evidence base for understanding more about QI approaches and how to achieve sustainable improvement.

  3. Looking for a precursor of spontaneous Sleep Slow Oscillations in human sleep: The role of the sigma activity

    PubMed Central

    Allegrini, Paolo; Bedini, Remo; Bergamasco, Massimo; Laurino, Marco; Sebastiani, Laura; Gemignani, Angelo

    2016-01-01

    Sleep Slow Oscillations (SSOs), paradigmatic EEG markers of cortical bistability (alternation between cellular downstates and upstates), and sleep spindles, paradigmatic EEG markers of thalamic rhythm, are two hallmarks of sleeping brain. Selective thalamic lesions are reportedly associated to reductions of spindle activity and its spectrum ~14 Hz (sigma), and to alterations of SSO features. This apparent, parallel behavior suggests that thalamo-cortical entrainment favors cortical bistability. Here we investigate temporally-causal associations between thalamic sigma activity and shape, topology, and dynamics of SSOs. We recorded sleep EEG and studied whether spatio-temporal variability of SSO amplitude, negative slope (synchronization in downstate falling) and detection rate are driven by cortical-sigma-activity expression (12–18 Hz), in 3 consecutive 1 s-EEG-epochs preceding each SSO event (Baselines). We analyzed: (i) spatial variability, comparing maps of baseline sigma power and of SSO features, averaged over the first sleep cycle; (ii) event-by-event shape variability, computing for each electrode correlations between baseline sigma power and amplitude/slope of related SSOs; (iii) event-by-event spreading variability, comparing baseline sigma power in electrodes showing an SSO event with the homologous ones, spared by the event. The scalp distribution of baseline sigma power mirrored those of SSO amplitude and slope; event-by-event variability in baseline sigma power was associated with that in SSO amplitude in fronto-central areas; within each SSO event, electrodes involved in cortical bistability presented higher baseline sigma activity than those free of SSO. In conclusion, spatio-temporal variability of thalamocortical entrainment, measured by background sigma activity, is a reliable estimate of the cortical proneness to bistability. PMID:26003553

  4. Identification of carbohydrate-binding domains in the attachment proteins of type 1 and type 3 reoviruses.

    PubMed

    Chappell, J D; Duong, J L; Wright, B W; Dermody, T S

    2000-09-01

    The reovirus attachment protein, sigma1, is responsible for strain-specific patterns of viral tropism in the murine central nervous system and receptor binding on cultured cells. The sigma1 protein consists of a fibrous tail domain proximal to the virion surface and a virion-distal globular head domain. To better understand mechanisms of reovirus attachment to cells, we conducted studies to identify the region of sigma1 that binds cell surface carbohydrate. Chimeric and truncated sigma1 proteins derived from prototype reovirus strains type 1 Lang (T1L) and type 3 Dearing (T3D) were expressed in insect cells by using a baculovirus vector. Assessment of expressed protein susceptibility to proteolytic cleavage, binding to anti-sigma1 antibodies, and oligomerization indicates that the chimeric and truncated sigma1 proteins are properly folded. To assess carbohydrate binding, recombinant sigma1 proteins were tested for the capacity to agglutinate mammalian erythrocytes and to bind sialic acid presented on glycophorin, the cell surface molecule bound by type 3 reovirus on human erythrocytes. Using a panel of two wild-type and ten chimeric and truncated sigma1 proteins, the sialic acid-binding domain of type 3 sigma1 was mapped to a region of sequence proposed to form the more amino terminal of two predicted beta-sheet structures in the tail. This unit corresponds to morphologic region T(iii) observed in computer-processed electron micrographs of sigma1 protein purified from virions. In contrast, the homologous region of T1L sigma1 sequence was not implicated in carbohydrate binding; rather, sequences in the distal portion of the tail known as the neck were required. Results of these studies demonstrate that a functional receptor-binding domain, which uses sialic acid as its ligand, is contained within morphologic region T(iii) of the type 3 sigma1 tail. Furthermore, our findings indicate that T1L and T3D sigma1 proteins contain different arrangements of receptor-binding domains.

  5. Operational excellence (six sigma) philosophy: Application to software quality assurance

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lackner, M.

    1997-11-01

    This report contains viewgraphs on operational excellence philosophy of six sigma applied to software quality assurance. This report outlines the following: goal of six sigma; six sigma tools; manufacturing vs administrative processes; Software quality assurance document inspections; map software quality assurance requirements document; failure mode effects analysis for requirements document; measuring the right response variables; and questions.

  6. Applying Sigma Metrics to Reduce Outliers.

    PubMed

    Litten, Joseph

    2017-03-01

    Sigma metrics can be used to predict assay quality, allowing easy comparison of instrument quality and predicting which tests will require minimal quality control (QC) rules to monitor the performance of the method. A Six Sigma QC program can result in fewer controls and fewer QC failures for methods with a sigma metric of 5 or better. The higher the number of methods with a sigma metric of 5 or better, the lower the costs for reagents, supplies, and control material required to monitor the performance of the methods. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Cesium frequency standard for lasers at. Sigma. = 1. 06. mu. m

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wallmeroth, K.; Letterer, R.

    1990-07-15

    High-resolution spectra of the {ital X}{sup 1}{Sigma}{sup +}{sub {ital g}}--{ital A}{sup 1}{Sigma}{sup +}{sub {ital u}} band of molecular cesium at {lambda}=1.06 {mu}m have been measured. An absolute wave-number reference table for lasers emitting at {Sigma} = 1.06 {mu}m has been established. The cesium resonances are calibrated with respect to the well-known molecular-iodine absorption lines at {Sigma} = 0.53 {mu}m. An accuracy of 10{sup {minus}7} has been achieved.

  8. Organochlorine pesticides and polychlorinated biphenyls levels in human milk from Chelem, Yucatán, México.

    PubMed

    Rodas-Ortíz, Juan Pablo; Ceja-Moreno, Victor; González-Navarrete, R L; Alvarado-Mejía, Jorge; Rodríguez-Hernández, Marissa E; Gold-Bouchot, Gerardo

    2008-03-01

    Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in human milk from Chelem, Yucatan, Mexico were analyzed. Relatively high levels of p,p'-DDE, gamma-chlordane, beta-hexacyclohexane (beta-HCH) and PCB congeners 170, 28, and 44 were found. Concentration profiles by OCP groups followed the next order: SigmaDDTs > SigmaChlordanes > SigmaHCHs > SigmaChlorobenzenes > SigmaDrins. Total OCPs showed a decreasing tendency with number of births (primipara and multipara and age ranks) but these differences were not significant. SigmaDDT levels were lower than in other studies in Mexico, but 36% of the samples exceeded the JMPR-FAO/WHO acceptable daily intake (ADI). About 60.53% of samples exceeded the ADI value for heptachlors.

  9. Dipole moments and transition probabilities of the a 3Sigma(+)g - b 3Sigma(+)u system of molecular hydrogen

    NASA Technical Reports Server (NTRS)

    Guberman, S.; Dalgarno, A.; Posen, A.; Kwok, T. L.

    1986-01-01

    Multiconfiguration variational calculations of the electronic wave functions of the a 3Sigma(+)g and b 3Sigma(+)u states of molecular hydrogen are presented, and the electric dipole transition moment between them (of interest in connection with stellar atmospheres and the UV spectrum of the Jovian planets) is obtained. The dipole moment is used to calculate the probabilities of radiative transitions from the discrete vibrational levels of the a 3Sigma(+)g state to the vibrational continuum of the repulsive b 3Sigma(+)u state as functions of the wavelength of the emitted photons. The total transition probabilities and radiative lifetimes of the levels v prime = 0-20 are presented.

  10. An Integrated Multilevel Converter with Sigma Delta Control for LED Lighting

    NASA Astrophysics Data System (ADS)

    Gerber, Daniel L.

    High brightness LEDs have become a mainstream lighting technology due to their efficiency, life span, and environmental benefits. As such, the lighting industry values LED drivers with low cost, small form factor, and long life span. Additional specifications that define a high quality LED driver are high efficiency, high power factor, wide-range dimming, minimal flicker, and a galvanically isolated output. The flyback LED driver is a popular topology that satisfies all these specifications, but it requires a bulky and costly flyback transformer. In addition, its passive methods for cancelling AC power ripple require electrolytic capacitors, which have been known to have life span issues. This dissertation details the design, construction, and verification of a novel LED driver that satisfies all the specifications. In addition, it does not require a flyback transformer or electrolytic capacitors, thus marking an improvement over the flyback driver on size, cost, and life span. This dissertation presents an integrated circuit (IC) LED driver, which features a pair of generalized multilevel converters that are controlled via sigma-delta modulation. The first is a multilevel rectifier responsible for power factor correction (PFC) and dimming. The PFC rectifier employs a second order sigma-delta loop to precisely control the input current harmonics and amplitude. The second is a bidirectional multilevel inverter used to cancel AC power ripple from the DC bus. This ripple-cancellation module transfers energy to and from a storage capacitor. It uses a first order sigma-delta loop with a preprogrammed waveform to swing the storage capacitor voltage. The system also contains an output stage that powers the LEDs with DC and provides for galvanic isolation. The output stage consists of an H-bridge stack that connects to the output through a small toroid transformer. The IC LED driver was simulated and prototyped on an ABCD silicon test chip. Testing and verification indicates functional performance for all the modules in the LED driver. The driver exhibits moderate efficiency at half voltage. Although the part was only testable to half voltage, loss models predict that its efficiency would be much higher at full voltage. The driver also meets specifications on the line current harmonics and ripple cancellation. This dissertation introduces multilevel circuit techniques to the IC and LED research space. The prototype's functional performance indicates that integrated multilevel converters are a viable topology for lighting and other similar applications.

  11. Regulatory and metabolic networks for the adaptation of Pseudomonas aeruginosa biofilms to urinary tract-like conditions.

    PubMed

    Tielen, Petra; Rosin, Nathalie; Meyer, Ann-Kathrin; Dohnt, Katrin; Haddad, Isam; Jänsch, Lothar; Klein, Johannes; Narten, Maike; Pommerenke, Claudia; Scheer, Maurice; Schobert, Max; Schomburg, Dietmar; Thielen, Bernhard; Jahn, Dieter

    2013-01-01

    Biofilms of the Gram-negative bacterium Pseudomonas aeruginosa are one of the major causes of complicated urinary tract infections with detrimental outcome. To develop novel therapeutic strategies the molecular adaption strategies of P. aeruginosa biofilms to the conditions of the urinary tract were investigated thoroughly at the systems level using transcriptome, proteome, metabolome and enzyme activity analyses. For this purpose biofilms were grown anaerobically in artificial urine medium (AUM). Obtained data were integrated bioinformatically into gene regulatory and metabolic networks. The dominating response at the transcriptome and proteome level was the adaptation to iron limitation via the broad Fur regulon including 19 sigma factors and up to 80 regulated target genes or operons. In agreement, reduction of the iron cofactor-dependent nitrate respiratory metabolism was detected. An adaptation of the central metabolism to lactate, citrate and amino acid as carbon sources with the induction of the glyoxylate bypass was observed, while other components of AUM like urea and creatinine were not used. Amino acid utilization pathways were found induced, while fatty acid biosynthesis was reduced. The high amounts of phosphate found in AUM explain the reduction of phosphate assimilation systems. Increased quorum sensing activity with the parallel reduction of chemotaxis and flagellum assembly underscored the importance of the biofilm life style. However, reduced formation of the extracellular polysaccharide alginate, typical for P. aeruginosa biofilms in lungs, indicated a different biofilm type for urinary tract infections. Furthermore, the obtained quorum sensing response results in an increased production of virulence factors like the extracellular lipase LipA and protease LasB and AprA explaining the harmful cause of these infections.

  12. Regulatory and Metabolic Networks for the Adaptation of Pseudomonas aeruginosa Biofilms to Urinary Tract-Like Conditions

    PubMed Central

    Dohnt, Katrin; Haddad, Isam; Jänsch, Lothar; Klein, Johannes; Narten, Maike; Pommerenke, Claudia; Scheer, Maurice; Schobert, Max; Schomburg, Dietmar; Thielen, Bernhard; Jahn, Dieter

    2013-01-01

    Biofilms of the Gram-negative bacterium Pseudomonas aeruginosa are one of the major causes of complicated urinary tract infections with detrimental outcome. To develop novel therapeutic strategies the molecular adaption strategies of P. aeruginosa biofilms to the conditions of the urinary tract were investigated thoroughly at the systems level using transcriptome, proteome, metabolome and enzyme activity analyses. For this purpose biofilms were grown anaerobically in artificial urine medium (AUM). Obtained data were integrated bioinformatically into gene regulatory and metabolic networks. The dominating response at the transcriptome and proteome level was the adaptation to iron limitation via the broad Fur regulon including 19 sigma factors and up to 80 regulated target genes or operons. In agreement, reduction of the iron cofactor-dependent nitrate respiratory metabolism was detected. An adaptation of the central metabolism to lactate, citrate and amino acid as carbon sources with the induction of the glyoxylate bypass was observed, while other components of AUM like urea and creatinine were not used. Amino acid utilization pathways were found induced, while fatty acid biosynthesis was reduced. The high amounts of phosphate found in AUM explain the reduction of phosphate assimilation systems. Increased quorum sensing activity with the parallel reduction of chemotaxis and flagellum assembly underscored the importance of the biofilm life style. However, reduced formation of the extracellular polysaccharide alginate, typical for P. aeruginosa biofilms in lungs, indicated a different biofilm type for urinary tract infections. Furthermore, the obtained quorum sensing response results in an increased production of virulence factors like the extracellular lipase LipA and protease LasB and AprA explaining the harmful cause of these infections. PMID:23967252

  13. [Study on application of SVM in prediction of coronary heart disease].

    PubMed

    Zhu, Yue; Wu, Jianghua; Fang, Ying

    2013-12-01

    Base on the data of blood pressure, plasma lipid, Glu and UA by physical test, Support Vector Machine (SVM) was applied to identify coronary heart disease (CHD) in patients and non-CHD individuals in south China population for guide of further prevention and treatment of the disease. Firstly, the SVM classifier was built using radial basis kernel function, liner kernel function and polynomial kernel function, respectively. Secondly, the SVM penalty factor C and kernel parameter sigma were optimized by particle swarm optimization (PSO) and then employed to diagnose and predict the CHD. By comparison with those from artificial neural network with the back propagation (BP) model, linear discriminant analysis, logistic regression method and non-optimized SVM, the overall results of our calculation demonstrated that the classification performance of optimized RBF-SVM model could be superior to other classifier algorithm with higher accuracy rate, sensitivity and specificity, which were 94.51%, 92.31% and 96.67%, respectively. So, it is well concluded that SVM could be used as a valid method for assisting diagnosis of CHD.

  14. A quantitative study of the benefits of co-regulation using the spoIIA operon as an example.

    PubMed

    Iber, Dagmar

    2006-01-01

    The distribution of most genes is not random, and functionally linked genes are often found in clusters. Several theories have been put forward to explain the emergence and persistence of operons in bacteria. Careful analysis of genomic data favours the co-regulation model, where gene organization into operons is driven by the benefits of coordinated gene expression and regulation. Direct evidence that coexpression increases the individual's fitness enough to ensure operon formation and maintenance is, however, still lacking. Here, a previously described quantitative model of the network that controls the transcription factor sigma(F) during sporulation in Bacillus subtilis is employed to quantify the benefits arising from both organization of the sporulation genes into the spoIIA operon and from translational coupling. The analysis shows that operon organization, together with translational coupling, is important because of the inherent stochastic nature of gene expression, which skews the ratios between protein concentrations in the absence of co-regulation. The predicted impact of different forms of gene regulation on fitness and survival agrees quantitatively with published sporulation efficiencies.

  15. The SigmaR1 chaperone drives breast and colorectal cancer cell migration by tuning SK3-dependent Ca2+ homeostasis.

    PubMed

    Gueguinou, M; Crottès, D; Chantôme, A; Rapetti-Mauss, R; Potier-Cartereau, M; Clarysse, L; Girault, A; Fourbon, Y; Jézéquel, P; Guérin-Charbonnel, C; Fromont, G; Martin, P; Pellissier, B; Schiappa, R; Chamorey, E; Mignen, O; Uguen, A; Borgese, F; Vandier, C; Soriani, O

    2017-06-22

    The remodeling of calcium homeostasis contributes to the cancer hallmarks and the molecular mechanisms involved in calcium channel regulation in tumors remain to be characterized. Here, we report that SigmaR1, a stress-activated chaperone, is required to increase calcium influx by triggering the coupling between SK3, a Ca 2+ -activated K + channel (KCNN3) and the voltage-independent calcium channel Orai1. We show that SigmaR1 physically binds SK3 in BC cells. Inhibition of SigmaR1 activity, either by molecular silencing or by the use of sigma ligand (igmesine), decreased SK3 current and Ca 2+ entry in breast cancer (BC) and colorectal cancer (CRC) cells. Interestingly, SigmaR1 inhibition diminished SK3 and/or Orai1 levels in lipid nanodomains isolated from BC cells. Analyses of tissue microarray from CRC patients showed higher SigmaR1 expression levels in cancer samples and a correlation with tumor grade. Moreover, the exploration of a cohort of 4937 BC patients indicated that high expression of SigmaR1 and Orai1 channels was significantly correlated to a lower overall survival. As the SK3/Orai1 tandem drives invasive process in CRC and bone metastasis progression in BC, our results may inaugurate innovative therapeutic approaches targeting SigmaR1 to control the remodeling of Ca 2+ homeostasis in epithelial cancers.

  16. Lean Six Sigma implementation and organizational culture.

    PubMed

    Knapp, Susan

    2015-01-01

    The purpose of this paper is to examine the relationship between four organizational cultural types defined by the Competing Values Framework and three Lean Six Sigma implementation components - management involvement, use of Lean Six Sigma methods and Lean Six Sigma infrastructure. The study involved surveying 446 human resource and quality managers from 223 hospitals located in Maine, New Hampshire, Vermont, Massachusetts and Rhode Island using the Organizational Culture Assessment Instrument. Findings - In total, 104 completed responses were received and analyzed using multivariate analysis of variance. Follow-up analysis of variances showed management support was significant, F(3, 100)=4.89, p < 0.01, η2=1.28; infrastructure was not significant, F(3, 100)=1.55, p=0.21, η2=0.05; and using Lean Six Sigma methods was also not significant, F(3, 100)=1.34, p=0.26, η2=0.04. Post hoc analysis identified group and development cultures having significant interactions with management support. The relationship between organizational culture and Lean Six Sigma in hospitals provides information on how specific cultural characteristics impact the Lean Six Sigma initiative key components. This information assists hospital staff who are considering implementing quality initiatives by providing an understanding of what cultural values correspond to effective Lean Six Sigma implementation. Managers understanding the quality initiative cultural underpinnings, are attentive to the culture-shared values and norm's influence can utilize strategies to better implement Lean Six Sigma.

  17. Synthesis of a new class of carbon-bonded anionic sigma complexes with 1,3-dimethyl-2,6-dioxo-5-(2,4,6-trinitrophenyl)-1,2,3,6-tetrahydropyrimidin-4-olate moiety as insensitive high energy density materials -- implications from impact sensitivity and thermal testings.

    PubMed

    Kulandaiya, Rajamani; Doraisamyraja, Kalaivani

    2015-01-01

    Poly nitro aromatic compounds are high energy density materials. Carbon-bonded anionic sigma complexes derived from them have remarkable thermal stability. At present there is a strong requirement for thermally stable insensitive high energy density materials (IHEDMs) in the energetic field which necessitates the present investigation. Three new carbon-bonded anionic sigma complexes were synthesized from 2-chloro-1,3,5-trinitrobenzene, 1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione (1,3-dimethylbarbituric acid) and bases such as triethanolamine, pyridine and N,N-diethylaniline, characterized by UV-VIS, IR, (1)H NMR, (13)C NMR and elemental analysis data. Their molecular structures were further ascertained through single crystal X-ray diffraction studies. TGA/DTA testings were undertaken at four different heating rates (5, 10, 20 and 40 K/min) and energy of activation was determined employing Ozawa and Kissinger plots. The reported carbon-bonded anionic sigma complexes were prepared through single pot synthesis in good yield with high purity. These complexes are molecular salts comprise of cation and anion moieties. Because of the salt-like nature, they are highly stable upto 300°C and decompose in two stages on further heating. They are stable towards impact of 2 kg mass hammer upto height limit (160 cm) of the instrument. The delocalization of the negative charge and various hydrogen bonds noticed in their crystals are the added factors of their thermal stability. The new insensitive high energy density materials of the present findings may receive attention in the field of energetics in future. Graphical AbstractA new class of carbon-bonded anionic sigma complexes as insensitive high energy density materials.

  18. Construction of in vitro transcription system for Corynebacterium glutamicum and its use in the recognition of promoters of different classes.

    PubMed

    Holátko, Jiří; Silar, Radoslav; Rabatinová, Alžbeta; Sanderová, Hana; Halada, Petr; Nešvera, Jan; Krásný, Libor; Pátek, Miroslav

    2012-10-01

    To facilitate transcription studies in Corynebacterium glutamicum, we have developed an in vitro transcription system for this bacterium used as an industrial producer of amino acids and a model organism for actinobacteria. This system consists of C. glutamicum RNA polymerase (RNAP) core (α2, β, β'), a sigma factor and a promoter-carrying DNA template, that is specifically recognized by the RNAP holoenzyme formed. The RNAP core was purified from the C. glutamicum strain with the modified rpoC gene, which produced His-tagged β' subunit. The C. glutamicum sigA and sigH genes were cloned and overexpressed using the Escherichia coli plasmid vector, and the sigma subunits σ(A) and σ(H) were purified by affinity chromatography. Using the reconstituted C. glutamicum holo-RNAPs, recognition of the σ(A)- and σ(H)-dependent promoters and synthesis of the specific transcripts was demonstrated. The developed in vitro transcription system is a novel tool that can be used to directly prove the specific recognition of a promoter by the particular σ factor(s) and to analyze transcriptional control by various regulatory proteins in C. glutamicum.

  19. Gene Expression Profiling of Transcription Factors of Helicobacter pylori under Different Environmental Conditions.

    PubMed

    De la Cruz, Miguel A; Ares, Miguel A; von Bargen, Kristine; Panunzi, Leonardo G; Martínez-Cruz, Jessica; Valdez-Salazar, Hilda A; Jiménez-Galicia, César; Torres, Javier

    2017-01-01

    Helicobacter pylori is a Gram-negative bacterium that colonizes the human gastric mucosa and causes peptic ulcers and gastric carcinoma. H. pylori strain 26695 has a small genome (1.67 Mb), which codes for few known transcriptional regulators that control bacterial metabolism and virulence. We analyzed by qRT-PCR the expression of 16 transcriptional regulators in H. pylori 26695, including the three sigma factors under different environmental conditions. When bacteria were exposed to acidic pH, urea, nickel, or iron, the sigma factors were differentially expressed with a particularly strong induction of fliA . The regulatory genes hrcA, hup , and crdR were highly induced in the presence of urea, nickel, and iron. In terms of biofilm formation fliA, flgR, hp1021, fur, nikR , and crdR were induced in sessile bacteria. Transcriptional expression levels of rpoD, flgR, hspR, hp1043 , and cheY were increased in contact with AGS epithelial cells. Kanamycin, chloramphenicol, and tetracycline increased or decreased expression of regulatory genes, showing that these antibiotics affect the transcription of H. pylori . Our data indicate that environmental cues which may be present in the human stomach modulate H. pylori transcription.

  20. Pip, a Novel Activator of Phenazine Biosynthesis in Pseudomonas chlororaphis PCL1391▿ †

    PubMed Central

    Girard, Geneviève; Barends, Sharief; Rigali, Sébastien; van Rij, E. Tjeerd; Lugtenberg, Ben J. J.; Bloemberg, Guido V.

    2006-01-01

    Secondary metabolites are important factors for interactions between bacteria and other organisms. Pseudomonas chlororaphis PCL1391 produces the antifungal secondary metabolite phenazine-1-carboxamide (PCN) that inhibits growth of Fusarium oxysporum f. sp. radius lycopersici the causative agent of tomato foot and root rot. Our previous work unraveled a cascade of genes regulating the PCN biosynthesis operon, phzABCDEFGH. Via a genetic screen, we identify in this study a novel TetR/AcrR regulator, named Pip (phenazine inducing protein), which is essential for PCN biosynthesis. A combination of a phenotypical characterization of a pip mutant, in trans complementation assays of various mutant strains, and electrophoretic mobility shift assays identified Pip as the fifth DNA-binding protein so far involved in regulation of PCN biosynthesis. In this regulatory pathway, Pip is positioned downstream of PsrA (Pseudomonas sigma factor regulator) and the stationary-phase sigma factor RpoS, while it is upstream of the quorum-sensing system PhzI/PhzR. These findings provide further evidence that the path leading to the expression of secondary metabolism gene clusters in Pseudomonas species is highly complex. PMID:16997957

  1. A Framework for Six Sigma Project Selection in Higher Educational Institutions, Using a Weighted Scorecard Approach

    ERIC Educational Resources Information Center

    Holmes, Monica C.; Jenicke, Lawrence O.; Hempel, Jessica L.

    2015-01-01

    Purpose: This paper discusses the importance of the Six Sigma selection process, describes a Six Sigma project in a higher educational institution and presents a weighted scorecard approach for project selection. Design/Methodology/Approach: A case study of the Six Sigma approach being used to improve student support at a university computer help…

  2. An Application of Six Sigma to Reduce Supplier Quality Cost

    NASA Astrophysics Data System (ADS)

    Gaikwad, Lokpriya Mohanrao; Teli, Shivagond Nagappa; Majali, Vijay Shashikant; Bhushi, Umesh Mahadevappa

    2016-01-01

    This article presents an application of Six Sigma to reduce supplier quality cost in manufacturing industry. Although there is a wider acceptance of Six Sigma in many organizations today, there is still a lack of in-depth case study of Six Sigma. For the present research the case study methodology was used. The company decided to reduce quality cost and improve selected processes using Six Sigma methodologies. Regarding the fact that there is a lack of case studies dealing with Six Sigma especially in individual manufacturing organization this article could be of great importance also for the practitioners. This paper discusses the quality and productivity improvement in a supplier enterprise through a case study. The paper deals with an application of Six Sigma define-measure-analyze-improve-control methodology in an industry which provides a framework to identify, quantify and eliminate sources of variation in an operational process in question, to optimize the operation variables, improve and sustain performance viz. process yield with well-executed control plans. Six Sigma improves the process performance (process yield) of the critical operational process, leading to better utilization of resources, decreases variations and maintains consistent quality of the process output.

  3. Application of Six Sigma towards improving surgical outcomes.

    PubMed

    Shukla, P J; Barreto, S G; Nadkarni, M S

    2008-01-01

    Six Sigma is a 'process excellence' tool targeting continuous improvement achieved by providing a methodology for improving key steps of a process. It is ripe for application into health care since almost all health care processes require a near-zero tolerance for mistakes. The aim of this study is to apply the Six Sigma methodology into a clinical surgical process and to assess the improvement (if any) in the outcomes and patient care. The guiding principles of Six Sigma, namely DMAIC (Define, Measure, Analyze, Improve, Control), were used to analyze the impact of double stapling technique (DST) towards improving sphincter preservation rates for rectal cancer. The analysis using the Six Sigma methodology revealed a Sigma score of 2.10 in relation to successful sphincter preservation. This score demonstrates an improvement over the previous technique (73% over previous 54%). This study represents one of the first clinical applications of Six Sigma in the surgical field. By understanding, accepting, and applying the principles of Six Sigma, we have an opportunity to transfer a very successful management philosophy to facilitate the identification of key steps that can improve outcomes and ultimately patient safety and the quality of surgical care provided.

  4. Observation of Bs production at the Y(5S) resonance.

    PubMed

    Bonvicini, G; Cinabro, D; Dubrovin, M; Lincoln, A; Bornheim, A; Pappas, S P; Weinstein, A J; Asner, D M; Edwards, K W; Briere, R A; Chen, G P; Chen, J; Ferguson, T; Tatishvili, G; Vogel, H; Watkins, M E; Rosner, J L; Adam, N E; Alexander, J P; Berkelman, K; Cassel, D G; Crede, V; Duboscq, J E; Ecklund, K M; Ehrlich, R; Fields, L; Gibbons, L; Gittelman, B; Gray, R; Gray, S W; Hartill, D L; Heltsley, B K; Hertz, D; Jones, C D; Kandaswamy, J; Kreinick, D L; Kuznetsov, V E; Mahlke-Krüger, H; Meyer, T O; Onyisi, P U E; Patterson, J R; Peterson, D; Phillips, E A; Pivarski, J; Riley, D; Ryd, A; Sadoff, A J; Schwarthoff, H; Shi, X; Shepherd, M R; Stroiney, S; Sun, W M; Urner, D; Wilksen, T; Weaver, K M; Weinberger, M; Athar, S B; Avery, P; Breva-Newell, L; Patel, R; Potlia, V; Stoeck, H; Yelton, J; Rubin, P; Cawlfield, C; Eisenstein, B I; Gollin, G D; Karliner, I; Kim, D; Lowrey, N; Naik, P; Sedlack, C; Selen, M; White, E J; Williams, J; Wiss, J; Besson, D; Pedlar, T K; Cronin-Hennessy, D; Gao, K Y; Gong, D T; Hietala, J; Kubota, Y; Klein, T; Lang, B W; Li, S Z; Poling, R; Scott, A W; Smith, A; Dobbs, S; Metreveli, Z; Seth, K K; Tomaradze, A; Zweber, P; Ernst, J; Arms, K; Severini, H; Dytman, S A; Love, W; Mehrabyan, S; Mueller, J A; Savinov, V; Li, Z; Lopez, A; Mendez, H; Ramirez, J; Huang, G S; Miller, D H; Pavlunin, V; Sanghi, B; Shipsey, I P J; Adams, G S; Anderson, M; Cummings, J P; Danko, I; Napolitano, J; He, Q; Muramatsu, H; Park, C S; Thorndike, E H; Coan, T E; Gao, Y S; Liu, F; Maravin, Y; Artuso, M; Boulahouache, C; Blusk, S; Butt, J; Dorjkhaidav, O; Li, J; Menaa, N; Mountain, R; Nandakumar, R; Randrianarivony, K; Redjimi, R; Sia, R; Skwarnicki, T; Stone, S; Wang, J C; Zhang, K; Csorna, S E

    2006-01-20

    Using the CLEO detector at the Cornell Electron Storage Ring, we have observed the Bs meson in e+e- annihilation at the Y(5S) resonance. We find 14 candidates consistent with Bs decays into final states with a J/psi or a Ds(*)- . The probability that we have observed a background fluctuation is less than 8 x 10(-10) . We have established that at the energy of the Y(5S) resonance Bs production proceeds predominantly through the creation of Bs*Bs* pairs. We find sigma(e+e- --> Bs*Bs*) = [0.11(-0.03))(+0.04)(stat) +/- 0.02(syst)]nb , and set the following limits: sigma(e+e- --> BsBs)/ sigma(e+ e- --> Bs*Bs*) <0.16 and [sigma(e+e- --> BsBs*) + sigma(e+e- --> Bs*Bs)]/sigma(e+e- -->Bs*Bs*) < 0.16 (90% C.L.). The mass of the Bs* meson is measured to be M(Bs*) = [5.414+/- 0.001(stat) +/- 0.003(syst)] GeV/c2 .

  5. A clinical and radiostereometric study of the cemented PFC-sigma prosthesis: a 5-year study of 29 cases with a fixed bearing.

    PubMed

    von Schewelov, Thord; Besjakov, Jack; Sanzén, Lennart; Carlsson, Ake

    2009-07-01

    The press-fit condylar (PFC) cruciate-retaining total knee prosthesis is well documented in the literature. In 1997, a modification of the femoral component was introduced, and the prosthesis was renamed PFC-Sigma. The alteration may influence the migratory and rotational pattern of the tibial component and thus long-time survival rate. In this radiostereometric analysis, we found that the micromotion of the PFC-Sigma prosthesis differs slightly from the original PFC design, an advantage of the PFC-Sigma prosthesis. The median maximum total point motion at 5 years was 0.64 mm for the PFC-Sigma design and 0.79 mm for the previous version of PFC (P = .9). However, the PFC-Sigma rotated less around the transverse (x) axis than did the PFC (medians, 0.22 mm and 0.48 mm, respectively; P = .04). From the radiostereometric, radiographic, and clinical data, we conclude that the PFC-Sigma knee prosthesis can be used with confidence.

  6. A numerical procedure for recovering true scattering coefficients from measurements with wide-beam antennas

    NASA Technical Reports Server (NTRS)

    Wang, Qinglin; Gogineni, S. P.

    1991-01-01

    A numerical procedure for estimating the true scattering coefficient, sigma(sup 0), from measurements made using wide-beam antennas. The use of wide-beam antennas results in an inaccurate estimate of sigma(sup 0) if the narrow-beam approximation is used in the retrieval process for sigma(sup 0). To reduce this error, a correction procedure was proposed that estimates the error resulting from the narrow-beam approximation and uses the error to obtain a more accurate estimate of sigma(sup 0). An exponential model was assumed to take into account the variation of sigma(sup 0) with incidence angles, and the model parameters are estimated from measured data. Based on the model and knowledge of the antenna pattern, the procedure calculates the error due to the narrow-beam approximation. The procedure is shown to provide a significant improvement in estimation of sigma(sup 0) obtained with wide-beam antennas. The proposed procedure is also shown insensitive to the assumed sigma(sup 0) model.

  7. Lean sigma--will it work for healthcare?

    PubMed

    Bahensky, James A; Roe, Janet; Bolton, Romy

    2005-01-01

    The manufacturing industry has been using Lean Sigma for years in pursuit of continuous improvement to obtain a competitive advantage. The objectives of these efforts are to use the Lean techniques for reducing cycle times and the Six Sigma concepts for reducing product defects. The Iowa Business Council with several advocates worked with the University of Iowa Hospital and Clinics (UIHC) and two other Iowa hospitals to determine whether Lean Sigma is adaptable in healthcare. A team of 15 people at UIHC used the Kaizen Breakthrough Methodology over a five-day period in an aggressive identification and elimination of non-value added activities in Radiology CT scanning. The results exceeded the initial project objectives and indicated that Lean Sigma is applicable in healthcare. Overall, the Lean Sigma project increased revenue by approximately $750,000 per year. The Kaizen process proved to be successful and interesting. Within three days, the team installed new work flow processes. This implementation-oriented approach is what differentiates Lean Sigma from other quality improvement processes.

  8. Induction of a robust immunity response against novel duck reovirus in ducklings using a subunit vaccine of sigma C protein

    PubMed Central

    Bi, Zhuangli; Zhu, Yingqi; Chen, Zongyan; Li, Chuanfeng; Wang, Yong; Wang, Guijun; Liu, Guangqing

    2016-01-01

    Novel duck reovirus (NDRV) disease emerged in China in 2011 and continues to cause high morbidity and about 5.0 to 50% mortality in ducklings. Currently there are no approved vaccines for the virus. This study aimed to assess the efficacy of a new vaccine created from the baculovirus and sigma C gene against NDRV. In this study, a recombinant baculovirus containing the sigma C gene was constructed, and the purified protein was used as a vaccine candidate in ducklings. The efficacy of sigma C vaccine was estimated according to humoral immune responses, cellular immune response and protection against NDRV challenge. The results showed that sigma C was highly expressed in Sf9 cells. Robust humoral and cellular immune responses were induced in all ducklings immunized with the recombinant sigma C protein. Moreover, 100% protection against lethal challenge with NDRV TH11 strain was observed. Summary, the recombinant sigma C protein could be utilized as a good candidate against NDRV infection. PMID:27974824

  9. Kinetics of O{sub 2}({sup 1{Sigma}}) formation in the reaction O{sub 2}({sup 1{Delta}}) + O{sub 2}({sup 1{Delta}}) {yields} O{sub 2}({sup 1{Sigma}}) + O{sub 2}({sup 3{Sigma}})

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zagidullin, M V; Khvatov, N A; Nyagashkin, A Yu

    2011-02-28

    The dependence of the ratio of specific powers of dimole radiation of singlet oxygen in the 634 nm band and in the b - X band of the O{sub 2}({sup 1{Sigma}}) molecule in the O{sub 2}(X) - O{sub 2}({sup 1{Delta}}) - O{sub 2}({sup 1{Sigma}}) - H{sub 2}O - CO{sub 2} mixture on the CO{sub 2} concentration is measured. As a result, the rate constant of the reaction O{sub 2}({sup 1{Delta}}) + O{sub 2}({sup 1{Delta}}) {yields} O{sub 2}({sup 1{Sigma}}) + O{sub 2}({sup 3{Sigma}}) at the temperature {approx}330 K is found to equal (4.5 {+-} 1.1) 10{sup -17} cm{sup 3} s{sup -1}.more » (active media)« less

  10. Doublet-spacing enhancement caused by {Lambda}N-{Sigma}N coupling in {sub {Lambda}L}i hypernuclear isotopes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Umeya, Atsushi; Harada, Toru; Research Center for Physics and Mathematics, Osaka Electro-Communication University, Neyagawa, Osaka 572-8530

    2011-03-15

    We theoretically investigate energy spacings of doublets in {sub {Lambda}L}i hypernuclear isotopes with A=7-10 in shell-model calculations with a {Lambda}N-{Sigma}N coupling effect. The calculated results show that the energy shifts are {Delta}{epsilon}=0.09-0.28 MeV and the {Sigma}-mixing probabilities are P{sub {Sigma}}=0.10%-0.34% in {Lambda} ground states for the isotopes because of the {Lambda}N-{Sigma}N coupling in the first-order perturbation. It is found that the energy spacing of the doublet is enhanced as a neutron number N increases; the contribution of the {Lambda}N-{Sigma}N coupling interaction is comparable to that of the {Lambda}N interaction in the neutron-rich {Lambda} hypernuclei. The coherent mechanism of this doublet-spacingmore » enhancement is also discussed in terms of Fermi-type and Gamow-Teller-type {Lambda}N-{Sigma}N couplings.« less

  11. The influence of grain boundary geometry on intergranular crack propagation in Ni[sub 3]Al

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hui Lin; Pope, D.P.

    1993-02-01

    The distribution of grain boundary types along intergranular cracks in Ni[sub 3]Al was measured, by [Sigma] value, and compared to the distribution in the bulk, using statistically significant sample sizes. It was found that low angle ([Sigma] 1) and symmetrical [Sigma]3 boundaries (twins) are particularly strong, and all high angle boundaries, independent of their [Sigma] values are weak. In particular, low [Sigma], high angle boundaries, as a group, are also weak. These results are in qualitative agreement with predictions based on the structural unit model and imply that the fracture strength of an intergranularly brittle polycrystalline aggregate can be increasedmore » only by increasing the fraction of low angle and symmetrical [Sigma]3 boundaries.« less

  12. MIT January Operational Internship Experience

    NASA Technical Reports Server (NTRS)

    Bosanac, Natasha; DeVivero, Charlie; James, Jillian; Perez-Martinez, Carla; Pino, Wendy; Wang, Andrew; Willett, Ezekiel; Williams, Kwami

    2010-01-01

    This viewgraph presentation describes the MIT January Operational Internship Experience (JOIE) program. The topics include: 1) Landing and Recovery; 2) Transportation; 3) Shuttle Processing; 4) Constellation Processing; 5) External Tank; 6) Launch Pad; 7) Ground Operations; 8) Hypergolic Propellants; 9) Environmental; 10) Logistics; 11) Six Sigma; 12) Systems Engineering; and 13) Human Factors.

  13. AlgU controls expression of virulence genes in Pseudomonas syringae pv. tomato DC3000

    USDA-ARS?s Scientific Manuscript database

    Plant pathogenic bacteria are able to integrate information about their environment and adjust gene expression to provide adaptive functions. AlgU, an ECF sigma factor encoded by Pseudomonas syringae, controls expression of genes for alginate biosynthesis and is active while the bacteria are associa...

  14. Using lean Six Sigma to improve hospital based outpatient imaging satisfaction.

    PubMed

    McDonald, Angelic P; Kirk, Randy

    2013-01-01

    Within the hospital based imaging department at Methodist Willowbrook, outpatient, inpatient, and emergency patients are all performed on the same equipment with the same staff. The critical nature of the patient is the deciding factor as to who gets done first and in what order procedures are performed. After an aggressive adoption of Intentional Tools, the imaging department was finally able to move from a two year mean Press Ganey, outpatient satisfaction average score of 91.2 and UHC percentile ranking of 37th to a mean average of 92.1 and corresponding UHC ranking of 60th percentile. It was at the 60th percentile ranking that the department flat lined. Using the Six Sigma DMAIC process, opportunity for further improvement was identified. A two week focus pilot was conducted specifically on areas identified through the Six Sigma process. The department was able to jump to 88th percentile ranking and a mean of 93.7. With pay for performance focusing on outpatient satisfaction and a financial incentive to improving and maintaining the highest scores, it was important to know where the imaging department should apply its financial resources to obtain the greatest impact.

  15. No association between the sigma receptor type 1 gene and schizophrenia: results of analysis and meta-analysis of case-control studies

    PubMed Central

    Uchida, Naohiko; Ujike, Hiroshi; Nakata, Kenji; Takaki, Manabu; Nomura, Akira; Katsu, Takeshi; Tanaka, Yuji; Imamura, Takaki; Sakai, Ayumu; Kuroda, Shigetoshi

    2003-01-01

    Background Several lines of evidence have supported possible roles of the sigma receptors in the etiology of schizophrenia and mechanisms of antipsychotic efficacy. An association study provided genetic evidence that the sigma receptor type 1 gene (SIGMAR1) was a possible susceptibility factor for schizophrenia, however, it was not replicated by a subsequent study. It is necessary to evaluate further the possibility that the SIGMAR1 gene is associated with susceptibility to schizophrenia. Methods A case-control association study between two polymorphisms of the SIGMAR1 gene, G-241T/C-240T and Gln2Pro, and schizophrenia in Japanese population, and meta-analysis including present and previous studies. Results There was no significant association of any allele or genotype of the polymorphisms with schizophrenia. Neither significant association was observed with hebephrenic or paranoid subtype of schizophrenia. Furthermore, a meta-analysis including the present and previous studies comprising 779 controls and 636 schizophrenics also revealed no significant association between the SIGMAR1 gene and schizophrenia. Conclusion In view of this evidence, it is likely that the SIGMAR1 gene does not confer susceptibility to schizophrenia. PMID:14567761

  16. No association between the sigma receptor type 1 gene and schizophrenia: results of analysis and meta-analysis of case-control studies.

    PubMed

    Uchida, Naohiko; Ujike, Hiroshi; Nakata, Kenji; Takaki, Manabu; Nomura, Akira; Katsu, Takeshi; Tanaka, Yuji; Imamura, Takaki; Sakai, Ayumu; Kuroda, Shigetoshi

    2003-10-21

    Several lines of evidence have supported possible roles of the sigma receptors in the etiology of schizophrenia and mechanisms of antipsychotic efficacy. An association study provided genetic evidence that the sigma receptor type 1 gene (SIGMAR1) was a possible susceptibility factor for schizophrenia, however, it was not replicated by a subsequent study. It is necessary to evaluate further the possibility that the SIGMAR1 gene is associated with susceptibility to schizophrenia. A case-control association study between two polymorphisms of the SIGMAR1 gene, G-241T/C-240T and Gln2Pro, and schizophrenia in Japanese population, and meta-analysis including present and previous studies. There was no significant association of any allele or genotype of the polymorphisms with schizophrenia. Neither significant association was observed with hebephrenic or paranoid subtype of schizophrenia. Furthermore, a meta-analysis including the present and previous studies comprising 779 controls and 636 schizophrenics also revealed no significant association between the SIGMAR1 gene and schizophrenia. In view of this evidence, it is likely that the SIGMAR1 gene does not confer susceptibility to schizophrenia.

  17. Gravitational microlensing - The effect of random motion of individual stars in the lensing galaxy

    NASA Technical Reports Server (NTRS)

    Kundic, Tomislav; Wambsganss, Joachim

    1993-01-01

    We investigate the influence of random motion of individual stars in the lensing galaxy on the light curve of a gravitationally lensed background quasar. We compare this with the effects of the transverse motion of the galaxy. We find that three-dimensional random motion of stars with a velocity dispersion sigma in each dimension is more effective in producing 'peaks' in a microlensed light curve by a factor a about 1.3 than motion of the galaxy with a transverse velocity v(t) = sigma. This effectiveness parameter a seems to depend only weakly on the surface mass density. With an assumed transverse velocity of v(t) = 600 km/s of the galaxy lensing the QSO 2237+0305 and a measured velocity dispersion of sigma = 215 km/s, the expected rate of maxima in the light curves calculated for bulk motion alone has to be increased by about 10 percent due to the random motion of stars. As a consequence, the average time interval Delta t between two high-magnification events is smaller than the time interval Delta(t) bulk, calculated for bulk motion alone, Delta t about 0.9 Delta(t) bulk.

  18. Synthesis and pharmacological evaluation of indole-based sigma receptor ligands

    PubMed Central

    Mésangeau, Christophe; Amata, Emanuele; Alsharif, Walid; Seminerio, Michael J.; Robson, Matthew J.; Matsumoto, Rae R.; Poupaert, Jacques H.; McCurdy, Christopher R.

    2011-01-01

    A series of novel indole-based analogues were prepared and their affinities for sigma receptors were determined using in vitro radioligand binding assays. The results of this study identified several compounds with nanomolar sigma-2 affinity and significant selectivity over sigma-1 receptors. In particular, 2-(4-(3-(4-fluorophenyl)indol-1-yl)butyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (9f) was found to display high affinity at sigma-2 receptors with good selectivity (σ-1/σ-2 = 395). The pharmacological binding profile for this compound was established with other relevant nonsigma sites. PMID:21899931

  19. Sigma Metrics Across the Total Testing Process.

    PubMed

    Charuruks, Navapun

    2017-03-01

    Laboratory quality control has been developed for several decades to ensure patients' safety, from a statistical quality control focus on the analytical phase to total laboratory processes. The sigma concept provides a convenient way to quantify the number of errors in extra-analytical and analytical phases through the defect per million and sigma metric equation. Participation in a sigma verification program can be a convenient way to monitor analytical performance continuous quality improvement. Improvement of sigma-scale performance has been shown from our data. New tools and techniques for integration are needed. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Analysis of p21-Activated Kinase Function in Neurofibromatosis Type 2

    DTIC Science & Technology

    2010-01-01

    6,6′-dithiobis) for 10 min, before stimulation with 10% FCS (PAA, Pasching, Austria), 0.5 μM forskolin (Sigma-Aldrich, St. Louis, USA), 10 nM β1...0.5 μM forskolin (Sigma-Aldrich), 10 nM β1- heregulin144–244 (Genentech), 0.5 mM 3-isobutyl-1-methylxanthin (IBMX, Sigma-Aldrich) and 2.5 μg/ml...0.5 μM forskolin (Sigma-Aldrich), 10 nM β1-heregulin144–244 (Genentech), 0.5 mM 3-isobutyl-1-methylxanthin and 2.5 μg/ml insulin (both from Sigma

  1. Ground state of excitonic molecules by the Green's-function Monte Carlo method

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lee, M.A.; Vashishta, P.; Kalia, R.K.

    1983-12-26

    The ground-state energy of excitonic molecules is evaluated as a function of the ratio of electron and hole masses, sigma, with use of the Green's-function Monte Carlo method. For all sigma, the Green's-function Monte Carlo energies are significantly lower than the variational estimates and in favorable agreement with experiments. In excitonic rydbergs, the binding energy of the positronium molecule (sigma = 1) is predicted to be -0.06 and for sigma<<1, the Green's-function Monte Carlo energies agree with the ''exact'' limiting behavior, E = -2.346+0.764sigma.

  2. Automated system for measurement, collection and processing of hydrometeorological data aboard scientific research vessels of the GUGMS (SIGMA-s)

    NASA Technical Reports Server (NTRS)

    Borisenkov, Y. P.; Fedorov, O. M.

    1974-01-01

    A report is made on the automated system known as SIGMA-s for the measurement, collection, and processing of hydrometeorological data aboard scientific research vessels of the Hydrometeorological Service. The various components of the system and the interfacing between them are described, as well as the projects that the system is equipped to handle.

  3. Assessing precision, bias and sigma-metrics of 53 measurands of the Alinity ci system.

    PubMed

    Westgard, Sten; Petrides, Victoria; Schneider, Sharon; Berman, Marvin; Herzogenrath, Jörg; Orzechowski, Anthony

    2017-12-01

    Assay performance is dependent on the accuracy and precision of a given method. These attributes can be combined into an analytical Sigma-metric, providing a simple value for laboratorians to use in evaluating a test method's capability to meet its analytical quality requirements. Sigma-metrics were determined for 37 clinical chemistry assays, 13 immunoassays, and 3 ICT methods on the Alinity ci system. Analytical Performance Specifications were defined for the assays, following a rationale of using CLIA goals first, then Ricos Desirable goals when CLIA did not regulate the method, and then other sources if the Ricos Desirable goal was unrealistic. A precision study was conducted at Abbott on each assay using the Alinity ci system following the CLSI EP05-A2 protocol. Bias was estimated following the CLSI EP09-A3 protocol using samples with concentrations spanning the assay's measuring interval tested in duplicate on the Alinity ci system and ARCHITECT c8000 and i2000 SR systems, where testing was also performed at Abbott. Using the regression model, the %bias was estimated at an important medical decisions point. Then the Sigma-metric was estimated for each assay and was plotted on a method decision chart. The Sigma-metric was calculated using the equation: Sigma-metric=(%TEa-|%bias|)/%CV. The Sigma-metrics and Normalized Method Decision charts demonstrate that a majority of the Alinity assays perform at least at five Sigma or higher, at or near critical medical decision levels. More than 90% of the assays performed at Five and Six Sigma. None performed below Three Sigma. Sigma-metrics plotted on Normalized Method Decision charts provide useful evaluations of performance. The majority of Alinity ci system assays had sigma values >5 and thus laboratories can expect excellent or world class performance. Laboratorians can use these tools as aids in choosing high-quality products, further contributing to the delivery of excellent quality healthcare for patients. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  4. Expression pattern of the type 1 sigma receptor in the brain and identity of critical anionic amino acid residues in the ligand-binding domain of the receptor.

    PubMed

    Seth, P; Ganapathy, M E; Conway, S J; Bridges, C D; Smith, S B; Casellas, P; Ganapathy, V

    2001-07-25

    The type 1 sigma receptor (sigmaR1) has been shown to participate in a variety of functions in the central nervous system. To identify the specific regions of the brain that are involved in sigmaR1 function, we analyzed the expression pattern of the receptor mRNA in the mouse brain by in situ hybridization. SigmaR1 mRNA was detectable primarily in the cerebral cortex, hippocampus, and Purkinje cells of cerebellum. To identify the critical anionic amino acid residues in the ligand-binding domain of sigmaR1, we employed two different approaches: chemical modification of anionic amino acid residues and site-directed mutagenesis. Chemical modification of anionic amino acids in sigmaR1 with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide reduced the ligand-binding activity markedly. Since it is known that a splice variant of this receptor which lacks exon 3 does not have the ability to bind sigma ligands, the ligand-binding domain with its critical anionic amino acid residues is likely to be present in or around the region coded by exon 3. Therefore, each of the anionic amino acids in this region was mutated individually and the influence of each mutation on ligand binding was assessed. These studies have identified two anionic amino acids, D126 and E172, that are obligatory for ligand binding. Even though the ligand-binding function was abolished by these two mutations, the expression of these mutants was normal at the protein level. These results show that sigmaR1 is expressed at high levels in specific areas of the brain that are involved in memory, emotion and motor functions. The results also provide important information on the chemical nature of the ligand-binding site of sigmaR1 that may be of use in the design of sigmaR1-specific ligands with potential for modulation of sigmaR1-related brain functions.

  5. The metal-carbonyl bond in Ni(CO)4 and Fe(CO)5 - A clear-cut analysis

    NASA Technical Reports Server (NTRS)

    Bauschlicher, C. W., Jr.; Bagus, P. S.

    1984-01-01

    A detailed analysis of the metal-carbonyl bonding in Ni(CO)4 and Fe(CO)5, based on the newly developed contained space orbital variation (CSOV) method, is carried out to investigate various contributing factors to the interaction. Three aspects about the metal-CO interaction are presented: (1) the frozen orbital repulsion between the metal 4s and the CO is large; (2) the metal to CO pi donation is energetically much more important than the CO to the metal sigma donation; and (3) the metal 4s and 4p orbitals make a very small contribution (smaller than 0.4 eV) to the interaction energy; the largest portion of this contribution arises from the CO to metal sigma donation.

  6. Shortening anomalies in supersymmetric theories

    DOE PAGES

    Gomis, Jaume; Komargodski, Zohar; Ooguri, Hirosi; ...

    2017-01-17

    We present new anomalies in two-dimensional N = (2, 2) superconformal theories. They obstruct the shortening conditions of chiral and twisted chiral multiplets at coincident points. This implies that marginal couplings cannot be promoted to background superfields in short representations. Therefore, standard results that follow from N = (2, 2) spurion analysis are invalidated. These anomalies appear only if supersymmetry is enhanced beyond N = (2; 2). These anomalies explain why the conformal manifolds of the K 3 and T 4 sigma models are not Kähler and do not factorize into chiral and twisted chiral moduli spaces and why theremore » are no N = (2, 2) gauged linear sigma models that cover these conformal manifolds. We also present these results from the point of view of the Riemann curvature of conformal manifolds.« less

  7. Shortening anomalies in supersymmetric theories

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gomis, Jaume; Komargodski, Zohar; Ooguri, Hirosi

    We present new anomalies in two-dimensional N = (2, 2) superconformal theories. They obstruct the shortening conditions of chiral and twisted chiral multiplets at coincident points. This implies that marginal couplings cannot be promoted to background superfields in short representations. Therefore, standard results that follow from N = (2, 2) spurion analysis are invalidated. These anomalies appear only if supersymmetry is enhanced beyond N = (2; 2). These anomalies explain why the conformal manifolds of the K 3 and T 4 sigma models are not Kähler and do not factorize into chiral and twisted chiral moduli spaces and why theremore » are no N = (2, 2) gauged linear sigma models that cover these conformal manifolds. We also present these results from the point of view of the Riemann curvature of conformal manifolds.« less

  8. The Zeeman effect in the (0,0) band of the A 7Pi-X 7Sigma(+) transition of manganese monohydride, MnH.

    PubMed

    Steimle, Timothy C; Wang, Hailing; Gengler, Jamie J; Stoll, Michael; Meijer, Gerard

    2008-10-28

    The Zeeman tuning of the P(1)(0) line (nu=17 568.35 cm(-1)) of the A (7)Pi-X (7)Sigma(+) (0,0) band of manganese monohydride, MnH, has been investigated. The laser induced fluorescence spectrum of a supersonic molecular beam sample was recorded at a resolution of approximately 40 MHz and with field strengths of up to 362.0 mT. The observed spectrum was successfully fitted using a traditional effective Zeeman Hamiltonian to determine an effective magnetic g-factor for the J=2 level of the F(1)-spin component of the A (7)Pi(v=0) state. Spectral predictions of the P(1)(0) line at field strengths used in magnetic trapping experiments are presented.

  9. The Sigma-1 Receptor as a Pluripotent Modulator in Living Systems.

    PubMed

    Su, Tsung-Ping; Su, Tzu-Chieh; Nakamura, Yoki; Tsai, Shang-Yi

    2016-04-01

    The sigma-1 receptor (Sig-1R) is an endoplasmic reticulum (ER) protein that resides specifically in the mitochondria-associated endoplasmic reticulum (ER) membrane (MAM), an interface between ER and mitochondria. In addition to being able to translocate to the plasma membrane (PM) to interact with ion channels and other receptors, Sig-1R also occurs at the nuclear envelope, where it recruits chromatin-remodeling factors to affect the transcription of genes. Sig-1Rs have also been reported to interact with other membranous or soluble proteins at other loci, including the cytosol, and to be involved in several central nervous system (CNS) diseases. Here, we propose that Sig-1R is a pluripotent modulator with resultant multiple functional manifestations in living systems. Published by Elsevier Ltd.

  10. Electro-deposition painting process improvement of cab truck by Six Sigma concept

    NASA Astrophysics Data System (ADS)

    Kawitu, Kitiya; Chutima, Parames

    2017-06-01

    The case study company is a manufacturer of trucks and currently facing a high rework cost due to the thickness of the electro-deposited paint (EDP) of the truck cab is lower than standard. In addition, the process capability is very low. The Six Sigma concept consisting of 5 phases (DMAIC) is applied to determine new parameter settings for each significant controllable factor. After the improvement, EDP thickness of the truck cab increases from 17.88μ to 20μ (i.e. standard = 20 ± 3μ). Moreover, the process capability indexes (Cp and Cpk) are increased from 0.9 to 1.43, and from 0.27 to 1.43, respectively. This improvement could save the rework cost about 1.6M THB per year.

  11. Sigma-1 Receptor as a Pluripotent Modulator in the Living System

    PubMed Central

    Su, Tsung-Ping; Su, Tzu-Chieh; Nakamura, Yoki; Tsai, Shang-Yi

    2016-01-01

    The sigma-1 receptor (Sig-1R) is an endoplasmic reticulum (ER) protein resides specifically at the interface between ER and mitochondria, called the MAM, where the Sig-1R is recently reported to be involved in certain CNS diseases. In addition to being able to translocate to the plasma membrane to interact with ion channels and other receptors, the Sig-1R is found to exist at the nuclear envelope where it recruits chromatin-remodeling factors to affect the transcription of genes. As well, thorough experimental and bioinformatic means, Sig-1Rs are reported to interact with other membranous or soluble proteins at other loci, including the cytosol. We propose that the Sig-1R is a pluripotent modulator with resultant multiple functional manifestations in the living system. PMID:26869505

  12. The effect of the sigma-1 receptor selective compound LS-1-137 on the DOI-induced head twitch response in mice.

    PubMed

    Malik, Maninder; Rangel-Barajas, Claudia; Mach, Robert H; Luedtke, Robert R

    2016-09-01

    Several receptor mediated pathways have been shown to modulate the murine head twitch response (HTR). However, the role of sigma receptors in the murine (±)-2,5-dimethoxy-4-iodoamphetamine (DOI)-induced HTR has not been previously investigated. We examined the ability of LS-1-137, a novel sigma-1 vs. sigma-2 receptor selective phenylacetamide, to modulate the DOI-induced HTR in DBA/2J mice. We also assessed the in vivo efficacy of reference sigma-1 receptor antagonists and agonists PRE-084 and PPCC. The effect of the sigma-2 receptor selective antagonist RHM-1-86 was also examined. Rotarod analysis was performed to monitor motor coordination after LS-1-137 administration. Radioligand binding techniques were used to determine the affinity of LS-1-137 at 5-HT2A and 5-HT2C receptors. LS-1-137 and the sigma-1 receptor antagonists haloperidol and BD 1047 were able to attenuate a DOI-induced HTR, indicating that LS-1-137 was acting in vivo as a sigma-1 receptor antagonist. LS-1-137 did not compromise rotarod performance within a dose range capable of attenuating the effects of DOI. Radioligand binding studies indicate that LS-1-137 exhibits low affinity binding at both 5-HT2A and 5-HT2C receptors. Based upon the results from these and our previous studies, LS-1-137 is a neuroprotective agent that attenuates the murine DOI-induced HTR independent of activity at 5-HT2 receptor subtypes, D2-like dopamine receptors, sigma-2 receptors and NMDA receptors. LS-1-137 appears to act as a sigma-1 receptor antagonist to inhibit the DOI-induced HTR. Therefore, the DOI-induced HTR can be used to assess the in vivo efficacy of sigma-1 receptor selective compounds. Copyright © 2016. Published by Elsevier Inc.

  13. Evaluating new HbA1c methods for adoption by the IFCC and NGSP reference networks using international quality targets.

    PubMed

    Lenters-Westra, Erna; English, Emma

    2017-08-28

    As a reference laboratory for HbA1c, it is essential to have accurate and precise HbA1c methods covering a range of measurement principles. We report an evaluation of the Abbott Enzymatic (Architect c4000), Roche Gen.3 HbA1c (Cobas c513) and Tosoh G11 using different quality targets. The effect of hemoglobin variants, other potential interferences and the performance in comparison to both the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and the National Glycohemoglobin Standardization Program (NGSP) reference systems was assessed using certified evaluation protocols. Each of the evaluated HbA1c methods had CVs <3% in SI units and <2% in NGSP units at 46 mmol/mol (6.4%) and 72 mmol/mol (8.7%) and passed the NGSP criteria when compared with six secondary reference measurement procedures (SRMPs). Sigma was 8.6 for Abbott Enzymatic, 3.3 for Roche Cobas c513 and 6.9 for Tosoh G11. No clinically significant interference was detected for the common Hb variants for the three methods. All three methods performed well and are suitable for clinical application in the analysis of HbA1c. Partly based on the result of this study, the Abbott Enzymatic method on the Architect c4000 and the Roche Gen.3 HbA1c on the Cobas c513 are now official, certified IFCC and NGSP SRMPs in the IFCC and NGSP networks. Sigma metrics quality criteria presented in a graph distinguish between good and excellent performance.

  14. Conformationally restricted analogs of BD1008 and an antisense oligodeoxynucleotide targeting sigma1 receptors produce anti-cocaine effects in mice.

    PubMed

    Matsumoto, R R; McCracken, K A; Friedman, M J; Pouw, B; De Costa, B R; Bowen, W D

    2001-05-11

    Cocaine's ability to interact with sigma receptors suggests that these proteins mediate some of its behavioral effects. Therefore, three novel sigma receptor ligands with antagonist activity were evaluated in Swiss Webster mice: BD1018 (3S-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane), BD1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine), and LR132 (1R,2S-(+)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidinyl)cyclohexylamine). Competition binding assays demonstrated that all three compounds have high affinities for sigma1 receptors. The three compounds vary in their affinities for sigma2 receptors and exhibit negligible affinities for dopamine, opioid, GABA(A) and NMDA receptors. In behavioral studies, pre-treatment of mice with BD1018, BD1063, or LR132 significantly attenuated cocaine-induced convulsions and lethality. Moreover, post-treatment with LR132 prevented cocaine-induced lethality in a significant proportion of animals. In contrast to the protection provided by the putative antagonists, the well-characterized sigma receptor agonist di-o-tolylguanidine (DTG) and the novel sigma receptor agonist BD1031 (3R-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane) each worsened the behavioral toxicity of cocaine. At doses where alone, they produced no significant effects on locomotion, BD1018, BD1063 and LR132 significantly attenuated the locomotor stimulatory effects of cocaine. To further validate the hypothesis that the anti-cocaine effects of the novel ligands involved antagonism of sigma receptors, an antisense oligodeoxynucleotide against sigma1 receptors was also shown to significantly attenuate the convulsive and locomotor stimulatory effects of cocaine. Together, the data suggests that functional antagonism of sigma receptors is capable of attenuating a number of cocaine-induced behaviors.

  15. Limitations of the planning organ at risk volume (PRV) concept.

    PubMed

    Stroom, Joep C; Heijmen, Ben J M

    2006-09-01

    Previously, we determined a planning target volume (PTV) margin recipe for geometrical errors in radiotherapy equal to M(T) = 2 Sigma + 0.7 sigma, with Sigma and sigma standard deviations describing systematic and random errors, respectively. In this paper, we investigated margins for organs at risk (OAR), yielding the so-called planning organ at risk volume (PRV). For critical organs with a maximum dose (D(max)) constraint, we calculated margins such that D(max) in the PRV is equal to the motion averaged D(max) in the (moving) clinical target volume (CTV). We studied margins for the spinal cord in 10 head-and-neck cases and 10 lung cases, each with two different clinical plans. For critical organs with a dose-volume constraint, we also investigated whether a margin recipe was feasible. For the 20 spinal cords considered, the average margin recipe found was: M(R) = 1.6 Sigma + 0.2 sigma with variations for systematic and random errors of 1.2 Sigma to 1.8 Sigma and -0.2 sigma to 0.6 sigma, respectively. The variations were due to differences in shape and position of the dose distributions with respect to the cords. The recipe also depended significantly on the volume definition of D(max). For critical organs with a dose-volume constraint, the PRV concept appears even less useful because a margin around, e.g., the rectum changes the volume in such a manner that dose-volume constraints stop making sense. The concept of PRV for planning of radiotherapy is of limited use. Therefore, alternative ways should be developed to include geometric uncertainties of OARs in radiotherapy planning.

  16. Local and global gravitational aspects of domain wall space-times

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cvetic, M.; Griffies, S.; Soleng, H.H.

    1993-09-15

    Local and global gravitational effects induced by eternal vacuum domain walls are studied. We concentrate on thin walls between nonequal and nonpositive cosmological constants on each side of the wall. The assumption of homogeneity, isotropy, and geodesic completeness of the space-time intrinsic to the wall as described in the comoving coordinate system and the constraint that the same symmetries hold in hypersurfaces parallel to the wall yield a general [ital Ansatz] for the line element of space-time. We restrict the problem further by demanding that the wall's surface energy density, [sigma], is positive and by requiring that the infinitely thinmore » wall represents a thin-wall limit of kinklike scalar field configuration. These vacuum domain walls fall in three classes depending on the value of their [sigma]: (1) extreme walls with [sigma]=[sigma][sub ext] are planar, static walls corresponding to supersymmetric configurations, (2) nonextreme walls with [sigma]=[sigma][sub non][gt][sigma][sub ext] correspond to expanding bubbles with observers on either side of the wall being [ital inside] the bubble, and (3) ultraextreme walls with [sigma]=[sigma][sub ultra][lt][sigma][sub ext] represent the bubbles of false vacuum decay. On the sides with less negative cosmological constant, the extreme, nonextreme, and ultraextreme walls exhibit no, repulsive, and attractive effective gravitational forces,'' respectively. These gravitational forces'' are global effects not caused by local curvature. Since the nonextreme wall encloses observers on both sides, the supersymmetric system has the lowest gravitational mass accessible to outside observers. It is conjectured that similar positive mass protection occurs in all physical systems and that no finite negative mass object can exist inside the universe.« less

  17. The Impact of a Single Nucleotide Polymorphism in SIGMAR1 on Depressive Symptoms in Major Depressive Disorder and Bipolar Disorder.

    PubMed

    Mandelli, Laura; Wang, Sheng-Min; Han, Changsu; Lee, Soo-Jung; Patkar, Ashwin A; Masand, Prakash S; Pae, Chi-Un; Serretti, Alessandro

    2017-03-01

    Ample evidence suggested a role of sigma-1 receptor in affective disorders since the interaction of numerous antidepressants with sigma receptors was discovered. A recent study on Japanese subjects found a genetic variant within the encoding gene SIGMAR1 (rs1800866A>C) associated with major depressive disorder (MDD). We aimed to evaluate the same polymorphism in both MDD and bipolar disorder (BD) as well as its relationship to response to treatment with antidepressants and mood stabilizers. A total of 238 MDD patients treated for an acute episode of depression, 132 BD patients in treatment with mood stabilizers for a manic or mixed episode, and 324 controls were genotyped for rs1800866. At discharge, response to treatments was evaluated in MDD and BD patients by the Hamilton Rating Scale for Depression (HRSD) and the Young Mania Rating Score (YMRS), respectively. In our Korean sample, allele frequencies were different from those reported in other Asian and non-Asian populations. The CC genotype was associated with BD and, as a trend, with MDD. No significant effect was observed on response to antidepressants in MDD or mood stabilizers in BD, although the CC genotype was more frequent among BD patients experiencing a mixed episode. The present findings are the first to propose the putative role of genetic variants within SIGMAR1 and sigma-1 receptor in BD. Sigma-1 receptor can modulate a number of central neurotransmitter systems as well as some other signaling pathways (e.g., neurotrophin and growth factor signaling) which are seemingly involved in BD and other mood disorders.

  18. Cocaine Effects on Dopaminergic Transmission Depend on a Balance between Sigma-1 and Sigma-2 Receptor Expression.

    PubMed

    Aguinaga, David; Medrano, Mireia; Vega-Quiroga, Ignacio; Gysling, Katia; Canela, Enric I; Navarro, Gemma; Franco, Rafael

    2018-01-01

    Sigma σ 1 and σ 2 receptors are targets of cocaine. Despite sharing a similar name, the two receptors are structurally unrelated and their physiological role is unknown. Cocaine increases the level of dopamine, a key neurotransmitter in CNS motor control and reward areas. While the drug also affects dopaminergic signaling by allosteric modulations exerted by σ 1 R interacting with dopamine D 1 and D 2 receptors, the potential regulation of dopaminergic transmission by σ 2 R is also unknown. We here demonstrate that σ 2 R may form heteroreceptor complexes with D 1 but not with D 2 receptors. Remarkably σ 1 , σ 2 , and D 1 receptors may form heterotrimers with particular signaling properties. Determination of cAMP levels, MAP kinase activation and label-free assays demonstrate allosteric interactions within the trimer. Importantly, the presence of σ 2 R induces bias in signal transduction as σ 2 R ligands increase cAMP signaling whereas reduce MAP kinase activation. These effects, which are opposite to those exerted via σ 1 R, suggest that the D 1 receptor-mediated signaling depends on the degree of trimer formation and the differential balance of sigma receptor and heteroreceptor expression in acute versus chronic cocaine consumption. Although the physiological role is unknown, the heteroreceptor complex formed by σ 1 , σ 2 , and D 1 receptors arise as relevant to convey the cocaine actions on motor control and reward circuits and as a key factor in acquisition of the addictive habit.

  19. Cocaine Effects on Dopaminergic Transmission Depend on a Balance between Sigma-1 and Sigma-2 Receptor Expression

    PubMed Central

    Aguinaga, David; Medrano, Mireia; Vega-Quiroga, Ignacio; Gysling, Katia; Canela, Enric I.; Navarro, Gemma; Franco, Rafael

    2018-01-01

    Sigma σ1 and σ2 receptors are targets of cocaine. Despite sharing a similar name, the two receptors are structurally unrelated and their physiological role is unknown. Cocaine increases the level of dopamine, a key neurotransmitter in CNS motor control and reward areas. While the drug also affects dopaminergic signaling by allosteric modulations exerted by σ1R interacting with dopamine D1 and D2 receptors, the potential regulation of dopaminergic transmission by σ2R is also unknown. We here demonstrate that σ2R may form heteroreceptor complexes with D1 but not with D2 receptors. Remarkably σ1, σ2, and D1 receptors may form heterotrimers with particular signaling properties. Determination of cAMP levels, MAP kinase activation and label-free assays demonstrate allosteric interactions within the trimer. Importantly, the presence of σ2R induces bias in signal transduction as σ2R ligands increase cAMP signaling whereas reduce MAP kinase activation. These effects, which are opposite to those exerted via σ1R, suggest that the D1 receptor-mediated signaling depends on the degree of trimer formation and the differential balance of sigma receptor and heteroreceptor expression in acute versus chronic cocaine consumption. Although the physiological role is unknown, the heteroreceptor complex formed by σ1, σ2, and D1 receptors arise as relevant to convey the cocaine actions on motor control and reward circuits and as a key factor in acquisition of the addictive habit. PMID:29483862

  20. Products and mechanism of secondary organic aerosol formation from reactions of n-alkanes with OH radicals in the presence of NOx.

    PubMed

    Lim, Yong Bin; Ziemann, Paul J

    2005-12-01

    Secondary organic aerosol (SOA) formation from reactions of n-alkanes with OH radicals in the presence of NOx was investigated in an environmental chamber using a thermal desorption particle beam mass spectrometer for particle analysis. SOA consisted of both first- and higher-generation products, all of which were nitrates. Major first-generation products were sigma-hydroxynitrates, while higher-generation products consisted of dinitrates, hydroxydinitrates, and substituted tetrahydrofurans containing nitrooxy, hydroxyl, and carbonyl groups. The substituted tetrahydrofurans are formed by a series of reactions in which sigma-hydroxycarbonyls isomerize to cyclic hemiacetals, which then dehydrate to form substituted dihydrofurans (unsaturated compounds) that quickly react with OH radicals to form lower volatility products. SOA yields ranged from approximately 0.5% for C8 to approximately 53% for C15, with a sharp increase from approximately 8% for C11 to approximately 50% for C13. This was probably due to an increase in the contribution of first-generation products, as well as other factors. For example, SOA formed from the C10 reaction contained no first-generation products, while for the C15 reaction SOA was approximately 40% first-generation and approximately 60% higher-generation products, respectively. First-generation sigma-hydroxycarbonyls are especially important in SOA formation, since their subsequent reactions can rapidly form low volatility compounds. In the atmosphere, substituted dihydrofurans created from sigma-hydroxycarbonyls will primarily react with O3 or NO3 radicals, thereby opening reaction pathways not normally accessible to saturated compounds.

  1. Constitutive properties of adult mammalian cardiac muscle cells

    NASA Technical Reports Server (NTRS)

    Zile, M. R.; Richardson, K.; Cowles, M. K.; Buckley, J. M.; Koide, M.; Cowles, B. A.; Gharpuray, V.; Cooper, G. 4th

    1998-01-01

    BACKGROUND: The purpose of this study was to determine whether changes in the constitutive properties of the cardiac muscle cell play a causative role in the development of diastolic dysfunction. METHODS AND RESULTS: Cardiocytes from normal and pressure-hypertrophied cats were embedded in an agarose gel, placed on a stretching device, and subjected to a change in stress (sigma), and resultant changes in cell strain (epsilon) were measured. These measurements were used to examine the passive elastic spring, viscous damping, and myofilament activation. The passive elastic spring was assessed in protocol A by increasing the sigma on the agarose gel at a constant rate to define the cardiocyte sigma-versus-epsilon relationship. Viscous damping was assessed in protocol B from the loop area between the cardiocyte sigma-versus-epsilon relationship during an increase and then a decrease in sigma. In both protocols, myofilament activation was minimized by a reduction in [Ca2+]i. Myofilament activation effects were assessed in protocol C by defining cardiocyte sigma versus epsilon during an increase in sigma with physiological [Ca2+]i. In protocol A, the cardiocyte sigma-versus-epsilon relationship was similar in normal and hypertrophied cells. In protocol B, the loop area was greater in hypertrophied than normal cardiocytes. In protocol C, the sigma-versus-epsilon relation in hypertrophied cardiocytes was shifted to the left compared with normal cells. CONCLUSIONS: Changes in viscous damping and myofilament activation in combination may cause pressure-hypertrophied cardiocytes to resist changes in shape during diastole and contribute to diastolic dysfunction.

  2. Autofluorescence spectroscopy of oral mucosa

    NASA Astrophysics Data System (ADS)

    Majumdar, S. K.; Uppal, A.; Gupta, P. K.

    1998-06-01

    We report the results of an in-vitro study on autofluorescence from pathologically characterized normal and malignant squamous tissues from the oral cavity. The study involved biopsy samples from 47 patients with oral cancer of which 11 patients had cancer of tongue, 17 of buccal mucosa and 19 of alveolus. The results of excitation and emission spectroscopy at several wavelengths (280 nm less than or equal to (lambda) exless than or equal to 460 nm; 340 nm less than or equal to (lambda) em less than or equal to 520 nm) showed that at (lambda) ex equals 337 nm and 400 nm the mean value for the spectrally integrated fluorescence intensity [(Sigma) (lambda ) IF((lambda) )] from the normal tissue sites was about a factor of 2 larger than that from the malignant tissue sites. At other excitation wavelengths the difference in (Sigma) (lambda ) IF((lambda) ) was not statistically significant. Similarly, for (lambda) em equals 390 nm and 460 nm, the intensity of the 340 nm band of the excitation spectra from normal tissues was observed to be a factor of 2 larger than that from malignant tissues. Analysis of these results suggests that NADH concentration is higher in normal oral tissues compared to the malignant. This contrasts with our earlier observation of an reduced NADH concentration in normal sites of breast tissues vis a vis malignant sites. For the 337 nm excited emission spectra a 10-variable MVLR score (using (Sigma) (lambda ) IF((lambda) ) and normalized intensities at nine wavelengths as input parameters) provided a sensitivity and specificity of 95.7% and 93.1% over the sample size investigated.

  3. 78 FR 39339 - Importer of Controlled Substances; Notice of Registration; SA INTL GMBH C/O., Sigma Aldrich Co., LLC

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-01

    ... Registration; SA INTL GMBH C/O., Sigma Aldrich Co., LLC By Notice dated March 20, 2013, and published in the Federal Register on March 28, 2013, 78 FR 19015, SA INTL GMBH C/O., Sigma Aldrich Co. LLC., 3500 Dekalb... registration of SA INTL GMBH C/O., Sigma Aldrich Co. LLC., to import the basic classes of controlled substances...

  4. Topography of Slow Sigma Power during Sleep is Associated with Processing Speed in Preschool Children.

    PubMed

    Doucette, Margaret R; Kurth, Salome; Chevalier, Nicolas; Munakata, Yuko; LeBourgeois, Monique K

    2015-11-04

    Cognitive development is influenced by maturational changes in processing speed, a construct reflecting the rapidity of executing cognitive operations. Although cognitive ability and processing speed are linked to spindles and sigma power in the sleep electroencephalogram (EEG), little is known about such associations in early childhood, a time of major neuronal refinement. We calculated EEG power for slow (10-13 Hz) and fast (13.25-17 Hz) sigma power from all-night high-density electroencephalography (EEG) in a cross-sectional sample of healthy preschool children (n = 10, 4.3 ± 1.0 years). Processing speed was assessed as simple reaction time. On average, reaction time was 1409 ± 251 ms; slow sigma power was 4.0 ± 1.5 μV²; and fast sigma power was 0.9 ± 0.2 μV². Both slow and fast sigma power predominated over central areas. Only slow sigma power was correlated with processing speed in a large parietal electrode cluster (p < 0.05, r ranging from -0.6 to -0.8), such that greater power predicted faster reaction time. Our findings indicate regional correlates between sigma power and processing speed that are specific to early childhood and provide novel insights into the neurobiological features of the EEG that may underlie developing cognitive abilities.

  5. Quantitation of apolipoprotein epsilon gene expression by competitive polymerase chain reaction in a patient with familial apolipoprotein E deficiency.

    PubMed

    Dobmeyer, J M; Rexin, M; Dobmeyer, T S; Klein, S A; Rossol, R; Feussner, G

    1998-06-22

    A simple method of obtaining semiquantitative and reliable data on apolipoprotein (apo) sigma gene expression is described. We detected apo sigma specific sequences by reverse transcription (rT)-PCR. For quantitative measurement, an apo sigma DNA standard was produced allowing the development of a competitive PCR-method. The efficiency of RNA extraction and cDNA synthesis was controlled by quantitation of a housekeeping gene (glyceraldehyde-3-phosphatedehydrogenase, G3PDH) in separate reactions. To imitate a defined induction of apo sigma gene expression, serial twofold dilutions of total RNA were reversely transcribed and the respective cDNAs used to perform a competitive apo sigma and G3PDH PCR. The change in apo sigma cDNA and G3PDH cDNA was 1.7-2.3-fold with an expected value of 2.0-fold. Standard deviations in three independently performed experiments were within a range of < 15% of the mean, indicating low intra-assay variation and high reproducibility. To illustrate this method, apo sigma gene expression was measured in a patient with complete lack of functional active apo E in comparison to healthy controls. The method presented here might be valuable in assessment of apo sigma gene expression in human disease.

  6. Sigma receptors: biology and therapeutic potential.

    PubMed

    Guitart, Xavier; Codony, Xavier; Monroy, Xavier

    2004-07-01

    More than 20 years after the identification of the sigma receptors as a unique binding site in the brain and in the peripheral organs, several questions regarding this receptor are still open. Only one of the subtypes of the receptor has been cloned to date, but the endogenous ligand still remains unknown, and the possible association of the receptor with a conventional second messenger system is controversial. From the very beginning, the sigma receptors were associated with various central nervous system disorders such as schizophrenia or movement disorders. Today, after hundreds of papers dealing with the importance of sigma receptors in brain function, it is widely accepted that sigma receptors represent a new and different avenue in the possible pharmacological treatment of several brain-related disorders. In this review, what is known about the biology of the sigma receptor regarding its putative structure and its distribution in the central nervous system is summarized first. The role of sigma receptors regulating cellular functions and other neurotransmitter systems is also addressed, as well as a short overview of the possible endogenous ligands. Finally, although no specific sigma ligand has reached the market, different pharmacological approaches to the alleviation and treatment of several central nervous system disorders and deficits, including schizophrenia, pain, memory deficits, etc., are discussed, with an overview of different compounds and their potential therapeutic use.

  7. Elastic-mathematical theory of cells and mitochondria in swelling process. II. Effect of temperature upon modulus of elasticity of membranous material of egg cells of sea urchin, Strongylocentrotus purpuratus, and of oyster, Crassostrea virginica.

    PubMed

    Mela, M J

    1968-01-01

    The elastic behavior of the cell wall as a function of the temperature has been studied with particular attention being given to the swelling of egg cells of Strongylocentrotus purpuratus and Crassostrea virginica in different sea water concentrations at different temperatures. It was found that the modulus of elasticity is a nonlinear function of temperature. At about 12-13 degrees C the modulus of elasticity (E) is constant, independent of the stress (sigma) and strain (epsilon(nu)) which exist at the cell wall; the membranous material follows Hooke's law, and E approximately 3 x 10(7) dyn/cm(2) for S. purpuratus and C. virginica. When the temperature is higher or lower than 12-13 degrees C, the modulus of elasticity increases, and the membranous material does not follow Hooke's law, but is almost directly proportional to the stresses existing at the cell wall. On increasing the stress, the function E(sigma) = E(sigma) approaches saturation. The corresponding stress-strain diagrams, sigma = sigma(epsilon(nu)), and the graphs, E(sigma) = E(sigma) and E(sigma) = E(t) are given. The cyto-elastic phenomena at the membrane are discussed.

  8. PECHCV, PECHFV, PEFHCV and PEFHFV: A set of atmospheric, primitive equation forecast models for the Northern Hemisphere, volume 3

    NASA Technical Reports Server (NTRS)

    Wellck, R. E.; Pearce, M. L.

    1976-01-01

    As part of the SEASAT program of NASA, a set of four hemispheric, atmospheric prediction models were developed. The models, which use a polar stereographic grid in the horizontal and a sigma coordinate in the vertical, are: (1) PECHCV - five sigma layers and a 63 x 63 horizontal grid, (2) PECHFV - ten sigma layers and a 63 x 63 horizontal grid, (3) PEFHCV - five sigma layers and a 187 x 187 horizontal grid, and (4) PEFHFV - ten sigma layers and a 187 x 187 horizontal grid. The models and associated computer programs are described.

  9. Quality assurance and management in microelectronics companies: ISO 9000 versus Six Sigma

    NASA Astrophysics Data System (ADS)

    Lupan, Razvan; Kobi, Abdessamad; Robledo, Christian; Bacivarov, Ioan; Bacivarov, Angelica

    2009-01-01

    A strategy for the implementation of the Six Sigma method as an improvement solution for the ISO 9000:2000 Quality Standard is proposed. Our approach is focused on integrating the DMAIC cycle of the Six Sigma method with the PDCA process approach, highly recommended by the standard ISO 9000:2000. The Six Sigma steps applied to each part of the PDCA cycle are presented in detail, giving some tools and training examples. Based on this analysis the authors conclude that applying Six Sigma philosophy to the Quality Standard implementation process is the best way to achieve the optimal results in quality progress and therefore in customers satisfaction.

  10. Effective conductivity of suspensions of hard spheres by Brownian motion simulation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chan Kim, I.; Torquato, S.

    1991-02-15

    A generalized Brownian motion simulation technique developed by Kim and Torquato (J. Appl. Phys. {bold 68}, 3892 (1990)) is applied to compute exactly'' the effective conductivity {sigma}{sub {ital e}} of heterogeneous media composed of regular and random distributions of hard spheres of conductivity {sigma}{sub 2} in a matrix of conductivity {sigma}{sub 1} for virtually the entire volume fraction range and for several values of the conductivity ratio {alpha}={sigma}{sub 2}/{sigma}{sub 1}, including superconducting spheres ({alpha}={infinity}) and perfectly insulating spheres ({alpha}=0). A key feature of the procedure is the use of {ital first}-{ital passage}-{ital time} equations in the two homogeneous phases andmore » at the two-phase interface. The method is shown to yield {sigma}{sub {ital e}} accurately with a comparatively fast execution time. The microstructure-sensitive analytical approximation of {sigma}{sub {ital e}} for dispersions derived by Torquato (J. Appl. Phys. {bold 58}, 3790 (1985)) is shown to be in excellent agreement with our data for random suspensions for the wide range of conditions reported here.« less

  11. Sigma model Q-balls and Q-stars

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Verbin, Y.

    2007-10-15

    A new kind of Q-balls is found: Q-balls in a nonlinear sigma model. Their main properties are presented together with those of their self-gravitating generalization, sigma model Q-stars. A simple special limit of solutions which are bound by gravity alone ('sigma stars') is also discussed briefly. The analysis is based on calculating the mass, global U(1) charge and binding energy for families of solutions parametrized by the central value of the scalar field. Two kinds (differing by the potential term) of the new sigma model Q-balls and Q-stars are analyzed. They are found to share some characteristics while differing inmore » other respects like their properties for weak central scalar fields which depend strongly on the form of the potential term. They are also compared with their ordinary counterparts and although similar in some respects, significant differences are found like the existence of an upper bound on the central scalar field. A special subset of the sigma model Q-stars contains those which do not possess a flat space limit. Their relation with sigma star solutions is discussed.« less

  12. Geographic variation in the relationships of temperature, salinity or sigma sub t versus plant nutrient concentrations in the world ocean. [silicic acid, nitrate, and phosphate concentration

    NASA Technical Reports Server (NTRS)

    Kamykowski, D.; Zentara, S. J.

    1985-01-01

    A NODC data set representing all regions of the world ocean was analyzed for temperature and sigma-t relationships with nitrate, phosphate or silicic acid. Six cubic regressions were for each ten degree square of latitude and longitude containing adequate data. World maps display the locations that allow the prediction of plant nutrient concentrations from temperature or sigma-t. Geographic coverage improves along the sequence: nitrate, phosphate, and silicic acid and is better for sigma-t than for temperature. Contour maps of the approximate temperature of sigma-t at which these nitrients are no longer measurable in a parcel of water are generated, based on a percentile analysis of the temperature or sigma-t at which less than a selected amount of plant nutrient occurs. Results are stored on magnetic tape in tabular form. The global potential to predict plant nutrient concentrations from remotely sensed temperature of sigma-t and to emphasize the latitudinally and longitudinally changing phytoplankton growth environment in present and past oceans is demonstrated.

  13. Digital phased array beamforming using single-bit delta-sigma conversion with non-uniform oversampling.

    PubMed

    Kozak, M; Karaman, M

    2001-07-01

    Digital beamforming based on oversampled delta-sigma (delta sigma) analog-to-digital (A/D) conversion can reduce the overall cost, size, and power consumption of phased array front-end processing. The signal resampling involved in dynamic delta sigma beamforming, however, disrupts synchronization between the modulators and demodulator, causing significant degradation in the signal-to-noise ratio. As a solution to this, we have explored a new digital beamforming approach based on non-uniform oversampling delta sigma A/D conversion. Using this approach, the echo signals received by the transducer array are sampled at time instants determined by the beamforming timing and then digitized by single-bit delta sigma A/D conversion prior to the coherent beam summation. The timing information involves a non-uniform sampling scheme employing different clocks at each array channel. The delta sigma coded beamsums obtained by adding the delayed 1-bit coded RF echo signals are then processed through a decimation filter to produce final beamforming outputs. The performance and validity of the proposed beamforming approach are assessed by means of emulations using experimental raw RF data.

  14. [Influence of transport parameters values on volume flows in the double-membrane system].

    PubMed

    Slezak, Andrzej; Bryll, Arkadiusz

    2005-01-01

    On the basis of Kedem-Katchalsky non-linear equations for the double-membrane system, research were carried out upon the influence of the transmembrane transport parameters, i.e. hydraulic permeability (Lp), reflection (sigma) and solute (omega) coefficients on the volume flows in the double-membrane system. The membrane system was composed of two membranes Ml and Mr characterized by coefficients, respectively Lpl, sigmal, omegal and Lp(r), sigmar, omegar, that separated the solutions at concentrations Cl, Cm, Cr. In order to show the influence of the membranes parameters values on the volume flow intensity, there were calculated the following dependencies: J(v sigma) = f omega(Lp)ii, Jv = f sigma(omega r)Lp,i), Jv = f sigma(sigma(omega r Lp,li), Jv = f sigma(sigma omega l Lp,ri) , (i = l, r), in conditions of set out mechanic pressure (Pl = Pr = Po = const.) and set concentrations (Cl = Cr = C = const.). The graphical pictures of the two first equations are hyperbolas and straight lines in particular cases, whereas the graphical pictures of further two dependencies are more complex.

  15. Microwave properties and characterization of co-evaporated BSCCO thin films

    NASA Technical Reports Server (NTRS)

    Miranda, F. A.; Chorey, C. M.; Stan, M. A.; Nordgren, C. E.; Kwor, R. Y.; Kalkur, T. S.

    1993-01-01

    An extensive characterization of Bi-Sr-Ca-Cu-O (BSCCO) thin films deposited by co-evaporation on LaAlO3 and SrTiO3 substrates was performed. The films had a T(sub c) (R = O) of approximately 78 K, and were predominantly c-axis oriented, with critical current densities (J(sub c)) at 4.5 K of 1.6 x 10(exp 6) and 1.1 x 10(exp 6) A cm(sup -2), for the samples on SrTiO3 and LaAlO3, respectively. The microwave properties of the films were examined by three techniques. The complex conductivity sigma(sub *) = sigma(sub 1) - j(sigma(sub 2)) and the magnetic penetration depth (A) were measured by power transmission at 30.6 GHz; the surface resistance (R(sub s)) was measured using a cavity resonator at 58.9 GHz, and the transmission line losses were determined by measuring the quality factor (Q) of a linear microstrip resonator at 10.4 and 20.2 GHz. The complex conductivity for the film on LaAlO3 was determined to be (2.0-j10) x 10(exp 5) S/m at 77 K. It was observed that in the superconducting state sigma(sub 1) deviates from both the Bardeen-Cooper-Schrieffer (BCS) theory and the two-fluid model. Values of lambda were found to be approximately 2.0 and 1.1 microns at 77 K and 20 K respectively, and were obtained for the film on LaAlO3. The value of lambda at 20 K was approximately three times larger than that of BSCCO single crystals. R(sub s) values of 865 and 1391 mOmega were obtained for the films on SrTiO3 and LaAlO3, respectively, at 77 K and 58.9 GHz. Unloaded Q factors at 20 K of approximately 1100 and 800 at 10.4 and 20.2 GHz respectively, were measured for the BSCCO resonator. Unloaded Q values of 290 and 405 at 20 K were obtained at 10.4 GHz and 20.2 GHz respectively, for an all gold (Au) resonator.

  16. Publisher's Note: Branching ratio of the electromagnetic decay of the Σ+(1385) Phys. Rev. D 85, 052004 (2012)

    NASA Astrophysics Data System (ADS)

    Keller, D.; Hicks, K.; Adhikari, K. P.; Adikaram, D.; Amaryan, M. J.; Anghinolfi, M.; Baghdasaryan, H.; Ball, J.; Battaglieri, M.; Bedlinskiy, I.; Biselli, A. S.; Bookwalter, C.; Boiarinov, S.; Branford, D.; Briscoe, W. J.; Brooks, W. K.; Burkert, V. D.; Carman, D. S.; Celentano, A.; Chandavar, S.; Cole, P. L.; Contalbrigo, M.; Crede, V.; D'Angelo, A.; Daniel, A.; Dashyan, N.; De Vita, R.; De Sanctis, E.; Djalali, C.; Doughty, D.; Dupre, R.; El Alaoui, A.; El Fassi, L.; Elouadrhiri, L.; Eugenio, P.; Fedotov, G.; Gabrielyan, M. Y.; Gevorgyan, N.; Gilfoyle, G. P.; Giovanetti, K. L.; Gohn, W.; Golovatch, E.; Gothe, R. W.; Graham, L.; Griffioen, K. A.; Guidal, M.; Guler, N.; Guo, L.; Hafidi, K.; Hakobyan, H.; Holtrop, M.; Ilieva, Y.; Ireland, D. G.; Ishkhanov, B. S.; Isupov, E. L.; Jo, H. S.; Joo, K.; Khandaker, M.; Khetarpal, P.; Kim, A.; Kim, W.; Klein, F. J.; Kubarovsky, A.; Kubarovsky, V.; Kuleshov, S. V.; Lu, H. Y.; MacGregor, I. J. D.; Mao, Y.; Markov, N.; Mayer, M.; McKinnon, B.; Meyer, C. A.; Mineeva, T.; Mirazita, M.; Mokeev, V.; Moutarde, H.; Munevar, E.; Nadel-Turonski, P.; Nasseripour, R.; Niccolai, S.; Niculescu, G.; Niculescu, I.; Osipenko, M.; Ostrovidov, A. I.; Paolone, M.; Pappalardo, L.; Paremuzyan, R.; Park, K.; Park, S.; Pasyuk, E.; Anefalos Pereira, S.; Pisano, S.; Pogorelko, O.; Pozdniakov, S.; Procureur, S.; Prok, Y.; Protopopescu, D.; Raue, B. A.; Ricco, G.; Rimal, D.; Ripani, M.; Ritchie, B. G.; Rosner, G.; Rossi, P.; Sabatié, F.; Saini, M. S.; Salgado, C.; Schott, D.; Schumacher, R. A.; Seraydaryan, H.; Sharabian, Y. G.; Smith, E. S.; Smith, G. D.; Sober, D. I.; Sokhan, D.; Stepanyan, S. S.; Stepanyan, S.; Stoler, P.; Strauch, S.; Taiuti, M.; Tang, W.; Taylor, C. E.; Tkachenko, S.; Vernarsky, B.; Vineyard, M. F.; Vlassov, A. V.; Voskanyan, H.; Voutier, E.; Watts, D. P.; Wood, M. H.; Zachariou, N.; Zana, L.; Zhao, B.; Zhao, Z. W.

    2012-03-01

    The CLAS detector was used to obtain the first ever measurement of the electromagnetic decay of the $\\Sigma^{*+}(1385)$ from the reaction $\\gamma p \\to K^0 \\Sigma^{*+}(1385)$. A real photon beam with a maximum energy of 3.8 GeV was incident on a liquid-hydrogen target, resulting in the photoproduction of the kaon and $\\Sigma^*$ hyperon. Kinematic fitting was used to separate the reaction channel from the background processes. The fitting algorithm exploited a new method to kinematically fit neutrons in the CLAS detector, leading to the partial width measurement of $250.0\\pm56.9(stat)^{+34.3}_{-41.2}(sys)$ keV. A U-spin symmetry test using the SU(3) flavor-multiplet representation yields predictions for the $\\Sigma^{*+}(1385)\\to\\Sigma^{+}\\gamma$ and $\\Sigma^{*0}(1385)\\to\\Lambda\\gamma$ partial widths that agree with the experimental measurements.

  17. Charmonium Decays of Y(4260), psi(4160), and psi(4040).

    PubMed

    Coan, T E; Gao, Y S; Liu, F; Artuso, M; Blusk, S; Butt, J; Li, J; Menaa, N; Mountain, R; Nisar, S; Randrianarivony, K; Redjimi, R; Sia, R; Skwarnicki, T; Stone, S; Wang, J C; Zhang, K; Csorna, S E; Bonvicini, G; Cinabro, D; Dubrovin, M; Lincoln, A; Asner, D M; Edwards, K W; Briere, R A; Brock, I; Chen, J; Ferguson, T; Tatishvili, G; Vogel, H; Watkins, M E; Rosner, J L; Adam, N E; Alexander, J P; Berkelman, K; Cassel, D G; Duboscq, J E; Ecklund, K M; Ehrlich, R; Fields, L; Galik, R S; Gibbons, L; Gray, R; Gray, S W; Hartill, D L; Heltsley, B K; Hertz, D; Jones, C D; Kandaswamy, J; Kreinick, D L; Kuznetsov, V E; Mahlke-Krüger, H; Meyer, T O; Onyisi, P U E; Patterson, J R; Peterson, D; Phillips, E A; Pivarski, J; Riley, D; Ryd, A; Sadoff, A J; Schwarthoff, H; Shi, X; Stroiney, S; Sun, W M; Wilksen, T; Weinberger, M; Athar, S B; Avery, P; Breva-Newell, L; Patel, R; Potlia, V; Stoeck, H; Yelton, J; Rubin, P; Cawlfield, C; Eisenstein, B I; Karliner, I; Kim, D; Lowrey, N; Naik, P; Sedlack, C; Selen, M; White, E J; Wiss, J; Shepherd, M R; Besson, D; Pedlar, T K; Cronin-Hennessy, D; Gao, K Y; Gong, D T; Hietala, J; Kubota, Y; Klein, T; Lang, B W; Poling, R; Scott, A W; Smith, A; Dobbs, S; Metreveli, Z; Seth, K K; Tomaradze, A; Zweber, P; Ernst, J; Severini, H; Dytman, S A; Love, W; Savinov, V; Aquines, O; Li, Z; Lopez, A; Mehrabyan, S; Mendez, H; Ramirez, J; Huang, G S; Miller, D H; Pavlunin, V; Sanghi, B; Shipsey, I P J; Xin, B; Adams, G S; Anderson, M; Cummings, J P; Danko, I; Napolitano, J; He, Q; Insler, J; Muramatsu, H; Park, C S; Thorndike, E H

    2006-04-28

    Using data collected with the CLEO detector operating at the CESR e+e- collider at sqrt[s]=3.97-4.26 GeV, we investigate 15 charmonium decay modes of the psi(4040), psi(4160), and Y(4260) resonances. We confirm, at 11 sigma significance, the BABAR Y(4260)-->pi+pi- J/psi discovery, make the first observation of Y(4260)--> pi(0)pi(0) J/psi (5.1 sigma), and find the first evidence for Y(4260)-->K+K- J/psi(3.7 sigma). We measure e+e- cross sections at sqrt[s]=4.26 GeV as sigma(pi+pi- J/psi)=58(+12)(-10)+/-4 pb, sigma(pi(0)pi(0) J/psi)=23(+12)(-8)+/-1 pb, and sigma(K+K- J/psi)=9(+9)(-5)+/-1 pb, in which the uncertainties are statistical and systematic, respectively. Upper limits are placed on other decay rates from all three resonances.

  18. Stabilization of He2(A(sup 3)Sigma(sub u)(+)) molecules in liquid helium by optical pumping for vacuum UV laser

    NASA Technical Reports Server (NTRS)

    Zmuidzinas, J. S. (Inventor)

    1978-01-01

    A technique is disclosed for achieving large populations of metastable spin-aligned He2(a 3 Sigma u +) molecules in superfluid helium to obtain lasing in the vacuum ultraviolet wavelength regime around 0.0800 micron m by electronically exciting liquid (superfluid) helium with a comparatively low-current electron beam and spin aligning the metastable molecules by means of optical pumping with a modestly-powered (100mW) circularly-polarized continuous wave laser operating at, for example, 0.9096 or 0.4650 micron m. Once a high concentration of spin-aligned He2 (a 3 Sigma u +) is achieved with lifetimes of a few milliseconds, a strong microwave signal destroys the spin alignment and induces a quick collisional transition of He2 (a 3 Sigma u +) molecules to the a 1 Sigma u + state and thereby a lasing transition to the X 1 Sigma g + state.

  19. Organochlorine pesticides and polychlorinated biphenyls in California sea lions (Zalophus californianus californianus) from the Gulf of California, México.

    PubMed

    Niño-Torres, Carlos Alberto; Gardner, Susan C; Zenteno-Savín, Tania; Ylitalo, Gina M

    2009-02-01

    We report concentrations of several classes of organochlorines (OCs) in the blubber of California sea lions (Zalophus californianus) from the Gulf of California. Summed OC levels measured in 34 wild-ranging animals were, in general, lower than those previously reported in sea lions from the eastern Pacific. The rank order of OCs was SigmaDDTs (mean=3400 ng g(-1 ) lipid weight [lw]) > SigmaPCBs (1400 ng g(-1 ) lw) > SigmaHCHs (50 ng g(-1 ) lw) >or= SigmaCHLORs (46 ng g(-1 ) lw). The most abundant OC measured was the DDT metabolite, p,p'-DDE. No significant differences in OC profiles were found between genders or rookeries. Although the mean concentrations of OCs measured in adult males and females were similar, only adult females had significantly higher (p<0.05) mean blubber concentrations of summation SigmaDDTs and summation SigmaHCHs than pups.

  20. A double Gerdien instrument for simultaneous bipolar air conductivity measurements on balloon platforms.

    PubMed

    Nicoll, K A; Harrison, R G

    2008-08-01

    A bipolar air conductivity instrument is described for use with a standard disposable meteorological radiosonde package. It is intended to provide electrical measurements at cloud boundaries, where the ratio of the bipolar air conductivities is affected by the presence of charged particles. The sensors are two identical Gerdien-type electrodes, which, through a voltage decay method, measure positive and negative air conductivities simultaneously. Voltage decay provides a thermally stable approach and a novel low current leakage electrometer switch is described which initiates the decay sequence. The radiosonde supplies power and telemetry, as well as measuring simultaneous meteorological data. A test flight using a tethered balloon determined positive (sigma(+)) and negative (sigma(-)) conductivities of sigma(+)=2.77+/-0.2 fS m(-1) and sigma(-)=2.82+/-0.2 fS m(-1), respectively, at 400 m aloft, with sigma(+)sigma(-)=0.98+/-0.04.

  1. A healthcare Lean Six Sigma System for postanesthesia care unit workflow improvement.

    PubMed

    Kuo, Alex Mu-Hsing; Borycki, Elizabeth; Kushniruk, Andre; Lee, Te-Shu

    2011-01-01

    The aim of this article is to propose a new model called Healthcare Lean Six Sigma System that integrates Lean and Six Sigma methodologies to improve workflow in a postanesthesia care unit. The methodology of the proposed model is fully described. A postanesthesia care unit case study is also used to demonstrate the benefits of using the Healthcare Lean Six Sigma System model by combining Lean and Six Sigma methodologies together. The new model bridges the service gaps between health care providers and patients, balances the requirements of health care managers, and delivers health care services to patients by taking the benefits of the Lean speed and Six Sigma high-quality principles. The full benefits of the new model will be realized when applied at both strategic and operational levels. For further research, we will examine how the proposed model is used in different real-world case studies.

  2. A comparison of methods for computing the sigma-coordinate pressure gradient force for flow over sloped terrain in a hybrid theta-sigma model

    NASA Technical Reports Server (NTRS)

    Johnson, D. R.; Uccellini, L. W.

    1983-01-01

    In connection with the employment of the sigma coordinates introduced by Phillips (1957), problems can arise regarding an accurate finite-difference computation of the pressure gradient force. Over steeply sloped terrain, the calculation of the sigma-coordinate pressure gradient force involves computing the difference between two large terms of opposite sign which results in large truncation error. To reduce the truncation error, several finite-difference methods have been designed and implemented. The present investigation has the objective to provide another method of computing the sigma-coordinate pressure gradient force. Phillips' method is applied for the elimination of a hydrostatic component to a flux formulation. The new technique is compared with four other methods for computing the pressure gradient force. The work is motivated by the desire to use an isentropic and sigma-coordinate hybrid model for experiments designed to study flow near mountainous terrain.

  3. High Resolution Displays In The Apple Macintosh And IBM PC Environments

    NASA Astrophysics Data System (ADS)

    Winegarden, Steven

    1989-07-01

    High resolution displays are one of the key elements that distinguish user oriented document finishing or publishing stations. A number of factors have been involved in bringing these to the desktop environment. At Sigma Designs we have concentrated on enhancing the capabilites of IBM PCs and compatibles and Apple Macintosh computer systems.

  4. Why HPT Will Continue to Be a Hard Sell

    ERIC Educational Resources Information Center

    Pearlstein, Richard B.

    2012-01-01

    Most executives have not heard of human performance technology (HPT), but a recent Google search showed 25 times more Google hits for "lean six sigma" than for "human performance technology." This article describes five factors that make HPT a hard sell: (1) HPT is not part of standard business jargon, (2) organizational executives associate…

  5. Effect of solution annealing temperature on precipitation in 2205 duplex stainless steel

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kashiwar, A., E-mail: akashiwar@gmail.com; Vennela, N. Phani, E-mail: phanivennela@gmail.com; Kamath, S.L., E-mail: kamath@iitb.ac.in

    2012-12-15

    In the present study, effect of solution annealing temperature (1050 Degree-Sign C and 1100 Degree-Sign C) and isothermal ageing (700 Degree-Sign C: 15 min to 6 h) on the microstructural changes in 2205 duplex stainless steel has been investigated systematically. Scanning electron microscopy and X-ray diffraction were adopted to follow the microstructural evolution, while an energy dispersive spectrometer attached to scanning electron microscope was used to obtain localised chemical information of various phases. The ferritic matrix of the two phase 2205 duplex stainless steel ({approx} 45% ferrite and {approx} 55% austenite) undergoes a series of metallurgical transformations during ageing-formation ofmore » secondary austenite ({gamma}{sub 2}) and precipitation of Cr and Mo rich intermetallic (chi-{chi} and sigma-{sigma}) phases. For solution annealing at 1050 Degree-Sign C, significant amount of carbides were observed in the ferrite grains after 1 h of ageing at 700 Degree-Sign C. {chi} Phase precipitated after the precipitation of carbides-preferentially at the ferrite-ferrite and also at the ferrite-austenite boundaries. {sigma} Phase was not observed in significant quantity even after 6 h of ageing. The sequence of precipitation in samples solution annealed at 1050 Degree-Sign C was found to be carbides {yields} {chi} {yields} {sigma}. On the contrary, for samples solution annealed at 1100 Degree-Sign C, the precipitation of {chi} phase was negligible. {chi} Phase precipitated before {sigma} phase, preferentially along the ferrite-ferrite grain boundaries and was later consumed in the {sigma} phase precipitation. The {sigma} phase precipitated via the eutectoid transformation of ferrite to yield secondary austenite {gamma}{sub 2} and {sigma} phase in the ferrite and along the ferrite-austenite grain boundaries. An increase in the volume fraction of {gamma}{sub 2} and {sigma} phase with simultaneous decrease in the ferrite was evidenced with ageing. - Highlights: Black-Right-Pointing-Pointer Effect of solution annealing temperature on microstructural evolution is studied. Black-Right-Pointing-Pointer {chi} Phase precipitated preferentially in the samples solution annealed at 1050 Degree-Sign C. Black-Right-Pointing-Pointer {sigma} Phase precipitated preferentially in the samples solution annealed at 1100 Degree-Sign C. Black-Right-Pointing-Pointer For SA at 1050 Degree-Sign C, the sequence of precipitation was carbides {yields} {chi} phase {yields} {sigma} phase. Black-Right-Pointing-Pointer For SA at 1100 Degree-Sign C, {sigma} phase precipitated via the eutectoid reaction: ferrite (F) {yields} {sigma} + {gamma}{sub 2}.« less

  6. Induction of a stable sigma factor SigR by translation-inhibiting antibiotics confers resistance to antibiotics.

    PubMed

    Yoo, Ji-Sun; Oh, Gyeong-Seok; Ryoo, Sungweon; Roe, Jung-Hye

    2016-06-27

    Antibiotic-producing streptomycetes are rich sources of resistance mechanisms against endogenous and exogenous antibiotics. An ECF sigma factor σ(R) (SigR) is known to govern the thiol-oxidative stress response in Streptomyces coelicolor. Amplification of this response is achieved by producing an unstable isoform of σ(R) called σ(R'). In this work, we present evidence that antibiotics induce the SigR regulon via a redox-independent pathway, leading to antibiotic resistance. The translation-inhibiting antibiotics enhanced the synthesis of stable σ(R), eliciting a prolonged response. WblC/WhiB7, a WhiB-like DNA-binding protein, is responsible for inducing sigRp1 transcripts encoding the stable σ(R). The amount of WblC protein and its binding to the sigRp1 promoter in vivo increased upon antibiotic treatment. A similar phenomenon appears to exist in Mycobacterium tuberculosis as well. These findings reveal a novel antibiotic-induced resistance mechanism conserved among actinomycetes, and also give an explicit example of overlap in cellular damage and defense mechanisms between thiol-oxidative and anti- translational stresses.

  7. Genome-wide characterization of monomeric transcriptional regulators in Mycobacterium tuberculosis.

    PubMed

    Feng, Lipeng; Chen, Zhenkang; Wang, Zhongwei; Hu, Yangbo; Chen, Shiyun

    2016-05-01

    Gene transcription catalysed by RNA polymerase is regulated by transcriptional regulators, which play central roles in the control of gene transcription in both eukaryotes and prokaryotes. In regulating gene transcription, many regulators form dimers that bind to DNA with repeated motifs. However, some regulators function as monomers, but their mechanisms of gene expression control are largely uncharacterized. Here we systematically characterized monomeric versus dimeric regulators in the tuberculosis causative agent Mycobacterium tuberculosis. Of the >160 transcriptional regulators annotated in M. tuberculosis, 154 transcriptional regulators were tested, 22 % probably act as monomers and most are annotated as hypothetical regulators. Notably, all members of the WhiB-like protein family are classified as monomers. To further investigate mechanisms of monomeric regulators, we analysed the actions of these WhiB proteins and found that the majority interact with the principal sigma factor σA, which is also a monomeric protein within the RNA polymerase holoenzyme. Taken together, our study for the first time globally classified monomeric regulators in M. tuberculosis and suggested a mechanism for monomeric regulators in controlling gene transcription through interacting with monomeric sigma factors.

  8. Induction of a stable sigma factor SigR by translation-inhibiting antibiotics confers resistance to antibiotics

    PubMed Central

    Yoo, Ji-Sun; Oh, Gyeong-Seok; Ryoo, Sungweon; Roe, Jung-Hye

    2016-01-01

    Antibiotic-producing streptomycetes are rich sources of resistance mechanisms against endogenous and exogenous antibiotics. An ECF sigma factor σR (SigR) is known to govern the thiol-oxidative stress response in Streptomyces coelicolor. Amplification of this response is achieved by producing an unstable isoform of σR called σR′. In this work, we present evidence that antibiotics induce the SigR regulon via a redox-independent pathway, leading to antibiotic resistance. The translation-inhibiting antibiotics enhanced the synthesis of stable σR, eliciting a prolonged response. WblC/WhiB7, a WhiB-like DNA-binding protein, is responsible for inducing sigRp1 transcripts encoding the stable σR. The amount of WblC protein and its binding to the sigRp1 promoter in vivo increased upon antibiotic treatment. A similar phenomenon appears to exist in Mycobacterium tuberculosis as well. These findings reveal a novel antibiotic-induced resistance mechanism conserved among actinomycetes, and also give an explicit example of overlap in cellular damage and defense mechanisms between thiol-oxidative and anti- translational stresses. PMID:27346454

  9. The Sigma-2 Receptor Selective Agonist Siramesine (Lu 28-179) Decreases Cocaine-Reinforced Pavlovian Learning and Alters Glutamatergic and Dopaminergic Input to the Striatum

    PubMed Central

    Klawonn, Anna M.; Nilsson, Anna; Rådberg, Carl F.; Lindström, Sarah H.; Ericson, Mia; Granseth, Björn; Engblom, David; Fritz, Michael

    2017-01-01

    Drug addiction is a chronic, debilitating disease that affects millions of people around the world causing a substantial societal burden. Despite decades of research efforts, treatment possibilities remain limited and relapse represents the most treatment-resistant element. Neurosteroid sigma-1 receptors have been meticulously studied in psychostimulant reinforced Pavlovian learning, while the sigma-2 receptor subtype has remained unexplored. Recent development of selective sigma-2 receptor ligands have now made it possible to investigate if the sigma-2 receptor system is a potential target to treat drug addiction. We examined the effect of the sigma-2 receptor agonist Siramesine (Lu 28-179) on cocaine-associated locomotion, Pavlovian learning, and reward neurocircuitry using electrophysiology recordings and in vivo microdialysis. We found that Siramesine significantly attenuated conditioned place preference acquisition and expression, as well as it completely blocked cocaine-primed reinstatement. Siramesine, in a similar manner as the selective sigma-1 receptor antagonist BD 1063, decreased acute locomotor responses to cocaine. Immunohistochemistry suggests co-expression of progesterone receptor membrane component 1/sigma-2 receptors and vesicular glutamate transporter 1 in presynaptic boutons of the nucleus accumbens (NAc). Whole-cell voltage clamp recordings of neurons in the NAc indicated that Siramesine decreases the presynaptic release probability of glutamate. Further, we demonstrated, via in vivo microdialysis, that Siramesine significantly decreased cocaine-evoked dopamine release in the striatum of freely moving mice. Collectively, these findings demonstrate that sigma-2 receptors regulate neurocircuitry responsible for positive reinforcement and thereby play a role in cocaine-reinforced Pavlovian behaviors. PMID:29066971

  10. Irreversible blockade of sigma-1 receptors by haloperidol and its metabolites in guinea pig brain and SH-SY5Y human neuroblastoma cells.

    PubMed

    Cobos, Enrique J; del Pozo, Esperanza; Baeyens, José M

    2007-08-01

    We evaluated the effect of haloperidol (HP) and its metabolites on [(3)H](+)-pentazocine binding to sigma(1) receptors in SH-SY5Y human neuroblastoma cells and guinea pig brain P(1), P(2) and P(3) subcellular fractions. Three days after a single i.p. injection in guinea pigs of HP (but not of other sigma(1) antagonists or (-)-sulpiride), [(3)H](+)-pentazocine binding to brain membranes was markedly decreased. Recovery of sigma(1) receptor density to steady state after HP-induced inactivation required more than 30 days. HP-metabolite II (reduced HP, 4-(4-chlorophenyl)-alpha-(4-fluorophenyl)-4-hydroxy-1-piperidinebutanol), but not HP-metabolite I (4-(4-chlorophenyl)-4-hydroxypiperidine), irreversibly blocked sigma(1) receptors in guinea pig brain homogenate and P(2) fraction in vitro. We found similar results in SH-SY5Y cells, which suggests that this process may also take place in humans. HP irreversibly inactivated sigma(1) receptors when it was incubated with brain homogenate and SH-SY5Y cells, but not when incubated with P(2) fraction membranes, which suggests that HP is metabolized to inactivate sigma(1) receptors. Menadione, an inhibitor of the ketone reductase activity that leads to the production of HP-metabolite II, completely prevented HP-induced inactivation of sigma(1) receptors in brain homogenates. These results suggest that HP may irreversibly inactivate sigma(1) receptors in guinea pig and human cells, probably after metabolism to reduced HP.

  11. Near Earth asteroids associated with the Sigma-Capricornids meteoroid stream

    NASA Astrophysics Data System (ADS)

    Gulchekhra, Kokhirova; Pulat, Babadzhanov; Umed, Khamroev

    The Near Earth Asteroids (NEAs) 2008BO16, 2011EC41, and 2013CT36 (http://newton.dm.\\unipi.it/neodys, 2013) have very similar orbits according to the D_{SH} criterion of Southworth, Hawkins (1963). Additionally, their orbits are classed as comet-like by the Tisserand invariant values (Kresak 1982; Kosai 1992). The orbital evolution investigation shows, that during one cycle of variations of the argument of perihelion omega, the asteroids cross the Earth’s orbit four times. Consequently, a developed meteoroid stream, possible associated with them, might produce four meteor showers (Babadzhanov, Obrubov 1992). Theoretical parameters of the predicted showers were calculated and identified with the observable nighttime sigma-Capricornids (Sekanina 1973; Jenniskens 2006) and chi-Sagittarids (Sekanina 1976), and daytime chi-Capricornids (Sekanina 1976) and Capricornids-Sagittarids (Sekanina 1973) meteor showers. The similar and comet-like orbits and association with the meteoroid stream producing four active showers are strong indications that these asteroids have a common cometary origin. Earlier the NEAs (2101) Adonis and 1995CS, which additionally is potentially hazardous asteroid (PHA), were recognized as dormant comets because of their link with the same meteoroid stream (Babadzhanov 2003). So, a conclusion was made, that either the considered NEAs are large sized splinters of the Adonis, or all five objects are fragments of a larger comet that was the parent body of the sigma-Capricornids meteoroid stream, and whose break-up occurred several tens of thousands years ago. During 2010-2011 years three fireballs were photographed by the Tajikistan fireball network (Babadzhanov, Kokhirova 2009), belonging to the sigma-Capricornids meteor shower. Taking into account the observations else six fireballs of this shower in the Canada and USA (Halliday et al. 1996; McCrosky et al. 1978), the mean radiant coordinates, the period of activity, as well as the mean daily radiant drift of the sigma-Capricornids were determined. Further to the PE criterion (Ceplecha, McCrosky 1976), the values of bulk density of the nine fireball producing meteoroids are in the range 0.2-3.5 g cm(-3) that suggests a non-homogeneous compound of the comet-progenitor of the sigma-Capricornids fireball shower. size{ References Babadzhanov, P.B., 2003, A&A,397, 319 Babadzhanov, P.B., Kokhirova, G.I., 2009, Izv. Ak. Nauk Resp. Taj.,2(135),46 Babadzhanov, P.B., Obrubov, Yu.V., 1992, Cel. Mech.& Dyn. Astron., v.54, p.111 Ceplecha, Z., McCrosky, R.E.J., 1976, J. Geophys. Res., 81, 6257 Halliday, I., Griffin, A.A., Blackwell, A.T., 1996, Met.& Planet. Sci., 31, 185 Jenniskens, P., 2006, Meteor showers and their parent comets, New- York: Cambridge Univ. Press, p. 790 Kosai, H., 1992, Cel. Mech. & Dyn. Astron., 54, 237 Kresak, L., 1982, BAC, 33, 104 McCrosky, R.E., Shao, C.Y., Posen, A., 1978, Meteoritika, 37, 44 Sekanina Z., 1973, Icarus, 18, 253 Sekanina Z., 1976, Icarus, 27, 265 Southworth, R.B., Hawkins, G.S., 1963, Smith. Cont. Aph. 7, 261}

  12. Chronic administration of the anabolic androgenic steroid nandrolone alters neurosteroid action at the sigma-1 receptor but not at the sigma-2 or NMDA receptors.

    PubMed

    Elfverson, Martin; Johansson, Tobias; Zhou, Qin; Le Grevès, Pierre; Nyberg, Fred

    2011-12-01

    Studies have shown that anabolic androgenic steroids (AASs) can induce profound changes to mental health. Commonly reported psychiatric side effects among AAS users include aggression, anxiety, depression, drug abuse and cognitive disabilities. In experimental animals, many of these effects have been associated with alterations in a number of neurotransmitter systems. We have observed that chronic administration of the AAS nandrolone (nandrolone decanoate) can affect excitatory amino acids as well as monoaminergic and peptidergic pathways in a way that is compatible with nandrolone-induced behavioural changes. The aim of the present work was to further explore the mechanisms underlying nandrolone-induced effects, with a particular focus on components known to be involved in aggression and cognitive function. Male rats were given daily injections of nandrolone decanoate for 14 days and the effects on neurosteroid interactions with sites on the N-methyl-D-aspartyl (NMDA) and sigma receptors were examined. These receptors were chosen because of their involvement in aggressive and cognitive behaviors and the hypothesis that nandrolone might affect the brain via interaction with neurosteroids. Radiolabelled [³H]ifenprodil was used in the binding studies because of its significant affinity for the NMDA and sigma receptors. The results indicated that [³H]ifenprodil binds to both sigma-1 and sigma-2 sites and can be displaced to a certain extent from both sites by the neurosteroids pregnenolone sulphate (PS), pregnanolone sulphate (3α5βS) and dehydroepiandrosterone sulphate (DHEAS). The remainder of the [³H]ifenprodil was displaced from the sigma-1 site by the sigma-1 receptor-selective ligand (+)-SKF 10,047. Chronic nandrolone treatment changed the sigma-1 receptor target for the neurosteroids but not for ifenprodil. The sigma-2 receptor site was unaltered by treatment with nandrolone decanoate. The results also indicated that the neurosteroid-induced allosteric modulation of the NMDA receptor subunit NR2B was not affected by nandrolone treatment. We conclude that chronic treatment with nandrolone changes the affinity of the neurosteroids PS, 3α5βS and DHEAS at the sigma-1 site but not at the sites on the sigma-2 receptor or the NMDA receptor subunit NR2B. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Six Sigma Quality Management System and Design of Risk-based Statistical Quality Control.

    PubMed

    Westgard, James O; Westgard, Sten A

    2017-03-01

    Six sigma concepts provide a quality management system (QMS) with many useful tools for managing quality in medical laboratories. This Six Sigma QMS is driven by the quality required for the intended use of a test. The most useful form for this quality requirement is the allowable total error. Calculation of a sigma-metric provides the best predictor of risk for an analytical examination process, as well as a design parameter for selecting the statistical quality control (SQC) procedure necessary to detect medically important errors. Simple point estimates of sigma at medical decision concentrations are sufficient for laboratory applications. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Evidence for the decay sigma+ --> pmu+ mu-.

    PubMed

    Park, H K; Burnstein, R A; Chakravorty, A; Chen, Y C; Choong, W S; Clark, K; Dukes, E C; Durandet, C; Felix, J; Fu, Y; Gidal, G; Gustafson, H R; Holmstrom, T; Huang, M; James, C; Jenkins, C M; Jones, T; Kaplan, D M; Lederman, L M; Leros, N; Longo, M J; Lopez, F; Lu, L C; Luebke, W; Luk, K B; Nelson, K S; Perroud, J-P; Rajaram, D; Rubin, H A; Volk, J; White, C G; White, S L; Zyla, P

    2005-01-21

    We report the first evidence for the decay Sigma(+)-->pmu(+)mu(-) from data taken by the HyperCP (E871) experiment at Fermilab. Based on three observed events, the branching ratio is B(Sigma(+)-->pmu(+)mu(-))=[8.6(+6.6)(-5.4)(stat)+/-5.5(syst)]x10(-8). The narrow range of dimuon masses may indicate that the decay proceeds via a neutral intermediate state, Sigma(+)-->pP(0),P0-->mu(+)mu(-) with a P0 mass of 214.3+/-0.5 MeV/c(2) and branching ratio B(Sigma(+)-->pP(0),P0-->mu(+)mu(-))=[3.1(+2.4)(-1.9)(stat)+/-1.5(syst)]x10(-8).

  15. Decahydrobenzoquinolin-5-one sigma receptor ligands: Divergent development of both sigma 1 and sigma 2 receptor selective examples.

    PubMed

    McLeod, Michael C; Aubé, Jeffrey; Frankowski, Kevin J

    2016-12-01

    Analogues of the decahydrobenzoquinolin-5-one class of sigma (σ) receptor ligands were used to probe the structure-activity relationship trends for this recently discovered series of σ ligands. In all, 29 representatives were tested for σ and opioid receptor affinity, leading to the identification of compounds possessing improved σ 1 selectivity and, for the first time in this series, examples possessing preferential σ 2 affinity. Several structural features associated with these selectivity trends have been identified. Two analogues of improved selectivity were evaluated in a binding panel of 43 CNS-relevant targets to confirm their sigma receptor preference. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. A study of fast ionic conductors by positron annihilation

    NASA Astrophysics Data System (ADS)

    Wang, Yung-Yu; Yang, Ju-Hua; Pan, Xiao-Liang; Lei, Zhen-Xi

    1988-06-01

    New fast ionic conductor systems of LiCl-LiF-B2O3 and LiF-B2O3 were studied by using the positron annihilation technique. It was found that the mid-life intensity I2 in positron annihilation has a linear relationship with the material's electrical conductivity log sigma. This result, combined with the measurement result on the linear annihilation parameter, indicated that the voids between microcrystals and network phases provided more transfer paths in the micro-crystalline LiF-LiCl-B2O3 system, which led to improved electrical conductivity in this type of material.

  17. Spaceborne Ocean Intelligence Network: SOIN - Fiscal Year 08/09 Year-End Summary

    DTIC Science & Technology

    2009-09-01

    de planification d’acquisition d’images de satellites commerciaux]) et le BT 4 (Entités océaniques d’après les images RSO). Le BT 2 est terminé à...colour assignment (r, g , or b). If a band is assigned to two colours, then two of r, g , or b are displayed next to the DN. If a band is assigned to...a DN is displayed for each r, g and b colour assignment, even if they are the same band. • Sigma-Nought Only works for RADARSAT-1 and RADARSAT-2

  18. Topography of Slow Sigma Power during Sleep is Associated with Processing Speed in Preschool Children

    PubMed Central

    Doucette, Margaret R.; Kurth, Salome; Chevalier, Nicolas; Munakata, Yuko; LeBourgeois, Monique K.

    2015-01-01

    Cognitive development is influenced by maturational changes in processing speed, a construct reflecting the rapidity of executing cognitive operations. Although cognitive ability and processing speed are linked to spindles and sigma power in the sleep electroencephalogram (EEG), little is known about such associations in early childhood, a time of major neuronal refinement. We calculated EEG power for slow (10–13 Hz) and fast (13.25–17 Hz) sigma power from all-night high-density electroencephalography (EEG) in a cross-sectional sample of healthy preschool children (n = 10, 4.3 ± 1.0 years). Processing speed was assessed as simple reaction time. On average, reaction time was 1409 ± 251 ms; slow sigma power was 4.0 ± 1.5 μV2; and fast sigma power was 0.9 ± 0.2 μV2. Both slow and fast sigma power predominated over central areas. Only slow sigma power was correlated with processing speed in a large parietal electrode cluster (p < 0.05, r ranging from −0.6 to −0.8), such that greater power predicted faster reaction time. Our findings indicate regional correlates between sigma power and processing speed that are specific to early childhood and provide novel insights into the neurobiological features of the EEG that may underlie developing cognitive abilities. PMID:26556377

  19. Integral cross sections for the direct excitation of the A 3 (sigma) u +, B 3 (pi) g, W 3 (delta) u, B' 3 (sigma) u -, a' 1 (sigma) u -, a 1 (pi) g, w 1 (delta) u, and C 3 (pi) u electronic states in

    NASA Technical Reports Server (NTRS)

    Johnson, P. V.; Malone, C. P.; Kanik, I.

    2005-01-01

    Integral cross sections for electron impact excitation out of the ground state (X 1(sigma)g +) to the A 3(sigma)u +, B 3(pi)g, W 3(delta)u, B' 3(sigma)u -, a' 1(sigma)u -, a 1(pi)g, w 1(delta)u, and states in N2 are reported at incident energies ranging between 10 and 100 eV. These data have been derived by integrating differential cross sections previously reported by this group. New differential cross section measurements for the a 1(pi)g state at 200 eV are also presented to extend the range of the reported integral cross sections for this state, which is responsible for the emissions of the Lyman-Birge-Hopfield band system (a 1(pi)g (rightwards arrow) X 1(sigma)g +). The present results are compared and critically evaluated against existing cross sec In general, the present cross sections are smaller than previous results at low impact energies from threshold through the excitation function peak regions. These lower cross sections have potentially significant implications on our understanding of UV emissions in the atmospheres of Earth and Titan.

  20. PBDEs, PBBs, and PCNs in three communities of free-ranging killer whales (Orcinus orca) from the northeastern Pacific Ocean.

    PubMed

    Rayne, Sierra; Ikonomou, Michael G; Ross, Peter S; Ellis, Graeme M; Barrett-Lennard, Lance G

    2004-08-15

    Polybrominated diphenyl ethers (PBDEs), polybrominated biphenyls (PBBs), and polychlorinated naphthalenes (PCNs) were quantified in blubber biopsy samples collected from free-ranging male and female killer whales (Orcinus orca) belonging to three distinct communities (southern residents, northern residents, and transients) from the northeastern Pacific Ocean. High concentrations of sigmaPBDE were observed in male southern residents (942+/-582 ng/g Iw), male and female transients (1015+/-605 and 885+/-706 ng/g Iw, respectively), and male and female northern residents (203+/-116 and 415+/-676 ng/g Iw, respectively). Because of large variation within sample groups, sigmaPBDE levels generally did not differ statistically with the exception of male northern residents, which had lower sigmaPBDE concentrations than male southern residents, male transients, and female transients, perhaps reflecting the consumption of less contaminated prey items. Male transient killer whales, which consume high trophic level prey including other cetaceans and occasionally spend time near populated areas, had sigmaPBDE concentrations approximately equal to southern residents. No significant age-related relationships were observed for sigmaPBDE concentrations. sigmaPBDE concentrations were approximately 1-3 orders of magnitude greater than those of sigmaPBB (3.0-31 ng/g Iw) and sigmaPCN (20-167 ng/g Iw) measured in a subset of samples, suggesting that PBDEs may represent a contaminant class of concern in these marine mammals.

  1. [Reducing patient waiting time for the outpatient phlebotomy service using six sigma].

    PubMed

    Kim, Yu Kyung; Song, Kyung Eun; Lee, Won Kil

    2009-04-01

    One of the challenging issues of the outpatient phlebotomy services at most hospitals is that patients have a long wait. The outpatient phlebotomy team of Kyungpook National University Hospital applied six sigma breakthrough methodologies to reduce the patient waiting time. The DMAIC (Define, Measure, Analyze, Improve, and Control) model was employed to approach the project. Two hundred patients visiting the outpatient phlebotomy section were asked to answer the questionnaires at inception of the study to ascertain root causes. After correction, we surveyed 285 patients for same questionnaires again to follow-up the effects. A defect was defined as extending patient waiting time so long and at the beginning of the project, the performance level was 2.61 sigma. Using fishbone diagram, all the possible reasons for extending patient waiting time were captured, and among them, 16 causes were proven to be statistically significant. Improvement plans including a new receptionist, automatic specimen transport system, and adding one phlebotomist were put into practice. As a result, the number of patients waited more than 5 min significantly decreased, and the performance level reached 3.0 sigma in December 2007 and finally 3.35 sigma in July 2008. Applying the six sigma, the performance level of waiting times for blood drawing exceeding five minutes were improved from 2.61 sigma to 3.35 sigma.

  2. Despite irreversible binding, PET tracer [11C]-SA5845 is suitable for imaging of drug competition at sigma receptors-the cases of ketamine and haloperidol.

    PubMed

    Kortekaas, Rudie; Maguire, R Paul; van Waarde, Aren; Leenders, Klaus L; Elsinga, Philip H

    2008-07-01

    Many psychotropic compounds bind to sigma receptors and several new sigma ligands are in development for psychiatric indications such as anxiety, attention deficit hyperactivity disorder, depression and psychosis. Of special interest for drug development are tomographic methods that can quantify the binding of promising sigma ligands in a regional manner. Here we present the development of such a method and the first evaluation of sigma ligand [11C]-SA5845 in a primate. Extensive pharmacokinetic modeling was done on tissue curves and a heart lumen curve. The effects of pretreatment and challenge with haloperidol were studied as well as those of pretreatment with +/- -ketamine. The tracer had a plasma half-life of 77+/-1.7min and was rapidly taken up by all brain areas. The binding pattern was consistent with binding to sigma receptors and compartment modeling showed there was considerable specific binding that was irreversible. We therefore calculated the net influx rate, Ki, with the Gjedde-Patlak linearization, as a measure of free receptors. As expected, Ki was very sensitive to the presence of competing ligands - -ketamine and/or haloperidol. Summarizing, the tracer is well suited for visualizing sigma receptors in the brain and moreover, the presented method is able to quantify, on a regional basis, specific binding of unlabeled ligands to sigma receptors.

  3. Environmental Professional’s Guide to Lean and Six Sigma: Executive Summary

    EPA Pesticide Factsheets

    Introduction to the guide that describes how Lean and Six Sigma relate to the environment and provides guidance on how environmental professionals can connect with Lean and Six Sigma activities to generate better environmental and operational results.

  4. Prediction of three sigma maximum dispersed density for aerospace applications

    NASA Technical Reports Server (NTRS)

    Charles, Terri L.; Nitschke, Michael D.

    1993-01-01

    Free molecular heating (FMH) is caused by the transfer of energy during collisions between the upper atmosphere molecules and a space vehicle. The dispersed free molecular heating on a surface is an important constraint for space vehicle thermal analyses since it can be a significant source of heating. To reduce FMH to a spacecraft, the parking orbit is often designed to a higher altitude at the expense of payload capability. Dispersed FMH is a function of both space vehicle velocity and atmospheric density, however, the space vehicle velocity variations are insignificant when compared to the atmospheric density variations. The density of the upper atmosphere molecules is a function of altitude, but also varies with other environmental factors, such as solar activity, geomagnetic activity, location, and time. A method has been developed to predict three sigma maximum dispersed density for up to 15 years into the future. This method uses a state-of-the-art atmospheric density code, MSIS 86, along with 50 years of solar data, NASA and NOAA solar activity predictions for the next 15 years, and an Aerospace Corporation correlation to account for density code inaccuracies to generate dispersed maximum density ratios denoted as 'K-factors'. The calculated K-factors can be used on a mission unique basis to calculate dispersed density, and hence dispersed free molecular heating rates. These more accurate K-factors can allow lower parking orbit altitudes, resulting in increased payload capability.

  5. σK of Clostridium acetobutylicum Is the First Known Sporulation-Specific Sigma Factor with Two Developmentally Separated Roles, One Early and One Late in Sporulation

    PubMed Central

    Al-Hinai, Mohab A.; Jones, Shawn W.

    2014-01-01

    Sporulation in the model endospore-forming organism Bacillus subtilis proceeds via the sequential and stage-specific activation of the sporulation-specific sigma factors, σH (early), σF, σE, σG, and σK (late). Here we show that the Clostridium acetobutylicum σK acts both early, prior to Spo0A expression, and late, past σG activation, thus departing from the B. subtilis model. The C. acetobutylicum sigK deletion (ΔsigK) mutant was unable to sporulate, and solventogenesis, the characteristic stationary-phase phenomenon for this organism, was severely diminished. Transmission electron microscopy demonstrated that the ΔsigK mutant does not develop an asymmetric septum and produces no granulose. Complementation of sigK restored sporulation and solventogenesis to wild-type levels. Spo0A and σG proteins were not detectable by Western analysis, while σF protein levels were significantly reduced in the ΔsigK mutant. spo0A, sigF, sigE, sigG, spoIIE, and adhE1 transcript levels were all downregulated in the ΔsigK mutant, while those of the sigH transcript were unaffected during the exponential and transitional phases of culture. These data show that σK is necessary for sporulation prior to spo0A expression. Plasmid-based expression of spo0A in the ΔsigK mutant from a nonnative promoter restored solventogenesis and the production of Spo0A, σF, σE, and σG, but not sporulation, which was blocked past the σG stage of development, thus demonstrating that σK is also necessary in late sporulation. sigK is expressed very early at low levels in exponential phase but is strongly upregulated during the middle to late stationary phase. This is the first sporulation-specific sigma factor shown to have two developmentally separated roles. PMID:24187083

  6. σK of Clostridium acetobutylicum is the first known sporulation-specific sigma factor with two developmentally separated roles, one early and one late in sporulation.

    PubMed

    Al-Hinai, Mohab A; Jones, Shawn W; Papoutsakis, Eleftherios T

    2014-01-01

    Sporulation in the model endospore-forming organism Bacillus subtilis proceeds via the sequential and stage-specific activation of the sporulation-specific sigma factors, σ(H) (early), σ(F), σ(E), σ(G), and σ(K) (late). Here we show that the Clostridium acetobutylicum σ(K) acts both early, prior to Spo0A expression, and late, past σ(G) activation, thus departing from the B. subtilis model. The C. acetobutylicum sigK deletion (ΔsigK) mutant was unable to sporulate, and solventogenesis, the characteristic stationary-phase phenomenon for this organism, was severely diminished. Transmission electron microscopy demonstrated that the ΔsigK mutant does not develop an asymmetric septum and produces no granulose. Complementation of sigK restored sporulation and solventogenesis to wild-type levels. Spo0A and σ(G) proteins were not detectable by Western analysis, while σ(F) protein levels were significantly reduced in the ΔsigK mutant. spo0A, sigF, sigE, sigG, spoIIE, and adhE1 transcript levels were all downregulated in the ΔsigK mutant, while those of the sigH transcript were unaffected during the exponential and transitional phases of culture. These data show that σ(K) is necessary for sporulation prior to spo0A expression. Plasmid-based expression of spo0A in the ΔsigK mutant from a nonnative promoter restored solventogenesis and the production of Spo0A, σ(F), σ(E), and σ(G), but not sporulation, which was blocked past the σ(G) stage of development, thus demonstrating that σ(K) is also necessary in late sporulation. sigK is expressed very early at low levels in exponential phase but is strongly upregulated during the middle to late stationary phase. This is the first sporulation-specific sigma factor shown to have two developmentally separated roles.

  7. An extracytoplasmic function sigma factor-dependent periplasmic glutathione peroxidase is involved in oxidative stress response of Shewanella oneidensis

    DOE PAGES

    Dai, Jingcheng; Wei, Hehong; Tian, Chunyuan; ...

    2015-01-01

    Background: Bacteria use alternative sigma factors (σs) to regulate condition-specific gene expression for survival and Shewanella harbors multiple ECF (extracytoplasmic function) σ genes and cognate anti-sigma factor genes. Here we comparatively analyzed two of the rpoE-like operons in the strain MR-1: rpoE-rseA-rseB-rseC and rpoE2-chrR. Results: RpoE was important for bacterial growth at low and high temperatures, in the minimal medium, and high salinity. The degP/htrA orthologue, required for growth of Escherichia coli and Pseudomonas aeruginosa at high temperature, is absent in Shewanella, while the degQ gene is RpoE-regulated and is required for bacterial growth at high temperature. RpoE2 was essentialmore » for the optimal growth in oxidative stress conditions because the rpoE2 mutant was sensitive to hydrogen peroxide and paraquat. The operon encoding a ferrochelatase paralogue (HemH2) and a periplasmic glutathione peroxidase (PgpD) was identified as RpoE2-dependent. PgpD exhibited higher activities and played a more important role in the oxidative stress responses than the cytoplasmic glutathione peroxidase CgpD under tested conditions. The rpoE2-chrR operon and the identified regulon genes, including pgpD and hemH2, are coincidently absent in several psychrophilic and/or deep-sea Shewanella strains. Conclusion: In S. oneidensis MR-1, the RpoE-dependent degQ gene is required for optimal growth under high temperature. The rpoE2 and RpoE2-dependent pgpD gene encoding a periplasmic glutathione peroxidase are involved in oxidative stress responses. But rpoE2 is not required for bacterial growth at low temperature and it even affected bacterial growth under salt stress, indicating that there is a tradeoff between the salt resistance and RpoE2-mediated oxidative stress responses.« less

  8. The Alternative Sigma Factor SigX Controls Bacteriocin Synthesis and Competence, the Two Quorum Sensing Regulated Traits in Streptococcus mutans

    PubMed Central

    Reck, Michael; Tomasch, Jürgen; Wagner-Döbler, Irene

    2015-01-01

    Two small quorum sensing (QS) peptides regulate competence in S. mutans in a cell density dependent manner: XIP (sigX inducing peptide) and CSP (competence stimulating peptide). Depending on the environmental conditions isogenic S. mutans cells can split into a competent and non-competent subpopulation. The origin of this population heterogeneity has not been experimentally determined and it is unknown how the two QS systems are connected. We developed a toolbox of single and dual fluorescent reporter strains and systematically knocked out key genes of the competence signaling cascade in the reporter strain backgrounds. By following signal propagation on the single cell level we discovered that the master regulator of competence, the alternative sigma factor SigX, directly controls expression of the response regulator for bacteriocin synthesis ComE. Consequently, a SigX binding motif (cin-box) was identified in the promoter region of comE. Overexpressing the genetic components involved in competence development demonstrated that ComRS represents the origin of bimodality and determines the modality of the downstream regulators SigX and ComE. Moreover these analysis showed that there is no direct regulatory link between the two QS signaling cascades. Competence is induced through a hierarchical XIP signaling cascade, which has no regulatory input from the CSP cascade. CSP exclusively regulates bacteriocin synthesis. We suggest renaming it mutacin inducing peptide (MIP). Finally, using phosphomimetic comE mutants we show that unimodal bacteriocin production is controlled posttranslationally, thus solving the puzzling observation that in complex media competence is observed in a subpopulation only, while at the same time all cells produce bacteriocins. The control of both bacteriocin synthesis and competence through the alternative sigma-factor SigX suggests that S. mutans increases its genetic repertoire via QS controlled predation on neighboring species in its natural habitat. PMID:26158727

  9. An extracytoplasmic function sigma factor-dependent periplasmic glutathione peroxidase is involved in oxidative stress response of Shewanella oneidensis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dai, Jingcheng; Wei, Hehong; Tian, Chunyuan

    Background: Bacteria use alternative sigma factors (σs) to regulate condition-specific gene expression for survival and Shewanella harbors multiple ECF (extracytoplasmic function) σ genes and cognate anti-sigma factor genes. Here we comparatively analyzed two of the rpoE-like operons in the strain MR-1: rpoE-rseA-rseB-rseC and rpoE2-chrR. Results: RpoE was important for bacterial growth at low and high temperatures, in the minimal medium, and high salinity. The degP/htrA orthologue, required for growth of Escherichia coli and Pseudomonas aeruginosa at high temperature, is absent in Shewanella, while the degQ gene is RpoE-regulated and is required for bacterial growth at high temperature. RpoE2 was essentialmore » for the optimal growth in oxidative stress conditions because the rpoE2 mutant was sensitive to hydrogen peroxide and paraquat. The operon encoding a ferrochelatase paralogue (HemH2) and a periplasmic glutathione peroxidase (PgpD) was identified as RpoE2-dependent. PgpD exhibited higher activities and played a more important role in the oxidative stress responses than the cytoplasmic glutathione peroxidase CgpD under tested conditions. The rpoE2-chrR operon and the identified regulon genes, including pgpD and hemH2, are coincidently absent in several psychrophilic and/or deep-sea Shewanella strains. Conclusion: In S. oneidensis MR-1, the RpoE-dependent degQ gene is required for optimal growth under high temperature. The rpoE2 and RpoE2-dependent pgpD gene encoding a periplasmic glutathione peroxidase are involved in oxidative stress responses. But rpoE2 is not required for bacterial growth at low temperature and it even affected bacterial growth under salt stress, indicating that there is a tradeoff between the salt resistance and RpoE2-mediated oxidative stress responses.« less

  10. Enhancement of epidemic spread by noise and stochastic resonance in spatial network models with viral dynamics.

    PubMed

    Tuckwell, H C; Toubiana, L; Vibert, J F

    2000-05-01

    We extend a previous dynamical viral network model to include stochastic effects. The dynamical equations for the viral and immune effector densities within a host population of size n are bilinear, and the noise is white, additive, and Gaussian. The individuals are connected with an n x n transmission matrix, with terms which decay exponentially with distance. In a single individual, for the range of noise parameters considered, it is found that increasing the amplitude of the noise tends to decrease the maximum mean virion level, and slightly accelerate its attainment. Two different spatial dynamical models are employed to ascertain the effects of environmental stochasticity on viral spread. In the first model transmission is unrestricted and there is no threshold within individuals. This model has the advantage that it can be analyzed using a Fokker-Planck approach. The noise is found both to synchronize and uniformize the trajectories of the viral levels across the population of infected individuals, and thus to promote the epidemic spread of the virus. Quantitative measures of the speed of spread and overall amplitude of the epidemic are obtained as functions of the noise and virulence parameters. The mean amplitude increases steadily without threshold effects for a fixed value of the virulence as the noise amplitude sigma is increased, and there is no evidence of a stochastic resonance. However, the speed of transmission, both with respect to its mean and variance, undergoes rapid increases as sigma changes by relatively small amounts. In the second, more realistic, model, there is a threshold for infection and an upper limit to the transmission rate. There may be no spread of infection at all in the absence of noise. With increasing noise level and a low threshold, the mean maximum virion level grows quickly and shows a broad-based stochastic resonance effect. When the threshold within individuals is increased, the mean population virion level increases only slowly as sigma increases, until a critical value is reached at which the mean infection level suddenly increases. Similar results are obtained when the parameters of the model are also randomized across the population. We conclude with a discussion and a description of a diffusion approximation for a model in which stochasticity arises through random contacts rather than fluctuation in ambient virion levels.

  11. A non-commutative *-algebra of Borel functions

    NASA Astrophysics Data System (ADS)

    Hart, Robert

    To the pair (E, sigma), where E is a countable Borel equivalence relation on a standard Borel space ( X, A ) and sigma a normalized Borel T -valued 2-cocycle on E, we associate a sequentially weakly closed Borel *-algebra B*r (E, sigma), contained in the bounded linear operators on ℓ2(E). Associated to B*r (E, sigma) is a natural (Borel) Cartan subalgebra (Definition 6.4.10) L( Bo (X)) isomorphic to the bounded Borel functions on X. Then L( Bo (X)) and its normalizer (the set of the unitaries u ∈ B*r (E, sigma) such that u* fu ∈ L( Bo (X)), f ∈ L( Bo (X))) countably generates the Borel *-algebra B*r (E, sigma). In this thesis, we study B*r (E, sigma) and in particular prove that: i) If E is smooth, then B*r (E, sigma) is a type I Borel *-algebra (Definition 6.3.10). ii) If E is a hyperfinite, then B*r (E, sigma) is a Borel AF-algebra (Definition 7.5.1). iii) Generalizing Kumjian's definition, we define a Borel twist Gamma over E and its associated sequentially closed Borel *-algebra B*r (Gamma). iv) Let a Borel Cartan pair ( B,B0 ) denote a sequentially closed Borel *-algebra B with a Borel Cartan subalgebra B0 , where B is countably B0 -generated. Generalizing Feldman-Moore's result, we prove that any pair ( B,B0 ) can be realized uniquely as a pair ( B*r (E, sigma), L( Bo (X))). Moreover, we show that the pair ( B*r (E), L( Bo (X))) is a complete invariant of the countable Borel equivalence relation E. v) We prove a Krieger type theorem, by showing that two aperiodic hyperfinite countable equivalence relations are isomorphic if and only if their associated Borel *-algebras B*r (E1) and B*r (E2) are isomorphic.

  12. Solubilization and characterization of haloperidol-sensitive (+)-( sup 3 H)SKF-10,047 binding sites (sigma sites) from rat liver membranes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    McCann, D.J.; Su, T.P.

    1991-05-01

    The zwitterionic detergent 3-((3-cholamidopropyl)dimethylamino)-1-propanesulfonate (CHAPS) produced optimal solubilization of (+)-({sup 3}H)SKF-10,047 binding sites from rat liver membranes at a concentration of 0.2%, well below the critical micellular concentration of the detergent. The pharmacological selectivity of the liver (+)-({sup 3}H)SKF-10,047 binding sites corresponds to that of sigma sites from rat and guinea pig brain. When the affinities of 18 different drugs at (+)-({sup 3}H)SKF-10,047 binding sites in membranes and solubilized preparations were compared, a correlation coefficient of 0.99 and a slope of 1.03 were obtained, indicating that the pharmacological selectivity of rat liver sigma sites is retained after solubilization. In addition,more » the binding of 20 nM ({sup 3}H)progesterone to solubilized rat liver preparations was found to exhibit a pharmacological selectivity appropriate for sigma sites. A stimulatory effect of phenytoin on (+)-({sup 3}H)SKF-10,047 binding to sigma sites persisted after solubilization. When the solubilized preparation was subjected to molecular sizing chromatography, a single peak exhibiting specific (+)-({sup 3}H)SKF-10,047 binding was obtained. The binding activity of this peak was stimulated symmetrically when assays were performed in the presence of 300 microM phenytoin. The molecular weight of the CHAPS-solubilized sigma site complex was estimated to be 450,000 daltons. After solubilization with CHAPS, rat liver sigma sites were enriched to 12 pmol/mg of protein. The present results demonstrate a successful solubilization of sigma sites from rat liver membranes and provide direct evidence that the gonadal steroid progesterone binds to sigma sites. The results also suggest that the anticonvulsant phenytoin binds to an associated allosteric site on the sigma site complex.« less

  13. Study of the strong {sigma}{sub c}{yields}{lambda}{sub c}{pi},{sigma}{sub c}*{yields}{lambda}{sub c}{pi} and {xi}{sub c}*{yields}{xi}{sub c}{pi} decays in a nonrelativistic quark model

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Albertus, C.; Nieves, J.; Hernandez, E.

    We present results for the strong widths corresponding to the {sigma}{sub c}{yields}{lambda}{sub c}{pi}, {sigma}{sub c}*{yields}{lambda}{sub c}{pi} and {xi}{sub c}*{yields}{xi}{sub c}{pi} decays. The calculations have been done in a nonrelativistic constituent quark model with wave functions that take advantage of the constraints imposed by heavy quark symmetry. Partial conservation of axial current hypothesis allows us to determine the strong vertices from an analysis of the axial current matrix elements. Our results {gamma}({sigma}{sub c}{sup ++}{yields}{lambda}{sub c}{sup +}{pi}{sup +})=2.41{+-}0.07{+-}0.02 MeV, {gamma}({sigma}{sub c}{sup +}{yields}{lambda}{sub c}{sup +}{pi}{sup 0})=2.79{+-}0.08{+-}0.02 MeV, {gamma}({sigma}{sub c}{sup 0}{yields}{lambda}{sub c}{sup +}{pi}{sup -})=2.37{+-}0.07{+-}0.02 MeV, {gamma}({sigma}{sub c}*{sup ++}{yields}{lambda}{sub c}{sup +}{pi}{sup +})=17.52{+-}0.74{+-}0.12 MeV, {gamma}({sigma}{sub c}*{supmore » +}{yields}{lambda}{sub c}{sup +}{pi}{sup 0})=17.31{+-}0.73{+-}0.12 MeV, {gamma}({sigma}{sub c}*{sup 0}{yields}{lambda}{sub c}{sup +}{pi}{sup -})=16.90{+-}0.71{+-}0.12 MeV, {gamma}({xi}{sub c}*{sup +}{yields}{xi}{sub c}{sup 0}{pi}{sup +}+{xi}{sub c}{sup +}{pi}{sup 0})=3.18{+-}0.10{+-}0.01 MeV, and {gamma}({xi}{sub c}*{sup 0}{yields}{xi}{sub c}{sup +}{pi}{sup -}+{xi}{sub c}{sup 0}{pi}{sup 0})=3.03{+-}0.10{+-}0.01 MeV are in good agreement with experimental determinations.« less

  14. CHARGING AND COAGULATION OF DUST IN PROTOPLANETARY PLASMA ENVIRONMENTS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Matthews, L. S.; Land, V.; Hyde, T. W., E-mail: lorin_matthews@baylor.edu

    2012-01-01

    Combining a particle-particle, particle-cluster, and cluster-cluster agglomeration model with an aggregate charging model, the coagulation and charging of dust particles in plasma environments relevant for protoplanetary disks have been investigated, including the effect of electron depletion in high dust density environments. The results show that charged aggregates tend to grow by adding small particles and clusters to larger particles and clusters, and that cluster-cluster aggregation is significantly more effective than particle-cluster aggregation. Comparisons of the grain structure show that with increasing aggregate charge the compactness factor, {phi}{sub {sigma}}, decreases and has a narrower distribution, indicating a fluffier structure. Neutral aggregatesmore » are more compact, with larger {phi}{sub {sigma}}, and exhibit a larger variation in fluffiness. Overall, increased aggregate charge leads to larger, fluffier, and more massive aggregates.« less

  15. High-resolution photoabsorption cross sections of E1Pi - X1Sigma(+) vibrational bands of CO-12 and CO-13

    NASA Technical Reports Server (NTRS)

    Stark, G.; Smith, P. L.; Ito, K.; Yoshino, K.

    1992-01-01

    Photodissociation following absorption of extreme-ultraviolet photons is an important factor in determining the abundance and isotropic fractionation of CO in diffuse and translucent interstellar clouds. The principal channel for destruction of CO-13 in such clouds begins with absorption in the (1,0) vibrational band of the E1Pi - X1Sigma(+) system; similarly, absorption in the (0,0) band begins a significant destruction channel for CO-12. Reliable modeling of the CO fractionation process depends critically upon the accuracy of the photoabsorption cross section for these bands. We have measured the cross sections for the relevant isotropic species and for the (1,0) band of CO-12. Our results, which are uncertain by about 10 percent, are for the most part larger than previous measurements.

  16. Scaling of Magnetic Reconnection in Relativistic Collisionless Pair Plasmas

    NASA Technical Reports Server (NTRS)

    Liu, Yi-Hsin; Guo, Fan; Daughton, William; Li, Hui; Hesse, Michael

    2015-01-01

    Using fully kinetic simulations, we study the scaling of the inflow speed of collisionless magnetic reconnection in electron-positron plasmas from the non-relativistic to ultra-relativistic limit. In the anti-parallel configuration, the inflow speed increases with the upstream magnetization parameter sigma and approaches the speed of light when sigma is greater than O(100), leading to an enhanced reconnection rate. In all regimes, the divergence of the pressure tensor is the dominant term responsible for breaking the frozen-in condition at the x-line. The observed scaling agrees well with a simple model that accounts for the Lorentz contraction of the plasma passing through the diffusion region. The results demonstrate that the aspect ratio of the diffusion region, modified by the compression factor of proper density, remains approximately 0.1 in both the non-relativistic and relativistic limits.

  17. Electron impact excitation of H2 - Rydberg band systems and the benchmark dissociative cross section for H Lyman-alpha

    NASA Technical Reports Server (NTRS)

    Shemansky, D. E.; Hall, D. T.; Ajello, J. M.

    1985-01-01

    The cross sections sigma R 1 (2p) for excitation of H Ly-alpha emission produced by electron impact on H2 is reexamined. A more accurate estimate for sigma R 1 (2p) is obtained based on Born approximation estimates of the H2 Rydberg system cross sections using measured relative excitation functions. The obtained value is (8.18 + or -1.2) x 10 to the -18th sq cm at 100 eV, a factor of 0.69 below the value universally applied to cross section measurements over the past decade. Cross sections for the H2 Rydberg systems fixed in magnitude by the Born approximation have also been obtained using experimentally determined excitation functions. Accurate analytic expressions for these cross sections allow the direct calculation of rate coefficients.

  18. Illumination system design for a three-aspherical-mirror projection camera for extreme-ultraviolet lithography.

    PubMed

    Li, Y; Kinoshita, H; Watanabe, T; Irie, S; Shirayone, S; Okazaki, S

    2000-07-01

    A scanning critical illumination system is designed to couple a synchrotron radiation source to a three-aspherical-mirror imaging system for extreme ultraviolet lithography. A static illumination area of H x V = 8 mm x 3 mm (where H is horizontal and V is vertical) can be obtained. Uniform intensity distribution and a large ring field of H x V = 150 mm x 3 mm can be achieved by scanning of the mirror of the condenser. The coherence factor (sigma) of this illumination system is approximately 0.6, with the same beam divergence in both the horizontal and the vertical directions. We describe the performance of the imaging optics at sigma = 0.6 to confirm that the illumination optics can meet the requirements for three-aspherical-mirror imaging optics with a feature size of 0.06 microm.

  19. Dielectric properties of lung tissue as a function of air content.

    PubMed

    Nopp, P; Rapp, E; Pfützner, H; Nakesch, H; Ruhsam, C

    1993-06-01

    Dielectric measurements were made on lung samples with different electrode systems in the frequency range 5 kHz-100 kHz. In the case of plate electrodes and spot electrodes, the effects of electrode polarization were partly corrected. An air filling factor F is defined, which is determined from the mass and volume of the sample. The results indicate that the electrical properties of lung tissue are highly dependent on the condition of the tissue. Furthermore they show that the conductivity sigma as well as the relative permittivity epsilon r decreases with increasing F. This is discussed using histological material. Using a simple theoretical model, the decrease of sigma and epsilon r is explained by the thinning of the alveolar walls as well as by the deformation of the epithelial cells and blood vessels through the expansion of the alveoli.

  20. Atmospheric Lifetime of CHF2Br, a Proposed Substitute for Halons.

    PubMed

    Talukdar, R; Mellouki, A; Gierczak, T; Burkholder, J B; McKeen, S A; Ravishankara, A R

    1991-05-03

    The rate coefficients, k(1), for the reaction of OH with CHF(2)Br have been measured using pulsed photolysis and discharge flow techniques at temperatures (T) between 233 and 432 K to be k(1), = (7.4 +/- 1.6) x 10(-13) exp[-(1300 +/- 100)/T] cubic centimeters per molecule per second. The ultraviolet absorption cross sections, sigma, of this molecule between 190 and 280 nanometers were measured at 296 K. The k(1), and sigma values were used in a one-dimensional model to obtain an atmospheric lifetime of approximately 7 years for CHF(2)Br. This lifetime is shorter by approximately factors of 10 and 2 than those for CF(3)Br and CF(2)ClBr, respectively. The ozone depletion potentials of the three compounds will reflect these lifetimes.

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