The BaeSR Two-Component Regulatory System Mediates Resistance to Condensed Tannins in Escherichia coli▿ †

PubMed Central

Zoetendal, Erwin G.; Smith, Alexandra H.; Sundset, Monica A.; Mackie, Roderick I.

2008-01-01

The gene expression profiles of Escherichia coli strains grown anaerobically with or without Acacia mearnsii (black wattle) extract were compared to identify tannin resistance strategies. The cell envelope stress protein gene spy and the multidrug transporter-encoding operon mdtABCD, both under the control of the BaeSR two-component regulatory system, were significantly up-regulated in the presence of tannins. BaeSR mutants were more tannin sensitive than their wild-type counterparts. PMID:18039828

Analysis of the activity and regulon of the two-component regulatory system encoded by Cjj1484 and Cjj1483 of Campylobacter jejuni

USDA-ARS?s Scientific Manuscript database

Campylobacter jejuni is a leading cause of bacterial diarrheal disease throughout the world and a frequent commensal in the intestinal tract of poultry and many other animals. For maintaining optimal growth and ability to colonize various hosts, C. jejuni depends upon two-component regulatory system...

A two-component regulatory system controls autoregulated serpin expression in Bifidobacterium breve UCC2003.

PubMed

Alvarez-Martin, Pablo; O'Connell Motherway, Mary; Turroni, Francesca; Foroni, Elena; Ventura, Marco; van Sinderen, Douwe

2012-10-01

This work reports on the identification and molecular characterization of a two-component regulatory system (2CRS), encoded by serRK, which is believed to control the expression of the ser(2003) locus in Bifidobacterium breve UCC2003. The ser(2003) locus consists of two genes, Bbr_1319 (sagA) and Bbr_1320 (serU), which are predicted to encode a hypothetical membrane-associated protein and a serpin-like protein, respectively. The response regulator SerR was shown to bind to the promoter region of ser(2003), and the probable recognition sequence of SerR was determined by a combinatorial approach of in vitro site-directed mutagenesis coupled to transcriptional fusion and electrophoretic mobility shift assays (EMSAs). The importance of the serRK 2CRS in the response of B. breve to protease-mediated induction was confirmed by generating a B. breve serR insertion mutant, which was shown to exhibit altered ser(2003) transcriptional induction patterns compared to the parent strain, UCC2003. Interestingly, the analysis of a B. breve serU mutant revealed that the SerRK signaling pathway appears to include a SerU-dependent autoregulatory loop.

A Two-Component Regulatory System Controls Autoregulated Serpin Expression in Bifidobacterium breve UCC2003

PubMed Central

Alvarez-Martin, Pablo; O'Connell Motherway, Mary; Turroni, Francesca; Foroni, Elena; Ventura, Marco

2012-01-01

This work reports on the identification and molecular characterization of a two-component regulatory system (2CRS), encoded by serRK, which is believed to control the expression of the ser2003 locus in Bifidobacterium breve UCC2003. The ser2003 locus consists of two genes, Bbr_1319 (sagA) and Bbr_1320 (serU), which are predicted to encode a hypothetical membrane-associated protein and a serpin-like protein, respectively. The response regulator SerR was shown to bind to the promoter region of ser2003, and the probable recognition sequence of SerR was determined by a combinatorial approach of in vitro site-directed mutagenesis coupled to transcriptional fusion and electrophoretic mobility shift assays (EMSAs). The importance of the serRK 2CRS in the response of B. breve to protease-mediated induction was confirmed by generating a B. breve serR insertion mutant, which was shown to exhibit altered ser2003 transcriptional induction patterns compared to the parent strain, UCC2003. Interestingly, the analysis of a B. breve serU mutant revealed that the SerRK signaling pathway appears to include a SerU-dependent autoregulatory loop. PMID:22843530

Inefficient coupling between proton transport and ATP synthesis may be the pathogenic mechanism for NARP and Leigh syndrome resulting from the T8993G mutation in mtDNA.

PubMed

Sgarbi, Gianluca; Baracca, Alessandra; Lenaz, Giorgio; Valentino, Lucia M; Carelli, Valerio; Solaini, Giancarlo

2006-05-01

Mutations in the ATP6 gene of mtDNA (mitochondrial DNA) have been shown to cause several different neurological disorders. The product of this gene is ATPase 6, an essential component of the F1F0-ATPase. In the present study we show that the function of the F1F0-ATPase is impaired in lymphocytes from ten individuals harbouring the mtDNA T8993G point mutation associated with NARP (neuropathy, ataxia and retinitis pigmentosa) and Leigh syndrome. We show that the impaired function of both the ATP synthase and the proton transport activity of the enzyme correlates with the amount of the mtDNA that is mutated, ranging from 13-94%. The fluorescent dye RH-123 (Rhodamine-123) was used as a probe to determine whether or not passive proton flux (i.e. from the intermembrane space to the matrix) is affected by the mutation. Under state 3 respiratory conditions, a slight difference in RH-123 fluorescence quenching kinetics was observed between mutant and control mitochondria that suggests a marginally lower F0 proton flux capacity in cells from patients. Moreover, independent of the cellular mutant load the specific inhibitor oligomycin induced a marked enhancement of the RH-123 quenching rate, which is associated with a block in proton conductivity through F0 [Linnett and Beechey (1979) Inhibitors of the ATP synthethase system. Methods Enzymol. 55, 472-518]. Overall, the results rule out the previously proposed proton block as the basis of the pathogenicity of the mtDNA T8993G mutation. Since the ATP synthesis rate was decreased by 70% in NARP patients compared with controls, we suggest that the T8993G mutation affects the coupling between proton translocation through F0 and ATP synthesis on F1. We discuss our findings in view of the current knowledge regarding the rotary mechanism of catalysis of the enzyme.

The Pseudomonas aeruginosa AlgZR two-component system coordinates multiple phenotypes

PubMed Central

Okkotsu, Yuta; Little, Alexander S.; Schurr, Michael J.

2014-01-01

Pseudomonas aeruginosa is an opportunistic pathogen that causes a multitude of infections. These infections can occur at almost any site in the body and are usually associated with a breach of the innate immune system. One of the prominent sites where P. aeruginosa causes chronic infections is within the lungs of cystic fibrosis patients. P. aeruginosa uses two-component systems that sense environmental changes to differentially express virulence factors that cause both acute and chronic infections. The P. aeruginosa AlgZR two component system is one of its global regulatory systems that affects the organism's fitness in a broad manner. This two-component system is absolutely required for two P. aeruginosa phenotypes: twitching motility and alginate production, indicating its importance in both chronic and acute infections. Additionally, global transcriptome analyses indicate that it regulates the expression of many different genes, including those associated with quorum sensing, type IV pili, type III secretion system, anaerobic metabolism, cyanide and rhamnolipid production. This review examines the complex AlgZR regulatory network, what is known about the structure and function of each protein, and how it relates to the organism's ability to cause infections. PMID:24999454

Comparative Analysis of Wolbachia Genomes Reveals Streamlining and Divergence of Minimalist Two-Component Systems

PubMed Central

Christensen, Steen; Serbus, Laura Renee

2015-01-01

Two-component regulatory systems are commonly used by bacteria to coordinate intracellular responses with environmental cues. These systems are composed of functional protein pairs consisting of a sensor histidine kinase and cognate response regulator. In contrast to the well-studied Caulobacter crescentus system, which carries dozens of these pairs, the streamlined bacterial endosymbiont Wolbachia pipientis encodes only two pairs: CckA/CtrA and PleC/PleD. Here, we used bioinformatic tools to compare characterized two-component system relays from C. crescentus, the related Anaplasmataceae species Anaplasma phagocytophilum and Ehrlichia chaffeensis, and 12 sequenced Wolbachia strains. We found the core protein pairs and a subset of interacting partners to be highly conserved within Wolbachia and these other Anaplasmataceae. Genes involved in two-component signaling were positioned differently within the various Wolbachia genomes, whereas the local context of each gene was conserved. Unlike Anaplasma and Ehrlichia, Wolbachia two-component genes were more consistently found clustered with metabolic genes. The domain architecture and key functional residues standard for two-component system proteins were well-conserved in Wolbachia, although residues that specify cognate pairing diverged substantially from other Anaplasmataceae. These findings indicate that Wolbachia two-component signaling pairs share considerable functional overlap with other α-proteobacterial systems, whereas their divergence suggests the potential for regulatory differences and cross-talk. PMID:25809075

Transportation of Large Wind Components: A Permitting and Regulatory Review

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

Levine, Aaron; Cook, Jeff

This report summarizes permitting and regulatory issues associated with transporting wind turbine blades, towers, and nacelles as well as large transformers (wind components). These wind components are commonly categorized as oversized and overweight (OSOW) and require specific permit approvals from state and local jurisdictions. The report was developed based on a Quadrennial Energy Review (QER) recommendation on logistical requirements for the transportation of 'oversized or high-consequence energy materials, equipment, and components.'

Long-term outcome of Leigh syndrome caused by the NARP-T8993C mtDNA mutation.

PubMed

Debray, François-Guillaume; Lambert, Marie; Lortie, Anne; Vanasse, Michel; Mitchell, Grant A

2007-09-01

Mutations at mitochondrial DNA (mtDNA) nucleotide 8993 can cause neurogenic weakness, ataxia and retinitis pigmentosa (NARP syndrome), or maternally inherited Leigh syndrome (LS), with a correlation between the amount of mutant mtDNA and the severity of the neurological disease. The T8993C mutation is generally considered to be clinically milder than the T8993G mutation but when the level of heteroplasmy exceeds 90%, progressive neurodegeneration has been found. We report on a long-term follow-up of a patient who presented at 4 years of age with typical LS but showed an unexpected resolution of his symptoms and a favorable outcome. At 18 years of age, his neurological examination was near normal, with neither peripheral neuropathy nor retinopathy. mtDNA analysis identified the presence of T8993C mutation at high level (>95%) in the patient's blood leukocytes. This case report and literature review emphasizes the variability of the phenotypic expression of the T8993C mutation and the need for caution in predictive counseling in such patients. (c) 2007 Wiley-Liss, Inc. Copyright 2007 Wiley-Liss, Inc.

Regulatory networks and connected components of the neutral space. A look at functional islands

NASA Astrophysics Data System (ADS)

Boldhaus, G.; Klemm, K.

2010-09-01

The functioning of a living cell is largely determined by the structure of its regulatory network, comprising non-linear interactions between regulatory genes. An important factor for the stability and evolvability of such regulatory systems is neutrality - typically a large number of alternative network structures give rise to the necessary dynamics. Here we study the discretized regulatory dynamics of the yeast cell cycle [Li et al., PNAS, 2004] and the set of networks capable of reproducing it, which we call functional. Among these, the empirical yeast wildtype network is close to optimal with respect to sparse wiring. Under point mutations, which establish or delete single interactions, the neutral space of functional networks is fragmented into ≈ 4.7 × 108 components. One of the smaller ones contains the wildtype network. On average, functional networks reachable from the wildtype by mutations are sparser, have higher noise resilience and fewer fixed point attractors as compared with networks outside of this wildtype component.

The BatR/BatS Two-Component Regulatory System Controls the Adaptive Response of Bartonella henselae during Human Endothelial Cell Infection ▿ † ‡

PubMed Central

Quebatte, Maxime; Dehio, Michaela; Tropel, David; Basler, Andrea; Toller, Isabella; Raddatz, Guenter; Engel, Philipp; Huser, Sonja; Schein, Hermine; Lindroos, Hillevi L.; Andersson, Siv G. E.; Dehio, Christoph

2010-01-01

Here, we report the first comprehensive study of Bartonella henselae gene expression during infection of human endothelial cells. Expression of the main cluster of upregulated genes, comprising the VirB type IV secretion system and its secreted protein substrates, is shown to be under the positive control of the transcriptional regulator BatR. We demonstrate binding of BatR to the promoters of the virB operon and a substrate-encoding gene and provide biochemical evidence that BatR and BatS constitute a functional two-component regulatory system. Moreover, in contrast to the acid-inducible (pH 5.5) homologs ChvG/ChvI of Agrobacterium tumefaciens, BatR/BatS are optimally activated at the physiological pH of blood (pH 7.4). By conservation analysis of the BatR regulon, we show that BatR/BatS are uniquely adapted to upregulate a genus-specific virulence regulon during hemotropic infection in mammals. Thus, we propose that BatR/BatS two-component system homologs represent vertically inherited pH sensors that control the expression of horizontally transmitted gene sets critical for the diverse host-associated life styles of the alphaproteobacteria. PMID:20418395

Endoribonuclease-Based Two-Component Repressor Systems for Tight Gene Expression Control in Plants

DOE PAGES

Liang, Yan; Richardson, Sarah; Yan, Jingwei; ...

2017-01-17

Tight control and multifactorial regulation of gene expression are important challenges in genetic engineering and are critical for the development of regulatory circuits. In meeting these challenges we will facilitate transgene expression regulation and support the fine-tuning of metabolic pathways to avoid the accumulation of undesired intermediates. By employing the endoribonuclease Csy4 and its recognition sequence from Pseudomonas aeruginosa and manipulating 5'UTR of mRNA, we developed a two-component expression–repression system to tightly control synthesis of transgene products. We demonstrated that this regulatory device was functional in monocotyledonous and dicotyledonous plant species, and showed that it can be used to repressmore » transgene expression by >400-fold and to synchronize transgene repression. In addition to tissue-specific transgene repression, this system offers stimuli-dependent expression control. Here, we identified 54 orthologous systems from various bacteria, using a bioinformatics approach and then validated in planta the activity for a few of those systems, demonstrating the potential diversity of such a two-component repressor system.« less

Endoribonuclease-Based Two-Component Repressor Systems for Tight Gene Expression Control in Plants

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

Liang, Yan; Richardson, Sarah; Yan, Jingwei

Tight control and multifactorial regulation of gene expression are important challenges in genetic engineering and are critical for the development of regulatory circuits. In meeting these challenges we will facilitate transgene expression regulation and support the fine-tuning of metabolic pathways to avoid the accumulation of undesired intermediates. By employing the endoribonuclease Csy4 and its recognition sequence from Pseudomonas aeruginosa and manipulating 5'UTR of mRNA, we developed a two-component expression–repression system to tightly control synthesis of transgene products. We demonstrated that this regulatory device was functional in monocotyledonous and dicotyledonous plant species, and showed that it can be used to repressmore » transgene expression by >400-fold and to synchronize transgene repression. In addition to tissue-specific transgene repression, this system offers stimuli-dependent expression control. Here, we identified 54 orthologous systems from various bacteria, using a bioinformatics approach and then validated in planta the activity for a few of those systems, demonstrating the potential diversity of such a two-component repressor system.« less

Development of disease-resistant rice using regulatory components of induced disease resistance

PubMed Central

Takatsuji, Hiroshi

2014-01-01

Infectious diseases cause huge crop losses annually. In response to pathogen attacks, plants activate defense systems that are mediated through various signaling pathways. The salicylic acid (SA) signaling pathway is the most powerful of these pathways. Several regulatory components of the SA signaling pathway have been identified, and are potential targets for genetic manipulation of plants’ disease resistance. However, the resistance associated with these regulatory components is often accompanied by fitness costs; that is, negative effects on plant growth and crop yield. Chemical defense inducers, such as benzothiadiazole and probenazole, act on the SA pathway and induce strong resistance to various pathogens without major fitness costs, owing to their ‘priming effect.’ Studies on how benzothiadiazole induces disease resistance in rice have identified WRKY45, a key transcription factor in the branched SA pathway, and OsNPR1/NH1. Rice plants overexpressing WRKY45 were extremely resistant to rice blast disease caused by the fungus Magnaporthe oryzae and bacterial leaf blight disease caused by Xanthomonas oryzae pv. oryzae (Xoo), the two major rice diseases. Disease resistance is often accompanied by fitness costs; however, WRKY45 overexpression imposed relatively small fitness costs on rice because of its priming effect. This priming effect was similar to that of chemical defense inducers, although the fitness costs were amplified by some environmental factors. WRKY45 is degraded by the ubiquitin–proteasome system, and the dual role of this degradation partly explains the priming effect. The synergistic interaction between SA and cytokinin signaling that activates WRKY45 also likely contributes to the priming effect. With a main focus on these studies, I review the current knowledge of SA-pathway-dependent defense in rice by comparing it with that in Arabidopsis, and discuss potential strategies to develop disease-resistant rice using signaling components

Relevance of the two-component sensor protein CiaH to acid and oxidative stress responses in Streptococcus pyogenes.

PubMed

Tatsuno, Ichiro; Isaka, Masanori; Okada, Ryo; Zhang, Yan; Hasegawa, Tadao

2014-03-28

The production of virulence proteins depends on environmental factors, and two-component regulatory systems are involved in sensing these factors. We previously established knockout strains in all suspected two-component regulatory sensor proteins of the emm1 clinical strain of S. pyogenes and examined their relevance to acid stimuli in a natural atmosphere. In the present study, their relevance to acid stimuli was re-examined in an atmosphere containing 5% CO2. The spy1236 (which is identical to ciaHpy) sensor knockout strain showed significant growth reduction compared with the parental strain in broth at pH 6.0, suggesting that the Spy1236 (CiaHpy) two-component sensor protein is involved in acid response of S. pyogenes. CiaH is also conserved in Streptococcus pneumoniae, and it has been reported that deletion of the gene for its cognate response regulator (ciaRpn) made the pneumococcal strains more sensitive to oxidative stress. In this report, we show that the spy1236 knockout mutant of S. pyogenes is more sensitive to oxidative stress than the parental strain. These results suggest that the two-component sensor protein CiaH is involved in stress responses in S. pyogenes.

The Yersinia pestis gcvB gene encodes two small regulatory RNA molecules

PubMed Central

McArthur, Sarah D; Pulvermacher, Sarah C; Stauffer, George V

2006-01-01

Background In recent years it has become clear that small non-coding RNAs function as regulatory elements in bacterial virulence and bacterial stress responses. We tested for the presence of the small non-coding GcvB RNAs in Y. pestis as possible regulators of gene expression in this organism. Results In this study, we report that the Yersinia pestis KIM6 gcvB gene encodes two small RNAs. Transcription of gcvB is activated by the GcvA protein and repressed by the GcvR protein. The gcvB-encoded RNAs are required for repression of the Y. pestis dppA gene, encoding the periplasmic-binding protein component of the dipeptide transport system, showing that the GcvB RNAs have regulatory activity. A deletion of the gcvB gene from the Y. pestis KIM6 chromosome results in a decrease in the generation time of the organism as well as a change in colony morphology. Conclusion The results of this study indicate that the Y. pestis gcvB gene encodes two small non-coding regulatory RNAs that repress dppA expression. A gcvB deletion is pleiotropic, suggesting that the sRNAs are likely involved in controlling genes in addition to dppA. PMID:16768793

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

PubMed

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

2017-11-01

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

Systematic mapping of two component response regulators to gene targets in a model sulfate reducing bacterium.

PubMed

Rajeev, Lara; Luning, Eric G; Dehal, Paramvir S; Price, Morgan N; Arkin, Adam P; Mukhopadhyay, Aindrila

2011-10-12

Two component regulatory systems are the primary form of signal transduction in bacteria. Although genomic binding sites have been determined for several eukaryotic and bacterial transcription factors, comprehensive identification of gene targets of two component response regulators remains challenging due to the lack of knowledge of the signals required for their activation. We focused our study on Desulfovibrio vulgaris Hildenborough, a sulfate reducing bacterium that encodes unusually diverse and largely uncharacterized two component signal transduction systems. We report the first systematic mapping of the genes regulated by all transcriptionally acting response regulators in a single bacterium. Our results enabled functional predictions for several response regulators and include key processes of carbon, nitrogen and energy metabolism, cell motility and biofilm formation, and responses to stresses such as nitrite, low potassium and phosphate starvation. Our study also led to the prediction of new genes and regulatory networks, which found corroboration in a compendium of transcriptome data available for D. vulgaris. For several regulators we predicted and experimentally verified the binding site motifs, most of which were discovered as part of this study. The gene targets identified for the response regulators allowed strong functional predictions to be made for the corresponding two component systems. By tracking the D. vulgaris regulators and their motifs outside the Desulfovibrio spp. we provide testable hypotheses regarding the functions of orthologous regulators in other organisms. The in vitro array based method optimized here is generally applicable for the study of such systems in all organisms.

A Retentive Memory of Tetrachloroethene Respiration in Sulfurospirillum halorespirans - involved Proteins and a possible link to Acetylation of a Two-Component Regulatory System.

PubMed

Türkowsky, Dominique; Esken, Jens; Goris, Tobias; Schubert, Torsten; Diekert, Gabriele; Jehmlich, Nico; von Bergen, Martin

2018-06-15

Organohalide respiration (OHR), comprising the reductive dehalogenation of halogenated organic compounds, is subject to a unique memory effect and long-term transcriptional downregulation of the involved genes in Sulfurospirillum multivorans. Gene expression ceases slowly over approximately 100 generations in the absence of tetrachloroethene (PCE). However, the molecular mechanisms of this regulation process are not understood. We show here that Sulfurospirillum halorespirans undergoes the same type of regulation when cultivated without chlorinated ethenes for a long period of time. In addition, we compared the proteomes of S. halorespirans cells cultivated in the presence of PCE with those of cells long- and short-term cultivated with nitrate as the sole electron acceptor. Important OHR-related proteins previously unidentified in S. multivorans include a histidine kinase, a putative quinol dehydrogenase membrane protein, and a PCE-induced porin. Since for some regulatory proteins a posttranslational regulation of activity by lysine acetylations is known, we also analyzed the acetylome of S. halorespirans, revealing that 32% of the proteome was acetylated in at least one condition. The data indicate that the response regulator and the histidine kinase of a two-component system most probably involved in induction of PCE respiration are highly acetylated during short-term cultivation with nitrate in the absence of PCE. The so far unique long-term downregulation of organohalide respiration is now identified in a second species suggesting a broader distribution of this regulatory phenomenon. An improved protein extraction method allowed the identification of proteins most probably involved in transcriptional regulation of OHR in Sulfurospirillum spp. Our data indicate that acetylations of regulatory proteins are involved in this extreme, sustained standby-mode of metabolic enzymes in the absence of a substrate. This first published acetylome of Epsilonproteobacteria

Systematic mapping of two component response regulators to gene targets in a model sulfate reducing bacterium

PubMed Central

2011-01-01

Background Two component regulatory systems are the primary form of signal transduction in bacteria. Although genomic binding sites have been determined for several eukaryotic and bacterial transcription factors, comprehensive identification of gene targets of two component response regulators remains challenging due to the lack of knowledge of the signals required for their activation. We focused our study on Desulfovibrio vulgaris Hildenborough, a sulfate reducing bacterium that encodes unusually diverse and largely uncharacterized two component signal transduction systems. Results We report the first systematic mapping of the genes regulated by all transcriptionally acting response regulators in a single bacterium. Our results enabled functional predictions for several response regulators and include key processes of carbon, nitrogen and energy metabolism, cell motility and biofilm formation, and responses to stresses such as nitrite, low potassium and phosphate starvation. Our study also led to the prediction of new genes and regulatory networks, which found corroboration in a compendium of transcriptome data available for D. vulgaris. For several regulators we predicted and experimentally verified the binding site motifs, most of which were discovered as part of this study. Conclusions The gene targets identified for the response regulators allowed strong functional predictions to be made for the corresponding two component systems. By tracking the D. vulgaris regulators and their motifs outside the Desulfovibrio spp. we provide testable hypotheses regarding the functions of orthologous regulators in other organisms. The in vitro array based method optimized here is generally applicable for the study of such systems in all organisms. PMID:21992415

Neuronal activity-regulated pentraxin expressed in medial prefrontal cortex neurons is not necessary for extinction of heroin self-administration.

PubMed

Blouin, Ashley M; Stern, Anna L; Han, Sungho; Theberge, Florence R; Wang, Chuansong; During, Matthew J; Baraban, Jay M; Reti, Irving M

2013-08-01

The medial prefrontal cortex (mPFC) plays a key role in extinction learning. Previously, we found that expression of a neuronal activity-regulated pentraxin (Narp) dominant-negative construct in the mPFC of mice blocked extinction of morphine-conditioned place preference. To further investigate the role of mPFC Narp in the extinction of drug seeking, we tested whether mPFC Narp is necessary for the extinction of heroin self-administration in rats. Specifically, we injected an adeno-associated viral vector expressing a dominant-negative form of Narp (NarpN) into the infralimbic region of the mPFC of rats and compared lever presses during extinction to those of rats injected with a control virus. In contrast to our previous study, we found that injection of NarpN did not affect extinction of heroin self-administration. Our findings suggest that mPFC Narp is necessary for extinction of opiate seeking in the Pavlovian-conditioned place preference paradigm but not in the operant paradigm of drug self-administration.

Gene expression of a two-component regulatory system associated with sunscreen biosynthesis in the cyanobacterium Nostoc punctiforme ATCC 29133.

PubMed

Janssen, Jacob; Soule, Tanya

2016-01-01

Long-wavelength ultraviolet radiation (UVA) can damage cells through photooxidative stress, leading to harmful photosensitized proteins and pigments in cyanobacteria. To mitigate damage, some cyanobacteria secrete the UVA-absorbing pigment scytonemin into their extracellular sheath. Comparative genomic analyses suggest that scytonemin biosynthesis is regulated by the two-component regulatory system (TCRS) proteins encoded by Npun_F1277 and Npun_F1278 in the cyanobacterium Nostoc punctiforme ATCC 29133. To understand the dynamics of these genes, their expression was measured following exposure to UVA, UVB, high visible (VIS) irradiance and oxidative stress for 20, 40 and 60 min. Overall, both genes had statistically similar patterns of expression for all four conditions and were generally upregulated, except for those exposed to UVB by 60 min and for the cells under oxidative stress. The greatest UVA response was an upregulation by 20 min, while the response to UVB was the most dramatic and persisted through 40 min. High VIS irradiance resulted in a modest upregulation, while oxidative stress caused a slight downregulation. Both genes were also found to occur on the same transcript. These results demonstrate that these genes are positively responding to several light-associated conditions, which suggests that this TCRS may regulate more than just scytonemin biosynthesis under UVA stress. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Divide and conquer: The Pseudomonas aeruginosa two-component hybrid SagS enables biofilm formation and recalcitrance of biofilm cells to antimicrobial agents via distinct regulatory circuits

PubMed Central

Petrova, Olga E.; Gupta, Kajal; Liao, Julie; Goodwine, James S.; Sauer, Karin

2017-01-01

The opportunistic pathogen Pseudomonas aeruginosa forms antimicrobial resistant biofilms through sequential steps requiring several two-component regulatory systems. The sensor-regulator hybrid SagS plays a central role in biofilm development by enabling the switch from the planktonic to the biofilm mode of growth, and by facilitating the transition of biofilm cells to a highly tolerant state. However, the mechanism by which SagS accomplishes both functions is unknown. SagS harbors a periplasmic sensory HmsP, and phosphorelay HisKA and Rec domains. We used SagS domain constructs and site-directed mutagenesis to elucidate how SagS performs its dual functions. We demonstrate that HisKA-Rec and the phospho-signaling between SagS and BfiS contribute to the switch to the biofilm mode of growth, but not to the tolerant state. Instead, expression of SagS domain constructs harboring HmsP rendered ΔsagS biofilm cells as recalcitrant to antimicrobial agents as wild-type biofilms, likely by restoring BrlR production and cellular c-di-GMP levels to wild-type levels. Restoration of biofilm tolerance by HmsP was independent of biofilm biomass accumulation, RsmA, RsmYZ, HptB, and BfiSR-downstream targets. Our findings thus suggest that SagS likely makes use of a “divide-and-conquer” mechanism to regulate its dual switch function, by activating two distinct regulatory networks via its individual domains. PMID:28263038

Epsilon-toxin production by Clostridium perfringens type D strain CN3718 is dependent upon the agr operon but not the VirS/VirR two-component regulatory system.

PubMed

Chen, Jianming; Rood, Julian I; McClane, Bruce A

2011-01-01

Clostridium perfringens type B and D strains cause enterotoxemias and enteritis in livestock after proliferating in the intestines and producing epsilon-toxin (ETX), alpha-toxin (CPA), and, usually, perfringolysin O (PFO). Although ETX is one of the most potent bacterial toxins, the regulation of ETX production by type B or D strains remains poorly understood. The present work determined that the type D strain CN3718 upregulates production of ETX upon close contact with enterocyte-like Caco-2 cells. This host cell-induced upregulation of ETX expression was mediated at the transcriptional level. Using an isogenic agrB null mutant and complemented strain, the agr operon was shown to be required when CN3718 produces ETX in broth culture or, via a secreted signal consistent with a quorum-sensing (QS) effect, upregulates ETX production upon contact with host cells. These findings provide the first insights into the regulation of ETX production, as well as additional evidence that the Agr-like QS system functions as a global regulator of C. perfringens toxin production. Since it was proposed previously that the Agr-like QS system regulates C. perfringens gene expression via the VirS/VirR two-component regulatory system, an isogenic virR null mutant of CN3718 was constructed to evaluate the importance of VirS/VirR for CN3718 toxin production. This mutation affected production of CPA and PFO, but not ETX, by CN3718. These results provide the first indication that C. perfringens toxin expression regulation by the Agr-like quorum-sensing system may not always act via the VirS/VirR two-component system. IMPORTANCE Mechanisms by which Clostridium perfringens type B and D strains regulate production of epsilon-toxin (ETX), a CDC class B select toxin, are poorly understood. Production of several other toxins expressed by C. perfringens is wholly or partially regulated by both the Agr-like quorum-sensing (QS) system and the VirS/VirR two-component regulatory system, so the

Interplay among Membrane-Bound Lytic Transglycosylase D1, the CreBC Two-Component Regulatory System, the AmpNG-AmpDI-NagZ-AmpR Regulatory Circuit, and L1/L2 β-Lactamase Expression in Stenotrophomonas maltophilia

PubMed Central

Huang, Yi-Wei; Wu, Chao-Jung; Hu, Rouh-Mei; Lin, Yi-Tsung

2015-01-01

Lytic transglycosylases (LTs) are an important class of enzymes involved in peptidoglycan (PG) cleavage, with the concomitant formation of an intramolecular 1,6-anhydromuramoyl reaction product. There are six annotated LT genes in the Stenotrophomonas maltophilia genome, including genes for five membrane-bound LTs (mltA, mltB1, mltB2, mltD1, and mltD2) and a gene for soluble LT (slt). Six LTs of S. maltophilia KJ were systematically mutated, yielding the ΔmltA, ΔmltB1, ΔmltB2, ΔmltD1, ΔmltD2, and Δslt mutants. Inactivation of mltD1 conferred a phenotype of elevated uninduced β-lactamase activity. The underlying mechanism responsible for this phenotype was elucidated by the construction of several mutants and determination of β-lactamase activity. The expression of the genes assayed was assessed by quantitative reverse transcriptase PCR and a promoter transcription fusion assay. The results demonstrate that ΔmltD1 mutant-mediated L1/L2 β-lactamase expression involved the creBC two-component regulatory system (TCS) and the ampNG-ampDI-nagZ-ampR regulatory circuit. The inactivation of mltD1 resulted in mltB1 and mltD2 upexpression in a creBC- and ampNG-dependent manner. The overexpressed MltB1 and MltD2 activity contributed to the expression of the L1/L2 β-lactamase genes via the ampNG-ampDI-nagZ-ampR regulatory circuit. These findings reveal, for the first time, a linkage between LTs, the CreBC TCS, the ampNG-ampDI-nagZ-ampR regulatory circuit, and L1/L2 β-lactamase expression in S. maltophilia. PMID:26282431

VfrB Is a Key Activator of the Staphylococcus aureus SaeRS Two-Component System.

PubMed

Krute, Christina N; Rice, Kelly C; Bose, Jeffrey L

2017-03-01

In previous studies, we identified the fatty acid kinase virulence factor regulator B (VfrB) as a potent regulator of α-hemolysin and other virulence factors in Staphylococcus aureus In this study, we demonstrated that VfrB is a positive activator of the SaeRS two-component regulatory system. Analysis of vfrB , saeR , and saeS mutant strains revealed that VfrB functions in the same pathway as SaeRS. At the transcriptional level, the promoter activities of SaeRS class I ( coa ) and class II ( hla ) target genes were downregulated during the exponential growth phase in the vfrB mutant, compared to the wild-type strain. In addition, saePQRS expression was decreased in the vfrB mutant strain, demonstrating a need for this protein in the autoregulation of SaeRS. The requirement for VfrB-mediated activation was circumvented when SaeS was constitutively active due to an SaeS (L18P) substitution. Furthermore, activation of SaeS via human neutrophil peptide 1 (HNP-1) overcame the dependence on VfrB for transcription from class I Sae promoters. Consistent with the role of VfrB in fatty acid metabolism, hla expression was decreased in the vfrB mutant with the addition of exogenous myristic acid. Lastly, we determined that aspartic acid residues D38 and D40, which are predicted to be key to VfrB enzymatic activity, were required for VfrB-mediated α-hemolysin production. Collectively, this study implicates VfrB as a novel accessory protein needed for the activation of SaeRS in S. aureus IMPORTANCE The SaeRS two-component system is a key regulator of virulence determinant production in Staphylococcus aureus Although the regulon of this two-component system is well characterized, the activation mechanisms, including the specific signaling molecules, remain elusive. Elucidating the complex regulatory circuit of SaeRS regulation is important for understanding how the system contributes to disease causation by this pathogen. To this end, we have identified the fatty acid kinase

Identification of a two-component signal transduction system involved in fimbriation of Porphyromonas gingivalis.

PubMed

Hayashi, J; Nishikawa, K; Hirano, R; Noguchi, T; Yoshimura, F

2000-01-01

Porphyromonas gingivalis, a periodontopathogen, is an oral anaerobic gram-negative bacterium with numerous fimbriae on the cell surface. Fimbriae have been considered to be an important virulence factor in this organism. We analyzed the genomic DNA of transposon-induced, fimbria-deficient mutants derived from ATCC 33277 and found that seven independent mutants had transposon insertions within the same restriction fragment. Cloning and sequencing of the disrupted region from one of the mutants revealed two adjacent open reading frames (ORFs) which seemed to encode a two-component signal transduction system. We also found that six of the mutants had insertions in a gene, fimS, a homologue of the genes encoding sensor kinase, and that the insertion in the remaining one disrupted the gene immediately downstream, fimR, a homologue of the response regulator genes in other bacteria. These findings suggest that this two-component regulatory system is involved in fimbriation of P. gingivalis.

Regulation of virulence by a two-component system in group B streptococcus.

PubMed

Jiang, Sheng-Mei; Cieslewicz, Michael J; Kasper, Dennis L; Wessels, Michael R

2005-02-01

Group B Streptococcus (GBS) is frequently carried in the gastrointestinal or genitourinary tract as a commensal organism, yet it has the potential to cause life-threatening infection in newborn infants, pregnant women, and individuals with chronic illness. Regulation of virulence factor expression may affect whether GBS behaves as an asymptomatic colonizer or an invasive pathogen, but little is known about how such factors are controlled in GBS. We now report the characterization of a GBS locus that encodes a two-component regulatory system similar to CsrRS (or CovRS) in Streptococcus pyogenes. Inactivation of csrR, encoding the putative response regulator, in two unrelated wild-type strains of GBS resulted in a marked increase in production of beta-hemolysin/cytolysin and a striking decrease in production of CAMP factor, an unrelated cytolytic toxin. Quantitative RNA hybridization experiments revealed that these two phenotypes were associated with a marked increase and decrease in expression of the corresponding genes, cylE and cfb, respectively. The CsrR mutant strains also displayed increased expression of scpB encoding C5a peptidase. Similar, but less marked, changes in gene expression were observed in CsrS (putative sensor component) mutants, evidence that CsrR and CsrS constitute a functional two-component system. Experimental infection studies in mice demonstrated reduced virulence of both CsrR and CsrS mutant strains relative to the wild type. Together, these results indicate that CsrRS regulates expression of multiple GBS virulence determinants and is likely to play an important role in GBS pathogenesis.

Modular and coordinated expression of immune system regulatory and signaling components in the developing and adult nervous system.

PubMed

Monzón-Sandoval, Jimena; Castillo-Morales, Atahualpa; Crampton, Sean; McKelvey, Laura; Nolan, Aoife; O'Keeffe, Gerard; Gutierrez, Humberto

2015-01-01

During development, the nervous system (NS) is assembled and sculpted through a concerted series of neurodevelopmental events orchestrated by a complex genetic programme. While neural-specific gene expression plays a critical part in this process, in recent years, a number of immune-related signaling and regulatory components have also been shown to play key physiological roles in the developing and adult NS. While the involvement of individual immune-related signaling components in neural functions may reflect their ubiquitous character, it may also reflect a much wider, as yet undescribed, genetic network of immune-related molecules acting as an intrinsic component of the neural-specific regulatory machinery that ultimately shapes the NS. In order to gain insights into the scale and wider functional organization of immune-related genetic networks in the NS, we examined the large scale pattern of expression of these genes in the brain. Our results show a highly significant correlated expression and transcriptional clustering among immune-related genes in the developing and adult brain, and this correlation was the highest in the brain when compared to muscle, liver, kidney and endothelial cells. We experimentally tested the regulatory clustering of immune system (IS) genes by using microarray expression profiling in cultures of dissociated neurons stimulated with the pro-inflammatory cytokine TNF-alpha, and found a highly significant enrichment of immune system-related genes among the resulting differentially expressed genes. Our findings strongly suggest a coherent recruitment of entire immune-related genetic regulatory modules by the neural-specific genetic programme that shapes the NS.

A Sensory Complex Consisting of an ATP-binding Cassette Transporter and a Two-component Regulatory System Controls Bacitracin Resistance in Bacillus subtilis*

PubMed Central

Dintner, Sebastian; Heermann, Ralf; Fang, Chong; Jung, Kirsten; Gebhard, Susanne

2014-01-01

Resistance against antimicrobial peptides in many Firmicutes bacteria is mediated by detoxification systems that are composed of a two-component regulatory system (TCS) and an ATP-binding cassette (ABC) transporter. The histidine kinases of these systems depend entirely on the transporter for sensing of antimicrobial peptides, suggesting a novel mode of signal transduction where the transporter constitutes the actual sensor. The aim of this study was to investigate the molecular mechanisms of this unusual signaling pathway in more detail, using the bacitracin resistance system BceRS-BceAB of Bacillus subtilis as an example. To analyze the proposed communication between TCS and the ABC transporter, we characterized their interactions by bacterial two-hybrid analyses and could show that the permease BceB and the histidine kinase BceS interact directly. In vitro pulldown assays confirmed this interaction, which was found to be independent of bacitracin. Because it was unknown whether BceAB-type transporters could detect their substrate peptides directly or instead recognized the peptide-target complex in the cell envelope, we next analyzed substrate binding by the transport permease, BceB. Direct and specific binding of bacitracin by BceB was demonstrated by surface plasmon resonance spectroscopy. Finally, in vitro signal transduction assays indicated that complex formation with the transporter influenced the autophosphorylation activity of the histidine kinase. Taken together, our findings clearly show the existence of a sensory complex composed of TCS and ABC transporters and provide the first functional insights into the mechanisms of stimulus perception, signal transduction, and antimicrobial resistance employed by Bce-like detoxification systems. PMID:25118291

A sensory complex consisting of an ATP-binding cassette transporter and a two-component regulatory system controls bacitracin resistance in Bacillus subtilis.

PubMed

Dintner, Sebastian; Heermann, Ralf; Fang, Chong; Jung, Kirsten; Gebhard, Susanne

2014-10-03

Resistance against antimicrobial peptides in many Firmicutes bacteria is mediated by detoxification systems that are composed of a two-component regulatory system (TCS) and an ATP-binding cassette (ABC) transporter. The histidine kinases of these systems depend entirely on the transporter for sensing of antimicrobial peptides, suggesting a novel mode of signal transduction where the transporter constitutes the actual sensor. The aim of this study was to investigate the molecular mechanisms of this unusual signaling pathway in more detail, using the bacitracin resistance system BceRS-BceAB of Bacillus subtilis as an example. To analyze the proposed communication between TCS and the ABC transporter, we characterized their interactions by bacterial two-hybrid analyses and could show that the permease BceB and the histidine kinase BceS interact directly. In vitro pulldown assays confirmed this interaction, which was found to be independent of bacitracin. Because it was unknown whether BceAB-type transporters could detect their substrate peptides directly or instead recognized the peptide-target complex in the cell envelope, we next analyzed substrate binding by the transport permease, BceB. Direct and specific binding of bacitracin by BceB was demonstrated by surface plasmon resonance spectroscopy. Finally, in vitro signal transduction assays indicated that complex formation with the transporter influenced the autophosphorylation activity of the histidine kinase. Taken together, our findings clearly show the existence of a sensory complex composed of TCS and ABC transporters and provide the first functional insights into the mechanisms of stimulus perception, signal transduction, and antimicrobial resistance employed by Bce-like detoxification systems. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Central role of a bacterial two-component gene regulatory system of previously unknown function in pathogen persistence in human saliva.

PubMed

Shelburne, Samuel A; Sumby, Paul; Sitkiewicz, Izabela; Granville, Chanel; DeLeo, Frank R; Musser, James M

2005-11-01

The molecular genetic mechanisms used by bacteria to persist in humans are poorly understood. Group A Streptococcus (GAS) causes the majority of bacterial pharyngitis cases in humans and is prone to persistently inhabit the upper respiratory tract. To gain information about how GAS survives in and infects the oropharynx, we analyzed the transcriptome of a serotype M1 strain grown in saliva. The dynamic pattern of changes in transcripts of genes [spy0874/0875, herein named sptR and sptS (sptR/S), for saliva persistence] encoding a two-component gene regulatory system of unknown function suggested that SptR/S contributed to persistence of GAS in saliva. Consistent with this idea, an isogenic nonpolar mutant strain (DeltasptR) was dramatically less able to survive in saliva compared with the parental strain. Iterative expression microarray analysis of bacteria grown in saliva revealed that transcripts of several known and putative GAS virulence factor genes were decreased significantly in the DeltasptR mutant strain. Compared with the parental strain, the isogenic mutant strain also had altered transcripts of multiple genes encoding proteins involved in complex carbohydrate acquisition and utilization pathways. Western immunoblot analysis and real-time PCR analysis of GAS in throat swabs taken from humans with pharyngitis confirmed the findings. We conclude that SptR/S optimizes persistence of GAS in human saliva, apparently by strategically influencing metabolic pathways and virulence factor production. The discovery of a genetic program that significantly increased persistence of a major human pathogen in saliva enhances understanding of how bacteria survive in the host and suggests new therapeutic strategies.

Identification of the transcription factor ZEB1 as a central component of the adipogenic gene regulatory network

PubMed Central

Gubelmann, Carine; Schwalie, Petra C; Raghav, Sunil K; Röder, Eva; Delessa, Tenagne; Kiehlmann, Elke; Waszak, Sebastian M; Corsinotti, Andrea; Udin, Gilles; Holcombe, Wiebke; Rudofsky, Gottfried; Trono, Didier; Wolfrum, Christian; Deplancke, Bart

2014-01-01

Adipose tissue is a key determinant of whole body metabolism and energy homeostasis. Unraveling the regulatory mechanisms underlying adipogenesis is therefore highly relevant from a biomedical perspective. Our current understanding of fat cell differentiation is centered on the transcriptional cascades driven by the C/EBP protein family and the master regulator PPARγ. To elucidate further components of the adipogenic gene regulatory network, we performed a large-scale transcription factor (TF) screen overexpressing 734 TFs in mouse pre-adipocytes and probed their effect on differentiation. We identified 22 novel pro-adipogenic TFs and characterized the top ranking TF, ZEB1, as being essential for adipogenesis both in vitro and in vivo. Moreover, its expression levels correlate with fat cell differentiation potential in humans. Genomic profiling further revealed that this TF directly targets and controls the expression of most early and late adipogenic regulators, identifying ZEB1 as a central transcriptional component of fat cell differentiation. DOI: http://dx.doi.org/10.7554/eLife.03346.001 PMID:25163748

Onsager vortex formation in two-component Bose–Einstein condensates in two-dimensional traps

NASA Astrophysics Data System (ADS)

Han, Junsik; Tsubota, Makoto

2018-03-01

We study numerically the dynamics of quantized vortices in two-dimensional one-component and two-component Bose–Einstein condensates (BECs) trapped by a harmonic and box potentials. In two-component miscible BECs, we confirmed the tendency of the formation of Onsager vortices in both traps. The vortices in one component separate spatially from those in the other component, which comes from their intercomponent-coupling. We also discuss the decay of the number of vortices.

Narcissistic admiration and rivalry: disentangling the bright and dark sides of narcissism.

PubMed

Back, Mitja D; Küfner, Albrecht C P; Dufner, Michael; Gerlach, Tanja M; Rauthmann, John F; Denissen, Jaap J A

2013-12-01

We present a process model that distinguishes 2 dimensions of narcissism: admiration and rivalry. We propose that narcissists' overarching goal of maintaining a grandiose self is pursued by 2 separate pathways, characterized by distinct cognitive, affective-motivational, and behavioral processes. In a set of 7 studies, we validated this 2-dimensional model using the newly developed Narcissistic Admiration and Rivalry Questionnaire (NARQ). We showed that narcissistic admiration and rivalry are positively correlated dimensions, yet they have markedly different nomological networks and distinct intra- and interpersonal consequences. The NARQ showed the hypothesized 2-dimensional multifaceted structure as well as very good internal consistencies (Study 1, N = 953), stabilities (Study 2, N = 93), and self-other agreements (Study 3, N = 96). Narcissistic admiration and rivalry showed unique relations to the Narcissistic Personality Inventory (NPI), the Big Five, self-esteem, pathological narcissism, and other narcissism-related traits like Machiavellianism, psychopathy, self-enhancement, and impulsivity (Study 4, Ns = 510-1,814). Despite the positive relation between admiration and rivalry, the 2 differentially predicted general interpersonal orientations and reactions to transgressions in friendships and romantic relationships (Study 5, N = 1,085), interpersonal perceptions during group interactions (Study 6, N = 202), and observed behaviors in experimental observations (Study 7, N = 96). For all studies, the NARQ outperformed the standard measure of narcissism, the NPI, in predicting outcome measures. Results underscore the utility of a 2-dimensional conceptualization and measurement of narcissism. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Protein interaction network topology uncovers melanogenesis regulatory network components within functional genomics datasets.

PubMed

Ho, Hsiang; Milenković, Tijana; Memisević, Vesna; Aruri, Jayavani; Przulj, Natasa; Ganesan, Anand K

2010-06-15

RNA-mediated interference (RNAi)-based functional genomics is a systems-level approach to identify novel genes that control biological phenotypes. Existing computational approaches can identify individual genes from RNAi datasets that regulate a given biological process. However, currently available methods cannot identify which RNAi screen "hits" are novel components of well-characterized biological pathways known to regulate the interrogated phenotype. In this study, we describe a method to identify genes from RNAi datasets that are novel components of known biological pathways. We experimentally validate our approach in the context of a recently completed RNAi screen to identify novel regulators of melanogenesis. In this study, we utilize a PPI network topology-based approach to identify targets within our RNAi dataset that may be components of known melanogenesis regulatory pathways. Our computational approach identifies a set of screen targets that cluster topologically in a human PPI network with the known pigment regulator Endothelin receptor type B (EDNRB). Validation studies reveal that these genes impact pigment production and EDNRB signaling in pigmented melanoma cells (MNT-1) and normal melanocytes. We present an approach that identifies novel components of well-characterized biological pathways from functional genomics datasets that could not have been identified by existing statistical and computational approaches.

Protein interaction network topology uncovers melanogenesis regulatory network components within functional genomics datasets

PubMed Central

2010-01-01

Background RNA-mediated interference (RNAi)-based functional genomics is a systems-level approach to identify novel genes that control biological phenotypes. Existing computational approaches can identify individual genes from RNAi datasets that regulate a given biological process. However, currently available methods cannot identify which RNAi screen "hits" are novel components of well-characterized biological pathways known to regulate the interrogated phenotype. In this study, we describe a method to identify genes from RNAi datasets that are novel components of known biological pathways. We experimentally validate our approach in the context of a recently completed RNAi screen to identify novel regulators of melanogenesis. Results In this study, we utilize a PPI network topology-based approach to identify targets within our RNAi dataset that may be components of known melanogenesis regulatory pathways. Our computational approach identifies a set of screen targets that cluster topologically in a human PPI network with the known pigment regulator Endothelin receptor type B (EDNRB). Validation studies reveal that these genes impact pigment production and EDNRB signaling in pigmented melanoma cells (MNT-1) and normal melanocytes. Conclusions We present an approach that identifies novel components of well-characterized biological pathways from functional genomics datasets that could not have been identified by existing statistical and computational approaches. PMID:20550706

A tale of two tasks: reversing the self-regulatory resource depletion effect.

PubMed

Converse, Patrick D; Deshon, Richard P

2009-09-01

This research examined the self-regulatory depletion model (e.g., M. Muraven & R. F. Baumeister, 2000). Although numerous studies support this model's prediction of decrements in self-regulation across tasks, the majority of this research has relied on a single paradigm in which two tasks are performed in succession. Other work related to learned industriousness (R. Eisenberger, 1992) and adaptation-level theory (H. Helson, 1964) indicates that self-regulatory behavior may remain stable or even improve as a result of prior self-regulatory activities in situations involving additional tasks. Three studies examined these differing perspectives with 2- and 3-task designs. Results indicated that, relative to low initial self-regulatory exertion, high exertion can lead to poorer or better subsequent self-regulation. These findings are consistent with an adaptation view of self-regulation, suggesting that the depletion effect may be only part of the picture of self-regulatory behavior over time.

Genetics Home Reference: neuropathy, ataxia, and retinitis pigmentosa

MedlinePlus

... Twitter Home Health Conditions NARP Neuropathy, ataxia, and retinitis pigmentosa Printable PDF Open All Close All Enable Javascript ... the expand/collapse boxes. Description Neuropathy, ataxia, and retinitis pigmentosa ( NARP ) is a condition that causes a variety ...

Genetics Home Reference: mitochondrial complex V deficiency

MedlinePlus

... can cause a condition called neuropathy, ataxia, and retinitis pigmentosa (NARP). NARP causes a variety of signs and ... have cognitive impairment and an eye disorder called retinitis pigmentosa that causes vision loss. A condition called Leigh ...

Onsager Vortex Formation in Two-component Bose-Einstein Condensates

NASA Astrophysics Data System (ADS)

Han, Junsik; Tsubota, Makoto

2018-06-01

We numerically study the dynamics of quantized vortices in two-dimensional two-component Bose-Einstein condensates (BECs) trapped by a box potential. For one-component BECs in a box potential, it is known that quantized vortices form Onsager vortices, which are clusters of same-sign vortices. We confirm that the vortices of the two components spatially separate from each other — even for miscible two-component BECs — suppressing the formation of Onsager vortices. This phenomenon is caused by the repulsive interaction between vortices belonging to different components, hence, suggesting a new possibility for vortex phase separation.

Two-component signal transduction in Corynebacterium glutamicum and other corynebacteria: on the way towards stimuli and targets.

PubMed

Bott, Michael; Brocker, Melanie

2012-06-01

In bacteria, adaptation to changing environmental conditions is often mediated by two-component signal transduction systems. In the prototypical case, a specific stimulus is sensed by a membrane-bound histidine kinase and triggers autophosphorylation of a histidine residue. Subsequently, the phosphoryl group is transferred to an aspartate residue of the cognate response regulator, which then becomes active and mediates a specific response, usually by activating and/or repressing a set of target genes. In this review, we summarize the current knowledge on two-component signal transduction in Corynebacterium glutamicum. This Gram-positive soil bacterium is used for the large-scale biotechnological production of amino acids and can also be applied for the synthesis of a wide variety of other products, such as organic acids, biofuels, or proteins. Therefore, C. glutamicum has become an important model organism in industrial biotechnology and in systems biology. The type strain ATCC 13032 possesses 13 two-component systems and the role of five has been elucidated in recent years. They are involved in citrate utilization (CitAB), osmoregulation and cell wall homeostasis (MtrAB), adaptation to phosphate starvation (PhoSR), adaptation to copper stress (CopSR), and heme homeostasis (HrrSA). As C. glutamicum does not only face changing conditions in its natural environment, but also during cultivation in industrial bioreactors of up to 500 m(3) volume, adaptability can also be crucial for good performance in biotechnological production processes. Detailed knowledge on two-component signal transduction and regulatory networks therefore will contribute to both the application and the systemic understanding of C. glutamicum and related species.

Regulatory gene networks and the properties of the developmental process

NASA Technical Reports Server (NTRS)

Davidson, Eric H.; McClay, David R.; Hood, Leroy

2003-01-01

Genomic instructions for development are encoded in arrays of regulatory DNA. These specify large networks of interactions among genes producing transcription factors and signaling components. The architecture of such networks both explains and predicts developmental phenomenology. Although network analysis is yet in its early stages, some fundamental commonalities are already emerging. Two such are the use of multigenic feedback loops to ensure the progressivity of developmental regulatory states and the prevalence of repressive regulatory interactions in spatial control processes. Gene regulatory networks make it possible to explain the process of development in causal terms and eventually will enable the redesign of developmental regulatory circuitry to achieve different outcomes.

Transcriptome Analysis of the Brucella abortus BvrR/BvrS Two-Component Regulatory System

PubMed Central

Viadas, Cristina; Rodríguez, María C.; Sangari, Felix J.; Gorvel, Jean-Pierre; García-Lobo, Juan M.; López-Goñi, Ignacio

2010-01-01

Background The two-component BvrR/BvrS system is essential for Brucella abortus virulence. It was shown previously that its dysfunction alters the expression of some major outer membrane proteins and the pattern of lipid A acylation. To determine the genes regulated by BvrR/BvrS, we performed a whole-genome microarray analysis using B. abortus RNA obtained from wild type and bvrR mutant cells grown in the same conditions. Methodology/Principal Findings A total of 127 differentially expressed genes were found: 83 were over expressed and 44 were less expressed in the bvrR mutant. Two operons, the phosphotransferase system and the maltose transport system, were down-regulated. Several genes involved in cell envelope or outer membrane biogenesis were differentially expressed: genes for outer membrane proteins (omp25a, omp25d), lipoproteins, LPS and fatty acid biosynthesis, stress response proteins, chaperones, flagellar genes, and twelve genes encoding ABC transport systems. Ten genes related with carbon metabolism (pckA and fumB among others) were up-regulated in the bvrR mutant, and denitrification genes (nirK, norC and nosZ) were also regulated. Notably, seven transcriptional regulators were affected, including VjbR, ExoR and OmpR that were less expressed in the bvrR mutant. Finally, the expression of eleven genes which have been previously related with Brucella virulence was also altered. Conclusions/Significance All these data corroborate the impact of BvrR/BvrS on cell envelope modulation, confirm that this system controls the carbon and nitrogen metabolism, and suggest a cross-talk among some regulators to adjust the Brucella physiology to the shift expected to occur during the transit from the extracellular to the intracellular niche. PMID:20422049

Altered Markers of Cortical γ-Aminobutyric Acid Neuronal Activity in Schizophrenia

PubMed Central

Kimoto, Sohei; Zaki, Mark M.; Bazmi, H. Holly; Lewis, David A.

2016-01-01

IMPORTANCE In schizophrenia, working memory deficits appear to reflect abnormalities in the generation of gamma oscillations in the dorsolateral prefrontal cortex. The generation of gamma oscillations requires the phasic excitation of inhibitory parvalbumin-containing interneurons. Thus, gamma oscillations depend, in part, on the number of synaptic glutamate receptors on parvalbumin interneurons. However, little is known about the molecular factors that regulate glutamate receptor–mediated excitation of parvalbumin interneurons in schizophrenia. OBJECTIVE To quantify in individuals with schizophrenia the expression of immediate early genes (NARP, ARC, and SGK1) regulating glutamate synaptic neurotransmission. DESIGN, SETTING, AND PARTICIPANTS Postmortem brain specimens (n = 206) were obtained from individuals with schizophrenia, bipolar disorder, or major depressive disorder and from well-matched healthy persons (controls). For a study of brain tissue, quantitative polymerase chain reaction, in situ hybridization, or microarray analyses were used to measure transcript levels in the dorsolateral prefrontal cortex at gray matter, laminar, and cellular levels of resolutions. This study was conducted between January 1, 2013, and November 30, 2014. MAIN OUTCOMES AND MEASURES Expression levels for NARP, ARC, and SGK1 messenger RNA (mRNA) were compared between specimens from individuals with schizophrenia and controls. Diagnostic specificity was assessed by quantifying NARP mRNA levels in specimens from individuals with mood disorders. RESULTS By quantitative polymerase chain reaction, levels of NARP mRNA were significantly lower by 25.6%in specimens from individuals with schizophrenia compared with the controls (mean [SD], 0.036 [0.018] vs 0.049 [0.015]; F1,114 = 21.0; P < .001). Levels of ARC (F1,112 = 0.93; P = .34) and SGK1 (F1,110 = 2.52; P = .12) were not significant. These findings were supported by in situ hybridization (NARP; individuals with schizophrenia vs

Effects of the Global Regulator CsrA on the BarA/UvrY Two-Component Signaling System

PubMed Central

Camacho, Martha I.; Alvarez, Adrian F.; Gonzalez Chavez, Ricardo; Romeo, Tony; Merino, Enrique

2014-01-01

The hybrid sensor kinase BarA and its cognate response regulator UvrY, members of the two-component signal transduction family, activate transcription of CsrB and CsrC noncoding RNAs. These two small RNAs act by sequestering the RNA binding protein CsrA, which posttranscriptionally regulates translation and/or stability of its target mRNAs. Here, we provide evidence that CsrA positively affects, although indirectly, uvrY expression, at both the transcriptional and translational levels. We also demonstrate that CsrA is required for properly switching BarA from its phosphatase to its kinase activity. Thus, the existence of a feedback loop mechanism that involves the Csr and BarA/UvrY global regulatory systems is exposed. PMID:25535275

Two regulatory RNA elements affect TisB-dependent depolarization and persister formation.

PubMed

Berghoff, Bork A; Hoekzema, Mirthe; Aulbach, Lena; Wagner, E Gerhart H

2017-03-01

Bacterial survival strategies involve phenotypic diversity which is generated by regulatory factors and noisy expression of effector proteins. The question of how bacteria exploit regulatory RNAs to make decisions between phenotypes is central to a general understanding of these universal regulators. We investigated the TisB/IstR-1 toxin-antitoxin system of Escherichia coli to appreciate the role of the RNA antitoxin IstR-1 in TisB-dependent depolarization of the inner membrane and persister formation. Persisters are phenotypic variants that have become transiently drug-tolerant by arresting growth. The RNA antitoxin IstR-1 sets a threshold for TisB-dependent depolarization under DNA-damaging conditions, resulting in two sub-populations: polarized and depolarized cells. Furthermore, our data indicate that an inhibitory 5' UTR structure in the tisB mRNA serves as a regulatory RNA element that delays TisB translation to avoid inappropriate depolarization when DNA damage is low. Investigation of the persister sub-population further revealed that both regulatory RNA elements affect persister levels as well as persistence time. This work provides an intriguing example of how bacteria exploit regulatory RNAs to control phenotypic heterogeneity. © 2016 John Wiley & Sons Ltd.

EmbRS a new two-component system that inhibits biofilm formation and saves Rubrivivax gelatinosus from sinking.

PubMed

Steunou, Anne Soisig; Liotenberg, Sylviane; Soler, Marie-Noêlle; Briandet, Romain; Barbe, Valérie; Astier, Chantal; Ouchane, Soufian

2013-06-01

Photosynthetic bacteria can switch from planktonic lifestyle to phototrophic biofilm in mats in response to environmental changes. The mechanisms of phototrophic biofilm formation are, however, not characterized. Herein, we report a two-component system EmbRS that controls the biofilm formation in a photosynthetic member of the Burkholderiales order, the purple bacterium Rubrivivax gelatinosus. EmbRS inactivation results in cells that form conspicuous bacterial veils and fast-sinking aggregates in liquid. Biofilm analyses indicated that EmbRS represses the production of an extracellular matrix and biofilm formation. Mapping of transposon mutants that partially or completely restore the wild-type (WT) phenotype allowed the identification of two gene clusters involved in polysaccharide synthesis, one fully conserved only in Thauera sp., a floc-forming wastewater bacterium. A second two-component system BmfRS and a putative diguanylate cyclase BdcA were also identified in this screen suggesting their involvement in biofilm formation in this bacterium. The role of polysaccharides in sinking of microorganisms and organic matter, as well as the importance and the evolution of such regulatory system in phototrophic microorganisms are discussed. © 2013 The Authors. Microbiology Open published by John Wiley & Sons Ltd.

Regulation of the Expression of Bacterial Multidrug Exporters by Two-Component Signal Transduction Systems.

PubMed

Nishino, Kunihiko

2018-01-01

Bacterial multidrug exporters confer resistance to a wide range of antibiotics, dyes, and biocides. Recent studies have shown that there are many multidrug exporters encoded in bacterial genome. For example, it was experimentally identified that E. coli has at least 20 multidrug exporters. Because many of these multidrug exporters have overlapping substrate spectra, it is intriguing that bacteria, with their economically organized genomes, harbor such large sets of multidrug exporter genes. The key to understanding how bacteria utilize these multiple exporters lies in the regulation of exporter expression. Bacteria have developed signaling systems for eliciting a variety of adaptive responses to their environments. These adaptive responses are often mediated by two-component regulatory systems. In this chapter, the method to identify response regulators that affect expression of multidrug exporters is described.

Regulatory Physiology

NASA Technical Reports Server (NTRS)

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

1999-01-01

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

Efficient implementation of one- and two-component analytical energy gradients in exact two-component theory

NASA Astrophysics Data System (ADS)

Franzke, Yannick J.; Middendorf, Nils; Weigend, Florian

2018-03-01

We present an efficient algorithm for one- and two-component analytical energy gradients with respect to nuclear displacements in the exact two-component decoupling approach to the one-electron Dirac equation (X2C). Our approach is a generalization of the spin-free ansatz by Cheng and Gauss [J. Chem. Phys. 135, 084114 (2011)], where the perturbed one-electron Hamiltonian is calculated by solving a first-order response equation. Computational costs are drastically reduced by applying the diagonal local approximation to the unitary decoupling transformation (DLU) [D. Peng and M. Reiher, J. Chem. Phys. 136, 244108 (2012)] to the X2C Hamiltonian. The introduced error is found to be almost negligible as the mean absolute error of the optimized structures amounts to only 0.01 pm. Our implementation in TURBOMOLE is also available within the finite nucleus model based on a Gaussian charge distribution. For a X2C/DLU gradient calculation, computational effort scales cubically with the molecular size, while storage increases quadratically. The efficiency is demonstrated in calculations of large silver clusters and organometallic iridium complexes.

Transplantation of prokaryotic two-component signaling pathways into mammalian cells.

PubMed

Hansen, Jonathan; Mailand, Erik; Swaminathan, Krishna Kumar; Schreiber, Joerg; Angelici, Bartolomeo; Benenson, Yaakov

2014-11-04

Signaling pathway engineering is a promising route toward synthetic biological circuits. Histidine-aspartate phosphorelays are thought to have evolved in prokaryotes where they form the basis for two-component signaling. Tyrosine-serine-threonine phosphorelays, exemplified by MAP kinase cascades, are predominant in eukaryotes. Recently, a prokaryotic two-component pathway was implemented in a plant species to sense environmental trinitrotoluene. We reasoned that "transplantation" of two-component pathways into mammalian host could provide an orthogonal and diverse toolkit for a variety of signal processing tasks. Here we report that two-component pathways could be partially reconstituted in mammalian cell culture and used for programmable control of gene expression. To enable this reconstitution, coding sequences of histidine kinase (HK) and response regulator (RR) components were codon-optimized for human cells, whereas the RRs were fused with a transactivation domain. Responsive promoters were furnished by fusing DNA binding sites in front of a minimal promoter. We found that coexpression of HKs and their cognate RRs in cultured mammalian cells is necessary and sufficient to strongly induce gene expression even in the absence of pathways' chemical triggers in the medium. Both loss-of-function and constitutive mutants behaved as expected. We further used the two-component signaling pathways to implement two-input logical AND, NOR, and OR gene regulation. Thus, two-component systems can be applied in different capacities in mammalian cells and their components can be used for large-scale synthetic gene circuits.

Antitumor action of 3-bromopyruvate implicates reorganized tumor growth regulatory components of tumor milieu, cell cycle arrest and induction of mitochondria-dependent tumor cell death.

PubMed

Yadav, Saveg; Kujur, Praveen Kumar; Pandey, Shrish Kumar; Goel, Yugal; Maurya, Babu Nandan; Verma, Ashish; Kumar, Ajay; Singh, Rana Pratap; Singh, Sukh Mahendra

2018-01-15

Evidences demonstrate that metabolic inhibitor 3-bromopyruvate (3-BP) exerts a potent antitumor action against a wide range of malignancies. However, the effect of 3-BP on progression of the tumors of thymic origin remains unexplored. Although, constituents of tumor microenvironment (TME) plays a pivotal role in regulation of tumor progression, it remains unclear if 3-BP can alter the composition of the crucial tumor growth regulatory components of the external surrounding of tumor cells. Thus, the present investigation attempts to understand the effect of 3-BP administration to a host bearing a progressively growing tumor of thymic origin on tumor growth regulatory soluble, cellular and biophysical components of tumor milieu vis-à-vis understanding its association with tumor progression, accompanying cell cycle events and mode of cell death. Further, the expression of cell survival regulatory molecules and hemodynamic characteristics of the tumor milieu were analysed to decipher mechanisms underlying the antitumor action of 3-BP. Administration of 3-BP to tumor-bearing hosts retarded tumor progression accompanied by induction of tumor cell death, cell cycle arrest, declined metabolism, inhibited mitochondrial membrane potential, elevated release of cytochrome c and altered hemodynamics. Moreover, 3-BP reconstituted the external milieu, in concurrence with deregulated glucose and pH homeostasis and increased tumor infiltration by NK cells, macrophages, and T lymphocytes. Further, 3-BP administration altered the expression of key regulatory molecules involved in glucose uptake, intracellular pH and tumor cell survival. The outcomes of this study will help in optimizing the therapeutic application of 3-BP by targeting crucial tumor growth regulatory components of tumor milieu. Copyright © 2017 Elsevier Inc. All rights reserved.

Two-component gravitating systems and the red giant-like structure

NASA Technical Reports Server (NTRS)

Fujimoto, Masayuki Y.; Tomisaka, Kohji

1992-01-01

The present study investigates the equilibria and evolution of gravitating systems composed of two components by approximating their equations of states to polytropes. The structures are explored in hydrostatic equilibrium systematically under the condition that two components interact with each other only through gravity. The systems are found to be characterized by four parameters, the ratio of central densities and the ratio of central thermal energies per unit mass, and the polytropic indices of two components. If the central density is much higher, the structure is little affected by the presence of the other component. If the difference in the central thermal energies is smaller than specified by beta-cri, the system adopts an equilibrium configuration for any mass ratio. Two-component systems necessarily evolve to have the red giantlike structure if one component suffers cooling faster than the other. It is concluded that the red giant structure is a general characteristic of gravitating systems for which there is an appropriate mechanism to decouple the constituent into the hotter and cooler components.

Two-component quantum Hall effects in topological flat bands

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

Zeng, Tian-Sheng; Zhu, Wei; Sheng, D. N.

2017-03-27

Here in this paper, we study quantum Hall states for two-component particles (hardcore bosons and fermions) loading in topological lattice models. By tuning the interplay of interspecies and intraspecies interactions, we demonstrate that two-component fractional quantum Hall states emerge at certain fractional filling factors ν = 1/2 for fermions (ν = 2/3 for bosons) in the lowest Chern band, classified by features from ground states including the unique Chern number matrix (inverse of the K matrix), the fractional charge and spin pumpings, and two parallel propagating edge modes. Moreover, we also apply our strategy to two-component fermions at integer fillingmore » factor ν = 2 , where a possible topological Neel antiferromagnetic phase is under intense debate very recently. For the typical π -flux checkerboard lattice, by tuning the onsite Hubbard repulsion, we establish a first-order phase transition directly from a two-component fermionic ν = 2 quantum Hall state at weak interaction to a topologically trivial antiferromagnetic insulator at strong interaction, and therefore exclude the possibility of an intermediate topological phase for our system.« less

The two-component signal system in rice (Oryza sativa L.): a genome-wide study of cytokinin signal perception and transduction.

PubMed

Du, Liming; Jiao, Fangchan; Chu, Jun; Jin, Gulei; Chen, Ming; Wu, Ping

2007-06-01

In this report we define the genes of two-component regulatory systems in rice through a comprehensive computational analysis of rice (Oryza sativa L.) genome sequence databases. Thirty-seven genes were identified, including 5 HKs (cytokinin-response histidine protein kinase) (OsHK1-4, OsHKL1), 5 HPs (histidine phosphotransfer proteins) (OsHP1-5), 15 type-A RRs (response regulators) (OsRR1-15), 7 type B RR genes (OsRR16-22), and 5 predicted pseudo-response regulators (OsPRR1-5). Protein motif organization, gene structure, phylogenetic analysis, chromosomal location, and comparative analysis between rice, maize, and Arabidopsis are described. Full-length cDNA clones of each gene were isolated from rice. Heterologous expression of each of the OsHKs in yeast mutants conferred histidine kinase function in a cytokinin-dependent manner. Nonconserved regions of individual cDNAs were used as probes in expression profiling experiments. This work provides a foundation for future functional dissection of the rice cytokinin two-component signaling pathway.

The Ca2+ induced two-component system, CvsSR regulates the Type III secretion system and the extracytoplasmic function sigma-factor AlgU in Pseudomonas syringae pv. tomato DC3000

USDA-ARS?s Scientific Manuscript database

Two-component systems (TCSs) of bacteria regulate many different aspects of the bacterial life cycle including pathogenesis. Most TCSs remain uncharacterized with no information about the signal(s) or regulatory targets and/or role in bacterial pathogenesis. Here, we characterize a TCS in the plant-...

An Introductory Idea for Teaching Two-Component Phase Diagrams

ERIC Educational Resources Information Center

Peckham, Gavin D.; McNaught, Ian J.

2011-01-01

The teaching of two-component phase diagrams has attracted little attention in this "Journal," and it is hoped that this article will make a useful contribution. Current physical chemistry textbooks describe two-component phase diagrams adequately, but do so in a piecemeal fashion one section at a time; first solid-liquid equilibria, then…

Tutorial on Quantification of Differences between Single- and Two-Component Two-Phase Flow and Heat Transfer

NASA Astrophysics Data System (ADS)

Delil, A. A. M.

2003-01-01

Single-component two-phase systems are envisaged for aerospace thermal control applications: Mechanically Pumped Loops, Vapour Pressure Driven Loops, Capillary Pumped Loops and Loop Heat Pipes. Thermal control applications are foreseen in different gravity environments: Micro-g, reduced-g for Mars or Moon bases, 1-g during terrestrial testing, and hyper-g in rotating spacecraft, during combat aircraft manoeuvres and in systems for outer planets. In the evaporator, adiabatic line and condenser sections of such single-component two-phase systems, the fluid is a mixture of the working liquid (for example ammonia, carbon dioxide, ethanol, or other refrigerants, etc.) and its saturated vapour. Results of two-phase two-component flow and heat transfer research (pertaining to liquid-gas mixtures, e.g. water/air, or argon or helium) are often applied to support research on flow and heat transfer in two-phase single-component systems. The first part of the tutorial updates the contents of two earlier tutorials, discussing various aerospace-related two-phase flow and heat transfer research. It deals with the different pressure gradient constituents of the total pressure gradient, with flow regime mapping (including evaporating and condensing flow trajectories in the flow pattern maps), with adiabatic flow and flashing, and with thermal-gravitational scaling issues. The remaining part of the tutorial qualitatively and quantitatively determines the differences between single- and two-component systems: Two systems that physically look similar and close, but in essence are fully different. It was already elucidated earlier that, though there is a certain degree of commonality, the differences will be anything but negligible, in many cases. These differences (quantified by some examples) illustrates how careful one shall be in interpreting data resulting from two-phase two-component simulations or experiments, for the development of single-component two-phase thermal control

Regulatory Flexibility: An Individual Differences Perspective on Coping and Emotion Regulation.

PubMed

Bonanno, George A; Burton, Charles L

2013-11-01

People respond to stressful events in different ways, depending on the event and on the regulatory strategies they choose. Coping and emotion regulation theorists have proposed dynamic models in which these two factors, the person and the situation, interact over time to inform adaptation. In practice, however, researchers have tended to assume that particular regulatory strategies are consistently beneficial or maladaptive. We label this assumption the fallacy of uniform efficacy and contrast it with findings from a number of related literatures that have suggested the emergence of a broader but as yet poorly defined construct that we refer to as regulatory flexibility. In this review, we articulate this broader construct and define both its features and limitations. Specifically, we propose a heuristic individual differences framework and review research on three sequential components of flexibility for which propensities and abilities vary: sensitivity to context, availability of a diverse repertoire of regulatory strategies, and responsiveness to feedback. We consider the methodological limitations of research on each component, review questions that future research on flexibility might address, and consider how the components might relate to each other and to broader conceptualizations about stability and change across persons and situations. © The Author(s) 2013.

Building Blocks of the Nexin-Dynein Regulatory Complex in Chlamydomonas Flagella*

PubMed Central

Lin, Jianfeng; Tritschler, Douglas; Song, Kangkang; Barber, Cynthia F.; Cobb, Jennifer S.; Porter, Mary E.; Nicastro, Daniela

2011-01-01

The directional flow generated by motile cilia and flagella is critical for many processes, including human development and organ function. Normal beating requires the control and coordination of thousands of dynein motors, and the nexin-dynein regulatory complex (N-DRC) has been identified as an important regulatory node for orchestrating dynein activity. The nexin link appears to be critical for the transformation of dynein-driven, linear microtubule sliding to flagellar bending, yet the molecular composition and mechanism of the N-DRC remain largely unknown. Here, we used proteomics with special attention to protein phosphorylation to analyze the composition of the N-DRC and to determine which subunits may be important for signal transduction. Two-dimensional electrophoresis and MALDI-TOF mass spectrometry of WT and mutant flagellar axonemes from Chlamydomonas identified 12 N-DRC-associated proteins, including all seven previously observed N-DRC components. Sequence and PCR analyses identified the mutation responsible for the phenotype of the sup-pf-4 strain, and biochemical comparison with a radial spoke mutant revealed two components that may link the N-DRC and the radial spokes. Phosphoproteomics revealed eight proteins with phosphorylated isoforms for which the isoform patterns changed with the genotype as well as two components that may play pivotal roles in N-DRC function through their phosphorylation status. These data were assembled into a model of the N-DRC that explains aspects of its regulatory function. PMID:21700706

Correlation Energies from the Two-Component Random Phase Approximation.

PubMed

Kühn, Michael

2014-02-11

The correlation energy within the two-component random phase approximation accounting for spin-orbit effects is derived. The resulting plasmon equation is rewritten-analogously to the scalar relativistic case-in terms of the trace of two Hermitian matrices for (Kramers-restricted) closed-shell systems and then represented as an integral over imaginary frequency using the resolution of the identity approximation. The final expression is implemented in the TURBOMOLE program suite. The code is applied to the computation of equilibrium distances and vibrational frequencies of heavy diatomic molecules. The efficiency is demonstrated by calculation of the relative energies of the Oh-, D4h-, and C5v-symmetric isomers of Pb6. Results within the random phase approximation are obtained based on two-component Kohn-Sham reference-state calculations, using effective-core potentials. These values are finally compared to other two-component and scalar relativistic methods, as well as experimental data.

DevS, a heme-containing two-component oxygen sensor of Mycobacterium tuberculosis.

PubMed

Ioanoviciu, Alexandra; Yukl, Erik T; Moënne-Loccoz, Pierre; de Montellano, Paul R Ortiz

2007-04-10

Mycobacterium tuberculosis can exist in the actively growing state of the overt disease or in a latent quiescent state that can be induced, among other things, by anaerobiosis. Eradication of the latent state is particularly difficult with the available drugs and requires prolonged treatment. DevS is a member of the DevS-DevR two-component regulatory system that is thought to mediate the cellular response to anaerobiosis. Here we report the cloning, expression, and initial characterization of a truncated version of DevS (DevS642) containing only the N-terminal GAF sensor domain (GAF-A) and of the full-length protein DevS. The DevS truncated construct quantitatively binds heme in a 1:1 stoichiometry, and the complex of the protein with ferrous heme reversibly binds O2, NO, and CO. UV-vis and resonance Raman spectroscopy of the wild-type protein and the H149A mutant confirm that His149 is the proximal ligand to the heme iron atom. While the heme-CO complex is present as two conformers in the GAF-A domain, a single set of [Fe-C-O] vibrations is observed with the full-length protein, suggesting that interactions between domains within DevS influence the distal pocket environment of the heme in the GAF-A domain.

Transport of Solar Wind Fluctuations: A Two-Component Model

NASA Technical Reports Server (NTRS)

Oughton, S.; Matthaeus, W. H.; Smith, C. W.; Breech, B.; Isenberg, P. A.

2011-01-01

We present a new model for the transport of solar wind fluctuations which treats them as two interacting incompressible components: quasi-two-dimensional turbulence and a wave-like piece. Quantities solved for include the energy, cross helicity, and characteristic transverse length scale of each component, plus the proton temperature. The development of the model is outlined and numerical solutions are compared with spacecraft observations. Compared to previous single-component models, this new model incorporates a more physically realistic treatment of fluctuations induced by pickup ions and yields improved agreement with observed values of the correlation length, while maintaining good observational accord with the energy, cross helicity, and temperature.

Two-component gravitational instability in spiral galaxies

NASA Astrophysics Data System (ADS)

Marchuk, A. A.; Sotnikova, N. Y.

2018-04-01

We applied a criterion of gravitational instability, valid for two-component and infinitesimally thin discs, to observational data along the major axis for seven spiral galaxies of early types. Unlike most papers, the dispersion equation corresponding to the criterion was solved directly without using any approximation. The velocity dispersion of stars in the radial direction σR was limited by the range of possible values instead of a fixed value. For all galaxies, the outer regions of the disc were analysed up to R ≤ 130 arcsec. The maximal and sub-maximal disc models were used to translate surface brightness into surface density. The largest destabilizing disturbance stars can exert on a gaseous disc was estimated. It was shown that the two-component criterion differs a little from the one-fluid criterion for galaxies with a large surface gas density, but it allows to explain large-scale star formation in those regions where the gaseous disc is stable. In the galaxy NGC 1167 star formation is entirely driven by the self-gravity of the stars. A comparison is made with the conventional approximations which also include the thickness effect and with models for different sound speed cg. It is shown that values of the effective Toomre parameter correspond to the instability criterion of a two-component disc Qeff < 1.5-2.5. This result is consistent with previous theoretical and observational studies.

Isolated case of mental retardation and ataxia due to a de novo mitochondrial T8993G mutation

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

De Coo, I.F.M.; Smeets, H.J.M.; Oost, B.A. van

1996-03-01

Neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP) and subacute necrotizing encephalomyelopathy (Leigh disease) are both associated with an alteration of nt 8993 in the mitochondrial ATPase 6 gene. In NARP, the T-to-G transversion at that position changes leucine into arginine. In Leigh syndrome, the same mutation can be found, as can a T-to-C transition, which changes this leucine into proline. Clinical manifestations occur for NARP when {approximately}60%-90% mutated mtDNA is present. In case of Leigh, these percentages usually exceed 95%. It is known that this mutation can segregate very rapidly within pedigrees. Here we report on a sporadic casemore » with mental retardation and ataxia without retinitis pigmentosa in which the T8993G mutation was found. 13 refs., 1 fig.« less

Stationary Wavelet-based Two-directional Two-dimensional Principal Component Analysis for EMG Signal Classification

NASA Astrophysics Data System (ADS)

Ji, Yi; Sun, Shanlin; Xie, Hong-Bo

2017-06-01

Discrete wavelet transform (WT) followed by principal component analysis (PCA) has been a powerful approach for the analysis of biomedical signals. Wavelet coefficients at various scales and channels were usually transformed into a one-dimensional array, causing issues such as the curse of dimensionality dilemma and small sample size problem. In addition, lack of time-shift invariance of WT coefficients can be modeled as noise and degrades the classifier performance. In this study, we present a stationary wavelet-based two-directional two-dimensional principal component analysis (SW2D2PCA) method for the efficient and effective extraction of essential feature information from signals. Time-invariant multi-scale matrices are constructed in the first step. The two-directional two-dimensional principal component analysis then operates on the multi-scale matrices to reduce the dimension, rather than vectors in conventional PCA. Results are presented from an experiment to classify eight hand motions using 4-channel electromyographic (EMG) signals recorded in healthy subjects and amputees, which illustrates the efficiency and effectiveness of the proposed method for biomedical signal analysis.

A Model of Yeast Cell-Cycle Regulation Based on a Standard Component Modeling Strategy for Protein Regulatory Networks.

PubMed

Laomettachit, Teeraphan; Chen, Katherine C; Baumann, William T; Tyson, John J

2016-01-01

To understand the molecular mechanisms that regulate cell cycle progression in eukaryotes, a variety of mathematical modeling approaches have been employed, ranging from Boolean networks and differential equations to stochastic simulations. Each approach has its own characteristic strengths and weaknesses. In this paper, we propose a "standard component" modeling strategy that combines advantageous features of Boolean networks, differential equations and stochastic simulations in a framework that acknowledges the typical sorts of reactions found in protein regulatory networks. Applying this strategy to a comprehensive mechanism of the budding yeast cell cycle, we illustrate the potential value of standard component modeling. The deterministic version of our model reproduces the phenotypic properties of wild-type cells and of 125 mutant strains. The stochastic version of our model reproduces the cell-to-cell variability of wild-type cells and the partial viability of the CLB2-dbΔ clb5Δ mutant strain. Our simulations show that mathematical modeling with "standard components" can capture in quantitative detail many essential properties of cell cycle control in budding yeast.

Novel Two-Component System of Streptococcus sanguinis Affecting Functions Associated with Viability in Saliva and Biofilm Formation.

PubMed

Camargo, Tarsila M; Stipp, Rafael N; Alves, Lívia A; Harth-Chu, Erika N; Höfling, José F; Mattos-Graner, Renata O

2018-04-01

Streptococcus sanguinis is a pioneer species of teeth and a common opportunistic pathogen of infective endocarditis. In this study, we identified a two-component system, S. sanguinis SptRS (SptRS Ss ), affecting S. sanguinis survival in saliva and biofilm formation. Isogenic mutants of sptR Ss (SKsptR) and sptS Ss (SKsptS) showed reduced cell counts in ex vivo assays of viability in saliva compared to those of parent strain SK36 and complemented mutants. Reduced counts of the mutants in saliva were associated with reduced growth rates in nutrient-poor medium (RPMI) and increased susceptibility to the deposition of C3b and the membrane attach complex (MAC) of the complement system, a defense component of saliva and serum. Conversely, sptR Ss and sptS Ss mutants showed increased biofilm formation associated with higher levels of production of H 2 O 2 and extracellular DNA. Reverse transcription-quantitative PCR (RT-qPCR) comparisons of strains indicated a global role of SptRS Ss in repressing genes for H 2 O 2 production (2.5- to 15-fold upregulation of spxB , spxR , vicR , tpk , and ackA in sptR Ss and sptS Ss mutants), biofilm formation, and/or evasion of host immunity (2.1- to 11.4-fold upregulation of srtA , pcsB , cwdP , iga , and nt5e ). Compatible with the homology of SptR Ss with AraC-type regulators, duplicate to multiple conserved repeats were identified in 1,000-bp regulatory regions of downstream genes, suggesting that SptR Ss regulates transcription by DNA looping. Significant transcriptional changes in the regulatory genes vicR , spxR , comE , comX , and mecA in the sptR Ss and sptS Ss mutants further indicated that SptRS Ss is part of a regulatory network that coordinates cell wall homeostasis, H 2 O 2 production, and competence. This study reveals that SptRS Ss is involved in the regulation of crucial functions for S. sanguinis persistence in the oral cavity. Copyright © 2018 American Society for Microbiology.

Analytical energy gradient for the two-component normalized elimination of the small component method

NASA Astrophysics Data System (ADS)

Zou, Wenli; Filatov, Michael; Cremer, Dieter

2015-06-01

The analytical gradient for the two-component Normalized Elimination of the Small Component (2c-NESC) method is presented. The 2c-NESC is a Dirac-exact method that employs the exact two-component one-electron Hamiltonian and thus leads to exact Dirac spin-orbit (SO) splittings for one-electron atoms. For many-electron atoms and molecules, the effect of the two-electron SO interaction is modeled by a screened nucleus potential using effective nuclear charges as proposed by Boettger [Phys. Rev. B 62, 7809 (2000)]. The effect of spin-orbit coupling (SOC) on molecular geometries is analyzed utilizing the properties of the frontier orbitals and calculated SO couplings. It is shown that bond lengths can either be lengthened or shortened under the impact of SOC where in the first case the influence of low lying excited states with occupied antibonding orbitals plays a role and in the second case the jj-coupling between occupied antibonding and unoccupied bonding orbitals dominates. In general, the effect of SOC on bond lengths is relatively small (≤5% of the scalar relativistic changes in the bond length). However, large effects are found for van der Waals complexes Hg2 and Cn2, which are due to the admixture of more bonding character to the highest occupied spinors.

Two component Feebly Interacting Massive Particle (FIMP) dark matter

NASA Astrophysics Data System (ADS)

Pandey, Madhurima; Majumdar, Debasish; Prasad Modak, Kamakshya

2018-06-01

We explore the idea of an alternative candidate for particle dark matter namely Feebly Interacting Massive Particle (FIMP) in the framework of a two component singlet scalar model. Singlet scalar dark matter has already been demonstrated to be a viable candidate for WIMP (Weakly Interacting Massive Particle) dark matter in literature. In the FIMP scenario, dark matter particles are slowly produced via "thermal freeze-in" mechanism in the early Universe and are never abundant enough to reach thermal equilibrium or to undergo pair annihilation inside the Universe's plasma due to their extremely small couplings. We demonstrate that for smaller couplings too, required for freeze-in process, a two component scalar dark matter model considered here could well be a viable candidate for FIMP . In this scenario, the Standard Model of particle physics is extended by two gauge singlet real scalars whose stability is protected by an unbroken Z2× Z'2 symmetry and they are assumed to acquire no VEV after Spontaneous Symmetry Breaking. We explore the viable mass regions in the present two scalar DM model that is in accordance with the FIMP scenario. We also explore the upper limits of masses of the two components from the consideration of their self interactions.

Network Modeling Reveals Prevalent Negative Regulatory Relationships between Signaling Sectors in Arabidopsis Immune Signaling

PubMed Central

Sato, Masanao; Tsuda, Kenichi; Wang, Lin; Coller, John; Watanabe, Yuichiro; Glazebrook, Jane; Katagiri, Fumiaki

2010-01-01

Biological signaling processes may be mediated by complex networks in which network components and network sectors interact with each other in complex ways. Studies of complex networks benefit from approaches in which the roles of individual components are considered in the context of the network. The plant immune signaling network, which controls inducible responses to pathogen attack, is such a complex network. We studied the Arabidopsis immune signaling network upon challenge with a strain of the bacterial pathogen Pseudomonas syringae expressing the effector protein AvrRpt2 (Pto DC3000 AvrRpt2). This bacterial strain feeds multiple inputs into the signaling network, allowing many parts of the network to be activated at once. mRNA profiles for 571 immune response genes of 22 Arabidopsis immunity mutants and wild type were collected 6 hours after inoculation with Pto DC3000 AvrRpt2. The mRNA profiles were analyzed as detailed descriptions of changes in the network state resulting from the genetic perturbations. Regulatory relationships among the genes corresponding to the mutations were inferred by recursively applying a non-linear dimensionality reduction procedure to the mRNA profile data. The resulting static network model accurately predicted 23 of 25 regulatory relationships reported in the literature, suggesting that predictions of novel regulatory relationships are also accurate. The network model revealed two striking features: (i) the components of the network are highly interconnected; and (ii) negative regulatory relationships are common between signaling sectors. Complex regulatory relationships, including a novel negative regulatory relationship between the early microbe-associated molecular pattern-triggered signaling sectors and the salicylic acid sector, were further validated. We propose that prevalent negative regulatory relationships among the signaling sectors make the plant immune signaling network a “sector-switching” network, which

The CpxRA two-component system contributes to Legionella pneumophila virulence.

PubMed

Tanner, Jennifer R; Li, Laam; Faucher, Sébastien P; Brassinga, Ann Karen C

2016-06-01

The bacterium Legionella pneumophila is capable of intracellular replication within freshwater protozoa as well as human macrophages, the latter of which results in the serious pneumonia Legionnaires' disease. A primary factor involved in these host cell interactions is the Dot/Icm Type IV secretion system responsible for translocating effector proteins needed to establish and maintain the bacterial replicative niche. Several regulatory factors have been identified to control the expression of the Dot/Icm system and effectors, one of which is the CpxRA two-component system, suggesting essentiality for virulence. In this study, we generated cpxR, cpxA and cpxRA in-frame null mutant strains to further delineate the role of the CpxRA system in bacterial survival and virulence. We found that cpxR is essential for intracellular replication within Acanthamoeba castellanii, but not in U937-derived macrophages. Transcriptome analysis revealed that CpxRA regulates a large number of virulence-associated proteins including Dot/Icm effectors as well as Type II secreted substrates. Furthermore, the cpxR and cpxRA mutant strains were more sodium resistant than the parental strain Lp02, and cpxRA expression reaches maximal levels during postexponential phase. Taken together, our findings suggest the CpxRA system is a key contributor to L. pneumophila virulence in protozoa via virulence factor regulation. © 2016 John Wiley & Sons Ltd.

Spin-orbit coupling calculations with the two-component normalized elimination of the small component method

NASA Astrophysics Data System (ADS)

Filatov, Michael; Zou, Wenli; Cremer, Dieter

2013-07-01

A new algorithm for the two-component Normalized Elimination of the Small Component (2cNESC) method is presented and tested in the calculation of spin-orbit (SO) splittings for a series of heavy atoms and their molecules. The 2cNESC is a Dirac-exact method that employs the exact two-component one-electron Hamiltonian and thus leads to exact Dirac SO splittings for one-electron atoms. For many-electron atoms and molecules, the effect of the two-electron SO interaction is modeled by a screened nucleus potential using effective nuclear charges as proposed by Boettger [Phys. Rev. B 62, 7809 (2000), 10.1103/PhysRevB.62.7809]. The use of the screened nucleus potential for the two-electron SO interaction leads to accurate spinor energy splittings, for which the deviations from the accurate Dirac Fock-Coulomb values are on the average far below the deviations observed for other effective one-electron SO operators. For hydrogen halides HX (X = F, Cl, Br, I, At, and Uus) and mercury dihalides HgX2 (X = F, Cl, Br, I) trends in spinor energies and SO splittings as obtained with the 2cNESC method are analyzed and discussed on the basis of coupling schemes and the electronegativity of X.

Critical thinking as a self-regulatory process component in teaching and learning.

PubMed

Phan, Huy P

2010-05-01

This article presents a theoretically grounded model of critical thinking and self-regulation in the context of teaching and learning. Critical thinking, deriving from an educational psychology perspective is a complex process of reflection that helps individuals become more analytical in their thinking and professional development. My conceptualisation in this discussion paper argues that both theoretical orientations (critical thinking and self-regulation) operate in a dynamic interactive system of teaching and learning. My argument, based on existing research evidence, suggests two important points: (i) critical thinking acts as another cognitive strategy of self-regulation that learners use in their learning, and (ii) critical thinking may be a product of various antecedents such as different self-regulatory strategies.

Implementation of Two-Component Time-Dependent Density Functional Theory in TURBOMOLE.

PubMed

Kühn, Michael; Weigend, Florian

2013-12-10

We report the efficient implementation of a two-component time-dependent density functional theory proposed by Wang et al. (Wang, F.; Ziegler, T.; van Lenthe, E.; van Gisbergen, S.; Baerends, E. J. J. Chem. Phys. 2005, 122, 204103) that accounts for spin-orbit effects on excitations of closed-shell systems by employing a noncollinear exchange-correlation kernel. In contrast to the aforementioned implementation, our method is based on two-component effective core potentials as well as Gaussian-type basis functions. It is implemented in the TURBOMOLE program suite for functionals of the local density approximation and the generalized gradient approximation. Accuracy is assessed by comparison of two-component vertical excitation energies of heavy atoms and ions (Cd, Hg, Au(+)) and small molecules (I2, TlH) to other two- and four-component approaches. Efficiency is demonstrated by calculating the electronic spectrum of Au20.

Components of the airport access system

NASA Technical Reports Server (NTRS)

1978-01-01

The organizations and agencies which make up or influence the airport access system are examined. These include the airport, the airline industry, the public and private transit agencies which provide ground access to the airport, and the regulatory agencies which affect all of these organizations and their actions. Each component, with the exception of the regulatory agencies is described in terms of its legal status, its sources of funds, and the nature of its relationship with the other components. Conclusions regarding the system components' effects on airport access and recommendations for changes which appear practical are presented.

Analytical energy gradient for the two-component normalized elimination of the small component method

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

Zou, Wenli; Filatov, Michael; Cremer, Dieter, E-mail: dcremer@smu.edu

2015-06-07

The analytical gradient for the two-component Normalized Elimination of the Small Component (2c-NESC) method is presented. The 2c-NESC is a Dirac-exact method that employs the exact two-component one-electron Hamiltonian and thus leads to exact Dirac spin-orbit (SO) splittings for one-electron atoms. For many-electron atoms and molecules, the effect of the two-electron SO interaction is modeled by a screened nucleus potential using effective nuclear charges as proposed by Boettger [Phys. Rev. B 62, 7809 (2000)]. The effect of spin-orbit coupling (SOC) on molecular geometries is analyzed utilizing the properties of the frontier orbitals and calculated SO couplings. It is shown thatmore » bond lengths can either be lengthened or shortened under the impact of SOC where in the first case the influence of low lying excited states with occupied antibonding orbitals plays a role and in the second case the jj-coupling between occupied antibonding and unoccupied bonding orbitals dominates. In general, the effect of SOC on bond lengths is relatively small (≤5% of the scalar relativistic changes in the bond length). However, large effects are found for van der Waals complexes Hg{sub 2} and Cn{sub 2}, which are due to the admixture of more bonding character to the highest occupied spinors.« less

A conserved two-component signal transduction system controls the response to phosphate starvation in Bifidobacterium breve UCC2003.

PubMed

Alvarez-Martin, Pablo; Fernández, Matilde; O'Connell-Motherway, Mary; O'Connell, Kerry Joan; Sauvageot, Nicolas; Fitzgerald, Gerald F; MacSharry, John; Zomer, Aldert; van Sinderen, Douwe

2012-08-01

This work reports on the identification and molecular characterization of the two-component regulatory system (2CRS) PhoRP, which controls the response to inorganic phosphate (P(i)) starvation in Bifidobacterium breve UCC2003. The response regulator PhoP was shown to bind to the promoter region of pstSCAB, specifying a predicted P(i) transporter system, as well as that of phoU, which encodes a putative P(i)-responsive regulatory protein. This interaction is assumed to cause transcriptional modulation under conditions of P(i) limitation. Our data suggest that the phoRP genes are subject to positive autoregulation and, together with pstSCAB and presumably phoU, represent the complete regulon controlled by the phoRP-encoded 2CRS in B. breve UCC2003. Determination of the minimal PhoP binding region combined with bioinformatic analysis revealed the probable recognition sequence of PhoP, designated here as the PHO box, which together with phoRP is conserved among many high-GC-content Gram-positive bacteria. The importance of the phoRP 2CRS in the response of B. breve to P(i) starvation conditions was confirmed by analysis of a B. breve phoP insertion mutant which exhibited decreased growth under phosphate-limiting conditions compared to its parent strain UCC2003.

A Conserved Two-Component Signal Transduction System Controls the Response to Phosphate Starvation in Bifidobacterium breve UCC2003

PubMed Central

Alvarez-Martin, Pablo; Fernández, Matilde; O'Connell-Motherway, Mary; O'Connell, Kerry Joan; Sauvageot, Nicolas; Fitzgerald, Gerald F.; MacSharry, John; Zomer, Aldert

2012-01-01

This work reports on the identification and molecular characterization of the two-component regulatory system (2CRS) PhoRP, which controls the response to inorganic phosphate (Pi) starvation in Bifidobacterium breve UCC2003. The response regulator PhoP was shown to bind to the promoter region of pstSCAB, specifying a predicted Pi transporter system, as well as that of phoU, which encodes a putative Pi-responsive regulatory protein. This interaction is assumed to cause transcriptional modulation under conditions of Pi limitation. Our data suggest that the phoRP genes are subject to positive autoregulation and, together with pstSCAB and presumably phoU, represent the complete regulon controlled by the phoRP-encoded 2CRS in B. breve UCC2003. Determination of the minimal PhoP binding region combined with bioinformatic analysis revealed the probable recognition sequence of PhoP, designated here as the PHO box, which together with phoRP is conserved among many high-GC-content Gram-positive bacteria. The importance of the phoRP 2CRS in the response of B. breve to Pi starvation conditions was confirmed by analysis of a B. breve phoP insertion mutant which exhibited decreased growth under phosphate-limiting conditions compared to its parent strain UCC2003. PMID:22635988

Anisotropic properties of phase separation in two-component dipolar Bose-Einstein condensates

NASA Astrophysics Data System (ADS)

Wang, Wei; Li, Jinbin

2018-03-01

Using Crank-Nicolson method, we calculate ground state wave functions of two-component dipolar Bose-Einstein condensates (BECs) and show that, due to dipole-dipole interaction (DDI), the condensate mixture displays anisotropic phase separation. The effects of DDI, inter-component s-wave scattering, strength of trap potential and particle numbers on the density profiles are investigated. Three types of two-component profiles are present, first cigar, along z-axis and concentric torus, second pancake (or blood cell), in xy-plane, and two non-uniform ellipsoid, separated by the pancake and third two dumbbell shapes.

The Two-Component System PhoPR of Clostridium acetobutylicum Is Involved in Phosphate-Dependent Gene Regulation ▿

PubMed Central

Fiedler, Tomas; Mix, Maren; Meyer, Uta; Mikkat, Stefan; Glocker, Michael O.; Bahl, Hubert; Fischer, Ralf-Jörg

2008-01-01

The phoPR gene locus of Clostridium acetobutylicum ATCC 824 comprises two genes, phoP and phoR. Deduced proteins are predicted to represent a response regulator and sensor kinase of a phosphate-dependent two-component regulatory system. We analyzed the expression patterns of phoPR in Pi-limited chemostat cultures and in response to Pi pulses. A basic transcription level under high-phosphate conditions was shown, and a significant increase in mRNA transcript levels was found when external Pi concentrations dropped below 0.3 mM. In two-dimensional gel electrophoresis experiments, a 2.5-fold increase in PhoP was observed under Pi-limiting growth conditions compared to growth with an excess of Pi. At least three different transcription start points for phoP were determined by primer extension analyses. Proteins PhoP and an N-terminally truncated *PhoR were individually expressed heterologously in Escherichia coli and purified. Autophosphorylation of *PhoR and phosphorylation of PhoP were shown in vitro. Electromobility shift assays proved that there was a specific binding of PhoP to the promoter region of the phosphate-regulated pst operon of C. acetobutylicum. PMID:18689481

Superfluid drag in the two-component Bose-Hubbard model

NASA Astrophysics Data System (ADS)

Sellin, Karl; Babaev, Egor

2018-03-01

In multicomponent superfluids and superconductors, co- and counterflows of components have, in general, different properties. A. F. Andreev and E. P. Bashkin [Sov. Phys. JETP 42, 164 (1975)] discussed, in the context of He3/He4 superfluid mixtures, that interparticle interactions produce a dissipationless drag. The drag can be understood as a superflow of one component induced by phase gradients of the other component. Importantly, the drag can be both positive (entrainment) and negative (counterflow). The effect is known to have crucial importance for many properties of diverse physical systems ranging from the dynamics of neutron stars and rotational responses of Bose mixtures of ultracold atoms to magnetic responses of multicomponent superconductors. Although substantial literature exists that includes the drag interaction phenomenologically, only a few regimes are covered by quantitative studies of the microscopic origin of the drag and its dependence on microscopic parameters. Here we study the microscopic origin and strength of the drag interaction in a quantum system of two-component bosons on a lattice with short-range interaction. By performing quantum Monte Carlo simulations of a two-component Bose-Hubbard model we obtain dependencies of the drag strength on the boson-boson interactions and properties of the optical lattice. Of particular interest are the strongly correlated regimes where the ratio of coflow and counterflow superfluid stiffnesses can diverge, corresponding to the case of saturated drag.

High temperature two component explosive

DOEpatents

Mars, James E.; Poole, Donald R.; Schmidt, Eckart W.; Wang, Charles

1981-01-01

A two component, high temperature, thermally stable explosive composition comprises a liquid or low melting oxidizer and a liquid or low melting organic fuel. The oxidizer and fuel in admixture are incapable of substantial spontaneous exothermic reaction at temperatures on the order of 475.degree. K. At temperatures on the order of 475.degree. K., the oxidizer and fuel in admixture have an activation energy of at least about 40 kcal/mol. As a result of the high activation energy, the preferred explosive compositions are nondetonable as solids at ambient temperature, and become detonable only when heated beyond the melting point. Preferable oxidizers are selected from alkali or alkaline earth metal nitrates, nitrites, perchlorates, and/or mixtures thereof. Preferred fuels are organic compounds having polar hydrophilic groups. The most preferred fuels are guanidinium nitrate, acetamide and mixtures of the two. Most preferred oxidizers are eutectic mixtures of lithium nitrate, potassium nitrate and sodium nitrate, of sodium nitrite, sodium nitrate and potassium nitrate, and of potassium nitrate, calcium nitrate and sodium nitrate.

Evolution of Multidrug Resistance during Staphylococcus aureus Infection Involves Mutation of the Essential Two Component Regulator WalKR

PubMed Central

Howden, Benjamin P.; McEvoy, Christopher R. E.; Allen, David L.; Chua, Kyra; Gao, Wei; Harrison, Paul F.; Bell, Jan; Coombs, Geoffrey; Bennett-Wood, Vicki; Porter, Jessica L.; Robins-Browne, Roy; Davies, John K.; Seemann, Torsten; Stinear, Timothy P.

2011-01-01

Antimicrobial resistance in Staphylococcus aureus is a major public health threat, compounded by emergence of strains with resistance to vancomycin and daptomycin, both last line antimicrobials. Here we have performed high throughput DNA sequencing and comparative genomics for five clinical pairs of vancomycin-susceptible (VSSA) and vancomycin-intermediate ST239 S. aureus (VISA); each pair isolated before and after vancomycin treatment failure. These comparisons revealed a frequent pattern of mutation among the VISA strains within the essential walKR two-component regulatory locus involved in control of cell wall metabolism. We then conducted bi-directional allelic exchange experiments in our clinical VSSA and VISA strains and showed that single nucleotide substitutions within either walK or walR lead to co-resistance to vancomycin and daptomycin, and caused the typical cell wall thickening observed in resistant clinical isolates. Ion Torrent genome sequencing confirmed no additional regulatory mutations had been introduced into either the walR or walK VISA mutants during the allelic exchange process. However, two potential compensatory mutations were detected within putative transport genes for the walK mutant. The minimal genetic changes in either walK or walR also attenuated virulence, reduced biofilm formation, and led to consistent transcriptional changes that suggest an important role for this regulator in control of central metabolism. This study highlights the dramatic impacts of single mutations that arise during persistent S. aureus infections and demonstrates the role played by walKR to increase drug resistance, control metabolism and alter the virulence potential of this pathogen. PMID:22102812

Integration of a complex regulatory cascade involving the SirA/BarA and Csr global regulatory systems that controls expression of the Salmonella SPI-1 and SPI-2 virulence regulons through HilD.

PubMed

Martínez, Luary C; Yakhnin, Helen; Camacho, Martha I; Georgellis, Dimitris; Babitzke, Paul; Puente, José L; Bustamante, Víctor H

2011-06-01

Salmonella pathogenicity islands 1 and 2 (SPI-1 and SPI-2) play key roles in the pathogenesis of Salmonella enterica. Previously, we showed that when Salmonella grows in Luria-Bertani medium, HilD, encoded in SPI-1, first induces the expression of hilA, located in SPI-1, and subsequently of the ssrAB operon, located in SPI-2. These genes code for HilA and the SsrA/B two-component system, the positive regulators of the SPI-1 and SPI-2 regulons respectively. In this study, we demonstrate that CsrA, a global regulatory RNA binding protein, post-transcriptionally regulates hilD expression by directly binding near the Shine-Dalgarno and translation initiation codon sequences of the hilD mRNA, preventing its translation and leading to its accelerated turnover. Negative regulation is counteracted by the global SirA/BarA two-component system, which directly activates the expression of CsrB and CsrC, two non-coding regulatory RNAs that sequester CsrA, thereby preventing it from binding to its target mRNAs. Our results illustrate the integration of global and specific regulators into a multifactorial regulatory cascade controlling the expression of virulence genes acquired by horizontal transfer events. © 2011 Blackwell Publishing Ltd.

Chloroplast two-component systems: evolution of the link between photosynthesis and gene expression

PubMed Central

Puthiyaveetil, Sujith; Allen, John F.

2009-01-01

Two-component signal transduction, consisting of sensor kinases and response regulators, is the predominant signalling mechanism in bacteria. This signalling system originated in prokaryotes and has spread throughout the eukaryotic domain of life through endosymbiotic, lateral gene transfer from the bacterial ancestors and early evolutionary precursors of eukaryotic, cytoplasmic, bioenergetic organelles—chloroplasts and mitochondria. Until recently, it was thought that two-component systems inherited from an ancestral cyanobacterial symbiont are no longer present in chloroplasts. Recent research now shows that two-component systems have survived in chloroplasts as products of both chloroplast and nuclear genes. Comparative genomic analysis of photosynthetic eukaryotes shows a lineage-specific distribution of chloroplast two-component systems. The components and the systems they comprise have homologues in extant cyanobacterial lineages, indicating their ancient cyanobacterial origin. Sequence and functional characteristics of chloroplast two-component systems point to their fundamental role in linking photosynthesis with gene expression. We propose that two-component systems provide a coupling between photosynthesis and gene expression that serves to retain genes in chloroplasts, thus providing the basis of cytoplasmic, non-Mendelian inheritance of plastid-associated characters. We discuss the role of this coupling in the chronobiology of cells and in the dialogue between nuclear and cytoplasmic genetic systems. PMID:19324807

Chloroplast two-component systems: evolution of the link between photosynthesis and gene expression.

PubMed

Puthiyaveetil, Sujith; Allen, John F

2009-06-22

Two-component signal transduction, consisting of sensor kinases and response regulators, is the predominant signalling mechanism in bacteria. This signalling system originated in prokaryotes and has spread throughout the eukaryotic domain of life through endosymbiotic, lateral gene transfer from the bacterial ancestors and early evolutionary precursors of eukaryotic, cytoplasmic, bioenergetic organelles-chloroplasts and mitochondria. Until recently, it was thought that two-component systems inherited from an ancestral cyanobacterial symbiont are no longer present in chloroplasts. Recent research now shows that two-component systems have survived in chloroplasts as products of both chloroplast and nuclear genes. Comparative genomic analysis of photosynthetic eukaryotes shows a lineage-specific distribution of chloroplast two-component systems. The components and the systems they comprise have homologues in extant cyanobacterial lineages, indicating their ancient cyanobacterial origin. Sequence and functional characteristics of chloroplast two-component systems point to their fundamental role in linking photosynthesis with gene expression. We propose that two-component systems provide a coupling between photosynthesis and gene expression that serves to retain genes in chloroplasts, thus providing the basis of cytoplasmic, non-Mendelian inheritance of plastid-associated characters. We discuss the role of this coupling in the chronobiology of cells and in the dialogue between nuclear and cytoplasmic genetic systems.

The YvqE two-component system controls biofilm formation and acid production in Streptococcus pyogenes.

PubMed

Isaka, Masanori; Tatsuno, Ichiro; Maeyama, Jun-Ichi; Matsui, Hideyuki; Zhang, Yan; Hasegawa, Tadao

2016-07-01

In Streptococcus pyogenes, proteins involved in determining virulence are controlled by stand-alone response regulators and by two-component regulatory systems. Previous studies reported that, compared to the parental strain, the yvqE sensor knockout strain showed significantly reduced growth and lower virulence. To determine the function of YvqE, we performed biofilm analysis and pH assays on yvqE mutants, and site-directed mutagenesis of YvqE. The yvqE deletion mutant showed a slower acid production rate, indicating that YvqE regulates acid production from sugar fermentation. The mutant strain, in which the Asp(26) residue in YvqE was replaced with Asn, affected biofilm formation, suggesting that this amino acid senses hydrogen ions produced by fermentative sugar metabolism. Signals received by YvqE were directly or indirectly responsible for inducing pilus expression. This study shows that at low environmental pH, biofilm formation in S. pyogenes is mediated by YvqE and suggests that regulation of pilus expression by environmental acidification could be directly under the control of YvqE. © 2016 APMIS. Published by John Wiley & Sons Ltd.

RitR is an archetype for a novel family of redox sensors in the streptococci that has evolved from two-component response regulators and is required for pneumococcal colonization

PubMed Central

Han, Lanlan; Morrissey, Julie A.; Clarke, Thomas B.; Yesilkaya, Hasan; Silvaggi, Nicholas R.

2018-01-01

To survive diverse host environments, the human pathogen Streptococcus pneumoniae must prevent its self-produced, extremely high levels of peroxide from reacting with intracellular iron. However, the regulatory mechanism(s) by which the pneumococcus accomplishes this balance remains largely enigmatic, as this pathogen and other related streptococci lack all known redox-sensing transcription factors. Here we describe a two-component-derived response regulator, RitR, as the archetype for a novel family of redox sensors in a subset of streptococcal species. We show that RitR works to both repress iron transport and enable nasopharyngeal colonization through a mechanism that exploits a single cysteine (Cys128) redox switch located within its linker domain. Biochemical experiments and phylogenetics reveal that RitR has diverged from the canonical two-component virulence regulator CovR to instead dimerize and bind DNA only upon Cys128 oxidation in air-rich environments. Atomic structures show that Cys128 oxidation initiates a “helical unravelling” of the RitR linker region, suggesting a mechanism by which the DNA-binding domain is then released to interact with its cognate regulatory DNA. Expanded computational studies indicate this mechanism could be shared by many microbial species outside the streptococcus genus. PMID:29750817

Fisheries regulatory regimes and resilience to climate change.

PubMed

Ojea, Elena; Pearlman, Isaac; Gaines, Steven D; Lester, Sarah E

2017-05-01

Climate change is already producing ecological, social, and economic impacts on fisheries, and these effects are expected to increase in frequency and magnitude in the future. Fisheries governance and regulations can alter socio-ecological resilience to climate change impacts via harvest control rules and incentives driving fisher behavior, yet there are no syntheses or conceptual frameworks for examining how institutions and their regulatory approaches can alter fisheries resilience to climate change. We identify nine key climate resilience criteria for fisheries socio-ecological systems (SES), defining resilience as the ability of the coupled system of interacting social and ecological components (i.e., the SES) to absorb change while avoiding transformation into a different undesirable state. We then evaluate the capacity of four fisheries regulatory systems that vary in their degree of property rights, including open access, limited entry, and two types of rights-based management, to increase or inhibit resilience. Our exploratory assessment of evidence in the literature suggests that these regulatory regimes vary widely in their ability to promote resilient fisheries, with rights-based approaches appearing to offer more resilience benefits in many cases, but detailed characteristics of the regulatory instruments are fundamental.

Counterbalancing Regulation in Response Memory of a Positively Autoregulated Two-Component System.

PubMed

Gao, Rong; Godfrey, Katherine A; Sufian, Mahir A; Stock, Ann M

2017-09-15

Fluctuations in nutrient availability often result in recurrent exposures to the same stimulus conditions. The ability to memorize the past event and use the "memory" to make adjustments to current behaviors can lead to a more efficient adaptation to the recurring stimulus. A short-term phenotypic memory can be conferred via carryover of the response proteins to facilitate the recurrent response, but the additional accumulation of response proteins can lead to a deviation from response homeostasis. We used the Escherichia coli PhoB/PhoR two-component system (TCS) as a model system to study how cells cope with the recurrence of environmental phosphate (Pi) starvation conditions. We discovered that "memory" of prior Pi starvation can exert distinct effects through two regulatory pathways, the TCS signaling pathway and the stress response pathway. Although carryover of TCS proteins can lead to higher initial levels of transcription factor PhoB and a faster initial response in prestarved cells than in cells not starved, the response enhancement can be overcome by an earlier and greater repression of promoter activity in prestarved cells due to the memory of the stress response. The repression counterbalances the carryover of the response proteins, leading to a homeostatic response whether or not cells are prestimulated. A computational model based on sigma factor competition was developed to understand the memory of stress response and to predict the homeostasis of other PhoB-regulated response proteins. Our insight into the history-dependent PhoBR response may provide a general understanding of how TCSs respond to recurring stimuli and adapt to fluctuating environmental conditions. IMPORTANCE Bacterial cells in their natural environments experience scenarios that are far more complex than are typically replicated in laboratory experiments. The architectures of signaling systems and the integration of multiple adaptive pathways have evolved to deal with such complexity

Counterbalancing Regulation in Response Memory of a Positively Autoregulated Two-Component System

PubMed Central

Gao, Rong; Godfrey, Katherine A.; Sufian, Mahir A.

2017-01-01

ABSTRACT Fluctuations in nutrient availability often result in recurrent exposures to the same stimulus conditions. The ability to memorize the past event and use the “memory” to make adjustments to current behaviors can lead to a more efficient adaptation to the recurring stimulus. A short-term phenotypic memory can be conferred via carryover of the response proteins to facilitate the recurrent response, but the additional accumulation of response proteins can lead to a deviation from response homeostasis. We used the Escherichia coli PhoB/PhoR two-component system (TCS) as a model system to study how cells cope with the recurrence of environmental phosphate (Pi) starvation conditions. We discovered that “memory” of prior Pi starvation can exert distinct effects through two regulatory pathways, the TCS signaling pathway and the stress response pathway. Although carryover of TCS proteins can lead to higher initial levels of transcription factor PhoB and a faster initial response in prestarved cells than in cells not starved, the response enhancement can be overcome by an earlier and greater repression of promoter activity in prestarved cells due to the memory of the stress response. The repression counterbalances the carryover of the response proteins, leading to a homeostatic response whether or not cells are prestimulated. A computational model based on sigma factor competition was developed to understand the memory of stress response and to predict the homeostasis of other PhoB-regulated response proteins. Our insight into the history-dependent PhoBR response may provide a general understanding of how TCSs respond to recurring stimuli and adapt to fluctuating environmental conditions. IMPORTANCE Bacterial cells in their natural environments experience scenarios that are far more complex than are typically replicated in laboratory experiments. The architectures of signaling systems and the integration of multiple adaptive pathways have evolved to deal

Mission Risk Reduction Regulatory Change Management

NASA Technical Reports Server (NTRS)

Scroggins, Sharon

2007-01-01

NASA Headquarters Environmental Management Division supports NASA's mission to pioneer the future in space exploration, scientific discovery, and aeronautics research by integrating environmental considerations into programs and projects early-on, thereby proactively reducing NASA's exposure to institutional, programmatic and operational risk. As part of this effort, NASA established the Principal Center for Regulatory Risk Analysis and Communication (RRAC PC) as a resource for detecting, analyzing, and communicating environmental regulatory risks to the NASA stakeholder community. The RRAC PC focuses on detecting emerging environmental regulations and other operational change drivers that may pose risks to NASA programs and facilities, and effectively communicating the potential risks. For example, regulatory change may restrict how and where certain activities or operations may be conducted. Regulatory change can also directly affect the ability to use certain materials by mandating a production phase-out or restricting usage applications of certain materials. Regulatory change can result in significant adverse impacts to NASA programs and facilities due to NASA's stringent performance requirements for materials and components related to human-rated space vehicles. Even if a regulation does not directly affect NASA operations, U.S. and international regulations can pose program risks indirectly through requirements levied on manufacturers and vendors of components and materials. For example, manufacturers can change their formulations to comply with new regulatory requirements. Such changes can require time-consuming and costly requalification certification for use in human spaceflight programs. The RRAC PC has implemented a system for proactively managing regulatory change to minimize potential adverse impacts to NASA programs and facilities. This presentation highlights the process utilized by the RRACPC to communicate regulatory change and the associated

Theory of Ostwald ripening in a two-component system

NASA Technical Reports Server (NTRS)

Baird, J. K.; Lee, L. K.; Frazier, D. O.; Naumann, R. J.

1986-01-01

When a two-component system is cooled below the minimum temperature for its stability, it separates into two or more immiscible phases. The initial nucleation produces grains (if solid) or droplets (if liquid) of one of the phases dispersed in the other. The dynamics by which these nuclei proceed toward equilibrium is called Ostwald ripening. The dynamics of growth of the droplets depends upon the following factors: (1) The solubility of the droplet depends upon its radius and the interfacial energy between it and the surrounding (continuous) phase. There is a critical radius determined by the supersaturation in the continuous phase. Droplets with radii smaller than critical dissolve, while droplets with radii larger grow. (2) The droplets concentrate one component and reject the other. The rate at which this occurs is assumed to be determined by the interdiffusion of the two components in the continuous phase. (3) The Ostwald ripening is constrained by conservation of mass; e.g., the amount of materials in the droplet phase plus the remaining supersaturation in the continuous phase must equal the supersaturation available at the start. (4) There is a distribution of droplet sizes associated with a mean droplet radius, which grows continuously with time. This distribution function satisfies a continuity equation, which is solved asymptotically by a similarity transformation method.

Time-dependent sorption of two novel fungicides in soils within a regulatory framework.

PubMed

Gulkowska, Anna; Buerge, Ignaz J; Poiger, Thomas; Kasteel, Roy

2016-12-01

Convincing experimental evidence suggests increased sorption of pesticides on soil over time, which, so far, has not been considered in the regulatory assessment of leaching to groundwater. Recently, Beulke and van Beinum (2012) proposed a guidance on how to conduct, analyse and use time-dependent sorption studies in pesticide registration. The applicability of the recommended experimental set-up and fitting procedure was examined for two fungicides, penflufen and fluxapyroxad, in four soils during a 170 day incubation experiment. The apparent distribution coefficient increased by a factor of 2.5-4.5 for penflufen and by a factor of 2.5-2.8 for fluxapyroxad. The recommended two-site, one-rate sorption model adequately described measurements of total mass and liquid phase concentration in the calcium chloride suspension and the calculated apparent distribution coefficient, passing all prescribed quality criteria for model fit and parameter reliability. The guidance is technically mature regarding the experimental set-up and parameterisation of the sorption model for the two moderately mobile and relatively persistent fungicides under investigation. These parameters can be used for transport modelling in soil, thereby recognising the existence of the experimentally observed, but in the regulatory leaching assessment of pesticides not yet routinely considered phenomenon of time-dependent sorption. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Cooling schemes for two-component fermions in layered optical lattices

NASA Astrophysics Data System (ADS)

Goto, Shimpei; Danshita, Ippei

2017-12-01

Recently, a cooling scheme for ultracold atoms in a bilayer optical lattice has been proposed (A. Kantian et al., arXiv:1609.03579). In their scheme, the energy offset between the two layers is increased dynamically such that the entropy of one layer is transferred to the other layer. Using the full-Hilbert-space approach, we compute cooling dynamics subjected to the scheme in order to show that their scheme fails to cool down two-component fermions. We develop an alternative cooling scheme for two-component fermions, in which the spin-exchange interaction of one layer is significantly reduced. Using both full-Hilbert-space and matrix-product-state approaches, we find that our scheme can decrease the temperature of the other layer by roughly half.

Goal-Directed Aiming: Two Components but Multiple Processes

ERIC Educational Resources Information Center

Elliott, Digby; Hansen, Steve; Grierson, Lawrence E. M.; Lyons, James; Bennett, Simon J.; Hayes, Spencer J.

2010-01-01

This article reviews the behavioral literature on the control of goal-directed aiming and presents a multiple-process model of limb control. The model builds on recent variants of Woodworth's (1899) two-component model of speed-accuracy relations in voluntary movement and incorporates ideas about dynamic online limb control based on prior…

Two-component regulators involved in the global control of virulence in Erwinia carotovora subsp. carotovora.

PubMed

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

1998-08-01

Production of extracellular, plant cell wall degrading enzymes, the main virulence determinants of the plant pathogen Erwinia carotovora subsp. carotovora, is coordinately controlled by a complex regulatory network. Insertion mutants in the exp (extracellular enzyme production) loci exhibit pleiotropic defects in virulence and the growth-phase-dependent transcriptional activation of genes encoding extracellular enzymes. Two new exp mutations, designated expA and expS, were characterized. Introduction of the corresponding wild-type alleles to the mutants complemented both the lack of virulence and the impaired production of plant cell wall degrading enzymes. The expA gene was shown to encode a 24-kDa polypeptide that is structurally and functionally related to the uvrY gene product of Escherichia coli and the GacA response regulator of Pseudomonas fluorescens. Functional similarity of expA and uvrY was demonstrated by genetic complementation. The expA gene is organized in an operon together with a uvrC-like gene, identical to the organization of uvrY and uvrC in E. coli. The unlinked expS gene encodes a putative sensor kinase that shows 92% identity to the recently described rpfA gene product from another E. carotovora subsp. carotovora strain. Our data suggest that ExpS and ExpA are members of two-component sensor kinase and response regulator families, respectively. These two proteins might interact in controlling virulence gene expression in E. carotovora subsp. carotovora.

Methods of producing epoxides from alkenes using a two-component catalyst system

DOEpatents

Kung, Mayfair C.; Kung, Harold H.; Jiang, Jian

2013-07-09

Methods for the epoxidation of alkenes are provided. The methods include the steps of exposing the alkene to a two-component catalyst system in an aqueous solution in the presence of carbon monoxide and molecular oxygen under conditions in which the alkene is epoxidized. The two-component catalyst system comprises a first catalyst that generates peroxides or peroxy intermediates during oxidation of CO with molecular oxygen and a second catalyst that catalyzes the epoxidation of the alkene using the peroxides or peroxy intermediates. A catalyst system composed of particles of suspended gold and titanium silicalite is one example of a suitable two-component catalyst system.

The Evolution of Two-Component Signal Transduction Systems

PubMed Central

Capra, Emily J.; Laub, Michael T.

2014-01-01

To exist in a wide range of environmental niches, bacteria must sense and respond to a myriad of external signals. A primary means by which this occurs is through two-component signal transduction pathways, typically comprised of a histidine kinase that receives the input stimuli and a response regulator that effects an appropriate change in cellular physiology. Histidine kinases and response regulators have an intrinsic modularity that separates signal input, phosphotransfer, and output response; this modularity has allowed bacteria to dramatically expand and diversify their signaling capabilities. Recent work has begun to reveal the molecular basis by which two-component proteins evolve. How and why do orthologous signaling proteins diverge? How do cells gain new pathways and recognize new signals? What changes are needed to insulate a new pathway from existing pathways? What constraints are there on gene duplication and lateral gene transfer? Here, we review progress made in answering these questions, highlighting how the integration of genome sequence data with experimental studies is providing major new insights. PMID:22746333

76 FR 60557 - Closure of the U.S. Nuclear Regulatory Commission's Two White Flint North Building Entrance

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-29

... Two White Flint North Building Entrance AGENCY: Nuclear Regulatory Commission. ACTION: Notice of... through the recently renovated One White Flint North (OWFN) building entrance lobby. Only NRC badged employees and contractors shall be permitted to use the Two White Flint North (TWFN) building entrance. NRC...

Structure and mechanism of the essential two-component signal-transduction system WalKR in Staphylococcus aureus

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

Ji, Quanjiang; Chen, Peter J.; Qin, Guangrong

Most low GC Gram-positive bacteria possess an essential walKR two-component system (TCS) for signal transduction involved in regulating cell wall homoeostasis. Despite the well-established intracellular regulatory mechanism, the role of this TCS in extracellular signal recognition and factors that modulate the activity of this TCS remain largely unknown. Here we identify the extracellular receptor of the kinase ‘WalK’ (erWalK) as a key hub for bridging extracellular signal input and intracellular kinase activity modulation in Staphylococcus aureus. Characterization of the crystal structure of erWalK revealed a canonical Per-Arnt-Sim (PAS) domain for signal sensing. Single amino-acid mutation of potential signal-transduction residues resultedmore » in severely impaired function of WalKR. A small molecule derived from structure-based virtual screening against erWalK is capable of selectively activating the walKR TCS. Lastly, the molecular level characterization of erWalK will not only facilitate exploration of natural signal(s) but also provide a template for rational design of erWalK inhibitors.« less

Structure and mechanism of the essential two-component signal-transduction system WalKR in Staphylococcus aureus

DOE PAGES

Ji, Quanjiang; Chen, Peter J.; Qin, Guangrong; ...

2016-03-18

Most low GC Gram-positive bacteria possess an essential walKR two-component system (TCS) for signal transduction involved in regulating cell wall homoeostasis. Despite the well-established intracellular regulatory mechanism, the role of this TCS in extracellular signal recognition and factors that modulate the activity of this TCS remain largely unknown. Here we identify the extracellular receptor of the kinase ‘WalK’ (erWalK) as a key hub for bridging extracellular signal input and intracellular kinase activity modulation in Staphylococcus aureus. Characterization of the crystal structure of erWalK revealed a canonical Per-Arnt-Sim (PAS) domain for signal sensing. Single amino-acid mutation of potential signal-transduction residues resultedmore » in severely impaired function of WalKR. A small molecule derived from structure-based virtual screening against erWalK is capable of selectively activating the walKR TCS. Lastly, the molecular level characterization of erWalK will not only facilitate exploration of natural signal(s) but also provide a template for rational design of erWalK inhibitors.« less

Turbulent Burning Velocities of Two-Component Fuel Mixtures of Methane, Propane and Hydrogen

NASA Astrophysics Data System (ADS)

Kido, Hiroyuki; Nakahara, Masaya; Hashimoto, Jun; Barat, Dilmurat

In order to clarify the turbulent burning velocity of multi-component fuel mixtures, both lean and rich two-component fuel mixtures, in which methane, propane and hydrogen were used as fuels, were prepared while maintaining the laminar burning velocity approximately constant. A distinct difference in the measured turbulent burning velocity at the same turbulence intensity is observed for two-component fuel mixtures having different addition rates of fuel, even the laminar burning velocities are approximately the same. The burning velocities of lean mixtures change almost constantly as the rate of addition changes, whereas the burning velocities of the rich mixtures show no such tendency. This trend can be explained qualitatively based on the mean local burning velocity, which is estimated by taking into account the preferential diffusion effect for each fuel component. In addition, a model of turbulent burning velocity proposed for single-component fuel mixtures may be applied to two-component fuel mixtures by considering the estimated mean local burning velocity of each fuel.

Disordered hyperuniformity in two-component nonadditive hard-disk plasmas

NASA Astrophysics Data System (ADS)

Lomba, Enrique; Weis, Jean-Jacques; Torquato, Salvatore

2017-12-01

We study the behavior of a classical two-component ionic plasma made up of nonadditive hard disks with additional logarithmic Coulomb interactions between them. Due to the Coulomb repulsion, long-wavelength total density fluctuations are suppressed and the system is globally hyperuniform. Short-range volume effects lead to phase separation or to heterocoordination for positive or negative nonadditivities, respectively. These effects compete with the hidden long-range order imposed by hyperuniformity. As a result, the critical behavior of the mixture is modified, with long-wavelength concentration fluctuations partially damped when the system is charged. It is also shown that the decrease of configurational entropy due to hyperuniformity originates from contributions beyond the two-particle level. Finally, despite global hyperuniformity, we show that in our system the spatial configuration associated with each component separately is not hyperuniform, i.e., the system is not "multihyperuniform."

Gamma-Ray Burst Optical Afterglows with Two-component Jets: Polarization Evolution Revisited

NASA Astrophysics Data System (ADS)

Lan, Mi-Xiang; Wu, Xue-Feng; Dai, Zi-Gao

2018-06-01

Gamma-ray bursts have been widely argued to originate from binary compact object mergers or core collapse of massive stars. Jets from these systems may have two components: an inner, narrow sub-jet and an outer, wider sub-jet. Such a jet subsequently interacts with its ambient gas, leading to a reverse shock (RS) and a forward shock. The magnetic field in the narrow sub-jet is very likely to be mixed by an ordered component and a random component during the afterglow phase. In this paper, we calculate light curves and polarization evolution of optical afterglows with this mixed magnetic field in the RS region of the narrow sub-jet in a two-component jet model. The resultant light curve has two peaks: an early peak arising from the narrow sub-jet and a late-time rebrightening due to the wider sub-jet. We find the polarization degree (PD) evolution under such a mixed magnetic field confined in the shock plane is very similar to that under the purely ordered magnetic field condition. The two-dimensional “mixed” magnetic fields confined in the shock plane are essentially the ordered magnetic fields only with different configurations. The position angle (PA) of the two-component jet can change gradually or abruptly by 90°. In particular, an abrupt 90° change of the PA occurs when the PD changes from its decline phase to the rise phase.

A complex regulatory network controls aerobic ethanol oxidation in Pseudomonas aeruginosa: indication of four levels of sensor kinases and response regulators.

PubMed

Mern, Demissew S; Ha, Seung-Wook; Khodaverdi, Viola; Gliese, Nicole; Görisch, Helmut

2010-05-01

In addition to the known response regulator ErbR (former AgmR) and the two-component regulatory system EraSR (former ExaDE), three additional regulatory proteins have been identified as being involved in controlling transcription of the aerobic ethanol oxidation system in Pseudomonas aeruginosa. Two putative sensor kinases, ErcS and ErcS', and a response regulator, ErdR, were found, all of which show significant similarity to the two-component flhSR system that controls methanol and formaldehyde metabolism in Paracoccus denitrificans. All three identified response regulators, EraR (formerly ExaE), ErbR (formerly AgmR) and ErdR, are members of the luxR family. The three sensor kinases EraS (formerly ExaD), ErcS and ErcS' do not contain a membrane domain. Apparently, they are localized in the cytoplasm and recognize cytoplasmic signals. Inactivation of gene ercS caused an extended lag phase on ethanol. Inactivation of both genes, ercS and ercS', resulted in no growth at all on ethanol, as did inactivation of erdR. Of the three sensor kinases and three response regulators identified thus far, only the EraSR (formerly ExaDE) system forms a corresponding kinase/regulator pair. Using reporter gene constructs of all identified regulatory genes in different mutants allowed the hierarchy of a hypothetical complex regulatory network to be established. Probably, two additional sensor kinases and two additional response regulators, which are hidden among the numerous regulatory genes annotated in the genome of P. aeruginosa, remain to be identified.

Adaptation to Environmental Stimuli within the Host: Two-Component Signal Transduction Systems of Mycobacterium tuberculosis

PubMed Central

Bretl, Daniel J.; Demetriadou, Chrystalla; Zahrt, Thomas C.

2011-01-01

Summary: Pathogenic microorganisms encounter a variety of environmental stresses following infection of their respective hosts. Mycobacterium tuberculosis, the etiological agent of tuberculosis, is an unusual bacterial pathogen in that it is able to establish lifelong infections in individuals within granulomatous lesions that are formed following a productive immune response. Adaptation to this highly dynamic environment is thought to be mediated primarily through transcriptional reprogramming initiated in response to recognition of stimuli, including low-oxygen tension, nutrient depletion, reactive oxygen and nitrogen species, altered pH, toxic lipid moieties, cell wall/cell membrane-perturbing agents, and other environmental cues. To survive continued exposure to these potentially adverse factors, M. tuberculosis encodes a variety of regulatory factors, including 11 complete two-component signal transduction systems (TCSSs) and several orphaned response regulators (RRs) and sensor kinases (SKs). This report reviews our current knowledge of the TCSSs present in M. tuberculosis. In particular, we discuss the biochemical and functional characteristics of individual RRs and SKs, the environmental stimuli regulating their activation, the regulons controlled by the various TCSSs, and the known or postulated role(s) of individual TCSSs in the context of M. tuberculosis physiology and/or pathogenesis. PMID:22126994

Components of Streptococcus pneumoniae suppress allergic airways disease and NKT cells by inducing regulatory T cells.

PubMed

Thorburn, Alison N; Foster, Paul S; Gibson, Peter G; Hansbro, Philip M

2012-05-01

Asthma is an allergic airways disease (AAD) caused by dysregulated immune responses and characterized by eosinophilic inflammation, mucus hypersecretion, and airway hyperresponsiveness (AHR). NKT cells have been shown to contribute to AHR in some mouse models. Conversely, regulatory T cells (Tregs) control aberrant immune responses and maintain homeostasis. Recent evidence suggests that Streptococcus pneumoniae induces Tregs that have potential to be harnessed therapeutically for asthma. In this study, mouse models of AAD were used to identify the S. pneumoniae components that have suppressive properties, and the mechanisms underlying suppression were investigated. We tested the suppressive capacity of type-3-polysaccharide (T3P), isolated cell walls, pneumolysoid (Ply) and CpG. When coadministered, T3P + Ply suppressed the development of: eosinophilic inflammation, Th2 cytokine release, mucus hypersecretion, and AHR. Importantly, T3P + Ply also attenuated features of AAD when administered during established disease. We show that NKT cells contributed to the development of AAD and also were suppressed by T3P + Ply treatment. Furthermore, adoptive transfer of NKT cells induced AHR, which also could be reversed by T3P + Ply. T3P + Ply-induced Tregs were essential for the suppression of NKT cells and AAD, which was demonstrated by Treg depletion. Collectively, our results show that the S. pneumoniae components T3P + Ply suppress AAD through the induction of Tregs that blocked the activity of NKT cells. These data suggest that S. pneumoniae components may have potential as a therapeutic strategy for the suppression of allergic asthma through the induction of Tregs and suppression of NKT cells.

Simple waves in a two-component Bose-Einstein condensate

NASA Astrophysics Data System (ADS)

Ivanov, S. K.; Kamchatnov, A. M.

2018-04-01

We study the dynamics of so-called simple waves in a two-component Bose-Einstein condensate. The evolution of the condensate is described by Gross-Pitaevskii equations which can be reduced for these simple wave solutions to a system of ordinary differential equations which coincide with those derived by Ovsyannikov for the two-layer fluid dynamics. We solve the Ovsyannikov system for two typical situations of large and small difference between interspecies and intraspecies nonlinear interaction constants. Our analytic results are confirmed by numerical simulations.

Effect of weld line positions on the tensile deformation of two-component metal injection moulding

NASA Astrophysics Data System (ADS)

Manonukul, Anchalee; Songkuea, Sukrit; Moonchaleanporn, Pongporn; Tange, Makiko

2017-12-01

Knowledge of the mechanical properties of two-component parts is critical for engineering functionally graded components. In this study, mono- and two-component tensile test specimens were metal injection moulded. Three different weld line positions were generated in the two-component specimens. Linear shrinkage of the two-component specimens was greater than that of the mono-component specimens because the incompatibility of sintering shrinkage of both materials causes biaxial stresses and enhances sintering. The mechanical properties of 316L stainless steel were affected by the addition of a coloured pigment used to identify the weld line position after injection moulding. For the two-component specimens, the yield stress and ultimate tensile stress were similar to those of 316L stainless steel. Because 316L and 630 (also known as 17-4PH) stainless steels were well-sintered at the interface, the mechanical properties of the weaker material (316L stainless steel) were dominant. However, the elongations of the two-component specimens were lower than those of the mono-component specimens. An interfacial zone with a microstructure that differed from those of the mono-material specimens was observed; its different microstructure was attributed to the gradual diffusion of nickel and copper.

Structural Basis for DNA Recognition by the Two-Component Response Regulator RcsB.

PubMed

Filippova, Ekaterina V; Zemaitaitis, Bozena; Aung, Theint; Wolfe, Alan J; Anderson, Wayne F

2018-02-27

RcsB is a highly conserved transcription regulator of the Rcs phosphorelay system, a complex two-component signal transduction system (N. Majdalani and S. Gottesman, Annu Rev Microbiol 59:379-405, 2005; A. J. Wolfe, Curr Opin Microbiol 13:204-209, 2010, https://doi.org/10.1016/j.mib.2010.01.002; D. J. Clarke, Future Microbiol 5:1173-1184, 2010, https://doi.org/10.2217/fmb.10.83). RcsB plays an important role in virulence and pathogenicity in human hosts by regulating biofilm formation. RcsB can regulate transcription alone or together with its auxiliary transcription regulators by forming heterodimers. This complexity allows RcsB to regulate transcription of more than 600 bacterial genes in response to different stresses (D. Wang et al., Mol Plant Microbe Interact 25:6-17, 2012, https://doi.org/10.1094/MPMI-08-11-0207). Despite increasing knowledge of RcsB importance, molecular mechanisms that drive the ability of RcsB to control transcription of a large number of genes remain unclear. Here, we present crystal structures of unphosphorylated RcsB in complex with the consensus DNA-binding sequence of 22-mer (DNA22) and 18-mer (DNA18) of the flhDC operon from Escherichia coli determined at 3.15- and 3.37-Å resolution, respectively. The results of our structural analysis combined with the results of in vitro binding assays provide valuable insights to the protein regulatory mechanism, demonstrate how RcsB recognizes target DNA sequences, and reveal a unique oligomeric state that allows RcsB to form homo- and heterodimers. This information will help us understand the complex mechanisms of transcriptional regulation by RcsB in bacteria. IMPORTANCE RcsB is a well-studied two-component response regulator of the Rcs phosphorelay system, conserved within the family Enterobacteriaceae , which includes many pathogens. It is a global regulator, controlling more than 5% of bacterial genes associated with capsule biosynthesis, flagellar biogenesis, cell wall biosynthesis

76 FR 14108 - Notice of Issuance of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-15

..., Revision 1, ``Control of Preheat Temperature for Welding of Low-Alloy Steel.'' FOR FURTHER INFORMATION... for Welding of Low-Alloy Steel,'' was issued with a temporary identification as Draft Regulatory Guide... implementing regulatory requirements related to the control of welding for low-alloy steel components during...

Preparation and analysis of a two-components breath figure at the nanoscale

NASA Astrophysics Data System (ADS)

Kofman, R.; Allione, M.; Celestini, F.; Barkay, Z.; Lereah, Y.

2008-12-01

Solid/liquid two-components Ga-Pb structures in isolated nanometer sized particles have been produced and studied by electron microscopy. Production is based on the breath figure technique and we investigate the way the two components are distributed. We clearly identify two growth regimes associated with the two different ways a Pb atom incorporates into a Ga nanodrop. Using TEM and SEM, the shape and microstructure of the nanoparticles are studied and the results obtained are in good agreement with the proposed model. The experimental technique used appears to be appropriate to produce Pb nanocrystals in liquid Ga nano-containers.

A two-component rain model for the prediction of attenuation statistics

NASA Technical Reports Server (NTRS)

Crane, R. K.

1982-01-01

A two-component rain model has been developed for calculating attenuation statistics. In contrast to most other attenuation prediction models, the two-component model calculates the occurrence probability for volume cells or debris attenuation events. The model performed significantly better than the International Radio Consultative Committee model when used for predictions on earth-satellite paths. It is expected that the model will have applications in modeling the joint statistics required for space diversity system design, the statistics of interference due to rain scatter at attenuating frequencies, and the duration statistics for attenuation events.

78 FR 19541 - Proposed Revision to Design of Structures, Components, Equipment and Systems

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-01

... NUCLEAR REGULATORY COMMISSION [NRC-2013-0041] Proposed Revision to Design of Structures, Components, Equipment and Systems AGENCY: Nuclear Regulatory Commission. ACTION: Standard review plan-draft..., ``Design of Structures, Components, Equipment, and Systems;'' and the request for comment on NUREG-0800...

Nonlinear low frequency electrostatic structures in a magnetized two-component auroral plasma

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

Rufai, O. R., E-mail: rajirufai@gmail.com; Scientific Computing, Memorial University of Newfoundland, St John's, Newfoundland and Labrador A1C 5S7; Bharuthram, R., E-mail: rbharuthram@uwc.ac.za

2016-03-15

Finite amplitude nonlinear ion-acoustic solitons, double layers, and supersolitons in a magnetized two-component plasma composed of adiabatic warm ions fluid and energetic nonthermal electrons are studied by employing the Sagdeev pseudopotential technique and assuming the charge neutrality condition at equilibrium. The model generates supersoliton structures at supersonic Mach numbers regime in addition to solitons and double layers, whereas in the unmagnetized two-component plasma case only, soliton and double layer solutions can be obtained. Further investigation revealed that wave obliqueness plays a critical role for the evolution of supersoliton structures in magnetized two-component plasmas. In addition, the effect of ion temperaturemore » and nonthermal energetic electron tends to decrease the speed of oscillation of the nonlinear electrostatic structures. The present theoretical results are compared with Viking satellite observations.« less

Modulating the level of components within plants

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

Bobzin, Steven Craig; Apuya, Nestor; Chiang, Karen

Materials and Methods for identifying lignin regulatory region-regulatory protein associations are disclosed. Materials and methods for modulating lignin accumulation are also disclosed. In addition, methods and materials for modulating (e.g., increasing or decreasing) the level of a component (e.g., protein, oil, lignin, carbon, a carotenoid, or a triterpenoid) in plants are disclosed.

Emerging principles of regulatory evolution.

PubMed

Prud'homme, Benjamin; Gompel, Nicolas; Carroll, Sean B

2007-05-15

Understanding the genetic and molecular mechanisms governing the evolution of morphology is a major challenge in biology. Because most animals share a conserved repertoire of body-building and -patterning genes, morphological diversity appears to evolve primarily through changes in the deployment of these genes during development. The complex expression patterns of developmentally regulated genes are typically controlled by numerous independent cis-regulatory elements (CREs). It has been proposed that morphological evolution relies predominantly on changes in the architecture of gene regulatory networks and in particular on functional changes within CREs. Here, we discuss recent experimental studies that support this hypothesis and reveal some unanticipated features of how regulatory evolution occurs. From this growing body of evidence, we identify three key operating principles underlying regulatory evolution, that is, how regulatory evolution: (i) uses available genetic components in the form of preexisting and active transcription factors and CREs to generate novelty; (ii) minimizes the penalty to overall fitness by introducing discrete changes in gene expression; and (iii) allows interactions to arise among any transcription factor and downstream CRE. These principles endow regulatory evolution with a vast creative potential that accounts for both relatively modest morphological differences among closely related species and more profound anatomical divergences among groups at higher taxonomical levels.

Considerations on comprehensive and off-line supercritical fluid chromatography x reversed-phase liquid chromatography for the analysis of triacylglycerols in fish oil.

PubMed

François, Isabelle; Pereira, Alberto dos Santos; Sandra, Pat

2010-06-01

The separation of the triacylglycerols in fish oil was performed by comprehensive and off-line supercritical fluid chromatography combined with RP-LC. The first dimension consisted of two serially coupled silver-ion (SI)-loaded columns operated with a supercritical mobile phase (supercritical fluid chromatography, SFC) in both the cases, whereas the second dimension was performed in non-aqueous RP mode (NARP-LC) on a 10-cm monolithic octadecyl silica (ODS) or a 45-cm long ODS column packed with 1.8 microm particles for the comprehensive and off-line separations, respectively. Despite the outstanding performance of the SI-SFC x NARP-LC interface, the high complexity of the sample rendered the online separation far from complete. The off-line approach gave much better separation mainly because of the higher peak capacity of the second-dimension column, but even in this case, the use of MS was mandatory to elucidate the different triacylglycerols in fish oil. The disadvantage of the off-line procedure was the long analysis time.

A Synthetical Two-Component Model with Peakon Solutions: One More Bi-Hamiltonian Case

NASA Astrophysics Data System (ADS)

Mengxia, Zhang; Xiaomin, Yang

2018-05-01

Compatible pairs of Hamiltonian operators for the synthetical two-component model of Xia, Qiao, and Zhou are derived systematically by means of the spectral gradient method. A new two-component system, which is bi-Hamiltonian, is presented. For this new system, the construction of its peakon solutions is considered.

Block algebra in two-component BKP and D type Drinfeld-Sokolov hierarchies

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

Li, Chuanzhong, E-mail: lichuanzhong@nbu.edu.cn; He, Jingsong, E-mail: hejingsong@nbu.edu.cn

We construct generalized additional symmetries of a two-component BKP hierarchy defined by two pseudo-differential Lax operators. These additional symmetry flows form a Block type algebra with some modified (or additional) terms because of a B type reduction condition of this integrable hierarchy. Further we show that the D type Drinfeld-Sokolov hierarchy, which is a reduction of the two-component BKP hierarchy, possess a complete Block type additional symmetry algebra. That D type Drinfeld-Sokolov hierarchy has a similar algebraic structure as the bigraded Toda hierarchy which is a differential-discrete integrable system.

On the locating-chromatic number for graphs with two homogenous components

NASA Astrophysics Data System (ADS)

Welyyanti, Des; Baskoro, Edy Tri; Simajuntak, Rinovia; Uttunggadewa, Saladin

2017-10-01

The locating-chromatic number of a graph was introduced by Chartrand et al. in 2002. The concept of the locating-chromatic number is a marriage between graph coloring and the notion of graph partition dimension. This concept is only for connected graphs. In [8], we extended this concept also for disconnected graphs. In this paper, we determine the locating- chromatic number of a graph with two components. In particular, we determine such values if the components are homogeneous and each component has locating-chromatic number 3.

Two-component Fermi-liquid theory - Equilibrium properties of liquid metallic hydrogen

NASA Technical Reports Server (NTRS)

Oliva, J.; Ashcroft, N. W.

1981-01-01

It is reported that the transition of condensed hydrogen from an insulating molecular crystal phase to a metallic liquid phase, at zero temperature and high pressure, appears possible. Liquid metallic hydrogen (LMH), comprising interpenetrating proton and electron fluids, would constitute a two-component Fermi liquid with both a very high component-mass ratio and long-range, species-dependent bare interactions. The low-temperature equilibrium properties of LMH are examined by means of a generalization to the case of two components of the phenomenological Landau Fermi-liquid theory, and the low-temperature specific heat, compressibility, thermal expansion coefficient and spin susceptibility are given. It is found that the specific heat and the thermal expansion coefficient are vastly greater in the liquid than in the corresponding solid, due to the presence of proton quasiparticle excitations in the liquid.

The Xanthomonas oryzae pv. oryzae PhoPQ Two-Component System Is Required for AvrXA21 Activity, hrpG Expression, and Virulence▿ †

PubMed Central

Lee, Sang-Won; Jeong, Kyu-Sik; Han, Sang-Wook; Lee, Seung-Eun; Phee, Bong-Kwan; Hahn, Tae-Ryong; Ronald, Pamela

2008-01-01

The rice pathogen recognition receptor, XA21, confers resistance to Xanthomonas oryzae pv. oryzae strains producing the type one system-secreted molecule, AvrXA21. X. oryzae pv. oryzae requires a regulatory two-component system (TCS) called RaxRH to regulate expression of eight rax (required for AvrXA21 activity) genes and to sense population cell density. To identify other key components in this critical regulatory circuit, we assayed proteins expressed in a raxR gene knockout strain. This survey led to the identification of the phoP gene encoding a response regulator that is up-regulated in the raxR knockout strain. Next we generated a phoP knockout strain and found it to be impaired in X. oryzae pv. oryzae virulence and no longer able to activate the response regulator HrpG (hypersensitive reaction and pathogenicity G) in response to low levels of Ca2+. The impaired virulence of the phoP knockout strain can be partially complemented by constitutive expression of hrpG, indicating that PhoP controls a key aspect of X. oryzae pv. oryzae virulence through regulation of hrpG. A gene encoding the cognate putative histidine protein kinase, phoQ, was also isolated. Growth curve analysis revealed that AvrXA21 activity is impaired in a phoQ knockout strain as reflected by enhanced growth of this strain in rice lines carrying XA21. These results suggest that the X. oryzae pv. oryzae PhoPQ TCS functions in virulence and in the production of AvrXA21 in partnership with RaxRH. PMID:18203830

Comparative analysis of gene regulatory networks: from network reconstruction to evolution.

PubMed

Thompson, Dawn; Regev, Aviv; Roy, Sushmita

2015-01-01

Regulation of gene expression is central to many biological processes. Although reconstruction of regulatory circuits from genomic data alone is therefore desirable, this remains a major computational challenge. Comparative approaches that examine the conservation and divergence of circuits and their components across strains and species can help reconstruct circuits as well as provide insights into the evolution of gene regulatory processes and their adaptive contribution. In recent years, advances in genomic and computational tools have led to a wealth of methods for such analysis at the sequence, expression, pathway, module, and entire network level. Here, we review computational methods developed to study transcriptional regulatory networks using comparative genomics, from sequence to functional data. We highlight how these methods use evolutionary conservation and divergence to reliably detect regulatory components as well as estimate the extent and rate of divergence. Finally, we discuss the promise and open challenges in linking regulatory divergence to phenotypic divergence and adaptation.

The two-component system GrvRS (EtaRS) regulates ace expression in Enterococcus faecalis OG1RF.

PubMed

Roh, Jung Hyeob; Singh, Kavindra V; La Rosa, Sabina Leanti; Cohen, Ana Luisa V; Murray, Barbara E

2015-01-01

Expression of ace (adhesin to collagen of Enterococcus faecalis), encoding a virulence factor in endocarditis and urinary tract infection models, has been shown to increase under certain conditions, such as in the presence of serum, bile salts, urine, and collagen and at 46 °C. However, the mechanism of ace/Ace regulation under different conditions is still unknown. In this study, we identified a two-component regulatory system GrvRS as the main regulator of ace expression under these stress conditions. Using Northern hybridization and β-galactosidase assays of an ace promoter-lacZ fusion, we found transcription of ace to be virtually absent in a grvR deletion mutant under the conditions that increase ace expression in wild-type OG1RF and in the complemented strain. Moreover, a grvR mutant revealed decreased collagen binding and biofilm formation as well as attenuation in a murine urinary tract infection model. Here we show that GrvR plays a major role in control of ace expression and E. faecalis virulence. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

The two-component afterglow of Swift GRB 050802

NASA Astrophysics Data System (ADS)

Oates, S. R.; de Pasquale, M.; Page, M. J.; Blustin, A. J.; Zane, S.; McGowan, K.; Mason, K. O.; Poole, T. S.; Schady, P.; Roming, P. W. A.; Page, K. L.; Falcone, A.; Gehrels, N.

2007-09-01

This paper investigates GRB 050802, one of the best examples of a Swift gamma-ray burst afterglow that shows a break in the X-ray light curve, while the optical counterpart decays as a single power law. This burst has an optically bright afterglow of 16.5 mag, detected throughout the 170-650nm spectral range of the Ultraviolet and Optical Telescope (UVOT) onboard Swift. Observations began with the X-ray Telescope and UVOT telescopes 286s after the initial trigger and continued for 1.2 ×106s. The X-ray light curve consists of three power-law segments: a rise until 420s, followed by a slow decay with α =0.63 +/-0.03 until 5000s, after which, the light curve decays faster with a slope of α3 =1.59 +/-0.03. The optical light curve decays as a single power law with αO =0.82 +/-0.03 throughout the observation. The X-ray data on their own are consistent with the break at 5000s being due to the end of energy injection. Modelling the optical to X-ray spectral energy distribution, we find that the optical afterglow cannot be produced by the same component as the X-ray emission at late times, ruling out a single-component afterglow. We therefore considered two-component jet models and find that the X-ray and optical emission is best reproduced by a model in which both components are energy injected for the duration of the observed afterglow and the X-ray break at 5000s is due to a jet break in the narrow component. This bright, well-observed burst is likely a guide for interpreting the surprising finding of Swift that bursts seldom display achromatic jet breaks.

Stable vortex-bright-soliton structures in two-component Bose-Einstein condensates.

PubMed

Law, K J H; Kevrekidis, P G; Tuckerman, Laurette S

2010-10-15

We report the numerical realization of robust two-component structures in 2D and 3D Bose-Einstein condensates with nontrivial topological charge in one component. We identify a stable symbiotic state in which a higher-dimensional bright soliton exists even in a homogeneous setting with defocusing interactions, due to the effective potential created by a stable vortex in the other component. The resulting vortex-bright-solitons, generalizations of the recently experimentally observed dark-bright solitons, are found to be very robust both in the homogeneous medium and in the presence of external confinement.

Two components of postseismic gravity changes of megathrust earthquakes from satellite gravimetry

NASA Astrophysics Data System (ADS)

Tanaka, Y.; Heki, K.

2013-12-01

There are several reports of the observations of gravity changes due to megathrust earthquakes with data set of Gravity Recovery And Climate Experiment (GRACE) satellite. We analyzed the co- and postseismic gravity changes of the three magnitude 9 class earthquakes, the 2004 Sumatra-Andaman, the 2010 Chile (Maule), and the 2011 Tohoku-Oki earthquakes, using the newly released data (Release 05 data) set. In addition to the coseismic steps, these earthquakes showed a common feature that the postseismic changes include two components with different polarity and time constants, i.e. rapid decreases over a few months, followed by slow increases lasting for years. This is shown in the auxiliary figure of this abstract. In this figure, the white circles are the data whose seasonal and secular changes were removed. The vertical translucent lines denote the earthquake occurrence times. All the three earthquakes suggest the existence of two postseismic gravity change components with two distinct time constants. The first (short-term) component showed geographical distribution similar to the coseismic changes, but the position of the largest gravity decrease shifted toward the trench. The short-term components can be related to afterslip, but their time constants and distributions showed significant deviation from gravity changes predicted by the afterslip models. The second (long-term) components are characterized by positive gravity changes with the peak close to the trench axis. The long-term components should be attributed to different or multiple mechanisms, e.g. viscous relaxation of rocks in the upper mantle [Han and Simons, 2008; Panet et al., 2007] and diffusion of supercritical water around the down-dip end of the ruptured fault [Ogawa and Heki, 2007]. Both of the two mechanisms can explain the postseismic gravity increase in this timescale to some extent, but there have been no decisive evidence to prove or disprove either one of these. But generally speaking

78 FR 15755 - Proposed Revision to Design of Structures, Components, Equipment and Systems; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-12

... NUCLEAR REGULATORY COMMISSION [NRC-2013-0041] Proposed Revision to Design of Structures, Components, Equipment and Systems; Correction AGENCY: Nuclear Regulatory Commission. ACTION: Standard review... for comments of the proposed revision in Chapter 3, ``Design of Structures, Components, Equipment, and...

Regulation of nrf operon expression in pathogenic enteric bacteria: sequence divergence reveals new regulatory complexity

PubMed Central

Godfrey, Rita E.; Lee, David J.; Busby, Stephen J. W.

2017-01-01

Summary The Escherichia coli K‐12 nrf operon encodes a periplasmic nitrite reductase, the expression of which is driven from a single promoter, pnrf. Expression from pnrf is activated by the FNR transcription factor in response to anaerobiosis and further increased in response to nitrite by the response regulator proteins, NarL and NarP. FNR‐dependent transcription is suppressed by the binding of two nucleoid associated proteins, IHF and Fis. As Fis levels increase in cells grown in rich medium, the positioning of its binding site, overlapping the promoter −10 element, ensures that pnrf is sharply repressed. Here, we investigate the expression of the nrf operon promoter from various pathogenic enteric bacteria. We show that pnrf from enterohaemorrhagic E. coli is more active than its K‐12 counterpart, exhibits substantial FNR‐independent activity and is insensitive to nutrient quality, due to an improved −10 element. We also demonstrate that the Salmonella enterica serovar Typhimurium core promoter is more active than previously thought, due to differences around the transcription start site, and that its expression is repressed by downstream sequences. We identify the CsrA RNA binding protein as being responsible for this, and show that CsrA differentially regulates the E. coli K‐12 and Salmonella nrf operons. PMID:28211111

Reflections on Teaching and Research: Two Inseparable Components in Higher Education

ERIC Educational Resources Information Center

Chan Fong Yee, Fanny

2014-01-01

Teaching and research are two inseparable components in higher education. There are continuous debates about the relationship between the two. Does good teaching always lead to good research, and vice versa? This paper critically examines the impact of current policy on the two academic practices and discusses how it shapes one's professional…

Coexistent three-component and two-component Weyl phonons in TiS, ZrSe, and HfTe

NASA Astrophysics Data System (ADS)

Li, Jiangxu; Xie, Qing; Ullah, Sami; Li, Ronghan; Ma, Hui; Li, Dianzhong; Li, Yiyi; Chen, Xing-Qiu

2018-02-01

In analogy to various fermions of electrons in topological semimetals, topological mechanical states with two types of bosons, Dirac and Weyl bosons, were reported in some macroscopic systems of kHz frequency, and those with a type of doubly-Weyl phonons in atomic vibrational framework of THz frequency of solid crystals were recently predicted. Here, through first-principles calculations, we have reported that the phonon spectra of the WC-type TiS, ZrSe, and HfTe commonly host the unique triply degenerate nodal points (TDNPs) and single two-component Weyl points (WPs) in THz frequency. Quasiparticle excitations near TDNPs of phonons are three-component bosons, beyond the conventional and known classifications of Dirac, Weyl, and doubly-Weyl phonons. Moreover, we have found that both TiS and ZrSe have five pairs of type-I Weyl phonons and a pair of type-II Weyl phonons, whereas HfTe only has four pairs of type-I Weyl phonons. They carry nonzero topological charges. On the (10 1 ¯0 ) crystal surfaces, we observe topological protected surface arc states connecting two WPs with opposite charges, which host modes that propagate nearly in one direction on the surface.

A two-component Bayesian mixture model to identify implausible gestational age.

PubMed

Mohammadian-Khoshnoud, Maryam; Moghimbeigi, Abbas; Faradmal, Javad; Yavangi, Mahnaz

2016-01-01

Background: Birth weight and gestational age are two important variables in obstetric research. The primary measure of gestational age is based on a mother's recall of her last menstrual period. This recall may cause random or systematic errors. Therefore, the objective of this study is to utilize Bayesian mixture model in order to identify implausible gestational age. Methods: In this cross-sectional study, medical documents of 502 preterm infants born and hospitalized in Hamadan Fatemieh Hospital from 2009 to 2013 were gathered. Preterm infants were classified to less than 28 weeks and 28 to 31 weeks. A two-component Bayesian mixture model was utilized to identify implausible gestational age; the first component shows the probability of correct and the second one shows the probability of incorrect classification of gestational ages. The data were analyzed through OpenBUGS 3.2.2 and 'coda' package of R 3.1.1. Results: The mean (SD) of the second component of less than 28 weeks and 28 to 31 weeks were 1179 (0.0123) and 1620 (0.0074), respectively. These values were larger than the mean of the first component for both groups which were 815.9 (0.0123) and 1061 (0.0074), respectively. Conclusion: Errors occurred in recording the gestational ages of these two groups of preterm infants included recording the gestational age less than the actual value at birth. Therefore, developing scientific methods to correct these errors is essential to providing desirable health services and adjusting accurate health indicators.

Two-component scattering model and the electron density spectrum

NASA Astrophysics Data System (ADS)

Zhou, A. Z.; Tan, J. Y.; Esamdin, A.; Wu, X. J.

2010-02-01

In this paper, we discuss a rigorous treatment of the refractive scintillation caused by a two-component interstellar scattering medium and a Kolmogorov form of density spectrum. It is assumed that the interstellar scattering medium is composed of a thin-screen interstellar medium (ISM) and an extended interstellar medium. We consider the case that the scattering of the thin screen concentrates in a thin layer represented by a δ function distribution and that the scattering density of the extended irregular medium satisfies the Gaussian distribution. We investigate and develop equations for the flux density structure function corresponding to this two-component ISM geometry in the scattering density distribution and compare our result with the observations. We conclude that the refractive scintillation caused by this two-component ISM scattering gives a more satisfactory explanation for the observed flux density variation than does the single extended medium model. The level of refractive scintillation is strongly sensitive to the distribution of scattering material along the line of sight (LOS). The theoretical modulation indices are comparatively less sensitive to the scattering strength of the thin-screen medium, but they critically depend on the distance from the observer to the thin screen. The logarithmic slope of the structure function is sensitive to the scattering strength of the thin-screen medium, but is relatively insensitive to the thin-screen location. Therefore, the proposed model can be applied to interpret the structure functions of flux density observed in pulsar PSR B2111 + 46 and PSR B0136 + 57. The result suggests that the medium consists of a discontinuous distribution of plasma turbulence embedded in the interstellar medium. Thus our work provides some insight into the distribution of the scattering along the LOS to the pulsar PSR B2111 + 46 and PSR B0136 + 57.

Electron acoustic-Langmuir solitons in a two-component electron plasma

NASA Astrophysics Data System (ADS)

McKenzie, J. F.

2003-04-01

We investigate the conditions under which ‘high-frequency’ electron acoustic Langmuir solitons can be constructed in a plasma consisting of protons and two electron populations: one ‘cold’ and the other ‘hot’. Conservation of total momentum can be cast as a structure equation either for the ‘cold’ or ‘hot’ electron flow speed in a stationary wave using the Bernoulli energy equations for each species. The linearized version of the governing equations gives the dispersion equation for the stationary waves of the system, from which follows the necessary but not sufficient conditions for the existence of soliton structures; namely that the wave speed must be less than the acoustic speed of the ‘hot’ electron component and greater than the low-frequency compound acoustic speed of the two electron populations. In this wave speed regime linear waves are ‘evanescent’, giving rise to the exponential growth or decay, which readily can give rise to non-linear effects that may balance dispersion and allow soliton formation. In general the ‘hot’ component must be more abundant than the ‘cold’ one and the wave is characterized by a compression of the ‘cold’ component and an expansion in the ‘hot’ component necessitating a potential dip. Both components are driven towards their sonic points; the ‘cold’ from above and the ‘hot’ from below. It is this transonic feature which limits the amplitude of the soliton. If the ‘hot’ component is not sufficiently abundant the window for soliton formation shrinks to a narrow speed regime which is quasi-transonic relative to the ‘hot’ electron acoustic speed, and it is shown that smooth solitons cannot be constructed. In the special case of a very cold electron population (i.e. ‘highly supersonic’) and the other population being very hot (i.e. ‘highly subsonic’) with adiabatic index 2, the structure equation simplifies and can be integrated in terms of elementary

Substrate temperature controls molecular orientation in two-component vapor-deposited glasses

DOE PAGES

Jiang, J.; Walters, D. M.; Zhou, D.; ...

2016-02-22

Vapor-deposited glasses can be anisotropic and molecular orientation is important for organic electronics applications. In organic light emitting diodes (OLEDs), for example, the orientation of dye molecules in two-component emitting layers significantly influences emission efficiency. Here we investigate how substrate temperature during vapor deposition influences the orientation of dye molecules in a model two-component system. We determine the average orientation of a linear blue light emitter 1,4-di-[4-( N,N-diphenyl)amino]styrylbenzene (DSA-Ph) in mixtures with aluminum-tris(8-hydroxyquinoline) (Alq 3) by spectroscopic ellipsometry and IR dichroism. We find that molecular orientation is controlled by the ratio of the substrate temperature during deposition and the glassmore » transition temperature of the mixture. Furthermore, these findings extend recent results for single component vapor-deposited glasses and suggest that, during vapor deposition, surface mobility allows partial equilibration towards orientations preferred at the free surface of the equilibrium liquid.« less

Modelling diameter distributions of two-cohort forest stands with various proportions of dominant species: a two-component mixture model approach.

Treesearch

Rafal Podlaski; Francis Roesch

2014-01-01

In recent years finite-mixture models have been employed to approximate and model empirical diameter at breast height (DBH) distributions. We used two-component mixtures of either the Weibull distribution or the gamma distribution for describing the DBH distributions of mixed-species, two-cohort forest stands, to analyse the relationships between the DBH components,...

Regulatory System for Stem/Progenitor Cell Niches in the Adult Rodent Pituitary

PubMed Central

Yoshida, Saishu; Kato, Takako; Kato, Yukio

2016-01-01

The anterior lobe of the pituitary gland is a master endocrine tissue composed of five types of endocrine cells. Although the turnover rate of pituitary endocrine cells is as low as about 1.6% per day, recent studies have demonstrated that Sex-determining region Y-box 2 (SOX2)+-cells exist as pituitary stem/progenitor cells in the adult anterior lobe and contribute to cell regeneration. Notably, SOX2+-pituitary stem/progenitor cells form two types of niches in this tissue: the marginal cell layer (MCL-niche) and the dense cell clusters scattering in the parenchyma (parenchymal-niche). However, little is known about the mechanisms and factors for regulating the pituitary stem/progenitor cell niches, as well as the functional differences between the two types of niches. Elucidation of the regulatory mechanisms in the niches might enable us to understand the cell regeneration system that acts in accordance with physiological demands in the adult pituitary. In this review, so as to reveal the regulatory mechanisms of the two types of niche, we summarize the regulatory factors and their roles in the adult rodent pituitary niches by focusing on three components: soluble factors, cell surface proteins and extracellular matrixes. PMID:26761002

Two-Dimensional One-Component Plasma on Flamm's Paraboloid

NASA Astrophysics Data System (ADS)

Fantoni, Riccardo; Téllez, Gabriel

2008-11-01

We study the classical non-relativistic two-dimensional one-component plasma at Coulomb coupling Γ=2 on the Riemannian surface known as Flamm's paraboloid which is obtained from the spatial part of the Schwarzschild metric. At this special value of the coupling constant, the statistical mechanics of the system are exactly solvable analytically. The Helmholtz free energy asymptotic expansion for the large system has been found. The density of the plasma, in the thermodynamic limit, has been carefully studied in various situations.

77 FR 16270 - Updated Aging Management Criteria for Reactor Vessel Internal Components of Pressurized Water...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-20

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0070] Updated Aging Management Criteria for Reactor Vessel Internal Components of Pressurized Water Reactors AGENCY: Nuclear Regulatory Commission. ACTION: Draft..., ``Updated Aging Management Criteria for PWR Reactor Vessel Internal Components.'' This draft LR-ISG revises...

77 FR 23513 - Updated Aging Management Criteria for Reactor Vessel Internal Components of Pressurized Water...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-19

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0070] Updated Aging Management Criteria for Reactor Vessel Internal Components of Pressurized Water Reactors AGENCY: Nuclear Regulatory Commission. ACTION: Draft...-ISG), LR-ISG-2011-04, ``Updated Aging Management Criteria for PWR Reactor Vessel Internal Components...

IFN-α and CD46 stimulation are associated with active lupus and skew natural T regulatory cell differentiation to type 1 regulatory T (Tr1) cells

PubMed Central

Le Buanec, Hélène; Gougeon, Marie-Lise; Mathian, Alexis; Lebon, Pierre; Dupont, Jean-Michel; Peltre, Gabriel; Hemon, Patrice; Schmid, Michel; Bizzini, Bernard; Künding, Thomas; Burny, Arsène; Bensussan, Armand; Amoura, Zahir; Gallo, Robert C.; Zagury, Daniel

2011-01-01

Immune suppressive activities exerted by regulatory T-cell subsets have several specific functions, including self-tolerance and regulation of adaptive immune reactions, and their dysfunction can lead to autoimmune diseases and contribute to AIDS and cancer. Two functionally distinct regulatory T-cell subsets are currently identified in peripheral tissues: thymus-developed natural T regulatory cells (nTregs) controlling self-tolerance and antiinflammatory IL-10–secreting type 1 regulatory T cells (Tr1) derived from Ag-stimulated T cells, which regulate inflammation-dependent adaptive immunity and minimize immunopathology. We establish herein that cell contact-mediated nTreg regulatory function is inhibited by inflammation, especially in the presence of the complement C3b receptor (CD46). Instead, as with other T-cell subsets, the latter inflammatory conditions of stimulation skew nTreg differentiation to Tr1 cells secreting IL-10, an effect potentiated by IFN-α. The clinical relevance of these findings was verified in a study of 152 lupus patients, in which we showed that lupus nTreg dysfunction is not due to intrinsic defects but is rather induced by C3b stimulation of CD46 and IFN-α and that these immune components of inflammation are directly associated with active lupus. These results provide a rationale for using anti–IFN-α Ab immunotherapy in lupus patients. PMID:22065791

78 FR 58580 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-24

... proposed rule change, FINRA would no longer require a customer to elect one of the two existing panel...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change...,\\2\\ a proposed rule change amending the Code of Arbitration Procedure for Customer Disputes...

Two-Component Systems Involved in Susceptibility to Nisin A in Streptococcus pyogenes

PubMed Central

Kawada-Matsuo, Miki; Tatsuno, Ichiro; Arii, Kaoru; Zendo, Takeshi; Oogai, Yuichi; Noguchi, Kazuyuki; Hasegawa, Tadao; Sonomoto, Kenji

2016-01-01

ABSTRACT Two-component systems (TCSs) are regulatory systems in bacteria that play important roles in sensing and adapting to the environment. In this study, we systematically evaluated the roles of TCSs in the susceptibility of the group A Streptococcus (GAS; Streptococcus pyogenes) SF370 strain to several types of lantibiotics. Using individual TCS deletion mutants, we found that the deletion of srtRK (spy_1081–spy_1082) in SF370 increased the susceptibility to nisin A, which is produced by Lactococcus lactis ATCC 11454, but susceptibility to other types of lantibiotics (nukacin ISK-1, produced by Staphylococcus warneri, and staphylococcin C55, produced by Staphylococcus aureus) was not altered in the TCS mutants tested. The expression of srtFEG (spy_1085 to spy_1087), which is located downstream of srtRK and is homologous to ABC transporters, was increased in response to nisin A. However, srtEFG expression was not induced by nisin A in the srtRK mutant. The inactivation of srtFEG increased the susceptibility to nisin A. These results suggest that SrtRK controls SrtFEG expression to alter the susceptibility to nisin A. Further experiments showed that SrtRK is required for coexistence with L. lactis ATCC 11454, which produces nisin A. Our results elucidate the important roles of S. pyogenes TCSs in the interactions between different bacterial species, including bacteriocin-producing bacteria. IMPORTANCE In this study, we focused on the association of TCSs with susceptibility to bacteriocins in S. pyogenes SF370, which has no ability to produce bacteriocins, and reported two major new findings. We demonstrated that the SrtRK TCS is related to susceptibility to nisin A by controlling the ABC transporter SrtFEG. We also showed that S. pyogenes SrtRK is important for survival when the bacteria are cocultured with nisin A-producing Lactococcus lactis. This report highlights the roles of TCSs in the colocalization of bacteriocin-producing bacteria and non

Implications of two-component dark matter induced by forbidden channels and thermal freeze-out

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

Aoki, Mayumi; Toma, Takashi, E-mail: mayumi@hep.s.kanazawa-u.ac.jp, E-mail: takashi.toma@tum.de

2017-01-01

We consider a model of two-component dark matter based on a hidden U(1) {sub D} symmetry, in which relic densities of the dark matter are determined by forbidden channels and thermal freeze-out. The hidden U(1) {sub D} symmetry is spontaneously broken to a residual Z{sub 4} symmetry, and the lightest Z{sub 4} charged particle can be a dark matter candidate. Moreover, depending on the mass hierarchy in the dark sector, we have two-component dark matter. We show that the relic density of the lighter dark matter component can be determined by forbidden annihilation channels which require larger couplings compared tomore » the normal freeze-out mechanism. As a result, a large self-interaction of the lighter dark matter component can be induced, which may solve small scale problems of ΛCDM model. On the other hand, the heavier dark matter component is produced by normal freeze-out mechanism. We find that interesting implications emerge between the two dark matter components in this framework. We explore detectabilities of these dark matter particles and show some parameter space can be tested by the SHiP experiment.« less

Evolution of the metabolic and regulatory networks associated with oxygen availability in two phytopathogenic enterobacteria

PubMed Central

2012-01-01

Background Dickeya dadantii and Pectobacterium atrosepticum are phytopathogenic enterobacteria capable of facultative anaerobic growth in a wide range of O2 concentrations found in plant and natural environments. The transcriptional response to O2 remains under-explored for these and other phytopathogenic enterobacteria although it has been well characterized for animal-associated genera including Escherichia coli and Salmonella enterica. Knowledge of the extent of conservation of the transcriptional response across orthologous genes in more distantly related species is useful to identify rates and patterns of regulon evolution. Evolutionary events such as loss and acquisition of genes by lateral transfer events along each evolutionary branch results in lineage-specific genes, some of which may have been subsequently incorporated into the O2-responsive stimulon. Here we present a comparison of transcriptional profiles measured using densely tiled oligonucleotide arrays for two phytopathogens, Dickeya dadantii 3937 and Pectobacterium atrosepticum SCRI1043, grown to mid-log phase in MOPS minimal medium (0.1% glucose) with and without O2. Results More than 7% of the genes of each phytopathogen are differentially expressed with greater than 3-fold changes under anaerobic conditions. In addition to anaerobic metabolism genes, the O2 responsive stimulon includes a variety of virulence and pathogenicity-genes. Few of these genes overlap with orthologous genes in the anaerobic stimulon of E. coli. We define these as the conserved core, in which the transcriptional pattern as well as genetic architecture are well preserved. This conserved core includes previously described anaerobic metabolic pathways such as fermentation. Other components of the anaerobic stimulon show variation in genetic content, genome architecture and regulation. Notably formate metabolism, nitrate/nitrite metabolism, and fermentative butanediol production, differ between E. coli and the phytopathogens

Three-particle correlation functions of quasi-two-dimensional one-component and binary colloid suspensions.

PubMed

Ho, Hau My; Lin, Binhua; Rice, Stuart A

2006-11-14

We report the results of experimental determinations of the triplet correlation functions of quasi-two-dimensional one-component and binary colloid suspensions in which the colloid-colloid interaction is short ranged. The suspensions studied range in density from modestly dilute to solid. The triplet correlation function of the one-component colloid system reveals extensive ordering deep in the liquid phase. At the same density the ordering of the larger diameter component in a binary colloid system is greatly diminished by a very small amount of the smaller diameter component. The possible utilization of information contained in the triplet correlation function in the theory of melting of a quasi-two-dimensional system is briefly discussed.

Exploring the Validity Range of the Polarimetric Two-Scale Two-Component Model for Soil Moisture Retrieval by Using AGRISAR Data

NASA Astrophysics Data System (ADS)

Di Martino, Gerardo; Iodice, Antonio; Natale, Antonio; Riccio, Daniele; Ruello, Giuseppe

2015-04-01

The recently proposed polarimetric two-scale two- component model (PTSTCM) in principle allows us obtaining a reasonable estimation of the soil moisture even in moderately vegetated areas, where the volumetric scattering contribution is non-negligible, provided that the surface component is dominant and the double-bounce component is negligible. Here we test the PTSTCM validity range by applying it to polarimetric SAR data acquired on areas for which, at the same times of SAR acquisitions, ground measurements of soil moisture were performed. In particular, we employ the AGRISAR'06 database, which includes data from several fields covering a period that spans all the phases of vegetation growth.

Two-component flux explanation for the high energy neutrino events at IceCube

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

Chen, Chien-Yi; Dev, P. S. Bhupal; Soni, Amarjit

In understanding the spectral and flavor composition of the astrophysical neutrino flux responsible for the recently observed ultrahigh-energy events at IceCube we see how important both astrophysics and particle physics are. Here, we perform a statistical likelihood analysis to the three-year IceCube data and derive the allowed range of the spectral index and flux normalization for various well-motivated physical flavor compositions at the source. While most of the existing analyses so far assume the flavor composition of the neutrinos at an astrophysical source to be (1:2:0), it seems rather unnatural to assume only one type of source, once we recognizemore » the possibility of at least two physical sources. Bearing this in mind, we entertain the possibility of a two-component source for the analysis of IceCube data. It appears that our two-component hypothesis explains some key features of the data better than a single-component scenario; i.e. it addresses the apparent energy gap between 400 TeV and about 1 PeV and easily accommodates the observed track-to-shower ratio. Given the extreme importance of the flavor composition for the correct interpretation of the underlying astrophysical processes as well as for the ramification for particle physics, this two-component flux should be tested as more data is accumulated.« less

Two-component flux explanation for the high energy neutrino events at IceCube

DOE PAGES

Chen, Chien-Yi; Dev, P. S. Bhupal; Soni, Amarjit

2015-10-01

In understanding the spectral and flavor composition of the astrophysical neutrino flux responsible for the recently observed ultrahigh-energy events at IceCube we see how important both astrophysics and particle physics are. Here, we perform a statistical likelihood analysis to the three-year IceCube data and derive the allowed range of the spectral index and flux normalization for various well-motivated physical flavor compositions at the source. While most of the existing analyses so far assume the flavor composition of the neutrinos at an astrophysical source to be (1:2:0), it seems rather unnatural to assume only one type of source, once we recognizemore » the possibility of at least two physical sources. Bearing this in mind, we entertain the possibility of a two-component source for the analysis of IceCube data. It appears that our two-component hypothesis explains some key features of the data better than a single-component scenario; i.e. it addresses the apparent energy gap between 400 TeV and about 1 PeV and easily accommodates the observed track-to-shower ratio. Given the extreme importance of the flavor composition for the correct interpretation of the underlying astrophysical processes as well as for the ramification for particle physics, this two-component flux should be tested as more data is accumulated.« less

Two-component Gaussian core model: Strong-coupling limit, Bjerrum pairs, and gas-liquid phase transition.

PubMed

Frydel, Derek; Levin, Yan

2018-01-14

In the present work, we investigate a gas-liquid transition in a two-component Gaussian core model, where particles of the same species repel and those of different species attract. Unlike a similar transition in a one-component system with particles having attractive interactions at long separations and repulsive interactions at short separations, a transition in the two-component system is not driven solely by interactions but by a specific feature of the interactions, the correlations. This leads to extremely low critical temperature, as correlations are dominant in the strong-coupling limit. By carrying out various approximations based on standard liquid-state methods, we show that a gas-liquid transition of the two-component system poses a challenging theoretical problem.

Two-component Gaussian core model: Strong-coupling limit, Bjerrum pairs, and gas-liquid phase transition

NASA Astrophysics Data System (ADS)

Frydel, Derek; Levin, Yan

2018-01-01

In the present work, we investigate a gas-liquid transition in a two-component Gaussian core model, where particles of the same species repel and those of different species attract. Unlike a similar transition in a one-component system with particles having attractive interactions at long separations and repulsive interactions at short separations, a transition in the two-component system is not driven solely by interactions but by a specific feature of the interactions, the correlations. This leads to extremely low critical temperature, as correlations are dominant in the strong-coupling limit. By carrying out various approximations based on standard liquid-state methods, we show that a gas-liquid transition of the two-component system poses a challenging theoretical problem.

Evolutionary rewiring of bacterial regulatory networks

PubMed Central

Taylor, Tiffany B.; Mulley, Geraldine; McGuffin, Liam J.; Johnson, Louise J.; Brockhurst, Michael A.; Arseneault, Tanya; Silby, Mark W.; Jackson, Robert W.

2015-01-01

Bacteria have evolved complex regulatory networks that enable integration of multiple intracellular and extracellular signals to coordinate responses to environmental changes. However, our knowledge of how regulatory systems function and evolve is still relatively limited. There is often extensive homology between components of different networks, due to past cycles of gene duplication, divergence, and horizontal gene transfer, raising the possibility of cross-talk or redundancy. Consequently, evolutionary resilience is built into gene networks - homology between regulators can potentially allow rapid rescue of lost regulatory function across distant regions of the genome. In our recent study [Taylor, et al. Science (2015), 347(6225)] we find that mutations that facilitate cross-talk between pathways can contribute to gene network evolution, but that such mutations come with severe pleiotropic costs. Arising from this work are a number of questions surrounding how this phenomenon occurs. PMID:28357301

On the Two Components of Turbulent Mixing Noise from Supersonic Jets

NASA Technical Reports Server (NTRS)

Tam, Christopher K. W.; Golebiowski, Michel; Seiner, J. M.

1996-01-01

It is argued that because of the lack of intrinsic length and time scales in the core part of the jet flow, the radiated noise spectrum of a high-speed jet should exhibit similarity. A careful analysis of all the axisymmetric supersonic jet noise spectra in the data-bank of the Jet Noise Laboratory of the NASA Langley Research Center has been carried out. Two similarity spectra, one for the noise from the large turbulence structures/instability waves of the jet flow, the other for the noise from the fine-scale turbulence, are identified. The two similarity spectra appear to be universal spectra for axisymmetric jets. They fit all the measured data including those from subsonic jets. Experimental evidence are presented showing that regardless of whether a jet is supersonic or subsonic the noise characteristics and generation mechanisms are the same. There is large turbulence structures/instability waves noise from subsonic jets. This noise component can be seen prominently inside the cone of silence of the fine-scale turbulence noise near the jet axis. For imperfectly expanded supersonic jets, a shock cell structure is formed inside the jet plume. Measured spectra are provided to demonstrate that the presence of a shock cell structure has little effect on the radiated turbulent mixing noise. The shape of the noise spectrum as well as the noise intensity remain practically the same as those of a fully expanded jet. However, for jets undergoing strong screeching, there is broadband noise amplification for both turbulent mixing noise components. It is discovered through a pilot study of the noise spectrum of rectangular and elliptic supersonic jets that the turbulent mixing noise of these jets is also made up of the same two noise components found in axisymmetric jets. The spectrum of each individual noise component also fits the corresponding similarity spectrum of axisymmetric jets.

Optical calibration of a new two-way optical component network analyzer

NASA Astrophysics Data System (ADS)

Tsao, Shyh-Lin; Ko, Chih-Han; Liou, Tai-Chi

2003-12-01

High-speed fiber communications show promising results recently [1,2]. Using of lightwave technology for measuring S parameters with optical component becoming important. For this purpose to develop a two-way network analyzer has been reported [3]. In this paper, we report the calibration method of a new two-way lightwave component analyze for applying in fiber optical signal processing elements. The background error and circulator wavelength response are all calibrated. We have designed a new probe for two-way optical component network analyzer. The probe is composed of frequency division multiplexer(FDM), electrical circulator, optical transmitter, optical receiver, and an optical circulator. We design 2-D grating structures as frequency division. The PCB we adopted is Kinstan GD1530 160 whose relative dielectric constantɛ= 4.3, length= 120 mm, and height= 1.8 mm. Two dimensional non-metal covered array square pads are designed on FR4 Glass-Epoxy board for FDM. The FDM can be achieved by the two dimensional non-metalized covered array square pads. Finally we use a single fiber ring resonator filter as our test samples. Comparing the numerical and experimental results, test the device we made. References [1] D. D. Curtis and E. E. Ames,"Optical Test Set for Microwave Fiber-Optic Network Analysis," IEEE Transactions on Microwave Theory and Techniques. , vol. 38, NO.5, pp. 552-559, 1990. [2] J. A. C. Bingham,"Multicarrier modulation for data transmission: an idea whose time has come," IEEE Commun. Magazine., pp. 5 -14, 1990. [3] M. Nakazawa, K. Suzuki, and Y. Kimura, " 3.2-5 Gbps 100km error-free soliton transmission with erbium amplifiers and repenters," IEEE Photonics Tech Lett.,vol.2,pp.216-219,1990.

Enhancer Variants Synergistically Drive Dysfunction of a Gene Regulatory Network In Hirschsprung Disease

DOE PAGES

Chatterjee, Sumantra; Kapoor, Ashish; Akiyama, Jennifer A.; ...

2016-09-29

Common sequence variants in cis-regulatory elements (CREs) are suspected etiological causes of complex disorders. We previously identified an intronic enhancer variant in the RET gene disrupting SOX10 binding and increasing Hirschsprung disease (HSCR) risk 4-fold. We now show that two other functionally independent CRE variants, one binding Gata2 and the other binding Rarb, also reduce Ret expression and increase risk 2- and 1.7-fold. By studying human and mouse fetal gut tissues and cell lines, we demonstrate that reduced RET expression propagates throughout its gene regulatory network, exerting effects on both its positive and negative feedback components. We also provide evidencemore » that the presence of a combination of CRE variants synergistically reduces RET expression and its effects throughout the GRN. These studies show how the effects of functionally independent non-coding variants in a coordinated gene regulatory network amplify their individually small effects, providing a model for complex disorders.« less

Enhancer Variants Synergistically Drive Dysfunction of a Gene Regulatory Network In Hirschsprung Disease

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

Chatterjee, Sumantra; Kapoor, Ashish; Akiyama, Jennifer A.

Common sequence variants in cis-regulatory elements (CREs) are suspected etiological causes of complex disorders. We previously identified an intronic enhancer variant in the RET gene disrupting SOX10 binding and increasing Hirschsprung disease (HSCR) risk 4-fold. We now show that two other functionally independent CRE variants, one binding Gata2 and the other binding Rarb, also reduce Ret expression and increase risk 2- and 1.7-fold. By studying human and mouse fetal gut tissues and cell lines, we demonstrate that reduced RET expression propagates throughout its gene regulatory network, exerting effects on both its positive and negative feedback components. We also provide evidencemore » that the presence of a combination of CRE variants synergistically reduces RET expression and its effects throughout the GRN. These studies show how the effects of functionally independent non-coding variants in a coordinated gene regulatory network amplify their individually small effects, providing a model for complex disorders.« less

76 FR 68514 - Request for a License To Export Reactor Components

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-04

... NUCLEAR REGULATORY COMMISSION Request for a License To Export Reactor Components Pursuant to 10.../docket Number Westinghouse Electric Company Complete reactor 12 Perform seismic China. LLC, August 18... qualification equipment. of AP1000 (design) nuclear reactors. For the Nuclear Regulatory Commission. Dated this...

State Space Model with hidden variables for reconstruction of gene regulatory networks.

PubMed

Wu, Xi; Li, Peng; Wang, Nan; Gong, Ping; Perkins, Edward J; Deng, Youping; Zhang, Chaoyang

2011-01-01

State Space Model (SSM) is a relatively new approach to inferring gene regulatory networks. It requires less computational time than Dynamic Bayesian Networks (DBN). There are two types of variables in the linear SSM, observed variables and hidden variables. SSM uses an iterative method, namely Expectation-Maximization, to infer regulatory relationships from microarray datasets. The hidden variables cannot be directly observed from experiments. How to determine the number of hidden variables has a significant impact on the accuracy of network inference. In this study, we used SSM to infer Gene regulatory networks (GRNs) from synthetic time series datasets, investigated Bayesian Information Criterion (BIC) and Principle Component Analysis (PCA) approaches to determining the number of hidden variables in SSM, and evaluated the performance of SSM in comparison with DBN. True GRNs and synthetic gene expression datasets were generated using GeneNetWeaver. Both DBN and linear SSM were used to infer GRNs from the synthetic datasets. The inferred networks were compared with the true networks. Our results show that inference precision varied with the number of hidden variables. For some regulatory networks, the inference precision of DBN was higher but SSM performed better in other cases. Although the overall performance of the two approaches is compatible, SSM is much faster and capable of inferring much larger networks than DBN. This study provides useful information in handling the hidden variables and improving the inference precision.

Regulatory RNAs

PubMed Central

Vazquez-Anderson, Jorge; Contreras, Lydia M

2013-01-01

RNAs have many important functional properties, including that they are independently controllable and highly tunable. As a result of these advantageous properties, their use in a myriad of sophisticated devices has been widely explored. Yet, the exploitation of RNAs for synthetic applications is highly dependent on the ability to characterize the many new molecules that continue to be discovered by large-scale sequencing and high-throughput screening techniques. In this review, we present an exhaustive survey of the most recent synthetic bacterial riboswitches and small RNAs while emphasizing their virtues in gene expression management. We also explore the use of these RNA components as building blocks in the RNA synthetic biology toolbox and discuss examples of synthetic RNA components used to rewire bacterial regulatory circuitry. We anticipate that this field will expand its catalog of smart devices by mimicking and manipulating natural RNA mechanisms and functions. PMID:24356572

Two-component duality and flavoring in the P+f model

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

Dash, J.W.; Jones, S.T.; Martin, A.

We show that modern Regge fits to rising ..pi..N total cross sections sigma/sub piN/ using the Harari-Freund P+f model of diffraction are not consistent with two-component duality. If a conventional Pomeron is chosen (dominant j-plane pole plus weak cuts), the resulting f is ''dual'' to the resonances plus one-half the background. Conversely, constraining the f-pole amplitude by duality does not allow a reasonable fit to sigma/sub piN/. In contrast, the P-f identity model of diffraction is shown to satisfy a modified form of two-component duality. We show that by incorporating flavoring renormalization, the P+f picture can be made consistent withmore » duality. The unflavored P intercept is 0.91 and the flavored P intercept is 1.1. Significant absorptive j-plane cuts are also required, though these are small enough to be consistent with dominant short-range order. Thus flavoring, which is so essential in P-f identity phenomenology, seems to play a positive role in diffraction scattering generally.« less

The CpxRA two-component system is essential for Citrobacter rodentium virulence.

PubMed

Thomassin, Jenny-Lee; Giannakopoulou, Natalia; Zhu, Lei; Gross, Jeremy; Salmon, Kristiana; Leclerc, Jean-Mathieu; Daigle, France; Le Moual, Hervé; Gruenheid, Samantha

2015-05-01

Citrobacter rodentium is a murine intestinal pathogen used as a model for the foodborne human pathogens enterohemorrhagic Escherichia coli and enteropathogenic E. coli. During infection, these pathogens use two-component signal transduction systems to detect and adapt to changing environmental conditions. In E. coli, the CpxRA two-component signal transduction system responds to envelope stress by modulating the expression of a myriad of genes. Quantitative real-time PCR showed that cpxRA was expressed in the colon of C57BL/6J mice infected with C. rodentium. To determine whether CpxRA plays a role during C. rodentium infection, a cpxRA deletion strain was generated and found to have a colonization defect during infection. This defect was independent of an altered growth rate or a defective type III secretion system, and single-copy chromosomal complementation of cpxRA restored virulence. The C. rodentium strains were then tested in C3H/HeJ mice, a lethal intestinal infection model. Mice infected with the ΔcpxRA strain survived infection, whereas mice infected with the wild-type or complemented strains succumbed to infection. Furthermore, we found that the cpxRA expression level was higher during early infection than at a later time point. Taken together, these data demonstrate that the CpxRA two-component signal transduction system is essential for the in vivo virulence of C. rodentium. In addition, these data suggest that fine-tuned cpxRA expression is important for infection. This is the first study that identifies a C. rodentium two-component transduction system required for pathogenesis. This study further indicates that CpxRA is an interesting target for therapeutics against enteric pathogens. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Laser cooling of a trapped two-component Fermi gas

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

Idziaszek, Z.; Centrum Fizyki Teoretycznej, Polska Akademia Nauk, 02-668 Warsaw; Santos, L.

2003-04-01

We study the collective Raman cooling of a trapped two-component Fermi gas using quantum master equation in the festina lente regime, where the heating due to photon reabsorption can be neglected. The Monte Carlo simulations show that three-dimensional temperatures of the order of 0.008T{sub F} can be achieved. We analyze the heating related to background losses, and show that our laser-cooling scheme can maintain the temperature of the gas without significant additional losses.

A self-regulatory approach to understanding boredom proneness.

PubMed

Struk, A A; Scholer, A A; Danckert, J

2015-07-29

We investigated the relationship between self-regulation and two types of boredom proneness (perceived lack of internal stimulation, perceived lack of external stimulation) using a variety of measures of self-regulation. These included a general measure of self-control, measures of both regulatory focus (i.e., promotion or a sensitivity to gains/non-gains vs. prevention or a sensitivity to losses/non-losses) and regulatory mode (i.e., assessment or the tendency to compare means and goals vs. locomotion or the tendency to initiate and maintain commitment to action), and measures of cognitive flexibility (i.e., a perceived sense of control and the tendency to seek alternative solutions). Results identified a unique set of factors related to each boredom proneness component. Trait self-control and prevention focus were associated with lower boredom propensity due to a lack of external stimulation. Locomotion and the tendency to seek alternatives were associated with lower boredom propensity due to a lack of internal stimulation. These findings suggest that effective goal pursuit is associated with reduced likelihood of experiencing boredom.

A two-component regulatory system, pehR-pehS, controls endopolygalacturonase production and virulence in the plant pathogen Erwinia carotovora subsp. carotovora.

PubMed

Flego, D; Marits, R; Eriksson, A R; Kõiv, V; Karlsson, M B; Heikinheimo, R; Palva, E T

2000-04-01

Genes coding for the main virulence determinants of the plant pathogen Erwinia carotovora subsp. carotovora, the plant cell wall-degrading enzymes, are under the coordinate control of global regulator systems including both positive and negative factors. In addition to this global control, some virulence determinants are subject to specific regulation. We have previously shown that mutations in the pehR locus result in reduced virulence and impaired production of one of these enzymes, an endopolygalacturonase (PehA). In contrast, these pehR strains produce essentially wild-type levels of other extracellular enzymes including pectate lyases and cellulases. In this work, we characterized the pehR locus and showed that the DNA sequence is composed of two genes, designated pehR and pehS, present in an operon. Mutations in either pehR or pehS caused a Peh-negative phenotype and resulted in reduced virulence on tobacco seedlings. Complementation experiments indicated that both genes are required for transcriptional activation of the endopolygalacturonase gene, pehA, as well as restoration of virulence. Structural characterization of the pehR-pehS operon demonstrated that the corresponding polypeptides are highly similar to the two-component transcriptional regulators PhoP-PhoQ of both Escherichia coli and Salmonella typhimurium. Functional similarity of PehR-PehS with PhoP-PhoQ of E. coli and S. typhimurium was demonstrated by genetic complementation.

Active Components of Ginger Potentiate β-Agonist–Induced Relaxation of Airway Smooth Muscle by Modulating Cytoskeletal Regulatory Proteins

PubMed Central

Zhang, Yi; Xu, Carrie; Wakita, Ryo; Emala, Charles W.

2014-01-01

β-Agonists are the first-line therapy to alleviate asthma symptoms by acutely relaxing the airway. Purified components of ginger relax airway smooth muscle (ASM), but the mechanisms are unclear. By elucidating these mechanisms, we can explore the use of phytotherapeutics in combination with traditional asthma therapies. The objectives of this study were to: (1) determine if 6-gingerol, 8-gingerol, or 6-shogaol potentiate β-agonist–induced ASM relaxation; and (2) define the mechanism(s) of action responsible for this potentiation. Human ASM was contracted in organ baths. Tissues were relaxed dose dependently with β-agonist, isoproterenol, in the presence of vehicle, 6-gingerol, 8-gingerol, or 6-shogaol (100 μM). Primary human ASM cells were used for cellular experiments. Purified phosphodiesterase (PDE) 4D or phospholipase C β enzyme was used to assess inhibitory activity of ginger components using fluorescent assays. A G-LISA assay was used to determine the effects of ginger constituents on Ras homolog gene family member A activation. Significant potentiation of isoproterenol-induced relaxation was observed with each of the ginger constituents. 6-Shogaol showed the largest shift in isoproterenol half-maximal effective concentration. 6-Gingerol, 8-gingerol, or 6-shogaol significantly inhibited PDE4D, whereas 8-gingerol and 6-shogaol also inhibited phospholipase C β activity. 6-Shogaol alone inhibited Ras homolog gene family member A activation. In human ASM cells, these constituents decreased phosphorylation of 17-kD protein kinase C–potentiated inhibitory protein of type 1 protein phosphatase and 8-gingerol decreased myosin light chain phosphorylation. Isolated components of ginger potentiate β-agonist–induced relaxation in human ASM. This potentiation involves PDE4D inhibition and cytoskeletal regulatory proteins. Together with β-agonists, 6-gingerol, 8-gingerol, or 6-shogaol may augment existing asthma therapy, resulting in relief of symptoms

A gene regulatory network armature for T-lymphocyte specification

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

Fung, Elizabeth-sharon

Choice of a T-lymphoid fate by hematopoietic progenitor cells depends on sustained Notch-Delta signaling combined with tightly-regulated activities of multiple transcription factors. To dissect the regulatory network connections that mediate this process, we have used high-resolution analysis of regulatory gene expression trajectories from the beginning to the end of specification; tests of the short-term Notchdependence of these gene expression changes; and perturbation analyses of the effects of overexpression of two essential transcription factors, namely PU.l and GATA-3. Quantitative expression measurements of >50 transcription factor and marker genes have been used to derive the principal components of regulatory change through whichmore » T-cell precursors progress from primitive multipotency to T-lineage commitment. Distinct parts of the path reveal separate contributions of Notch signaling, GATA-3 activity, and downregulation of PU.l. Using BioTapestry, the results have been assembled into a draft gene regulatory network for the specification of T-cell precursors and the choice of T as opposed to myeloid dendritic or mast-cell fates. This network also accommodates effects of E proteins and mutual repression circuits of Gfil against Egr-2 and of TCF-l against PU.l as proposed elsewhere, but requires additional functions that remain unidentified. Distinctive features of this network structure include the intense dose-dependence of GATA-3 effects; the gene-specific modulation of PU.l activity based on Notch activity; the lack of direct opposition between PU.l and GATA-3; and the need for a distinct, late-acting repressive function or functions to extinguish stem and progenitor-derived regulatory gene expression.« less

Heat transfer in condensing and evaporating two-component, two-phase flow inside a horizontal tube

NASA Astrophysics Data System (ADS)

Duval, W. M. B.

The effect of adding a small amount of oil to condensing and evaporation refrigerant R-12 following inside a horizontal tube is investigated both experimentally and analytically. Analytically, the problem is addressed assuming annular flow inside the tube. The analysis is based on the momentum and energy equations with the heat transfer in the liquid film determined using the Reynolds analogy between turbulent heat and momentum transfer. Two separate methods are developed for extending this model to include the effects of the two-component nature of the flow. Experimentally, two-phase local heat transfer measurements and flow pattern visualization are made for both condensation and evaporation. From the measurements, correlations are developed to predict two-phase heat transfer for the range of 0%, 2% and 5% oil fraction by mass flow.

2012 Global Summit on Regulatory Science (GSRS-2012)--modernizing toxicology.

PubMed

Miller, Margaret A; Tong, Weida; Fan, Xiaohui; Slikker, William

2013-01-01

Regulatory science encompasses the tools, models, techniques, and studies needed to assess and evaluate product safety, efficacy, quality, and performance. Several recent publications have emphasized the role of regulatory science in improving global health, supporting economic development and fostering innovation. As for other scientific disciplines, research in regulatory science is the critical element underpinning the development and advancement of regulatory science as a modern scientific discipline. As a regulatory agency in the 21st century, the Food and Drug Administration (FDA) has an international component that underpins its domestic mission; foods, drugs, and devices are developed and imported to the United States from across the world. The Global Summit on Regulatory Science, an international conference for discussing innovative technologies, approaches, and partnerships that enhance the translation of basic science into regulatory applications, is providing leadership for the advancement of regulatory sciences within the global context. Held annually, this international conference provides a platform where regulators, policy makers, and bench scientists from various countries can exchange views on how to develop, apply, and implement innovative methodologies into regulatory assessments in their respective countries, as well as developing a harmonized strategy to improve global public health through global collaboration.

78 FR 57904 - Request for a License To Export; Reactor Components

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-20

... NUCLEAR REGULATORY COMMISSION Request for a License To Export; Reactor Components Pursuant to 10..., systems, related reactors. operation of AP- XR177, 11006121. equipment, and 1000 (design) spare parts. nuclear reactors. Dated this 16th day of September 2013 in Rockville, Maryland. For The Nuclear Regulatory...

Two-Component Systems Involved in Susceptibility to Nisin A in Streptococcus pyogenes.

PubMed

Kawada-Matsuo, Miki; Tatsuno, Ichiro; Arii, Kaoru; Zendo, Takeshi; Oogai, Yuichi; Noguchi, Kazuyuki; Hasegawa, Tadao; Sonomoto, Kenji; Komatsuzawa, Hitoshi

2016-10-01

Two-component systems (TCSs) are regulatory systems in bacteria that play important roles in sensing and adapting to the environment. In this study, we systematically evaluated the roles of TCSs in the susceptibility of the group A Streptococcus (GAS; Streptococcus pyogenes) SF370 strain to several types of lantibiotics. Using individual TCS deletion mutants, we found that the deletion of srtRK (spy_1081-spy_1082) in SF370 increased the susceptibility to nisin A, which is produced by Lactococcus lactis ATCC 11454, but susceptibility to other types of lantibiotics (nukacin ISK-1, produced by Staphylococcus warneri, and staphylococcin C55, produced by Staphylococcus aureus) was not altered in the TCS mutants tested. The expression of srtFEG (spy_1085 to spy_1087), which is located downstream of srtRK and is homologous to ABC transporters, was increased in response to nisin A. However, srtEFG expression was not induced by nisin A in the srtRK mutant. The inactivation of srtFEG increased the susceptibility to nisin A. These results suggest that SrtRK controls SrtFEG expression to alter the susceptibility to nisin A. Further experiments showed that SrtRK is required for coexistence with L. lactis ATCC 11454, which produces nisin A. Our results elucidate the important roles of S. pyogenes TCSs in the interactions between different bacterial species, including bacteriocin-producing bacteria. In this study, we focused on the association of TCSs with susceptibility to bacteriocins in S. pyogenes SF370, which has no ability to produce bacteriocins, and reported two major new findings. We demonstrated that the SrtRK TCS is related to susceptibility to nisin A by controlling the ABC transporter SrtFEG. We also showed that S. pyogenes SrtRK is important for survival when the bacteria are cocultured with nisin A-producing Lactococcus lactis This report highlights the roles of TCSs in the colocalization of bacteriocin-producing bacteria and non-bacteriocin-producing bacteria. Our

Trail communication regulated by two trail pheromone components in the fungus-growing termite Odontotermes formosanus (Shiraki).

PubMed

Wen, Ping; Ji, Bao-Zhong; Sillam-Dussès, David

2014-01-01

The eusocial termites are well accomplished in chemical communication, but how they achieve the communication using trace amount of no more than two pheromone components is mostly unknown. In this study, the foraging process and trail pheromones of the fungus-growing termite Odontotermes formosanus (Shiraki) were systematically studied and monitored in real-time using a combination of techniques, including video analysis, solid-phase microextraction, gas chromatography coupled with either mass spectrometry or an electroantennographic detector, and bioassays. The trail pheromone components in foraging workers were (3Z)-dodec-3-en-1-ol and (3Z,6Z)-dodeca-3,6-dien-1-ol secreted by their sternal glands. Interestingly, ratio of the two components changed according to the behaviors that the termites were displaying. This situation only occurs in termites whereas ratios of pheromone components are fixed and species-specific for other insect cuticular glands. Moreover, in bioassays, the active thresholds of the two components ranged from 1 fg/cm to 10 pg/cm according to the behavioral contexts or the pheromonal exposure of tested workers. The two components did not act in synergy. (3Z)-Dodec-3-en-1-ol induced orientation behavior of termites that explore their environment, whereas (3Z,6Z)-dodeca-3,6-dien-1-ol had both an orientation effect and a recruitment effect when food was discovered. The trail pheromone of O. formosanus was regulated both quantitatively by the increasing number of workers involved in the early phases of foraging process, and qualitatively by the change in ratio of the two pheromone components on sternal glandular cuticle in the food-collecting workers. In bioassays, the responses of workers to the pheromone were also affected by the variation in pheromone concentration and component ratio in the microenvironment. Thus, this termite could exchange more information with nestmates using the traces of the two trail pheromone components that can be easily

Trail Communication Regulated by Two Trail Pheromone Components in the Fungus-Growing Termite Odontotermes formosanus (Shiraki)

PubMed Central

Wen, Ping; Ji, Bao-Zhong; Sillam-Dussès, David

2014-01-01

The eusocial termites are well accomplished in chemical communication, but how they achieve the communication using trace amount of no more than two pheromone components is mostly unknown. In this study, the foraging process and trail pheromones of the fungus-growing termite Odontotermes formosanus (Shiraki) were systematically studied and monitored in real-time using a combination of techniques, including video analysis, solid-phase microextraction, gas chromatography coupled with either mass spectrometry or an electroantennographic detector, and bioassays. The trail pheromone components in foraging workers were (3Z)-dodec-3-en-1-ol and (3Z,6Z)-dodeca-3,6-dien-1-ol secreted by their sternal glands. Interestingly, ratio of the two components changed according to the behaviors that the termites were displaying. This situation only occurs in termites whereas ratios of pheromone components are fixed and species-specific for other insect cuticular glands. Moreover, in bioassays, the active thresholds of the two components ranged from 1 fg/cm to 10 pg/cm according to the behavioral contexts or the pheromonal exposure of tested workers. The two components did not act in synergy. (3Z)-Dodec-3-en-1-ol induced orientation behavior of termites that explore their environment, whereas (3Z,6Z)-dodeca-3,6-dien-1-ol had both an orientation effect and a recruitment effect when food was discovered. The trail pheromone of O. formosanus was regulated both quantitatively by the increasing number of workers involved in the early phases of foraging process, and qualitatively by the change in ratio of the two pheromone components on sternal glandular cuticle in the food-collecting workers. In bioassays, the responses of workers to the pheromone were also affected by the variation in pheromone concentration and component ratio in the microenvironment. Thus, this termite could exchange more information with nestmates using the traces of the two trail pheromone components that can be easily

Complexation in two-component chlortetracycline-melanin solutions

NASA Astrophysics Data System (ADS)

Lapina, V. A.; Pershukevich, P. P.; Dontsov, A. E.; Bel'Kov, M. V.

2008-01-01

The spectra and kinetics of fluorescence of two-component solutions of the chlortetracycline (CHTC)-DOPA-melanin (melanin or ME) system in water have been investigated. The data obtained have been compared to similar data for solutions of CHTC-melanosome from bull eye (MB), which contains natural melanin, in K-phosphate buffer at pH 7.4. The overall results indicate the occurrence of complexation between molecules of CHTC and ME as they are being excited. The studies of complexation in the solution of CHTC-MB in the buffer are complicated by the formation of a CHTC-buffer complex. The effect of optical radiation in the range 330-750 nm on the CHTC-ME complex shows selectivity: the greatest change in the spectrum occurs when the wavelength of the exciting radiation coincides with the long-wavelength band maximum of the fluorescence excitation spectrum of the CHTC-ME complex in aqueous solution. In this range, CHTC and especially ME show high photochemical stability. The nature of the radiation effect on the studied compounds in the hard UV range (λ < 330 nm) differs greatly from that in the range 330-750 nm. It is apparently accompanied by significant photochemical transmutations of all system components. By comparing the characteristics of the CHTC-ME systems with those of the related drug doxycycline (DC-ME), the conclusion has been made that the chlorine atom plays a vital role in formation of the short-wavelength band in the fluorescence spectrum of the CHTC-ME complex.

The formation of bulges, discs and two-component galaxies in the CANDELS Survey at z < 3

NASA Astrophysics Data System (ADS)

Margalef-Bentabol, Berta; Conselice, Christopher J.; Mortlock, Alice; Hartley, Will; Duncan, Kenneth; Ferguson, Harry C.; Dekel, Avishai; Primack, Joel R.

2016-09-01

We examine a sample of 1495 galaxies in the CANDELS fields to determine the evolution of two-component galaxies, including bulges and discs, within massive galaxies at the epoch 1 < z < 3 when the Hubble sequence forms. We fit all of our galaxies' light profiles with a single Sérsic fit, as well as with a combination of exponential and Sérsic profiles. The latter is done in order to describe a galaxy with an inner and an outer component, or bulge and disc component. We develop and use three classification methods (visual, F-test and the residual flux fraction) to separate our sample into one-component galaxies (disc/spheroids-like galaxies) and two-component galaxies (galaxies formed by an `inner part' or bulge and an `outer part' or disc). We then compare the results from using these three different ways to classify our galaxies. We find that the fraction of galaxies selected as two-component galaxies increases on average 50 per cent from the lowest mass bin to the most massive galaxies, and decreases with redshift by a factor of 4 from z = 1 to 3. We find that single Sérsic `disc-like' galaxies have the highest relative number densities at all redshifts, and that two-component galaxies have the greatest increase and become at par with Sérsic discs by z = 1. We also find that the systems we classify as two-component galaxies have an increase in the sizes of their outer components, or `discs', by about a factor of 3 from z = 3 to 1.5, while the inner components or `bulges' stay roughly the same size. This suggests that these systems are growing from the inside out, whilst the bulges or protobulges are in place early in the history of these galaxies. This is also seen to a lesser degree in the growth of single `disc-like' galaxies versus `spheroid-like' galaxies over the same epoch.

Further two-dimensional code development for Stirling space engine components

NASA Technical Reports Server (NTRS)

Ibrahim, Mounir; Tew, Roy C.; Dudenhoefer, James E.

1990-01-01

The development of multidimensional models of Stirling engine components is described. Two-dimensional parallel plate models of an engine regenerator and a cooler were used to study heat transfer under conditions of laminar, incompressible oscillating flow. Substantial differences in the nature of the temperature variations in time over the cycle were observed for the cooler as contrasted with the regenerator. When the two-dimensional cooler model was used to calculate a heat transfer coefficient, it yields a very different result from that calculated using steady-flow correlations. Simulation results for the regenerator and the cooler are presented.

Low-intensity electric fields induce two distinct response components in neocortical neuronal populations

PubMed Central

Xu, Weifeng; Wolff, Brian S.

2014-01-01

Low-intensity alternating electric fields applied to the scalp are capable of modulating cortical activity and brain functions, but the underlying mechanisms remain largely unknown. Here, we report two distinct components of voltage-sensitive dye signals induced by low-intensity, alternating electric fields in rodent cortical slices: a “passive component,” which corresponds to membrane potential changes directly induced by the electric field; and an “active component,” which is a widespread depolarization that is dependent on excitatory synaptic transmission. The passive component is stationary, with amplitude and phase accurately reflecting the cortical cytoarchitecture. In contrast, the active component is initiated from a local “hot spot” of activity and spreads to a large population as a propagating wave with rich local dynamics. The propagation of the active component may play a role in modulating large-scale cortical activity by spreading a low level of excitation from a small initiation point to a vast neuronal population. PMID:25122710

util_2comp: Planck-based two-component dust model utilities

NASA Astrophysics Data System (ADS)

Meisner, Aaron

2014-11-01

The util_2comp software utilities generate predictions of far-infrared Galactic dust emission and reddening based on a two-component dust emission model fit to Planck HFI, DIRBE and IRAS data from 100 GHz to 3000 GHz. These predictions and the associated dust temperature map have angular resolution of 6.1 arcminutes and are available over the entire sky. Implementations in IDL and Python are included.

Information theory in systems biology. Part I: Gene regulatory and metabolic networks.

PubMed

Mousavian, Zaynab; Kavousi, Kaveh; Masoudi-Nejad, Ali

2016-03-01

"A Mathematical Theory of Communication", was published in 1948 by Claude Shannon to establish a framework that is now known as information theory. In recent decades, information theory has gained much attention in the area of systems biology. The aim of this paper is to provide a systematic review of those contributions that have applied information theory in inferring or understanding of biological systems. Based on the type of system components and the interactions between them, we classify the biological systems into 4 main classes: gene regulatory, metabolic, protein-protein interaction and signaling networks. In the first part of this review, we attempt to introduce most of the existing studies on two types of biological networks, including gene regulatory and metabolic networks, which are founded on the concepts of information theory. Copyright © 2015 Elsevier Ltd. All rights reserved.

Portrait of Candida Species Biofilm Regulatory Network Genes.

PubMed

Araújo, Daniela; Henriques, Mariana; Silva, Sónia

2017-01-01

Most cases of candidiasis have been attributed to Candida albicans, but Candida glabrata, Candida parapsilosis and Candida tropicalis, designated as non-C. albicans Candida (NCAC), have been identified as frequent human pathogens. Moreover, Candida biofilms are an escalating clinical problem associated with significant rates of mortality. Biofilms have distinct developmental phases, including adhesion/colonisation, maturation and dispersal, controlled by complex regulatory networks. This review discusses recent advances regarding Candida species biofilm regulatory network genes, which are key components for candidiasis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Design of a Novel Two-Component Hybrid Dermal Scaffold for the Treatment of Pressure Sores.

PubMed

Sharma, Vaibhav; Kohli, Nupur; Moulding, Dale; Afolabi, Halimat; Hook, Lilian; Mason, Chris; García-Gareta, Elena

2017-11-01

The aim of this study is to design a novel two-component hybrid scaffold using the fibrin/alginate porous hydrogel Smart Matrix combined to a backing layer of plasma polymerized polydimethylsiloxane (Sil) membrane to make the fibrin-based dermal scaffold more robust for the treatment of the clinically challenging pressure sores. A design criteria are established, according to which the Sil membranes are punched to avoid collection of fluid underneath. Manual peel test shows that native silicone does not attach to the fibrin/alginate component while the plasma polymerized silicone membranes are firmly bound to fibrin/alginate. Structural characterization shows that the fibrin/alginate matrix is intact after the addition of the Sil membrane. By adding a Sil membrane to the original fibrin/alginate scaffold, the resulting two-component scaffolds have a significantly higher shear or storage modulus G'. In vitro cell studies show that dermal fibroblasts remain viable, proliferate, and infiltrate the two-component hybrid scaffolds during the culture period. These results show that the design of a novel two-component hybrid dermal scaffold is successful according to the proposed design criteria. To the best of the authors' knowledge, this is the first study that reports the combination of a fibrin-based scaffold with a plasma-polymerized silicone membrane. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Model of Yeast Cell-Cycle Regulation Based on a Standard Component Modeling Strategy for Protein Regulatory Networks

PubMed Central

Laomettachit, Teeraphan; Chen, Katherine C.; Baumann, William T.

2016-01-01

To understand the molecular mechanisms that regulate cell cycle progression in eukaryotes, a variety of mathematical modeling approaches have been employed, ranging from Boolean networks and differential equations to stochastic simulations. Each approach has its own characteristic strengths and weaknesses. In this paper, we propose a “standard component” modeling strategy that combines advantageous features of Boolean networks, differential equations and stochastic simulations in a framework that acknowledges the typical sorts of reactions found in protein regulatory networks. Applying this strategy to a comprehensive mechanism of the budding yeast cell cycle, we illustrate the potential value of standard component modeling. The deterministic version of our model reproduces the phenotypic properties of wild-type cells and of 125 mutant strains. The stochastic version of our model reproduces the cell-to-cell variability of wild-type cells and the partial viability of the CLB2-dbΔ clb5Δ mutant strain. Our simulations show that mathematical modeling with “standard components” can capture in quantitative detail many essential properties of cell cycle control in budding yeast. PMID:27187804

Fingering instabilities and pattern formation in a two-component dipolar Bose-Einstein condensate

NASA Astrophysics Data System (ADS)

Xi, Kui-Tian; Byrnes, Tim; Saito, Hiroki

2018-02-01

We study fingering instabilities and pattern formation at the interface of an oppositely polarized two-component Bose-Einstein condensate with strong dipole-dipole interactions in three dimensions. It is shown that the rotational symmetry is spontaneously broken by fingering instability when the dipole-dipole interactions are strengthened. Frog-shaped and mushroom-shaped patterns emerge during the dynamics due to the dipolar interactions. We also demonstrate the spontaneous density modulation and domain growth of a two-component dipolar BEC in the dynamics. Bogoliubov analyses in the two-dimensional approximation are performed, and the characteristic lengths of the domains are estimated analytically. Patterns resembling those in magnetic classical fluids are modulated when the number ratio of atoms, the trap ratio of the external potential, or tilted polarization with respect to the z direction is varied.

Two-component fluid membranes near repulsive walls: Linearized hydrodynamics of equilibrium and nonequilibrium states.

PubMed

Sankararaman, Sumithra; Menon, Gautam I; Sunil Kumar, P B

2002-09-01

We study the linearized hydrodynamics of a two-component fluid membrane near a repulsive wall, using a model that incorporates curvature-concentration coupling as well as hydrodynamic interactions. This model is a simplified version of a recently proposed one [J.-B. Manneville et al., Phys. Rev. E 64, 021908 (2001)] for nonequilibrium force centers embedded in fluid membranes, such as light-activated bacteriorhodopsin pumps incorporated in phospholipid egg phosphatidyl choline (EPC) bilayers. The pump-membrane system is modeled as an impermeable, two-component bilayer fluid membrane in the presence of an ambient solvent, in which one component, representing active pumps, is described in terms of force dipoles displaced with respect to the bilayer midpoint. We first discuss the case in which such pumps are rendered inactive, computing the mode structure in the bulk as well as the modification of hydrodynamic properties by the presence of a nearby wall. These results should apply, more generally, to equilibrium fluid membranes comprised of two components, in which the effects of curvature-concentration coupling are significant, above the threshold for phase separation. We then discuss the fluctuations and mode structure in the steady state of active two-component membranes near a repulsive wall. We find that proximity to the wall smoothens membrane height fluctuations in the stable regime, resulting in a logarithmic scaling of the roughness even for initially tensionless membranes. This explicitly nonequilibrium result is a consequence of the incorporation of curvature-concentration coupling in our hydrodynamic treatment. This result also indicates that earlier scaling arguments which obtained an increase in the roughness of active membranes near repulsive walls upon neglecting the role played by such couplings may need to be reevaluated.

Comparing genomes to computer operating systems in terms of the topology and evolution of their regulatory control networks

PubMed Central

Yan, Koon-Kiu; Fang, Gang; Bhardwaj, Nitin; Alexander, Roger P.; Gerstein, Mark

2010-01-01

The genome has often been called the operating system (OS) for a living organism. A computer OS is described by a regulatory control network termed the call graph, which is analogous to the transcriptional regulatory network in a cell. To apply our firsthand knowledge of the architecture of software systems to understand cellular design principles, we present a comparison between the transcriptional regulatory network of a well-studied bacterium (Escherichia coli) and the call graph of a canonical OS (Linux) in terms of topology and evolution. We show that both networks have a fundamentally hierarchical layout, but there is a key difference: The transcriptional regulatory network possesses a few global regulators at the top and many targets at the bottom; conversely, the call graph has many regulators controlling a small set of generic functions. This top-heavy organization leads to highly overlapping functional modules in the call graph, in contrast to the relatively independent modules in the regulatory network. We further develop a way to measure evolutionary rates comparably between the two networks and explain this difference in terms of network evolution. The process of biological evolution via random mutation and subsequent selection tightly constrains the evolution of regulatory network hubs. The call graph, however, exhibits rapid evolution of its highly connected generic components, made possible by designers’ continual fine-tuning. These findings stem from the design principles of the two systems: robustness for biological systems and cost effectiveness (reuse) for software systems. PMID:20439753

Comparing genomes to computer operating systems in terms of the topology and evolution of their regulatory control networks.

PubMed

Yan, Koon-Kiu; Fang, Gang; Bhardwaj, Nitin; Alexander, Roger P; Gerstein, Mark

2010-05-18

The genome has often been called the operating system (OS) for a living organism. A computer OS is described by a regulatory control network termed the call graph, which is analogous to the transcriptional regulatory network in a cell. To apply our firsthand knowledge of the architecture of software systems to understand cellular design principles, we present a comparison between the transcriptional regulatory network of a well-studied bacterium (Escherichia coli) and the call graph of a canonical OS (Linux) in terms of topology and evolution. We show that both networks have a fundamentally hierarchical layout, but there is a key difference: The transcriptional regulatory network possesses a few global regulators at the top and many targets at the bottom; conversely, the call graph has many regulators controlling a small set of generic functions. This top-heavy organization leads to highly overlapping functional modules in the call graph, in contrast to the relatively independent modules in the regulatory network. We further develop a way to measure evolutionary rates comparably between the two networks and explain this difference in terms of network evolution. The process of biological evolution via random mutation and subsequent selection tightly constrains the evolution of regulatory network hubs. The call graph, however, exhibits rapid evolution of its highly connected generic components, made possible by designers' continual fine-tuning. These findings stem from the design principles of the two systems: robustness for biological systems and cost effectiveness (reuse) for software systems.

Facing regulatory challenges of on-line hemodiafiltration.

PubMed

Kümmerle, Wolfgang

2011-01-01

On-line hemodiafiltration (on-line HDF) is the result of a vision that triggered multifarious changes in very different areas. Driven by the idea to offer better medical treatment for renal patients, technological innovations were developed and established that also constituted new challenges in the field of regulatory affairs. The existing regulations predominantly addressed the quality and safety of those products needed to perform dialysis treatment which were supplied by industrial manufacturers. However, the complexity of treatment system required for the provision of on-line fluids demanded a holistic approach encompassing all components involved. Hence, focus was placed not only on single products, but much more on their interfacing, and the clinical infrastructure, in particular, had to undergo substantial changes. The overall understanding of the interaction between such factors, quite different in their nature, was crucial to overcome the arising regulatory obstacles. This essay describes the evolution of the on-line HDF procedure from the regulatory point of view. A simplified diagram demonstrates the path taken from the former regulatory understanding to the realization of necessary changes. That achievement was only possible through 'management of preview' and consequent promotion of technical and medical innovations as well as regulatory re-evaluations. Copyright © 2011 S. Karger AG, Basel.

The decoupling of the glass transitions in the two-component p-spin spherical model

NASA Astrophysics Data System (ADS)

Ikeda, Harukuni; Ikeda, Atsushi

2016-07-01

Binary mixtures of large and small particles with a disparate size ratio exhibit a rich phenomenology at their glass transition points. In order to gain insights on such systems, we introduce and study a two-component version of the p-spin spherical spin glass model. We employ the replica method to calculate the free energy and the phase diagram. We show that when the strengths of the interactions of each component are not widely separated, the model has only one glass phase characterized by the conventional one-step replica symmetry breaking. However when the strengths of the interactions are well separated, the model has three glass phases depending on the temperature and component ratio. One is the ‘single’ glass phase in which only the spins of one component are frozen while the spins of the other component remain mobile. This phase is characterized by the one-step replica symmetry breaking. The second is the ‘double’ glass phase obtained by cooling the single glass phase further, in which the spins of the remaining mobile component are also frozen. This phase is characterized by the two-step replica symmetry breaking. The third is also the ‘double’ glass phase, which, however, is formed by the simultaneous freezing of the spins of both components at the same temperatures and is characterized by the one-step replica symmetry breaking. We discuss the implications of these results for the glass transitions of binary mixtures.

Hologram interferometry in automotive component vibration testing

NASA Astrophysics Data System (ADS)

Brown, Gordon M.; Forbes, Jamie W.; Marchi, Mitchell M.; Wales, Raymond R.

1993-02-01

An ever increasing variety of automotive component vibration testing is being pursued at Ford Motor Company, U.S.A. The driving force for use of hologram interferometry in these tests is the continuing need to design component structures to meet more stringent functional performance criteria. Parameters such as noise and vibration, sound quality, and reliability must be optimized for the lightest weight component possible. Continually increasing customer expectations and regulatory pressures on fuel economy and safety mandate that vehicles be built from highly optimized components. This paper includes applications of holographic interferometry for powertrain support structure tuning, body panel noise reduction, wiper system noise and vibration path analysis, and other vehicle component studies.

The Two-Component Virial Theorem and the Physical Properties of Stellar Systems.

PubMed

Dantas; Ribeiro; Capelato; de Carvalho RR

2000-01-01

Motivated by present indirect evidence that galaxies are surrounded by dark matter halos, we investigate whether their physical properties can be described by a formulation of the virial theorem that explicitly takes into account the gravitational potential term representing the interaction of the dark halo with the baryonic or luminous component. Our analysis shows that the application of such a "two-component virial theorem" not only accounts for the scaling relations displayed by, in particular, elliptical galaxies, but also for the observed properties of all virialized stellar systems, ranging from globular clusters to galaxy clusters.

Comparison of Dynamical Behaviors Between Monofunctional and Bifunctional Two-Component Signaling Modules

NASA Astrophysics Data System (ADS)

Yang, Xiyan; Wu, Yahao; Yuan, Zhanjiang

2015-06-01

Two-component signaling modules exist extensively in bacteria and microbes. These modules can be, based on their distinct network structures, divided into two types: the monofunctional system (denoted by MFS) where the sensor kinase (SK) modulates only phosphorylation of the response regulator (RR), and the bifunctional system (denoted by BFS) where the SK catalyzes both phosphorylation and dephosphorylation of the RR. Here, we analyze dynamical behaviors of these two systems based on stability theory, focusing on differences between them. The analysis of the deterministic behavior indicates that there is no difference between the two modules, that is, each system has the unique stable steady state. However, there are significant differences in stochastic behavior between them. Specifically, if the mean phosphorylated SK level is kept the same for the two modules, then the variance and the Fano factor for the phosphorylated RR in the BFS are always no less than those in the MFS, indicating that bifunctionality always enhances fluctuations. The correlation between the phosphorylated SK and the phosphorylated RR in the BFS is always positive mainly due to competition between system components, but this correlation in the MFS may be positive, almost zero, or negative, depending on the ratio between two rate constants. Our overall analysis indicates that differences between dynamical behaviors of monofunctional and bifunctional signaling modules are mainly in the stochastic rather than deterministic aspect.

Comparing a motivational and a self-regulatory intervention to adopt an oral self-care regimen: a two-sequential randomized crossover trial.

PubMed

Lhakhang, Pempa; Gholami, Maryam; Knoll, Nina; Schwarzer, Ralf

2015-01-01

A sequential intervention to facilitate the adoption and maintenance of dental flossing was conducted among 205 students in India, aged 18-26 years. Two experimental groups received different treatment sequences and were observed at three assessment points, 34 days apart. One group received first a motivational intervention (intention, outcome expectancies, and risk perception, followed by a self-regulatory intervention (planning, self-efficacy, and action control). The second group received the same intervention in the opposite order. Both intervention sequences yielded gains in terms of flossing, planning, self-efficacy, and action control. However, at Time 2, those who had received the self-regulatory intervention first, were superior to their counterparts who had received the motivational intervention first. At Time 3, differences vanished as everyone had then received both interventions. Thus, findings highlight the benefits of a self-regulatory compared to a mere motivational intervention.

Safety of plant-made pharmaceuticals: product development and regulatory considerations based on case studies of two autologous human cancer vaccines.

PubMed

Tusé, Daniel

2011-03-01

Guidelines issued by regulatory agencies for the development of plant-made pharmaceutical (PMP) products provide criteria for product manufacturing and characterization, safety determination, containment and mitigation of environmental risks. Features of plant-made products do not always enable an easy fit within the criteria subscribed to by regulators. The unconventional nature of plant-based manufacturing processes and peculiarities of plant biology relative to that of traditional biological production systems have led to special considerations in the regulatory scrutiny of PMP. Presented in this review are case studies of two plant-made autologous (patient-specific) cancer vaccines, the nature of which introduced challenges to conventional and standardized development and preclinical evaluation routes. The rationale presented to FDA by the sponsors of each vaccine to build consensus and obtain variances to existing guidelines is discussed. While development of many plant-made biologics can be accomplished within the existing regulatory framework, the development of specialized products can be defended with rational arguments based on strong science.

Taxi Regulatory Revision in Oakland and Berkeley, California : Two Case Studies

DOT National Transportation Integrated Search

1983-06-01

A case study was performed of regulatory changes pertaining to taxicabs in Oakland and neighboring Berkeley, CA. In Oakland rates were approximately doubled and limits on the number of taxi permits removed. Companies were allowed to levy a per-trip s...

Molecular Orientation in Two Component Vapor-Deposited Glasses: Effect of Substrate Temperature and Molecular Shape

NASA Astrophysics Data System (ADS)

Powell, Charles; Jiang, Jing; Walters, Diane; Ediger, Mark

Vapor-deposited glasses are widely investigated for use in organic electronics including the emitting layers of OLED devices. These materials, while macroscopically homogenous, have anisotropic packing and molecular orientation. By controlling this orientation, outcoupling efficiency can be increased by aligning the transition dipole moment of the light-emitting molecules parallel to the substrate. Light-emitting molecules are typically dispersed in a host matrix, as such, it is imperative to understand molecular orientation in two-component systems. In this study we examine two-component vapor-deposited films and the orientations of the constituent molecules using spectroscopic ellipsometry, UV-vis and IR spectroscopy. The role of temperature, composition and molecular shape as it effects molecular orientation is examined for mixtures of DSA-Ph in Alq3 and in TPD. Deposition temperature relative to the glass transition temperature of the two-component mixture is the primary controlling factor for molecular orientation. In mixtures of DSA-Ph in Alq3, the linear DSA-Ph has a horizontal orientation at low temperatures and slight vertical orientation maximized at 0.96Tg,mixture, analogous to one-component films.

A stock market forecasting model combining two-directional two-dimensional principal component analysis and radial basis function neural network.

PubMed

Guo, Zhiqiang; Wang, Huaiqing; Yang, Jie; Miller, David J

2015-01-01

In this paper, we propose and implement a hybrid model combining two-directional two-dimensional principal component analysis ((2D)2PCA) and a Radial Basis Function Neural Network (RBFNN) to forecast stock market behavior. First, 36 stock market technical variables are selected as the input features, and a sliding window is used to obtain the input data of the model. Next, (2D)2PCA is utilized to reduce the dimension of the data and extract its intrinsic features. Finally, an RBFNN accepts the data processed by (2D)2PCA to forecast the next day's stock price or movement. The proposed model is used on the Shanghai stock market index, and the experiments show that the model achieves a good level of fitness. The proposed model is then compared with one that uses the traditional dimension reduction method principal component analysis (PCA) and independent component analysis (ICA). The empirical results show that the proposed model outperforms the PCA-based model, as well as alternative models based on ICA and on the multilayer perceptron.

A Stock Market Forecasting Model Combining Two-Directional Two-Dimensional Principal Component Analysis and Radial Basis Function Neural Network

PubMed Central

Guo, Zhiqiang; Wang, Huaiqing; Yang, Jie; Miller, David J.

2015-01-01

In this paper, we propose and implement a hybrid model combining two-directional two-dimensional principal component analysis ((2D)2PCA) and a Radial Basis Function Neural Network (RBFNN) to forecast stock market behavior. First, 36 stock market technical variables are selected as the input features, and a sliding window is used to obtain the input data of the model. Next, (2D)2PCA is utilized to reduce the dimension of the data and extract its intrinsic features. Finally, an RBFNN accepts the data processed by (2D)2PCA to forecast the next day's stock price or movement. The proposed model is used on the Shanghai stock market index, and the experiments show that the model achieves a good level of fitness. The proposed model is then compared with one that uses the traditional dimension reduction method principal component analysis (PCA) and independent component analysis (ICA). The empirical results show that the proposed model outperforms the PCA-based model, as well as alternative models based on ICA and on the multilayer perceptron. PMID:25849483

Large-scale models reveal the two-component mechanics of striated muscle.

PubMed

Jarosch, Robert

2008-12-01

This paper provides a comprehensive explanation of striated muscle mechanics and contraction on the basis of filament rotations. Helical proteins, particularly the coiled-coils of tropomyosin, myosin and alpha-actinin, shorten their H-bonds cooperatively and produce torque and filament rotations when the Coulombic net-charge repulsion of their highly charged side-chains is diminished by interaction with ions. The classical "two-component model" of active muscle differentiated a "contractile component" which stretches the "series elastic component" during force production. The contractile components are the helically shaped thin filaments of muscle that shorten the sarcomeres by clockwise drilling into the myosin cross-bridges with torque decrease (= force-deficit). Muscle stretch means drawing out the thin filament helices off the cross-bridges under passive counterclockwise rotation with torque increase (= stretch activation). Since each thin filament is anchored by four elastic alpha-actinin Z-filaments (provided with force-regulating sites for Ca(2+) binding), the thin filament rotations change the torsional twist of the four Z-filaments as the "series elastic components". Large scale models simulate the changes of structure and force in the Z-band by the different Z-filament twisting stages A, B, C, D, E, F and G. Stage D corresponds to the isometric state. The basic phenomena of muscle physiology, i. e. latency relaxation, Fenn-effect, the force-velocity relation, the length-tension relation, unexplained energy, shortening heat, the Huxley-Simmons phases, etc. are explained and interpreted with the help of the model experiments.

rSNPBase 3.0: an updated database of SNP-related regulatory elements, element-gene pairs and SNP-based gene regulatory networks

PubMed Central

2018-01-01

Abstract Here, we present the updated rSNPBase 3.0 database (http://rsnp3.psych.ac.cn), which provides human SNP-related regulatory elements, element-gene pairs and SNP-based regulatory networks. This database is the updated version of the SNP regulatory annotation database rSNPBase and rVarBase. In comparison to the last two versions, there are both structural and data adjustments in rSNPBase 3.0: (i) The most significant new feature is the expansion of analysis scope from SNP-related regulatory elements to include regulatory element–target gene pairs (E–G pairs), therefore it can provide SNP-based gene regulatory networks. (ii) Web function was modified according to data content and a new network search module is provided in the rSNPBase 3.0 in addition to the previous regulatory SNP (rSNP) search module. The two search modules support data query for detailed information (related-elements, element-gene pairs, and other extended annotations) on specific SNPs and SNP-related graphic networks constructed by interacting transcription factors (TFs), miRNAs and genes. (3) The type of regulatory elements was modified and enriched. To our best knowledge, the updated rSNPBase 3.0 is the first data tool supports SNP functional analysis from a regulatory network prospective, it will provide both a comprehensive understanding and concrete guidance for SNP-related regulatory studies. PMID:29140525

Investigation of the adhesion interface obtained through two-component injection molding

NASA Astrophysics Data System (ADS)

Fetecau, Catalin; Stan, Felicia; Dobrea, Daniel

2011-01-01

In this paper we study the interface strength obtained through two-component (2C) injection molding of LDPE-HDPE polymers. First, numerical simulation of the over-molding process is carried out using Moldflow technology. Second, butt-joint specimens were produced by over-molding under different process condition, and tested. Two injection sequences were considered, injection of LDPE on HDPE polymer, and HDLE on LDPE, respectively. To investigate the effects of the mold surface roughness on the polymers adhesion at interface, different inserts with different roughness are employed.

Efficient two-component relativistic method for large systems

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

Nakai, Hiromi; Research Institute for Science and Engineering, Waseda University, Tokyo 169-8555; CREST, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012

This paper reviews a series of theoretical studies to develop efficient two-component (2c) relativistic method for large systems by the author’s group. The basic theory is the infinite-order Douglas-Kroll-Hess (IODKH) method for many-electron Dirac-Coulomb Hamiltonian. The local unitary transformation (LUT) scheme can effectively produce the 2c relativistic Hamiltonian, and the divide-and-conquer (DC) method can achieve linear-scaling of Hartree-Fock and electron correlation methods. The frozen core potential (FCP) theoretically connects model potential calculations with the all-electron ones. The accompanying coordinate expansion with a transfer recurrence relation (ACE-TRR) scheme accelerates the computations of electron repulsion integrals with high angular momenta and longmore » contractions.« less

Vortices in a rotating two-component Bose–Einstein condensate with tunable interactions and harmonic potential

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

Zhang, Xiao-Fei, E-mail: xfzhang@ntsc.ac.cn; Du, Zhi-Jing; Tan, Ren-Bing

We consider a pair of coupled nonlinear Schrödinger equations modeling a rotating two-component Bose–Einstein condensate with tunable interactions and harmonic potential, with emphasis on the structure of vortex states by varying the strength of inter-component interaction, rotational frequency, and the aspect ratio of the harmonic potential. Our results show that the inter-component interaction greatly enhances the effect of rotation. For the case of isotropic harmonic potential and small inter-component interaction, the initial vortex structure remains unchanged. As the ratio of inter- to intra-component interactions increases, each component undergoes a transition from a vortex lattice (vortex line) in an isotropic (anisotropic)more » harmonic potential to an alternatively arranged stripe pattern, and eventually to the interwoven “serpentine” vortex sheets. Moreover, in the case of anisotropic harmonic potential the system can develop to a rotating droplet structure. -- Highlights: •Different vortex structures are obtained within the full parameter space. •Effects of system parameters on the ground state structure are discussed. •Phase transition between different vortex structures is also examined. •Present one possible way to obtain the rotating droplet structure. •Provide many possibilities to manipulate vortex in two-component BEC.« less

FAMA Is an Essential Component for the Differentiation of Two Distinct Cell Types, Myrosin Cells and Guard Cells, in Arabidopsis[W

PubMed Central

Shirakawa, Makoto; Ueda, Haruko; Nagano, Atsushi J.; Shimada, Tomoo; Kohchi, Takayuki; Hara-Nishimura, Ikuko

2014-01-01

Brassicales plants, including Arabidopsis thaliana, have an ingenious two-compartment defense system, which sequesters myrosinase from the substrate glucosinolate and produces a toxic compound when cells are damaged by herbivores. Myrosinase is stored in vacuoles of idioblast myrosin cells. The molecular mechanism that regulates myrosin cell development remains elusive. Here, we identify the basic helix-loop-helix transcription factor FAMA as an essential component for myrosin cell development along Arabidopsis leaf veins. FAMA is known as a regulator of stomatal development. We detected FAMA expression in myrosin cell precursors in leaf primordia in addition to stomatal lineage cells. FAMA deficiency caused defects in myrosin cell development and in the biosynthesis of myrosinases THIOGLUCOSIDE GLUCOHYDROLASE1 (TGG1) and TGG2. Conversely, ectopic FAMA expression conferred myrosin cell characteristics to hypocotyl and root cells, both of which normally lack myrosin cells. The FAMA interactors ICE1/SCREAM and its closest paralog SCREAM2/ICE2 were essential for myrosin cell development. DNA microarray analysis identified 32 candidate genes involved in myrosin cell development under the control of FAMA. This study provides a common regulatory pathway that determines two distinct cell types in leaves: epidermal guard cells and inner-tissue myrosin cells. PMID:25304202

Biosimilars: Key regulatory considerations and similarity assessment tools

PubMed Central

Wang, Xiao‐Zhuo Michelle; Conlon, Hugh D.; Anderson, Scott; Ryan, Anne M.; Bose, Arindam

2017-01-01

Abstract A biosimilar drug is defined in the US Food and Drug Administration (FDA) guidance document as a biopharmaceutical that is highly similar to an already licensed biologic product (referred to as the reference product) notwithstanding minor differences in clinically inactive components and for which there are no clinically meaningful differences in purity, potency, and safety between the two products. The development of biosimilars is a challenging, multistep process. Typically, the assessment of similarity involves comprehensive structural and functional characterization throughout the development of the biosimilar in an iterative manner and, if required by the local regulatory authority, an in vivo nonclinical evaluation, all conducted with direct comparison to the reference product. In addition, comparative clinical pharmacology studies are conducted with the reference product. The approval of biosimilars is highly regulated although varied across the globe in terms of nomenclature and the precise criteria for demonstrating similarity. Despite varied regulatory requirements, differences between the proposed biosimilar and the reference product must be supported by strong scientific evidence that these differences are not clinically meaningful. This review discusses the challenges faced by pharmaceutical companies in the development of biosimilars. PMID:28842986

Synthesis and Characterization of Two Component Alloy Nanoparticles

NASA Astrophysics Data System (ADS)

Tabatabaei, Salomeh

Alloying is an old trick used to produce new materials by synergistically combining at least two components. New developments in nanoscience have enabled new degrees of freedom, such as size, solubility and concentration of the alloying element to be utilized in the design of the physical properties of alloy nanoparticles (ANPs). ANPs as multi-functional materials have applications in catalysis, biomedical technologies and electronics. Phase diagrams of ANPs are very little known and may not represent that of bulk picture, furthermore, ANPs with different crystallite orientation and compositions could remain far from equilibrium. Here, we studied the synthesis and stability of Au-Sn and Ag-Ni ANPs with chemical reduction method at room temperature. Due to the large difference in the redox potentials of Au and Sn, co-reduction is not a reproducible method. However, two step successive reductions was found to be more reliable to generate Au-Sn ANPs which consists of forming clusters in the first step (either without capping agent or with weakly coordinated surfactant molecules) and then undergoing a second reduction step in the presence of another metal salt. Our observation also showed that capping agents (Cetrimonium bromide or (CTAB)) and Polyacrylic acid (PAA)) play a key role in the alloying process and shorter length capping agent (PAA) may facilitate the diffusion of individual components and thus enabling better alloying. Different molar ratios of Sn and Au precursors were used to study the effect of alloying elements on the melting point and the crystalline structures and melting points were determined by various microscopy and spectroscopy techniques and differential scanning calorimetry (DSC). A significant depression (up to150°C) in the melting transition was observed for the Au-Sn ANPs compared to the bulk eutectic point (Tm 280°C) due to the size and shape effect. Au-Sn ANPs offer a unique set of advantages as lead-free solder material which can

FK506 biosynthesis is regulated by two positive regulatory elements in Streptomyces tsukubaensis

PubMed Central

2012-01-01

Background FK506 (Tacrolimus) is an important immunosuppressant, produced by industrial biosynthetic processes using various Streptomyces species. Considering the complex structure of FK506, it is reasonable to expect complex regulatory networks controlling its biosynthesis. Regulatory elements, present in gene clusters can have a profound influence on the final yield of target product and can play an important role in development of industrial bioprocesses. Results Three putative regulatory elements, namely fkbR, belonging to the LysR-type family, fkbN, a large ATP-binding regulator of the LuxR family (LAL-type) and allN, a homologue of AsnC family regulatory proteins, were identified in the FK506 gene cluster from Streptomyces tsukubaensis NRRL 18488, a progenitor of industrial strains used for production of FK506. Inactivation of fkbN caused a complete disruption of FK506 biosynthesis, while inactivation of fkbR resulted in about 80% reduction of FK506 yield. No functional role in the regulation of the FK506 gene cluster has been observed for the allN gene. Using RT-PCR and a reporter system based on a chalcone synthase rppA, we demonstrated, that in the wild type as well as in fkbN- and fkbR-inactivated strains, fkbR is transcribed in all stages of cultivation, even before the onset of FK506 production, whereas fkbN expression is initiated approximately with the initiation of FK506 production. Surprisingly, inactivation of fkbN (or fkbR) does not abolish the transcription of the genes in the FK506 gene cluster in general, but may reduce expression of some of the tested biosynthetic genes. Finally, introduction of a second copy of the fkbR or fkbN genes under the control of the strong ermE* promoter into the wild type strain resulted in 30% and 55% of yield improvement, respectively. Conclusions Our results clearly demonstrate the positive regulatory role of fkbR and fkbN genes in FK506 biosynthesis in S. tsukubaensis NRRL 18488. We have shown that regulatory

Effects of nutritional components on aging

PubMed Central

Lee, Dongyeop; Hwang, Wooseon; Artan, Murat; Jeong, Dae-Eun; Lee, Seung-Jae

2015-01-01

Nutrients including carbohydrates, proteins, lipids, vitamins, and minerals regulate various physiological processes and are essential for the survival of organisms. Reduced overall caloric intake delays aging in various organisms. However, the role of each nutritional component in the regulation of lifespan is not well established. In this review, we describe recent studies focused on the regulatory role of each type of nutrient in aging. Moreover, we will discuss how the amount or composition of each nutritional component may influence longevity or health in humans. PMID:25339542

Machine for applying a two component resin to a roadway surface

DOEpatents

Huszagh, Donald W.

1985-01-01

A portable machine for spraying two component resins onto a roadway, the machine having a pneumatic control system, including apparatus for purging the machine of mixed resin with air and then removing remaining resin with solvent. Interlocks prevent contamination of solvent and resin, and mixed resin can be purged in the event of a power failure.

Machine for applying a two component resin to a roadway surface

DOEpatents

Huszagh, D.W.

1984-01-01

A portable machine for spraying two component resins onto a roadway, the machine having a pneumatic control system, including means for purging the machine of mixed resin with air and then removing remaining resin with solvent. Interlocks prevent contamination of solvent and resin, and mixed resin can be purged in the event of a power failure.

Functional analysis of two sterol regulatory element binding proteins in Penicillium digitatum

PubMed Central

Ruan, Ruoxin; Wang, Mingshuang; Liu, Xin; Sun, Xuepeng; Chung, Kuang-Ren

2017-01-01

The sterol regulatory element binding proteins (SREBPs) are key regulators for sterol homeostasis in most fungi. In the citrus postharvest pathogen Penicillium digitatum, the SREBP homolog is required for fungicide resistance and regulation of CYP51 expression. In this study, we identified another SREBP transcription factor PdSreB in P. digitatum, and the biological functions of both SREBPs were characterized and compared. Inactivation of PdsreA, PdsreB or both genes in P. digitatum reduced ergosterol contents and increased sensitivities to sterol 14-α-demethylation inhibitors (DMIs) and cobalt chloride. Fungal strains impaired at PdsreA but not PdsreB increased sensitivity to tridemorph and an iron chelator 2,2’-dipyridyl. Virulence assays on citrus fruit revealed that fungal strains impaired at PdsreA, PdsreB or both induce maceration lesions similar to those induced by wild-type. However, ΔPdsreA, ΔPdsreB or the double mutant strain rarely produce aerial mycelia on infected citrus fruit peels. RNA-Seq analysis showed the broad regulatory functions of both SREBPs in biosynthesis, transmembrane transportation and stress responses. Our results provide new insights into the conserved and differentiated regulatory functions of SREBP homologs in plant pathogenic fungi. PMID:28467453

Two component X-ray emission from RS CVn binaries

NASA Technical Reports Server (NTRS)

Swank, J. H.; White, N. E.; Holt, S. S.; Becker, R. H.

1980-01-01

A summary of results from the solid state spectrometer on the Einstein Observatory for 7 RS CVn binaries is presented. The spectra of all require two emission components, evidenced by line emission characteristic of plasma at 4 to 8 x 10 to the 6th power and bremsstrahlung characteristic of 20 to 100 x 10 to the 6th power K. The data are interpreted in terms of magnetic coronal loops similar to those seen on the Sun, although with different characteristic parameters. The emission regions could be defined by separate magnetic structures. For pressure less than approximately 10 dynes/sq cm the low temperature plasma would be confined within the stellar radii, while the high temperature plasma would, for the synchronous close binaries, fill the binary orbits. However, for loop pressures exceeding 100 dynes/sq cm, the high temperature components would also be confined to within the stellar radii, in loops covering only small fractions of the stellar surfaces. While the radio properties and the occurrence of X-ray flares suggest the larger emission regions, the observations of time variations leave the ambiguity unresolved.

Patient Autonomy for the Management of Chronic Conditions: A Two-Component Re-conceptualization

PubMed Central

Naik, Aanand D.; Dyer, Carmel B.; Kunik, Mark E.; McCullough, Laurence B.

2010-01-01

The clinical application of the concept of patient autonomy has centered on the ability to deliberate and make treatment decisions (decisional autonomy) to the virtual exclusion of the capacity to execute the treatment plan (executive autonomy). However, the one-component concept of autonomy is problematic in the context of multiple chronic conditions. Adherence to complex treatments commonly breaks down when patients have functional, educational, and cognitive barriers that impair their capacity to plan, sequence, and carry out tasks associated with chronic care. The purpose of this article is to call for a two-component re-conceptualization of autonomy and to argue that the clinical assessment of capacity for patients with chronic conditions should be expanded to include both autonomous decision making and autonomous execution of the agreed-upon treatment plan. We explain how the concept of autonomy should be expanded to include both decisional and executive autonomy, describe the biopsychosocial correlates of the two-component concept of autonomy, and recommend diagnostic and treatment strategies to support patients with deficits in executive autonomy. PMID:19180389

Phosphatase activity tunes two-component system sensor detection threshold.

PubMed

Landry, Brian P; Palanki, Rohan; Dyulgyarov, Nikola; Hartsough, Lucas A; Tabor, Jeffrey J

2018-04-12

Two-component systems (TCSs) are the largest family of multi-step signal transduction pathways in biology, and a major source of sensors for biotechnology. However, the input concentrations to which biosensors respond are often mismatched with application requirements. Here, we utilize a mathematical model to show that TCS detection thresholds increase with the phosphatase activity of the sensor histidine kinase. We experimentally validate this result in engineered Bacillus subtilis nitrate and E. coli aspartate TCS sensors by tuning their detection threshold up to two orders of magnitude. We go on to apply our TCS tuning method to recently described tetrathionate and thiosulfate sensors by mutating a widely conserved residue previously shown to impact phosphatase activity. Finally, we apply TCS tuning to engineer B. subtilis to sense and report a wide range of fertilizer concentrations in soil. This work will enable the engineering of tailor-made biosensors for diverse synthetic biology applications.

Phosphate Sink Containing Two-Component Signaling Systems as Tunable Threshold Devices

PubMed Central

Amin, Munia; Kothamachu, Varun B.; Feliu, Elisenda; Scharf, Birgit E.; Porter, Steven L.; Soyer, Orkun S.

2014-01-01

Synthetic biology aims to design de novo biological systems and reengineer existing ones. These efforts have mostly focused on transcriptional circuits, with reengineering of signaling circuits hampered by limited understanding of their systems dynamics and experimental challenges. Bacterial two-component signaling systems offer a rich diversity of sensory systems that are built around a core phosphotransfer reaction between histidine kinases and their output response regulator proteins, and thus are a good target for reengineering through synthetic biology. Here, we explore the signal-response relationship arising from a specific motif found in two-component signaling. In this motif, a single histidine kinase (HK) phosphotransfers reversibly to two separate output response regulator (RR) proteins. We show that, under the experimentally observed parameters from bacteria and yeast, this motif not only allows rapid signal termination, whereby one of the RRs acts as a phosphate sink towards the other RR (i.e. the output RR), but also implements a sigmoidal signal-response relationship. We identify two mathematical conditions on system parameters that are necessary for sigmoidal signal-response relationships and define key parameters that control threshold levels and sensitivity of the signal-response curve. We confirm these findings experimentally, by in vitro reconstitution of the one HK-two RR motif found in the Sinorhizobium meliloti chemotaxis pathway and measuring the resulting signal-response curve. We find that the level of sigmoidality in this system can be experimentally controlled by the presence of the sink RR, and also through an auxiliary protein that is shown to bind to the HK (yielding Hill coefficients of above 7). These findings show that the one HK-two RR motif allows bacteria and yeast to implement tunable switch-like signal processing and provides an ideal basis for developing threshold devices for synthetic biology applications. PMID:25357192

rSNPBase 3.0: an updated database of SNP-related regulatory elements, element-gene pairs and SNP-based gene regulatory networks.

PubMed

Guo, Liyuan; Wang, Jing

2018-01-04

Here, we present the updated rSNPBase 3.0 database (http://rsnp3.psych.ac.cn), which provides human SNP-related regulatory elements, element-gene pairs and SNP-based regulatory networks. This database is the updated version of the SNP regulatory annotation database rSNPBase and rVarBase. In comparison to the last two versions, there are both structural and data adjustments in rSNPBase 3.0: (i) The most significant new feature is the expansion of analysis scope from SNP-related regulatory elements to include regulatory element-target gene pairs (E-G pairs), therefore it can provide SNP-based gene regulatory networks. (ii) Web function was modified according to data content and a new network search module is provided in the rSNPBase 3.0 in addition to the previous regulatory SNP (rSNP) search module. The two search modules support data query for detailed information (related-elements, element-gene pairs, and other extended annotations) on specific SNPs and SNP-related graphic networks constructed by interacting transcription factors (TFs), miRNAs and genes. (3) The type of regulatory elements was modified and enriched. To our best knowledge, the updated rSNPBase 3.0 is the first data tool supports SNP functional analysis from a regulatory network prospective, it will provide both a comprehensive understanding and concrete guidance for SNP-related regulatory studies. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Emotion: The Self-regulatory Sense

PubMed Central

2014-01-01

While emotion is a central component of human health and well-being, traditional approaches to understanding its biological function have been wanting. A dynamic systems model, however, broadly redefines and recasts emotion as a primary sensory system—perhaps the first sensory system to have emerged, serving the ancient autopoietic function of “self-regulation.” Drawing upon molecular biology and revelations from the field of epigenetics, the model suggests that human emotional perceptions provide an ongoing stream of “self-relevant” sensory information concerning optimally adaptive states between the organism and its immediate environment, along with coupled behavioral corrections that honor a universal self-regulatory logic, one still encoded within cellular signaling and immune functions. Exemplified by the fundamental molecular circuitry of sensorimotor control in the E coli bacterium, the model suggests that the hedonic (affective) categories emerge directly from positive and negative feedback processes, their good/bad binary appraisals relating to dual self-regulatory behavioral regimes—evolutionary purposes, through which organisms actively participate in natural selection, and through which humans can interpret optimal or deficit states of balanced being and becoming. The self-regulatory sensory paradigm transcends anthropomorphism, unites divergent theoretical perspectives and isolated bodies of literature, while challenging time-honored assumptions. While suppressive regulatory strategies abound, it suggests that emotions are better understood as regulating us, providing a service crucial to all semantic language, learning systems, evaluative decision-making, and fundamental to optimal physical, mental, and social health. PMID:24808986

Radiochromatographic assay of N-acyl-phosphatidylethanolamine-specific phospholipase D activity.

PubMed

Fezza, Filomena; Gasperi, Valeria; Mazzei, Cinzia; Maccarrone, Mauro

2005-04-01

A radiochromatographic method has been set up to assay the activity of N-acyl-phosphatidylethanolamine-specific phospholipase D (NAPE-PLD), based on reversed-phase high-performance liquid chromatography (HPLC) and online scintillation counting. The anandamide (N-arachidonoylethanolamine, AEA), product released by NAPE-PLD from the N-arachidonoyl-phosphatidylethanolamine (NArPE) substrate, was separated using a C18 column eluted with methanol-water-acetic acid and was quantified with an external standard method. Baseline separation of AEA and NArPE was completed in less than 15 min, with a detection limit of 0.5 fmol AEA at a signal-to-noise ratio of 4:1. The sensitivity and accuracy of the radiochromatographic procedure allowed detection and characterization of NAPE-PLD activity in very tiny tissue samples or in samples where the enzymatic activity is very low. With this method, we could determine the kinetic constants (i.e., apparent Michaelis-Menten constant (Km) of 40.0+/-5.6 microM and maximum velocity (Vmax) of 22.2+/-3.5 pmol/min per milligram protein toward NArPE) and the distribution of NAPE-PLD activity in brain areas and peripheral tissues of mouse. In addition, we could collect unprecedented evidence that compounds widely used in studies of the endocannabinoid system (e.g., AEA and congeners, receptor a(nta)gonists and inhibitors of AEA degradation) can also affect NAPE-PLD activity.

Does GLP enhance the quality of toxicological evidence for regulatory decisions?

PubMed Central

Borgert, Christopher J.; Becker, Richard A.; Carlton, Betsy D.; Hanson, Mark; Kwiatkowski, Patricia L.; Sue Marty, Mary; McCarty, Lynn S.; Quill, Terry F.; Solomon, Keith; Van Der Kraak, Glen; Witorsch, Raphael J.; Don Yi, Kun

2016-01-01

There is debate over whether the requirements of GLP are appropriate standards for evaluating the quality of toxicological data used to formulate regulations. A group promoting the importance of non-monotonic dose responses for endocrine disruptors contend that scoring systems giving primacy to GLP are biased against non-GLP studies from the literature and are merely record-keeping exercises to prevent fraudulent reporting of data from non-published guideline toxicology studies. They argue that guideline studies often employ insensitive species and outdated methods, and ignore the perspectives of subject-matter experts in endocrine disruption, who should be the sole arbiters of data quality. We believe regulatory agencies should use both non-GLP and GLP studies, that GLP requirements assure fundamental tenets of study integrity not typically addressed by journal peer-review, and that use of standardized test guidelines and GLP promotes consistency, reliability, comparability, and harmonization of various types of studies used by regulatory agencies worldwide. This debate suffers two impediments to progress: a conflation of different phases of study interpretation and levels of data validity, and a misleading characterization of many essential components of GLP and regulatory toxicology. Herein we provide clarifications critical for removing those impediments. PMID:27208076

Rapid evolution of cis-regulatory sequences via local point mutations

NASA Technical Reports Server (NTRS)

Stone, J. R.; Wray, G. A.

2001-01-01

Although the evolution of protein-coding sequences within genomes is well understood, the same cannot be said of the cis-regulatory regions that control transcription. Yet, changes in gene expression are likely to constitute an important component of phenotypic evolution. We simulated the evolution of new transcription factor binding sites via local point mutations. The results indicate that new binding sites appear and become fixed within populations on microevolutionary timescales under an assumption of neutral evolution. Even combinations of two new binding sites evolve very quickly. We predict that local point mutations continually generate considerable genetic variation that is capable of altering gene expression.

Sociotechnical systems as a framework for regulatory system design and evaluation: Using Work Domain Analysis to examine a new regulatory system.

PubMed

Carden, Tony; Goode, Natassia; Read, Gemma J M; Salmon, Paul M

2017-03-15

Like most work systems, the domain of adventure activities has seen a series of serious incidents and subsequent calls to improve regulation. Safety regulation systems aim to promote safety and reduce accidents. However, there is scant evidence they have led to improved safety outcomes. In fact there is some evidence that the poor integration of regulatory system components has led to adverse safety outcomes in some contexts. Despite this, there is an absence of methods for evaluating regulatory and compliance systems. This article argues that sociotechnical systems theory and methods provide a suitable framework for evaluating regulatory systems. This is demonstrated through an analysis of a recently introduced set of adventure activity regulations. Work Domain Analysis (WDA) was used to describe the regulatory system in terms of its functional purposes, values and priority measures, purpose-related functions, object-related processes and cognitive objects. This allowed judgement to be made on the nature of the new regulatory system and on the constraints that may impact its efficacy following implementation. Importantly, the analysis suggests that the new system's functional purpose of ensuring safe activities is not fully supported in terms of the functions and objects available to fulfil them. Potential improvements to the design of the system are discussed along with the implications for regulatory system design and evaluation across the safety critical domains generally. Copyright © 2017 Elsevier Ltd. All rights reserved.

Calculations of electric dipole moments and static dipole polarizabilities based on the two-component normalized elimination of the small component method.

PubMed

Yoshizawa, Terutaka; Zou, Wenli; Cremer, Dieter

2016-11-14

The analytical energy gradient and Hessian of the two-component Normalized Elimination of the Small Component (2c-NESC) method with regard to the components of the electric field are derived and used to calculate spin-orbit coupling (SOC) corrected dipole moments and dipole polarizabilities of molecules, which contain elements with high atomic number. Calculated 2c-NESC dipole moments and isotropic polarizabilities agree well with the corresponding four-component-Dirac Hartree-Fock or density functional theory values. SOC corrections for the electrical properties are in general small, but become relevant for the accurate prediction of these properties when the molecules in question contain sixth and/or seventh period elements (e.g., the SO effect for At 2 is about 10% of the 2c-NESC polarizability). The 2c-NESC changes in the electric molecular properties are rationalized in terms of spin-orbit splitting and SOC-induced mixing of frontier orbitals with the same j = l + s quantum numbers.

Calculations of electric dipole moments and static dipole polarizabilities based on the two-component normalized elimination of the small component method

NASA Astrophysics Data System (ADS)

Yoshizawa, Terutaka; Zou, Wenli; Cremer, Dieter

2016-11-01

The analytical energy gradient and Hessian of the two-component Normalized Elimination of the Small Component (2c-NESC) method with regard to the components of the electric field are derived and used to calculate spin-orbit coupling (SOC) corrected dipole moments and dipole polarizabilities of molecules, which contain elements with high atomic number. Calculated 2c-NESC dipole moments and isotropic polarizabilities agree well with the corresponding four-component-Dirac Hartree-Fock or density functional theory values. SOC corrections for the electrical properties are in general small, but become relevant for the accurate prediction of these properties when the molecules in question contain sixth and/or seventh period elements (e.g., the SO effect for At2 is about 10% of the 2c-NESC polarizability). The 2c-NESC changes in the electric molecular properties are rationalized in terms of spin-orbit splitting and SOC-induced mixing of frontier orbitals with the same j = l + s quantum numbers.

18 CFR 367.51 - Components of construction.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Components of construction. 367.51 Section 367.51 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... short life, including small portable tools and implements, must not be charged to service company...

18 CFR 367.51 - Components of construction.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Components of construction. 367.51 Section 367.51 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... short life, including small portable tools and implements, must not be charged to service company...

18 CFR 367.51 - Components of construction.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Components of construction. 367.51 Section 367.51 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... short life, including small portable tools and implements, must not be charged to service company...

18 CFR 367.51 - Components of construction.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Components of construction. 367.51 Section 367.51 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... short life, including small portable tools and implements, must not be charged to service company...

A two-component Matched Interface and Boundary (MIB) regularization for charge singularity in implicit solvation

NASA Astrophysics Data System (ADS)

Geng, Weihua; Zhao, Shan

2017-12-01

We present a new Matched Interface and Boundary (MIB) regularization method for treating charge singularity in solvated biomolecules whose electrostatics are described by the Poisson-Boltzmann (PB) equation. In a regularization method, by decomposing the potential function into two or three components, the singular component can be analytically represented by the Green's function, while other components possess a higher regularity. Our new regularization combines the efficiency of two-component schemes with the accuracy of the three-component schemes. Based on this regularization, a new MIB finite difference algorithm is developed for solving both linear and nonlinear PB equations, where the nonlinearity is handled by using the inexact-Newton's method. Compared with the existing MIB PB solver based on a three-component regularization, the present algorithm is simpler to implement by circumventing the work to solve a boundary value Poisson equation inside the molecular interface and to compute related interface jump conditions numerically. Moreover, the new MIB algorithm becomes computationally less expensive, while maintains the same second order accuracy. This is numerically verified by calculating the electrostatic potential and solvation energy on the Kirkwood sphere on which the analytical solutions are available and on a series of proteins with various sizes.

Structural insight into partner specificity and phosphoryl transfer in two-component signal transduction.

PubMed

Casino, Patricia; Rubio, Vicente; Marina, Alberto

2009-10-16

The chief mechanism used by bacteria for sensing their environment is based on two conserved proteins: a sensor histidine kinase (HK) and an effector response regulator (RR). The signal transduction process involves highly conserved domains of both proteins that mediate autokinase, phosphotransfer, and phosphatase activities whose output is a finely tuned RR phosphorylation level. Here, we report the structure of the complex between the entire cytoplasmic portion of Thermotoga maritima class I HK853 and its cognate, RR468, as well as the structure of the isolated RR468, both free and BeF(3)(-) bound. Our results provide insight into partner specificity in two-component systems, recognition of the phosphorylation state of each partner, and the catalytic mechanism of the phosphatase reaction. Biochemical analysis shows that the HK853-catalyzed autokinase reaction proceeds by a cis autophosphorylation mechanism within the HK subunit. The results suggest a model for the signal transduction mechanism in two-component systems.

The NtrY-NtrX two-component system is involved in controlling nitrate assimilation in Herbaspirillum seropedicae strain SmR1.

PubMed

Bonato, Paloma; Alves, Lysangela R; Osaki, Juliana H; Rigo, Liu U; Pedrosa, Fabio O; Souza, Emanuel M; Zhang, Nan; Schumacher, Jörg; Buck, Martin; Wassem, Roseli; Chubatsu, Leda S

2016-11-01

Herbaspirillum seropedicae is a diazotrophic β-Proteobacterium found endophytically associated with gramineae (Poaceae or graminaceous plants) such as rice, sorghum and sugar cane. In this work we show that nitrate-dependent growth in this organism is regulated by the master nitrogen regulatory two-component system NtrB-NtrC, and by NtrY-NtrX, which functions to specifically regulate nitrate metabolism. NtrY is a histidine kinase sensor protein predicted to be associated with the membrane and NtrX is the response regulator partner. The ntrYntrX genes are widely distributed in Proteobacteria. In α-Proteobacteria they are frequently located downstream from ntrBC, whereas in β-Proteobacteria these genes are located downstream from genes encoding an RNA methyltransferase and a proline-rich protein with unknown function. The NtrX protein of α-Proteobacteria has an AAA+ domain, absent in those from β-Proteobacteria. An ntrY mutant of H. seropedicae showed the wild-type nitrogen fixation phenotype, but the nitrate-dependent growth was abolished. Gene fusion assays indicated that NtrY is involved in the expression of genes coding for the assimilatory nitrate reductase as well as the nitrate-responsive two-component system NarX-NarL (narK and narX promoters, respectively). The purified NtrX protein was capable of binding the narK and narX promoters, and the binding site at the narX promoter for the NtrX protein was determined by DNA footprinting. In silico analyses revealed similar sequences in other promoter regions of H. seropedicae that are related to nitrate assimilation, supporting the role of the NtrY-NtrX system in regulating nitrate metabolism in H. seropedicae. © 2016 Federation of European Biochemical Societies.

Architecture of the human regulatory network derived from ENCODE data.

PubMed

Gerstein, Mark B; Kundaje, Anshul; Hariharan, Manoj; Landt, Stephen G; Yan, Koon-Kiu; Cheng, Chao; Mu, Xinmeng Jasmine; Khurana, Ekta; Rozowsky, Joel; Alexander, Roger; Min, Renqiang; Alves, Pedro; Abyzov, Alexej; Addleman, Nick; Bhardwaj, Nitin; Boyle, Alan P; Cayting, Philip; Charos, Alexandra; Chen, David Z; Cheng, Yong; Clarke, Declan; Eastman, Catharine; Euskirchen, Ghia; Frietze, Seth; Fu, Yao; Gertz, Jason; Grubert, Fabian; Harmanci, Arif; Jain, Preti; Kasowski, Maya; Lacroute, Phil; Leng, Jing Jane; Lian, Jin; Monahan, Hannah; O'Geen, Henriette; Ouyang, Zhengqing; Partridge, E Christopher; Patacsil, Dorrelyn; Pauli, Florencia; Raha, Debasish; Ramirez, Lucia; Reddy, Timothy E; Reed, Brian; Shi, Minyi; Slifer, Teri; Wang, Jing; Wu, Linfeng; Yang, Xinqiong; Yip, Kevin Y; Zilberman-Schapira, Gili; Batzoglou, Serafim; Sidow, Arend; Farnham, Peggy J; Myers, Richard M; Weissman, Sherman M; Snyder, Michael

2012-09-06

Transcription factors bind in a combinatorial fashion to specify the on-and-off states of genes; the ensemble of these binding events forms a regulatory network, constituting the wiring diagram for a cell. To examine the principles of the human transcriptional regulatory network, we determined the genomic binding information of 119 transcription-related factors in over 450 distinct experiments. We found the combinatorial, co-association of transcription factors to be highly context specific: distinct combinations of factors bind at specific genomic locations. In particular, there are significant differences in the binding proximal and distal to genes. We organized all the transcription factor binding into a hierarchy and integrated it with other genomic information (for example, microRNA regulation), forming a dense meta-network. Factors at different levels have different properties; for instance, top-level transcription factors more strongly influence expression and middle-level ones co-regulate targets to mitigate information-flow bottlenecks. Moreover, these co-regulations give rise to many enriched network motifs (for example, noise-buffering feed-forward loops). Finally, more connected network components are under stronger selection and exhibit a greater degree of allele-specific activity (that is, differential binding to the two parental alleles). The regulatory information obtained in this study will be crucial for interpreting personal genome sequences and understanding basic principles of human biology and disease.

Dynamical modeling and analysis of large cellular regulatory networks

NASA Astrophysics Data System (ADS)

Bérenguier, D.; Chaouiya, C.; Monteiro, P. T.; Naldi, A.; Remy, E.; Thieffry, D.; Tichit, L.

2013-06-01

The dynamical analysis of large biological regulatory networks requires the development of scalable methods for mathematical modeling. Following the approach initially introduced by Thomas, we formalize the interactions between the components of a network in terms of discrete variables, functions, and parameters. Model simulations result in directed graphs, called state transition graphs. We are particularly interested in reachability properties and asymptotic behaviors, which correspond to terminal strongly connected components (or "attractors") in the state transition graph. A well-known problem is the exponential increase of the size of state transition graphs with the number of network components, in particular when using the biologically realistic asynchronous updating assumption. To address this problem, we have developed several complementary methods enabling the analysis of the behavior of large and complex logical models: (i) the definition of transition priority classes to simplify the dynamics; (ii) a model reduction method preserving essential dynamical properties, (iii) a novel algorithm to compact state transition graphs and directly generate compressed representations, emphasizing relevant transient and asymptotic dynamical properties. The power of an approach combining these different methods is demonstrated by applying them to a recent multilevel logical model for the network controlling CD4+ T helper cell response to antigen presentation and to a dozen cytokines. This model accounts for the differentiation of canonical Th1 and Th2 lymphocytes, as well as of inflammatory Th17 and regulatory T cells, along with many hybrid subtypes. All these methods have been implemented into the software GINsim, which enables the definition, the analysis, and the simulation of logical regulatory graphs.

18 CFR 367.51 - Components of construction.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Components of construction. 367.51 Section 367.51 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... in other items in this section. (3)(i) Materials and supplies includes the purchase price at the...

Transcriptomic insights into citrus segment membrane's cell wall components relating to fruit sensory texture.

PubMed

Wang, Xun; Lin, Lijin; Tang, Yi; Xia, Hui; Zhang, Xiancong; Yue, Maolan; Qiu, Xia; Xu, Ke; Wang, Zhihui

2018-04-23

During fresh fruit consumption, sensory texture is one factor that affects the organoleptic qualities. Chemical components of plant cell walls, including pectin, cellulose, hemicellulose and lignin, play central roles in determining the textural qualities. To explore the genes and regulatory pathways involved in fresh citrus' perceived sensory texture, we performed mRNA-seq analyses of the segment membranes of two citrus cultivars, Shiranui and Kiyomi, with different organoleptic textures. Segment membranes were sampled at two developmental stages of citrus fruit, the beginning and end of the expansion period. More than 3000 differentially expressed genes were identified. The gene ontology analysis revealed that more categories were significantly enriched in 'Shiranui' than in 'Kiyomi' at both developmental stages. In total, 108 significantly enriched pathways were obtained, with most belonging to metabolism. A detailed transcriptomic analysis revealed potential critical genes involved in the metabolism of cell wall structures, for example, GAUT4 in pectin synthesis, CESA1, 3 and 6, and SUS4 in cellulose synthesis, CSLC5, XXT1 and XXT2 in hemicellulose synthesis, and CSE in lignin synthesis. Low levels, or no expression, of genes involved in cellulose and hemicellulose, such as CESA4, CESA7, CESA8, IRX9 and IRX14, confirmed that secondary cell walls were negligible or absent in citrus segment membranes. A chemical component analysis of the segment membranes from mature fruit revealed that the pectin, cellulose and lignin contents, and the segment membrane's weight (% of segment) were greater in 'Kiyomi'. Organoleptic quality of citrus is easily overlooked. It is mainly determined by sensory texture perceived in citrus segment membrane properties. We performed mRNA-seq analyses of citrus segment membranes to explore the genes and regulatory pathways involved in fresh citrus' perceived sensory texture. Transcriptomic data showed high repeatability between two

75 FR 62436 - Notice of Issuance of Regulatory Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-08

... Power Plants,'' includes in its scope safety- related structures, systems, and components (SSCs) that... monitor the effectiveness of maintenance for protective coatings within its scope (as discrete systems or... and Management System (ADAMS) under Accession No. ML102230359. Electronic copies of Regulatory Guide 1...

The Umov effect in application to an optically thin two-component cloud of cosmic dust

NASA Astrophysics Data System (ADS)

Zubko, Evgenij; Videen, Gorden; Zubko, Nataliya; Shkuratov, Yuriy

2018-04-01

The Umov effect is an inverse correlation between linear polarization of the sunlight scattered by an object and its geometric albedo. The Umov effect has been observed in particulate surfaces, such as planetary regoliths, and recently it also was found in single-scattering small dust particles. Using numerical modeling, we study the Umov effect in a two-component mixture of small irregularly shaped particles. Such a complex chemical composition is suggested in cometary comae and other types of optically thin clouds of cosmic dust. We find that the two-component mixtures of small particles also reveal the Umov effect regardless of the chemical composition of their end-member components. The interrelation between log(Pmax) and log(A) in a two-component mixture of small irregularly shaped particles appears either in a straight linear form or in a slightly curved form. This curvature tends to decrease while the index n in a power-law size distribution r-n grows; at n > 2.5, the log(Pmax)-log(A) diagrams are almost straight linear in appearance. The curvature also noticeably decreases with the packing density of constituent material in irregularly shaped particles forming the mixture. That such a relation exists suggest the Umov effect may also be observed in more complex mixtures.

The Umov effect in application to an optically thin two-component cloud of cosmic dust

NASA Astrophysics Data System (ADS)

Zubko, Evgenij; Videen, Gorden; Zubko, Nataliya; Shkuratov, Yuriy

2018-07-01

The Umov effect is an inverse correlation between linear polarization of the sunlight scattered by an object and its geometric albedo. The Umov effect has been observed in particulate surfaces, such as planetary regoliths, and recently it also was found in single-scattering small dust particles. Using numerical modelling, we study the Umov effect in a two-component mixture of small irregularly shaped particles. Such a complex chemical composition is suggested in cometary comae and other types of optically thin clouds of cosmic dust. We find that the two-component mixtures of small particles also reveal the Umov effect regardless of the chemical composition of their end-member components. The interrelation between log(Pmax) and log(A) in a two-component mixture of small irregularly shaped particles appears either in a straight linear form or in a slightly curved form. This curvature tends to decrease while the index n in a power-law size distribution r-n grows; at n > 2.5, the log(Pmax)-log(A) diagrams are almost straight linear in appearance. The curvature also noticeably decreases with the packing density of constituent material in irregularly shaped particles forming the mixture. That such a relation exists suggests the Umov effect may also be observed in more complex mixtures.

Nonautonomous dark soliton solutions in two-component Bose—Einstein condensates with a linear time-dependent potential

NASA Astrophysics Data System (ADS)

Li, Qiu-Yan; Wang, Shuang-Jin; Li, Zai-Dong

2014-06-01

We report the analytical nonautonomous soliton solutions (NSSs) for two-component Bose—Einstein condensates with the presence of a time-dependent potential. These solutions show that the time-dependent potential can affect the velocity of NSS. The velocity shows the characteristic of both increasing and oscillation with time. A detailed analysis for the asymptotic behavior of NSSs demonstrates that the collision of two NSSs of each component is elastic.

Monte Carlo simulation of two-component bilayers: DMPC/DSPC mixtures.

PubMed Central

Sugár, I P; Thompson, T E; Biltonen, R L

1999-01-01

In this paper, we describe a relatively simple lattice model of a two-component, two-state phospholipid bilayer. Application of Monte Carlo methods to this model permits simulation of the observed excess heat capacity versus temperature curves of dimyristoylphosphatidylcholine (DMPC)/distearoylphosphatidylcholine (DSPC) mixtures as well as the lateral distributions of the components and properties related to these distributions. The analysis of the bilayer energy distribution functions reveals that the gel-fluid transition is a continuous transition for DMPC, DSPC, and all DMPC/DSPC mixtures. A comparison of the thermodynamic properties of DMPC/DSPC mixtures with the configurational properties shows that the temperatures characteristics of the configurational properties correlate well with the maxima in the excess heat capacity curves rather than with the onset and completion temperatures of the gel-fluid transition. In the gel-fluid coexistence region, we also found excellent agreement between the threshold temperatures at different system compositions detected in fluorescence recovery after photobleaching experiments and the temperatures at which the percolation probability of the gel clusters is 0.36. At every composition, the calculated mole fraction of gel state molecules at the fluorescence recovery after photobleaching threshold is 0.34 and, at the percolation threshold of gel clusters, it is 0.24. The percolation threshold mole fraction of gel or fluid lipid depends on the packing geometry of the molecules and the interchain interactions. However, it is independent of temperature, system composition, and state of the percolating cluster. PMID:10096905

[Regulatory T cells].

PubMed

Marinić, Igor; Gagro, Alenka; Rabatić, Sabina

2006-12-01

Regulatory T-cells are a subset of T cells that have beene extensively studied in modern immunology. They are important for the maintenance of peripheral tolerance, and have an important role in various clinical conditions such as allergy, autoimmune disorders, tumors, infections, and in transplant medicine. Basically, this population has a suppressive effect on the neighboring immune cells, thus contributing to the local modulation and control of immune response. There are two main populations of regulatory T cells - natural regulatory T cells, which form a distinct cellular lineage, develop in thymus and perform their modulatory action through direct intercellular contact, along with the secreted cytokines; and inducible regulatory T cells, which develop in the periphery after contact with the antigen that is presented on the antigen presenting cell, and their primary mode of action is through the interleukin 10 (IL-10) and transforming growth factor beta (TGF-alpha) cytokines. Natural regulatory T cells are activated through T cell receptor after contact with specific antigen and inhibit proliferation of other T cells in an antigen independent manner. One of the major difficulties in the research of regulatory T cells is the lack of specific molecular markers that would identify these cells. Natural regulatory T cells constitutively express surface molecule CD25, but many other surface and intracellular molecules (HLA-DR, CD122, CD45RO, CD62, CTLA-4, GITR, PD-1, Notch, FOXP3, etc.) are being investigated for further phenotypic characterization of these cells. Because regulatory T cells have an important role in establishing peripheral tolerance, their importance is manifested in a number of clinical conditions. In the IPEX syndrome (immunodysregulation, polyendocrinopathy and enteropathy, X-linked), which is caused by mutation in Foxp3 gene that influences the development and function of regulatory T cells, patients develop severe autoimmune reactions that

Network motifs – recurring circuitry components in biological systems

EPA Science Inventory

Environmental perturbations, elicited by chemicals, dietary supplements, and drugs, can alter the dynamics of the molecular circuits and networks operating in cells, leading to multiple disease endpoints. Multi-component signal transduction pathways and gene regulatory circuits u...

A Copper-Activated Two-Component System Interacts with Zinc and Imipenem Resistance in Pseudomonas aeruginosa▿

PubMed Central

Caille, Olivier; Rossier, Claude; Perron, Karl

2007-01-01

The effects of copper (Cu) on trace metal and antibiotic resistance of Pseudomonas aeruginosa have been investigated. Cu treatments induced resistance not only to this metal but also, surprisingly, to zinc (Zn). Quantitative reverse transcription-PCR (qRT-PCR) revealed that after Cu treatment the transcription of the czcRS two-component system (TCS) operon was enhanced as well as that of the czcCBA operon encoding an efflux pump specific for zinc, cadmium, and cobalt. Cu treatments at the same time caused a decrease in the production of OprD porin, resulting in resistance to the carbapenem antibiotic imipenem. The CzcR regulator was known to repress oprD. However, Cu was still able to decrease the production of OprD and induce imipenem resistance in a czcRS knockout mutant. This strongly suggested that another Cu-dependent regulatory system was acting negatively on oprD expression. TCS regulator genes copR-copS have been shown to be involved in Cu tolerance in P. aeruginosa. qRT-PCR showed that overproduction of the CopR or of the CzcR regulator resulted in increased transcription of the czcC gene as well as in a decrease in oprD gene transcription, either in the wild-type strain or in the czcRS knockout mutant. Overproduction experiments suggest that a metal-dependent mechanism operates at the posttranscriptional level to control the production of the CzcCBA efflux pump. This study shows that CopR is a new negative regulator of OprD porin and that it links Zn, Cu, and imipenem resistances by interacting with the CzcRS TCS. PMID:17449606

76 FR 74831 - Aging Management of Stainless Steel Structures and Components in Treated Borated Water

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-01

... exposed to treated borated water. In response to a request from the Nuclear Energy Institute (NEI), the... NUCLEAR REGULATORY COMMISSION [NRC-2011-0256] Aging Management of Stainless Steel Structures and Components in Treated Borated Water AGENCY: Nuclear Regulatory Commission. ACTION: Draft interim staff...

Preferential flow systems amended with biogeochemical components: imaging of a two-dimensional study

NASA Astrophysics Data System (ADS)

Pales, Ashley R.; Li, Biting; Clifford, Heather M.; Kupis, Shyla; Edayilam, Nimisha; Montgomery, Dawn; Liang, Wei-zhen; Dogan, Mine; Tharayil, Nishanth; Martinez, Nicole; Moysey, Stephen; Powell, Brian; Darnault, Christophe J. G.

2018-04-01

The vadose zone is a highly interactive heterogeneous system through which water enters the subsurface system by infiltration. This paper details the effects of simulated plant exudate and soil component solutions upon unstable flow patterns in a porous medium (ASTM silica sand; US Silica, Ottawa, IL, USA) through the use of two-dimensional tank light transmission method (LTM). The contact angle (θ) and surface tension (γ) of two simulated plant exudate solutions (i.e., oxalate and citrate) and two soil component solutions (i.e., tannic acid and Suwannee River natural organic matter, SRNOM) were analyzed to determine the liquid-gas and liquid-solid interface characteristics of each. To determine if the unstable flow formations were dependent on the type and concentration of the simulated plant exudates and soil components, the analysis of the effects of the simulated plant exudate and soil component solutions were compared to a control solution (Hoagland nutrient solution with 0.01 M NaCl). Fingering flow patterns, vertical and horizontal water saturation profiles, water saturation at the fingertips, finger dimensions and velocity, and number of fingers were obtained using the light transmission method. Significant differences in the interface properties indicated a decrease between the control and the plant exudate and soil component solutions tested; specifically, the control (θ = 64.5° and γ = 75.75 mN m-1) samples exhibited a higher contact angle and surface tension than the low concentration of citrate (θ = 52.6° and γ = 70.8 mN m-1). Wetting front instability and fingering flow phenomena were reported in all infiltration experiments. The results showed that the plant exudates and soil components influenced the soil infiltration as differences in finger geometries, velocities, and water saturation profiles were detected when compared to the control. Among the tested solutions and concentrations of soil components, the largest finger width (10.19 cm

77 FR 48570 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving a Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-14

... Underlying Securities) of the NASDAQ Options Market rules.\\11\\ Additionally, the Target Component's and the...\\ Additionally, the Target Component's and the Benchmark Component's trading volume (in all markets in which the...-Regulatory Organizations; The NASDAQ Stock Market LLC; Order Approving a Proposed Rule Change Relating to the...

Two highly-related regulatory subunits of PP2A exert opposite effects on TGF-β/Activin/Nodal signalling

PubMed Central

Batut, Julie; Schmierer, Bernhard; Cao, Jing; Raftery, Laurel A.; Hill, Caroline S.; Howell, Michael

2016-01-01

Summary We identify Bα (PPP2R2A) and Bδ (PPP2R2D), two highly-related members of the B family of regulatory subunits of the protein phosphatase PP2A, as important modulators of TGF-β/Activin/Nodal signalling, which affect the pathway in opposite ways. Knockdown of Bα in Xenopus embryos or mammalian tissue culture cells suppresses TGF-β/Activin/Nodal-dependent responses, whereas knockdown of Bδ enhances these responses. Moreover, in Drosophila, overexpression of Smad2 rescues a severe wing phenotype caused by overexpression of the single Drosophila PP2A B subunit, Twins. We show that in vertebrates Bα enhances TGF-β/Activin/Nodal signalling by stabilising the basal levels of type I receptor, whereas Bδ negatively modulates these pathways by restricting receptor activity. Thus, these highly-related members of the same subfamily of PP2A regulatory subunits differentially regulate TGF-β/Activin/Nodal signalling to elicit opposing biological outcomes. PMID:18697906

Modeling gene regulatory network motifs using statecharts

PubMed Central

2012-01-01

Background Gene regulatory networks are widely used by biologists to describe the interactions among genes, proteins and other components at the intra-cellular level. Recently, a great effort has been devoted to give gene regulatory networks a formal semantics based on existing computational frameworks. For this purpose, we consider Statecharts, which are a modular, hierarchical and executable formal model widely used to represent software systems. We use Statecharts for modeling small and recurring patterns of interactions in gene regulatory networks, called motifs. Results We present an improved method for modeling gene regulatory network motifs using Statecharts and we describe the successful modeling of several motifs, including those which could not be modeled or whose models could not be distinguished using the method of a previous proposal. We model motifs in an easy and intuitive way by taking advantage of the visual features of Statecharts. Our modeling approach is able to simulate some interesting temporal properties of gene regulatory network motifs: the delay in the activation and the deactivation of the "output" gene in the coherent type-1 feedforward loop, the pulse in the incoherent type-1 feedforward loop, the bistability nature of double positive and double negative feedback loops, the oscillatory behavior of the negative feedback loop, and the "lock-in" effect of positive autoregulation. Conclusions We present a Statecharts-based approach for the modeling of gene regulatory network motifs in biological systems. The basic motifs used to build more complex networks (that is, simple regulation, reciprocal regulation, feedback loop, feedforward loop, and autoregulation) can be faithfully described and their temporal dynamics can be analyzed. PMID:22536967

Separation of the Components of a Commercial Analgesic Tablet: A Two-Week Sequence Comparing Purification by Two-Base Extraction and Column Chromatography

ERIC Educational Resources Information Center

Revell, Kevin D.

2011-01-01

A new laboratory experiment is described in which students compare two benchtop separation methods to isolate the three active components of the commercial analgesic Excedrin. In the two-week sequence, aspirin, acetaminophen, and caffeine are separated using either a two-base liquid-liquid extraction or silica column chromatography. Students then…

Two stages and three components of the postural preparation to action.

PubMed

Krishnan, Vennila; Aruin, Alexander S; Latash, Mark L

2011-07-01

Previous studies of postural preparation to action/perturbation have primarily focused on anticipatory postural adjustments (APAs), the changes in muscle activation levels resulting in the production of net forces and moments of force. We hypothesized that postural preparation to action consists of two stages: (1) Early postural adjustments (EPAs), seen a few hundred ms prior to an expected external perturbation and (2) APAs seen about 100 ms prior to the perturbation. We also hypothesized that each stage consists of three components, anticipatory synergy adjustments seen as changes in covariation of the magnitudes of commands to muscle groups (M-modes), changes in averaged across trials levels of muscle activation, and mechanical effects such as shifts of the center of pressure. Nine healthy participants were subjected to external perturbations created by a swinging pendulum while standing in a semi-squatting posture. Electrical activity of twelve trunk and leg muscles and displacements of the center of pressure were recorded and analyzed. Principal component analysis was used to identify four M-modes within the space of muscle activations using indices of integrated muscle activation. This analysis was performed twice, over two phases, 400-700 ms prior to the perturbation and over 200 ms just prior to the perturbation. Similar robust results were obtained using the data from both phases. An index of a multi-M-mode synergy stabilizing the center of pressure displacement was computed using the framework of the uncontrolled manifold hypothesis. The results showed high synergy indices during quiet stance. Each of the two stages started with a drop in the synergy index followed by a change in the averaged across trials activation levels in postural muscles. There was a very long electromechanical delay during the early postural adjustments and a much shorter delay during the APAs. Overall, the results support our main hypothesis on the two stages and three components

Implementation of two-component advective flow solution in XSPEC

NASA Astrophysics Data System (ADS)

Debnath, Dipak; Chakrabarti, Sandip K.; Mondal, Santanu

2014-05-01

Spectral and temporal properties of black hole candidates can be explained reasonably well using Chakrabarti-Titarchuk solution of two-component advective flow (TCAF). This model requires two accretion rates, namely the Keplerian disc accretion rate and the halo accretion rate, the latter being composed of a sub-Keplerian, low-angular-momentum flow which may or may not develop a shock. In this solution, the relevant parameter is the relative importance of the halo (which creates the Compton cloud region) rate with respect to the Keplerian disc rate (soft photon source). Though this model has been used earlier to manually fit data of several black hole candidates quite satisfactorily, for the first time, we made it user friendly by implementing it into XSPEC software of Goddard Space Flight Center (GSFC)/NASA. This enables any user to extract physical parameters of the accretion flows, such as two accretion rates, the shock location, the shock strength, etc., for any black hole candidate. We provide some examples of fitting a few cases using this model. Most importantly, unlike any other model, we show that TCAF is capable of predicting timing properties from the spectral fits, since in TCAF, a shock is responsible for deciding spectral slopes as well as quasi-periodic oscillation frequencies. L86

Acoustics of two-component porous materials with anisotropic tortuosity

NASA Astrophysics Data System (ADS)

Albers, Bettina; Wilmanski, Krzysztof

2012-11-01

The paper is devoted to the analysis of monochromatic waves in two-component poroelastic materials described by a Biot-like model whose stress-strain relations are isotropic but the permeability is anisotropic. This anisotropy is induced by the anisotropy of the tortuosity which is given by a second order symmetric tensor. This is a new feature of the model while in earlier papers only isotropic permeabilities were considered. We show that this new model describes four modes of propagation. For our special choice of orientation of the direction of propagation these are two pseudo longitudinal modes P1 and P2, one pseudo transversal mode S2 and one transversal mode S1. The latter becomes also pseudo transversal in the general case of anisotropy. We analyze the speeds of propagation and the attenuation of these waves as well as the polarization properties in dependence on the orientation of the principal directions of the tortuosity. We indicate the practical importance of different shear (transversal) modes of propagation in a possible new nondestructive test of geophysical materials.

78 FR 41434 - Proposed Revisions to Design of Structures, Components, Equipment and Systems

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-10

..., Components, Equipment and Systems AGENCY: Nuclear Regulatory Commission. ACTION: Standard review plan-draft... Systems, Piping Components and their Associated Supports,'' of NUREG-0800, ``Standard Review Plan for the Review of Safety Analysis Reports for Nuclear Power Plants: LWR Edition.'' DATES: Submit comments by...

A connecter-like factor, CacA, links RssB/RpoS and the CpxR/CpxA two-component system in Salmonella

PubMed Central

2012-01-01

Background Bacteria integrate numerous environmental stimuli when generating cellular responses. Increasing numbers of examples describe how one two-component system (TCS) responds to signals detected by the sensor of another TCS. However, the molecular mechanisms underlying this phenomenon remain poorly defined. Results Here, we report a connector-like factor that affects the activity of the CpxR/CpxA two-component system in Salmonella enterica serovar Typhimurium. We isolated a clone that induced the expression of a cpxP-lac gene fusion from a high-copy-number plasmid pool of random Salmonella genomic fragments. A 63-amino acid protein, CacA, was responsible for the CpxA/CpxR-dependent activation of the cpxP gene. The CpxR-activated genes cpxP and spy exhibited approximately 30% and 50% reductions in transcription, respectively, in a clean cacA deletion mutant strain in comparison to wild-type. From 33 response regulator (RR) deletion mutants, we identified that the RssB regulator represses cacA transcription. Substitution mutations in a conserved -10 region harboring the RNA polymerase recognition sequence, which is well conserved with a known RpoS -10 region consensus sequence, rendered the cacA promoter RpoS-independent. The CacA-mediated induction of cpxP transcription was affected in a trxA deletion mutant, which encodes thioredoxin 1, suggesting a role for cysteine thiol-disulfide exchange(s) in CacA-dependent Cpx activation. Conclusions We identified CacA as an activator of the CpxR/CpxA system in the plasmid clone. We propose that CacA may integrate the regulatory status of RssB/RpoS into the CpxR/CpxA system. Future investigations are necessary to thoroughly elucidate how CacA activates the CpxR/CpxA system. PMID:23031642

A connecter-like factor, CacA, links RssB/RpoS and the CpxR/CpxA two-component system in Salmonella.

PubMed

Kato, Akinori; Hayashi, Hironori; Nomura, Wataru; Emori, Haruka; Hagihara, Kei; Utsumi, Ryutaro

2012-10-02

Bacteria integrate numerous environmental stimuli when generating cellular responses. Increasing numbers of examples describe how one two-component system (TCS) responds to signals detected by the sensor of another TCS. However, the molecular mechanisms underlying this phenomenon remain poorly defined. Here, we report a connector-like factor that affects the activity of the CpxR/CpxA two-component system in Salmonella enterica serovar Typhimurium. We isolated a clone that induced the expression of a cpxP-lac gene fusion from a high-copy-number plasmid pool of random Salmonella genomic fragments. A 63-amino acid protein, CacA, was responsible for the CpxA/CpxR-dependent activation of the cpxP gene. The CpxR-activated genes cpxP and spy exhibited approximately 30% and 50% reductions in transcription, respectively, in a clean cacA deletion mutant strain in comparison to wild-type. From 33 response regulator (RR) deletion mutants, we identified that the RssB regulator represses cacA transcription. Substitution mutations in a conserved -10 region harboring the RNA polymerase recognition sequence, which is well conserved with a known RpoS -10 region consensus sequence, rendered the cacA promoter RpoS-independent. The CacA-mediated induction of cpxP transcription was affected in a trxA deletion mutant, which encodes thioredoxin 1, suggesting a role for cysteine thiol-disulfide exchange(s) in CacA-dependent Cpx activation. We identified CacA as an activator of the CpxR/CpxA system in the plasmid clone. We propose that CacA may integrate the regulatory status of RssB/RpoS into the CpxR/CpxA system. Future investigations are necessary to thoroughly elucidate how CacA activates the CpxR/CpxA system.

An infinite-order two-component relativistic Hamiltonian by a simple one-step transformation.

PubMed

Ilias, Miroslav; Saue, Trond

2007-02-14

The authors report the implementation of a simple one-step method for obtaining an infinite-order two-component (IOTC) relativistic Hamiltonian using matrix algebra. They apply the IOTC Hamiltonian to calculations of excitation and ionization energies as well as electric and magnetic properties of the radon atom. The results are compared to corresponding calculations using identical basis sets and based on the four-component Dirac-Coulomb Hamiltonian as well as Douglas-Kroll-Hess and zeroth-order regular approximation Hamiltonians, all implemented in the DIRAC program package, thus allowing a comprehensive comparison of relativistic Hamiltonians within the finite basis approximation.

Rac1 GTPase activates the WAVE regulatory complex through two distinct binding sites.

PubMed

Chen, Baoyu; Chou, Hui-Ting; Brautigam, Chad A; Xing, Wenmin; Yang, Sheng; Henry, Lisa; Doolittle, Lynda K; Walz, Thomas; Rosen, Michael K

2017-09-26

The Rho GTPase Rac1 activates the WAVE regulatory complex (WRC) to drive Arp2/3 complex-mediated actin polymerization, which underpins diverse cellular processes. Here we report the structure of a WRC-Rac1 complex determined by cryo-electron microscopy. Surprisingly, Rac1 is not located at the binding site on the Sra1 subunit of the WRC previously identified by mutagenesis and biochemical data. Rather, it binds to a distinct, conserved site on the opposite end of Sra1. Biophysical and biochemical data on WRC mutants confirm that Rac1 binds to both sites, with the newly identified site having higher affinity and both sites required for WRC activation. Our data reveal that the WRC is activated by simultaneous engagement of two Rac1 molecules, suggesting a mechanism by which cells may sense the density of active Rac1 at membranes to precisely control actin assembly.

Two-dimensional multi-component photometric decomposition of CALIFA galaxies

NASA Astrophysics Data System (ADS)

Méndez-Abreu, J.; Ruiz-Lara, T.; Sánchez-Menguiano, L.; de Lorenzo-Cáceres, A.; Costantin, L.; Catalán-Torrecilla, C.; Florido, E.; Aguerri, J. A. L.; Bland-Hawthorn, J.; Corsini, E. M.; Dettmar, R. J.; Galbany, L.; García-Benito, R.; Marino, R. A.; Márquez, I.; Ortega-Minakata, R. A.; Papaderos, P.; Sánchez, S. F.; Sánchez-Blazquez, P.; Spekkens, K.; van de Ven, G.; Wild, V.; Ziegler, B.

2017-02-01

We present a two-dimensional multi-component photometric decomposition of 404 galaxies from the Calar Alto Legacy Integral Field Area data release 3 (CALIFA-DR3). They represent all possible galaxies with no clear signs of interaction and not strongly inclined in the final CALIFA data release. Galaxies are modelled in the g, r, and I Sloan Digital Sky Survey (SDSS) images including, when appropriate, a nuclear point source, bulge, bar, and an exponential or broken disc component. We use a human-supervised approach to determine the optimal number of structures to be included in the fit. The dataset, including the photometric parameters of the CALIFA sample, is released together with statistical errors and a visual analysis of the quality of each fit. The analysis of the photometric components reveals a clear segregation of the structural composition of galaxies with stellar mass. At high masses (log (M⋆/M⊙) > 11), the galaxy population is dominated by galaxies modelled with a single Sérsic or a bulge+disc with a bulge-to-total (B/T) luminosity ratio B/T > 0.2. At intermediate masses (9.5 < log (M⋆/M⊙) < 11), galaxies described with bulge+disc but B/T < 0.2 are preponderant, whereas, at the low mass end (log (M⋆/M⊙) < 9.5), the prevailing population is constituted by galaxies modelled with either purediscs or nuclear point sources+discs (I.e., no discernible bulge). We obtain that 57% of the volume corrected sample of disc galaxies in the CALIFA sample host a bar. This bar fraction shows a significant drop with increasing galaxy mass in the range 9.5 < log (M⋆/M⊙) < 11.5. The analyses of the extended multi-component radial profile result in a volume-corrected distribution of 62%, 28%, and 10% for the so-called Type I (pure exponential), Type II (down-bending), and Type III (up-bending) disc profiles, respectively. These fractions are in discordance with previous findings. We argue that the different methodologies used to detect the breaks are the

Two different ways for waveguides and optoelectronics components on top of C-MOS

NASA Astrophysics Data System (ADS)

Fedeli, J. M.; Jeannot, S.; Kostrzewa, M.; Di Cioccio, L.; Jousseaume, V.; Orobtchouk, R.; Maury, P.; Zussy, M.

2006-02-01

While fabrication of photonic components at the wafer level is a long standing goal of integrated optics, new applications such as optical interconnects are introducing new challenges for waveguides and optoelectronic component fabrication. Indeed, global interconnects are expected to face severe limitations in the near future. To face this problem, optical links on top of a CMOS circuits could be an alternative. The critical points to perform an optical link on a chip are firstly the realization of compact passive optical distribution and secondly the report of optoelectronic components for the sources and detectors. This paper presents two different approaches for the integration of both waveguides and optoelectronic components. In a first "total bonding" approach, waveguides have been elaborated using classical "Silicon On Insulators" technology and then reported using molecular bonding on top off Si wafers. The S0I substrate was then chemically etched, after what InP dies were moleculary bonded on top of the waveguides. With this approach, optical components with low loses and a good equilibrium are demonsrated. Using molecular bonding, InP dies were reported with no degradation of the optoelectronic properties of the films. In a second approach, using PECVD silicon nitride or amorphous silicon coupled to PECVD silicon oxide, basic optical components are demonstrated. This low temperature technology is compatible with a microelectronic Back End process, allowing an integration of the waveguides directly on top of CMOS circuits. InP dies can then be bonded on top of the waveguides.

Two efficient label-equivalence-based connected-component labeling algorithms for 3-D binary images.

PubMed

He, Lifeng; Chao, Yuyan; Suzuki, Kenji

2011-08-01

Whenever one wants to distinguish, recognize, and/or measure objects (connected components) in binary images, labeling is required. This paper presents two efficient label-equivalence-based connected-component labeling algorithms for 3-D binary images. One is voxel based and the other is run based. For the voxel-based one, we present an efficient method of deciding the order for checking voxels in the mask. For the run-based one, instead of assigning each foreground voxel, we assign each run a provisional label. Moreover, we use run data to label foreground voxels without scanning any background voxel in the second scan. Experimental results have demonstrated that our voxel-based algorithm is efficient for 3-D binary images with complicated connected components, that our run-based one is efficient for those with simple connected components, and that both are much more efficient than conventional 3-D labeling algorithms.

Many-body physics in two-component Bose–Einstein condensates in a cavity: fragmented superradiance and polarization

NASA Astrophysics Data System (ADS)

Lode, Axel U. J.; Diorico, Fritz S.; Wu, RuGway; Molignini, Paolo; Papariello, Luca; Lin, Rui; Lévêque, Camille; Exl, Lukas; Tsatsos, Marios C.; Chitra, R.; Mauser, Norbert J.

2018-05-01

We consider laser-pumped one-dimensional two-component bosons in a parabolic trap embedded in a high-finesse optical cavity. Above a threshold pump power, the photons that populate the cavity modify the effective atom trap and mediate a coupling between the two components of the Bose–Einstein condensate. We calculate the ground state of the laser-pumped system and find different stages of self-organization depending on the power of the laser. The modified potential and the laser-mediated coupling between the atomic components give rise to rich many-body physics: an increase of the pump power triggers a self-organization of the atoms while an even larger pump power causes correlations between the self-organized atoms—the BEC becomes fragmented and the reduced density matrix acquires multiple macroscopic eigenvalues. In this fragmented superradiant state, the atoms can no longer be described as two-level systems and the mapping of the system to the Dicke model breaks down.

A Selective-Echo Method for Chemical-Shift Imaging of Two-Component Systems

NASA Astrophysics Data System (ADS)

Gerald, Rex E., II; Krasavin, Anatoly O.; Botto, Robert E.

A simple and effective method for selectively imaging either one of two chemical species in a two-component system is presented and demonstrated experimentally. The pulse sequence employed, selective- echo chemical- shift imaging (SECSI), is a hybrid (frequency-selective/ T1-contrast) technique that is executed in a short period of time, utilizes the full Boltzmann magnetization of each chemical species to form the corresponding image, and requires only hard pulses of quadrature phase. This approach provides a direct and unambiguous representation of the spatial distribution of the two chemical species. In addition, the performance characteristics and the advantages of the SECSI sequence are compared on a common basis to those of other pulse sequences.

Gauge-origin independent formalism of two-component relativistic framework based on unitary transformation in nuclear magnetic shielding constant

NASA Astrophysics Data System (ADS)

Hayami, Masao; Seino, Junji; Nakai, Hiromi

2018-03-01

This article proposes a gauge-origin independent formalism of the nuclear magnetic shielding constant in the two-component relativistic framework based on the unitary transformation. The proposed scheme introduces the gauge factor and the unitary transformation into the atomic orbitals. The two-component relativistic equation is formulated by block-diagonalizing the Dirac Hamiltonian together with gauge factors. This formulation is available for arbitrary relativistic unitary transformations. Then, the infinite-order Douglas-Kroll-Hess (IODKH) transformation is applied to the present formulation. Next, the analytical derivatives of the IODKH Hamiltonian for the evaluation of the nuclear magnetic shielding constant are derived. Results obtained from the numerical assessments demonstrate that the present formulation removes the gauge-origin dependence completely. Furthermore, the formulation with the IODKH transformation gives results that are close to those in four-component and other two-component relativistic schemes.

Regulatory Snapshots: integrative mining of regulatory modules from expression time series and regulatory networks.

PubMed

Gonçalves, Joana P; Aires, Ricardo S; Francisco, Alexandre P; Madeira, Sara C

2012-01-01

Explaining regulatory mechanisms is crucial to understand complex cellular responses leading to system perturbations. Some strategies reverse engineer regulatory interactions from experimental data, while others identify functional regulatory units (modules) under the assumption that biological systems yield a modular organization. Most modular studies focus on network structure and static properties, ignoring that gene regulation is largely driven by stimulus-response behavior. Expression time series are key to gain insight into dynamics, but have been insufficiently explored by current methods, which often (1) apply generic algorithms unsuited for expression analysis over time, due to inability to maintain the chronology of events or incorporate time dependency; (2) ignore local patterns, abundant in most interesting cases of transcriptional activity; (3) neglect physical binding or lack automatic association of regulators, focusing mainly on expression patterns; or (4) limit the discovery to a predefined number of modules. We propose Regulatory Snapshots, an integrative mining approach to identify regulatory modules over time by combining transcriptional control with response, while overcoming the above challenges. Temporal biclustering is first used to reveal transcriptional modules composed of genes showing coherent expression profiles over time. Personalized ranking is then applied to prioritize prominent regulators targeting the modules at each time point using a network of documented regulatory associations and the expression data. Custom graphics are finally depicted to expose the regulatory activity in a module at consecutive time points (snapshots). Regulatory Snapshots successfully unraveled modules underlying yeast response to heat shock and human epithelial-to-mesenchymal transition, based on regulations documented in the YEASTRACT and JASPAR databases, respectively, and available expression data. Regulatory players involved in functionally enriched

Regulatory Snapshots: Integrative Mining of Regulatory Modules from Expression Time Series and Regulatory Networks

PubMed Central

Gonçalves, Joana P.; Aires, Ricardo S.; Francisco, Alexandre P.; Madeira, Sara C.

2012-01-01

Explaining regulatory mechanisms is crucial to understand complex cellular responses leading to system perturbations. Some strategies reverse engineer regulatory interactions from experimental data, while others identify functional regulatory units (modules) under the assumption that biological systems yield a modular organization. Most modular studies focus on network structure and static properties, ignoring that gene regulation is largely driven by stimulus-response behavior. Expression time series are key to gain insight into dynamics, but have been insufficiently explored by current methods, which often (1) apply generic algorithms unsuited for expression analysis over time, due to inability to maintain the chronology of events or incorporate time dependency; (2) ignore local patterns, abundant in most interesting cases of transcriptional activity; (3) neglect physical binding or lack automatic association of regulators, focusing mainly on expression patterns; or (4) limit the discovery to a predefined number of modules. We propose Regulatory Snapshots, an integrative mining approach to identify regulatory modules over time by combining transcriptional control with response, while overcoming the above challenges. Temporal biclustering is first used to reveal transcriptional modules composed of genes showing coherent expression profiles over time. Personalized ranking is then applied to prioritize prominent regulators targeting the modules at each time point using a network of documented regulatory associations and the expression data. Custom graphics are finally depicted to expose the regulatory activity in a module at consecutive time points (snapshots). Regulatory Snapshots successfully unraveled modules underlying yeast response to heat shock and human epithelial-to-mesenchymal transition, based on regulations documented in the YEASTRACT and JASPAR databases, respectively, and available expression data. Regulatory players involved in functionally enriched

Generation of oscillating gene regulatory network motifs

NASA Astrophysics Data System (ADS)

van Dorp, M.; Lannoo, B.; Carlon, E.

2013-07-01

Using an improved version of an evolutionary algorithm originally proposed by François and Hakim [Proc. Natl. Acad. Sci. USAPNASA60027-842410.1073/pnas.0304532101 101, 580 (2004)], we generated small gene regulatory networks in which the concentration of a target protein oscillates in time. These networks may serve as candidates for oscillatory modules to be found in larger regulatory networks and protein interaction networks. The algorithm was run for 105 times to produce a large set of oscillating modules, which were systematically classified and analyzed. The robustness of the oscillations against variations of the kinetic rates was also determined, to filter out the least robust cases. Furthermore, we show that the set of evolved networks can serve as a database of models whose behavior can be compared to experimentally observed oscillations. The algorithm found three smallest (core) oscillators in which nonlinearities and number of components are minimal. Two of those are two-gene modules: the mixed feedback loop, already discussed in the literature, and an autorepressed gene coupled with a heterodimer. The third one is a single gene module which is competitively regulated by a monomer and a dimer. The evolutionary algorithm also generated larger oscillating networks, which are in part extensions of the three core modules and in part genuinely new modules. The latter includes oscillators which do not rely on feedback induced by transcription factors, but are purely of post-transcriptional type. Analysis of post-transcriptional mechanisms of oscillation may provide useful information for circadian clock research, as recent experiments showed that circadian rhythms are maintained even in the absence of transcription.

Different Evolutionary Modifications as a Guide to Rewire Two-Component Systems

PubMed Central

Krueger, Beate; Friedrich, Torben; Förster, Frank; Bernhardt, Jörg; Gross, Roy; Dandekar, Thomas

2012-01-01

Two-component systems (TCS) are short signalling pathways generally occurring in prokaryotes. They frequently regulate prokaryotic stimulus responses and thus are also of interest for engineering in biotechnology and synthetic biology. The aim of this study is to better understand and describe rewiring of TCS while investigating different evolutionary scenarios. Based on large-scale screens of TCS in different organisms, this study gives detailed data, concrete alignments, and structure analysis on three general modification scenarios, where TCS were rewired for new responses and functions: (i) exchanges in the sequence within single TCS domains, (ii) exchange of whole TCS domains; (iii) addition of new components modulating TCS function. As a result, the replacement of stimulus and promotor cassettes to rewire TCS is well defined exploiting the alignments given here. The diverged TCS examples are non-trivial and the design is challenging. Designed connector proteins may also be useful to modify TCS in selected cases. PMID:22586357

Transterm: a database to aid the analysis of regulatory sequences in mRNAs

PubMed Central

Jacobs, Grant H.; Chen, Augustine; Stevens, Stewart G.; Stockwell, Peter A.; Black, Michael A.; Tate, Warren P.; Brown, Chris M.

2009-01-01

Messenger RNAs, in addition to coding for proteins, may contain regulatory elements that affect how the protein is translated. These include protein and microRNA-binding sites. Transterm (http://mRNA.otago.ac.nz/Transterm.html) is a database of regions and elements that affect translation with two major unique components. The first is integrated results of analysis of general features that affect translation (initiation, elongation, termination) for species or strains in Genbank, processed through a standard pipeline. The second is curated descriptions of experimentally determined regulatory elements that function as translational control elements in mRNAs. Transterm focuses on protein binding sites, particularly those in 3′-untranslated regions (3′-UTR). For this release the interface has been extensively updated based on user feedback. The data is now accessible by strain rather than species, for example there are 10 Escherichia coli strains (genomes) analysed separately. In addition to providing a repository of data, the database also provides tools for users to query their own mRNA sequences. Users can search sequences for Transterm or user defined regulatory elements, including protein or miRNA targets. Transterm also provides a central core of links to related resources for complementary analyses. PMID:18984623

Two-component dark-bright solitons in three-dimensional atomic Bose-Einstein condensates.

PubMed

Wang, Wenlong; Kevrekidis, P G

2017-03-01

In the present work, we revisit two-component Bose-Einstein condensates in their fully three-dimensional (3D) form. Motivated by earlier studies of dark-bright solitons in the 1D case, we explore the stability of these structures in their fully 3D form in two variants. In one the dark soliton is planar and trapping a planar bright (disk) soliton. In the other case, a dark spherical shell soliton creates an effective potential in which a bright spherical shell of atoms is trapped in the second component. We identify these solutions as numerically exact states (up to a prescribed accuracy) and perform a Bogolyubov-de Gennes linearization analysis that illustrates that both structures can be dynamically stable in suitable intervals of sufficiently low chemical potentials. We corroborate this finding theoretically by analyzing the stability via degenerate perturbation theory near the linear limit of the system. When the solitary waves are found to be unstable, we explore their dynamical evolution via direct numerical simulations which, in turn, reveal wave forms that are more robust. Finally, using the SO(2) symmetry of the model, we produce multi-dark-bright planar or shell solitons involved in pairwise oscillatory motion.

Two-component Thermal Dust Emission Model: Application to the Planck HFI Maps

NASA Astrophysics Data System (ADS)

Meisner, Aaron M.; Finkbeiner, Douglas P.

2014-06-01

We present full-sky, 6.1 arcminute resolution maps of dust optical depth and temperature derived by fitting the Finkbeiner et al. (1999) two-component dust emission model to the Planck HFI and IRAS 100 micron maps. This parametrization of the far infrared thermal dust SED as the sum of two modified blackbodies serves as an important alternative to the commonly adopted single modified blackbody dust emission model. We expect our Planck-based maps of dust temperature and optical depth to form the basis for a next-generation, high-resolution extinction map which will additionally incorporate small-scale detail from WISE imaging.

THE IMPLICIT CONTRIBUTION OF SLAB MODES TO THE PERPENDICULAR DIFFUSION COEFFICIENT OF PARTICLES INTERACTING WITH TWO-COMPONENT TURBULENCE

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

Shalchi, A., E-mail: andreasm4@yahoo.com

2016-10-20

We explore the transport of energetic particles in two-component turbulence in which the stochastic magnetic field is assumed to be a superposition of slab and two-dimensional modes. It is known that in magnetostatic slab turbulence, the motion of particles across the mean magnetic field is subdiffusive. If a two-dimensional component is added, diffusion is recovered. It was also shown before that in two-component turbulence, the slab modes do not explicitly contribute to the perpendicular diffusion coefficient. In the current paper, the implicit contribution of slab modes is explored and it is shown that this contribution leads to a reduction ofmore » the perpendicular diffusion coefficient. This effect improves the agreement between simulations and analytical theory. Furthermore, the obtained results are relevant for investigations of diffusive shock acceleration.« less

A two-way street: regulatory interplay between RNA polymerase and nascent RNA structure

PubMed Central

Zhang, Jinwei; Landick, Robert

2016-01-01

The vectorial (5′-to-3′ at varying velocity) synthesis of RNA by cellular RNA polymerases creates a rugged kinetic landscape, demarcated by frequent, sometimes long-lived pauses. In addition to myriad gene-regulatory roles, these pauses temporally and spatially program the co-transcriptional, hierarchical folding of biologically active RNAs. Conversely, these RNA structures, which form inside or near the RNA exit channel, interact with the polymerase and adjacent protein factors to influence RNA synthesis by modulating pausing, termination, antitermination, and slippage. Here we review the evolutionary origin, mechanistic underpinnings, and regulatory consequences of this interplay between RNA polymerase and nascent RNA structure. We categorize and attempt to rationalize the extensive linkage between the transcriptional machinery and its product, and provide a framework for future studies. PMID:26822487

A Two-Way Street: Regulatory Interplay between RNA Polymerase and Nascent RNA Structure.

PubMed

Zhang, Jinwei; Landick, Robert

2016-04-01

The vectorial (5'-to-3' at varying velocity) synthesis of RNA by cellular RNA polymerases (RNAPs) creates a rugged kinetic landscape, demarcated by frequent, sometimes long-lived, pauses. In addition to myriad gene-regulatory roles, these pauses temporally and spatially program the co-transcriptional, hierarchical folding of biologically active RNAs. Conversely, these RNA structures, which form inside or near the RNA exit channel, interact with the polymerase and adjacent protein factors to influence RNA synthesis by modulating pausing, termination, antitermination, and slippage. Here, we review the evolutionary origin, mechanistic underpinnings, and regulatory consequences of this interplay between RNAP and nascent RNA structure. We categorize and rationalize the extensive linkage between the transcriptional machinery and its product, and provide a framework for future studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Multi-scale diffuse interface modeling of multi-component two-phase flow with partial miscibility

NASA Astrophysics Data System (ADS)

Kou, Jisheng; Sun, Shuyu

2016-08-01

In this paper, we introduce a diffuse interface model to simulate multi-component two-phase flow with partial miscibility based on a realistic equation of state (e.g. Peng-Robinson equation of state). Because of partial miscibility, thermodynamic relations are used to model not only interfacial properties but also bulk properties, including density, composition, pressure, and realistic viscosity. As far as we know, this effort is the first time to use diffuse interface modeling based on equation of state for modeling of multi-component two-phase flow with partial miscibility. In numerical simulation, the key issue is to resolve the high contrast of scales from the microscopic interface composition to macroscale bulk fluid motion since the interface has a nanoscale thickness only. To efficiently solve this challenging problem, we develop a multi-scale simulation method. At the microscopic scale, we deduce a reduced interfacial equation under reasonable assumptions, and then we propose a formulation of capillary pressure, which is consistent with macroscale flow equations. Moreover, we show that Young-Laplace equation is an approximation of this capillarity formulation, and this formulation is also consistent with the concept of Tolman length, which is a correction of Young-Laplace equation. At the macroscopical scale, the interfaces are treated as discontinuous surfaces separating two phases of fluids. Our approach differs from conventional sharp-interface two-phase flow model in that we use the capillary pressure directly instead of a combination of surface tension and Young-Laplace equation because capillarity can be calculated from our proposed capillarity formulation. A compatible condition is also derived for the pressure in flow equations. Furthermore, based on the proposed capillarity formulation, we design an efficient numerical method for directly computing the capillary pressure between two fluids composed of multiple components. Finally, numerical tests

IUE observations of the hot components in two symbiotic stars

NASA Technical Reports Server (NTRS)

Michalitsianos, A. G.; Hobbs, R. W.; Maran, S. P.; Kafatos, M.

1980-01-01

Recent IUE observations reveal striking differences in the UV spectra of two symbiotic stars, R Aqr and RW Hya. RW Hya is found to be an unexpectedly intense source of UV radiation. The measurements reported demonstrate the presence of a hot component in each star, supporting the view that each is a binary system with a luminous red primary and a hot, subluminous companion. In one case, the hot companion manifests itself by exciting a compact nebulosity; in the other case the continuous spectrum of the hot star is directly detected, while the continuum of nebulosity excited by the hot star is detected at longer wavelengths.

A magic bullet to specifically eliminate mutated mitochondrial genomes from patients' cells

PubMed Central

Moraes, Carlos T

2014-01-01

When mitochondrial diseases result from mutations found in the mitochondrial DNA, engineered mitochondrial-targeted nucleases such as mitochondrial-targeted zinc finger nucleases are shown to specifically eliminate the mutated molecules, leaving the wild-type mitochondrial DNA intact to replicate and restore normal copy number. In this issue, Gammage and colleagues successfully apply this improved technology on patients' cells with two types of genetic alterations responsible for neuropathy ataxia and retinitis pigmentosa (NARP) syndrome and Kearns Sayre syndrome and progressive external ophthalmoplegia (PEO). PMID:24623377

Simultaneous two component squeezing in generalized q-coherent states

NASA Technical Reports Server (NTRS)

Mcdermott, Roger J.; Solomon, Allan I.

1994-01-01

Using a generalization of the q-commutation relations, we develop a formalism in which it is possible to define generalized q-bosonic operators. This formalism includes both types of the usual q-deformed bosons as special cases. The coherent states of these operators show interesting and novel noise reduction properties including simultaneous squeezing in both field components, unlike the conventional case in which squeezing is permitted in only one component. This also contrasts with the usual quantum group deformation which also only permits one component squeezing.

The evolution of cichlid fish egg-spots is linked with a cis-regulatory change

PubMed Central

Santos, M. Emília; Braasch, Ingo; Boileau, Nicolas; Meyer, Britta S.; Sauteur, Loïc; Böhne, Astrid; Belting, Heinz-Georg; Affolter, Markus; Salzburger, Walter

2014-01-01

The origin of novel phenotypic characters is a key component in organismal diversification; yet, the mechanisms underlying the emergence of such evolutionary novelties are largely unknown. Here we examine the origin of egg-spots, an evolutionary innovation of the most species-rich group of cichlids, the haplochromines, where these conspicuous male fin colour markings are involved in mating. Applying a combination of RNAseq, comparative genomics and functional experiments, we identify two novel pigmentation genes, fhl2a and fhl2b, and show that especially the more rapidly evolving b-paralog is associated with egg-spot formation. We further find that egg-spot bearing haplochromines, but not other cichlids, feature a transposable element in the cis-regulatory region of fhl2b. Using transgenic zebrafish, we finally demonstrate that this region shows specific enhancer activities in iridophores, a type of pigment cells found in egg-spots, suggesting that a cis-regulatory change is causally linked to the gain of expression in egg-spot bearing haplochromines. PMID:25296686

A global regulatory science agenda for vaccines.

PubMed

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

2013-04-18

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

Genome-wide network of regulatory genes for construction of a chordate embryo.

PubMed

Shoguchi, Eiichi; Hamaguchi, Makoto; Satoh, Nori

2008-04-15

Animal development is controlled by gene regulation networks that are composed of sequence-specific transcription factors (TF) and cell signaling molecules (ST). Although housekeeping genes have been reported to show clustering in the animal genomes, whether the genes comprising a given regulatory network are physically clustered on a chromosome is uncertain. We examined this question in the present study. Ascidians are the closest living relatives of vertebrates, and their tadpole-type larva represents the basic body plan of chordates. The Ciona intestinalis genome contains 390 core TF genes and 119 major ST genes. Previous gene disruption assays led to the formulation of a basic chordate embryonic blueprint, based on over 3000 genetic interactions among 79 zygotic regulatory genes. Here, we mapped the regulatory genes, including all 79 regulatory genes, on the 14 pairs of Ciona chromosomes by fluorescent in situ hybridization (FISH). Chromosomal localization of upstream and downstream regulatory genes demonstrates that the components of coherent developmental gene networks are evenly distributed over the 14 chromosomes. Thus, this study provides the first comprehensive evidence that the physical clustering of regulatory genes, or their target genes, is not relevant for the genome-wide control of gene expression during development.

Measuring and Modeling the U.S. Regulatory Ecosystem

NASA Astrophysics Data System (ADS)

Bommarito, Michael J., II; Katz, Daniel Martin

2017-09-01

Over the last 23 years, the U.S. Securities and Exchange Commission has required over 34,000 companies to file over 165,000 annual reports. These reports, the so-called "Form 10-Ks," contain a characterization of a company's financial performance and its risks, including the regulatory environment in which a company operates. In this paper, we analyze over 4.5 million references to U.S. Federal Acts and Agencies contained within these reports to measure the regulatory ecosystem, in which companies are organisms inhabiting a regulatory environment. While individuals across the political, economic, and academic world frequently refer to trends in this regulatory ecosystem, far less attention has been paid to supporting such claims with large-scale, longitudinal data. In this paper, in addition to positing a model of regulatory ecosystems, we document an increase in the regulatory energy per filing, i.e., a warming "temperature." We also find that the diversity of the regulatory ecosystem has been increasing over the past two decades. These findings support the claim that regulatory activity and complexity are increasing, and this framework contributes an important step towards improving academic and policy discussions around legal complexity and regulation.

Composite fermion basis for two-component Bose gases

NASA Astrophysics Data System (ADS)

Meyer, Marius; Liabotro, Ola

The composite fermion (CF) construction is known to produce wave functions that are not necessarily orthogonal, or even linearly independent, after projection. While usually not a practical issue in the quantum Hall regime, we have previously shown that it presents a technical challenge for rotating Bose gases with low angular momentum. These are systems where the CF approach yield surprisingly good approximations to the exact eigenstates of weak short-range interactions, and so solving the problem of linearly dependent wave functions is of interest. It can also be useful for studying CF excitations for fermions. Here we present several ways of constructing a basis for the space of ``simple CF states'' for two-component rotating Bose gases in the lowest Landau level, and prove that they all give a basis. Using the basis, we study the structure of the lowest-lying state using so-called restricted wave functions. We also examine the scaling of the overlap between the exact and CF wave functions at the maximal possible angular momentum for simple states. This work was financially supported by the Research Council of Norway.

Salivaricin P, One of a Family of Two-Component Antilisterial Bacteriocins Produced by Intestinal Isolates of Lactobacillus salivarius▿

PubMed Central

Barrett, Eoin; Hayes, Maria; O'Connor, Paula; Gardiner, Gillian; Fitzgerald, Gerald F.; Stanton, Catherine; Ross, R. Paul; Hill, Colin

2007-01-01

Lactobacillus salivarius DPC6005, a porcine intestinal isolate, produces a two-component bacteriocin, salivaricin P, with homology to ABP-118 produced by a human probiotic L. salivarius strain. Indeed, molecular characterization revealed that while the peptides Sln1 and ABP-118α are identical, their companion peptides (Sln2 and ABP-118β, respectively) differ by two amino acids. This observation suggests that two-component bacteriocins may be a common feature of intestinal L. salivarius strains. PMID:17416691

Two-component Structure in the Entanglement Spectrum of Highly Excited States

NASA Astrophysics Data System (ADS)

Yang, Zhi-Cheng; Chamon, Claudio; Hamma, Alioscia; Mucciolo, Eduardo

We study the entanglement spectrum of highly excited eigenstates of two known models which exhibit a many-body localization transition, namely the one-dimensional random-field Heisenberg model and the quantum random energy model. Our results indicate that the entanglement spectrum shows a ``two-component'' structure: a universal part that is associated to Random Matrix Theory, and a non-universal part that is model dependent. The non-universal part manifests the deviation of the highly excited eigenstate from a true random state even in the thermalized phase where the Eigenstate Thermalization Hypothesis holds. The fraction of the spectrum containing the universal part decreases continuously as one approaches the critical point and vanishes in the localized phase in the thermodynamic limit. We use the universal part fraction to construct a new order parameter for the many-body delocalized-to-localized transition. Two toy models based on Rokhsar-Kivelson type wavefunctions are constructed and their entanglement spectra are shown to exhibit the same structure.

Calculations of atomic magnetic nuclear shielding constants based on the two-component normalized elimination of the small component method

NASA Astrophysics Data System (ADS)

Yoshizawa, Terutaka; Zou, Wenli; Cremer, Dieter

2017-04-01

A new method for calculating nuclear magnetic resonance shielding constants of relativistic atoms based on the two-component (2c), spin-orbit coupling including Dirac-exact NESC (Normalized Elimination of the Small Component) approach is developed where each term of the diamagnetic and paramagnetic contribution to the isotropic shielding constant σi s o is expressed in terms of analytical energy derivatives with regard to the magnetic field B and the nuclear magnetic moment 𝝁 . The picture change caused by renormalization of the wave function is correctly described. 2c-NESC/HF (Hartree-Fock) results for the σiso values of 13 atoms with a closed shell ground state reveal a deviation from 4c-DHF (Dirac-HF) values by 0.01%-0.76%. Since the 2-electron part is effectively calculated using a modified screened nuclear shielding approach, the calculation is efficient and based on a series of matrix manipulations scaling with (2M)3 (M: number of basis functions).

Enhanced Spectral Anisotropies Near the Proton-Cyclotron Scale: Possible Two-Component Structure in Hall-FLR MHD Turbulence Simulations

NASA Technical Reports Server (NTRS)

Ghosh, Sanjoy; Goldstein, Melvyn L.

2011-01-01

Recent analysis of the magnetic correlation function of solar wind fluctuations at 1 AU suggests the existence of two-component structure near the proton-cyclotron scale. Here we use two-and-one-half dimensional and three-dimensional compressible MHD models to look for two-component structure adjacent the proton-cyclotron scale. Our MHD system incorporates both Hall and Finite Larmor Radius (FLR) terms. We find that strong spectral anisotropies appear adjacent the proton-cyclotron scales depending on selections of initial condition and plasma beta. These anisotropies are enhancements on top of related anisotropies that appear in standard MHD turbulence in the presence of a mean magnetic field and are suggestive of one turbulence component along the inertial scales and another component adjacent the dissipative scales. We compute the relative strengths of linear and nonlinear accelerations on the velocity and magnetic fields to gauge the relative influence of terms that drive the system with wave-like (linear) versus turbulent (nonlinear) dynamics.

Production of pseudoinfectious yellow fever virus with a two-component genome.

PubMed

Shustov, Alexandr V; Mason, Peter W; Frolov, Ilya

2007-11-01

Application of genetically modified, deficient-in-replication flaviviruses that are incapable of developing productive, spreading infection is a promising means of designing safe and effective vaccines. Here we describe a two-component genome yellow fever virus (YFV) replication system in which each of the genomes encodes complete sets of nonstructural proteins that form the replication complex but expresses either only capsid or prM/E instead of the entire structural polyprotein. Upon delivery to the same cell, these genomes produce together all of the viral structural proteins, and cells release a combination of virions with both types of genomes packaged into separate particles. In tissue culture, this modified YFV can be further passaged at an escalating scale by using a high multiplicity of infection (MOI). However, at a low MOI, only one of the genomes is delivered into the cells, and infection cannot spread. The replicating prM/E-encoding genome produces extracellular E protein in the form of secreted subviral particles that are known to be an effective immunogen. The presented strategy of developing viruses defective in replication might be applied to other flaviviruses, and these two-component genome viruses can be useful for diagnostic or vaccine applications, including the delivery and expression of heterologous genes. In addition, the achieved separation of the capsid-coding sequence and the cyclization signal in the YFV genome provides a new means for studying the mechanism of the flavivirus packaging process.

The mechanism of signal transduction by two-component systems.

PubMed

Casino, Patricia; Rubio, Vicente; Marina, Alberto

2010-12-01

Two-component systems, composed of a homodimeric histidine kinase (HK) and a response regulator (RR), are major signal transduction devices in bacteria. Typically the signal triggers HK autophosphorylation at one His residue, followed by phosphoryl transfer from the phospho-His to an Asp residue in the RR. Signal extinction frequently involves phospho-RR dephosphorylation by a phosphatase activity of the HK. Our understanding of these reactions and of the determinants of partner specificity among HK-RR couples has been greatly increased by recent crystal structures and biochemical experiments on HK-RR complexes. Cis-autophosphorylation (one subunit phosphorylates itself) occurs in some HKs while trans-autophosphorylation takes place in others. We review and integrate this new information, discuss the mechanism of the three reactions and propose a model for transmembrane signaling by these systems. Copyright © 2010 Elsevier Ltd. All rights reserved.

Regulatory Mechanisms Underlying Oil Palm Fruit Mesocarp Maturation, Ripening, and Functional Specialization in Lipid and Carotenoid Metabolism1[W][OA

PubMed Central

Tranbarger, Timothy J.; Dussert, Stéphane; Joët, Thierry; Argout, Xavier; Summo, Marilyne; Champion, Antony; Cros, David; Omore, Alphonse; Nouy, Bruno; Morcillo, Fabienne

2011-01-01

Fruit provide essential nutrients and vitamins for the human diet. Not only is the lipid-rich fleshy mesocarp tissue of the oil palm (Elaeis guineensis) fruit the main source of edible oil for the world, but it is also the richest dietary source of provitamin A. This study examines the transcriptional basis of these two outstanding metabolic characters in the oil palm mesocarp. Morphological, cellular, biochemical, and hormonal features defined key phases of mesocarp development. A 454 pyrosequencing-derived transcriptome was then assembled for the developmental phases preceding and during maturation and ripening, when high rates of lipid and carotenoid biosynthesis occur. A total of 2,629 contigs with differential representation revealed coordination of metabolic and regulatory components. Further analysis focused on the fatty acid and triacylglycerol assembly pathways and during carotenogenesis. Notably, a contig similar to the Arabidopsis (Arabidopsis thaliana) seed oil transcription factor WRINKLED1 was identified with a transcript profile coordinated with those of several fatty acid biosynthetic genes and the high rates of lipid accumulation, suggesting some common regulatory features between seeds and fruits. We also focused on transcriptional regulatory networks of the fruit, in particular those related to ethylene transcriptional and GLOBOSA/PISTILLATA-like proteins in the mesocarp and a central role for ethylene-coordinated transcriptional regulation of type VII ethylene response factors during ripening. Our results suggest that divergence has occurred in the regulatory components in this monocot fruit compared with those identified in the dicot tomato (Solanum lycopersicum) fleshy fruit model. PMID:21487046

Similar bowtie structures and distinct largest strong components are identified in the transcriptional regulatory networks of Arabidopsis thaliana during photomorphogenesis and heat shock.

PubMed

Luo, Shitao; Zhang, Fengming; Ruan, Yingfei; Li, Jie; Zhang, Zheng; Sun, Yan; Deng, Shixiong; Peng, Rui

2018-06-01

Photomorphogenesis and heat shock are critical biological processes of plants. A recent research constructed the transcriptional regulatory networks (TRNs) of Arabidopsis thaliana during these processes using DNase-seq. In this study, by strong decomposition, we revealed that each of these TRNs can be represented as a similar bowtie structure with only one non-trivial and distinct strong component. We further identified distinct patterns of variation of a few light-related genes in these bowtie structures during photomorphogenesis. These results suggest that bowtie structure may be a common property of TRNs of plants, and distinct variation patterns of genes in bowtie structures of TRNs during biological processes may reflect distinct functions. Overall, our study provides an insight into the molecular mechanisms underlying photomorphogenesis and heat shock, and emphasizes the necessity to investigate the strong connectivity structures while studying TRNs. Copyright © 2018 Elsevier B.V. All rights reserved.

76 FR 13928 - Amendment to the International Traffic in Arms Regulations: Replacement Parts/Components and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-15

... International Traffic in Arms Regulations: Replacement Parts/Components and Incorporated Articles AGENCY... incorporated articles. DATES: The Department of State will accept comments on this proposed rule until April 14... Controls Policy, Attn: Regulatory Changes--Replacement Parts/Components and Incorporated Articles, Bureau...

Two-component end mills with multilayer composite nano-structured coatings as a viable alternative to monolithic carbide end mills

NASA Astrophysics Data System (ADS)

Vereschaka, Alexey; Mokritskii, Boris; Mokritskaya, Elena; Sharipov, Oleg; Oganyan, Maksim

2018-03-01

The paper deals with the challenges of the application of two-component end mills, which represent a combination of a carbide cutting part and a shank made of cheaper structural material. The calculations of strains and deformations of composite mills were carried out in comparison with solid carbide mills, with the use of the finite element method. The study also involved the comparative analysis of accuracy parameters of machining with monolithic mills and two-component mills with various shank materials. As a result of the conducted cutting tests in milling aluminum alloy with monolithic and two-component end mills with specially developed multilayer composite nano-structured coatings, it has been found that the use of such coatings can reduce strains and, correspondingly, deformations, which can improve the accuracy of machining. Thus, the application of two-component end mills with multilayer composite nano-structured coatings can provide a reduction in the cost of machining while maintaining or even improving the tool life and machining accuracy parameters.

Integrating non-coding RNAs in JAK-STAT regulatory networks

PubMed Central

Witte, Steven; Muljo, Stefan A

2014-01-01

Being a well-characterized pathway, JAK-STAT signaling serves as a valuable paradigm for studying the architecture of gene regulatory networks. The discovery of untranslated or non-coding RNAs, namely microRNAs and long non-coding RNAs, provides an opportunity to elucidate their roles in such networks. In principle, these regulatory RNAs can act as downstream effectors of the JAK-STAT pathway and/or affect signaling by regulating the expression of JAK-STAT components. Examples of interactions between signaling pathways and non-coding RNAs have already emerged in basic cell biology and human diseases such as cancer, and can potentially guide the identification of novel biomarkers or drug targets for medicine. PMID:24778925

Two structural components in CNGA3 support regulation of cone CNG channels by phosphoinositides.

PubMed

Dai, Gucan; Peng, Changhong; Liu, Chunming; Varnum, Michael D

2013-04-01

Cyclic nucleotide-gated (CNG) channels in retinal photoreceptors play a crucial role in vertebrate phototransduction. The ligand sensitivity of photoreceptor CNG channels is adjusted during adaptation and in response to paracrine signals, but the mechanisms involved in channel regulation are only partly understood. Heteromeric cone CNGA3 (A3) + CNGB3 (B3) channels are inhibited by membrane phosphoinositides (PIP(n)), including phosphatidylinositol 3,4,5-triphosphate (PIP(3)) and phosphatidylinositol 4,5-bisphosphate (PIP(2)), demonstrating a decrease in apparent affinity for cyclic guanosine monophosphate (cGMP). Unlike homomeric A1 or A2 channels, A3-only channels paradoxically did not show a decrease in apparent affinity for cGMP after PIP(n) application. However, PIP(n) induced an ∼2.5-fold increase in cAMP efficacy for A3 channels. The PIP(n)-dependent change in cAMP efficacy was abolished by mutations in the C-terminal region (R643Q/R646Q) or by truncation distal to the cyclic nucleotide-binding domain (613X). In addition, A3-613X unmasked a threefold decrease in apparent cGMP affinity with PIP(n) application to homomeric channels, and this effect was dependent on conserved arginines within the N-terminal region of A3. Together, these results indicate that regulation of A3 subunits by phosphoinositides exhibits two separable components, which depend on structural elements within the N- and C-terminal regions, respectively. Furthermore, both N and C regulatory modules in A3 supported PIP(n) regulation of heteromeric A3+B3 channels. B3 subunits were not sufficient to confer PIP(n) sensitivity to heteromeric channels formed with PIP(n)-insensitive A subunits. Finally, channels formed by mixtures of PIP(n)-insensitive A3 subunits, having complementary mutations in N- and/or C-terminal regions, restored PIP(n) regulation, implying that intersubunit N-C interactions help control the phosphoinositide sensitivity of cone CNG channels.

Two structural components in CNGA3 support regulation of cone CNG channels by phosphoinositides

PubMed Central

Dai, Gucan; Peng, Changhong; Liu, Chunming

2013-01-01

Cyclic nucleotide-gated (CNG) channels in retinal photoreceptors play a crucial role in vertebrate phototransduction. The ligand sensitivity of photoreceptor CNG channels is adjusted during adaptation and in response to paracrine signals, but the mechanisms involved in channel regulation are only partly understood. Heteromeric cone CNGA3 (A3) + CNGB3 (B3) channels are inhibited by membrane phosphoinositides (PIPn), including phosphatidylinositol 3,4,5-triphosphate (PIP3) and phosphatidylinositol 4,5-bisphosphate (PIP2), demonstrating a decrease in apparent affinity for cyclic guanosine monophosphate (cGMP). Unlike homomeric A1 or A2 channels, A3-only channels paradoxically did not show a decrease in apparent affinity for cGMP after PIPn application. However, PIPn induced an ∼2.5-fold increase in cAMP efficacy for A3 channels. The PIPn-dependent change in cAMP efficacy was abolished by mutations in the C-terminal region (R643Q/R646Q) or by truncation distal to the cyclic nucleotide-binding domain (613X). In addition, A3-613X unmasked a threefold decrease in apparent cGMP affinity with PIPn application to homomeric channels, and this effect was dependent on conserved arginines within the N-terminal region of A3. Together, these results indicate that regulation of A3 subunits by phosphoinositides exhibits two separable components, which depend on structural elements within the N- and C-terminal regions, respectively. Furthermore, both N and C regulatory modules in A3 supported PIPn regulation of heteromeric A3+B3 channels. B3 subunits were not sufficient to confer PIPn sensitivity to heteromeric channels formed with PIPn-insensitive A subunits. Finally, channels formed by mixtures of PIPn-insensitive A3 subunits, having complementary mutations in N- and/or C-terminal regions, restored PIPn regulation, implying that intersubunit N–C interactions help control the phosphoinositide sensitivity of cone CNG channels. PMID:23530136

Two-component vector solitons in defocusing Kerr-type media with spatially modulated nonlinearity

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

Zhong, Wei-Ping, E-mail: zhongwp6@126.com; Texas A and M University at Qatar, P.O. Box 23874 Doha; Belić, Milivoj

2014-12-15

We present a class of exact solutions to the coupled (2+1)-dimensional nonlinear Schrödinger equation with spatially modulated nonlinearity and a special external potential, which describe the evolution of two-component vector solitons in defocusing Kerr-type media. We find a robust soliton solution, constructed with the help of Whittaker functions. For specific choices of the topological charge, the radial mode number and the modulation depth, the solitons may exist in various forms, such as the half-moon, necklace-ring, and sawtooth vortex-ring patterns. Our results show that the profile of such solitons can be effectively controlled by the topological charge, the radial mode number,more » and the modulation depth. - Highlights: • Two-component vector soliton clusters in defocusing Kerr-type media are reported. • These soliton clusters are constructed with the help of Whittaker functions. • The half-moon, necklace-ring and vortex-ring patterns are found. • The profile of these solitons can be effectively controlled by three soliton parameters.« less

45 CFR 17.4 - Regulatory investigations and trial-type proceedings.

Code of Federal Regulations, 2011 CFR

2011-10-01

... RELEASE OF ADVERSE INFORMATION TO NEWS MEDIA § 17.4 Regulatory investigations and trial-type proceedings... economic harm may occur unless the public is notified immediately, it may release information to news media... operating component shall rely on the news media to the extent necessary to provide such notice even though...

45 CFR 17.4 - Regulatory investigations and trial-type proceedings.

Code of Federal Regulations, 2010 CFR

2010-10-01

... RELEASE OF ADVERSE INFORMATION TO NEWS MEDIA § 17.4 Regulatory investigations and trial-type proceedings... economic harm may occur unless the public is notified immediately, it may release information to news media... operating component shall rely on the news media to the extent necessary to provide such notice even though...

45 CFR 17.4 - Regulatory investigations and trial-type proceedings.

Code of Federal Regulations, 2012 CFR

2012-10-01

... RELEASE OF ADVERSE INFORMATION TO NEWS MEDIA § 17.4 Regulatory investigations and trial-type proceedings... economic harm may occur unless the public is notified immediately, it may release information to news media... operating component shall rely on the news media to the extent necessary to provide such notice even though...

45 CFR 17.4 - Regulatory investigations and trial-type proceedings.

Code of Federal Regulations, 2013 CFR

2013-10-01

... RELEASE OF ADVERSE INFORMATION TO NEWS MEDIA § 17.4 Regulatory investigations and trial-type proceedings... economic harm may occur unless the public is notified immediately, it may release information to news media... operating component shall rely on the news media to the extent necessary to provide such notice even though...

45 CFR 17.4 - Regulatory investigations and trial-type proceedings.

Code of Federal Regulations, 2014 CFR

2014-10-01

... RELEASE OF ADVERSE INFORMATION TO NEWS MEDIA § 17.4 Regulatory investigations and trial-type proceedings... economic harm may occur unless the public is notified immediately, it may release information to news media... operating component shall rely on the news media to the extent necessary to provide such notice even though...

Investigation of low-latitude hydrogen emission in terms of a two-component interstellar gas model

NASA Technical Reports Server (NTRS)

Baker, P. L.; Burton, W. B.

1975-01-01

High-resolution 21-cm hydrogen line observations at low galactic latitude are analyzed to determine the large-scale distribution of galactic hydrogen. Distribution parameters are found by model fitting, optical depth effects are computed using a two-component gas model suggested by the observations, and calculations are made for a one-component uniform spin-temperature gas model to show the systematic departures between this model and data obtained by incorrect treatment of the optical depth effects. Synthetic 21-cm line profiles are computed from the two-component model, and the large-scale trends of the observed emission profiles are reproduced together with the magnitude of the small-scale emission irregularities. Values are determined for the thickness of the galactic hydrogen disk between half density points, the total observed neutral hydrogen mass of the galaxy, and the central number density of the intercloud hydrogen atoms. It is shown that typical hydrogen clouds must be between 1 and 13 pc in diameter and that optical thinness exists on large-scale despite the presence of optically thin gas.

Expression of Genes Involved in Bacteriocin Production and Self-Resistance in Lactobacillus brevis 174A Is Mediated by Two Regulatory Proteins.

PubMed

Noda, Masafumi; Miyauchi, Rumi; Danshiitsoodol, Narandalai; Matoba, Yasuyuki; Kumagai, Takanori; Sugiyama, Masanori

2018-04-01

We have previously shown that the lactic acid bacterium Lactobacillus brevis 174A, isolated from Citrus iyo fruit, produces a bacteriocin designated brevicin 174A, which is comprised of two antibacterial polypeptides (designated brevicins 174A-β and 174A-γ). We have also found a gene cluster, composed of eight open reading frames (ORFs), that contains genes for the biosynthesis of brevicin 174A, self-resistance to its own bacteriocin, and two transcriptional regulatory proteins. Some lactic acid bacterial strains have a system to start the production of bacteriocin at an adequate stage of growth. Generally, the system consists of a membrane-bound histidine protein kinase (HPK) that senses a specific environmental stimulus and a corresponding response regulator (RR) that mediates the cellular response. We have previously shown that although the HPK- and RR-encoding genes are not found on the brevicin 174A biosynthetic gene cluster in the 174A strain, two putative regulatory genes, designated breD and breG , are in the gene cluster. In the present study, we demonstrate that the expression of brevicin 174A production and self-resistance is positively controlled by two transcriptional regulatory proteins, designated BreD and BreG. BreD is expressed together with BreE as the self-resistance determinant of L. brevis 174A. DNase I footprinting analysis and a promoter assay demonstrated that BreD binds to the breED promoter as a positive autoregulator. The present study also demonstrates that BreG, carrying a transmembrane domain, binds to the common promoter of breB and breC , encoding brevicins 174A-β and 174A-γ, respectively, for positive regulation. IMPORTANCE The problem of the appearance of bacteria that are resistant to practical antibiotics and the increasing demand for safe foods have increased interest in replacing conventional antibiotics with bacteriocin produced by the lactic acid bacteria. This antibacterial substance can inhibit the growth of pathogenic

Retention Forces between Titanium and Zirconia Components of Two-Part Implant Abutments with Different Techniques of Surface Modification.

PubMed

von Maltzahn, Nadine Freifrau; Holstermann, Jan; Kohorst, Philipp

2016-08-01

The adhesive connection between titanium base and zirconia coping of two-part abutments may be responsible for the failure rate. A high mechanical stability between both components is essential for the long-term success. The aim of the present in-vitro study was to evaluate the influence of different surface modification techniques and resin-based luting agents on the retention forces between titanium and zirconia components in two-part implant abutments. A total of 120 abutments with a titanium base bonded to a zirconia coping were investigated. Two different resin-based luting agents (Panavia F 2.0 and RelyX Unicem) and six different surface modifications were used to fix these components, resulting in 12 test groups (n = 10). The surface of the test specimens was mechanically pretreated with aluminium oxide blasting in combination with application of two surface activating primers (Alloy Primer, Clearfil Ceramic Primer) or a tribological conditioning (Rocatec), respectively. All specimens underwent 10,000 thermal cycles between 5°C and 55°C in a moist environment. A pull-off test was then conducted to determine retention forces between the titanium and zirconia components, and statistical analysis was performed (two-way anova). Finally, fracture surfaces were analyzed by light and scanning electron microscopy. No significant differences were found between Panavia F 2.0 and RelyX Unicem. However, the retention forces were significantly influenced by the surface modification technique used (p < 0.001). For both luting agents, the highest retention forces were found when adhesion surfaces of both the titanium bases and the zirconia copings were pretreated with aluminium oxide blasting, and with the application of Clearfil Ceramic Primer. Surface modification techniques crucially influence the retention forces between titanium and zirconia components in two-part implant abutments. All adhesion surfaces should be pretreated by sandblasting. Moreover, a

BayesPI-BAR: a new biophysical model for characterization of regulatory sequence variations

PubMed Central

Wang, Junbai; Batmanov, Kirill

2015-01-01

Sequence variations in regulatory DNA regions are known to cause functionally important consequences for gene expression. DNA sequence variations may have an essential role in determining phenotypes and may be linked to disease; however, their identification through analysis of massive genome-wide sequencing data is a great challenge. In this work, a new computational pipeline, a Bayesian method for protein–DNA interaction with binding affinity ranking (BayesPI-BAR), is proposed for quantifying the effect of sequence variations on protein binding. BayesPI-BAR uses biophysical modeling of protein–DNA interactions to predict single nucleotide polymorphisms (SNPs) that cause significant changes in the binding affinity of a regulatory region for transcription factors (TFs). The method includes two new parameters (TF chemical potentials or protein concentrations and direct TF binding targets) that are neglected by previous methods. The new method is verified on 67 known human regulatory SNPs, of which 47 (70%) have predicted true TFs ranked in the top 10. Importantly, the performance of BayesPI-BAR, which uses principal component analysis to integrate multiple predictions from various TF chemical potentials, is found to be better than that of existing programs, such as sTRAP and is-rSNP, when evaluated on the same SNPs. BayesPI-BAR is a publicly available tool and is able to carry out parallelized computation, which helps to investigate a large number of TFs or SNPs and to detect disease-associated regulatory sequence variations in the sea of genome-wide noncoding regions. PMID:26202972

TWO DISTINCT-ABSORPTION X-RAY COMPONENTS FROM TYPE IIn SUPERNOVAE: EVIDENCE FOR ASPHERICITY IN THE CIRCUMSTELLAR MEDIUM

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

Katsuda, Satoru; Tsuboi, Yohko; Maeda, Keiichi

2016-12-01

We present multi-epoch X-ray spectral observations of three Type IIn supernovae (SNe), SN 2005kd, SN 2006jd, and SN 2010jl, acquired with Chandra , XMM-Newton , Suzaku , and Swift . Previous extensive X-ray studies of SN 2010jl have revealed that X-ray spectra are dominated by thermal emission, which likely arises from a hot plasma heated by a forward shock propagating into a massive circumstellar medium (CSM). Interestingly, an additional soft X-ray component was required to reproduce the spectra at a period of ∼1–2 years after the SN explosion. Although this component is likely associated with the SN, its origin remained an open question. Wemore » find a similar, additional soft X-ray component from the other two SNe IIn as well. Given this finding, we present a new interpretation for the origin of this component; it is thermal emission from a forward shock essentially identical to the hard X-ray component, but directly reaches us from a void of the dense CSM. Namely, the hard and soft components are responsible for the heavily and moderately absorbed components, respectively. The co-existence of the two components with distinct absorptions as well as the delayed emergence of the moderately absorbed X-ray component could be evidence for asphericity of the CSM. We show that the X-ray spectral evolution can be qualitatively explained by considering a torus-like geometry for the dense CSM. Based on our X-ray spectral analyses, we estimate the radius of the torus-like CSM to be on the order of ∼5 × 10{sup 16} cm.« less

Two negative cis-regulatory regions involved in fruit-specific promoter activity from watermelon (Citrullus vulgaris S.).

PubMed

Yin, Tao; Wu, Hanying; Zhang, Shanglong; Lu, Hongyu; Zhang, Lingxiao; Xu, Yong; Chen, Daming; Liu, Jingmei

2009-01-01

A 1.8 kb 5'-flanking region of the large subunit of ADP-glucose pyrophosphorylase, isolated from watermelon (Citrullus vulgaris S.), has fruit-specific promoter activity in transgenic tomato plants. Two negative regulatory regions, from -986 to -959 and from -472 to -424, were identified in this promoter region by fine deletion analyses. Removal of both regions led to constitutive expression in epidermal cells. Gain-of-function experiments showed that these two regions were sufficient to inhibit RFP (red fluorescent protein) expression in transformed epidermal cells when fused to the cauliflower mosaic virus (CaMV) 35S minimal promoter. Gel mobility shift experiments demonstrated the presence of leaf nuclear factors that interact with these two elements. A TCCAAAA motif was identified in these two regions, as well as one in the reverse orientation, which was confirmed to be a novel specific cis-element. A quantitative beta-glucuronidase (GUS) activity assay of stable transgenic tomato plants showed that the activities of chimeric promoters harbouring only one of the two cis-elements, or both, were approximately 10-fold higher in fruits than in leaves. These data confirm that the TCCAAAA motif functions as a fruit-specific element by inhibiting gene expression in leaves.

Two negative cis-regulatory regions involved in fruit-specific promoter activity from watermelon (Citrullus vulgaris S.)

PubMed Central

Yin, Tao; Wu, Hanying; Zhang, Shanglong; Liu, Jingmei; Lu, Hongyu; Zhang, Lingxiao; Xu, Yong; Chen, Daming

2009-01-01

A 1.8 kb 5′-flanking region of the large subunit of ADP-glucose pyrophosphorylase, isolated from watermelon (Citrullus vulgaris S.), has fruit-specific promoter activity in transgenic tomato plants. Two negative regulatory regions, from –986 to –959 and from –472 to –424, were identified in this promoter region by fine deletion analyses. Removal of both regions led to constitutive expression in epidermal cells. Gain-of-function experiments showed that these two regions were sufficient to inhibit RFP (red fluorescent protein) expression in transformed epidermal cells when fused to the cauliflower mosaic virus (CaMV) 35S minimal promoter. Gel mobility shift experiments demonstrated the presence of leaf nuclear factors that interact with these two elements. A TCCAAAA motif was identified in these two regions, as well as one in the reverse orientation, which was confirmed to be a novel specific cis-element. A quantitative β-glucuronidase (GUS) activity assay of stable transgenic tomato plants showed that the activities of chimeric promoters harbouring only one of the two cis-elements, or both, were ∼10-fold higher in fruits than in leaves. These data confirm that the TCCAAAA motif functions as a fruit-specific element by inhibiting gene expression in leaves. PMID:19073962

Subnuclear organization and trafficking of regulatory proteins: implications for biological control and cancer.

PubMed

Stein, G S; van Wijnen, A J; Stein, J L; Lian, J B; Montecino, M; Zaidi, K; Javed, A

2000-01-01

The regulated and regulatory components that interrelate nuclear structure and function must be experimentally established. A formidable challenge is to define further the control of transcription factor targeting to acceptor sites associated with the nuclear matrix. It will be important to determine whether acceptor proteins are associated with a pre-existing core-filament structural lattice or whether a compositely organized scaffold of regulatory factors is dynamically assembled. An inclusive model for all steps in the targeting of proteins to subnuclear sites cannot yet be proposed. However, this model must account for the apparent diversity of intranuclear targeting signals. It is also important to assess the extent to which regulatory discrimination is mediated by subnuclear domain-specific trafficking signals. Furthermore, the checkpoints that monitor subnuclear distribution of regulatory factors and the sorting steps that ensure both structural and functional fidelity of nuclear domains in which replication and expression of genes occur must be biochemically and mechanistically defined. There is emerging recognition that placement of regulatory components of gene expression must be temporally and spatially coordinated to facilitate biological control. The consequences of breaches in nuclear structure-function relationships are observed in an expanding series of diseases that include cancer [Weis et al., 1994; Rogaia et al., 1997; Yano et al., 1997; Rowley, 1998; Zeng et al., 1998; McNeil et al., 1999; Tao and Levine, 1999a] and neurological disorders [Skinner et al., 1997]. As the repertoire of architecture-associated regulatory factors and cofactors expands, workers in the field are becoming increasingly confident that nuclear organization contributes significantly to control of transcription. To gain increased appreciation for the complexities of subnuclear organization and gene regulation, we must continue to characterize mechanisms that direct

Multi-scale diffuse interface modeling of multi-component two-phase flow with partial miscibility

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

Kou, Jisheng; Sun, Shuyu, E-mail: shuyu.sun@kaust.edu.sa; School of Mathematics and Statistics, Xi'an Jiaotong University, Xi'an 710049

2016-08-01

In this paper, we introduce a diffuse interface model to simulate multi-component two-phase flow with partial miscibility based on a realistic equation of state (e.g. Peng–Robinson equation of state). Because of partial miscibility, thermodynamic relations are used to model not only interfacial properties but also bulk properties, including density, composition, pressure, and realistic viscosity. As far as we know, this effort is the first time to use diffuse interface modeling based on equation of state for modeling of multi-component two-phase flow with partial miscibility. In numerical simulation, the key issue is to resolve the high contrast of scales from themore » microscopic interface composition to macroscale bulk fluid motion since the interface has a nanoscale thickness only. To efficiently solve this challenging problem, we develop a multi-scale simulation method. At the microscopic scale, we deduce a reduced interfacial equation under reasonable assumptions, and then we propose a formulation of capillary pressure, which is consistent with macroscale flow equations. Moreover, we show that Young–Laplace equation is an approximation of this capillarity formulation, and this formulation is also consistent with the concept of Tolman length, which is a correction of Young–Laplace equation. At the macroscopical scale, the interfaces are treated as discontinuous surfaces separating two phases of fluids. Our approach differs from conventional sharp-interface two-phase flow model in that we use the capillary pressure directly instead of a combination of surface tension and Young–Laplace equation because capillarity can be calculated from our proposed capillarity formulation. A compatible condition is also derived for the pressure in flow equations. Furthermore, based on the proposed capillarity formulation, we design an efficient numerical method for directly computing the capillary pressure between two fluids composed of multiple components. Finally

Precision laser surveying instrument using atmospheric turbulence compensation by determining the absolute displacement between two laser beam components

DOEpatents

Veligdan, James T.

1993-01-01

Atmospheric effects on sighting measurements are compensated for by adjusting any sighting measurements using a correction factor that does not depend on atmospheric state conditions such as temperature, pressure, density or turbulence. The correction factor is accurately determined using a precisely measured physical separation between two color components of a light beam (or beams) that has been generated using either a two-color laser or two lasers that project different colored beams. The physical separation is precisely measured by fixing the position of a short beam pulse and measuring the physical separation between the two fixed-in-position components of the beam. This precisely measured physical separation is then used in a relationship that includes the indexes of refraction for each of the two colors of the laser beam in the atmosphere through which the beam is projected, thereby to determine the absolute displacement of one wavelength component of the laser beam from a straight line of sight for that projected component of the beam. This absolute displacement is useful to correct optical measurements, such as those developed in surveying measurements that are made in a test area that includes the same dispersion effects of the atmosphere on the optical measurements. The means and method of the invention are suitable for use with either single-ended systems or a double-ended systems.

A two-component signal transduction pathway regulates manganese homeostasis in Synechocystis 6803, a photosynthetic organism.

PubMed

Ogawa, Teruo; Bao, Ding Hui; Katoh, Hirokazu; Shibata, Mari; Pakrasi, Himadri B; Bhattacharyya-Pakrasi, Maitrayee

2002-08-09

Elemental manganese is essential for the production of molecular oxygen by cyanobacteria, plants, and algae. In the cyanobacterium Synechocystis sp. PCC 6803, transcription of the mntCAB operon, encoding a high affinity Mn transporter, occurs under Mn starvation (nm Mn) conditions but not in Mn-sufficient (microm Mn) growth medium. Using a strain in which the promoter of this operon directs the transcription of the luxAB reporter genes, we determined that inactivation of the slr0640 gene, which encodes a histidine kinase sensor protein component of a two-component signal transduction system, resulted in constitutive high levels of lux luminescence. Systematic targeted inactivation mutagenesis also identified slr1837 as the gene encoding the corresponding response regulator protein. We have named these two genes manS (manganese-sensor) and manR (manganese-regulator), respectively. A polyhistidine-tagged form of the ManS protein was localized in the Synechocystis 6803 cell membrane. Directed replacement of the conserved catalytic His-205 residue of this protein by Leu abolished its activity, although the mutated protein was present in cyanobacterial membrane. This mutant also showed suboptimal rates of Mn uptake under either Mn-starved or Mn-sufficient growth condition. These data suggest that the ManS/ManR two-component system plays a central role in the homeostasis of manganese in Synechocystis 6803 cells.

77 FR 27815 - Aging Management of Stainless Steel Structures and Components in Treated Borated Water

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-11

... NUCLEAR REGULATORY COMMISSION [NRC-2011-0256] Aging Management of Stainless Steel Structures and... Guidance (LR-ISG), LR-ISG-2011-01, ``Aging Management of Stainless Steel Structures and Components in...) Report for the aging management of stainless steel structures and components exposed to treated borated...

The Portuguese electric system and the role of the Portuguese regulatory entity

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

Santana, J.

1998-07-01

According to the organization model of the Portuguese Electric System, there is the coexistence of two subsystems with different characteristics: the Public Electric System, which has public service obligations and the Independent Electric System which does not have such obligations, and part of it obeys a market logic. Nowadays, the Public Electric System is the main component of the electric sector, however there are reasons to believe that the Independent System can increase its participation. The 1995 Portuguese legislation established the existence of an independent structure to regulate the electric sector: the Electric Sector Regulatory Entity. In this paper, themore » organization of this entity is described, as well as its objectives and main powers.« less

Two-component Superfluid Hydrodynamics of Neutron Star Cores

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

Kobyakov, D. N.; Pethick, C. J., E-mail: dmitry.kobyakov@appl.sci-nnov.ru, E-mail: pethick@nbi.dk

2017-02-20

We consider the hydrodynamics of the outer core of a neutron star under conditions when both neutrons and protons are superfluid. Starting from the equation of motion for the phases of the wave functions of the condensates of neutron pairs and proton pairs, we derive the generalization of the Euler equation for a one-component fluid. These equations are supplemented by the conditions for conservation of neutron number and proton number. Of particular interest is the effect of entrainment, the fact that the current of one nucleon species depends on the momenta per nucleon of both condensates. We find that themore » nonlinear terms in the Euler-like equation contain contributions that have not always been taken into account in previous applications of superfluid hydrodynamics. We apply the formalism to determine the frequency of oscillations about a state with stationary condensates and states with a spatially uniform counterflow of neutrons and protons. The velocities of the coupled sound-like modes of neutrons and protons are calculated from properties of uniform neutron star matter evaluated on the basis of chiral effective field theory. We also derive the condition for the two-stream instability to occur.« less

Valley-polarized edge pseudomagnetoplasmons in graphene: A two-component hydrodynamic model

NASA Astrophysics Data System (ADS)

Zhang, Ya; Guo, Bin; Zhai, Feng; Jiang, Wei

2018-03-01

By means of a nonlinear two-component hydrodynamic model, we study the valley-polarized collective motion of electrons in a strained graphene sheet. The self-consistent numerical solution in real space indicates the existence of valley-polarized edge plasmons due to a strain-induced pseudomagnetic field. The valley polarization of the edge pseudomagnetoplasmon can occur in a specific valley, depending on the pseudomagnetic field and the electron density in equilibrium. A full valley polarization is achieved at the edge of the graphene sheet for a pseudomagnetic field of tens of Tesla, which is a realistic value in current experimental technologies.

Two-Component Structure in the Entanglement Spectrum of Highly Excited States

NASA Astrophysics Data System (ADS)

Yang, Zhi-Cheng; Chamon, Claudio; Hamma, Alioscia; Mucciolo, Eduardo R.

2015-12-01

We study the entanglement spectrum of highly excited eigenstates of two known models that exhibit a many-body localization transition, namely the one-dimensional random-field Heisenberg model and the quantum random energy model. Our results indicate that the entanglement spectrum shows a "two-component" structure: a universal part that is associated with random matrix theory, and a nonuniversal part that is model dependent. The nonuniversal part manifests the deviation of the highly excited eigenstate from a true random state even in the thermalized phase where the eigenstate thermalization hypothesis holds. The fraction of the spectrum containing the universal part decreases as one approaches the critical point and vanishes in the localized phase in the thermodynamic limit. We use the universal part fraction to construct an order parameter for measuring the degree of randomness of a generic highly excited state, which is also a promising candidate for studying the many-body localization transition. Two toy models based on Rokhsar-Kivelson type wave functions are constructed and their entanglement spectra are shown to exhibit the same structure.

Gravitropism in Phycomyces: violation of the so-called resultant law - evidence for two response components.

PubMed

Göttig, M; Galland, P

2014-01-01

We investigated gravitropic bending of sporangiophores of the zygomycete fungus Phycomyces blakesleeanus in response to centrifugal accelerations to test the so-called resultant law of gravitropism ('Resultantengesetz'; Jahrbuch der wissenschaftlichen Botanik, 71, 325, 1929; Der Geotropismus der Pflanzen, Gustav Fischer, Jena, Germany, 1932), which predicts that gravitropic organs orient in a centrifuge rotor parallel to the stimulus vector resulting from the centrifugal acceleration and gravity. Sporangiophores of wild-type strain C171 carAcarR and of several gravitropism mutants were subjected for 7 h to centrifugal accelerations in a dynamic range between 0.01 and 3 × g. The stimulus-response curves that were obtained for C171 carA carR, C2 carA geo and C148 carA geo madC were complex and displayed two response components: a low-acceleration component between 0.01 and 0.5 × g and a high-acceleration component above 0.5 × g. The low acceleration component is characterised by bending angles exceeding those predicted by the resultant law and kinetics faster than that of the second component; in contrast, the high-acceleration component is characterised by bending slightly below the predicted level and kinetics slower than that of the first component. Sporangiophores of the wild-type C171 centrifuged horizontally displayed the opposite behaviour, i.e. low accelerations diminished and high accelerations slightly enhanced bending. Further proof for the existence of the two response components was provided by the phenotype of gravitropism mutants that either lacked the first response component or which caused its overexpression. The tropism mutant C148 with defective madC gene, which codes for a RasGap protein (Fungal Genetics Reports, 60 (Suppl.), Abstract # 211, 2013), displayed hypergravitropism and concomitant deviations from the resultant law that were twice as high as in the wild-type C171. Gravitropism mutants with defects in the genes madF, madG and

An internal regulatory element controls troponin I gene expression

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

Yutzey, K.E.; Kline, R.L.; Konieczmy, S.F.

1989-04-01

During skeletal myogenesis, approximately 20 contractile proteins and related gene products temporally accumulate as the cells fuse to form multinucleated muscle fibers. In most instances, the contractile protein genes are regulated transcriptionally, which suggests that a common molecular mechanism may coordinate the expression of this diverse and evolutionarily unrelated gene set. Recent studies have examined the muscle-specific cis-acting elements associated with numerous contractile protein genes. All of the identified regulatory elements are positioned in the 5'-flanking regions, usually within 1,500 base pairs of the transcription start site. Surprisingly, a DNA consensus sequence that is common to each contractile protein genemore » has not been identified. In contrast to the results of these earlier studies, the authors have found that the 5'-flanking region of the quail troponin I (TnI) gene is not sufficient to permit the normal myofiber transcriptional activation of the gene. Instead, the TnI gene utilizes a unique internal regulatory element that is responsible for the correct myofiber-specific expression pattern associated with the TnI gene. This is the first example in which a contractile protein gene has been shown to rely primarily on an internal regulatory element to elicit transcriptional activation during myogenesis. The diversity of regulatory elements associated with the contractile protein genes suggests that the temporal expression of the genes may involve individual cis-trans regulatory components specific for each gene.« less

An internal regulatory element controls troponin I gene expression.

PubMed Central

Yutzey, K E; Kline, R L; Konieczny, S F

1989-01-01

During skeletal myogenesis, approximately 20 contractile proteins and related gene products temporally accumulate as the cells fuse to form multinucleated muscle fibers. In most instances, the contractile protein genes are regulated transcriptionally, which suggests that a common molecular mechanism may coordinate the expression of this diverse and evolutionarily unrelated gene set. Recent studies have examined the muscle-specific cis-acting elements associated with numerous contractile protein genes. All of the identified regulatory elements are positioned in the 5'-flanking regions, usually within 1,500 base pairs of the transcription start site. Surprisingly, a DNA consensus sequence that is common to each contractile protein gene has not been identified. In contrast to the results of these earlier studies, we have found that the 5'-flanking region of the quail troponin I (TnI) gene is not sufficient to permit the normal myofiber transcriptional activation of the gene. Instead, the TnI gene utilizes a unique internal regulatory element that is responsible for the correct myofiber-specific expression pattern associated with the TnI gene. This is the first example in which a contractile protein gene has been shown to rely primarily on an internal regulatory element to elicit transcriptional activation during myogenesis. The diversity of regulatory elements associated with the contractile protein genes suggests that the temporal expression of the genes may involve individual cis-trans regulatory components specific for each gene. Images PMID:2725509

Transportation of Large Wind Components: A Review of Existing Geospatial Data

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

Mooney, Meghan; Maclaurin, Galen

2016-09-01

This report features the geospatial data component of a larger project evaluating logistical and infrastructure requirements for transporting oversized and overweight (OSOW) wind components. The goal of the larger project was to assess the status and opportunities for improving the infrastructure and regulatory practices necessary to transport wind turbine towers, blades, and nacelles from current and potential manufacturing facilities to end-use markets. The purpose of this report is to summarize existing geospatial data on wind component transportation infrastructure and to provide a data gap analysis, identifying areas for further analysis and data collection.

Two negative regulatory systems of root nodule symbiosis - how are symbiotic benefits and costs balanced?

PubMed

Nishida, Hanna; Suzaki, Takuya

2018-05-30

Root nodule symbiosis is one of the best-characterized mutualistic relationships between plants-microbes symbiosis, where mainly leguminous species can obtain nitrogen sources fixed by nitrogen-fixing rhizobia through the formation of symbiotic organs root nodules. In order to drive this symbiotic process, plants need to provide carbon sources that should be used for their growth. Therefore, a balance between the benefits of obtaining nitrogen sources and the costs of losing carbon sources needs to be maintained during root nodule symbiosis. Plants have developed at least two negative regulatory systems of root nodule symbiosis. One strategy involves the regulation of nodule number in response to rhizobial infection. For this regulation, a systemic long-range signaling between roots and shoots called autoregulation of nodulation has a pivotal role. Another strategy involves the regulation of root nodule symbiosis in response to nitrate, the most abundant form of nitrogen nutrients in the soil. Recent studies indicate that a long-distance signaling is shared between the two strategies, where NIN and NRSYM1, two paralogous RWP-RK transcription factors, can activate the production of nodulation-related CLE peptides in response to different inputs. Here, we give an overview of such progress in our understanding of molecular mechanisms relevant to the control of the symbiotic balance, including their biological significance.

Major regulatory mechanisms involved in sperm motility

PubMed Central

Pereira, Rute; Sá, Rosália; Barros, Alberto; Sousa, Mário

2017-01-01

The genetic bases and molecular mechanisms involved in the assembly and function of the flagellum components as well as in the regulation of the flagellar movement are not fully understood, especially in humans. There are several causes for sperm immotility, of which some can be avoided and corrected, whereas other are related to genetic defects and deserve full investigation to give a diagnosis to patients. This review was performed after an extensive literature search on the online databases PubMed, ScienceDirect, and Web of Science. Here, we review the involvement of regulatory pathways responsible for sperm motility, indicating possible causes for sperm immotility. These included the calcium pathway, the cAMP-dependent protein kinase pathway, the importance of kinases and phosphatases, the function of reactive oxygen species, and how the regulation of cell volume and osmolarity are also fundamental components. We then discuss main gene defects associated with specific morphological abnormalities. Finally, we slightly discuss some preventive and treatments approaches to avoid development of conditions that are associated with unspecified sperm immotility. We believe that in the near future, with the development of more powerful techniques, the genetic causes of sperm immotility and the regulatory mechanisms of sperm motility will be better understand, thus enabling to perform a full diagnosis and uncover new therapies. PMID:26680031

Two component-three dimensional catalysis

DOEpatents

Schwartz, Michael; White, James H.; Sammells, Anthony F.

2002-01-01

This invention relates to catalytic reactor membranes having a gas-impermeable membrane for transport of oxygen anions. The membrane has an oxidation surface and a reduction surface. The membrane is coated on its oxidation surface with an adherent catalyst layer and is optionally coated on its reduction surface with a catalyst that promotes reduction of an oxygen-containing species (e.g., O.sub.2, NO.sub.2, SO.sub.2, etc.) to generate oxygen anions on the membrane. The reactor has an oxidation zone and a reduction zone separated by the membrane. A component of an oxygen containing gas in the reduction zone is reduced at the membrane and a reduced species in a reactant gas in the oxidation zone of the reactor is oxidized. The reactor optionally contains a three-dimensional catalyst in the oxidation zone. The adherent catalyst layer and the three-dimensional catalyst are selected to promote a desired oxidation reaction, particularly a partial oxidation of a hydrocarbon.

Identification by GC-EAD of the two-component trail-following pheromone of Prorhinotermes simplex (Isoptera, Rhinotermitidae, Prorhinotermitinae).

PubMed

Sillam-Dussès, David; Kalinová, Blanka; Jiros, Pavel; Brezinová, Anna; Cvacka, Josef; Hanus, Robert; Sobotník, Jan; Bordereau, Christian; Valterová, Irena

2009-08-01

GC/MS analysis confirmed that neocembrene is the major component of the trail pheromone in the three species of the termite genus Prorhinotermes (P. simplex, P. canalifrons, P. inopinatus). In addition, EAG and GC-EAD experiments with P. simplex strongly suggest that dodecatrienol is a quantitatively minor component but a qualitatively important component of this trail pheromone. Trail-following bioassays confirmed the two-component nature of the trail pheromone. This is the first report of the use of the GC-EAD for the identification of trail pheromone in termites. These original results underline once again the special phylogenetic status of the Prorhinotermitinae among Rhinotermitidae.

Development of instrumentation for measurements of two components of velocity with a single sensing element

NASA Astrophysics Data System (ADS)

Byers, C. P.; Fu, M. K.; Fan, Y.; Hultmark, M.

2018-02-01

A novel method of obtaining two orthogonal velocity components with high spatial and temporal resolution is investigated. Both components are obtained utilizing a single sensing nanoribbon by combining the two independent operating modes of classic hot wire anemometry and the newly discovered elastic filament velocimetry (EFV). In contrast to hot wire anemometry, EFV measures fluid velocity through correlating the fluid forcing with the internal strain of the wire. In order to utilize both modes of operation, a system that switches between the two operating modes is built and characterized, and the theoretically predicted sensing response time in water is compared to experimental results. The sensing system is capable of switching between the two modes of operation at a frequency of 100 kHz with minimal attenuation with an uncompensated repetition rate up to 3 kHz or up to 10 kHz utilizing modest signal compensation. While further characterization of the sensor performance in air is needed, this methodology enables a technique for obtaining well-resolved yet cost-efficient directional measurements of flow velocities which, for example, can be used for distributed measurements of velocity or measurements of turbulent stresses with excellent spatial resolution.

Nutrition quality, body size and two components of mating behavior in Drosophila melanogaster.

PubMed

Pavković-Lucić, Sofija; Kekić, Vladimir

2010-01-01

Two components of mating behavior, mating latency and duration of copulation, were investigated in Drosophila melanogaster males from three different "nutritional" strains, reared for more than 35 generations on banana, tomato and cornmeal-agar-yeast substrates. Males from different strains did not differ according to mating latency and duration of copulation. Also, the sizes of males from different strains did not contribute to these behavioral traits.

Condensates of p-wave pairs are exact solutions for rotating two-component Bose gases.

PubMed

Papenbrock, T; Reimann, S M; Kavoulakis, G M

2012-02-17

We derive exact analytical results for the wave functions and energies of harmonically trapped two-component Bose-Einstein condensates with weakly repulsive interactions under rotation. The isospin symmetric wave functions are universal and do not depend on the matrix elements of the two-body interaction. The comparison with the results from numerical diagonalization shows that the ground state and low-lying excitations consist of condensates of p-wave pairs for repulsive contact interactions, Coulomb interactions, and the repulsive interactions between aligned dipoles.

Remarks on the regularity criteria of three-dimensional magnetohydrodynamics system in terms of two velocity field components

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

Yamazaki, Kazuo

2014-03-15

We study the three-dimensional magnetohydrodynamics system and obtain its regularity criteria in terms of only two velocity vector field components eliminating the condition on the third component completely. The proof consists of a new decomposition of the four nonlinear terms of the system and estimating a component of the magnetic vector field in terms of the same component of the velocity vector field. This result may be seen as a component reduction result of many previous works [C. He and Z. Xin, “On the regularity of weak solutions to the magnetohydrodynamic equations,” J. Differ. Equ. 213(2), 234–254 (2005); Y. Zhou,more » “Remarks on regularities for the 3D MHD equations,” Discrete Contin. Dyn. Syst. 12(5), 881–886 (2005)].« less

76 FR 16842 - Request for a License To Export Reactor Components

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-25

... NUCLEAR REGULATORY COMMISSION Request for a License To Export Reactor Components Pursuant to 10.... Mechanical Corporation. coolant pump 1000 (design) maintenance, and systems, related reactors. operation of AP- equipment, and 1000 (design) spare parts. nuclear reactors. February 10, 2011 February 23, 2011...

Cis-regulatory somatic mutations and gene-expression alteration in B-cell lymphomas.

PubMed

Mathelier, Anthony; Lefebvre, Calvin; Zhang, Allen W; Arenillas, David J; Ding, Jiarui; Wasserman, Wyeth W; Shah, Sohrab P

2015-04-23

With the rapid increase of whole-genome sequencing of human cancers, an important opportunity to analyze and characterize somatic mutations lying within cis-regulatory regions has emerged. A focus on protein-coding regions to identify nonsense or missense mutations disruptive to protein structure and/or function has led to important insights; however, the impact on gene expression of mutations lying within cis-regulatory regions remains under-explored. We analyzed somatic mutations from 84 matched tumor-normal whole genomes from B-cell lymphomas with accompanying gene expression measurements to elucidate the extent to which these cancers are disrupted by cis-regulatory mutations. We characterize mutations overlapping a high quality set of well-annotated transcription factor binding sites (TFBSs), covering a similar portion of the genome as protein-coding exons. Our results indicate that cis-regulatory mutations overlapping predicted TFBSs are enriched in promoter regions of genes involved in apoptosis or growth/proliferation. By integrating gene expression data with mutation data, our computational approach culminates with identification of cis-regulatory mutations most likely to participate in dysregulation of the gene expression program. The impact can be measured along with protein-coding mutations to highlight key mutations disrupting gene expression and pathways in cancer. Our study yields specific genes with disrupted expression triggered by genomic mutations in either the coding or the regulatory space. It implies that mutated regulatory components of the genome contribute substantially to cancer pathways. Our analyses demonstrate that identifying genomically altered cis-regulatory elements coupled with analysis of gene expression data will augment biological interpretation of mutational landscapes of cancers.

KIC 2557430: A Triple System Containing One γ Dor and Two Flaring Components?

NASA Astrophysics Data System (ADS)

Kamil, Ceren; Dal, Hasan Ali

2017-07-01

The results are presented for eclipsing binary KIC 2557430. The mass ratio was computed as 0.868 ± 0.002, while the inclination (i) was found as 69°.75 ± 0°.01 with T 2 = 6271±1 K. 50 frequencies were found in the period analysis. 48 frequencies of them are caused due to the primary component, a γ Doradus star, while two of them are caused by the cool spots. 69 flares were detected in the analyses. Two OPEA models were derived for flares, which indicates that the flares were come from two different sources. The Plateau value was found to be 1.4336 ± 0.1104 s for Source 1, which is seen as possible the secondary component and 0.7550 ± 0.0677 s for Source 2, which is seen as possible third body. The half-life value was computed as 2278.1 s for Group 1 and 1811.2 s for Group 2. The flare frequency N 1 was found to be 0.02726 h -1 and N 2 was computed as 0.00002 for Group 1, while N 1 was found to be 0.01977 h -1 and N 2 was computed as 0.00001 for Group 2. In a results, KIC 2557430 is a possible triple system consisting of a γ Doradus-type star, a chromospherically active star, and also a flaring third body.

EGRINs (Environmental Gene Regulatory Influence Networks) in Rice That Function in the Response to Water Deficit, High Temperature, and Agricultural Environments[OPEN

PubMed Central

Hafemeister, Christoph; Nicotra, Adrienne B.; Jagadish, S.V. Krishna; Bonneau, Richard; Purugganan, Michael

2016-01-01

Environmental gene regulatory influence networks (EGRINs) coordinate the timing and rate of gene expression in response to environmental signals. EGRINs encompass many layers of regulation, which culminate in changes in accumulated transcript levels. Here, we inferred EGRINs for the response of five tropical Asian rice (Oryza sativa) cultivars to high temperatures, water deficit, and agricultural field conditions by systematically integrating time-series transcriptome data, patterns of nucleosome-free chromatin, and the occurrence of known cis-regulatory elements. First, we identified 5447 putative target genes for 445 transcription factors (TFs) by connecting TFs with genes harboring known cis-regulatory motifs in nucleosome-free regions proximal to their transcriptional start sites. We then used network component analysis to estimate the regulatory activity for each TF based on the expression of its putative target genes. Finally, we inferred an EGRIN using the estimated transcription factor activity (TFA) as the regulator. The EGRINs include regulatory interactions between 4052 target genes regulated by 113 TFs. We resolved distinct regulatory roles for members of the heat shock factor family, including a putative regulatory connection between abiotic stress and the circadian clock. TFA estimation using network component analysis is an effective way of incorporating multiple genome-scale measurements into network inference. PMID:27655842

Kinetics and mechanism of the oxidation process of two-component Fe-Al alloys

NASA Technical Reports Server (NTRS)

Przewlocka, H.; Siedlecka, J.

1982-01-01

The oxidation process of two-component Fe-Al alloys containing up to 7.2% Al and from 18 to 30% Al was studied. Kinetic measurements were conducted using the isothermal gravimetric method in the range of 1073-1223 K and 1073-1373 K for 50 hours. The methods used in studies of the mechanism of oxidation included: X-ray microanalysis, X-ray structural analysis, metallographic analysis and marker tests.

Nuclear Weapon Accident Response Procedures (NARP)

DTIC Science & Technology

2005-02-22

C5.5.5. Communications. The Communications element establishes timely external ommunications to higher HQ and ensures internal communications among...effective SR effort. They should be considered by the OSC from the ns . 7.1 C7.10.10.3. Loss of work by C7.10.10.4. Impact on tourism

Mutational Activation of the AmgRS Two-Component System in Aminoglycoside-Resistant Pseudomonas aeruginosa

PubMed Central

Lau, Calvin Ho-Fung; Fraud, Sebastien; Jones, Marcus; Peterson, Scott N.; Poole, Keith

2013-01-01

The amgRS operon encodes a presumed membrane stress-responsive two-component system linked to intrinsic aminoglycoside resistance in Pseudomonas aeruginosa. Genome sequencing of a lab isolate showing modest pan-aminoglycoside resistance, strain K2979, revealed a number of mutations, including a substitution in amgS that produced an R182C change in the AmgS sensor kinase product of this gene. Introduction of this mutation into an otherwise wild-type strain recapitulated the resistance phenotype, while correcting the mutation in the resistant mutant abrogated the resistant phenotype, confirming that the amgS mutation is responsible for the aminoglycoside resistance of strain K2979. The amgSR182 mutation promoted an AmgR-dependent, 2- to 3-fold increase in expression of the AmgRS target genes htpX and PA5528, mirroring the impact of aminoglycoside exposure of wild-type cells on htpX and PA5528 expression. This suggests that amgSR182 is a gain-of-function mutation that activates AmgS and the AmgRS two-component system in promoting modest resistance to aminoglycosides. Screening of several pan-aminoglycoside-resistant clinical isolates of P. aeruginosa revealed three that showed elevated htpX and PA5528 expression and harbored single amino acid-altering mutations in amgS (V121G or D106N) and no mutations in amgR. Introduction of the amgSV121G mutation into wild-type P. aeruginosa generated a resistance phenotype reminiscent of the amgSR182 mutant and produced a 2- to 3-fold increase in htpX and PA5528 expression, confirming that it, too, is a gain-of-function aminoglycoside resistance-promoting mutation. These results highlight the contribution of amgS mutations and activation of the AmgRS two-component system to acquired aminoglycoside resistance in lab and clinical isolates of P. aeruginosa. PMID:23459488

Shearing of nanoscopic bridges in two-component thin liquid layers between chemically patterned walls.

PubMed

Hemming, C J; Patey, G N

2004-10-01

Bridge phases associated with a phase transition between two liquid phases occur when a two-component liquid mixture is confined between chemically patterned walls. In the bulk the liquid mixture with components A, B undergoes phase separation into an A-rich phase and a B-rich phase. The walls bear stripes attractive to A. In the bridge phase A-rich and B-rich regions alternate. Grand canonical Monte Carlo studies are performed with the alignment between stripes on opposite walls varied. Misalignment of the stripes places the nanoscopic liquid bridges under shear strain. The bridges exert a Hookean restoring force on the walls for small displacements from equilibrium. As the strain increases there are deviations from Hooke's law. Eventually there is an abrupt yielding of the bridges. Molecular dynamics simulations show the bridges form or disintegrate on time scales which are fast compared to wall motion and transport of molecules into or from the confined space. Some interesting possible applications of the phenomena are discussed. (c) 2004 American Institute of Physics

Identification of gold sensing peptide by integrative proteomics and a bacterial two-component system

NASA Astrophysics Data System (ADS)

Ng, I.-Son; Yu, You-Jin; Yi, Ying-Chen; Tan, Shih-I.; Huang, Bo-Chuan; Han, Yin-Lung

2017-12-01

The proteomics strategy was utilized to analyze and identify the gold adsorption proteins from Tepidimonas fonticaldi AT-A2, due to its outstanding performance in gold-binding and recovery. The results showed that three small proteins, including histidine biosynthesis protein (HisIE), iron donor protein (CyaY) and hypothetical protein_65aa, have a higher ability to adsorb gold ions because of the negatively charged domains or metal binding sites. On the other hand, the Salmonella PmrA/PmrB two-component system first replaces the iron (III)-binding motif using the peptide sequence from hypothetical protein_65aa, and this is then used to reveal the sensing and responsiveness to gold metal ions, which is totally different from the performance of traditional gold binding peptide (GBP) on the crystals on the surface of gold (111). We have successfully demonstrated an integrative proteomics and bacterial two-component system to explore the novel gold binding peptide. Finally, the heterologous over-expression of gold binding peptide by E. coli and the equilibrium of binding capacity for Au(III) have been conducted.

A cis-regulatory module activating transcription in the suspensor contains five cis-regulatory elements

DOE PAGES

Henry, Kelli F.; Kawashima, Tomokazu; Goldberg, Robert B.

2015-03-22

Little is known about the molecular mechanisms by which the embryo proper and suspensor of plant embryos activate specific gene sets shortly after fertilization. We analyzed the upstream region of the Scarlet Runner Bean ( Phaseolus coccineus) G564 gene in order to understand how genes are activated specifically in the suspensor during early embryo development. Previously, we showed that a 54-bp fragment of the G564 upstream region is sufficient for suspensor transcription and contains at least three required cis-regulatory sequences, including the 10-bp motif (5'-GAAAAGCGAA-3'), the 10 bp-like motif (5'-GAAAAACGAA-3'), and Region 2 motif (partial sequence 5'-TTGGT-3'). Here, we usemore » site-directed mutagenesis experiments in transgenic tobacco globularstage embryos to identify two additional cis-regulatory elements within the 54-bp cis-regulatory module that are required for G564 suspensor transcription: the Fifth motif (5'-GAGTTA-3') and a third 10-bp-related sequence (5'-GAAAACCACA-3'). Further deletion of the 54-bp fragment revealed that a 47-bp fragment containing the five motifs (the 10-bp, 10-bp-like, 10-bp-related, Region 2 and Fifth motifs) is sufficient for suspensor transcription, and represents a cis-regulatory module. A consensus sequence for each type of motif was determined by comparing motif sequences shown to activate suspensor transcription. Phylogenetic analyses suggest that the regulation of G564 is evolutionarily conserved. Lastly, a homologous cis-regulatory module was found upstream of the G564 ortholog in the Common Bean (Phaseolus vulgaris), indicating that the regulation of G564 is evolutionarily conserved in closely related bean species.« less

A cis-regulatory module activating transcription in the suspensor contains five cis-regulatory elements

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

Henry, Kelli F.; Kawashima, Tomokazu; Goldberg, Robert B.

Little is known about the molecular mechanisms by which the embryo proper and suspensor of plant embryos activate specific gene sets shortly after fertilization. We analyzed the upstream region of the Scarlet Runner Bean ( Phaseolus coccineus) G564 gene in order to understand how genes are activated specifically in the suspensor during early embryo development. Previously, we showed that a 54-bp fragment of the G564 upstream region is sufficient for suspensor transcription and contains at least three required cis-regulatory sequences, including the 10-bp motif (5'-GAAAAGCGAA-3'), the 10 bp-like motif (5'-GAAAAACGAA-3'), and Region 2 motif (partial sequence 5'-TTGGT-3'). Here, we usemore » site-directed mutagenesis experiments in transgenic tobacco globularstage embryos to identify two additional cis-regulatory elements within the 54-bp cis-regulatory module that are required for G564 suspensor transcription: the Fifth motif (5'-GAGTTA-3') and a third 10-bp-related sequence (5'-GAAAACCACA-3'). Further deletion of the 54-bp fragment revealed that a 47-bp fragment containing the five motifs (the 10-bp, 10-bp-like, 10-bp-related, Region 2 and Fifth motifs) is sufficient for suspensor transcription, and represents a cis-regulatory module. A consensus sequence for each type of motif was determined by comparing motif sequences shown to activate suspensor transcription. Phylogenetic analyses suggest that the regulation of G564 is evolutionarily conserved. Lastly, a homologous cis-regulatory module was found upstream of the G564 ortholog in the Common Bean (Phaseolus vulgaris), indicating that the regulation of G564 is evolutionarily conserved in closely related bean species.« less

A cis-regulatory module activating transcription in the suspensor contains five cis-regulatory elements.

PubMed

Henry, Kelli F; Kawashima, Tomokazu; Goldberg, Robert B

2015-06-01

Little is known about the molecular mechanisms by which the embryo proper and suspensor of plant embryos activate specific gene sets shortly after fertilization. We analyzed the upstream region of the Scarlet Runner Bean (Phaseolus coccineus) G564 gene in order to understand how genes are activated specifically in the suspensor during early embryo development. Previously, we showed that a 54-bp fragment of the G564 upstream region is sufficient for suspensor transcription and contains at least three required cis-regulatory sequences, including the 10-bp motif (5'-GAAAAGCGAA-3'), the 10 bp-like motif (5'-GAAAAACGAA-3'), and Region 2 motif (partial sequence 5'-TTGGT-3'). Here, we use site-directed mutagenesis experiments in transgenic tobacco globular-stage embryos to identify two additional cis-regulatory elements within the 54-bp cis-regulatory module that are required for G564 suspensor transcription: the Fifth motif (5'-GAGTTA-3') and a third 10-bp-related sequence (5'-GAAAACCACA-3'). Further deletion of the 54-bp fragment revealed that a 47-bp fragment containing the five motifs (the 10-bp, 10-bp-like, 10-bp-related, Region 2 and Fifth motifs) is sufficient for suspensor transcription, and represents a cis-regulatory module. A consensus sequence for each type of motif was determined by comparing motif sequences shown to activate suspensor transcription. Phylogenetic analyses suggest that the regulation of G564 is evolutionarily conserved. A homologous cis-regulatory module was found upstream of the G564 ortholog in the Common Bean (Phaseolus vulgaris), indicating that the regulation of G564 is evolutionarily conserved in closely related bean species.

Canadian regulatory perspectives on genome engineered crops

PubMed Central

Smyth, Stuart J.

2017-01-01

ABSTRACT New breeding techniques in plant agriculture exploded upon the scene about two years ago, in 2014. While these innovative plant breeding techniques, soon to be led by CRISPR/Cas9, initially appear to hold tremendous promise for plant breeding, if not a revolution for the industry, the question of how the products of these technologies will be regulated is rapidly becoming a key aspect of the technology's future potential. Regulation of innovative technologies and products has always lagged that of the science, but in the past decade, regulatory systems in many jurisdictions have become gridlocked as they try to regulate genetically modified (GM) crops. This regulatory incapability to efficiently assess and approve innovative new agricultural products is particularly important for new plant breeding techniques as if these techniques are classified as genetically modified breeding techniques, then their acceptance and future will diminish considerably as they will be rejected by the European Union. Conversely, if the techniques are accepted as conventional plant breeding, then the future is blindingly bright. This article examines the international debate about the regulation of new plant breeding techniques and then assesses how the Canadian regulatory system has approached the regulation of these technologies through two more public product approvals, GM apples and GM potatoes, then discusses other crop variety approval and those in the regulatory pipeline. PMID:27858499

77 FR 74883 - Aging Management of Stainless Steel Structures and Components in Treated Borated Water; Revision 1

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-18

... NUCLEAR REGULATORY COMMISSION [NRC-2011-0256] Aging Management of Stainless Steel Structures and..., ``Aging Management of Stainless Steel Structures and Components in Treated Borated Water,'' which was... Staff Guidance LR-ISG-2011-01, ``Aging Management of Stainless Steel Structures and Components in...

Favorable genomic environments for cis-regulatory evolution: A novel theoretical framework.

PubMed

Maeso, Ignacio; Tena, Juan J

2016-09-01

Cis-regulatory changes are arguably the primary evolutionary source of animal morphological diversity. With the recent explosion of genome-wide comparisons of the cis-regulatory content in different animal species is now possible to infer general principles underlying enhancer evolution. However, these studies have also revealed numerous discrepancies and paradoxes, suggesting that the mechanistic causes and modes of cis-regulatory evolution are still not well understood and are probably much more complex than generally appreciated. Here, we argue that the mutational mechanisms and genomic regions generating new regulatory activities must comply with the constraints imposed by the molecular properties of cis-regulatory elements (CREs) and the organizational features of long-range chromatin interactions. Accordingly, we propose a new integrative evolutionary framework for cis-regulatory evolution based on two major premises for the origin of novel enhancer activity: (i) an accessible chromatin environment and (ii) compatibility with the 3D structure and interactions of pre-existing CREs. Mechanisms and DNA sequences not fulfilling these premises, will be less likely to have a measurable impact on gene expression and as such, will have a minor contribution to the evolution of gene regulation. Finally, we discuss current comparative cis-regulatory data under the light of this new evolutionary model, and propose that the two most prominent mechanisms for the evolution of cis-regulatory changes are the overprinting of ancestral CREs and the exaptation of transposable elements. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Regulatory Evaluation of Vaccines for Human Use.

PubMed

Baylor, Norman W

2016-01-01

A vaccine is an immunogen, the administration of which is intended to stimulate the immune system to result in the prevention, amelioration, or therapy of any disease or infection (US Food and Drug Administration. Guidance for Industry: content and format of chemistry, manufacturing, and controls information and establishment description information for a vaccine or related product). A vaccine may be a live attenuated preparation of microorganisms, inactivated (killed) whole organisms, living irradiated cells, crude fractions, or purified immunogens, including those derived from recombinant DNA in a host cell, conjugates formed by covalent linkage of components, synthetic antigens, polynucleotides (such as the plasmid DNA vaccines), living vectored cells expressing specific heterologous immunogens, or cells pulsed with immunogen. Vaccines are highly complex products that differ from small molecule drugs because of the biological nature of the source materials such as those derived from microorganisms as well as the various cell substrates from which some are derived. Regardless of the technology used, because of their complexities, vaccines must undergo extensive characterization and testing. Special expertise and procedures are needed for their manufacture, control, and regulation. The Food and Drug Administration (FDA) is the National Regulatory Authority (NRA) in the United States responsible for assuring quality, safety, and effectiveness of all human medical products, including vaccines for human use.The Center for Biologics Evaluation and Research (CBER) within the US FDA is responsible for overseeing the regulation of therapeutic and preventative vaccines against infectious diseases. Authority for the regulation of vaccines resides in Section 351 of the Public Health Service Act and specific sections of the Federal Food, Drug, and Cosmetic Act (FD&C). Vaccines are regulated as biologics and licensed based on the demonstration of safety and effectiveness. The

Learning by the Market: Regulatory Regionalism, Bologna, and Accountability Communities

ERIC Educational Resources Information Center

Jayasuriya, Kanishka

2010-01-01

Over the last two decades institutions of higher education have been subject to new modes of regulatory governance. This essay applies a "regulatory lens" to higher education governance with a view to understanding the sometimes contradictory relationship between the globalisation and regionalisation of higher education and the…

78 FR 30384 - Federal Regulatory Enforcement Fairness Hearing; Region X Regulatory Fairness Board

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-22

... SMALL BUSINESS ADMINISTRATION Federal Regulatory Enforcement Fairness Hearing; Region X Regulatory... Regional (Region X) Small Business Regulatory Fairness Board. SUMMARY: The (SBA) Office of the National... Region X Regulatory Fairness Board must contact Jos[eacute] M[eacute]ndez by May 30, 2013 in writing, by...

Two-component mixture model: Application to palm oil and exchange rate

NASA Astrophysics Data System (ADS)

Phoong, Seuk-Yen; Ismail, Mohd Tahir; Hamzah, Firdaus Mohamad

2014-12-01

Palm oil is a seed crop which is widely adopt for food and non-food products such as cookie, vegetable oil, cosmetics, household products and others. Palm oil is majority growth in Malaysia and Indonesia. However, the demand for palm oil is getting growth and rapidly running out over the years. This phenomenal cause illegal logging of trees and destroy the natural habitat. Hence, the present paper investigates the relationship between exchange rate and palm oil price in Malaysia by using Maximum Likelihood Estimation via Newton-Raphson algorithm to fit a two components mixture model. Besides, this paper proposes a mixture of normal distribution to accommodate with asymmetry characteristics and platykurtic time series data.

Collective modes in two-dimensional one-component-plasma with logarithmic interaction

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

Khrapak, Sergey A.; Forschungsgruppe Komplexe Plasmen, Deutsches Zentrum für Luft- und Raumfahrt, Oberpfaffenhofen; Joint Institute for High Temperatures, Russian Academy of Sciences, Moscow

The collective modes of a familiar two-dimensional one-component-plasma with the repulsive logarithmic interaction between the particles are analysed using the quasi-crystalline approximation (QCA) combined with the molecular dynamic simulation of the equilibrium structural properties. It is found that the dispersion curves in the strongly coupled regime are virtually independent of the coupling strength. Arguments based on the excluded volume consideration for the radial distribution function allow us to derive very simple expressions for the dispersion relations, which show excellent agreement with the exact QCA dispersion over the entire domain of wavelengths. Comparison with the results of the conventional fluid analysismore » is performed, and the difference is explained.« less

10 CFR 50.69 - Risk-informed categorization and treatment of structures, systems and components for nuclear...

Code of Federal Regulations, 2012 CFR

2012-01-01

..., systems and components for nuclear power reactors. 50.69 Section 50.69 Energy NUCLEAR REGULATORY..., systems and components for nuclear power reactors. (a) Definitions. Risk-Informed Safety Class (RISC)-1... holder of a license to operate a light water reactor (LWR) nuclear power plant under this part; a holder...

10 CFR 50.69 - Risk-informed categorization and treatment of structures, systems and components for nuclear...

Code of Federal Regulations, 2013 CFR

2013-01-01

..., systems and components for nuclear power reactors. 50.69 Section 50.69 Energy NUCLEAR REGULATORY..., systems and components for nuclear power reactors. (a) Definitions. Risk-Informed Safety Class (RISC)-1... holder of a license to operate a light water reactor (LWR) nuclear power plant under this part; a holder...

10 CFR 50.69 - Risk-informed categorization and treatment of structures, systems and components for nuclear...

Code of Federal Regulations, 2014 CFR

2014-01-01

..., systems and components for nuclear power reactors. 50.69 Section 50.69 Energy NUCLEAR REGULATORY..., systems and components for nuclear power reactors. (a) Definitions. Risk-Informed Safety Class (RISC)-1... holder of a license to operate a light water reactor (LWR) nuclear power plant under this part; a holder...

Regulatory factors governing adenosine-to-inosine (A-to-I) RNA editing.

PubMed

Hong, HuiQi; Lin, Jaymie Siqi; Chen, Leilei

2015-03-31

Adenosine-to-inosine (A-to-I) RNA editing, the most prevalent mode of transcript modification in higher eukaryotes, is catalysed by the adenosine deaminases acting on RNA (ADARs). A-to-I editing imposes an additional layer of gene regulation as it dictates various aspects of RNA metabolism, including RNA folding, processing, localization and degradation. Furthermore, editing events in exonic regions contribute to proteome diversity as translational machinery decodes inosine as guanosine. Although it has been demonstrated that dysregulated A-to-I editing contributes to various diseases, the precise regulatory mechanisms governing this critical cellular process have yet to be fully elucidated. However, integration of previous studies revealed that regulation of A-to-I editing is multifaceted, weaving an intricate network of auto- and transregulations, including the involvement of virus-originated factors like adenovirus-associated RNA. Taken together, it is apparent that tipping of any regulatory components will have profound effects on A-to-I editing, which in turn contributes to both normal and aberrant physiological conditions. A complete understanding of this intricate regulatory network may ultimately be translated into new therapeutic strategies against diseases driven by perturbed RNA editing events. Herein, we review the current state of knowledge on the regulatory mechanisms governing A-to-I editing and propose the role of other co-factors that may be involved in this complex regulatory process.

Regulatory issues in international maritime transport

DOT National Transportation Integrated Search

2001-08-11

This report focuses on regulations governing international liner and bulk shipping. The report discusses the web of regulatory measures that surround these two segments of the shipping industry, and which have a considerable impact on its performance...

Regulatory issues for computerized electrocardiographic devices.

PubMed

Muni, Neal I; Ho, Charles; Mallis, Elias

2004-01-01

Computerized electrocardiogram (ECG) devices are regulated in the U.S. by the FDA Center for Devices and Radiological Health (CDRH). This article aims to highlight the salient points of the FDA regulatory review process, including the important distinction between a "tool" claim and a "clinical" claim in the intended use of a computerized ECG device. Specifically, a tool claim relates to the ability of the device to accurately measure a certain ECG parameter, such as T-wave alternans (TWA), while a clinical claim imputes a particular health hazard associated with the identified parameter, such as increased risk of ventricular tachyarrhythmia or sudden death. Given that both types of claims are equally important and receive the same regulatory scrutiny, the manufacturer of a new ECG diagnostic device should consider the distinction and regulatory pathways for approval between the two types of claims discussed in this paper.

Environmental risk assessment of biocidal products: identification of relevant components and reliability of a component-based mixture assessment.

PubMed

Coors, Anja; Vollmar, Pia; Heim, Jennifer; Sacher, Frank; Kehrer, Anja

2018-01-01

Biocidal products are mixtures of one or more active substances (a.s.) and a broad range of formulation additives. There is regulatory guidance currently under development that will specify how the combined effects of the a.s. and any relevant formulation additives shall be considered in the environmental risk assessment of biocidal products. The default option is a component-based approach (CBA) by which the toxicity of the product is predicted from the toxicity of 'relevant' components using concentration addition. Hence, unequivocal and practicable criteria are required for identifying the 'relevant' components to ensure protectiveness of the CBA, while avoiding unnecessary workload resulting from including by default components that do not significantly contribute to the product toxicity. The present study evaluated a set of different criteria for identifying 'relevant' components using confidential information on the composition of 21 wood preservative products. Theoretical approaches were complemented by experimentally testing the aquatic toxicity of seven selected products. For three of the seven tested products, the toxicity was underestimated for the most sensitive endpoint (green algae) by more than factor 2 if only the a.s. were considered in the CBA. This illustrated the necessity of including at least some additives along with the a.s. Considering additives that were deemed 'relevant' by the tentatively established criteria reduced the underestimation of toxicity for two of the three products. A lack of data for one specific additive was identified as the most likely reason for the remaining toxicity underestimation of the third product. In three other products, toxicity was overestimated by more than factor 2, while prediction and observation fitted well for the seventh product. Considering all additives in the prediction increased only the degree of overestimation. Supported by theoretical calculations and experimental verifications, the present

Two new intermediate polars with a soft X-ray component

NASA Astrophysics Data System (ADS)

Anzolin, G.; de Martino, D.; Bonnet-Bidaud, J.-M.; Mouchet, M.; Gänsicke, B. T.; Matt, G.; Mukai, K.

2008-10-01

Aims: We analyze the first X-ray observations with XMM-Newton of 1RXS J070407.9+262501 and 1RXS 180340.0+401214, in order to characterize their broad-band temporal and spectral properties, also in the UV/optical domain, and to confirm them as intermediate polars. Methods: For both objects, we performed a timing analysis of the X-ray and UV/optical light curves to detect the white dwarf spin pulsations and study their energy dependence. For 1RXS 180340.0+401214 we also analyzed optical spectroscopic data to determine the orbital period. X-ray spectra were analyzed in the 0.2-10.0 keV range to characterize the emission properties of both sources. Results: We find that the X-ray light curves of both systems are energy dependent and are dominated, below 3-5 keV, by strong pulsations at the white dwarf rotational periods (480 s for 1RXS J070407.9+262501 and 1520.5 s for 1RXS 180340.0+401214). In 1RXS 180340.0+401214 we also detect an X-ray beat variability at 1697 s which, together with our new optical spectroscopy, favours an orbital period of 4.4 h that is longer than previously estimated. Both systems show complex spectra with a hard (temperature up to 40 keV) optically thin and a soft (kT ~ 85-100 eV) optically thick components heavily absorbed by material partially covering the X-ray sources. Conclusions: Our observations confirm the two systems as intermediate polars and also add them as new members of the growing group of “soft” systems which show the presence of a soft X-ray blackbody component. Differences in the temperatures of the blackbodies are qualitatively explained in terms of reprocessing over different sizes of the white dwarf spot. We suggest that systems showing cooler soft X-ray blackbody components also possess white dwarfs irradiated by cyclotron radiation. Based on observations obtained with XMM-Newton, an ESA science mission with instruments and contributions directly funded by ESA Member States and NASA, and with the Observatoire de Haute

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

PubMed Central

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

2016-01-01

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

Estimating times of surgeries with two component procedures: comparison of the lognormal and normal models.

PubMed

Strum, David P; May, Jerrold H; Sampson, Allan R; Vargas, Luis G; Spangler, William E

2003-01-01

Variability inherent in the duration of surgical procedures complicates surgical scheduling. Modeling the duration and variability of surgeries might improve time estimates. Accurate time estimates are important operationally to improve utilization, reduce costs, and identify surgeries that might be considered outliers. Surgeries with multiple procedures are difficult to model because they are difficult to segment into homogenous groups and because they are performed less frequently than single-procedure surgeries. The authors studied, retrospectively, 10,740 surgeries each with exactly two CPTs and 46,322 surgical cases with only one CPT from a large teaching hospital to determine if the distribution of dual-procedure surgery times fit more closely a lognormal or a normal model. The authors tested model goodness of fit to their data using Shapiro-Wilk tests, studied factors affecting the variability of time estimates, and examined the impact of coding permutations (ordered combinations) on modeling. The Shapiro-Wilk tests indicated that the lognormal model is statistically superior to the normal model for modeling dual-procedure surgeries. Permutations of component codes did not appear to differ significantly with respect to total procedure time and surgical time. To improve individual models for infrequent dual-procedure surgeries, permutations may be reduced and estimates may be based on the longest component procedure and type of anesthesia. The authors recommend use of the lognormal model for estimating surgical times for surgeries with two component procedures. Their results help legitimize the use of log transforms to normalize surgical procedure times prior to hypothesis testing using linear statistical models. Multiple-procedure surgeries may be modeled using the longest (statistically most important) component procedure and type of anesthesia.

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

PubMed

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

2017-01-01

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

The Nature of Integration among PCK Components: A Case Study of Two Experienced Chemistry Teachers

ERIC Educational Resources Information Center

Aydin, Sevgi; Boz, Yezdan

2013-01-01

In this qualitative case study, we examined the nature of integration among pedagogical content knowledge (PCK) components. To attain the goal, two experienced chemistry teachers' teaching redox reactions and electrochemical cells was observed. The data were collected through card-sorting activity, content representation (CoRe) tool, observation,…

Discrete Boltzmann modeling of Rayleigh-Taylor instability in two-component compressible flows.

PubMed

Lin, Chuandong; Xu, Aiguo; Zhang, Guangcai; Luo, Kai Hong; Li, Yingjun

2017-11-01

A discrete Boltzmann model (DBM) is proposed to probe the Rayleigh-Taylor instability (RTI) in two-component compressible flows. Each species has a flexible specific-heat ratio and is described by one discrete Boltzmann equation (DBE). Independent discrete velocities are adopted for the two DBEs. The collision and force terms in the DBE account for the molecular collision and external force, respectively. Two types of force terms are exploited. In addition to recovering the modified Navier-Stokes equations in the hydrodynamic limit, the DBM has the capability of capturing detailed nonequilibrium effects. Furthermore, we use the DBM to investigate the dynamic process of the RTI. The invariants of tensors for nonequilibrium effects are presented and studied. For low Reynolds numbers, both global nonequilibrium manifestations and the growth rate of the entropy of mixing show three stages (i.e., the reducing, increasing, and then decreasing trends) in the evolution of the RTI. On the other hand, the early reducing tendency is suppressed and even eliminated for high Reynolds numbers. Relevant physical mechanisms are analyzed and discussed.

On the evolution process of two-component dark matter in the Sun

NASA Astrophysics Data System (ADS)

Chen, Chian-Shu; Lin, Yen-Hsun

2018-04-01

We introduce dark matter (DM) evolution process in the Sun under a two-component DM (2DM) scenario. Both DM species χ and ξ with masses heavier than 1 GeV are considered. In this picture, both species could be captured by the Sun through DM-nucleus scattering and DM self-scatterings, e.g. χχ and ξξ collisions. In addition, the heterogeneous self-scattering due to χ and ξ collision is essentially possible in any 2DM models. This new introduced scattering naturally weaves the evolution processes of the two DM species that was assumed to evolve independently. Moreover, the heterogeneous self-scattering enhances the number of DM being captured in the Sun mutually. This effect significantly exists in a broad range of DM mass spectrum. We have studied this phenomena and its implication for the solar-captured DM annihilation rate. It would be crucial to the DM indirect detection when the two masses are close. General formalism of the 2DM evolution in the Sun as well as its kinematics are studied.

Functional annotation of regulatory pathways.

PubMed

Pandey, Jayesh; Koyutürk, Mehmet; Kim, Yohan; Szpankowski, Wojciech; Subramaniam, Shankar; Grama, Ananth

2007-07-01

Standardized annotations of biomolecules in interaction networks (e.g. Gene Ontology) provide comprehensive understanding of the function of individual molecules. Extending such annotations to pathways is a critical component of functional characterization of cellular signaling at the systems level. We propose a framework for projecting gene regulatory networks onto the space of functional attributes using multigraph models, with the objective of deriving statistically significant pathway annotations. We first demonstrate that annotations of pairwise interactions do not generalize to indirect relationships between processes. Motivated by this result, we formalize the problem of identifying statistically overrepresented pathways of functional attributes. We establish the hardness of this problem by demonstrating the non-monotonicity of common statistical significance measures. We propose a statistical model that emphasizes the modularity of a pathway, evaluating its significance based on the coupling of its building blocks. We complement the statistical model by an efficient algorithm and software, Narada, for computing significant pathways in large regulatory networks. Comprehensive results from our methods applied to the Escherichia coli transcription network demonstrate that our approach is effective in identifying known, as well as novel biological pathway annotations. Narada is implemented in Java and is available at http://www.cs.purdue.edu/homes/jpandey/narada/.

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

PubMed

Sarwar, Zaara; Garza, Anthony G

2016-02-01

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

Origin and evolution of two-component debris discs and an application to the q1 Eridani system

NASA Astrophysics Data System (ADS)

Schüppler, Christian; Krivov, Alexander V.; Löhne, Torsten; Booth, Mark; Kirchschlager, Florian; Wolf, Sebastian

2016-09-01

Many debris discs reveal a two-component structure, with an outer Kuiper-belt analogue and a warm inner component whose origin is still a matter of debate. One possibility is that warm emission stems from an `asteroid belt' closer in to the star. We consider a scenario in which a set of giant planets is formed in an initially extended planetesimal disc. These planets carve a broad gap around their orbits, splitting up the disc into the outer and the inner belts. After the gas dispersal, both belts undergo collisional evolution in a steady-state regime. This scenario is explored with detailed collisional simulations involving realistic physics to describe a long-term collisional depletion of the two-component disc. We find that the inner disc may be able to retain larger amounts of material at older ages than thought before on the basis of simplified analytic models. We show that the proposed scenario is consistent with a suite of thermal emission and scattered light observational data for a bright two-temperature debris disc around a nearby solar-type star q1 Eridani. This implies a Solar system-like architecture of the system, with an outer massive `Kuiper belt', an inner `asteroid belt', and a few Neptune- to Jupiter-mass planets in between.

Rayleigh-Taylor instability and mushroom-pattern formation in a two-component Bose-Einstein condensate

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

Sasaki, Kazuki; Suzuki, Naoya; Saito, Hiroki

2009-12-15

The Rayleigh-Taylor instability at the interface in an immiscible two-component Bose-Einstein condensate is investigated using the mean field and Bogoliubov theories. Rayleigh-Taylor fingers are found to grow from the interface and mushroom patterns are formed. Quantized vortex rings and vortex lines are then generated around the mushrooms. The Rayleigh-Taylor instability and mushroom-pattern formation can be observed in a trapped system.

Identification of heterotic loci associated with grain yield and its components using two CSSL test populations in maize

PubMed Central

Wang, Hongqiu; Zhang, Xiangge; Yang, Huili; Liu, Xiaoyang; Li, Huimin; Yuan, Liang; Li, Weihua; Fu, Zhiyuan; Tang, Jihua; Kang, Dingming

2016-01-01

Heterosis has widely been used to increase grain yield and quality. In this study, the genetic basis of heterosis on grain yield and its main components in maize were examined over 2 years in two locations in two test populations constructed from a set of 184 chromosome segment substitution lines (CSSLs) and two inbred lines (Zheng58 and Xun9058). Of the 169 heterotic loci (HL) associated with grain yield and its five components identified in CSSL × Zheng58 and CSSL × Xun9058 test populations, only 25 HL were detected in both populations. The comparison of quantitative trait loci (QTLs) detected in the CSSL population with HL detected in the two test populations revealed that only 15.46% and 17.35% of the HL in the given populations respectively, shared the same chromosomal regions as that of the corresponding QTLs and showed dominant effects as well as pleiotropism with additive and dominant effects. In addition, most of the HL (74.23% and 74.49%) had overdominant effects. These results suggest that overdominance is the main contributor to the effects of heterosis on grain yield and its components in maize, and different HL are associated with heterosis for different traits in different hybrids. PMID:27917917

Computational Studies of the Active and Inactive Regulatory Domains of Response Regulator PhoP Using Molecular Dynamics Simulations.

PubMed

Qing, Xiao-Yu; Steenackers, Hans; Venken, Tom; De Maeyer, Marc; Voet, Arnout

2017-11-01

The response regulator PhoP is part of the PhoP/PhoQ two-component system, which is responsible for regulating the expression of multiple genes involved in controlling virulence, biofilm formation, and resistance to antimicrobial peptides. Therefore, modulating the transcriptional function of the PhoP protein is a promising strategy for developing new antimicrobial agents. There is evidence suggesting that phosphorylation-mediated dimerization in the regulatory domain of PhoP is essential for its transcriptional function. Disruption or stabilization of protein-protein interactions at the dimerization interface may inhibit or enhance the expression of PhoP-dependent genes. In this study, we performed molecular dynamics simulations on the active and inactive dimers and monomers of the PhoP regulatory domains, followed by pocket-detecting screenings and a quantitative hot-spot analysis in order to assess the druggability of the protein. Consistent with prior hypothesis, the calculation of the binding free energy shows that phosphorylation enhances dimerization of PhoP. Furthermore, we have identified two different putative binding sites at the dimerization active site (the α4-β5-α5 face) with energetic "hot-spot" areas, which could be used to search for modulators of protein-protein interactions. This study delivers insight into the dynamics and druggability of the dimerization interface of the PhoP regulatory domain, and may serve as a basis for the rational identification of new antimicrobial drugs. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

NASA's Agency-Wide Strategy for Environmental Regulatory Risk Analysis and Communication

NASA Technical Reports Server (NTRS)

Duda, Kristen; Scroggins, Sharon

2008-01-01

NASA's mission is to pioneer the future in space exploration, scientific discovery, and aeronautics research. To help enable existing and future programs to pursue this mission, NASA has established the Principal Center for Regulatory Risk Analysis and Communication (RRAC PC) to proactively identify, analyze, and communicate environmental regulatory risks to the NASA community. The RRAC PC is chartered to evaluate the risks posed to NASA Programs and facilities by environmentally related drivers. The RRAC PC focuses on emerging environmental regulations, as well as risks related to operational changes that can trigger existing environmental requirements. Changing regulations have the potential to directly affect program activities. For example, regulatory changes can restrict certain activities or operations by mandating changes in how operations may be done or limiting where or how certain operations can take place. Regulatory changes also can directly affect the ability to use certain materials by mandating a production phase-out or restricting usage applications of certain materials. Such changes can result in NASA undertaking material replacement efforts. Even if a regulation does not directly affect NASA operations, U.S. and international regulations can pose program risks indirectly through requirements levied on manufacturers and vendors of components and materials. For example, manufacturers can change their formulations to comply with new regulatory requirements. Such changes can require time-consuming and costly requalification certification for use in human spaceflight programs. The RRAC PC has implemented several strategies for proactively managing regulatory change to minimize potential adverse impacts to NASA Programs and facilities. This presentation highlights the lessons learned through establishing the RRAC PC, the process by which the RRAC PC monitors and distributes information about emerging regulatory requirements, and the cross

NASA's Agency-wide Strategy for Environmental Regulatory Risk Analysis and Communication

NASA Technical Reports Server (NTRS)

Duda, Kristen; Scroggins. Sharon

2008-01-01

NASA's mission is to pioneer the future in space exploration, scientific discovery, and aeronautics research. To help enable existing and future programs to pursue this mission, NASA has established the Principal Center for Regulatory Risk Analysis and Communication (RRAC PC) to proactively identify, analyze, and communicate environmental regulatory risks to the NASA community. The RRAC PC is chartered to evaluate the risks posed to NASA Programs and facilities by environmentally related drivers. The RRAC PC focuses on emerging environmental regulations, as well as risks related to operational changes that can trigger existing environmental requirements. Changing regulations have the potential to directly affect program activities. For example, regulatory changes can restrict certain activities or operations by mandating changes in how operations may be done or limiting where or how certain operations can take place. Regulatory changes also can directly affect the ability to use certain materials by mandating a production phase-out or restricting usage aPi'iications of certain materials. Such changes can result in NASA undertaking material replacement efforts. Even if a regulation does not directly affect NASA operations, U.S. and international regulations can pose program risks indirectly through requirements levied on manufacturers and vendors of components and materials. For example, manufacturers can change their formulations to comply with new regulatory requirements. Such changes can require time-consuming and costly requalification certification for use in human spaceflight programs. The RRAC PC has implemented several strategies for proactively managing regulatory change to minimize potential adverse impacts to NASA Programs and facilities. This presentation highlights the lessons learned through establishing the RRAC PC, the process by which the RRAC PC monitors and distributes information about emerging regulatory requirements, and the cross

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

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-18

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

Improved ganoderic acids production in Ganoderma lucidum by wood decaying components

PubMed Central

Hu, Yanru; Ahmed, Shakeel; Li, Jiawei; Luo, Biaobiao; Gao, Zengyan; Zhang, Qiyun; Li, Xiaohua; Hu, Xuebo

2017-01-01

Ganoderma lucidum is a legendary Traditional Chinese Medicine (TCM) over a few thousands of years and one kind of its major active components are Ganoderic acids (GAs). GAs are largely produced in the mushroom primordium and fruiting body but much less in mycelium stage. However, little is known on the underlying regulatory mechanism. As a saprophytic fungus, G. lucidum solely obtains nutrients by wood decaying. Wood in general contains sophisticated chemical components with diverse structural units. To explore a strategy that extensively leads to GAs induction in the submerged liquid fermentation, all chemical components that might be possibly from the wood decaying were tested individually as GAs inducers. It was found that GAs production increased 85.96% by 1.5% microcrystalline cellulose (MCC) and 63.90% by 0.5% D-galactose. The transcription level of a few rate-limiting or chemically diverting enzymes responsible for GAs biosynthesis was greatly induced by MCC and D-galactose. The concentration and time-course titration study indicated that these two chemicals might not be utilized as carbon sources but they played a comprehensive role in the secondary metabolites synthesis. Our data indicated that MCC and D-galactose might be further industrialized for higher GAs production in G. lucidum in submerged fermentation. PMID:28422185

Regulatory element-based prediction identifies new susceptibility regulatory variants for osteoporosis.

PubMed

Yao, Shi; Guo, Yan; Dong, Shan-Shan; Hao, Ruo-Han; Chen, Xiao-Feng; Chen, Yi-Xiao; Chen, Jia-Bin; Tian, Qing; Deng, Hong-Wen; Yang, Tie-Lin

2017-08-01

Despite genome-wide association studies (GWASs) have identified many susceptibility genes for osteoporosis, it still leaves a large part of missing heritability to be discovered. Integrating regulatory information and GWASs could offer new insights into the biological link between the susceptibility SNPs and osteoporosis. We generated five machine learning classifiers with osteoporosis-associated variants and regulatory features data. We gained the optimal classifier and predicted genome-wide SNPs to discover susceptibility regulatory variants. We further utilized Genetic Factors for Osteoporosis Consortium (GEFOS) and three in-house GWASs samples to validate the associations for predicted positive SNPs. The random forest classifier performed best among all machine learning methods with the F1 score of 0.8871. Using the optimized model, we predicted 37,584 candidate SNPs for osteoporosis. According to the meta-analysis results, a list of regulatory variants was significantly associated with osteoporosis after multiple testing corrections and contributed to the expression of known osteoporosis-associated protein-coding genes. In summary, combining GWASs and regulatory elements through machine learning could provide additional information for understanding the mechanism of osteoporosis. The regulatory variants we predicted will provide novel targets for etiology research and treatment of osteoporosis.

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

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-10

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. AD06-6-000] Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission; Notice of Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission March 2, 2010. The Federal Energy Regulatory Commission (FERC)...

Mouse regulatory DNA landscapes reveal global principles of cis-regulatory evolution.

PubMed

Vierstra, Jeff; Rynes, Eric; Sandstrom, Richard; Zhang, Miaohua; Canfield, Theresa; Hansen, R Scott; Stehling-Sun, Sandra; Sabo, Peter J; Byron, Rachel; Humbert, Richard; Thurman, Robert E; Johnson, Audra K; Vong, Shinny; Lee, Kristen; Bates, Daniel; Neri, Fidencio; Diegel, Morgan; Giste, Erika; Haugen, Eric; Dunn, Douglas; Wilken, Matthew S; Josefowicz, Steven; Samstein, Robert; Chang, Kai-Hsin; Eichler, Evan E; De Bruijn, Marella; Reh, Thomas A; Skoultchi, Arthur; Rudensky, Alexander; Orkin, Stuart H; Papayannopoulou, Thalia; Treuting, Piper M; Selleri, Licia; Kaul, Rajinder; Groudine, Mark; Bender, M A; Stamatoyannopoulos, John A

2014-11-21

To study the evolutionary dynamics of regulatory DNA, we mapped >1.3 million deoxyribonuclease I-hypersensitive sites (DHSs) in 45 mouse cell and tissue types, and systematically compared these with human DHS maps from orthologous compartments. We found that the mouse and human genomes have undergone extensive cis-regulatory rewiring that combines branch-specific evolutionary innovation and loss with widespread repurposing of conserved DHSs to alternative cell fates, and that this process is mediated by turnover of transcription factor (TF) recognition elements. Despite pervasive evolutionary remodeling of the location and content of individual cis-regulatory regions, within orthologous mouse and human cell types the global fraction of regulatory DNA bases encoding recognition sites for each TF has been strictly conserved. Our findings provide new insights into the evolutionary forces shaping mammalian regulatory DNA landscapes. Copyright © 2014, American Association for the Advancement of Science.

Recurrent rewiring and emergence of RNA regulatory networks.

PubMed

Wilinski, Daniel; Buter, Natascha; Klocko, Andrew D; Lapointe, Christopher P; Selker, Eric U; Gasch, Audrey P; Wickens, Marvin

2017-04-04

Alterations in regulatory networks contribute to evolutionary change. Transcriptional networks are reconfigured by changes in the binding specificity of transcription factors and their cognate sites. The evolution of RNA-protein regulatory networks is far less understood. The PUF (Pumilio and FBF) family of RNA regulatory proteins controls the translation, stability, and movements of hundreds of mRNAs in a single species. We probe the evolution of PUF-RNA networks by direct identification of the mRNAs bound to PUF proteins in budding and filamentous fungi and by computational analyses of orthologous RNAs from 62 fungal species. Our findings reveal that PUF proteins gain and lose mRNAs with related and emergent biological functions during evolution. We demonstrate at least two independent rewiring events for PUF3 orthologs, independent but convergent evolution of PUF4/5 binding specificity and the rewiring of the PUF4/5 regulons in different fungal lineages. These findings demonstrate plasticity in RNA regulatory networks and suggest ways in which their rewiring occurs.

Toward a Regulatory Framework for the Waterpipe.

PubMed

Salloum, Ramzi G; Asfar, Taghrid; Maziak, Wasim

2016-10-01

Waterpipe smoking has been dramatically increasing among youth worldwide and in the United States. Despite its general association with misperceptions of reduced harm, evidence suggests this is a harmful and dependence-inducing tobacco use method that represents a threat to public health. Waterpipe products continue to be generally unregulated, which likely has contributed to their spread. The Family Smoking Prevention and Tobacco Control Act of 2009 granted the US Food and Drug Administration (FDA) the authority to regulate waterpipe products, and the FDA finalized a rule extending its authority over waterpipe products in May 2016. This critical step in addressing the alarming increase in waterpipe smoking in the United States has created urgency for research to provide the evidence needed for effective regulatory initiatives for waterpipe products. We aim to stimulate such research by providing a framework that addresses the scope of waterpipe products and their unique context and use patterns. The proposed framework identifies regulatory targets for waterpipe product components (i.e., tobacco, charcoal, and device), the waterpipe café setting, and its marketing environment dominated by Internet promotion.

Noncoding RNA:RNA Regulatory Networks in Cancer

PubMed Central

Chan, Jia Jia; Tay, Yvonne

2018-01-01

Noncoding RNAs (ncRNAs) constitute the majority of the human transcribed genome. This largest class of RNA transcripts plays diverse roles in a multitude of cellular processes, and has been implicated in many pathological conditions, especially cancer. The different subclasses of ncRNAs include microRNAs, a class of short ncRNAs; and a variety of long ncRNAs (lncRNAs), such as lincRNAs, antisense RNAs, pseudogenes, and circular RNAs. Many studies have demonstrated the involvement of these ncRNAs in competitive regulatory interactions, known as competing endogenous RNA (ceRNA) networks, whereby lncRNAs can act as microRNA decoys to modulate gene expression. These interactions are often interconnected, thus aberrant expression of any network component could derail the complex regulatory circuitry, culminating in cancer development and progression. Recent integrative analyses have provided evidence that new computational platforms and experimental approaches can be harnessed together to distinguish key ceRNA interactions in specific cancers, which could facilitate the identification of robust biomarkers and therapeutic targets, and hence, more effective cancer therapies and better patient outcome and survival. PMID:29702599

Toward a Regulatory Framework for the Waterpipe

PubMed Central

Salloum, Ramzi G.; Asfar, Taghrid

2016-01-01

Waterpipe smoking has been dramatically increasing among youth worldwide and in the United States. Despite its general association with misperceptions of reduced harm, evidence suggests this is a harmful and dependence-inducing tobacco use method that represents a threat to public health. Waterpipe products continue to be generally unregulated, which likely has contributed to their spread. The Family Smoking Prevention and Tobacco Control Act of 2009 granted the US Food and Drug Administration (FDA) the authority to regulate waterpipe products, and the FDA finalized a rule extending its authority over waterpipe products in May 2016. This critical step in addressing the alarming increase in waterpipe smoking in the United States has created urgency for research to provide the evidence needed for effective regulatory initiatives for waterpipe products. We aim to stimulate such research by providing a framework that addresses the scope of waterpipe products and their unique context and use patterns. The proposed framework identifies regulatory targets for waterpipe product components (i.e., tobacco, charcoal, and device), the waterpipe café setting, and its marketing environment dominated by Internet promotion. PMID:27552262

76 FR 12769 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-08

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate...,\\2\\ notice is hereby given that on February 16, 2011, the Financial Industry Regulatory Authority... CFR 240.19b-4(f)(3). I. Self-Regulatory Organization's Statement of the Terms of Substance of the...

Self-selection of two diet components by Tenebrio molitor (Coleoptera: Tenebrionidae) larvae and its impact on fitness.

PubMed

Morales-Ramos, J A; Rojas, M G; Shapiro-Ilan, D I; Tedders, W L

2011-10-01

We studied the ability of Tenebrio molitor L. (Coleoptera: Tenebrionidae) to self-select optimal ratios of two dietary components to approach nutritional balance and maximum fitness. Relative consumption of wheat bran and dry potato flakes was determined among larvae feeding on four different ratios of these components (10, 20, 30, and 40% potato). Groups of early instars were provided with a measured amount of food and the consumption of each diet component was measured at the end of 4 wk and again 3 wk later. Consumption of diet components by T. molitor larvae deviated significantly from expected ratios indicating nonrandom self-selection. Mean percentages of dry potato consumed were 11.98, 19.16, 19.02, and 19.27% and 11.89, 20.48, 24.67, and 25.97% during the first and second experimental periods for diets with 10, 20, 30, and 40% potato, respectively. Life table analysis was used to determine the fitness of T. molitor developing in the four diet mixtures in a no-choice experiment. The diets were compared among each other and a control diet of wheat bran only. Doubling time was significantly shorter in groups consuming 10 and 20% potato than the control and longer in groups feeding on 30 and 40% potato. The self-selected ratios of the two diet components approached 20% potato, which was the best ratio for development and second best for population growth. Our findings show dietary self-selection behavior in T. molitor larvae, and these findings may lead to new methods for optimizing dietary supplements for T. molitor.

Thermoset nanocomposites from two-component waterborne polyurethanes and cellulose whiskers.

PubMed

Wu, Guo-min; Chen, Jian; Huo, Shu-ping; Liu, Gui-feng; Kong, Zhen-wu

2014-05-25

We prepared thermoset nancomposites from biomass-based two-component waterborne polyurethane (2K-WPU) and cellulose namowhiskers (CNWs). Due to the formation of hydrogen bonds, the viscosity of 2K-WPU dispersion was found to be increased with the addition of CNWs. SEM images showed "sea-island structure" corresponding to the microphase separation between CNWs nano-filler and the 2K-WPU matrix. The α-relaxation temperature (Tα) and glass transition temperature (Tg) increased with the increase of CNWs content, which was due to the formation of a rigid CNWs nano-phase acting as crosslinking points in the 2K-WPU matrix. Mechanical properties from tensile test showed Young's modulus and tensile strength of 2K-WPU/CNWs nanocomposites were reinforced by the addition of CNWs. Thermo-stability of 2K-WPU/CNWs nanocomposites decreased slightly with the increase of CNWs content, which could be attributed to the increased thermal conductivity of the material after adding CNWs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Signature of Two-Component Advective Flow in several Black Hole candidates obtained through time-of-arrival analysis of RXTE/ASM Data

NASA Astrophysics Data System (ADS)

Ghosh, Arindam; Chakrabarti, Sandip K.

2018-05-01

We study several Galactic black hole candidates using long-time RXTE/ASM X-ray data to search for telltale signatures of differences in viscous timescales in the two components used in the Two-Component Advective Flow (TCAF) paradigm. In high-mass X-ray binaries (HMXBs) mainly winds are accreted. This nearly inviscid and dominant sub-Keplerian flow falls almost freely towards the black hole. A standard Keplerian disc can form out of this sub-Keplerian matter in presence of a significant viscosity and could be small in size. However, in low-mass X-ray binaries (LMXBs), highly viscous and larger Keplerian accretion disc is expected to form inside the sub-Keplerian disc due to the Roche-lobe overflow. Due to two viscous timescales in these two components, it is expected to have a larger lag between the times-of-arrival of these components in LMXBs than that in HMXBs. Direct cross-correlation between the photon fluxes will not reveal this lag since they lack linear dependence; however, they are coupled through the viscous processes which bring in both matter. To quantify the aforesaid time lag, we introduce an index (Θ), which is a proxy of the usual photon index (Γ). Thus, when Θ, being dynamically responsive to both fluxes, is considered as a reference, the arrival time lag between the two fluxes in LMXBs is found to be much larger than that in HMXBs. Our result establishes the presence of two dynamical components in accretion and shows that the Keplerian disc size indeed is smaller in HMXBs as compared to that in LMXBs.

10 CFR 60.135 - Criteria for the waste package and its components.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Section 60.135 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) DISPOSAL OF HIGH-LEVEL RADIOACTIVE WASTES... for the waste package and its components. (a) High-level-waste package design in general. (1) Packages... package's permanent written records. (c) Waste form criteria for HLW. High-level radioactive waste that is...

Multibody model reduction by component mode synthesis and component cost analysis

NASA Technical Reports Server (NTRS)

Spanos, J. T.; Mingori, D. L.

1990-01-01

The classical assumed-modes method is widely used in modeling the dynamics of flexible multibody systems. According to the method, the elastic deformation of each component in the system is expanded in a series of spatial and temporal functions known as modes and modal coordinates, respectively. This paper focuses on the selection of component modes used in the assumed-modes expansion. A two-stage component modal reduction method is proposed combining Component Mode Synthesis (CMS) with Component Cost Analysis (CCA). First, each component model is truncated such that the contribution of the high frequency subsystem to the static response is preserved. Second, a new CMS procedure is employed to assemble the system model and CCA is used to further truncate component modes in accordance with their contribution to a quadratic cost function of the system output. The proposed method is demonstrated with a simple example of a flexible two-body system.

Reconstructing directed gene regulatory network by only gene expression data.

PubMed

Zhang, Lu; Feng, Xi Kang; Ng, Yen Kaow; Li, Shuai Cheng

2016-08-18

Accurately identifying gene regulatory network is an important task in understanding in vivo biological activities. The inference of such networks is often accomplished through the use of gene expression data. Many methods have been developed to evaluate gene expression dependencies between transcription factor and its target genes, and some methods also eliminate transitive interactions. The regulatory (or edge) direction is undetermined if the target gene is also a transcription factor. Some methods predict the regulatory directions in the gene regulatory networks by locating the eQTL single nucleotide polymorphism, or by observing the gene expression changes when knocking out/down the candidate transcript factors; regrettably, these additional data are usually unavailable, especially for the samples deriving from human tissues. In this study, we propose the Context Based Dependency Network (CBDN), a method that is able to infer gene regulatory networks with the regulatory directions from gene expression data only. To determine the regulatory direction, CBDN computes the influence of source to target by evaluating the magnitude changes of expression dependencies between the target gene and the others with conditioning on the source gene. CBDN extends the data processing inequality by involving the dependency direction to distinguish between direct and transitive relationship between genes. We also define two types of important regulators which can influence a majority of the genes in the network directly or indirectly. CBDN can detect both of these two types of important regulators by averaging the influence functions of candidate regulator to the other genes. In our experiments with simulated and real data, even with the regulatory direction taken into account, CBDN outperforms the state-of-the-art approaches for inferring gene regulatory network. CBDN identifies the important regulators in the predicted network: 1. TYROBP influences a batch of genes that are

Evaluation of solution stability for two-component polydisperse systems by small-angle scattering

NASA Astrophysics Data System (ADS)

Kryukova, A. E.; Konarev, P. V.; Volkov, V. V.

2017-12-01

The article is devoted to the modelling of small-angle scattering data using the program MIXTURE designed for the study of polydisperse multicomponent mixtures. In this work we present the results of solution stability studies for theoretical small-angle scattering data sets from two-component models. It was demonstrated that the addition of the noise to the data influences the stability range of the restored structural parameters. The recommendations for the optimal minimization schemes that permit to restore the volume size distributions for polydisperse systems are suggested.

Numerical verification of two-component dental implant in the context of fatigue life for various load cases.

PubMed

Szajek, Krzysztof; Wierszycki, Marcin

2016-01-01

Dental implant designing is a complex process which considers many limitations both biological and mechanical in nature. In earlier studies, a complete procedure for improvement of two-component dental implant was proposed. However, the optimization tasks carried out required assumption on representative load case, which raised doubts on optimality for the other load cases. This paper deals with verification of the optimal design in context of fatigue life and its main goal is to answer the question if the assumed load scenario (solely horizontal occlusal load) leads to the design which is also "safe" for oblique occlussal loads regardless the angle from an implant axis. The verification is carried out with series of finite element analyses for wide spectrum of physiologically justified loads. The design of experiment methodology with full factorial technique is utilized. All computations are done in Abaqus suite. The maximal Mises stress and normalized effective stress amplitude for various load cases are discussed and compared with the assumed "safe" limit (equivalent of fatigue life for 5e6 cycles). The obtained results proof that coronial-appical load component should be taken into consideration in the two component dental implant when fatigue life is optimized. However, its influence in the analyzed case is small and does not change the fact that the fatigue life improvement is observed for all components within whole range of analyzed loads.

Uncovering MicroRNA and Transcription Factor Mediated Regulatory Networks in Glioblastoma

PubMed Central

Sun, Jingchun; Gong, Xue; Purow, Benjamin; Zhao, Zhongming

2012-01-01

Glioblastoma multiforme (GBM) is the most common and lethal brain tumor in humans. Recent studies revealed that patterns of microRNA (miRNA) expression in GBM tissue samples are different from those in normal brain tissues, suggesting that a number of miRNAs play critical roles in the pathogenesis of GBM. However, little is yet known about which miRNAs play central roles in the pathology of GBM and their regulatory mechanisms of action. To address this issue, in this study, we systematically explored the main regulation format (feed-forward loops, FFLs) consisting of miRNAs, transcription factors (TFs) and their impacting GBM-related genes, and developed a computational approach to construct a miRNA-TF regulatory network. First, we compiled GBM-related miRNAs, GBM-related genes, and known human TFs. We then identified 1,128 3-node FFLs and 805 4-node FFLs with statistical significance. By merging these FFLs together, we constructed a comprehensive GBM-specific miRNA-TF mediated regulatory network. Then, from the network, we extracted a composite GBM-specific regulatory network. To illustrate the GBM-specific regulatory network is promising for identification of critical miRNA components, we specifically examined a Notch signaling pathway subnetwork. Our follow up topological and functional analyses of the subnetwork revealed that six miRNAs (miR-124, miR-137, miR-219-5p, miR-34a, miR-9, and miR-92b) might play important roles in GBM, including some results that are supported by previous studies. In this study, we have developed a computational framework to construct a miRNA-TF regulatory network and generated the first miRNA-TF regulatory network for GBM, providing a valuable resource for further understanding the complex regulatory mechanisms in GBM. The observation of critical miRNAs in the Notch signaling pathway, with partial verification from previous studies, demonstrates that our network-based approach is promising for the identification of new and important

Two distinct auto-regulatory loops operate at the PU.1 locus in B cells and myeloid cells

PubMed Central

Leddin, Mathias; Perrod, Chiara; Hoogenkamp, Maarten; Ghani, Saeed; Assi, Salam; Heinz, Sven; Wilson, Nicola K.; Follows, George; Schönheit, Jörg; Vockentanz, Lena; Mosammam, Ali M.; Chen, Wei; Tenen, Daniel G.; Westhead, David R.; Göttgens, Berthold

2011-01-01

The transcription factor PU.1 occupies a central role in controlling myeloid and early B-cell development, and its correct lineage-specific expression is critical for the differentiation choice of hematopoietic progenitors. However, little is known of how this tissue-specific pattern is established. We previously identified an upstream regulatory cis element whose targeted deletion in mice decreases PU.1 expression and causes leukemia. We show here that the upstream regulatory cis element alone is insufficient to confer physiologic PU.1 expression in mice but requires the cooperation with other, previously unidentified elements. Using a combination of transgenic studies, global chromatin assays, and detailed molecular analyses we present evidence that PU.1 is regulated by a novel mechanism involving cross talk between different cis elements together with lineage-restricted autoregulation. In this model, PU.1 regulates its expression in B cells and macrophages by differentially associating with cell type–specific transcription factors at one of its cis-regulatory elements to establish differential activity patterns at other elements. PMID:21239694

2L-PCA: a two-level principal component analyzer for quantitative drug design and its applications.

PubMed

Du, Qi-Shi; Wang, Shu-Qing; Xie, Neng-Zhong; Wang, Qing-Yan; Huang, Ri-Bo; Chou, Kuo-Chen

2017-09-19

A two-level principal component predictor (2L-PCA) was proposed based on the principal component analysis (PCA) approach. It can be used to quantitatively analyze various compounds and peptides about their functions or potentials to become useful drugs. One level is for dealing with the physicochemical properties of drug molecules, while the other level is for dealing with their structural fragments. The predictor has the self-learning and feedback features to automatically improve its accuracy. It is anticipated that 2L-PCA will become a very useful tool for timely providing various useful clues during the process of drug development.

10 CFR 73.46 - Fixed site physical protection systems, subsystems, components, and procedures.

Code of Federal Regulations, 2014 CFR

2014-01-01

..., components, and procedures. 73.46 Section 73.46 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) PHYSICAL... Energy couriers engaged in the transport of special nuclear material. The search function for detection... of Energy vehicles engaged in transporting special nuclear material and emergency vehicles under...

10 CFR 73.46 - Fixed site physical protection systems, subsystems, components, and procedures.

Code of Federal Regulations, 2012 CFR

2012-01-01

..., components, and procedures. 73.46 Section 73.46 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) PHYSICAL... Energy couriers engaged in the transport of special nuclear material. The search function for detection... of Energy vehicles engaged in transporting special nuclear material and emergency vehicles under...

Regulatory fit effects on perceived fiscal exchange and tax compliance

PubMed Central

Leder, Susanne; Mannetti, Lucia; Hölzl, Erik; Kirchler, Erich

2010-01-01

Paying taxes can be considered a contribution to the welfare of a society. But even though tax payments are redistributed to citizens in the form of public goods and services, taxpayers often do not perceive many benefits from paying taxes. Information campaigns about the use of taxes for financing public goods and services could increase taxpayers’ understanding of the importance of taxes, strengthen their perception of fiscal exchange and consequently also increase tax compliance. Two studies examined how fit between framing of information and taxpayers’ regulatory focus affects perceived fiscal exchange and tax compliance. Taxpayers should perceive the exchange between tax payments and provision of public goods and services as higher if information framing suits their regulatory focus. Study 1 supported this hypothesis for induced regulatory focus. Study 2 replicated the findings for chronic regulatory focus and further demonstrated that regulatory fit also affects tax compliance. The results provide further evidence for findings from previous studies concerning regulatory fit effects on tax attitudes and extend these findings to a context with low tax morale. PMID:20890461

Regulatory RNAs and the HptB/RetS signalling pathways fine-tune Pseudomonas aeruginosa pathogenesis

PubMed Central

Bordi, Christophe; Lamy, Marie-Cécile; Ventre, Isabelle; Termine, Elise; Hachani, Abderrahman; Fillet, Sandy; Roche, Béatrice; Bleves, Sophie; Méjean, Vincent; Lazdunski, Andrée; Filloux, Alain

2010-01-01

Bacterial pathogenesis often depends on regulatory networks, two-component systems and small RNAs (sRNAs). In Pseudomonas aeruginosa, the RetS sensor pathway downregulates expression of two sRNAs, rsmY and rsmZ. Consequently, biofilm and the Type Six Secretion System (T6SS) are repressed, whereas the Type III Secretion System (T3SS) is activated. We show that the HptB signalling pathway controls biofilm and T3SS, and fine-tunes P. aeruginosa pathogenesis. We demonstrate that RetS and HptB intersect at the GacA response regulator, which directly controls sRNAs production. Importantly, RetS controls both sRNAs, whereas HptB exclusively regulates rsmY expression. We reveal that HptB signalling is a complex regulatory cascade. This cascade involves a response regulator, with an output domain belonging to the phosphatase 2C family, and likely an anti-anti-σ factor. This reveals that the initial input in the Gac system comes from several signalling pathways, and the final output is adjusted by a differential control on rsmY and rsmZ. This is exemplified by the RetS-dependent but HptB-independent control on T6SS. We also demonstrate a redundant action of the two sRNAs on T3SS gene expression, while the impact on pel gene expression is additive. These features underpin a novel mechanism in the fine-tuned regulation of gene expression. PMID:20398205

Controlled expression of nif and isc iron-sulfur protein maturation components reveals target specificity and limited functional replacement between the two systems.

PubMed

Dos Santos, Patricia C; Johnson, Deborah C; Ragle, Brook E; Unciuleac, Mihaela-Carmen; Dean, Dennis R

2007-04-01

The nitrogen-fixing organism Azotobacter vinelandii contains at least two systems that catalyze formation of [Fe-S] clusters. One of these systems is encoded by nif genes, whose products supply [Fe-S] clusters required for maturation of nitrogenase. The other system is encoded by isc genes, whose products are required for maturation of [Fe-S] proteins that participate in general metabolic processes. The two systems are similar in that they include an enzyme for the mobilization of sulfur (NifS or IscS) and an assembly scaffold (NifU or IscU) upon which [Fe-S] clusters are formed. Normal cellular levels of the Nif system, which supplies [Fe-S] clusters for the maturation of nitrogenase, cannot also supply [Fe-S] clusters for the maturation of other cellular [Fe-S] proteins. Conversely, when produced at the normal physiological levels, the Isc system cannot supply [Fe-S] clusters for the maturation of nitrogenase. In the present work we found that such target specificity for IscU can be overcome by elevated production of NifU. We also found that NifU, when expressed at normal levels, is able to partially replace the function of IscU if cells are cultured under low-oxygen-availability conditions. In contrast to the situation with IscU, we could not establish conditions in which the function of IscS could be replaced by NifS. We also found that elevated expression of the Isc components, as a result of deletion of the regulatory iscR gene, improved the capacity for nitrogen-fixing growth of strains deficient in either NifU or NifS.

Frustrated spin chains in strong magnetic field: Dilute two-component Bose gas regime

NASA Astrophysics Data System (ADS)

Kolezhuk, A. K.; Heidrich-Meisner, F.; Greschner, S.; Vekua, T.

2012-02-01

We study the ground state of frustrated spin-S chains in a strong magnetic field in the immediate vicinity of saturation. In strongly frustrated chains, the magnon dispersion has two degenerate minima at inequivalent momenta ±Q, and just below the saturation field the system can be effectively represented as a dilute one-dimensional lattice gas of two species of bosons that correspond to magnons with momenta around ±Q. We present a theory of effective interactions in such a dilute magnon gas that allows us to make quantitative predictions for arbitrary values of the spin. With the help of this method, we are able to establish the magnetic phase diagram of frustrated chains close to saturation and study phase transitions between several nontrivial states, including a two-component Luttinger liquid, a vector chiral phase, and phases with bound magnons. We study those phase transitions numerically and find a good agreement with our analytical predictions.

Two-Component Structure of the Radio Source 0014+813 from VLBI Observations within the CONT14 Program

NASA Astrophysics Data System (ADS)

Titov, O. A.; Lopez, Yu. R.

2018-03-01

We consider a method of reconstructing the structure delay of extended radio sources without constructing their radio images. The residuals derived after the adjustment of geodetic VLBI observations are used for this purpose. We show that the simplest model of a radio source consisting of two point components can be represented by four parameters (the angular separation of the components, the mutual orientation relative to the poleward direction, the flux-density ratio, and the spectral index difference) that are determined for each baseline of a multi-baseline VLBI network. The efficiency of this approach is demonstrated by estimating the coordinates of the radio source 0014+813 observed during the two-week CONT14 program organized by the International VLBI Service (IVS) in May 2014. Large systematic deviations have been detected in the residuals of the observations for the radio source 0014+813. The averaged characteristics of the radio structure of 0014+813 at a frequency of 8.4 GHz can be calculated from these deviations. Our modeling using four parameters has confirmed that the source consists of two components at an angular separation of 0.5 mas in the north-south direction. Using the structure delay when adjusting the CONT14 observations leads to a correction of the average declination estimate for the radio source 0014+813 by 0.070 mas.

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

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-26

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

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

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-30

...The Office of the Comptroller of the Currency (OCC), Board of Governors of the Federal Reserve System (Board), and the Federal Deposit Insurance Corporation (FDIC) (collectively, the agencies) are seeking comment on three Notices of Proposed Rulemaking (NPR) that would revise and replace the agencies' current capital rules. In this NPR, the agencies are proposing to revise their risk-based and leverage capital requirements consistent with agreements reached by the Basel Committee on Banking Supervision (BCBS) in ``Basel III: A Global Regulatory Framework for More Resilient Banks and Banking Systems'' (Basel III). The proposed revisions would include implementation of a new common equity tier 1 minimum capital requirement, a higher minimum tier 1 capital requirement, and, for banking organizations subject to the advanced approaches capital rules, a supplementary leverage ratio that incorporates a broader set of exposures in the denominator measure. Additionally, consistent with Basel III, the agencies are proposing to apply limits on a banking organization's capital distributions and certain discretionary bonus payments if the banking organization does not hold a specified amount of common equity tier 1 capital in addition to the amount necessary to meet its minimum risk- based capital requirements. This NPR also would establish more conservative standards for including an instrument in regulatory capital. As discussed in the proposal, the revisions set forth in this NPR are consistent with section 171 of the Dodd-Frank Wall Street Reform and Consumer Protection Act (Dodd-Frank Act), which requires the agencies to establish minimum risk-based and leverage capital requirements. In connection with the proposed changes to the agencies' capital rules in this NPR, the agencies are also seeking comment on the two related NPRs published elsewhere in today's Federal Register. The two related NPRs are discussed further in the SUPPLEMENTARY INFORMATION.

Multilayer regulatory mechanisms control cleavage factor I proteins in filamentous fungi

PubMed Central

Rodríguez-Romero, J.; Franceschetti, M.; Bueno, E.; Sesma, A.

2015-01-01

Cleavage factor I (CFI) proteins are core components of the polyadenylation machinery that can regulate several steps of mRNA life cycle, including alternative polyadenylation, splicing, export and decay. Here, we describe the regulatory mechanisms that control two fungal CFI protein classes in Magnaporthe oryzae: Rbp35/CfI25 complex and Hrp1. Using mutational, genetic and biochemical studies we demonstrate that cellular concentration of CFI mRNAs is a limited indicator of their protein abundance. Our results suggest that several post-transcriptional mechanisms regulate Rbp35/CfI25 complex and Hrp1 in the rice blast fungus, some of which are also conserved in other ascomycetes. With respect to Rbp35, these include C-terminal processing, RGG-dependent localization and cleavage, C-terminal autoregulatory domain and regulation by an upstream open reading frame of Rbp35-dependent TOR signalling pathway. Our proteomic analyses suggest that Rbp35 regulates the levels of proteins involved in melanin and phenylpropanoids synthesis, among others. The drastic reduction of fungal CFI proteins in carbon-starved cells suggests that the pre-mRNA processing pathway is altered. Our findings uncover broad and multilayer regulatory mechanisms controlling fungal polyadenylation factors, which have profound implications in pre-mRNA maturation. This area of research offers new avenues for fungicide design by targeting fungal-specific proteins that globally affect thousands of mRNAs. PMID:25514925

Unique Biofilm Signature, Drug Susceptibility and Decreased Virulence in Drosophila through the Pseudomonas aeruginosa Two-Component System PprAB

PubMed Central

Giraud, Caroline; Bernard, Christophe S.; Calderon, Virginie; Ewald, Friederike; Plésiat, Patrick; Nguyen, Cathy; Grunwald, Didier; Attree, Ina; Jeannot, Katy; Fauvarque, Marie-Odile

2012-01-01

Bacterial biofilm is considered as a particular lifestyle helping cells to survive hostile environments triggered by a variety of signals sensed and integrated through adequate regulatory pathways. Pseudomonas aeruginosa, a Gram-negative bacterium causing severe infections in humans, forms biofilms and is a fantastic example for fine-tuning of the transition between planktonic and community lifestyles through two-component systems (TCS). Here we decipher the regulon of the P. aeruginosa response regulator PprB of the TCS PprAB. We identified genes under the control of this TCS and once this pathway is activated, analyzed and dissected at the molecular level the PprB-dependent phenotypes in various models. The TCS PprAB triggers a hyper-biofilm phenotype with a unique adhesive signature made of BapA adhesin, a Type 1 secretion system (T1SS) substrate, CupE CU fimbriae, Flp Type IVb pili and eDNA without EPS involvement. This unique signature is associated with drug hyper-susceptibility, decreased virulence in acutely infected flies and cytotoxicity toward various cell types linked to decreased Type III secretion (T3SS). Moreover, once the PprB pathway is activated, decreased virulence in orally infected flies associated with enhanced biofilm formation and dissemination defect from the intestinal lumen toward the hemolymph compartment is reported. PprB may thus represent a key bacterial adaptation checkpoint of multicellular and aggregative behavior triggering the production of a unique matrix associated with peculiar antibiotic susceptibility and attenuated virulence, a particular interesting breach for therapeutic intervention to consider in view of possible eradication of P. aeruginosa biofilm-associated infections. PMID:23209420

Linearmycins Activate a Two-Component Signaling System Involved in Bacterial Competition and Biofilm Morphology

PubMed Central

2017-01-01

ABSTRACT Bacteria use two-component signaling systems to adapt and respond to their competitors and changing environments. For instance, competitor bacteria may produce antibiotics and other bioactive metabolites and sequester nutrients. To survive, some species of bacteria escape competition through antibiotic production, biofilm formation, or motility. Specialized metabolite production and biofilm formation are relatively well understood for bacterial species in isolation. How bacteria control these functions when competitors are present is not well studied. To address fundamental questions relating to the competitive mechanisms of different species, we have developed a model system using two species of soil bacteria, Bacillus subtilis and Streptomyces sp. strain Mg1. Using this model, we previously found that linearmycins produced by Streptomyces sp. strain Mg1 cause lysis of B. subtilis cells and degradation of colony matrix. We identified strains of B. subtilis with mutations in the two-component signaling system yfiJK operon that confer dual phenotypes of specific linearmycin resistance and biofilm morphology. We determined that expression of the ATP-binding cassette (ABC) transporter yfiLMN operon, particularly yfiM and yfiN, is necessary for biofilm morphology. Using transposon mutagenesis, we identified genes that are required for YfiLMN-mediated biofilm morphology, including several chaperones. Using transcriptional fusions, we found that YfiJ signaling is activated by linearmycins and other polyene metabolites. Finally, using a truncated YfiJ, we show that YfiJ requires its transmembrane domain to activate downstream signaling. Taken together, these results suggest coordinated dual antibiotic resistance and biofilm morphology by a single multifunctional ABC transporter promotes competitive fitness of B. subtilis. IMPORTANCE DNA sequencing approaches have revealed hitherto unexplored diversity of bacterial species in a wide variety of environments that

Inference of cancer-specific gene regulatory networks using soft computing rules.

PubMed

Wang, Xiaosheng; Gotoh, Osamu

2010-03-24

Perturbations of gene regulatory networks are essentially responsible for oncogenesis. Therefore, inferring the gene regulatory networks is a key step to overcoming cancer. In this work, we propose a method for inferring directed gene regulatory networks based on soft computing rules, which can identify important cause-effect regulatory relations of gene expression. First, we identify important genes associated with a specific cancer (colon cancer) using a supervised learning approach. Next, we reconstruct the gene regulatory networks by inferring the regulatory relations among the identified genes, and their regulated relations by other genes within the genome. We obtain two meaningful findings. One is that upregulated genes are regulated by more genes than downregulated ones, while downregulated genes regulate more genes than upregulated ones. The other one is that tumor suppressors suppress tumor activators and activate other tumor suppressors strongly, while tumor activators activate other tumor activators and suppress tumor suppressors weakly, indicating the robustness of biological systems. These findings provide valuable insights into the pathogenesis of cancer.

77 FR 43620 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-25

... self-regulatory organization consents, the Commission shall either approve the proposed rule change...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Designation of a Longer Period for Commission Action on Proposed Rule Change Relating to the Handling of Stop and Stop Limit...

Two-Component Noncollinear Time-Dependent Spin Density Functional Theory for Excited State Calculations.

PubMed

Egidi, Franco; Sun, Shichao; Goings, Joshua J; Scalmani, Giovanni; Frisch, Michael J; Li, Xiaosong

2017-06-13

We present a linear response formalism for the description of the electronic excitations of a noncollinear reference defined via Kohn-Sham spin density functional methods. A set of auxiliary variables, defined using the density and noncollinear magnetization density vector, allows the generalization of spin density functional kernels commonly used in collinear DFT to noncollinear cases, including local density, GGA, meta-GGA and hybrid functionals. Working equations and derivations of functional second derivatives with respect to the noncollinear density, required in the linear response noncollinear TDDFT formalism, are presented in this work. This formalism takes all components of the spin magnetization into account independent of the type of reference state (open or closed shell). As a result, the method introduced here is able to afford a nonzero local xc torque on the spin magnetization while still satisfying the zero-torque theorem globally. The formalism is applied to a few test cases using the variational exact-two-component reference including spin-orbit coupling to illustrate the capabilities of the method.

Diverse Cis-Regulatory Mechanisms Contribute to Expression Evolution of Tandem Gene Duplicates

PubMed Central

Baudouin-Gonzalez, Luís; Santos, Marília A; Tempesta, Camille; Sucena, Élio; Roch, Fernando; Tanaka, Kohtaro

2017-01-01

Abstract Pairs of duplicated genes generally display a combination of conserved expression patterns inherited from their unduplicated ancestor and newly acquired domains. However, how the cis-regulatory architecture of duplicated loci evolves to produce these expression patterns is poorly understood. We have directly examined the gene-regulatory evolution of two tandem duplicates, the Drosophila Ly6 genes CG9336 and CG9338, which arose at the base of the drosophilids between 40 and 60 Ma. Comparing the expression patterns of the two paralogs in four Drosophila species with that of the unduplicated ortholog in the tephritid Ceratitis capitata, we show that they diverged from each other as well as from the unduplicated ortholog. Moreover, the expression divergence appears to have occurred close to the duplication event and also more recently in a lineage-specific manner. The comparison of the tissue-specific cis-regulatory modules (CRMs) controlling the paralog expression in the four Drosophila species indicates that diverse cis-regulatory mechanisms, including the novel tissue-specific enhancers, differential inactivation, and enhancer sharing, contributed to the expression evolution. Our analysis also reveals a surprisingly variable cis-regulatory architecture, in which the CRMs driving conserved expression domains change in number, location, and specificity. Altogether, this study provides a detailed historical account that uncovers a highly dynamic picture of how the paralog expression patterns and their underlying cis-regulatory landscape evolve. We argue that our findings will encourage studying cis-regulatory evolution at the whole-locus level to understand how interactions between enhancers and other regulatory levels shape the evolution of gene expression. PMID:28961967

Team structure and regulatory focus: the impact of regulatory fit on team dynamic.

PubMed

Dimotakis, Nikolaos; Davison, Robert B; Hollenbeck, John R

2012-03-01

We report a within-teams experiment testing the effects of fit between team structure and regulatory task demands on task performance and satisfaction through average team member positive affect and helping behaviors. We used a completely crossed repeated-observations design in which 21 teams enacted 2 tasks with different regulatory focus characteristics (prevention and promotion) in 2 organizational structures (functional and divisional), resulting in 84 observations. Results suggested that salient regulatory demands inherent in the task interacted with structure to determine objective and subjective team-level outcomes, such that functional structures were best suited to (i.e., had best fit with) tasks with a prevention regulatory focus and divisional structures were best suited to tasks with a promotion regulatory focus. This contingency finding integrates regulatory focus and structural contingency theories, and extends them to the team level with implications for models of performance, satisfaction, and team dynamics.

The diffusion of innovation in nursing regulatory policy: removing a barrier to medication administration training for child care providers.

PubMed

Torre, Carolyn T; Crowley, Angela A

2011-08-01

Safe medication administration is an essential component of high-quality child care. Its achievement in New Jersey was impeded by a controversy over whether teaching child care providers medication administration involves registered nurses in the process of nursing delegation. Through the theoretical framework of the Diffusion of Innovation, this paper examines how the interpretation of regulatory policy related to nursing practice in New Jersey was adjusted by the Board of Nursing following a similar interpretation of regulatory policy by the Board of Nursing in Connecticut. This adjustment enabled New Jersey nurses to continue medication administration training for child care providers. National data supporting the need for training child care providers in medication administration is presented, the Diffusion of Innovation paradigm is described; the Connecticut case and the New Jersey dilemma are discussed; the diffusion process between the two states is analyzed and an assessment of the need for further change is made.

Antibacterial activity of the essential oil and main components of two Dracocephalum species from Iran.

PubMed

Sonboli, Ali; Gholipour, Abbas; Yousefzadi, Morteza

2012-01-01

The antibacterial activity of Dracocephalum polychaetum and D. surmandinum essential oils and two main components were investigated. Essential oils of the plants were analysed by GC and GC-MS. Twenty-three components were characterised in the essential oil of D. polychaetum. The oil was rich in oxygenated (73.1%) and hydrocarbon (25.0%) monoterpenes including perilla aldehyde (63.4 %) and limonene (22.1%) as the major constituents. From 25 identified compounds (97.8%) in the oil of D. surmandinum perilla aldehyde (54.3%) and limonene (30.1%) were the main constituents. The bioassays exhibited that all of the Gram-positive and Gram-negative bacteria tested were highly inhibited in the presence of the oils and main components investigated. The most sensitive microorganism to the oils was found to be Staphylococcus epidermidis with the lowest MIC value of 0.3 mgmL(-1). The resistant Gram-negative Pseudomonas aeruginosa was highly inhibited by the oil of D. polychaetum with MIC value of 2.4 mgmL(-1).

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

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-01

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

76 FR 25397 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-04

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change To Amend the By- Laws of FINRA Regulation, Inc. With Regard to District Committees April 28, 2011. I. Introduction On February 25, 2011, the Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-08

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

Regulatory logic of pan-neuronal gene expression in C. elegans

PubMed Central

Stefanakis, Nikolaos; Carrera, Ines; Hobert, Oliver

2015-01-01

While neuronal cell types display an astounding degree of phenotypic diversity, most if not all neuron types share a core panel of terminal features. However, little is known about how pan-neuronal expression patterns are genetically programmed. Through an extensive analysis of the cis-regulatory control regions of a battery of pan-neuronal C.elegans genes, including genes involved in synaptic vesicle biology and neuropeptide signaling, we define a common organizational principle in the regulation of pan-neuronal genes in the form of a surprisingly complex array of seemingly redundant, parallel-acting cis-regulatory modules that direct expression to broad, overlapping domains throughout the nervous system. These parallel-acting cis-regulatory modules are responsive to a multitude of distinct trans-acting factors. Neuronal gene expression programs therefore fall into two fundamentally distinct classes. Neuron type-specific genes are generally controlled by discrete and non-redundantly acting regulatory inputs, while pan-neuronal gene expression is controlled by diverse, coincident and seemingly redundant regulatory inputs. PMID:26291158

Assessment of Individual Differences in Regulatory Focus among Cigarette Smokers

PubMed Central

Haaga, David A. F.; Friedman-Wheeler, Dara G.; McIntosh, Elizabeth; Ahrens, Anthony H.

2008-01-01

Smoking cessation programs might benefit from tailoring messages to individual differences in regulatory focus (see Higgins, 1997), but there is little evidence on the stability or convergent validity of regulatory focus measures. In two studies, smokers completed four measures of regulatory focus: (a) Regulatory Focus Questionnaire (RFQ); (b) actual-ideal and actual-ought self-discrepancies; (c) response duration in naming name ideal or ought self-guides; and (d) reaction time for lexical decisions about one’s ideal or ought self-guides. Study 1 included a one-month retest. Retest reliability was adequate, but convergent validity was poor. Questionnaire and self-discrepancy measures were unrelated to each other or to the reaction time measures. To facilitate future studies of tailored health behavior change interventions, research is needed to determine whether weak convergent validity resulted from (a) invalidity of some or all of the regulatory focus measures or (b) validity of each for measuring a different aspect of the construct. PMID:18958291

Object-Place Recognition Learning Triggers Rapid Induction of Plasticity-Related Immediate Early Genes and Synaptic Proteins in the Rat Dentate Gyrus

PubMed Central

Soulé, Jonathan; Penke, Zsuzsa; Kanhema, Tambudzai; Alme, Maria Nordheim; Laroche, Serge; Bramham, Clive R.

2008-01-01

Long-term recognition memory requires protein synthesis, but little is known about the coordinate regulation of specific genes. Here, we examined expression of the plasticity-associated immediate early genes (Arc, Zif268, and Narp) in the dentate gyrus following long-term object-place recognition learning in rats. RT-PCR analysis from dentate gyrus tissue collected shortly after training did not reveal learning-specific changes in Arc mRNA expression. In situ hybridization and immunohistochemistry were therefore used to assess possible sparse effects on gene expression. Learning about objects increased the density of granule cells expressing Arc, and to a lesser extent Narp, specifically in the dorsal blade of the dentate gyrus, while Zif268 expression was elevated across both blades. Thus, object-place recognition triggers rapid, blade-specific upregulation of plasticity-associated immediate early genes. Furthermore, Western blot analysis of dentate gyrus homogenates demonstrated concomitant upregulation of three postsynaptic density proteins (Arc, PSD-95, and α-CaMKII) with key roles in long-term synaptic plasticity and long-term memory. PMID:19190776

Vapour-mediated sensing and motility in two-component droplets

NASA Astrophysics Data System (ADS)

Cira, N. J.; Benusiglio, A.; Prakash, M.

2015-03-01

Controlling the wetting behaviour of liquids on surfaces is important for a variety of industrial applications such as water-repellent coatings and lubrication. Liquid behaviour on a surface can range from complete spreading, as in the `tears of wine' effect, to minimal wetting as observed on a superhydrophobic lotus leaf. Controlling droplet movement is important in microfluidic liquid handling, on self-cleaning surfaces and in heat transfer. Droplet motion can be achieved by gradients of surface energy. However, existing techniques require either a large gradient or a carefully prepared surface to overcome the effects of contact line pinning, which usually limit droplet motion. Here we show that two-component droplets of well-chosen miscible liquids such as propylene glycol and water deposited on clean glass are not subject to pinning and cause the motion of neighbouring droplets over a distance. Unlike the canonical predictions for these liquids on a high-energy surface, these droplets do not spread completely but exhibit an apparent contact angle. We demonstrate experimentally and analytically that these droplets are stabilized by evaporation-induced surface tension gradients and that they move in response to the vapour emitted by neighbouring droplets. Our fundamental understanding of this robust system enabled us to construct a wide variety of autonomous fluidic machines out of everyday materials.

75 FR 6422 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-09

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Order Approving Proposed Rule Change... Incorporated NYSE Rule 411(a)(ii)(5) as Part of the Process of Developing the Consolidated FINRA Rulebook February 2, 2010. On December 4, 2009, the Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a...

Regulatory ozone modeling: status, directions, and research needs.

PubMed Central

Georgopoulos, P G

1995-01-01

The Clean Air Act Amendments (CAAA) of 1990 have established selected comprehensive, three-dimensional, Photochemical Air Quality Simulation Models (PAQSMs) as the required regulatory tools for analyzing the urban and regional problem of high ambient ozone levels across the United States. These models are currently applied to study and establish strategies for meeting the National Ambient Air Quality Standard (NAAQS) for ozone in nonattainment areas; State Implementation Plans (SIPs) resulting from these efforts must be submitted to the U.S. Environmental Protection Agency (U.S. EPA) in November 1994. The following presentation provides an overview and discussion of the regulatory ozone modeling process and its implications. First, the PAQSM-based ozone attainment demonstration process is summarized in the framework of the 1994 SIPs. Then, following a brief overview of the representation of physical and chemical processes in PAQSMs, the essential attributes of standard modeling systems currently in regulatory use are presented in a nonmathematical, self-contained format, intended to provide a basic understanding of both model capabilities and limitations. The types of air quality, emission, and meteorological data needed for applying and evaluating PAQSMs are discussed, as well as the sources, availability, and limitations of existing databases. The issue of evaluating a model's performance in order to accept it as a tool for policy making is discussed, and various methodologies for implementing this objective are summarized. Selected interim results from diagnostic analyses, which are performed as a component of the regulatory ozone modeling process for the Philadelphia-New Jersey region, are also presented to provide some specific examples related to the general issues discussed in this work. Finally, research needs related to a) the evaluation and refinement of regulatory ozone modeling, b) the characterization of uncertainty in photochemical modeling, and c

Coordination of meristem and boundary functions by transcription factors in the SHOOT MERISTEMLESS regulatory network.

PubMed

Scofield, Simon; Murison, Alexander; Jones, Angharad; Fozard, John; Aida, Mitsuhiro; Band, Leah R; Bennett, Malcolm; Murray, James A H

2018-04-30

The Arabidopsis homeodomain transcription factor SHOOT MERISTEMLESS (STM) is crucial for shoot apical meristem (SAM) function, yet the components and structure of the STM gene regulatory network (GRN) are largely unknown. Here, we show that transcriptional regulators are overrepresented among STM-regulated genes and, using these as GRN components in Bayesian network analysis, we infer STM GRN associations and reveal regulatory relationships between STM and factors involved in multiple aspects of SAM function. These include hormone regulation, TCP-mediated control of cell differentiation, AIL/PLT-mediated regulation of pluripotency and phyllotaxis, and specification of meristem-organ boundary zones via CUC1. We demonstrate a direct positive transcriptional feedback loop between STM and CUC1, despite their distinct expression patterns in the meristem and organ boundary, respectively. Our further finding that STM activates expression of the CUC1-targeting microRNA miR164c combined with mathematical modelling provides a potential solution for this apparent contradiction, demonstrating that these proposed regulatory interactions coupled with STM mobility could be sufficient to provide a mechanism for CUC1 localisation at the meristem-organ boundary. Our findings highlight the central role for the STM GRN in coordinating SAM functions. © 2018. Published by The Company of Biologists Ltd.

Dual Nature of Translational Control by Regulatory BC RNAs ▿

PubMed Central

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

2011-01-01

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

Independent component analysis-based source-level hyperlink analysis for two-person neuroscience studies

NASA Astrophysics Data System (ADS)

Zhao, Yang; Dai, Rui-Na; Xiao, Xiang; Zhang, Zong; Duan, Lian; Li, Zheng; Zhu, Chao-Zhe

2017-02-01

Two-person neuroscience, a perspective in understanding human social cognition and interaction, involves designing immersive social interaction experiments as well as simultaneously recording brain activity of two or more subjects, a process termed "hyperscanning." Using newly developed imaging techniques, the interbrain connectivity or hyperlink of various types of social interaction has been revealed. Functional near-infrared spectroscopy (fNIRS)-hyperscanning provides a more naturalistic environment for experimental paradigms of social interaction and has recently drawn much attention. However, most fNIRS-hyperscanning studies have computed hyperlinks using sensor data directly while ignoring the fact that the sensor-level signals contain confounding noises, which may lead to a loss of sensitivity and specificity in hyperlink analysis. In this study, on the basis of independent component analysis (ICA), a source-level analysis framework is proposed to investigate the hyperlinks in a fNIRS two-person neuroscience study. The performance of five widely used ICA algorithms in extracting sources of interaction was compared in simulative datasets, and increased sensitivity and specificity of hyperlink analysis by our proposed method were demonstrated in both simulative and real two-person experiments.

76 FR 39812 - Scotts Miracle-Gro Co.; Regulatory Status of Kentucky Bluegrass Genetically Engineered for...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-07

...] Scotts Miracle-Gro Co.; Regulatory Status of Kentucky Bluegrass Genetically Engineered for Herbicide... engineered for herbicide tolerance without the use of plant pest components, does not meet the definition of... has been genetically engineered for herbicide tolerance, does not meet the definition of a regulated...

Integrated Module and Gene-Specific Regulatory Inference Implicates Upstream Signaling Networks

PubMed Central

Roy, Sushmita; Lagree, Stephen; Hou, Zhonggang; Thomson, James A.; Stewart, Ron; Gasch, Audrey P.

2013-01-01

Regulatory networks that control gene expression are important in diverse biological contexts including stress response and development. Each gene's regulatory program is determined by module-level regulation (e.g. co-regulation via the same signaling system), as well as gene-specific determinants that can fine-tune expression. We present a novel approach, Modular regulatory network learning with per gene information (MERLIN), that infers regulatory programs for individual genes while probabilistically constraining these programs to reveal module-level organization of regulatory networks. Using edge-, regulator- and module-based comparisons of simulated networks of known ground truth, we find MERLIN reconstructs regulatory programs of individual genes as well or better than existing approaches of network reconstruction, while additionally identifying modular organization of the regulatory networks. We use MERLIN to dissect global transcriptional behavior in two biological contexts: yeast stress response and human embryonic stem cell differentiation. Regulatory modules inferred by MERLIN capture co-regulatory relationships between signaling proteins and downstream transcription factors thereby revealing the upstream signaling systems controlling transcriptional responses. The inferred networks are enriched for regulators with genetic or physical interactions, supporting the inference, and identify modules of functionally related genes bound by the same transcriptional regulators. Our method combines the strengths of per-gene and per-module methods to reveal new insights into transcriptional regulation in stress and development. PMID:24146602

12 CFR 562.2 - Regulatory reports.

Code of Federal Regulations, 2010 CFR

2010-01-01

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

Biosimilars in psoriasis: Clinical practice and regulatory perspectives in Latin America.

PubMed

de la Cruz, Claudia; de Carvalho, André V E; Dorantes, Gladys L; Londoño Garcia, Angela M; Gonzalez, Cesar; Maskin, Matías; Podoswa, Nancy; Redfern, Jan S; Valenzuela, Fernando; van der Walt, Joelle; Romiti, Ricardo

2017-01-01

Latin American countries view biosimilar agents as an effective approach to curtail health-care expenditures while maintaining the safety and efficacy profile of their branded innovator comparators. To understand the complexities of the regulatory landscape and key therapeutic issues for use of biosimilars to treat moderate to severe psoriasis in Latin America, the International Psoriasis Council convened dermatology experts from Argentina, Brazil, Chile, Colombia and Mexico in October 2015 to review the definition, approval, marketing and future of biosimilars in each country and develop a consensus statement. The regulatory framework for marketing approval of biosimilars in Latin America is currently a mosaic of disparate, country-specific, regulatory review processes, rules and standards, with considerable heterogeneity in clarity and specificity. Regulations in Argentina, Brazil, Chile and Mexico have undergone multiple refinements whereas Colombia is finalizing draft guidelines. Verification of the similarity in quality, safety and efficacy of biosimilars to the innovator biologic remains a key challenge for policy makers and regulatory authorities. Other key regulatory challenges include: naming of agents and traceability, pharmacovigilance, extrapolation of indications, and interchangeability and substitution. An urgent need exists for more Latin American countries to establish national psoriasis registries and to integrate their common components into a multinational psoriasis network, thereby enhancing their interpretative power and impact. A Latin American psoriasis network similar to PSONET in Europe would assist health-care providers, pharmaceutical companies, regulators and patients to fully comprehend specific products being prescribed and dispensed and to identify potential regional trends or differences in safety or outcomes. © 2016 Japanese Dermatological Association.

Large-scale Models Reveal the Two-component Mechanics of Striated Muscle

PubMed Central

Jarosch, Robert

2008-01-01

This paper provides a comprehensive explanation of striated muscle mechanics and contraction on the basis of filament rotations. Helical proteins, particularly the coiled-coils of tropomyosin, myosin and α-actinin, shorten their H-bonds cooperatively and produce torque and filament rotations when the Coulombic net-charge repulsion of their highly charged side-chains is diminished by interaction with ions. The classical “two-component model” of active muscle differentiated a “contractile component” which stretches the “series elastic component” during force production. The contractile components are the helically shaped thin filaments of muscle that shorten the sarcomeres by clockwise drilling into the myosin cross-bridges with torque decrease (= force-deficit). Muscle stretch means drawing out the thin filament helices off the cross-bridges under passive counterclockwise rotation with torque increase (= stretch activation). Since each thin filament is anchored by four elastic α-actinin Z-filaments (provided with force-regulating sites for Ca2+ binding), the thin filament rotations change the torsional twist of the four Z-filaments as the “series elastic components”. Large scale models simulate the changes of structure and force in the Z-band by the different Z-filament twisting stages A, B, C, D, E, F and G. Stage D corresponds to the isometric state. The basic phenomena of muscle physiology, i. e. latency relaxation, Fenn-effect, the force-velocity relation, the length-tension relation, unexplained energy, shortening heat, the Huxley-Simmons phases, etc. are explained and interpreted with the help of the model experiments. PMID:19330099

Two Genetic Loci Produce Distinct Carbohydrate-Rich Structural Components of the Pseudomonas aeruginosa Biofilm Matrix

PubMed Central

Friedman, Lisa; Kolter, Roberto

2004-01-01

Pseudomonas aeruginosa forms biofilms, which are cellular aggregates encased in an extracellular matrix. Molecular genetics studies of three common autoaggregative phenotypes, namely wrinkled colonies, pellicles, and solid-surface-associated biofilms, led to the identification of two loci, pel and psl, that are involved in the production of carbohydrate-rich components of the biofilm matrix. The pel gene cluster is involved in the production of a glucose-rich matrix material in P. aeruginosa strain PA14 (L. Friedman and R. Kolter, Mol. Microbiol. 51:675-690, 2004). Here we investigate the role of the pel gene cluster in P. aeruginosa strain ZK2870 and identify a second genetic locus, termed psl, involved in the production of a mannose-rich matrix material. The 11 predicted protein products of the psl genes are homologous to proteins involved in carbohydrate processing. P. aeruginosa is thus able to produce two distinct carbohydrate-rich matrix materials. Either carbohydrate-rich matrix component appears to be sufficient for mature biofilm formation, and at least one of them is required for mature biofilm formation in P. aeruginosa strains PA14 and ZK2870. PMID:15231777

Two genetic loci produce distinct carbohydrate-rich structural components of the Pseudomonas aeruginosa biofilm matrix.

PubMed

Friedman, Lisa; Kolter, Roberto

2004-07-01

Pseudomonas aeruginosa forms biofilms, which are cellular aggregates encased in an extracellular matrix. Molecular genetics studies of three common autoaggregative phenotypes, namely wrinkled colonies, pellicles, and solid-surface-associated biofilms, led to the identification of two loci, pel and psl, that are involved in the production of carbohydrate-rich components of the biofilm matrix. The pel gene cluster is involved in the production of a glucose-rich matrix material in P. aeruginosa strain PA14 (L. Friedman and R. Kolter, Mol. Microbiol. 51:675-690, 2004). Here we investigate the role of the pel gene cluster in P. aeruginosa strain ZK2870 and identify a second genetic locus, termed psl, involved in the production of a mannose-rich matrix material. The 11 predicted protein products of the psl genes are homologous to proteins involved in carbohydrate processing. P. aeruginosa is thus able to produce two distinct carbohydrate-rich matrix materials. Either carbohydrate-rich matrix component appears to be sufficient for mature biofilm formation, and at least one of them is required for mature biofilm formation in P. aeruginosa strains PA14 and ZK2870. Copyright 2004 American Society for Microbiology

75 FR 7532 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-19

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate... is hereby given that on February 4, 2010, Financial Industry Regulatory Authority, Inc. (``FINRA...) (SEC Approves Consolidated FINRA Rules Governing Financial Responsibility). FINRA announced in...

Quantifying Components of Soil Respiration and Their Response to Abiotic Factors in Two Typical Subtropical Forest Stands, Southwest China

PubMed Central

Yu, Lei; Wang, Yujie; Wang, Yunqi; Sun, Suqi; Liu, Liziyuan

2015-01-01

Separating the components of soil respiration and understanding the roles of abiotic factors at a temporal scale among different forest types are critical issues in forest ecosystem carbon cycling. This study quantified the proportions of autotrophic (R A) and heterotrophic (R H) in total soil (R T) respiration using trenching and litter removal. Field studies were conducted in two typical subtropical forest stands (broadleaf and needle leaf mixed forest; bamboo forest) at Jinyun Mountain, near the Three Georges Reservoir in southwest China, during the growing season (Apr.–Sep.) from 2010 to 2012. The effects of air temperature (AT), soil temperature (ST) and soil moisture (SM) at 6cm depth, solar radiation (SR), pH on components of soil respiration were analyzed. Results show that: 1) SR, AT, and ST exhibited a similar temporal trend. The observed abiotic factors showed slight interannual variability for the two forest stands. 2) The contributions of R H and R A to R T for broadleaf and needle leaf mixed forest were 73.25% and 26.75%, respectively, while those for bamboo forest were 89.02% and 10.98%, respectively; soil respiration peaked from June to July. In both stands, CO2 released from the decomposition of soil organic matter (SOM), the strongest contributor to R T, accounted for over 63% of R H. 3) AT and ST were significantly positively correlated with R T and its components (p<0.05), and were major factors affecting soil respiration. 4) Components of soil respiration were significantly different between two forest stands (p<0.05), indicating that vegetation types played a role in soil respiration and its components. PMID:25680112

A tale of three labels: translating the JUPITER trial data into regulatory claims.

PubMed

Ridker, Paul M

2011-08-01

Whether a pivotal randomized trial will be interpreted in a similar and consistent manner by different regulatory agencies is uncertain as policy perspectives may play a role in data interpretation and the translation of trial results into clinical practice. Using a contemporary example, to compare and contrast regulatory claims in the United States, Europe, and Canada that derive from a pivotal clinical trial. The recently completed JUPITER trial of rosuvastatin as compared to placebo conducted among 17,802 men and women with LDL-C <130 mg/dL and hsCRP ≥ 2 mg/L, provides the only available data on rosuvastatin for primary prevention of cardiovascular disease. Thus, the JUPITER trial provides an opportunity to compare and contrast how regulatory agencies in the United States, Canada, and Europe chose to interpret an identical database. Labeling indications based on earlier statin trials of primary and secondary prevention were also reviewed. JUPITER demonstrated a 44% reduction (p < 0.000001) in the trial pre-specified primary endpoint (nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina, coronary revascularization, or cardiovascular death) with no evidence of heterogeneity across geographic regions. In response to these data, the US Food and Drug Administration label for rosuvastatin in primary prevention came closest to the actual JUPITER trial population by stipulating that those eligible for treatment should be older men and women with hsCRP >2 mg/L, plus one additional risk factor for heart disease. The Canadian label is silent on age and hsCRP (the major trial inclusion criterion), stipulating instead that treatment can be considered for those with 'at least two conventional risk factors for cardiovascular disease,' a group more inclusive than that studied. In contrast, the European Medicines Agency label limits treatment only to 'high risk individuals' ignoring hsCRP and using instead a post hoc definition of 'high risk

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

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-29

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

A twin study of self-regulatory eating in early childhood: Estimates of genetic and environmental influence, and measurement considerations

PubMed Central

Faith, Myles S.; Pietrobelli, Angelo; Heo, Moonseong; Johnson, Susan L.; Keller, Kathleen L.; Heymsfield, Steven B.; Allison, David B.

2016-01-01

Objective Children differ greatly in their ability to self-regulate food intake for reasons that are poorly understood. This laboratory-based twin study tested genetic and environmental contributions to self-regulatory eating and body fat in early childhood. Methods Sixty-nine 4 to 7 year-old same-sex twin pairs, including 40 monozygotic (MZ) and 29 dizygotic (DZ) pairs, were studied. Self-regulatory eating was operationalized as the percentage compensation index (COMPX%), assessed by a “preload” challenge in which lunch intake was measured following a low- (3 kcal) or high-calorie (159 kcal) drink. Body fat indexes also were measured. The familial association for COMPX% was estimated by an intraclass correlation, and biometric analyses estimated heritability. Results Children ate more at lunch following the low- compared to high-energy preload (p< 0.001), although variability in COMPX% was considerable. Compensation was significantly poorer among African American and Hispanic compared to European American children, and among girls compared to boys. There was a familial association for self-regulatory eating (ρ= 0.23, p= 0.03) but no significant genetic component. Twenty two percent of the variance in COMPX% was due to shared environmental (‘household’) factors, with the remaining variance attributable to child-specific (‘unique’ or ‘random’) environments. Poorer self-regulatory eating was associated with greater percent body fat (r= −0.21, p= 0.04). Conclusions Self-regulatory eating was influenced by environmental factors, especially those differing among siblings. The absence of a significant genetic effect may reflect age of the sample or could be artifactual due to measurement issues that need to be considered in future studies. PMID:22249227

Establishment of apoptotic regulatory network for genetic markers of colorectal cancer.

PubMed

Hao, Yibin; Shan, Guoyong; Nan, Kejun

2017-03-01

Our purpose is to screen out genetic markers applicable to early diagnosis for colorectal cancer and to establish apoptotic regulatory network model for colorectal cancer, thereby providing theoretical evidence and targeted therapy for early diagnosis of colorectal cancer. Taking databases including CNKI, VIP, Wanfang data, Pub Med, and MEDLINE as main sources of literature retrieval, literatures associated with genetic markers applied to early diagnosis of colorectal cancer were searched to perform comprehensive and quantitative analysis by Meta analysis, hence screening genetic markers used in early diagnosis of colorectal cancer. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were employed to establish apoptotic regulatory network model based on screened genetic markers, and then verification experiment was conducted. Through Meta analysis, seven genetic markers were screened out, including WWOX, K-ras, COX-2, p53, APC, DCC and PTEN, among which DCC shows highest diagnostic efficiency. GO analysis of genetic markers found that six genetic markers played role in biological process, molecular function and cellular component. It was indicated in apoptotic regulatory network built by KEGG analysis and verification experiment that WWOX could promote tumor cell apoptotic in colorectal cancer and elevate expression level of p53. The apoptotic regulatory model of colorectal cancer established in this study provides clinically theoretical evidence and targeted therapy for early diagnosis of colorectal cancer.

Influence of local-field corrections on Thomson scattering in collision-dominated two-component plasmas.

PubMed

Fortmann, Carsten; Wierling, August; Röpke, Gerd

2010-02-01

The dynamic structure factor, which determines the Thomson scattering spectrum, is calculated via an extended Mermin approach. It incorporates the dynamical collision frequency as well as the local-field correction factor. This allows to study systematically the impact of electron-ion collisions as well as electron-electron correlations due to degeneracy and short-range interaction on the characteristics of the Thomson scattering signal. As such, the plasmon dispersion and damping width is calculated for a two-component plasma, where the electron subsystem is completely degenerate. Strong deviations of the plasmon resonance position due to the electron-electron correlations are observed at increasing Brueckner parameters r(s). These results are of paramount importance for the interpretation of collective Thomson scattering spectra, as the determination of the free electron density from the plasmon resonance position requires a precise theory of the plasmon dispersion. Implications due to different approximations for the electron-electron correlation, i.e., different forms of the one-component local-field correction, are discussed.

Lactoferricin B Inhibits the Phosphorylation of the Two-Component System Response Regulators BasR and CreB*

PubMed Central

Ho, Yu-Hsuan; Sung, Tzu-Cheng; Chen, Chien-Sheng

2012-01-01

Natural antimicrobial peptides provide fundamental protection for multicellular organisms from microbes, such as Lactoferricin B (Lfcin B). Many studies have shown that Lfcin B penetrates the cell membrane and has intracellular activities. To elucidate the intracellular behavior of Lfcin B, we first used Escherichia coli K12 proteome chips to identify the intracellular targets of Lfcin B. The results showed that Lfcin B binds to two response regulators, BasR and CreB, of the two-component system. For further analysis, we conducted several in vitro and in vivo experiments and utilized bioinformatics methods. The electrophoretic mobility shift assays and kinase assays indicate that Lfcin B inhibits the phosphorylation of the response regulators (BasR and CreB) and their cognate sensor kinases (BasS and CreC). Antibacterial assays showed that Lfcin B reduced E. coli's tolerance to environmental stimuli, such as excessive ferric ions and minimal medium conditions. This is the first study to show that an antimicrobial peptide inhibits the growth of bacteria by influencing the phosphorylation of a two-component system directly. PMID:22138548

Lactoferricin B inhibits the phosphorylation of the two-component system response regulators BasR and CreB.

PubMed

Ho, Yu-Hsuan; Sung, Tzu-Cheng; Chen, Chien-Sheng

2012-04-01

Natural antimicrobial peptides provide fundamental protection for multicellular organisms from microbes, such as Lactoferricin B (Lfcin B). Many studies have shown that Lfcin B penetrates the cell membrane and has intracellular activities. To elucidate the intracellular behavior of Lfcin B, we first used Escherichia coli K12 proteome chips to identify the intracellular targets of Lfcin B. The results showed that Lfcin B binds to two response regulators, BasR and CreB, of the two-component system. For further analysis, we conducted several in vitro and in vivo experiments and utilized bioinformatics methods. The electrophoretic mobility shift assays and kinase assays indicate that Lfcin B inhibits the phosphorylation of the response regulators (BasR and CreB) and their cognate sensor kinases (BasS and CreC). Antibacterial assays showed that Lfcin B reduced E. coli's tolerance to environmental stimuli, such as excessive ferric ions and minimal medium conditions. This is the first study to show that an antimicrobial peptide inhibits the growth of bacteria by influencing the phosphorylation of a two-component system directly.

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

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-08

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

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

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-13

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

77 FR 34379 - Notice of Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-11

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. AD06-6-000] Notice of Joint Meeting of the Nuclear Regulatory Commission and the Federal Energy Regulatory Commission The Federal Energy Regulatory Commission (FERC) and the Nuclear Regulatory Commission (NRC) will hold a joint meeting...

Analytical Chemistry in the Regulatory Science of Medical Devices.

PubMed

Wang, Yi; Guan, Allan; Wickramasekara, Samanthi; Phillips, K Scott

2018-06-12

In the United States, regulatory science is the science of developing new tools, standards, and approaches to assess the safety, efficacy, quality, and performance of all Food and Drug Administration-regulated products. Good regulatory science facilitates consumer access to innovative medical devices that are safe and effective throughout the Total Product Life Cycle (TPLC). Because the need to measure things is fundamental to the regulatory science of medical devices, analytical chemistry plays an important role, contributing to medical device technology in two ways: It can be an integral part of an innovative medical device (e.g., diagnostic devices), and it can be used to support medical device development throughout the TPLC. In this review, we focus on analytical chemistry as a tool for the regulatory science of medical devices. We highlight recent progress in companion diagnostics, medical devices on chips for preclinical testing, mass spectrometry for postmarket monitoring, and detection/characterization of bacterial biofilm to prevent infections.

Integration of a splicing regulatory network within the meiotic gene expression program of Saccharomyces cerevisiae

PubMed Central

Munding, Elizabeth M.; Igel, A. Haller; Shiue, Lily; Dorighi, Kristel M.; Treviño, Lisa R.; Ares, Manuel

2010-01-01

Splicing regulatory networks are essential components of eukaryotic gene expression programs, yet little is known about how they are integrated with transcriptional regulatory networks into coherent gene expression programs. Here we define the MER1 splicing regulatory network and examine its role in the gene expression program during meiosis in budding yeast. Mer1p splicing factor promotes splicing of just four pre-mRNAs. All four Mer1p-responsive genes also require Nam8p for splicing activation by Mer1p; however, other genes require Nam8p but not Mer1p, exposing an overlapping meiotic splicing network controlled by Nam8p. MER1 mRNA and three of the four Mer1p substrate pre-mRNAs are induced by the transcriptional regulator Ume6p. This unusual arrangement delays expression of Mer1p-responsive genes relative to other genes under Ume6p control. Products of Mer1p-responsive genes are required for initiating and completing recombination and for activation of Ndt80p, the activator of the transcriptional network required for subsequent steps in the program. Thus, the MER1 splicing regulatory network mediates the dependent relationship between the UME6 and NDT80 transcriptional regulatory networks in the meiotic gene expression program. This study reveals how splicing regulatory networks can be interlaced with transcriptional regulatory networks in eukaryotic gene expression programs. PMID:21123654

Cannabis regulatory science: risk-benefit considerations for mental disorders.

PubMed

Borodovsky, Jacob T; Budney, Alan J

2018-05-29

The evolving legal cannabis landscape in the US continues to present novel regulatory challenges that necessitate the development of a Cannabis Regulatory Science. Two specific issues of concern within Cannabis Regulatory Science are (1) the impact that cannabis use has on the incidence, prevalence, and severity of mental disorders, and (2) how cannabis laws and regulations modify this impact. This paper first provides several conceptual points that are useful for evaluating the relationship between cannabis use and mental disorders. Second, it selectively reviews and comments on data relevant to the relationship between cannabis use and depression, several forms of anxiety, post-traumatic stress disorder, schizophrenia, and bipolar disorder. Next, regulatory and public health parallels between the nascent cannabis industry and the pharmaceutical, tobacco, and alcohol industries are discussed. The focus is on specific types of industry practices that may harm those with or at risk for mental disorders. Recommendations are then offered for legal cannabis regulations that could mitigate this harm. Last, future research goals are discussed for building the field of Cannabis Regulatory Science and addressing the potential negative impact of cannabis on those with mental disorders.

75 FR 5834 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-04

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Update Certain Cross-References and Make Other Various Non-Substantive..., 2010, Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange...

77 FR 36029 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-15

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Update Rule Cross-References and Make Non- Substantive Technical..., Financial Industry Regulatory Authority, Inc. (``FINRA'') (f/k/a National Association of Securities Dealers...

76 FR 32246 - Self-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-03

...-Regulatory Organizations; Financial Industry Regulatory Authority, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change To Update Rule Cross-References and Make Non- Substantive Technical..., Financial Industry Regulatory Authority, Inc. (``FINRA'') filed with the Securities and Exchange Commission...

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

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-28

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

The Reconstruction and Analysis of Gene Regulatory Networks.

PubMed

Zheng, Guangyong; Huang, Tao

2018-01-01

In post-genomic era, an important task is to explore the function of individual biological molecules (i.e., gene, noncoding RNA, protein, metabolite) and their organization in living cells. For this end, gene regulatory networks (GRNs) are constructed to show relationship between biological molecules, in which the vertices of network denote biological molecules and the edges of network present connection between nodes (Strogatz, Nature 410:268-276, 2001; Bray, Science 301:1864-1865, 2003). Biologists can understand not only the function of biological molecules but also the organization of components of living cells through interpreting the GRNs, since a gene regulatory network is a comprehensively physiological map of living cells and reflects influence of genetic and epigenetic factors (Strogatz, Nature 410:268-276, 2001; Bray, Science 301:1864-1865, 2003). In this paper, we will review the inference methods of GRN reconstruction and analysis approaches of network structure. As a powerful tool for studying complex diseases and biological processes, the applications of the network method in pathway analysis and disease gene identification will be introduced.

Evaluating brief motivational and self-regulatory hand hygiene interventions: a cross-over longitudinal design.

PubMed

Lhakhang, Pempa; Lippke, Sonia; Knoll, Nina; Schwarzer, Ralf

2015-02-04

Frequent handwashing can prevent infections, but non-compliance to hand hygiene is pervasive. Few theory- and evidence-based interventions to improve regular handwashing are available. Therefore, two intervention modules, a motivational and a self-regulatory one, were designed and evaluated. In a longitudinal study, 205 young adults, aged 18 to 26 years, were randomized into two intervention groups. The Mot-SelfR group received first a motivational intervention (Mot; risk perception and outcome expectancies) followed by a self-regulatory intervention (SelfR; perceived self-efficacy and planning) 17 days later. The SelfR-Mot group received the same two intervention modules in the opposite order. Follow-up data were assessed 17 and 34 days after the baseline. Both intervention sequences led to an increase in handwashing frequency, intention, self-efficacy, and planning. Also, overall gains were found for the self-regulatory module (increased planning and self-efficacy levels) and the motivational module (intention). Within groups, the self-regulatory module appeared to be more effective than the motivational module, independent of sequence. Self-regulatory interventions can help individuals to exhibit more handwashing. Sequencing may be important as a motivation module (Mot) first helps to set the goal and a self-regulatory module (SelfR) then helps to translate this goal into actual behavior, but further research is needed to evaluate mechanisms.

10 CFR 110.26 - General license for the export of nuclear reactor components.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 2 2014-01-01 2014-01-01 false General license for the export of nuclear reactor components. 110.26 Section 110.26 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) EXPORT AND IMPORT OF NUCLEAR EQUIPMENT AND MATERIAL Licenses § 110.26 General license for the export of nuclear reactor...

10 CFR 110.26 - General license for the export of nuclear reactor components.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false General license for the export of nuclear reactor components. 110.26 Section 110.26 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) EXPORT AND IMPORT OF NUCLEAR EQUIPMENT AND MATERIAL Licenses § 110.26 General license for the export of nuclear reactor...

10 CFR 110.26 - General license for the export of nuclear reactor components.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 2 2013-01-01 2013-01-01 false General license for the export of nuclear reactor components. 110.26 Section 110.26 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) EXPORT AND IMPORT OF NUCLEAR EQUIPMENT AND MATERIAL Licenses § 110.26 General license for the export of nuclear reactor...

10 CFR 110.26 - General license for the export of nuclear reactor components.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false General license for the export of nuclear reactor components. 110.26 Section 110.26 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) EXPORT AND IMPORT OF NUCLEAR EQUIPMENT AND MATERIAL Licenses § 110.26 General license for the export of nuclear reactor...

10 CFR 110.26 - General license for the export of nuclear reactor components.

Code of Federal Regulations, 2012 CFR