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Sample records for exon1 n-terminus triggers

  1. Capping of the N-terminus of PSD-95 by calmodulin triggers its postsynaptic release.

    PubMed

    Zhang, Yonghong; Matt, Lucas; Patriarchi, Tommaso; Malik, Zulfiqar A; Chowdhury, Dhrubajyoti; Park, Deborah K; Renieri, Alessandra; Ames, James B; Hell, Johannes W

    2014-06-17

    Postsynaptic density protein-95 (PSD-95) is a central element of the postsynaptic architecture of glutamatergic synapses. PSD-95 mediates postsynaptic localization of AMPA receptors and NMDA receptors and plays an important role in synaptic plasticity. PSD-95 is released from postsynaptic membranes in response to Ca(2+) influx via NMDA receptors. Here, we show that Ca(2+)/calmodulin (CaM) binds at the N-terminus of PSD-95. Our NMR structure reveals that both lobes of CaM collapse onto a helical structure of PSD-95 formed at its N-terminus (residues 1-16). This N-terminal capping of PSD-95 by CaM blocks palmitoylation of C3 and C5, which is required for postsynaptic PSD-95 targeting and the binding of CDKL5, a kinase important for synapse stability. CaM forms extensive hydrophobic contacts with Y12 of PSD-95. The PSD-95 mutant Y12E strongly impairs binding to CaM and Ca(2+)-induced release of PSD-95 from the postsynaptic membrane in dendritic spines. Our data indicate that CaM binding to PSD-95 serves to block palmitoylation of PSD-95, which in turn promotes Ca(2+)-induced dissociation of PSD-95 from the postsynaptic membrane.

  2. Novel P2 promoter-derived HNF4{alpha} isoforms with different N-terminus generated by alternate exon insertion

    SciTech Connect

    Huang, Jianmin; Levitsky, Lynne L.; Rhoads, David B.

    2009-04-15

    Hepatocyte nuclear factor 4{alpha} (HNF4{alpha}) is a critical transcription factor for pancreas and liver development and functions in islet {beta} cells to maintain glucose homeostasis. Mutations in the human HNF4A gene lead to maturity onset diabetes of the young (MODY1) and polymorphisms are associated with increased risk for type 2 diabetes mellitus (T2DM). Expression of six HNF4{alpha} variants, three each from two developmentally regulated promoters, has been firmly established. We have now detected a new set of HNF4{alpha} variants designated HNF4{alpha}10-12 expressed from distal promoter P2. These variants, generated by inclusion of previously undetected exon 1E (human = 222 nt, rodent = 136 nt) following exon 1D have an altered N-terminus but identical remaining reading frame. HNF4{alpha}10-{alpha}12 are expressed in pancreatic islets (and liver) and exhibit transactivation potentials similar to the corresponding {alpha}7-{alpha}9 isoforms. DNA-binding analyses implied much higher protein levels of HNF4{alpha}10-{alpha}12 in liver than expected from the RT-PCR data. Our results provide evidence for a more complex expression pattern of HNF4{alpha} than previously appreciated. We recommend inclusion of exon 1E and nearby DNA sequences in screening for HNF4{alpha} mutations and polymorphisms in genetic analyses of MODY1 and T2DM.

  3. Aggregation Behavior of Chemically Synthesized, Full-Length Huntingtin Exon1

    PubMed Central

    2015-01-01

    Repeat length disease thresholds vary among the 10 expanded polyglutamine (polyQ) repeat diseases, from about 20 to about 50 glutamine residues. The unique amino acid sequences flanking the polyQ segment are thought to contribute to these repeat length thresholds. The specific portions of the flanking sequences that modulate polyQ properties are not always clear, however. This ambiguity may be important in Huntington’s disease (HD), for example, where in vitro studies of aggregation mechanisms have led to distinctly different mechanistic models. Most in vitro studies of the aggregation of the huntingtin (HTT) exon1 fragment implicated in the HD mechanism have been conducted on inexact molecules that are imprecise either on the N-terminus (recombinantly produced peptides) or on the C-terminus (chemically synthesized peptides). In this paper, we investigate the aggregation properties of chemically synthesized HTT exon1 peptides that are full-length and complete, containing both normal and expanded polyQ repeat lengths, and compare the results directly to previously investigated molecules containing truncated C-termini. The results on the full-length peptides are consistent with a two-step aggregation mechanism originally developed based on studies of the C-terminally truncated analogues. Thus, we observe relatively rapid formation of spherical oligomers containing from 100 to 600 HTT exon1 molecules and intermediate formation of short protofibril-like structures containing from 500 to 2600 molecules. In contrast to this relatively rapid assembly, mature HTT exon1 amyloid requires about one month to dissociate in vitro, which is similar to the time required for neuronal HTT exon1 aggregates to disappear in vivo after HTT production is discontinued. PMID:24921664

  4. Phosphorylation and Ionic Strength Alter the LRAP-HAP Interface in the N-terminus

    SciTech Connect

    Lu, Junxia; Xu, Yimin; Shaw, Wendy J.

    2013-04-02

    strength when phosphorylated. These observations suggest that ionic strength and dephosphorylation may provide switching mechanisms to trigger a change in the function of the N-terminus. This research was supported by NIH-NIDCR Grant DE-015347. The research was performed at the Pacific Northwest National Laboratory (PNNL), a facility operated by Battelle for the U.S. Department of Energy.

  5. The Apical Sorting Signal for human GLUT9b resides in the N-terminus

    PubMed Central

    Bibee, Kristin P.; Augustin, Robert; Gazit, Vered; Moley, Kelle H.

    2016-01-01

    The two splice variants of human glucose transporter 9 (hGLUT9) are targeted to different polarized membranes. hGLUT9a traffics to the basolateral membrane, whereas hGLUT9b traffics to the apical region. This study examines the sorting mechanism of these variants, which differ only in their N-terminal domain. Mutating a di-leucine motif unique to GLUT9a did not affect targeting. Chimeric proteins were made using GLUT1, a basolaterally targeted transporter, and GLUT3, an apically targeted protein whose signal lies in the C-terminus. Overexpression of the chimeric proteins in polarized cells demonstrates that the N-terminus of hGLUT9b contains a signal capable of redirecting GLUT1 to the apical membrane. The N-terminus of hGLUT9a, however, does not contain a basolateral signal sufficient enough to redirect GLUT3. Portions of the GLUT9a N-terminus were substituted with corresponding portions of the GLUT9b N-terminus to determine the motif responsible for apical targeting. The first 16 amino acids were not found to be a sufficient apical signal. The last ten amino acids of the N-termini differ only in amino acid class at one location. In the B-form, leucine, a hydrophobic residue, is substituted for lysine, a basic residue, found in the A-form. However, mutation of the leucine in hGLUT9b to a lysine resulted in retention of the apical signal. We therefore believe the apical signal exists as an interplay between the final ten amino acids of the N-terminus and another motif within the protein such as the intracellular loop or other motifs within the N-terminus. PMID:23361362

  6. The N-terminus of TDP-43 promotes its oligomerization and enhances DNA binding affinity

    SciTech Connect

    Chang, Chung-ke; Wu, Tzong-Huah; Wu, Chu-Ya; Chiang, Ming-hui; Toh, Elsie Khai-Woon; Hsu, Yin-Chih; Lin, Ku-Feng; Liao, Yu-heng; Huang, Tai-huang; Huang, Joseph Jen-Tse

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer The N-terminus of TDP-43 contains an independently folded structural domain (NTD). Black-Right-Pointing-Pointer The structural domains of TDP-43 are arranged in a beads-on-a-string fashion. Black-Right-Pointing-Pointer The NTD promotes TDP-43 oligomerization in a concentration-dependent manner. Black-Right-Pointing-Pointer The NTD may assist nucleic acid-binding activity of TDP-43. -- Abstract: TDP-43 is a DNA/RNA-binding protein associated with different neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD-U). Here, the structural and physical properties of the N-terminus on TDP-43 have been carefully characterized through a combination of nuclear magnetic resonance (NMR), circular dichroism (CD) and fluorescence anisotropy studies. We demonstrate for the first time the importance of the N-terminus in promoting TDP-43 oligomerization and enhancing its DNA-binding affinity. An unidentified structural domain in the N-terminus is also disclosed. Our findings provide insights into the N-terminal domain function of TDP-43.

  7. Structure of the human MLH1 N-terminus: implications for predisposition to Lynch syndrome

    SciTech Connect

    Wu, Hong; Zeng, Hong; Lam, Robert; Tempel, Wolfram; Kerr, Iain D.; Min, Jinrong

    2015-07-28

    The crystal structure of the human MLH1 N-terminus is reported at 2.30 Å resolution. The overall structure is described along with an analysis of two clinically important mutations. Mismatch repair prevents the accumulation of erroneous insertions/deletions and non-Watson–Crick base pairs in the genome. Pathogenic mutations in the MLH1 gene are associated with a predisposition to Lynch and Turcot’s syndromes. Although genetic testing for these mutations is available, robust classification of variants requires strong clinical and functional support. Here, the first structure of the N-terminus of human MLH1, determined by X-ray crystallography, is described. The structure shares a high degree of similarity with previously determined prokaryotic MLH1 homologs; however, this structure affords a more accurate platform for the classification of MLH1 variants.

  8. Structural and functional insights into the N-terminus of Schizosaccharomyces pombe Cdc5.

    PubMed

    Collier, Scott E; Voehler, Markus; Peng, Dungeng; Ohi, Ryoma; Gould, Kathleen L; Reiter, Nicholas J; Ohi, Melanie D

    2014-10-21

    The spliceosome is a dynamic macromolecular machine composed of five small nuclear ribonucleoparticles (snRNPs), the NineTeen Complex (NTC), and other proteins that catalyze the removal of introns mature to form the mature message. The NTC, named after its founding member Saccharomyces cerevisiae Prp19, is a conserved spliceosome subcomplex composed of at least nine proteins. During spliceosome assembly, the transition to an active spliceosome correlates with stable binding of the NTC, although the mechanism of NTC function is not understood. Schizosaccharomyces pombe Cdc5, a core subunit of the NTC, is an essential protein required for pre-mRNA splicing. The highly conserved Cdc5 N-terminus contains two canonical Myb (myeloblastosis) repeats (R1 and R2) and a third domain (D3) that was previously classified as a Myb-like repeat. Although the N-terminus of Cdc5 is required for its function, how R1, R2, and D3 each contribute to functionality is unclear. Using a combination of yeast genetics, structural approaches, and RNA binding assays, we show that R1, R2, and D3 are all required for the function of Cdc5 in cells. We also show that the N-terminus of Cdc5 binds RNA in vitro. Structural and functional analyses of Cdc5-D3 show that, while this domain does not adopt a Myb fold, Cdc5-D3 preferentially binds double-stranded RNA. Our data suggest that the Cdc5 N-terminus interacts with RNA structures proposed to be near the catalytic core of the spliceosome.

  9. N-Terminus of the Protein Kinase CLK1 Induces SR Protein Hyper-Phosphorylation

    PubMed Central

    Aubol, Brandon E.; Plocinik, Ryan M.; Keshwani, Malik M.; McGlone, Maria L.; Hagopian, Jonathan C.; Ghosh, Gourisankar; Fu, Xiang-Dong; Adams, Joseph A.

    2016-01-01

    SR proteins are essential splicing factors that are regulated through multisite phosphorylation of their RS (arginine-serine-rich) domains by two major families of protein kinases. The SRPKs efficiently phosphorylate the arginine-serine dipeptides in the RS domain using a conserved docking groove in the kinase domain. In contrast, CLKs lack a docking groove and phosphorylate both arginine-serine and serine-proline dipeptides, modifications that generate a hyper-phosphorylated state important for unique SR protein-dependent splicing activities. All CLKs contain long, flexible N-terminal extensions (140-300 residues) that resemble the RS domains present in their substrate SR proteins. We showed that the N-terminus in CLK1 contacts both the kinase domain and the RS domain of the SR protein SRSF1. This interaction not only is essential for facilitating hyper-phosphorylation but also induces cooperative binding of SRSF1 to RNA. The N-terminus of CLK1 enhances the total phosphoryl contents of a panel of physiological substrates including SRSF1, SRSF2, SRSF5 and Tra2β1 by 2–3-fold. These findings suggest that CLK1-dependent hyper-phosphorylation is the result of a general mechanism in which the N-terminus acts as a bridge connecting the kinase domain and the RS domain of the SR protein. PMID:24869919

  10. Monoclonal antibodies against the muscle-specific N-terminus of dystrophin: Characterization of dystrophin in a muscular dystrophy patient with a frameshift deletion of Exons 3-7

    SciTech Connect

    Thanh, L. T.; Man, N. thi; Morris, G.E. ); Love, D.R.; Davies, K.E. ); Helliwell, T.R. )

    1993-07-01

    The first three exons of the human muscle dystrophin gene were expressed as a [beta]-galactosidase fusion protein. 1-his protein was then used to prepare two monoclonal antibodies (mAbs) which react with native dystrophin on frozen muscle sections and with denatured dystrophin on western blots but which do not cross-react with the distrophin-related protein, utrophin. Both mAbs recognized dystrophin in muscular dystrophy (MD) patients with deletions of exon 3, and further mapping with 11 overlapping synthetic peptides showed that they both recognize an epitope encoded by the muscle-specific exon 1. Neither mAb recognizes the brain dystrophin isoform, confirming the prediction from mRNA data that this has a different N-terminus. One Becker MD patient with a frameshift deletion of exons 3-7 is shown to produce dystrophin which reacts with the N-terminal mAbs, as well as with mAbs which bind on the C-terminal side of the deletion. The data suggest that transcription begins at the normal muscle dystrophin promoter and that the normal reading frame is restored after the deletion. A number of mechanisms have been proposed for restoration of the reading frame after deletion of exons 3-7, but those which predict dystrophin with an abnormal N-terminus do not appear to be major mechanisms in this patient. 27 refs., 6 figs.

  11. The N-terminus of survivin is a mitochondrial-targeting sequence and Src regulator

    PubMed Central

    Dunajová, Lucia; Cash, Emily; Markus, Robert; Rochette, Sophie; Townley, Amelia R.

    2016-01-01

    ABSTRACT Survivin (also known as BIRC5) is a cancer-associated protein that exists in several locations in the cell. Its cytoplasmic residence in interphase cells is governed by CRM1 (also known as XPO1)-mediated nuclear exportation, and its localisation during mitosis to the centromeres and midzone microtubules is that of a canonical chromosomal passenger protein. In addition to these well-established locations, survivin is also a mitochondrial protein, but how it gets there and its function therein is presently unclear. Here, we show that the first ten amino acids at the N-terminus of survivin are sufficient to target GFP to the mitochondria in vivo, and ectopic expression of this decapeptide decreases cell adhesion and accelerates proliferation. The data support a signalling mechanism in which this decapeptide regulates the tyrosine kinase Src, leading to reduced focal adhesion plaques and disruption of F-actin organisation. This strongly suggests that the N-terminus of survivin is a mitochondrial-targeting sequence that regulates Src, and that survivin acts in concert with Src to promote tumorigenesis. PMID:27246243

  12. An N-terminal nuclear export signal regulates trafficking and aggregation of Huntingtin (Htt) protein exon 1.

    PubMed

    Zheng, Zhiqiang; Li, Aimin; Holmes, Brandon B; Marasa, Jayne C; Diamond, Marc I

    2013-03-01

    Huntington disease is a dominantly inherited neurodegenerative condition caused by polyglutamine expansion in the N terminus of the huntingtin protein (Htt). The first 17 amino acids (N17) of Htt play a key role in regulating its toxicity and aggregation. Both nuclear export and cytoplasm retention functions have been ascribed to N17. We have determined that N17 acts as a nuclear export sequence (NES) within Htt exon and when fused to yellow fluorescent protein. We have defined amino acids within N17 that constitute the nuclear export sequence (NES). Mutation of any of the conserved residues increases nuclear accumulation of Htt exon 1. Nuclear export of Htt is sensitive to leptomycin B and is reduced by knockdown of exportin 1. In HEK293 cells, NES mutations decrease overall Htt aggregation but increase the fraction of cells with nuclear inclusions. In primary cultured neurons, NES mutations increase nuclear accumulation and increase overall aggregation. This work defines a bona fide nuclear export sequence within N17 and links it to effects on protein aggregation. This may help explain the important role of N17 in controlling Htt toxicity. PMID:23319588

  13. Structural characterization of the HIV-1 Vpr N terminus: evidence of cis/trans-proline isomerism.

    PubMed

    Bruns, Karsten; Fossen, Torgils; Wray, Victor; Henklein, Peter; Tessmer, Uwe; Schubert, Ulrich

    2003-10-31

    The 96-residue human immunodeficiency virus (HIV) accessory protein Vpr serves manifold functions in the retroviral life cycle including augmentation of viral replication in non-dividing host cells, induction of G2 cell cycle arrest, and modulation of HIV-induced apoptosis. Using a combination of dynamic light scattering, circular dichroism, and NMR spectroscopy the N terminus of Vpr is shown to be a unique domain of the molecule that behaves differently from the C-terminal domain in terms of self-association and secondary structure folding. Interestingly, the four highly conserved proline residues in the N terminus are predicted to have a high propensity for cis/trans isomerism. Thus the high resolution structure and folding of a synthetic N-terminal peptide (Vpr1-40) and smaller fragments thereof have been investigated. 1H NMR data indicate Vpr1-40 possesses helical structure between residues 17-32, and for the first time, this helix, which is bound by proline residues, was observed even in aqueous solution devoid of any detergent supplements. In addition, NMR data revealed that all of the proline residues undergo a cis/ trans isomerism to such an extent that approximately 40% of all Vpr molecules possess at least one proline in a cis conformation. This phenomenon of cis/trans isomerism, which is unprecedented for HIV-1 Vpr, not only provides an explanation for the molecular heterogeneity observed in the full-length molecule but also indicates that in vivo the folding and function of Vpr should depend on a cis/trans-proline isomerase activity, particularly as two of the proline residues in positions 14 and 35 show considerable amounts of cis isomers. This prediction correlates well with our recent observation (Zander, K., Sherman, M. P., Tessmer, U., Bruns, K., Wray, V., Prechtel, A. T., Schubert, E., Henklein, P., Luban, J., Neidleman, J., Greene, W. C., and Schubert, U. (2003) J. Biol. Chem. 278, 43170-43181) of a functional interaction between the major

  14. The importance of the N-terminus of T7 endonuclease I in the interaction with DNA junctions.

    PubMed

    Freeman, Alasdair D J; Déclais, Anne-Cécile; Lilley, David M J

    2013-01-23

    T7 endonuclease I is a dimeric nuclease that is selective for four-way DNA junctions. Previous crystallographic studies have found that the N-terminal 16 amino acids are not visible, neither in the presence nor in the absence of DNA. We have now investigated the effect of deleting the N-terminus completely or partially. N-terminal deleted enzyme binds more tightly to DNA junctions but cleaves them more slowly. While deletion of the N-terminus does not measurably affect the global structure of the complex, the presence of the peptide is required to generate a local opening at the center of the DNA junction that is observed by 2-aminopurine fluorescence. Complete deletion of the peptide leads to a cleavage rate that is 3 orders of magnitude slower and an activation enthalpy that is 3-fold higher, suggesting that the most important interaction of the peptide is with the reaction transition state. Taken together, these data point to an important role of the N-terminus in generating a central opening of the junction that is required for the cleavage reaction to proceed properly. In the absence of this, we find that a cruciform junction is no longer subject to bilateral cleavage, but instead, just one strand is cleaved. Thus, the N-terminus is required for a productive resolution of the junction.

  15. Structural and dynamic evolution of the amphipathic N-terminus diversifies enzyme thermostability in the glycoside hydrolase family 12.

    PubMed

    Jiang, Xukai; Chen, Guanjun; Wang, Lushan

    2016-08-21

    Understanding the molecular mechanism underlying protein thermostability is central to the process of efficiently engineering thermostable cellulases, which can provide potential advantages in accelerating the conversion of biomass into clean biofuels. Here, we explored the general factors that diversify enzyme thermostability in the glycoside hydrolase family 12 (GH12) using comparative molecular dynamics (MD) simulations coupled to a bioinformatics approach. The results indicated that protein stability is not equally distributed over the whole structure: the N-terminus is the most thermal-sensitive region of the enzymes with a β-sandwich architecture and it tends to lose its secondary structure during the course of protein unfolding. Furthermore, we found that the total interaction energy within the N-terminus is appreciably correlated with enzyme thermostability. Interestingly, the internal interactions within the N-terminus are organized in a special amphipathic pattern in which a hydrophobic packing cluster and a hydrogen bonding cluster lie at the two ends of the N-terminus. Finally, bioinformatics analysis demonstrated that the amphipathic pattern is highly conserved in GH12 and besides that, the evolution of the amino acids in the N-terminal region is an inherent mechanism underlying the diversity of enzyme thermostability. Taken together, our results demonstrate that the N-terminus is generally the structure that determines enzyme thermostability in GH12, and thereby it is also an ideal engineering target. The dynameomics study of a protein family can give a general view of protein functions, which will offer a wide range of applications in future protein engineering. PMID:27425569

  16. The N-terminus of the norepinephrine transporter regulates the magnitude and selectivity of the transporter-associated leak current.

    PubMed

    Binda, Francesca; Lute, Brandon J; Dipace, Concetta; Blakely, Randy D; Galli, Aurelio

    2006-03-01

    The norepinephrine (NE) transporter (NET) mediates the removal of NE from synaptic spaces and is a major target for antidepressants, amphetamine and cocaine. Previously, we have shown that syntaxin 1A (SYN 1A) supports human NET (hNET) cell surface expression, that hNET/SYN 1A interactions are direct and mediated by the hNET N-terminus, and that the hNET/SYN 1A association limits substrate-induced hNET-associated currents [Sung, U., Apparsundaram, S., Galli, A., Kahlig, K.M., Savchenko, V., Schroeter, S., Quick, M.W., Blakely, R.D., 2003. A regulated interaction of syntaxin 1A with the antidepressant-sensitive norepinephrine transporter establishes catecholamine clearance capacity. J. Neurosci. 23, 1697-1709]. These data raise the possibility that the hNET N-terminus, and potentially its interaction with SYN 1A, might regulate other hNET conductance states, including the hNET-mediated leak current. Importantly for monoamine transporters, the leak conductance has been shown to play a critical role in regulating cell membrane potential and possibly neuronal excitability [Quick, M.W., 2003. Regulating the conducting states of a mammalian serotonin transporter. Neuron 40, 537-549]. Here we demonstrate that deletion of the binding domain for SYN 1A in the NET N-terminus robustly enhances the NET-mediated leak current as well as its selectivity for Cl- permeation under particular intracellular ionic compositions. In addition, we show that the NET N-terminus coordinates the ability of intracellular Na+ and Cl- to regulate the leak conductance. These data suggest that the NET N-terminus regulates and defines the ionic specificity of the NET-mediated leak current.

  17. Antibody evasion by the N terminus of murid herpesvirus-4 glycoprotein B

    PubMed Central

    Gillet, Laurent; Stevenson, Philip G

    2007-01-01

    Herpesviruses characteristically transmit infection from immune hosts. Although their success in escaping neutralization by pre-formed antibody is indisputable, the underlying molecular mechanisms remain largely unknown. Glycoprotein B (gB) is the most conserved component of the herpesvirus entry machinery and its N terminus (gB-NT) is a common neutralization target. We used murid herpesvirus-4 to determine how gB-NT contributes to the virus–antibody interaction. Deleting gB-NT had no obvious impact on virus replication, but paradoxically increased virion neutralization by immune sera. This reflected greater antibody access to neutralization epitopes on gH/gL, with which gB was associated. gB-NT itself was variably protected against antibody by O-linked glycans; on virions from epithelial cells it was protected almost completely. gB-NT therefore provides a protective and largely protected cover for a vulnerable part of gH/gL. The conservation of predicted glycosylation sites in other mammalian herpesvirus gB-NTs suggests that this evasion mechanism is widespread. Interestingly, the gB-NT glycans that blocked antibody binding could be targeted for neutralization instead by a lectin, suggesting a means of therapeutic counterattack. PMID:18034158

  18. Localization of the Intracellular Activity Domain of Pasteurella multocida Toxin to the N Terminus

    PubMed Central

    Wilson, Brenda A.; Ponferrada, Virgilio G.; Vallance, Jefferson E.; Ho, Mengfei

    1999-01-01

    We have shown that Pasteurella multocida toxin (PMT) directly causes transient activation of Gqα protein that is coupled to phosphatidylinositol-specific phospholipase Cβ1 in Xenopus oocytes (B. A. Wilson, X. Zhu, M. Ho, and L. Lu, J. Biol. Chem. 272:1268–1275, 1997). We found that antibodies directed against an N-terminal peptide of PMT inhibited the toxin-induced response in Xenopus oocytes, but antibodies against a C-terminal peptide did not. To test whether the intracellular activity domain of PMT is localized to the N terminus, we conducted a deletion mutational analysis of the PMT protein, using the Xenopus oocyte system as a means of screening for toxin activity. Using PCR and conventional cloning techniques, we cloned from a toxinogenic strain of P. multocida the entire toxA gene, encoding the 1,285-amino-acid PMT protein, and expressed the recombinant toxin as a His-tagged fusion protein in Escherichia coli. We subsequently generated a series of N-terminal and C-terminal deletion mutants and expressed the His-tagged PMT fragments in E. coli. These proteins were screened for cytotoxic activity on cultured Vero cells and for intracellular activity in the Xenopus oocyte system. Only the full-length protein without the His tag exhibited activity on Vero cells. The full-length PMT and N-terminal fragments containing the first 500 residues elicited responses in oocytes, but the C-terminal 780 amino acid fragment did not. Our results confirm that the intracellular activity domain of PMT is localized to the N-terminal 500 amino acids of the protein and that the C terminus is required for entry into cells. PMID:9864199

  19. N-terminus-modified Hec1 suppresses tumour growth by interfering with kinetochore-microtubule dynamics.

    PubMed

    Orticello, M; Fiore, M; Totta, P; Desideri, M; Barisic, M; Passeri, D; Lenzi, J; Rosa, A; Orlandi, A; Maiato, H; Del Bufalo, D; Degrassi, F

    2015-06-01

    Mitotic proteins are attractive targets to develop molecular cancer therapeutics due to the intimate interdependence between cell proliferation and mitosis. In this work, we have explored the therapeutic potential of the kinetochore (KT) protein Hec1 (Highly Expressed in Cancer protein 1) as a molecular target to produce massive chromosome missegregation and cell death in cancer cells. Hec1 is a constituent of the Ndc80 complex, which mediates KT-microtubule (MT) attachments at mitosis and is upregulated in various cancer types. We expressed Hec1 fused with enhanced green fluorescent protein (EGFP) at its N-terminus MT-interaction domain in HeLa cells and showed that expression of this modified Hec1, which localized at KTs, blocked cell proliferation and promoted apoptosis in tumour cells. EGFP-Hec1 was extremely potent in tumour cell killing and more efficient than siRNA-induced Hec1 depletion. In striking contrast, normal cells showed no apparent cell proliferation defects or cell death following EGFP-Hec1 expression. Live-cell imaging demonstrated that cancer cell death was associated with massive chromosome missegregation within multipolar spindles after a prolonged mitotic arrest. Moreover, EGFP-Hec1 expression was found to increase KT-MT attachment stability, providing a molecular explanation for the abnormal spindle architecture and the cytotoxic activity of this modified protein. Consistent with cell culture data, EGFP-Hec1 expression was found to strongly inhibit tumour growth in a mouse xenograft model by disrupting mitosis and inducing multipolar spindles. Taken together, these findings demonstrate that stimulation of massive chromosome segregation defects can be used as an anti-cancer strategy through the activation of mitotic catastrophe after a multipolar mitosis. Importantly, this study represents a clear proof of concept that targeting KT proteins required for proper KT-MT attachment dynamics constitutes a powerful approach in cancer therapy.

  20. The N-terminus of classical swine fever virus (CSFV) nonstructural protein 2 modulates viral genome RNA replication.

    PubMed

    Li, Ling; Wu, Rui; Zheng, Fengwei; Zhao, Cheng; Pan, Zishu

    2015-12-01

    Pestivirus nonstructural protein 2 (NS2) is a multifunctional, hydrophobic protein with an important but poorly understood role in viral RNA replication and infectious virus production. In the present study, based on sequence analysis, we mutated several representative conserved residues within the N-terminus of NS2 of classical swine fever virus (CSFV) and investigated how these mutations affected viral RNA replication and infectious virus production. Our results demonstrated that the mutation of two aspartic acids, NS2/D60A or NS2/D60K and NS2/D78K, in the N-terminus of NS2 abolished infectious virus production and that the substitution of arginine for alanine at position 100 (NS2/R100A) resulted in significantly decreased viral titer. The serial passage of cells containing viral genomic RNA molecules generated the revertants NS2/A60D, NS2/K60D and NS2/K78D, leading to the recovery of infectious virus. In the context of the NS2/R100A mutant, the NS2/I90L mutation compensated for infectious virus production. The regulatory roles of the indicated amino acid residues were identified to occur at the viral RNA replication level. These results revealed a novel function for the NS2 N-terminus of CSFV in modulating viral RNA replication. PMID:26232654

  1. Spontaneous Inward Opening of the Dopamine Transporter Is Triggered by PIP2-Regulated Dynamics of the N-Terminus

    PubMed Central

    2015-01-01

    We present the dynamic mechanism of concerted motions in a full-length molecular model of the human dopamine transporter (hDAT), a member of the neurotransmitter/sodium symporter (NSS) family, involved in state-to-state transitions underlying function. The findings result from an analysis of unbiased atomistic molecular dynamics simulation trajectories (totaling >14 μs) of the hDAT molecule immersed in lipid membrane environments with or without phosphatidylinositol 4,5-biphosphate (PIP2) lipids. The N-terminal region of hDAT (N-term) is shown to have an essential mechanistic role in correlated rearrangements of specific structural motifs relevant to state-to-state transitions in the hDAT. The mechanism involves PIP2-mediated electrostatic interactions between the N-term and the intracellular loops of the transporter molecule. Quantitative analyses of collective motions in the trajectories reveal that these interactions correlate with the inward-opening dynamics of hDAT and are allosterically coupled to the known functional sites of the transporter. The observed large-scale motions are enabled by specific reconfiguration of the network of ionic interactions at the intracellular end of the protein. The isomerization to the inward-facing state in hDAT is accompanied by concomitant movements in the extracellular vestibule and results in the release of an Na+ ion from the Na2 site and destabilization of the substrate dopamine in the primary substrate binding S1 site. The dynamic mechanism emerging from the findings highlights the involvement of the PIP2-regulated interactions between the N-term and the intracellular loop 4 in the functionally relevant conformational transitions that are also similar to those found to underlie state-to-state transitions in the leucine transporter (LeuT), a prototypical bacterial homologue of the NSS. PMID:26255829

  2. IUGR increases chromatin-remodeling factor Brg1 expression and binding to GR exon 1.7 promoter in newborn male rat hippocampus.

    PubMed

    Ke, Xingrao; McKnight, Robert A; Gracey Maniar, Lia E; Sun, Ying; Callaway, Christopher W; Majnik, Amber; Lane, Robert H; Cohen, Susan S

    2015-07-15

    Intrauterine growth restriction (IUGR) increases the risk for neurodevelopment delay and neuroendocrine reprogramming in both humans and rats. Neuroendocrine reprogramming involves the glucocorticoid receptor (GR) gene that is epigenetically regulated in the hippocampus. Using a well-characterized rodent model, we have previously shown that IUGR increases GR exon 1.7 mRNA variant and total GR expressions in male rat pup hippocampus. Epigenetic regulation of GR transcription may involve chromatin remodeling of the GR gene. A key chromatin remodeler is Brahma-related gene-1(Brg1), a member of the ATP-dependent SWItch/Sucrose NonFermentable (SWI/SNF) chromatin remodeling complex. Brg1 regulates gene expression by affecting nucleosome repositioning and recruiting transcriptional components to target promoters. We hypothesized that IUGR would increase hippocampal Brg1 expression and binding to GR exon 1.7 promoter, as well as alter nucleosome positioning over GR promoters in newborn male pups. Further, we hypothesized that IUGR would lead to accumulation of specificity protein 1 (Sp1) and RNA pol II at GR exon 1.7 promoter. Indeed, we found that IUGR increased Brg1 expression and binding to GR exon 1.7 promoter. We also found that increased Brg1 binding to GR exon 1.7 promoter was associated with accumulation of Sp1 and RNA pol II carboxy terminal domain pSer-5 (a marker of active transcription). Furthermore, the transcription start site of GR exon 1.7 was located within a nucleosome-depleted region. We speculate that changes in hippocampal Brg1 expression mediate GR expression and subsequently trigger neuroendocrine reprogramming in male IUGR rats. PMID:25972460

  3. Aminoacylase 3 binds to and cleaves the N-terminus of the hepatitis C virus core protein

    PubMed Central

    Tsirulnikov, Kirill; Abuladze, Natalia; Vahi, Ritu; Hasnain, Huma; Phillips, Martin; Ryan, Christopher M.; Atanasov, Ivo; Faull, Kym F.; Kurtz, Ira; Pushkin, Alexander

    2012-01-01

    Aminoacylase 3 (AA3) mediates deacetylation of N-acetyl aromatic amino acids and mercapturic acids. Deacetylation of mercapturic acids of exo- and endobiotics are likely involved in their toxicity. AA3 is predominantly expressed in kidney, and to a lesser extent in liver, brain, and blood. AA3 has been recently reported to interact with the hepatitis C virus core protein (HCVCP) in the yeast two-hybrid system. Here we demonstrate that AA3 directly binds to HCVCP (Kd~10 μM) that may by implicated in HCV pathogenesis. AA3 also revealed a weak endopeptidase activity towards the N-terminus of HCVCP. PMID:23010594

  4. Role of the N terminus in enzyme activity, stability and specificity in thermophilic esterases belonging to the HSL family.

    PubMed

    Mandrich, Luigi; Merone, Luigia; Pezzullo, Margherita; Cipolla, Laura; Nicotra, Francesco; Rossi, Mosè; Manco, Giuseppe

    2005-01-21

    A superposition between the structures of Alicyclobacillus acidocaldarius esterase 2 (EST2) and Burkholderia cepacia lipase, the latter complexed with a phosphonate inhibitor, allowed us to hypothesize for the EST2 N terminus a role in restricting the access to the active site and therefore in modulating substrate specificity. In order to test this hypothesis we generated by site-directed mutagenesis some truncated versions of EST2 and its double mutant M211S/R215L (S/L) at the N terminus. In parallel, an analysis of the Sulfolobus solfataricus P2 genome allowed us to identify a gene coding for a putative esterase of the HSL family having a natural deletion of the corresponding region. The product of this gene and the above-mentioned EST2 mutants were expressed in Escherichia coli, purified and characterised. These studies support the notion that the N terminus affects substrate specificity other than several other enzyme parameters. Although the deletions afforded a tenfold and 550-fold decrease in catalytic efficiency towards the best substrate pNP-hexanoate at 50 degrees C for EST2 and S/L, respectively, the analysis of the specific activities with different triacylglycerols with respect to pNP-hexanoate showed that their ratios were higher for deleted versus non-deleted enzymes, on all tested substrates. In particular, the above ratios for glyceryl tridecanoate were 30-fold and 14-fold higher in S/L and EST2 deleted forms, respectively, compared with their full-length versions. This behaviour was confirmed by the analysis of the S.solfataricus esterase, which showed similar specific activities on pNP-hexanoate and triacylglycerols; in addition, higher activities on the latter substrates were observed in comparison with EST2, S/L and their deleted forms. Finally, a dramatic effect on thermophilicity and thermostability in the EST2 deleted forms was observed. This is the first report highlighting the importance of the "cap" domain in the HSL family, since the N

  5. A functional dissection of PTEN N-terminus: implications in PTEN subcellular targeting and tumor suppressor activity.

    PubMed

    Gil, Anabel; Rodríguez-Escudero, Isabel; Stumpf, Miriam; Molina, María; Cid, Víctor J; Pulido, Rafael

    2015-01-01

    Spatial regulation of the tumor suppressor PTEN is exerted through alternative plasma membrane, cytoplasmic, and nuclear subcellular locations. The N-terminal region of PTEN is important for the control of PTEN subcellular localization and function. It contains both an active nuclear localization signal (NLS) and an overlapping PIP2-binding motif (PBM) involved in plasma membrane targeting. We report a comprehensive mutational and functional analysis of the PTEN N-terminus, including a panel of tumor-related mutations at this region. Nuclear/cytoplasmic partitioning in mammalian cells and PIP3 phosphatase assays in reconstituted S. cerevisiae defined categories of PTEN N-terminal mutations with distinct PIP3 phosphatase and nuclear accumulation properties. Noticeably, most tumor-related mutations that lost PIP3 phosphatase activity also displayed impaired nuclear localization. Cell proliferation and soft-agar colony formation analysis in mammalian cells of mutations with distinctive nuclear accumulation and catalytic activity patterns suggested a contribution of both properties to PTEN tumor suppressor activity. Our functional dissection of the PTEN N-terminus provides the basis for a systematic analysis of tumor-related and experimentally engineered PTEN mutations.

  6. A Functional Dissection of PTEN N-Terminus: Implications in PTEN Subcellular Targeting and Tumor Suppressor Activity

    PubMed Central

    Gil, Anabel; Rodríguez-Escudero, Isabel; Stumpf, Miriam; Molina, María; Cid, Víctor J.; Pulido, Rafael

    2015-01-01

    Spatial regulation of the tumor suppressor PTEN is exerted through alternative plasma membrane, cytoplasmic, and nuclear subcellular locations. The N-terminal region of PTEN is important for the control of PTEN subcellular localization and function. It contains both an active nuclear localization signal (NLS) and an overlapping PIP2-binding motif (PBM) involved in plasma membrane targeting. We report a comprehensive mutational and functional analysis of the PTEN N-terminus, including a panel of tumor-related mutations at this region. Nuclear/cytoplasmic partitioning in mammalian cells and PIP3 phosphatase assays in reconstituted S. cerevisiae defined categories of PTEN N-terminal mutations with distinct PIP3 phosphatase and nuclear accumulation properties. Noticeably, most tumor-related mutations that lost PIP3 phosphatase activity also displayed impaired nuclear localization. Cell proliferation and soft-agar colony formation analysis in mammalian cells of mutations with distinctive nuclear accumulation and catalytic activity patterns suggested a contribution of both properties to PTEN tumor suppressor activity. Our functional dissection of the PTEN N-terminus provides the basis for a systematic analysis of tumor-related and experimentally engineered PTEN mutations. PMID:25875300

  7. Structure of the Tuberous Sclerosis Complex 2 (TSC2) N Terminus Provides Insight into Complex Assembly and Tuberous Sclerosis Pathogenesis.

    PubMed

    Zech, Reinhard; Kiontke, Stephan; Mueller, Uwe; Oeckinghaus, Andrea; Kümmel, Daniel

    2016-09-16

    Tuberous sclerosis complex (TSC) is caused by mutations in the TSC1 and TSC2 tumor suppressor genes. The gene products hamartin and tuberin form the TSC complex that acts as GTPase-activating protein for Rheb and negatively regulates the mammalian target of rapamycin complex 1 (mTORC1). Tuberin contains a RapGAP homology domain responsible for inactivation of Rheb, but functions of other protein domains remain elusive. Here we show that the TSC2 N terminus interacts with the TSC1 C terminus to mediate complex formation. The structure of the TSC2 N-terminal domain from Chaetomium thermophilum and a homology model of the human tuberin N terminus are presented. We characterize the molecular requirements for TSC1-TSC2 interactions and analyze pathological point mutations in tuberin. Many mutations are structural and produce improperly folded protein, explaining their effect in pathology, but we identify one point mutant that abrogates complex formation without affecting protein structure. We provide the first structural information on TSC2/tuberin with novel insight into the molecular function.

  8. N-terminus conservation in the anchor polypeptide of a prokaryotic and eukaryotic alga. [Nostoc; Porphydium cruentum

    SciTech Connect

    Gantt, E.; Lipschultz, C.A.; Cunningham, F.X. Jr.; Mimuro, M.

    1987-04-01

    Energy flow between the extrinsic phycobilisomes and the photosystems within thylakoids, is probably mediated by a blue anchor polypeptide. Polypeptides in the 94 kD range, purified by LiDS-PAGE from phycobilisomes of Nostoc and Porphyrdium cruentum, crossreacted with anti-Nostoc-94 (although weakly with the latter). Though rich in ASP and GLU, the polypeptides were very hydrophobic, and low in MET, CYS, and HIS. Partial sequence of the N-terminus shows considerable homology 1 - 5 - 10 - 15 - 20 N: (S)-V-K-A-S-G-G-S-S-V-A-(R)-P-Q-L-Y-Q-(G)-L-(A)-V- P: V-()-K-A-S-G-G-S-P-V-V-K-P-Q-L-Y-(K)-()-A-(S)- between the species. There is a lack of homology when compared with ..cap alpha.. and ..beta.. polypeptides of allophycocyanin with rod linkers of phycobilisomes and other phycobiliproteins. Polypeptides of 94 and 92 kD from thylakoids of Nostoc, also immunoreactive with anti-94, were blocked at the N-terminus.

  9. Change in plasma immunoreactive N-terminus, C-terminus, and 4,000-dalton midportion of atrial natriuretic factor prohormone with hemodialysis.

    PubMed

    Winters, C J; Vesely, D L

    1991-01-01

    Plasma concentrations of the immunoreactive N-terminus, C-terminus and 4,000-dalton midportion of the N-terminus of the atrial natriuretic factor (ANF) prohormone were measured before and after hemodialysis in 13 patients with end-stage renal disease. There was a significant (p less than 0.001) fall in the mean plasma concentration of the C-terminus (i.e. ANF, amino acids 99-126 of the prohormone) from 123 +/- 25 to 80 +/- 22 fmol/ml (mean +/- SEM) with dialysis. The whole N-terminus, on the other hand, increased from 9,336 +/- 2,011 to 11,021 +/- 2,134 fmol/ml after dialysis (p less than 0.002). Pro ANF 31-67 (i.e. amino acids 31-67 of the prohormone) increased postdialysis from 27,775 +/- 4,300 to 31,040 +/- 4,840 fmol/ml (p less than 0.003). Only 1.5% of pro ANF 1-98 and pro ANF 31-67 were cleared by the dialyzer membrane while 15% of ANF crossed the membrane. Thus, with hemodialysis the C-terminus decreases while the N-terminus and pro ANF 31-67 from the midportion of the N-terminus of the ANF prohormone increase in plasma which is partially explained by their respective abilities to cross the dialyzer membrane.

  10. N-terminus of seed caleosins is essential for lipid droplet sorting but not for lipid accumulation.

    PubMed

    Purkrtová, Zita; Chardot, Thierry; Froissard, Marine

    2015-08-01

    Caleosin, a calcium-binding protein associated with plant lipid droplets, stimulates lipid accumulation when heterologously expressed in Saccharomyces cerevisiae. Accumulated lipids are stored in cytoplasmic lipid droplets that are stabilised by incorporated caleosin. We designed a set of mutants affecting putative crucial sites for caleosin function and association with lipid droplets, i.e. the N-terminus, the EF-hand motif and the proline-knot motif. We investigated the effect of introduced mutations on caleosin capacity to initiate lipid accumulation and on caleosin sorting within cell as well as on its association with lipid droplets. Our results strongly suggest that the N-terminal domain is essential for proper protein sorting and targeting to lipid droplets but not for enhancing lipid accumulation. PMID:26032334

  11. Phosphorylation and cellular function of the human Rpa2 N-terminus in the budding yeast Saccharomyces cerevisiae.

    PubMed

    Ghospurkar, Padmaja L; Wilson, Timothy M; Liu, Shengqin; Herauf, Anna; Steffes, Jenna; Mueller, Erica N; Oakley, Gregory G; Haring, Stuart J

    2015-02-01

    Maintenance of genome integrity is critical for proper cell growth. This occurs through accurate DNA replication and repair of DNA lesions. A key factor involved in both DNA replication and the DNA damage response is the heterotrimeric single-stranded DNA (ssDNA) binding complex Replication Protein A (RPA). Although the RPA complex appears to be structurally conserved throughout eukaryotes, the primary amino acid sequence of each subunit can vary considerably. Examination of sequence differences along with the functional interchangeability of orthologous RPA subunits or regions could provide insight into important regions and their functions. This might also allow for study in simpler systems. We determined that substitution of yeast Replication Factor A (RFA) with human RPA does not support yeast cell viability. Exchange of a single yeast RFA subunit with the corresponding human RPA subunit does not function due to lack of inter-species subunit interactions. Substitution of yeast Rfa2 with domains/regions of human Rpa2 important for Rpa2 function (i.e., the N-terminus and the loop 3-4 region) supports viability in yeast cells, and hybrid proteins containing human Rpa2 N-terminal phospho-mutations result in similar DNA damage phenotypes to analogous yeast Rfa2 N-terminal phospho-mutants. Finally, the human Rpa2 N-terminus (NT) fused to yeast Rfa2 is phosphorylated in a manner similar to human Rpa2 in human cells, indicating that conserved kinases recognize the human domain in yeast. The implication is that budding yeast represents a potential model system for studying not only human Rpa2 N-terminal phosphorylation, but also phosphorylation of Rpa2 N-termini from other eukaryotic organisms.

  12. Abnormal Methylation Status of the GNAS Exon 1A Region in Pseudohypohyperparathyroidism Combined With Turner Syndrome.

    PubMed

    Zhu, Jie; Wang, Dong; Ren, An; Xing, Yan; Zhang, Dongliang; Wei, Jun; Yu, Ning; Xing, Xuenong; Ye, Shandong

    2015-12-01

    Pseudohypohyperparathyroidism (PHHP) is a rare type of pseudohypoparathyroidism (PHP), which seems to have a normal skeletal response to parathyroid hormone but shows renal resistance. Almost all patients with PHHP have PHP Ib, a subtype of PHP that is usually caused by GNAS methylation defects, often in exon 1A. Some features of Albright hereditary osteodystrophy can occasionally be found in patients with PHHP, but these features are also common in Turner syndrome. The authors report on an extremely rare case of a patient with PHHP and Turner syndrome, a 47-year-old woman who sought medical attention for hypocalcemia and elevated parathyroid hormone. She had no family history of hypocalcemia and no STX16 gene deletions. She had a mosaic karyotype of 46, X, del(X)(p11.4)/45, XO. Pyrosequencing was performed to determine the GNAS exon 1A methylation. The degree of methylation found in exon 1A of the patient was lower than her unaffected relatives.

  13. The N-Terminus of the Floral Arabidopsis TGA Transcription Factor PERIANTHIA Mediates Redox-Sensitive DNA-Binding

    PubMed Central

    Gutsche, Nora; Zachgo, Sabine

    2016-01-01

    The Arabidopsis TGA transcription factor (TF) PERIANTHIA (PAN) regulates the formation of the floral organ primordia as revealed by the pan mutant forming an abnormal pentamerous arrangement of the outer three floral whorls. The Arabidopsis TGA bZIP TF family comprises 10 members, of which PAN and TGA9/10 control flower developmental processes and TGA1/2/5/6 participate in stress-responses. For the TGA1 protein it was shown that several cysteines can be redox-dependently modified. TGA proteins interact in the nucleus with land plant-specific glutaredoxins, which may alter their activities posttranslationally. Here, we investigated the DNA-binding of PAN to the AAGAAT motif under different redox-conditions. The AAGAAT motif is localized in the second intron of the floral homeotic regulator AGAMOUS (AG), which controls stamen and carpel development as well as floral determinacy. Whereas PAN protein binds to this regulatory cis-element under reducing conditions, the interaction is strongly reduced under oxidizing conditions in EMSA studies. The redox-sensitive DNA-binding is mediated via a special PAN N-terminus, which is not present in other Arabidopsis TGA TFs and comprises five cysteines. Two N-terminal PAN cysteines, Cys68 and Cys87, were shown to form a disulfide bridge and Cys340, localized in a C-terminal putative transactivation domain, can be S-glutathionylated. Comparative land plant analyses revealed that the AAGAAT motif exists in asterid and rosid plant species. TGA TFs with N-terminal extensions of variable length were identified in all analyzed seed plants. However, a PAN-like N-terminus exists only in the rosids and exclusively Brassicaceae homologs comprise four to five of the PAN N-terminal cysteines. Redox-dependent modifications of TGA cysteines are known to regulate the activity of stress-related TGA TFs. Here, we show that the N-terminal PAN cysteines participate in a redox-dependent control of the PAN interaction with a highly conserved

  14. Interaction of the N-terminus of sterol carrier protein 2 with membranes: role of membrane curvature.

    PubMed Central

    Huang, H; Ball, J M; Billheimer, J T; Schroeder, F

    1999-01-01

    Although neither the physiological function nor the mechanism of action of sterol carrier protein 2 (SCP(2)) is yet completely clear, it is thought that SCP(2) interacts with membranes to elicit its biological effects. The results presented here show that the SCP(2) N-terminus, composed of two amphipathic alpha-helices, interacted preferentially with highly curved but not lower-curvature membranes containing anionic phospholipid. CD spectra of SCP(2) showed up to 1. 2-fold increased alpha-helical content, on the interaction of SCP(2) with small unilamellar vesicles (SUV) (median radius 10-14 nm) but less with large unilamellar vesicles (LUV) (median radius 52-60 nm). Although enhanced interaction with the SUV membranes was due in part to the radius of curvature and to the greater exposure of acidic phospholipid in the outer leaflet of the bilayer, simply increasing the molar percentage of acidic phospholipid in the LUV membranes had much less effect on SCP(2) binding. A similar preferential interaction was observed with highly curved SUV as opposed to LUV for the SCP(2) N-terminal peptide (1-32)SCP(2) as well as structurally modified peptides in the order (1-32)SCP(2)=(10-32)SCP(2)>(1-24)SCP(2)>>(1-E20-32)SCP(2). The CD results were confirmed with an independent filtration binding assay, which showed that SCP(2) bound 5-fold more to SUV than LUV, whereas its N-terminal peptides bound up to 4-fold better in the order (1-32)SCP(2)=(10-32)SCP(2)>(1-24)SCP(2)>(1-E20-32)SCP(2). Finally, cholesterol potentiated the binding of SCP(2) and N-terminal peptides to anionic-phospholipid-containing SUV but not LUV. These findings were consistent with the SCP(2) N-terminus being a membrane-binding domain that was highly dependent on membrane surface curvature as well as on lipid composition. PMID:10567245

  15. The N-Terminus of the Floral Arabidopsis TGA Transcription Factor PERIANTHIA Mediates Redox-Sensitive DNA-Binding.

    PubMed

    Gutsche, Nora; Zachgo, Sabine

    2016-01-01

    The Arabidopsis TGA transcription factor (TF) PERIANTHIA (PAN) regulates the formation of the floral organ primordia as revealed by the pan mutant forming an abnormal pentamerous arrangement of the outer three floral whorls. The Arabidopsis TGA bZIP TF family comprises 10 members, of which PAN and TGA9/10 control flower developmental processes and TGA1/2/5/6 participate in stress-responses. For the TGA1 protein it was shown that several cysteines can be redox-dependently modified. TGA proteins interact in the nucleus with land plant-specific glutaredoxins, which may alter their activities posttranslationally. Here, we investigated the DNA-binding of PAN to the AAGAAT motif under different redox-conditions. The AAGAAT motif is localized in the second intron of the floral homeotic regulator AGAMOUS (AG), which controls stamen and carpel development as well as floral determinacy. Whereas PAN protein binds to this regulatory cis-element under reducing conditions, the interaction is strongly reduced under oxidizing conditions in EMSA studies. The redox-sensitive DNA-binding is mediated via a special PAN N-terminus, which is not present in other Arabidopsis TGA TFs and comprises five cysteines. Two N-terminal PAN cysteines, Cys68 and Cys87, were shown to form a disulfide bridge and Cys340, localized in a C-terminal putative transactivation domain, can be S-glutathionylated. Comparative land plant analyses revealed that the AAGAAT motif exists in asterid and rosid plant species. TGA TFs with N-terminal extensions of variable length were identified in all analyzed seed plants. However, a PAN-like N-terminus exists only in the rosids and exclusively Brassicaceae homologs comprise four to five of the PAN N-terminal cysteines. Redox-dependent modifications of TGA cysteines are known to regulate the activity of stress-related TGA TFs. Here, we show that the N-terminal PAN cysteines participate in a redox-dependent control of the PAN interaction with a highly conserved

  16. A d-Amino Acid at the N-Terminus of a Protein Abrogates Its Degradation by the N-End Rule Pathway

    PubMed Central

    2015-01-01

    Eukaryotes have evolved the ubiquitin (Ub)/proteasome system to degrade polypeptides. The Ub/proteasome system is one way that cells regulate cytosolic protein and amino acids levels through the recognition and ubiquitination of a protein’s N-terminus via E1, E2, and E3 enzymes. The process by which the N-terminus stimulates intracellular protein degradation is referred to as the N-end rule. Characterization of the N-end rule has been limited to only the natural l-amino acids. Using a cytosolic delivery platform derived from anthrax lethal toxin, we probed the stability of mixed chirality proteins, containing one d-amino acid on the N-terminus of otherwise all l-proteins. In all cases, we observed that one N-terminal d-amino acid stabilized the cargo protein to proteasomal degradation with respect to the N-end rule. We found that since the mixed chirality proteins were not polyubiquitinated, they evaded N-end-mediated proteasomal degradation. Evidently, a subtle change on the N-terminus of a natural protein can enhance its intracellular lifetime. PMID:26807441

  17. The DNA Damage Response and Checkpoint Adaptation in Saccharomyces cerevisiae: Distinct Roles for the Replication Protein A2 (Rfa2) N-Terminus

    PubMed Central

    Ghospurkar, Padmaja L.; Wilson, Timothy M.; Severson, Amber L.; Klein, Sarah J.; Khaku, Sakina K.; Walther, André P.; Haring, Stuart J.

    2015-01-01

    In response to DNA damage, two general but fundamental processes occur in the cell: (1) a DNA lesion is recognized and repaired, and (2) concomitantly, the cell halts the cell cycle to provide a window of opportunity for repair to occur. An essential factor for a proper DNA-damage response is the heterotrimeric protein complex Replication Protein A (RPA). Of particular interest is hyperphosphorylation of the 32-kDa subunit, called RPA2, on its serine/threonine-rich amino (N) terminus following DNA damage in human cells. The unstructured N-terminus is often referred to as the phosphorylation domain and is conserved among eukaryotic RPA2 subunits, including Rfa2 in Saccharomyces cerevisiae. An aspartic acid/alanine-scanning and genetic interaction approach was utilized to delineate the importance of this domain in budding yeast. It was determined that the Rfa2 N-terminus is important for a proper DNA-damage response in yeast, although its phosphorylation is not required. Subregions of the Rfa2 N-terminus important for the DNA-damage response were also identified. Finally, an Rfa2 N-terminal hyperphosphorylation-mimetic mutant behaves similarly to another Rfa1 mutant (rfa1-t11) with respect to genetic interactions, DNA-damage sensitivity, and checkpoint adaptation. Our data indicate that post-translational modification of the Rfa2 N-terminus is not required for cells to deal with “repairable” DNA damage; however, post-translational modification of this domain might influence whether cells proceed into M-phase in the continued presence of unrepaired DNA lesions as a “last-resort” mechanism for cell survival. PMID:25595672

  18. The characterization of a novel S100A1 binding site in the N-terminus of TRPM1.

    PubMed

    Jirku, Michaela; Lansky, Zdenek; Bednarova, Lucie; Sulc, Miroslav; Monincova, Lenka; Majer, Pavel; Vyklicky, Ladislav; Vondrasek, Jiri; Teisinger, Jan; Bousova, Kristyna

    2016-09-01

    Transient receptor potential melastatin-1 channel (TRPM1) is an important mediator of calcium influx into the cell that is expressed in melanoma and ON-bipolar cells. Similar to other members of the TRP channel family, the intracellular N- and C- terminal domains of TRPM1 are expected to play important roles in the modulation of TRPM1 receptor function. Among the most commonly occurring modulators of TRP channels are the cytoplasmically expressed calcium binding proteins calmodulin and S100 calcium-binding protein A1 (S100A1), but the interaction of TRPM1 with S100A1 has not been described yet. Here, using a combination of biophysical and bioinformatics methods, we have determined that the N-terminal L242-E344 region of TRPM1 is a S100A1 binding domain. We show that formation of the TRPM1/S100A1 complex is calcium-dependent. Moreover, our structural model of the complex explained data obtained from fluorescence spectroscopy measurements revealing that the complex formation is facilitated through interactions of clusters positively charged (K271A, R273A, R274A) and hydrophobic (L263A, V270A, L276A) residues at the N-terminus of TRPM1. Taken together, our data suggest a molecular mechanism for the potential regulation of TRPM1 by S100A1. PMID:27435061

  19. Folding Landscape of Mutant Huntingtin Exon1: Diffusible Multimers, Oligomers and Fibrils, and No Detectable Monomer.

    PubMed

    Sahoo, Bankanidhi; Arduini, Irene; Drombosky, Kenneth W; Kodali, Ravindra; Sanders, Laurie H; Greenamyre, J Timothy; Wetzel, Ronald

    2016-01-01

    Expansion of the polyglutamine (polyQ) track of the Huntingtin (HTT) protein above 36 is associated with a sharply enhanced risk of Huntington's disease (HD). Although there is general agreement that HTT toxicity resides primarily in N-terminal fragments such as the HTT exon1 protein, there is no consensus on the nature of the physical states of HTT exon1 that are induced by polyQ expansion, nor on which of these states might be responsible for toxicity. One hypothesis is that polyQ expansion induces an alternative, toxic conformation in the HTT exon1 monomer. Alternative hypotheses posit that the toxic species is one of several possible aggregated states. Defining the nature of the toxic species is particularly challenging because of facile interconversion between physical states as well as challenges to identifying these states, especially in vivo. Here we describe the use of fluorescence correlation spectroscopy (FCS) to characterize the detailed time and repeat length dependent self-association of HTT exon1-like fragments both with chemically synthesized peptides in vitro and with cell-produced proteins in extracts and in living cells. We find that, in vitro, mutant HTT exon1 peptides engage in polyQ repeat length dependent dimer and tetramer formation, followed by time dependent formation of diffusible spherical and fibrillar oligomers and finally by larger, sedimentable amyloid fibrils. For expanded polyQ HTT exon1 expressed in PC12 cells, monomers are absent, with tetramers being the smallest molecular form detected, followed in the incubation time course by small, diffusible aggregates at 6-9 hours and larger, sedimentable aggregates that begin to build up at 12 hrs. In these cell cultures, significant nuclear DNA damage appears by 6 hours, followed at later times by caspase 3 induction, mitochondrial dysfunction, and cell death. Our data thus defines limits on the sizes and concentrations of different physical states of HTT exon1 along the reaction profile

  20. Folding Landscape of Mutant Huntingtin Exon1: Diffusible Multimers, Oligomers and Fibrils, and No Detectable Monomer

    PubMed Central

    Sahoo, Bankanidhi; Arduini, Irene; Drombosky, Kenneth W.; Kodali, Ravindra; Sanders, Laurie H.; Greenamyre, J. Timothy; Wetzel, Ronald

    2016-01-01

    Expansion of the polyglutamine (polyQ) track of the Huntingtin (HTT) protein above 36 is associated with a sharply enhanced risk of Huntington’s disease (HD). Although there is general agreement that HTT toxicity resides primarily in N-terminal fragments such as the HTT exon1 protein, there is no consensus on the nature of the physical states of HTT exon1 that are induced by polyQ expansion, nor on which of these states might be responsible for toxicity. One hypothesis is that polyQ expansion induces an alternative, toxic conformation in the HTT exon1 monomer. Alternative hypotheses posit that the toxic species is one of several possible aggregated states. Defining the nature of the toxic species is particularly challenging because of facile interconversion between physical states as well as challenges to identifying these states, especially in vivo. Here we describe the use of fluorescence correlation spectroscopy (FCS) to characterize the detailed time and repeat length dependent self-association of HTT exon1-like fragments both with chemically synthesized peptides in vitro and with cell-produced proteins in extracts and in living cells. We find that, in vitro, mutant HTT exon1 peptides engage in polyQ repeat length dependent dimer and tetramer formation, followed by time dependent formation of diffusible spherical and fibrillar oligomers and finally by larger, sedimentable amyloid fibrils. For expanded polyQ HTT exon1 expressed in PC12 cells, monomers are absent, with tetramers being the smallest molecular form detected, followed in the incubation time course by small, diffusible aggregates at 6–9 hours and larger, sedimentable aggregates that begin to build up at 12 hrs. In these cell cultures, significant nuclear DNA damage appears by 6 hours, followed at later times by caspase 3 induction, mitochondrial dysfunction, and cell death. Our data thus defines limits on the sizes and concentrations of different physical states of HTT exon1 along the reaction

  1. Huntingtin exon 1 fibrils feature an interdigitated β-hairpin–based polyglutamine core

    PubMed Central

    Hoop, Cody L.; Lin, Hsiang-Kai; Kar, Karunakar; Magyarfalvi, Gábor; Lamley, Jonathan M.; Boatz, Jennifer C.; Mandal, Abhishek; Lewandowski, Józef R.; Wetzel, Ronald

    2016-01-01

    Polyglutamine expansion within the exon1 of huntingtin leads to protein misfolding, aggregation, and cytotoxicity in Huntington’s disease. This incurable neurodegenerative disease is the most prevalent member of a family of CAG repeat expansion disorders. Although mature exon1 fibrils are viable candidates for the toxic species, their molecular structure and how they form have remained poorly understood. Using advanced magic angle spinning solid-state NMR, we directly probe the structure of the rigid core that is at the heart of huntingtin exon1 fibrils and other polyglutamine aggregates, via measurements of long-range intramolecular and intermolecular contacts, backbone and side-chain torsion angles, relaxation measurements, and calculations of chemical shifts. These experiments reveal the presence of β-hairpin–containing β-sheets that are connected through interdigitating extended side chains. Despite dramatic differences in aggregation behavior, huntingtin exon1 fibrils and other polyglutamine-based aggregates contain identical β-strand–based cores. Prior structural models, derived from X-ray fiber diffraction and computational analyses, are shown to be inconsistent with the solid-state NMR results. Internally, the polyglutamine amyloid fibrils are coassembled from differently structured monomers, which we describe as a type of “intrinsic” polymorphism. A stochastic polyglutamine-specific aggregation mechanism is introduced to explain this phenomenon. We show that the aggregation of mutant huntingtin exon1 proceeds via an intramolecular collapse of the expanded polyglutamine domain and discuss the implications of this observation for our understanding of its misfolding and aggregation mechanisms. PMID:26831073

  2. Posttranslational modification at the N terminus of the human adenovirus type 12 E1A 235R tumor antigen.

    PubMed Central

    Lucher, L A; Brackmann, K H; Symington, J S; Green, M

    1986-01-01

    The adenovirus E1A transforming region, which encodes immortalization, partial cell transformation, and gene activation functions, expresses two early mRNAs, 13S and 12S. Multiple-T antigen species with different electrophoretic mobilities are formed from each mRNA, presumably by unknown posttranslational modifications. The adenovirus type 12 (Ad12) 13S and 12S mRNAs encode E1A T antigens of 266 and 235 amino acid residues (266R and 235R), respectively. To study possible posttranslational processing at the N and C termini and to distinguish between the Ad12 266R and 235R T antigens, we prepared antibodies targeted to synthetic peptides encoded at the common C (peptide 204) and N (peptide 202) termini of the 266R and 235R T antigens and at the unique internal domain of the 266R T antigen (peptide 206). The specificity of each anti-peptide antibody was confirmed by immunoprecipitation of the 266R and 235R T antigens produced in Escherichia coli. Immunoprecipitation analysis of the E1A T antigens synthesized in Ad12-infected KB cells revealed the following. Antibody to the common C terminus recognized three T antigens with apparent Mrs of 43,000, 42,000, and 39,000 (43K, 42K, and 39K). All three forms were phosphorylated and were present in both the nucleus and the cytoplasm. The 43K and 42K T antigens were rapidly synthesized during a 10-min pulse with [35S]methionine in Ad12-infected cells. The 43K T antigen had a half-life of 20 min, the 42K T antigen had a longer half-life of about 40 min, and the 39K T antigen became the predominant E1A T antigen. Antibodies to the unique region immunoprecipitated the 43K T antigen but not the 42K and 39K T antigens. Antibody to the N terminus immunoprecipitated the 43K and 42K T antigens but not the 39K T antigen, suggesting that the 39K T antigen possessed a modified N terminus. Partial N-terminal amino acid sequence analysis showed that the 43K and 42K T antigens contain methionine at residues 1 and 5, as predicted from the

  3. Mutational analysis of the N-terminus in Schistocerca gregaria ion-transport peptide expressed in Drosophila Kc1 cells.

    PubMed

    Zhao, Y; Meredith, J; Brock, H W; Phillips, J E

    2005-01-01

    The functions of the 6-7 amino acid N-terminal domain conserved in insect and crustacean members of the hyperglycemic hormone (CHH) family were assayed by site-directed mutagenesis of Schistocerca gregaria ion-transport peptide (SchgrITP). Mutant peptides were expressed in Drosophila Kc1 cells and tested in a biological assay measuring stimulation of active Cl(-) transport across the locust ileum. We exchanged the N-terminal domain of SchgrITP with that of the shrimp Penaeus japonicus hyperglycemic hormone leaving the remainder of SchgrITP intact. The chimeric peptide was completely inactive in the ileal bioassay, showing that the N-terminus of SchgrITP is essential and that the 2 amino acids (phenylalanine-3 and aspartate-4) conserved in the shrimp and locust peptides are not sufficient for function. We made all possible alanine substitutions in the SchgrITP N-terminal domain. Only phenylalanines 2 and 3 were essential for function in the locust ileal bioassay. All N-terminal mutations were cleaved correctly from the prepropeptide, and expressed in similar concentrations as wild-type ITP suggesting the specific amino acids are not essential for these functions. Post-translational modification may explain a minor ITP isomorph observed in Drosophila Kc1 cell expression. Alanine substitution at position 2 produced a weak ITP antagonist. These structure-function studies, the first for any member of the CHH family, show that both conserved and unconserved amino acids contribute to SchgrITP ion-transport function and that the conserved aspartate in position 4 is required for a yet uncharacterized function.

  4. The N-Terminus of Murine Leukaemia Virus p12 Protein Is Required for Mature Core Stability

    PubMed Central

    Wight, Darren J.; Boucherit, Virginie C.; Wanaguru, Madushi; Elis, Efrat; Hirst, Elizabeth M. A.; Li, Wilson; Ehrlich, Marcelo; Bacharach, Eran; Bishop, Kate N.

    2014-01-01

    The murine leukaemia virus (MLV) gag gene encodes a small protein called p12 that is essential for the early steps of viral replication. The N- and C-terminal regions of p12 are sequentially acting domains, both required for p12 function. Defects in the C-terminal domain can be overcome by introducing a chromatin binding motif into the protein. However, the function of the N-terminal domain remains unknown. Here, we undertook a detailed analysis of the effects of p12 mutation on incoming viral cores. We found that both reverse transcription complexes and isolated mature cores from N-terminal p12 mutants have altered capsid complexes compared to wild type virions. Electron microscopy revealed that mature N-terminal p12 mutant cores have different morphologies, although immature cores appear normal. Moreover, in immunofluorescent studies, both p12 and capsid proteins were lost rapidly from N-terminal p12 mutant viral cores after entry into target cells. Importantly, we determined that p12 binds directly to the MLV capsid lattice. However, we could not detect binding of an N-terminally altered p12 to capsid. Altogether, our data imply that p12 stabilises the mature MLV core, preventing premature loss of capsid, and that this is mediated by direct binding of p12 to the capsid shell. In this manner, p12 is also retained in the pre-integration complex where it facilitates tethering to mitotic chromosomes. These data also explain our previous observations that modifications to the N-terminus of p12 alter the ability of particles to abrogate restriction by TRIM5alpha and Fv1, factors that recognise viral capsid lattices. PMID:25356837

  5. Role of the ρ1 GABA(C) receptor N-terminus in assembly, trafficking and function.

    PubMed

    Wong, Lik-Wei; Tae, Han-Shen; Cromer, Brett A

    2014-12-17

    The GABAC receptor and closely related GABAA receptor are members of the pentameric ligand-gated ion channels (pLGICs) superfamily and mediate inhibitory fast synaptic transmission in the nervous system. Each pLGIC subunit comprises an N-terminal extracellular agonist-binding domain followed by a channel domain and a variable intracellular domain. Available structural information shows that the core of the agonist-binding domain is a β sandwich of ten β-strands, which form the agonist-binding pocket at the subunit interface. This β-sandwich is preceded by an N-terminal α-helix in eukaryotic structures but not in prokaryotic structures. The N-terminal α-helix has been shown to be functionally essential in α7 nicotinic acetylcholine receptors. Sequence analysis of GABAC and GABAA receptors predicts an α-helix in a similar position but preceded by 8 to 46 additional residues, of unknown function, which we term the N-terminal extension. To test the functional role of both the N-terminal extension and the putative N-terminal α-helix in the ρ1 GABAC receptor, we created a series of deletions from the N-terminus. The N-terminal extension was not functionally essential, but its removal did reduce both cell surface expression and cooperativity of agonist-gated channel function. Further deletion of the putative N-terminal α-helix abolished receptor function by preventing cell-surface expression. Our results further demonstrate the essential role of the N-terminal α-helix in the assembly and trafficking of eukaryotic pLGICs. They also provide evidence that the N-terminal extension, although not essential, contributes to receptor assembly, trafficking and conformational changes associated with ligand gating.

  6. Atomic Structure and Biochemical Characterization of an RNA Endonuclease in the N Terminus of Andes Virus L Protein

    PubMed Central

    Fernández-García, Yaiza; Reguera, Juan; Busch, Carola; Witte, Gregor; Sánchez-Ramos, Oliberto; Betzel, Christian; Cusack, Stephen; Günther, Stephan; Reindl, Sophia

    2016-01-01

    Andes virus (ANDV) is a human-pathogenic hantavirus. Hantaviruses presumably initiate their mRNA synthesis by using cap structures derived from host cell mRNAs, a mechanism called cap-snatching. A signature for a cap-snatching endonuclease is present in the N terminus of hantavirus L proteins. In this study, we aimed to solve the atomic structure of the ANDV endonuclease and characterize its biochemical features. However, the wild-type protein was refractory to expression in Escherichia coli, presumably due to toxic enzyme activity. To circumvent this problem, we introduced attenuating mutations in the domain that were previously shown to enhance L protein expression in mammalian cells. Using this approach, 13 mutant proteins encompassing ANDV L protein residues 1–200 were successfully expressed and purified. Protein stability and nuclease activity of the mutants was analyzed and the crystal structure of one mutant was solved to a resolution of 2.4 Å. Shape in solution was determined by small angle X-ray scattering. The ANDV endonuclease showed structural similarities to related enzymes of orthobunya-, arena-, and orthomyxoviruses, but also differences such as elongated shape and positively charged patches surrounding the active site. The enzyme was dependent on manganese, which is bound to the active site, most efficiently cleaved single-stranded RNA substrates, did not cleave DNA, and could be inhibited by known endonuclease inhibitors. The atomic structure in conjunction with stability and activity data for the 13 mutant enzymes facilitated inference of structure–function relationships in the protein. In conclusion, we solved the structure of a hantavirus cap-snatching endonuclease, elucidated its catalytic properties, and present a highly active mutant form, which allows for inhibitor screening. PMID:27300328

  7. Computational modeling of the N-terminus of the human dopamine transporter and its interaction with PIP2-containing membranes

    PubMed Central

    Khelashvili, George; Doktorova, Milka; Sahai, Michelle A.; Johner, Niklaus; Shi, Lei; Weinstein, Harel

    2015-01-01

    The dopamine transporter (DAT) is a transmembrane protein belonging to the family of Neurotransmitter:Sodium Symporters (NSS). Members of the NSS are responsible for the clearance of neurotransmitters from the synaptic cleft, and for their translocation back into the presynaptic nerve terminal. The DAT contains long intracellular N- and C-terminal domains that are strongly implicated in the transporter function. The N-terminus (N-term), in particular, regulates the reverse transport (efflux) of the substrate through DAT. Currently, the molecular mechanisms of the efflux remain elusive in large part due to lack of structural information on the N-terminal segment. Here we report a computational model of the N-term of the human DAT (hDAT), obtained through an ab initio structure prediction, in combination with extensive atomistic molecular dynamics (MD) simulations in the context of a lipid membrane. Our analysis reveals that whereas the N-term is a highly dynamic domain, it contains secondary structure elements that remain stable in the long MD trajectories of interactions with the bilayer (totaling >2.2 µs). Combining MD simulations with continuum mean-field modeling we found that the N-term engages with lipid membranes through electrostatic interactions with the charged lipids PIP2 (phosphatidylinositol 4,5-Biphosphate) or PS (phosphatidylserine) that are present in these bilayers. We identify specific motifs along the N-term implicated in such interactions and show that differential modes of N-term/membrane association result in differential positioning of the structured segments on the membrane surface. These results will inform future structure-based studies that will elucidate the mechanistic role of the N-term in DAT function. PMID:25739722

  8. Atomic Structure and Biochemical Characterization of an RNA Endonuclease in the N Terminus of Andes Virus L Protein.

    PubMed

    Fernández-García, Yaiza; Reguera, Juan; Busch, Carola; Witte, Gregor; Sánchez-Ramos, Oliberto; Betzel, Christian; Cusack, Stephen; Günther, Stephan; Reindl, Sophia

    2016-06-01

    Andes virus (ANDV) is a human-pathogenic hantavirus. Hantaviruses presumably initiate their mRNA synthesis by using cap structures derived from host cell mRNAs, a mechanism called cap-snatching. A signature for a cap-snatching endonuclease is present in the N terminus of hantavirus L proteins. In this study, we aimed to solve the atomic structure of the ANDV endonuclease and characterize its biochemical features. However, the wild-type protein was refractory to expression in Escherichia coli, presumably due to toxic enzyme activity. To circumvent this problem, we introduced attenuating mutations in the domain that were previously shown to enhance L protein expression in mammalian cells. Using this approach, 13 mutant proteins encompassing ANDV L protein residues 1-200 were successfully expressed and purified. Protein stability and nuclease activity of the mutants was analyzed and the crystal structure of one mutant was solved to a resolution of 2.4 Å. Shape in solution was determined by small angle X-ray scattering. The ANDV endonuclease showed structural similarities to related enzymes of orthobunya-, arena-, and orthomyxoviruses, but also differences such as elongated shape and positively charged patches surrounding the active site. The enzyme was dependent on manganese, which is bound to the active site, most efficiently cleaved single-stranded RNA substrates, did not cleave DNA, and could be inhibited by known endonuclease inhibitors. The atomic structure in conjunction with stability and activity data for the 13 mutant enzymes facilitated inference of structure-function relationships in the protein. In conclusion, we solved the structure of a hantavirus cap-snatching endonuclease, elucidated its catalytic properties, and present a highly active mutant form, which allows for inhibitor screening.

  9. Atomic Structure and Biochemical Characterization of an RNA Endonuclease in the N Terminus of Andes Virus L Protein.

    PubMed

    Fernández-García, Yaiza; Reguera, Juan; Busch, Carola; Witte, Gregor; Sánchez-Ramos, Oliberto; Betzel, Christian; Cusack, Stephen; Günther, Stephan; Reindl, Sophia

    2016-06-01

    Andes virus (ANDV) is a human-pathogenic hantavirus. Hantaviruses presumably initiate their mRNA synthesis by using cap structures derived from host cell mRNAs, a mechanism called cap-snatching. A signature for a cap-snatching endonuclease is present in the N terminus of hantavirus L proteins. In this study, we aimed to solve the atomic structure of the ANDV endonuclease and characterize its biochemical features. However, the wild-type protein was refractory to expression in Escherichia coli, presumably due to toxic enzyme activity. To circumvent this problem, we introduced attenuating mutations in the domain that were previously shown to enhance L protein expression in mammalian cells. Using this approach, 13 mutant proteins encompassing ANDV L protein residues 1-200 were successfully expressed and purified. Protein stability and nuclease activity of the mutants was analyzed and the crystal structure of one mutant was solved to a resolution of 2.4 Å. Shape in solution was determined by small angle X-ray scattering. The ANDV endonuclease showed structural similarities to related enzymes of orthobunya-, arena-, and orthomyxoviruses, but also differences such as elongated shape and positively charged patches surrounding the active site. The enzyme was dependent on manganese, which is bound to the active site, most efficiently cleaved single-stranded RNA substrates, did not cleave DNA, and could be inhibited by known endonuclease inhibitors. The atomic structure in conjunction with stability and activity data for the 13 mutant enzymes facilitated inference of structure-function relationships in the protein. In conclusion, we solved the structure of a hantavirus cap-snatching endonuclease, elucidated its catalytic properties, and present a highly active mutant form, which allows for inhibitor screening. PMID:27300328

  10. Identification of a Novel Coregulator, SH3YL1, That Interacts With the Androgen Receptor N-Terminus

    PubMed Central

    Blessing, Alicia M.; Ganesan, Sathya; Rajapakshe, Kimal; Ying Sung, Ying; Reddy Bollu, Lakshmi; Shi, Yan; Cheung, Edwin; Coarfa, Cristian; Chang, Jeffrey T.; McDonnell, Donald P.

    2015-01-01

    Nuclear receptor (NR)-mediated transcriptional activity is a dynamic process that is regulated by the binding of ligands that induce distinct conformational changes in the NR. These structural alterations lead to the differential recruitment of coregulators (coactivators or corepressors) that control the expression of NR-regulated genes. Here, we show that a stretch of proline residues located within the N-terminus of androgen receptor (AR) is a bona fide coregulator binding surface, the disruption of which reduces the androgen-dependent proliferation and migration of prostate cancer (PCa) cells. Using T7 phage display, we identified a novel AR-interacting protein, Src homology 3 (SH3)-domain containing, Ysc84-like 1 (SH3YL1), whose interaction with the receptor is dependent upon this polyproline domain. As with mutations within the AR polyproline domain, knockdown of SH3YL1 attenuated androgen-mediated cell growth and migration. RNA expression analysis revealed that SH3YL1 was required for the induction of a subset of AR-modulated genes. Notable was the observation that ubinuclein 1 (UBN1), a key member of a histone H3.3 chaperone complex, was a transcriptional target of the AR/SH3YL1 complex, correlated with aggressive PCa in patients, and was necessary for the maximal androgen-mediated proliferation and migration of PCa cells. Collectively, these data highlight the importance of an amino-terminal activation domain, its associated coregulator, and downstream transcriptional targets in regulating cellular processes of pathological importance in PCa. PMID:26305679

  11. The N Terminus of Type III Secretion Needle Protein YscF from Yersinia pestis Functions To Modulate Innate Immune Responses

    PubMed Central

    Osei-Owusu, Patrick; Jessen Condry, Danielle L.; Toosky, Melody; Roughead, William; Bradley, David S.

    2015-01-01

    The type III secretion system is employed by many pathogens, including the genera Yersinia, Shigella, Pseudomonas, and Salmonella, to deliver effector proteins into eukaryotic cells. The injectisome needle is formed by the polymerization of a single protein, e.g., YscF (Yersinia pestis), PscF (Pseudomonas aeruginosa), PrgI (Salmonella enterica SPI-1), SsaG (Salmonella enterica SPI-2), or MxiH (Shigella flexneri). In this study, we demonstrated that the N termini of some needle proteins, particularly the N terminus of YscF from Yersinia pestis, influences host immune responses. The N termini of several needle proteins were truncated and tested for the ability to induce inflammatory responses in a human monocytic cell line (THP-1 cells). Truncated needle proteins induced proinflammatory cytokines to different magnitudes than the corresponding wild-type proteins, except SsaG. Notably, N-terminally truncated YscF induced significantly higher activation of NF-κB and/or AP-1 and higher induction of proinflammatory cytokines, suggesting that a function of the N terminus of YscF is interference with host sensing of YscF, consistent with Y. pestis pathogenesis. To directly test the ability of the N terminus of YscF to suppress cytokine induction, a YscF-SsaG chimera with 15 N-terminal amino acids from YscF added to SsaG was constructed. The chimeric YscF-SsaG induced lower levels of cytokines than wild-type SsaG. However, the addition of 15 random amino acids to SsaG had no effect on NF-κB/AP-1 activation. These results suggest that the N terminus of YscF can function to decrease cytokine induction, perhaps contributing to a favorable immune environment leading to survival of Y. pestis within the eukaryotic host. PMID:25644012

  12. Importance of two consecutive methionines at the N-terminus of a cellulose synthase (PtdCesA8A) for normal wood cellulose synthesis in aspen.

    PubMed

    Liu, Yunxia; Xu, Fuyu; Gou, Jiqing; Al-Haddad, Jameel; Telewski, Frank W; Bae, Hyeun-Jong; Joshi, Chandrashekhar P

    2012-11-01

    All known orthologs of a secondary wall-associated cellulose synthase (CesA) gene from Arabidopsis, AtCesA8, encode CesA proteins with two consecutive methionines at their N-termini (MM or 2M). Here, we report that these 2Ms in an aspen ortholog of AtCesA8, PtdCesA8A, are important for maintaining normal wood cellulose biosynthesis in aspen trees. Overexpression of an altered PtdCesA8A cDNA encoding a PtdCesA8A protein missing one methionine at the N-terminus (1M) in aspen resulted in substantial decrease in cellulose content and caused negative effects on wood strength, suggesting that both methionines are essential for proper CesA expression and function in developing xylem tissues. Transcripts from a pair of paralogous native PtdCesA8 genes, as well as introduced PtdCesA8A:1M transgenes were significantly reduced in developing xylem tissues of transgenic aspen plants, suggestive of a co-suppression event. Overexpression of a native PtdCesA8A cDNA encoding a CesA protein with 2Ms at the N-terminus did not cause any such phenotypic changes. These results suggest the importance of 2Ms present at the N-terminus of PtdCesA8A protein during cellulose synthesis in aspen.

  13. The N-terminus of the Montano virus nucleocapsid protein possesses broadly cross-reactive conformation-dependent epitopes conserved in rodent-borne hantaviruses.

    PubMed

    Saasa, Ngonda; Yoshida, Haruka; Shimizu, Kenta; Sánchez-Hernández, Cornelio; Romero-Almaraz, María de Lourdes; Koma, Takaaki; Sanada, Takahiro; Seto, Takahiro; Yoshii, Kentaro; Ramos, Celso; Yoshimatsu, Kumiko; Arikawa, Jiro; Takashima, Ikuo; Kariwa, Hiroaki

    2012-06-20

    The hantavirus nucleocapsid (N) protein is an important immunogen that stimulates a strong and cross-reactive immune response in humans and rodents. A large proportion of the response to N protein has been found to target its N-terminus. However, the exact nature of this bias towards the N-terminus is not yet fully understood. We characterized six monoclonal antibodies (mAbs) against the N protein of Montano virus (MTNV), a Mexican hantavirus. Five of these mAbs recognized eight American hantaviruses and six European and Asian hantaviruses, but not the Soricomorpha-borne Thottapalayam hantavirus. The N protein-reactive binding regions of the five mAbs were mapped to discontinuous epitopes within the N-terminal 13-51 amino acid residues, while a single serotype-specific mAb was mapped to residues 1-25 and 49-75. Our findings suggest that discontinuous epitopes at the N-terminus are conserved, at least in rodent-borne hantaviruses, and that they contribute considerably to N protein cross-reactivity.

  14. A homozygous deletion of exon 1 in WISP3 causes progressive pseudorheumatoid dysplasia in two siblings

    PubMed Central

    Neerinckx, Barbara; Thues, Cedric; Wouters, Carine; Lechner, Sarah; Westhovens, Rene; Van Esch, Hilde

    2015-01-01

    Progressive pseudorheumatoid dysplasia (PPD) is a rare autosomal recessive disease that causes progressive joint stiffness and pain. It is associated with loss-of-function mutations in the WISP3 gene. We describe two sisters suffering from PPD in whom molecular genetic analysis revealed a homozygous deletion of exon 1 and of the 5′UTR of the WISP3 gene. This is the first time that a gross deletion has been described as the causal mutation in PPD. PMID:27081554

  15. Abnormal Methylation Status of the GNAS Exon 1A Region in Pseudohypohyperparathyroidism Combined With Turner Syndrome.

    PubMed

    Zhu, Jie; Wang, Dong; Ren, An; Xing, Yan; Zhang, Dongliang; Wei, Jun; Yu, Ning; Xing, Xuenong; Ye, Shandong

    2015-12-01

    Pseudohypohyperparathyroidism (PHHP) is a rare type of pseudohypoparathyroidism (PHP), which seems to have a normal skeletal response to parathyroid hormone but shows renal resistance. Almost all patients with PHHP have PHP Ib, a subtype of PHP that is usually caused by GNAS methylation defects, often in exon 1A. Some features of Albright hereditary osteodystrophy can occasionally be found in patients with PHHP, but these features are also common in Turner syndrome. The authors report on an extremely rare case of a patient with PHHP and Turner syndrome, a 47-year-old woman who sought medical attention for hypocalcemia and elevated parathyroid hormone. She had no family history of hypocalcemia and no STX16 gene deletions. She had a mosaic karyotype of 46, X, del(X)(p11.4)/45, XO. Pyrosequencing was performed to determine the GNAS exon 1A methylation. The degree of methylation found in exon 1A of the patient was lower than her unaffected relatives. PMID:26488942

  16. Molecular Interaction between the Chaperone Hsc70 and the N-terminal Flank of Huntingtin Exon 1 Modulates Aggregation*

    PubMed Central

    Monsellier, Elodie; Redeker, Virginie; Ruiz-Arlandis, Gemma; Bousset, Luc; Melki, Ronald

    2015-01-01

    The aggregation of polyglutamine (polyQ)-containing proteins is at the origin of nine neurodegenerative diseases. Molecular chaperones prevent the aggregation of polyQ-containing proteins. The exact mechanism by which they interact with polyQ-containing, aggregation-prone proteins and interfere with their assembly is unknown. Here we dissect the mechanism of interaction between a huntingtin exon 1 fragment of increasing polyQ lengths (HttEx1Qn), the aggregation of which is tightly associated with Huntington's disease, and molecular chaperone Hsc70. We show that Hsc70, together with its Hsp40 co-chaperones, inhibits HttEx1Qn aggregation and modifies the structural, seeding, and infectious properties of the resulting fibrils in a polyQ-independent manner. We demonstrate that Hsc70 binds the 17-residue-long N-terminal flank of HttEx1Qn, and we map Hsc70-HttEx1Qn surface interfaces at the residue level. Finally, we show that this interaction competes with homotypic interactions between the N termini of different HttEx1Qn molecules that trigger the aggregation process. Our results lay the foundations of future therapeutic strategies targeting huntingtin aggregation in Huntington disease. PMID:25505179

  17. Direct identification of all oncogenic mutants in KRAS exon 1 by cycling temperature capillary electrophoresis.

    PubMed

    Bjørheim, Jens; Gaudernack, Gustav; Giercksky, Karl-Erik; Ekstrøm, Per O

    2003-01-01

    Over the past few decades, advances in genetics and molecular biology have revolutionized our understanding of cancer initiation and progression. Molecular progression models outlining genetic events have been developed for many solid tumors, including colon cancer. Previous reports in the literature have shown a relationship between different KRAS mutations and prognosis and response to medical treatment in colon cancer patients. Furthermore, the presence of a mutated KRAS has been correlated with different clinicopathological variables including age and gender of patients and tumor location. To our knowledge, few institutions screen for KRAS mutations on regular basis in colon cancer patients despite such evidence that knowledge of KRAS exon 1 status is informative. Here, we report on a mutation analysis method adapted to a 96-capillary electrophoresis instrument that allows identification of all 12 oncogenic mutations in KRAS exon 1 under denaturing conditions. To determine the optimal parameters, a series of DNA constructs generated by site-directed mutagenesis was analyzed and the migration times of all mutant peaks were measured. A classification tree was then made based on the differences in migration time between the mutants and an internal standard. A randomized series of 500 samples constructed with mutagenesis as well as 60 blind samples from sporadic colon carcinomas was analyzed to test the method. No wild-type samples were scored as mutants and all mutants were correctly identified. Post polymerase chain reaction (PCR) analysis time of 96 samples was performed within 40 min. PMID:12652573

  18. The Unique N-terminus of the UbcH10 E2 Enzyme Controls the Threshold for APC Activation and Enhances Checkpoint Regulation of the APC

    PubMed Central

    Summers, Matthew K.; Pan, Borlan; Mukhyala, Kiran; Jackson, Peter K.

    2008-01-01

    Summary In vitro, the Anaphase Promoting Complex (APC) E3 ligase functions with E2 ubiquitin conjugating enzymes of the E2–C and Ubc4/5 families to ubiquitinate substrates. However, only the use of the E2–C family, notably UbcH10, is genetically well validated. Here, we biochemically demonstrate preferential use of UbcH10 by the APC, specified by the E2 core domain. Importantly, an additional E2–E3 interaction mediated by the N-terminal extension of UbcH10 regulates APC activity. Mutating the highly conserved N-terminus increases substrate ubiquitination, the number of substrate lysines targeted, allows ubiquitination of APC substrates lacking their destruction-boxes, increases resistance to the APC inhibitors Emi1 and BubR1 in vitro, and bypasses the spindle checkpoint in vivo. Fusion of the UbcH10 N-terminus to UbcH5 restricts ubiquitination activity, but does not direct specific interactions with the APC. Thus, UbcH10 combines a specific E2–E3 interface and regulation via its N-terminal extension to limit APC activity for substrate selection and checkpoint control. PMID:18722180

  19. Conserved amino acids within the N-terminus of the West Nile virus NS4A protein contribute to virus replication, protein stability and membrane proliferation.

    PubMed

    Ambrose, R L; Mackenzie, J M

    2015-07-01

    The West Nile virus strain Kunjin virus (WNVKUN) NS4A protein is a multifunctional protein involved in many aspects of the virus life-cycle and is a major component of the WNVKUN replication complex (RC). Previously we identified a conserved region in the C-terminus of NS4A regulating proteolytic processing and RC assembly, and now investigate key conserved residues in the N-terminus of NS4A and their contribution to WNVKUN replication. Mutation of P13 completely ablated replication, whereas, mutation of P48 and D49, near the first transmembrane helix, and G66 within the helix, showed variable defects in replication, virion secretion and membrane proliferation. Intriguingly, the P48 and G66 NS4A mutants resulted in specific proteasome depletion of NS4A that could in part be rescued with a proteasome inhibitor. Our results suggest that the N-terminus of NS4A contributes to correct folding and stability, essential for facilitating the essential roles of NS4A during replication.

  20. Exploring the structure of the 100 amino-acid residue long N-terminus of the plant antenna protein CP29.

    PubMed

    Shabestari, Maryam Hashemi; Wolfs, Cor J A M; Spruijt, Ruud B; van Amerongen, Herbert; Huber, Martina

    2014-03-18

    The structure of the unusually long (∼100 amino-acid residues) N-terminal domain of the light-harvesting protein CP29 of plants is not defined in the crystal structure of this membrane protein. We studied the N-terminus using two electron paramagnetic resonance (EPR) approaches: the rotational diffusion of spin labels at 55 residues with continuous-wave EPR, and three sets of distances with a pulsed EPR method. The N-terminus is relatively structured. Five regions that differ considerably in their dynamics are identified. Two regions have low rotational diffusion, one of which shows α-helical character suggesting contact with the protein surface. This immobile part is flanked by two highly dynamic, unstructured regions (loops) that cover residues 10-22 and 82-91. These loops may be important for the interaction with other light-harvesting proteins. The region around residue 4 also has low rotational diffusion, presumably because it attaches noncovalently to the protein. This section is close to a phosphorylation site (Thr-6) in related proteins, such as those encoded by the Lhcb4.2 gene. Phosphorylation might influence the interaction with other antenna complexes, thereby regulating the supramolecular organization in the thylakoid membrane.

  1. Conserved amino acids within the N-terminus of the West Nile virus NS4A protein contribute to virus replication, protein stability and membrane proliferation

    SciTech Connect

    Ambrose, R.L.; Mackenzie, J.M.

    2015-07-15

    The West Nile virus strain Kunjin virus (WNV{sub KUN}) NS4A protein is a multifunctional protein involved in many aspects of the virus life-cycle and is a major component of the WNV{sub KUN} replication complex (RC). Previously we identified a conserved region in the C-terminus of NS4A regulating proteolytic processing and RC assembly, and now investigate key conserved residues in the N-terminus of NS4A and their contribution to WNV{sub KUN} replication. Mutation of P13 completely ablated replication, whereas, mutation of P48 and D49, near the first transmembrane helix, and G66 within the helix, showed variable defects in replication, virion secretion and membrane proliferation. Intriguingly, the P48 and G66 NS4A mutants resulted in specific proteasome depletion of NS4A that could in part be rescued with a proteasome inhibitor. Our results suggest that the N-terminus of NS4A contributes to correct folding and stability, essential for facilitating the essential roles of NS4A during replication. - Highlights: • Mutation of Proline13 of the WNV NS4A protein is lethal to replication. • 1st TMB helix of NS4A contributes to protein stability and membrane remodelling. • Unstable mutants of NS4A can be rescued with a proteasome inhibitor. • This study (and of others) contributes to a functional mapping of the NS4A protein.

  2. Ipomoelin, a Jacalin-Related Lectin with a Compact Tetrameric Association and Versatile Carbohydrate Binding Properties Regulated by Its N Terminus

    PubMed Central

    Chang, Wei-Chieh; Liu, Kai-Lun; Hsu, Fang-Ciao; Jeng, Shih-Tong; Cheng, Yi-Sheng

    2012-01-01

    Many proteins are induced in the plant defense response to biotic stress or mechanical wounding. One group is lectins. Ipomoelin (IPO) is one of the wound-inducible proteins of sweet potato (Ipomoea batatas cv. Tainung 57) and is a Jacalin-related lectin (JRL). In this study, we resolved the crystal structures of IPO in its apo form and in complex with carbohydrates such as methyl α-D-mannopyranoside (Me-Man), methyl α-D-glucopyranoside (Me-Glc), and methyl α-D-galactopyranoside (Me-Gal) in different space groups. The packing diagrams indicated that IPO might represent a compact tetrameric association in the JRL family. The protomer of IPO showed a canonical β-prism fold with 12 strands of β-sheets but with 2 additional short β-strands at the N terminus. A truncated IPO (ΔN10IPO) by removing the 2 short β-strands of the N terminus was used to reveal its role in a tetrameric association. Gel filtration chromatography confirmed IPO as a tetrameric form in solution. Isothermal titration calorimetry determined the binding constants (KA) of IPO and ΔN10IPO against various carbohydrates. IPO could bind to Me-Man, Me-Glc, and Me-Gal with similar binding constants. In contrast, ΔN10IPO showed high binding ability to Me-Man and Me-Glc but could not bind to Me-Gal. Our structural and functional analysis of IPO revealed that its compact tetrameric association and carbohydrate binding polyspecificity could be regulated by the 2 additional N-terminal β-strands. The versatile carbohydrate binding properties of IPO might play a role in plant defense. PMID:22808208

  3. Multisite tyrosine phosphorylation of the N-terminus of Mint1/X11α by Src kinase regulates the trafficking of amyloid precursor protein.

    PubMed

    Dunning, Christopher J R; Black, Hannah L; Andrews, Katie L; Davenport, Elizabeth C; Conboy, Michael; Chawla, Sangeeta; Dowle, Adam A; Ashford, David; Thomas, Jerry R; Evans, Gareth J O

    2016-05-01

    Mint/X11 is one of the four neuronal trafficking adaptors that interact with amyloid precursor protein (APP) and are linked with its cleavage to generate β-amyloid peptide, a key player in the pathology of Alzheimer's disease. How APP switches between adaptors at different stages of the secretory pathway is poorly understood. Here, we show that tyrosine phosphorylation of Mint1 regulates the destination of APP. A canonical SH2-binding motif ((202) YEEI) was identified in the N-terminus of Mint1 that is phosphorylated on tyrosine by C-Src and recruits the active kinase for sequential phosphorylation of further tyrosines (Y191 and Y187). A single Y202F mutation in the Mint1 N-terminus inhibits C-Src binding and tyrosine phosphorylation. Previous studies observed that co-expression of wild-type Mint1 and APP causes accumulation of APP in the trans-Golgi. Unphosphorylatable Mint1 (Y202F) or pharmacological inhibition of Src reduced the accumulation of APP in the trans-Golgi of heterologous cells. A similar result was observed in cultured rat hippocampal neurons where Mint1(Y202F) permitted the trafficking of APP to more distal neurites than the wild-type protein. These data underline the importance of the tyrosine phosphorylation of Mint1 as a critical switch for determining the destination of APP. The regulation of amyloid precursor protein (APP) trafficking is poorly understood. We have discovered that the APP adapter, Mint1, is phosphorylated by C-Src kinase. Mint1 causes APP accumulation in the trans-Golgi network, whereas inhibition of Src or mutation of Mint1-Y202 permits APP recycling. The phosphorylation status of Mint1 could impact on the pathological trafficking of APP in Alzheimer's disease. PMID:26865271

  4. Comparative functional analysis of Jembrana disease virus Tat protein on lentivirus long terminal repeat promoters: evidence for flexibility at its N-terminus

    PubMed Central

    Su, Yang; Deng, Gang; Gai, Yuanming; Li, Yue; Gao, Yang; Du, Jiansen; Geng, Yunqi; Chen, Qimin; Qiao, Wentao

    2009-01-01

    Background Jembrana disease virus (JDV) encodes a potent regulatory protein Tat that strongly stimulates viral expression by transactivating the long terminal repeat (LTR) promoter. JDV Tat (jTat) promotes the transcription from its own LTR as well as non-cognate LTRs, by recruiting host transcription factors and facilitating transcriptional elongation. Here, we compared the sequence requirements of jTat for transactivation of JDV, bovine immunodeficiency virus (BIV) and human immunodeficiency virus (HIV) LTRs. Results In this study, we identified the minimal protein sequence for LTR activation using jTat truncation mutants. We found that jTat N-terminal residues were indispensable for transactivating the HIV LTR. In contrast, transactivation of BIV and JDV LTRs depended largely on an arginine-rich motif and some flanking residues. Competitive inhibition assay and knockdown analysis showed that P-TEFb was required for jTat-mediated LTR transactivation, and a mammalian two-hybrid assay revealed the robust interaction of jTat with cyclin T1. In addition, HIV LTR transactivation was largely affected by fusion protein at the jTat N-terminus despite the fact that the cyclin T1-binding affinity was not altered. Furthermore, the jTat N-terminal sequence enabled HIV Tat to transactivate BIV and JDV LTRs, suggesting the flexibility at the jTat N-terminus. Conclusion This study showed the distinct sequence requirements of jTat for HIV, BIV and JDV LTR activation. Residues responsible for interaction with cyclin T1 and transactivation response element are the key determinants for transactivation of its cognate LTR. N-terminal residues in jTat may compensate for transactivation of the HIV LTR, based on the flexibility. PMID:19860923

  5. De novo exon 1 missense mutations of SKI and Shprintzen-Goldberg syndrome: two new cases and a clinical review.

    PubMed

    Au, P Y Billie; Racher, Hilary E; Graham, John M; Kramer, Nancy; Lowry, R Brian; Parboosingh, Jillian S; Innes, A Micheil

    2014-03-01

    Shprintzen-Goldberg syndrome (OMIM #182212) is a connective tissue disorder characterized by craniosynostosis, distinctive craniofacial features, skeletal abnormalities, marfanoid body habitus, aortic dilatation, and intellectual disability. Mutations in exon 1 of SKI have recently been identified as being responsible for approximately 90% of reported individuals diagnosed clinically with Shprintzen-Goldberg syndrome. SKI is a known regulator of TGFβ signaling. Therefore, like Marfan syndrome and Loeys-Dietz syndrome, Shprintzen-Goldberg syndrome is likely caused by deregulated TGFβ signals, explaining the considerable phenotypic overlap between these three disorders. We describe two additional patients with exon 1 SKI mutations and review the clinical features and literature of Shprintzen-Goldberg syndrome.

  6. Application of protein N-terminal amidase in enzymatic synthesis of dipeptides containing acidic amino acids specifically at the N-terminus.

    PubMed

    Arai, Toshinobu; Noguchi, Atsushi; Takano, Eriko; Kino, Kuniki

    2013-04-01

    Dipeptides exhibit unique physiological functions and physical properties, e.g., l-aspartyl-l-phenylalanine-methyl ester (Asp-Phe-OMe, aspartame) as an artificial sweetener, and functional studies of peptides have been carried out in various fields. Therefore, to establish a manufacturing process for the useful dipeptides, we investigated its enzymatic synthesis by utilizing an l-amino acid ligase (Lal), which catalyzes dipeptide synthesis in an ATP-dependent manner. Many Lals were obtained, but the Lals recognizing acidic amino acids as N-terminal substrates have not been identified. To increase the variety of dipeptides that are enzymatically synthesized, we proposed a two-step synthesis: Asn-Xaa and Gln-Xaa (Asn, l-asparagine; Gln, l-glutamine; and Xaa, arbitrary amino acids) synthesized by Lals were continuously deamidated by a novel amidase, yielding Asp-Xaa and Glu-Xaa (Asp, l-aspartic acid; and Glu, l-glutamic acid). We searched for amidases that specifically deamidate the N-terminus of Asn or Gln in dipeptides since none have been previously reported. We focused on the protein N-terminal amidase from Saccharomyces cerevisiae (NTA1), and assayed its activity toward dipeptides. Our findings showed that NTA1 deamidated l-asparaginyl-l-valine (Asn-Val) and l-glutaminyl-glycine (Gln-Gly), but did not deamidate l-valyl-l-asparagine and l-alanyl-l-glutamine, suggesting that this deamidation activity is N-terminus specific. The specific activity toward Asn-Val and Gln-Gly were 190 ± 30 nmol min(-1) mg(-1)·protein and 136 ± 6 nmol min(-1) mg(-1)·protein. Additionally, we examined some characteristics of NTA1. Acidic dipeptide synthesis was examined by a combination of Lals and NTA1, resulting in the synthesis of 12 kinds of Asp-Xaa, including Asp-Phe, a precursor of aspartame, and 11 kinds of Glu-Xaa.

  7. In vivo reconstitution of a homodimeric cytochrome b559 like structure: The role of the N-terminus α-subunit from Synechocystis sp. PCC 6803.

    PubMed

    Luján, María A; Martínez, Jesús I; Alonso, Pablo J; Torrado, Alejandro; Roncel, Mercedes; Ortega, José M; Sancho, Javier; Picorel, Rafael

    2015-11-01

    The cytochrome b559 is a heme-bridged heterodimeric protein with two subunits, α and β. Both subunits from Synechocystis sp. PCC 6803 have previously been cloned and overexpressed in Escherichia coli and in vivo reconstitution experiments have been carried out. The formation of homodimers in the bacterial membrane with endogenous heme was only observed in the case of the β-subunit (β/β) but not with the full length α-subunit. In the present work, reconstitution of a homodimer (α/α) cytochrome b559 like structure was possible using a chimeric N-terminus α-subunit truncated before the amino acid isoleucine 17, eliminating completely a short amphipathic α-helix that lays on the surface of the membrane. Overexpression and in vivo reconstitution in the bacteria was clearly demonstrated by the brownish color of the culture pellet and the use of a commercial monoclonal antibody against the fusion protein carrier, the maltoside binding protein, and polyclonal antibodies against a synthetic peptide of the α-subunit from Thermosynechococcus elongatus. Moreover, a simple partial purification after membrane solubilization with Triton X-100 confirmed that the overexpressed protein complex corresponded with the maltoside binding protein-chimeric α-subunit cytochrome b559 like structure. The features of the new structure were determined by UV-Vis, electron paramagnetic resonance and redox potentiometric techniques. Ribbon representations of all possible structures are also shown to better understand the mechanism of the cytochrome b559 maturation in the bacterial cytoplasmic membrane.

  8. Evidence for auto-inhibition by the N terminus of hADAR2 and activation by dsRNA binding.

    PubMed

    Macbeth, Mark R; Lingam, Arunth T; Bass, Brenda L

    2004-10-01

    Adenosine deaminases that act on RNA (ADARs) catalyze adenosine to inosine conversion in RNA that is largely double stranded. Human ADAR2 (hADAR2) contains two double-stranded RNA binding motifs (dsRBMs), separated by a 90-amino acid linker, and these are followed by the C-terminal catalytic domain. We assayed enzymatic activity of N-terminal deletion constructs of hADAR2 to determine the role of the dsRBMs and the intervening linker peptide. We found that a truncated protein consisting of one dsRBM and the deaminase domain was capable of deaminating a short 15-bp substrate. In contrast, full-length hADAR2 was inactive on this short substrate. In addition, we observed that the N terminus, which was deleted from the truncated protein, inhibits editing activity when added in trans. We propose that the N-terminal domain of hADAR2 contains sequences that cause auto-inhibition of the enzyme. Our results suggest activation requires binding to an RNA substrate long enough to accommodate interactions with both dsRBMs.

  9. Modular elements of the TPR domain in the Mps1 N terminus differentially target Mps1 to the centrosome and kinetochore.

    PubMed

    Marquardt, Joseph R; Perkins, Jennifer L; Beuoy, Kyle J; Fisk, Harold A

    2016-07-12

    Faithful segregation of chromosomes to two daughter cells is regulated by the formation of a bipolar mitotic spindle and the spindle assembly checkpoint, ensuring proper spindle function. Here we show that the proper localization of the kinase Mps1 (monopolar spindle 1) is critical to both these processes. Separate elements in the Mps1 N-terminal extension (NTE) and tetratricopeptide repeat (TPR) domains govern localization to either the kinetochore or the centrosome. The third TPR (TPR3) and the TPR-capping helix (C-helix) are each sufficient to target Mps1 to the centrosome. TPR3 binds to voltage-dependent anion channel 3, but although this is sufficient for centrosome targeting of Mps1, it is not necessary because of the presence of the C-helix. A version of Mps1 lacking both elements cannot localize to or function at the centrosome, but maintains kinetochore localization and spindle assembly checkpoint function, indicating that TPR3 and the C-helix define a bipartite localization determinant that is both necessary and sufficient to target Mps1 to the centrosome but dispensable for kinetochore targeting. In contrast, elements required for kinetochore targeting (the NTE and first two TPRs) are dispensable for centrosomal localization and function. These data are consistent with a separation of Mps1 function based on localization determinants within the N terminus.

  10. The N-terminus of histone H2B, but not that of histone H3 or its phosphorylation, is essential for chromosome condensation

    PubMed Central

    de la Barre, Anne-Elisabeth; Angelov, Dimitri; Molla, Annie; Dimitrov, Stefan

    2001-01-01

    We have studied the role of individual histone N-termini and the phosphorylation of histone H3 in chromosome condensation. Nucleosomes, reconstituted with histone octamers containing different combinations of recombinant full-length and tailless histones, were used as competitors for chromosome assembly in Xenopus egg extracts. Nucleosomes reconstituted with intact octamers inhibited chromosome condensation as efficiently as the native ones, while tailless nucleosomes were unable to affect this process. Importantly, the addition to the extract of particles containing only intact histone H2B strongly interfered with chromosome formation while such an effect was not observed with particles lacking the N-terminal tail of H2B. This demonstrates that the inhibition effect observed in the presence of competitor nucleosomes is mainly due to the N-terminus of this histone, which, therefore, is essential for chromosome condensation. Nucleosomes in which all histones but H3 were tailless did not impede chromosome formation. In addition, when competitor nucleosome particles were reconstituted with full-length H2A, H2B and H4 and histone H3 mutated at the phosphorylable serine 10 or serine 28, their inhibiting efficiency was identical to that of the native particles. Hence, the tail of H3, whether intact or phosphorylated, is not important for chromosome condensation. A novel hypothesis, termed ‘the ready production label’ was suggested to explain the role of histone H3 phosphorylation during cell division. PMID:11707409

  11. N terminus determinants of MinC from Neisseria gonorrhoeae mediate interaction with FtsZ but do not affect interaction with MinD or homodimerization.

    PubMed

    Greco-Stewart, V; Ramirez-Arcos, S; Liao, M; Dillon, J R

    2007-06-01

    While bacterial cell division has been widely studied in rod-shaped bacteria, the mechanism of cell division in round (coccal) bacteria remains largely enigmatic. In the present study, interaction between the cell division inhibitor MinC from Neisseria gonorrhoeae (MinC(Ng)) and the gonococcal cell division proteins MinD(Ng) and FtsZ(Ng) are demonstrated. Protein truncation and site-directed mutagenic approaches determined which N-terminal residues were essential for cell division inhibition by MinC(Ng) using cell morphology as an indicator of protein functionality. Truncation from or mutation at the 13th amino acid of the N terminus of MinC(Ng) resulted in loss of protein function. Bioinformatic analyses predicted that point mutations of L35P and L68P would affect the alpha-helical conformation of the protein and we experimentally showed that these mutations alter the functionality of MinC(Ng). The bacterial two-hybrid system showed that interaction of MinC(Ng) with FtsZ(Ng) is abrogated upon truncation of 13 N-terminal residues while MinC(Ng)-MinD(Ng) interaction or MinC(Ng) homodimerization is unaffected. These data confirm interactions among gonococcal cell division proteins and determine the necessity of the 13th amino acid for MinC(Ng) function. PMID:17287984

  12. Identification of a novel domain at the N terminus of caveolin-1 that controls rear polarization of the protein and caveolae formation.

    PubMed

    Sun, Xing-Hui; Flynn, Daniel C; Castranova, Vincent; Millecchia, Lyndell L; Beardsley, Andrew R; Liu, Jun

    2007-03-01

    When cells are migrating, caveolin-1, the principal protein component of caveolae, is excluded from the leading edge and polarized at the cell rear. The dynamic feature depends on a specific sequence motif that directs intracellular trafficking of the protein. Deletion mutation analysis revealed a putative polarization domain at the N terminus of caveolin-1, between amino acids 32-60. Alanine substitution identified a minimal sequence of 10 residues ((46)TKEIDLVNRD(55)) necessary for caveolin-1 rear polarization. Interestingly, deletion of amino acids 1-60 did not prevent the polarization of caveolin-1 in human umbilical vein endothelial cells or wild-type mouse embryonic fibroblasts because of an interaction of Cav(61-178) mutant with endogenous caveolin-1. Surprisingly, expression of the depolarization mutant in caveolin-1 null cells dramatically impeded caveolae formation. Furthermore, knockdown of caveolae formation by methyl-beta-cyclodextrin failed to prevent wild-type caveolin-1 rear polarization. Importantly, genetic depletion of caveolin-1 led to disoriented migration, which can be rescued by full-length caveolin-1 but not the depolarization mutant, indicating a role of caveolin-1 polarity in chemotaxis. Thus, we have identified a sequence motif that is essential for caveolin-1 rear polarization and caveolae formation. PMID:17213184

  13. Turnip yellow mosaic virus forms infectious particles without the native beta-annulus structure and flexible coat protein N-terminus.

    PubMed

    Powell, Joshua D; Barbar, Elisar; Dreher, Theo W

    2012-01-20

    Structural studies have implicated the TYMV N-terminal amino acids of the coat protein (CP) in both static (virion stabilization) and dynamic (RNA encapsidation and disencapsidation) roles. We have deleted residues 2-5, 2-10 and 2-26 from the N-terminus and expressed the mutant CPs in E. coli to assess assembly in the absence of genomic RNA and in plant infections to assess infectivity and virion properties. In E. coli, the deletion constructs formed virus-like particles, but in decreased yield. All mutants were infectious in Chinese cabbage, producing normal symptoms but with a slight delay and decreased viral yields. Virions were progressively less stable with increasing deletion size and also more accessible to small molecules. These results show that the N-terminal 26 amino acids are not essential for viral processes in vivo, although removal of these residues decreases stability and increases porosity, both important factors for virion integrity and survival outside the host. PMID:22078163

  14. The N-terminus of Mcm10 is important for interaction with the 9-1-1 clamp and in resistance to DNA damage

    PubMed Central

    Alver, Robert C.; Zhang, Tianji; Josephrajan, Ajeetha; Fultz, Brandy L.; Hendrix, Chance J.; Das-Bradoo, Sapna; Bielinsky, Anja-Katrin

    2014-01-01

    Accurate replication of the genome requires the evolutionarily conserved minichromosome maintenance protein, Mcm10. Although the details of the precise role of Mcm10 in DNA replication are still debated, it interacts with the Mcm2-7 core helicase, the lagging strand polymerase, DNA polymerase-α and the replication clamp, proliferating cell nuclear antigen. Loss of these interactions caused by the depletion of Mcm10 leads to chromosome breakage and cell cycle checkpoint activation. However, whether Mcm10 has an active role in DNA damage prevention is unknown. Here, we present data that establish a novel role of the N-terminus of Mcm10 in resisting DNA damage. We show that Mcm10 interacts with the Mec3 subunit of the 9-1-1 clamp in response to replication stress evoked by UV irradiation or nucleotide shortage. We map the interaction domain with Mec3 within the N-terminal region of Mcm10 and demonstrate that its truncation causes UV light sensitivity. This sensitivity is not further enhanced by a deletion of MEC3, arguing that MCM10 and MEC3 operate in the same pathway. Since Rad53 phosphorylation in response to UV light appears to be normal in N-terminally truncated mcm10 mutants, we propose that Mcm10 may have a role in replication fork restart or DNA repair. PMID:24972833

  15. Synthesis and properties of peptide nucleic acid labeled at the N-terminus with HiLyte Fluor 488 fluorescent dye.

    PubMed

    Hnedzko, Dziyana; McGee, Dennis W; Rozners, Eriks

    2016-09-15

    Fluorescently labeled peptide nucleic acids (PNAs) are important tools in fundamental research and biomedical applications. However, synthesis of labeled PNAs, especially using modern and expensive dyes, is less explored than similar preparations of oligonucleotide dye conjugates. Herein, we present a simple procedure for labeling of the PNA N-terminus with HiLyte Fluor 488 as the last step of solid phase PNA synthesis. A minimum excess of 1.25equiv of activated carboxylic acid achieved labeling yields close to 90% providing a good compromise between the price of dye and the yield of product and significant improvement over previous literature procedures. The HiLyte Fluor 488-labeled PNAs retained the RNA binding ability and in live cell fluorescence microscopy experiments were brighter and significantly more photostable than PNA labeled with carboxyfluorescein. In contrast to fluorescein-labeled PNA, the fluorescence of PNAs labeled with HiLyte Fluor 488 was independent of pH in the biologically relevant range of 5-8. The potential of HiLyte Fluor 488-labeling for studies of PNA cellular uptake and distribution was demonstrated in several cell lines.

  16. Synthesis and properties of peptide nucleic acid labeled at the N-terminus with HiLyte Fluor 488 fluorescent dye.

    PubMed

    Hnedzko, Dziyana; McGee, Dennis W; Rozners, Eriks

    2016-09-15

    Fluorescently labeled peptide nucleic acids (PNAs) are important tools in fundamental research and biomedical applications. However, synthesis of labeled PNAs, especially using modern and expensive dyes, is less explored than similar preparations of oligonucleotide dye conjugates. Herein, we present a simple procedure for labeling of the PNA N-terminus with HiLyte Fluor 488 as the last step of solid phase PNA synthesis. A minimum excess of 1.25equiv of activated carboxylic acid achieved labeling yields close to 90% providing a good compromise between the price of dye and the yield of product and significant improvement over previous literature procedures. The HiLyte Fluor 488-labeled PNAs retained the RNA binding ability and in live cell fluorescence microscopy experiments were brighter and significantly more photostable than PNA labeled with carboxyfluorescein. In contrast to fluorescein-labeled PNA, the fluorescence of PNAs labeled with HiLyte Fluor 488 was independent of pH in the biologically relevant range of 5-8. The potential of HiLyte Fluor 488-labeling for studies of PNA cellular uptake and distribution was demonstrated in several cell lines. PMID:27430566

  17. A C-terminal Hydrophobic, Solvent-protected Core and a Flexible N-terminus are Potentially Required for Human Papillomavirus 18 E7 Protein Functionality

    SciTech Connect

    Liu, S.; Tian, Y; Greenaway, F; Sun, M

    2010-01-01

    The oncogenic potential of the high-risk human papillomavirus (HPV) relies on the expression of genes specifying the E7 and E6 proteins. To investigate further the variation in oligomeric structure that has been reported for different E7 proteins, an HPV-18 E7 cloned from a Hispanic woman with cervical intraepithelial neoplasia was purified to homogeneity most probably as a stable monomeric protein in aqueous solution. We determined that one zinc ion is present per HPV-18 E7 monomer by amino acid and inductively coupled plasma-atomic emission spectroscopy analysis. Intrinsic fluorescence and circular dichroism spectroscopic results indicate that the zinc ion is important for the correct folding and thermal stability of HPV-18 E7. Hydroxyl radical mediated protein footprinting coupled to mass spectrometry and other biochemical and biophysical data indicate that near the C-terminus, the four cysteines of the two Cys-X{sub 2}-Cys motifs that are coordinated to the zinc ion form a solvent inaccessible core. The N-terminal LXCXE pRb binding motif region is hydroxyl radical accessible and conformationally flexible. Both factors, the relative flexibility of the pRb binding motif at the N-terminus and the C-terminal metal-binding hydrophobic solvent-protected core, combine together and facilitate the biological functions of HPV-18 E7.

  18. Variation in the androgen receptor gene exon 1 CAG repeat correlates with manifestations of autoimmunity in women with lupus.

    PubMed

    Olsen, Nancy J; Benko, Ann L; Kovacs, William J

    2014-01-01

    Clinical and experimental evidence support a role for gonadal steroids in modulating the expression and course of autoimmune diseases such as lupus. Whether or not inherited variation in sensitivity to circulating androgenic hormones could influence the manifestations of such disease is, however, unknown. We sought to determine whether differences in androgen sensitivity conferred by variation in the exon 1 CAG repeat region of the androgen receptor (AR) gene were associated with differences in the clinical or humoral immune manifestations of lupus in a cohort of female subjects. We found that shorter AR CAG repeat lengths in lupus subjects correlated with a higher Systemic Lupus Erythematosus Disease Activity Index score, higher ANA levels, and expression of a broader array of IgG autoantibodies. Our findings of more severe clinical manifestations and more exuberant humoral autoimmunity in women with a shorter AR exon 1 CAG repeat length suggest a role for genetically determined sensitivity to androgens as a modulator of autoimmune processes. PMID:24711544

  19. Mice with an isoform-ablating Mecp2 exon 1 mutation recapitulate the neurologic deficits of Rett syndrome.

    PubMed

    Yasui, Dag H; Gonzales, Michael L; Aflatooni, Justin O; Crary, Florence K; Hu, Daniel J; Gavino, Bryant J; Golub, Mari S; Vincent, John B; Carolyn Schanen, N; Olson, Carl O; Rastegar, Mojgan; Lasalle, Janine M

    2014-05-01

    Mutations in MECP2 cause the neurodevelopmental disorder Rett syndrome (RTT OMIM 312750). Alternative inclusion of MECP2/Mecp2 exon 1 with exons 3 and 4 encodes MeCP2-e1 or MeCP2-e2 protein isoforms with unique amino termini. While most MECP2 mutations are located in exons 3 and 4 thus affecting both isoforms, MECP2 exon 1 mutations but not exon 2 mutations have been identified in RTT patients, suggesting that MeCP2-e1 deficiency is sufficient to cause RTT. As expected, genetic deletion of Mecp2 exons 3 and/or 4 recapitulates RTT-like neurologic defects in mice. However, Mecp2 exon 2 knockout mice have normal neurologic function. Here, a naturally occurring MECP2 exon 1 mutation is recapitulated in a mouse model by genetic engineering. A point mutation in the translational start codon of Mecp2 exon 1, transmitted through the germline, ablates MeCP2-e1 translation while preserving MeCP2-e2 production in mouse brain. The resulting MeCP2-e1 deficient mice developed forelimb stereotypy, hindlimb clasping, excessive grooming and hypo-activity prior to death between 7 and 31 weeks. MeCP2-e1 deficient mice also exhibited abnormal anxiety, sociability and ambulation. Despite MeCP2-e1 and MeCP2-e2 sharing, 96% amino acid identity, differences were identified. A fraction of phosphorylated MeCP2-e1 differed from the bulk of MeCP2 in subnuclear localization and co-factor interaction. Furthermore, MeCP2-e1 exhibited enhanced stability compared with MeCP2-e2 in neurons. Therefore, MeCP2-e1 deficient mice implicate MeCP2-e1 as the sole contributor to RTT with non-redundant functions.

  20. An in vitro peptide complementation assay for CYT-18-dependent group I intron splicing reveals a new role for the N-terminus.

    PubMed

    Geng, Chun; Paukstelis, Paul J

    2014-03-01

    The mitochondrial tyrosyl tRNA synthetase from Neurospora crassa (CYT-18 protein) is a bifunctional group I intron splicing cofactor. CYT-18 is capable of splicing multiple group I introns from a wide variety of sources by stabilizing the catalytically active intron structures. CYT-18 and mt TyrRSs from related fungal species have evolved to assist in group I intron splicing in part by the accumulation of three N-terminal domain insertions. Biochemical and structural analysis indicate that the N-terminal insertions serve primarily to create a structure-stabilizing scaffold for critical tertiary interactions between the two major RNA domains of group I introns. Previous studies concluded that the primarily α-helical N-terminal insertion, H0, contributes to protein stability and is necessary for splicing the N. crassa ND1 intron but is dispensable for splicing the N. crassa mitochondrial LSU intron. Here, we show that CYT-18 with a complete H0 deletion retains residual ND1 intron splicing activity and that addition of the missing N-terminus in trans is capable of restoring a significant portion of its splicing activity. The development of this peptide complementation assay has allowed us to explore important characteristics of the CYT-18/group I intron interaction including the stoichiometry of H0 in intron splicing and the importance of specific H0 residues. Evaluation of truncated H0 peptides in this assay and a re-examination of the CYT-18 crystal structure suggest a previously unknown structural role of the first five N-terminal residues of CYT-18. These residues interact directly with another splicing insertion, making H0 a central structural element responsible for connecting all three N-terminal splicing insertions.

  1. NMR structures of anti-HIV D-peptides derived from the N-terminus of viral chemokine vMIP-II

    SciTech Connect

    Mori, Mayuko; Liu Dongxiang; Kumar, Santosh; Huang Ziwei; E-mail: ziweihuang@burnham.org

    2005-09-30

    The viral macrophage inflammatory protein-II (vMIP-II) encoded by Kaposi's sarcoma-associated herpesvirus has unique biological activities in that it blocks the cell entry by several different human immunodeficiency virus type 1 (HIV-1) strains via chemokine receptors including CXCR4 and CCR5. In this paper, we report the solution structure of all-D-amino acid peptides derived from the N-terminus of vMIP-II, which have been shown to have strong CXCR4 binding activity and potently inhibit HIV-1 entry via CXCR4, by using long mixing time two-dimensional nuclear Overhauser enhancement spectroscopy experiments. Both of all-D-peptides vMIP-II (1-10) and vMIP-II (1-21), which are designated as DV3 and DV1, respectively, have higher CXCR4 binding ability than their L-peptide counterparts. They are partially structured in aqueous solution, displaying a turn-like structure over residues 5-8. The small temperature coefficients of His-6 amide proton for both peptides also suggest the formation of a small hydrophobic pocket centered on His-6. The structural features of DV3 are very similar to the reported solution structure of all-L-peptide vMIP-II (1-10) [M.P. Crump, E. Elisseeva, J. Gong, I. Clark-Lewis, B.D. Sykes, Structure/function of human herpesvirus-8 MIP-II (1-71) and the antagonist N-terminal segment (1-10), FEBS Lett. 489 (2001) 171], which is consistent with the notion that D- and L-enantiomeric peptides can adopt mirror image conformations. The NMR structures of the D-peptides provide a structural basis to understand their mechanism of action and design new peptidomimetic analogs to further explore the structure-activity relationship of D-peptide ligand binding to CXCR4.

  2. Engineering the Expression and Characterization of Two Novel Laccase Isoenzymes from Coprinus comatus in Pichia pastoris by Fusing an Additional Ten Amino Acids Tag at N-Terminus

    PubMed Central

    Gu, Chunjuan; Zheng, Fei; Long, Liangkun; Wang, Jing; Ding, Shaojun

    2014-01-01

    The detail understanding of physiological/biochemical characteristics of individual laccase isoenzymes in fungi is necessary for fundamental and application purposes, but our knowledge is still limited for most of fungi due to difficult to express laccases heterologously. In this study, two novel laccase genes, named lac3 and lac4, encoding proteins of 547 and 532-amino acids preceded by 28 and 16-residue signal peptides, respectively, were cloned from the edible basidiomycete Coprinus comatus. They showed 70% identity but much lower homology with other fungal laccases at protein level (less than 58%). Two novel laccase isoenzymes were successfully expressed in Pichia pastoris by fusing an additional 10 amino acids (Thr-Pro-Phe-Pro-Pro-Phe-Asn-Thr-Asn-Ser) tag at N-terminus, and the volumetric activities could be dramatically enhanced from undetectable level to 689 and 1465 IU/l for Lac3 and Lac4, respectively. Both laccases possessed the lowest Km and highest kcat/Km value towards syringaldazine, followed by ABTS, guaiacol and 2,6-dimethylphenol similar as the low redox potential laccases from other microorganisms. Lac3 and Lac4 showed resistant to SDS, and retained 31.86% and 43.08% activity in the presence of 100 mM SDS, respectively. Lac3 exhibited higher decolorization efficiency than Lac4 for eleven out of thirteen different dyes, which may attribute to the relatively higher catalytic efficiency of Lac3 than Lac4 (in terms of kcat/Km) towards syringaldazine and ABTS. The mild synergistic decolorization by two laccases was observed for triphenylmethane dyes but not for anthraquinone and azo dyes. PMID:24710109

  3. Distinct Roles of Ser-764 and Lys-773 at the N Terminus of von Willebrand Factor in Complex Assembly with Coagulation Factor VIII*

    PubMed Central

    Castro-Núñez, Lydia; Bloem, Esther; Boon-Spijker, Mariëtte G.; van der Zwaan, Carmen; van den Biggelaar, Maartje; Mertens, Koen; Meijer, Alexander B.

    2013-01-01

    Complex formation between coagulation factor VIII (FVIII) and von Willebrand factor (VWF) is of critical importance to protect FVIII from rapid in vivo clearance and degradation. We have now employed a chemical footprinting approach to identify regions on VWF involved in FVIII binding. To this end, lysine amino acid residues of VWF were chemically modified in the presence of FVIII or activated FVIII, which does not bind VWF. Nano-LC-MS analysis showed that the lysine residues of almost all identified VWF peptides were not differentially modified upon incubation of VWF with FVIII or activated FVIII. However, Lys-773 of peptide Ser-766–Leu-774 was protected from chemical modification in the presence of FVIII. In addition, peptide Ser-764–Arg-782, which comprises the first 19 amino acid residues of mature VWF, showed a differential modification of both Lys-773 and the α-amino group of Ser-764. To verify the role of Lys-773 and the N-terminal Ser-764 in FVIII binding, we employed VWF variants in which either Lys-773 or Ser-764 was replaced with Ala. Surface plasmon resonance analysis and competition studies revealed that VWF(K773A) exhibited reduced binding to FVIII and the FVIII light chain, which harbors the VWF-binding site. In contrast, VWF(S764A) revealed more effective binding to FVIII and the FVIII light chain compared with WT VWF. The results of our study show that the N terminus of VWF is critical for the interaction with FVIII and that Ser-764 and Lys-773 have opposite roles in the binding mechanism. PMID:23168412

  4. Distinct roles of Ser-764 and Lys-773 at the N terminus of von Willebrand factor in complex assembly with coagulation factor VIII.

    PubMed

    Castro-Núñez, Lydia; Bloem, Esther; Boon-Spijker, Mariëtte G; van der Zwaan, Carmen; van den Biggelaar, Maartje; Mertens, Koen; Meijer, Alexander B

    2013-01-01

    Complex formation between coagulation factor VIII (FVIII) and von Willebrand factor (VWF) is of critical importance to protect FVIII from rapid in vivo clearance and degradation. We have now employed a chemical footprinting approach to identify regions on VWF involved in FVIII binding. To this end, lysine amino acid residues of VWF were chemically modified in the presence of FVIII or activated FVIII, which does not bind VWF. Nano-LC-MS analysis showed that the lysine residues of almost all identified VWF peptides were not differentially modified upon incubation of VWF with FVIII or activated FVIII. However, Lys-773 of peptide Ser-766-Leu-774 was protected from chemical modification in the presence of FVIII. In addition, peptide Ser-764-Arg-782, which comprises the first 19 amino acid residues of mature VWF, showed a differential modification of both Lys-773 and the α-amino group of Ser-764. To verify the role of Lys-773 and the N-terminal Ser-764 in FVIII binding, we employed VWF variants in which either Lys-773 or Ser-764 was replaced with Ala. Surface plasmon resonance analysis and competition studies revealed that VWF(K773A) exhibited reduced binding to FVIII and the FVIII light chain, which harbors the VWF-binding site. In contrast, VWF(S764A) revealed more effective binding to FVIII and the FVIII light chain compared with WT VWF. The results of our study show that the N terminus of VWF is critical for the interaction with FVIII and that Ser-764 and Lys-773 have opposite roles in the binding mechanism. PMID:23168412

  5. In vivo reconstitution of a homodimeric cytochrome b559 like structure: The role of the N-terminus α-subunit from Synechocystis sp. PCC 6803.

    PubMed

    Luján, María A; Martínez, Jesús I; Alonso, Pablo J; Torrado, Alejandro; Roncel, Mercedes; Ortega, José M; Sancho, Javier; Picorel, Rafael

    2015-11-01

    The cytochrome b559 is a heme-bridged heterodimeric protein with two subunits, α and β. Both subunits from Synechocystis sp. PCC 6803 have previously been cloned and overexpressed in Escherichia coli and in vivo reconstitution experiments have been carried out. The formation of homodimers in the bacterial membrane with endogenous heme was only observed in the case of the β-subunit (β/β) but not with the full length α-subunit. In the present work, reconstitution of a homodimer (α/α) cytochrome b559 like structure was possible using a chimeric N-terminus α-subunit truncated before the amino acid isoleucine 17, eliminating completely a short amphipathic α-helix that lays on the surface of the membrane. Overexpression and in vivo reconstitution in the bacteria was clearly demonstrated by the brownish color of the culture pellet and the use of a commercial monoclonal antibody against the fusion protein carrier, the maltoside binding protein, and polyclonal antibodies against a synthetic peptide of the α-subunit from Thermosynechococcus elongatus. Moreover, a simple partial purification after membrane solubilization with Triton X-100 confirmed that the overexpressed protein complex corresponded with the maltoside binding protein-chimeric α-subunit cytochrome b559 like structure. The features of the new structure were determined by UV-Vis, electron paramagnetic resonance and redox potentiometric techniques. Ribbon representations of all possible structures are also shown to better understand the mechanism of the cytochrome b559 maturation in the bacterial cytoplasmic membrane. PMID:26183783

  6. Cross-talk between the octarepeat domain and the fifth binding site of prion protein driven by the interaction of copper(II) with the N-terminus.

    PubMed

    Di Natale, Giuseppe; Turi, Ildikó; Pappalardo, Giuseppe; Sóvágó, Imre; Rizzarelli, Enrico

    2015-03-01

    Prion diseases are a group of neurodegenerative diseases based on the conformational conversion of the normal form of the prion protein (PrP(C)) to the disease-related scrapie isoform (PrP(Sc)). Copper(II) coordination to PrP(C) has attracted considerable interest for almost 20 years, mainly due to the possibility that such an interaction would be an important event for the physiological function of PrP(C). In this work, we report the copper(II) coordination features of the peptide fragment Ac(PEG11)3PrP(60-114) [Ac = acetyl] as a model for the whole N-terminus of the PrP(C) metal-binding domain. We studied the complexation properties of the peptide by means of potentiometric, UV/Vis, circular dichroism and electrospray ionisation mass spectrometry techniques. The results revealed that the preferred histidyl binding sites largely depend on the pH and copper(II)/peptide ratio. Formation of macrochelate species occurs up to a 2:1 metal/peptide ratio in the physiological pH range and simultaneously involves the histidyl residues present both inside and outside the octarepeat domain. However, at increased copper(II)/peptide ratios amide-bound species form, especially within the octarepeat domain. On the contrary, at basic pH the amide-bound species predominate at any copper/peptide ratio and are formed preferably with the binding sites of His96 and His111, which is similar to the metal-binding-affinity order observed in our previous studies. PMID:25649151

  7. Demonstration of physical proximity between the N terminus and the S4-S5 linker of the human ether-a-go-go-related gene (hERG) potassium channel.

    PubMed

    de la Peña, Pilar; Alonso-Ron, Carlos; Machín, Angeles; Fernández-Trillo, Jorge; Carretero, Luis; Domínguez, Pedro; Barros, Francisco

    2011-05-27

    Potassium channels encoded by the human ether-à-go-go-related gene (hERG) contribute to cardiac repolarization as a result of their characteristic gating properties. The hERG channel N terminus acts as a crucial determinant in gating. It is also known that the S4-S5 linker couples the voltage-sensing machinery to the channel gate. Moreover, this linker has been repeatedly proposed as an interaction site for the distal portion of the N terminus controlling channel gating, but direct evidence for such an interaction is still lacking. In this study, we used disulfide bond formation between pairs of engineered cysteines to demonstrate the close proximity between the beginning of the N terminus and the S4-S5 linker. Currents from channels with introduced cysteines were rapidly and strongly attenuated by an oxidizing agent, this effect being maximal for cysteine pairs located around amino acids 3 and 542 of the hERG sequence. The state-dependent modification of the double-mutant channels, but not the single-cysteine mutants, and the ability to readily reverse modification with the reducing agent dithiothreitol indicate that a disulfide bond is formed under oxidizing conditions, locking the channels in a non-conducting state. We conclude that physical interactions between the N-terminal-most segment of the N terminus and the S4-S5 linker constitute an essential component of the hERG gating machinery, thus providing a molecular basis for previous data and indicating an important contribution of these cytoplasmic domains in controlling its unusual gating and hence determining its physiological role in setting the electrical behavior of cardiac and other cell types.

  8. DNA Methylation in the Exon 1 Region and Complex Regulation of Twist1 Expression in Gastric Cancer Cells

    PubMed Central

    Sakamoto, Ayuna; Akiyama, Yoshimitsu; Shimada, Shu; Zhu, Wei-Guo; Yuasa, Yasuhito; Tanaka, Shinji

    2015-01-01

    Twist1 overexpression is frequently observed in various cancers including gastric cancer (GC). Although DNA methylation of the Twist1 gene has been reported in cancer cells, the mechanisms underlying transcriptional activation remain uncertain. In this study, we first examined epigenetic alterations of the Twist1 using Twist1 transcription-positive and -negative cell lines that are derived from our established diffuse-type GC mouse model. Treatment with a DNA demethylation agent 5-aza-dC re-activated Twist1 expression in Twist1 expression-negative GC cells. According to methylation-specific PCR and bisulfite sequencing analysis, methylation at the CpG-rich region within Twist1 coding exon 1, rather than its promoter region, was tightly linked to transcriptional silencing of the Twist1 expression in mouse GC cells. Chromatin immunoprecipitation assays revealed that active histone mark H3K4me3 was enriched in Twist1 expression-positive cells, and inactive histone mark H3K9me3 was enriched in Twist1 expression-negative cells. The expression levels of Suv39h1 and Suv39h2, histone methyltransferases for H3K9me3, were inversely correlated with Twist1 expression, and knockdown of Suv39h1 or Suv39h2 induced Twist1 expression. Moreover, Sp1 transcription factor bound to the exon 1 CpG-rich region in Twist1 expression-positive cell lines, and Twist1 expression was diminished by mithramycin, which that interferes with Sp1 binding to CpG-rich regulatory sequences. Our studies suggested that the Twist1 transcription in GC cells might be regulated through potential cooperation of DNA methylation, histone modification in complex with Sp1 binding to CpG-rich regions within the exon 1 region. PMID:26695186

  9. Novel polymorphism in exon 1 of the melatonin receptor gene unassociated with reproductive characteristics of buffaloes in the Amazon Region.

    PubMed

    Barbosa, E M; Souza, B B; Guimarães, R C; Azevedo, J S N; Gonçalves, E C; Ribeiro, H F L; Rolim Filho, S T; Silva Filho, E

    2016-01-01

    The objective of this study was to sequence part of the exon 1 in the melatonin receptor 1A gene (MTRN1A) in buffaloes to detect a novel polymorphism with which to associate reproductive characteristics, such as age at first birth and the interval between births, in buffaloes from the northeastern region of the State of Pará (Brazil). Buffalo hair samples (77) were collected from the Terra Firme region of Pará. DNA was extracted and polymerase chain reactions (PCRs) were carried out with a primer that was designed using the GenBank accession No. AY524665 reference sequence. PCR products were purified and sequenced. After editing and analysis of the sequences, a mutation was observed at the 62nd position in exon 1 of MTRN1A (T↔C), which corresponded with a change in the 21st amino acid from leucine to proline. All possible genotypes were observed, with the most common being genotype CC (0.481). The allele frequencies were T = 0.377 and C = 0.623. Statistical analysis of FIS showed inbreeding within the sample group (FIS = 0.397) and deviations from the Hardy- Weinberg equilibrium were observed (P < 0.05). Associations between genotypes and reproductive characteristics were not significant (P > 0.05). Although the related SNP was not synonymous, there were no observable effects on the reproductive characteristics under investigation. As such, it would be ideal to detect other SNPs in exon 1 of the MTRN1A gene that can be associated with reproductive characteristics in Amazonian buffaloes. PMID:27421017

  10. B- and C-RAF display essential differences in their binding to Ras: the isotype-specific N terminus of B-RAF facilitates Ras binding.

    PubMed

    Fischer, Andreas; Hekman, Mirko; Kuhlmann, Jürgen; Rubio, Ignacio; Wiese, Stefan; Rapp, Ulf R

    2007-09-01

    Recruitment of RAF kinases to the plasma membrane was initially proposed to be mediated by Ras proteins via interaction with the RAF Ras binding domain (RBD). Data reporting that RAF kinases possess high affinities for particular membrane lipids support a new model in which Ras-RAF interactions may be spatially restricted to the plane of the membrane. Although the coupling features of Ras binding to the isolated RAF RBD were investigated in great detail, little is known about the interactions of the processed Ras with the functional and full-length RAF kinases. Here we present a quantitative analysis of the binding properties of farnesylated and nonfarnesylated H-Ras to both full-length B- and C-RAF in the presence and absence of lipid environment. Although isolated RBD fragments associate with high affinity to both farnesylated and nonfarnesylated H-Ras, the full-length RAF kinases revealed fundamental differences with respect to Ras binding. In contrast to C-RAF that requires farnesylated H-Ras, cytosolic B-RAF associates effectively and with significantly higher affinity with both farnesylated and nonfarnesylated H-Ras. To investigate the potential farnesyl binding site(s) we prepared several N-terminal fragments of C-RAF and found that in the presence of cysteine-rich domain only the farnesylated form of H-Ras binds with high association rates. The extreme N terminus of B-RAF turned out to be responsible for the facilitation of lipid independent Ras binding to B-RAF, since truncation of this region resulted in a protein that changed its kinase properties and resembles C-RAF. In vivo studies using PC12 and COS7 cells support in vitro results. Co-localization measurements using labeled Ras and RAF documented essential differences between B- and C-RAF with respect to association with Ras. Taken together, these data suggest that the activation of B-RAF, in contrast to C-RAF, may take place both at the plasma membrane and in the cytosolic environment.

  11. Novel Mutation in Exon 1 of the BMP15 Gene and its Association with Reproduction Traits in Sheep.

    PubMed

    Nadri, S; Zamani, P; Ahmadi, A

    2016-10-01

    The BMP15 gene is a growth factor and a member of the transforming growth factor β (TGFβ) superfamily, specifically expressed in oocytes. In the present study, polymorphism of BMP15 gene exon 1 was studied using single strand conformational polymorphism (SSCP) and direct DNA sequencing methods in 170 Mehraban and Lori sheep ewes. A 231-bp fragment in BMP15 exon 1 was amplified by PCR reactions. Two genotypes (GG and AG) with a new point mutation at position 121 bp of the studied fragment (c.379G>A in reference GenBank number AF236078.1 sequence), deducing an amino acid exchange in the codified amino acid sequence (p.Glu41Lys) were identified in the studied populations. The AG and GG frequencies were 74.4% and 25.6% in Mehraban and 44.7% and 55.3% in Lori sheep, respectively. Frequencies of the A and G alleles were 37.2% and 62.8% in Mehraban and 22.4% and 77.6% in Lori sheep, respectively. Two different secondary structures of protein were predicted for encoded precursor protein. The genotypes GG and AG did not have any significant association with the studied reproductive traits, but the AA genotype is likely to have a lethal or sterility effect.

  12. Novel Mutation in Exon 1 of the BMP15 Gene and its Association with Reproduction Traits in Sheep.

    PubMed

    Nadri, S; Zamani, P; Ahmadi, A

    2016-10-01

    The BMP15 gene is a growth factor and a member of the transforming growth factor β (TGFβ) superfamily, specifically expressed in oocytes. In the present study, polymorphism of BMP15 gene exon 1 was studied using single strand conformational polymorphism (SSCP) and direct DNA sequencing methods in 170 Mehraban and Lori sheep ewes. A 231-bp fragment in BMP15 exon 1 was amplified by PCR reactions. Two genotypes (GG and AG) with a new point mutation at position 121 bp of the studied fragment (c.379G>A in reference GenBank number AF236078.1 sequence), deducing an amino acid exchange in the codified amino acid sequence (p.Glu41Lys) were identified in the studied populations. The AG and GG frequencies were 74.4% and 25.6% in Mehraban and 44.7% and 55.3% in Lori sheep, respectively. Frequencies of the A and G alleles were 37.2% and 62.8% in Mehraban and 22.4% and 77.6% in Lori sheep, respectively. Two different secondary structures of protein were predicted for encoded precursor protein. The genotypes GG and AG did not have any significant association with the studied reproductive traits, but the AA genotype is likely to have a lethal or sterility effect. PMID:27565869

  13. Molecular genetic analysis of exons 1 to 6 of the APC gene in non-polyposis familial colorectal cancer.

    PubMed

    Joyce, J A; Froggatt, N J; Davies, R; Evans, D G; Trembath, R; Barton, D E; Maher, E R

    1995-12-01

    Familial adenomatous polyposis coli is caused by constitutional mutations in the APC gene. The hallmark of familial adenomatous polyposis coli is the presence of numerous (> 100) colorectal polyps, but mutations in the 5' end of the APC gene have been associated with familial colorectal cancer without florid polyposis. Although familial adenomatous polyposis coli accounts for only a minority of familial colorectal cancer cases, we hypothesised that APC mutations which were not associated with florid polyposis might make a significant contribution to nonpolyposis familial colorectal cancer. To investigate this possibility, we analysed 40 unrelated patients with familial colorectal cancer without classical familial adenomatous polyposis coli for mutations in exons 1 to 6 (codons 1 to 243) of the APC gene. No mutations were detected, but a C-->T polymorphism at nucleotide 333 (Arg-->Trp at codon 99) was identified. No 5' APC mutations were detected in two patients with desmoid tumours and a family history of colorectal cancer and polyps. We conclude that mutations in exons 1 to 6 of the APC gene are infrequent in patients with familial colorectal cancer who do not have many colorectal polyps. PMID:8835324

  14. Alterations in exon 1 of c-myc and expression of p62c-myc in cervical squamous cell carcinoma.

    PubMed Central

    O'Leary, J J; Landers, R J; Crowley, M; Healy, I; Kealy, W F; Hogan, J; Doyle, C T

    1997-01-01

    AIMS: To examine human papillomavirus (HPV) positive and negative squamous cell carcinomas of the cervix for structural alterations in exon 1 c-myc; and to investigate the expression pattern of p62, the protein product of c-myc. MATERIAL: Archival paraffin wax embedded tissues of cervical squamous cell carcinomas, stage I and II, retrieved from the files of the department of pathology, University College Cork, Ireland: 40 cases were examined for alterations in exon 1 of c-myc; 57 cases were used for immunocytochemical p62 analysis. METHODS: c-myc exon 1 PCR on HPV positive and negative stage I and II cervical squamous cell carcinomas was performed using primers designed to fragile sites in exon 1 of the c-myc oncogene, which are frequently involved in translocation phenomena and deletions in other neoplasms. This region is bordered by two promoter sequences P1 and P2. In addition, the expression of p62 was evaluated using the monoclonal antibody Mycl-9E10. RESULTS: Alterations in exon 1 of c-myc were shown in 7.5% of squamous cell carcinomas of the cervix. Changes in exon 1 and 2 of c-myc were also found in COLO 320 cells and Raji cells. These alterations were due to small deletions within exon 1 of c-myc, but point polymorphisms occurring within the priming sites (in one case) may also have occurred. The alterations uncovered appeared "clonal," as replicate samples showed the same amplicon band pattern. Expression of c-myc was variable, with cytoplasmic staining patterns predominating. All cases which showed exon 1 alterations were HPV positive and had strong nuclear positivity on p62 immunocytochemistry. CONCLUSIONS: Alterations in exon 1 of c-myc occur in a minority of cervical cancers and there was increased expression of p62 in a cohort of HPV positive and negative cervical squamous cell carcinomas. Exon 1 alterations may provide an alternative route to c-myc activation in early squamous cell carcinoma. Images PMID:9462237

  15. The N Terminus of Pro-endothelial Monocyte-activating Polypeptide II (EMAP II) Regulates Its Binding with the C Terminus, Arginyl-tRNA Synthetase, and Neurofilament Light Protein*

    PubMed Central

    Xu, Haiming; Malinin, Nikolay L.; Awasthi, Niranjan; Schwarz, Roderich E.; Schwarz, Margaret A.

    2015-01-01

    Pro-endothelial monocyte-activating polypeptide II (EMAP II), one component of the multi-aminoacyl tRNA synthetase complex, plays multiple roles in physiological and pathological processes of protein translation, signal transduction, immunity, lung development, and tumor growth. Recent studies have determined that pro-EMAP II has an essential role in maintaining axon integrity in central and peripheral neural systems where deletion of the C terminus of pro-EMAP II has been reported in a consanguineous Israeli Bedouin kindred suffering from Pelizaeus-Merzbacher-like disease. We hypothesized that the N terminus of pro-EMAP II has an important role in the regulation of protein-protein interactions. Using a GFP reporter system, we defined a putative leucine zipper in the N terminus of human pro-EMAP II protein (amino acid residues 1–70) that can form specific strip-like punctate structures. Through GFP punctum analysis, we uncovered that the pro-EMAP II C terminus (amino acids 147–312) can repress GFP punctum formation. Pulldown assays confirmed that the binding between the pro-EMAP II N terminus and its C terminus is mediated by a putative leucine zipper. Furthermore, the pro-EMAP II 1–70 amino acid region was identified as the binding partner of arginyl-tRNA synthetase, a polypeptide of the multi-aminoacyl tRNA synthetase complex. We also determined that the punctate GFP pro-EMAP II 1–70 amino acid aggregate colocalizes and binds to the neurofilament light subunit protein that is associated with pathologic neurofilament network disorganization and degeneration of motor neurons. These findings indicate the structure and binding interaction of pro-EMAP II protein and suggest a role of this protein in pathological neurodegenerative diseases. PMID:25724651

  16. The extreme N-terminus of the Caulobacter crescentus surface-layer protein directs export of passenger proteins from the cytoplasm but is not required for secretion of the native protein.

    PubMed

    Bingle, W H; Le, K D; Smit, J

    1996-07-01

    The paracrystalline surface layer (S-layer) of Caulobacter crescentus is composed of a single protein (RsaA, 1026 amino acids) that associates noncovalently with the lipopolysaccharide of the outer membrane. Like many other extracellular proteins of Gram-negative bacteria, the S-layer protein is not processed during transport to the cell surface. To study the secretion of RsaA, several N-terminal deletions of the protein were made by modifying the 5'-region of the rsaA gene. This analysis showed that portions of the N-terminus totalling the first 775 N-terminal amino acids (75% of the protein) could be removed from RsaA without abolishing secretion of the remainder of the protein. Although the RsaA N-terminus was not required for secretion, an N-terminal domain consisting of either 34 or 52 RsaA-derived amino acids promoted export of the alkaline phosphatase reporter (PhoA) and a cellulase reporter (delta CenA) from the cytoplasm; using the cellulase reporter, the efficiency of hybrid protein export was estimated at 9%. No enzyme activity was detected in the cell-free culture fluids as the result of expressing any gene fusion, indicating that no hybrid protein was completely secreted from the cell. RsaA:PhoA hybrid proteins were also exported from the E. coli cytoplasm, a bacterium not expected to contain the necessary machinery for the secretion of RsaA. Taken together, these data indicate that the secretion pathway of RsaA relies on a C-terminal secretion signal and that once separated from the context of the native protein, the extreme N-terminus of RsaA can act as an inefficient cryptic export signal that is not used during native RsaA secretion.

  17. Mutation analysis of exon1 of bone morphogenetic protein-15 gene in Iranian patients with polycystic ovarian syndrome

    PubMed Central

    Mehdizadeh, Anahita; Sheikhha, Mohammad Hasan; Kalantar, Seyed Mehdi; Aali, Bibi Shahnaz; Ghanei, Azam

    2016-01-01

    Background: With the prevalence of 6-10%, polycystic ovarian syndrome (PCOS) is considered the most common endocrinological disorder affecting women in their reproductive age. It has been suggested that genetic factors participate in the development of PCOS. Follicular development has been considered as one of the impaired processes in PCOS. Bone morphogenetic protein-15 (BMP-15) gene is a candidate gene in follicular development and its variants may play role in pathogenesis of PCOS. Objective: To investigate whether BMP-15 gene mutations are present in Iranian women with PCOS. Materials and Methods: In this cross-sectional study 5 ml venous blood samples was taken from 70 PCOS women referring to Afzalipour Hospital, Kerman University of Medical Sciences, Kerman, Iran, between January to December 2014. Genomic DNA was extracted from the blood sample by salting out method. Then a set of PCR reactions for exon1 of BMP-15 gene was performed using specific primers followed by genotyping with direct sequencing. Results: Two different polymorphisms were found in the gene under study. In total 20 patients (28.6%) were heterozygote (C/G), and 2 patients (2.86%) were homozygous (G/G) for c.-9C>G in 5´UTR promoter region of BMP-15 gene (rs3810682). In addition, in the coding region of exon1, three patients (4.3%) were heterozygote (G/A) for c.A308G (rs41308602). Two PCOS patients (2.86%) appeared to have both c.-9C>G (C/G) and c.A308G (G/A) variants simultaneously. Conclusion: Our research detected two polymorphisms of BMP-15 gene among PCOS patients, indicating that even though it cannot be concluded that variants of BMP-15 gene are the principal cause of polycystic ovarian syndrome; they could be involved in pathogenic process in development of PCOS.

  18. Mutation analysis of exon1 of bone morphogenetic protein-15 gene in Iranian patients with polycystic ovarian syndrome

    PubMed Central

    Mehdizadeh, Anahita; Sheikhha, Mohammad Hasan; Kalantar, Seyed Mehdi; Aali, Bibi Shahnaz; Ghanei, Azam

    2016-01-01

    Background: With the prevalence of 6-10%, polycystic ovarian syndrome (PCOS) is considered the most common endocrinological disorder affecting women in their reproductive age. It has been suggested that genetic factors participate in the development of PCOS. Follicular development has been considered as one of the impaired processes in PCOS. Bone morphogenetic protein-15 (BMP-15) gene is a candidate gene in follicular development and its variants may play role in pathogenesis of PCOS. Objective: To investigate whether BMP-15 gene mutations are present in Iranian women with PCOS. Materials and Methods: In this cross-sectional study 5 ml venous blood samples was taken from 70 PCOS women referring to Afzalipour Hospital, Kerman University of Medical Sciences, Kerman, Iran, between January to December 2014. Genomic DNA was extracted from the blood sample by salting out method. Then a set of PCR reactions for exon1 of BMP-15 gene was performed using specific primers followed by genotyping with direct sequencing. Results: Two different polymorphisms were found in the gene under study. In total 20 patients (28.6%) were heterozygote (C/G), and 2 patients (2.86%) were homozygous (G/G) for c.-9C>G in 5´UTR promoter region of BMP-15 gene (rs3810682). In addition, in the coding region of exon1, three patients (4.3%) were heterozygote (G/A) for c.A308G (rs41308602). Two PCOS patients (2.86%) appeared to have both c.-9C>G (C/G) and c.A308G (G/A) variants simultaneously. Conclusion: Our research detected two polymorphisms of BMP-15 gene among PCOS patients, indicating that even though it cannot be concluded that variants of BMP-15 gene are the principal cause of polycystic ovarian syndrome; they could be involved in pathogenic process in development of PCOS. PMID:27679828

  19. The activity of cAMP-phosphodiesterase 4D7 (PDE4D7) is regulated by protein kinase A-dependent phosphorylation within its unique N-terminus

    PubMed Central

    Byrne, Ashleigh M.; Elliott, Christina; Hoffmann, Ralf; Baillie, George S.

    2015-01-01

    The cyclic AMP phosphodiesterases type 4 (PDE4s) are expressed in a cell specific manner, with intracellular targeting directed by unique N-terminal anchor domains. All long form PDE4s are phosphorylated and activated by PKA phosphorylation within their upstream conserved region 1 (UCR1). Here, we identify and characterise a novel PKA site (serine 42) within the N-terminal region of PDE4D7, an isoform whose activity is known to be important in prostate cancer progression and ischemic stroke. In contrast to the UCR1 site, PKA phosphorylation of the PDE4D7 N-terminus appears to occur constitutively and inhibits PDE4 activity to allow cAMP signalling under basal conditions. PMID:25680530

  20. Inhibitors of the hepatitis C virus NS3 protease with basic amine functionality at the P3-amino acid N-terminus: discovery and optimization of a new series of P2-P4 macrocycles.

    PubMed

    Harper, Steven; Ferrara, Marco; Crescenzi, Benedetta; Pompei, Marco; Palumbi, Maria Cecilia; DiMuzio, Jillian M; Donghi, Monica; Fiore, Fabrizio; Koch, Uwe; Liverton, Nigel J; Pesci, Silvia; Petrocchi, Alessia; Rowley, Michael; Summa, Vincenzo; Gardelli, Cristina

    2009-08-13

    In a follow-up to our recent disclosure of P2-P4 macrocyclic inhibitors of the hepatitis C virus (HCV) NS3 protease (e.g., 1, Chart 1), we report a new but related compound series featuring a basic amine at the N-terminus of the P3-amino acid residue. Replacement of the electroneutral P3-amino acid capping group (which is a feature of almost all tripeptide-like inhibitors of NS3 reported to date) with a basic group is not only tolerated but can result in advantageous cell based potency. Optimization of this new class of P3-amine based inhibitors gave compounds such as 25 and 26 that combine excellent cell based activity with pharmacokinetic properties that are attractive for an antiviral targeting HCV.

  1. Disruption of hydrogen bonds between major histocompatibility complex class II and the peptide N-terminus is not sufficient to form a human leukocyte antigen-DM receptive state of major histocompatibility complex class II.

    PubMed

    Schulze, Monika-Sarah E D; Anders, Anne-Kathrin; Sethi, Dhruv K; Call, Melissa J

    2013-01-01

    Peptide presentation by MHC class II is of critical importance to the function of CD4+ T cells. HLA-DM resides in the endosomal pathway and edits the peptide repertoire of newly synthesized MHC class II molecules before they are exported to the cell surface. HLA-DM ensures MHC class II molecules bind high affinity peptides by targeting unstable MHC class II:peptide complexes for peptide exchange. Research over the past decade has implicated the peptide N-terminus in modulating the ability of HLA-DM to target a given MHC class II:peptide combination. In particular, attention has been focused on both the hydrogen bonds between MHC class II and peptide, and the occupancy of the P1 anchor pocket. We sought to solve the crystal structure of a HLA-DR1 molecule containing a truncated hemagglutinin peptide missing three N-terminal residues compared to the full-length sequence (residues 306-318) to determine the nature of the MHC class II:peptide species that binds HLA-DM. Here we present structural evidence that HLA-DR1 that is loaded with a peptide truncated to the P1 anchor residue such that it cannot make select hydrogen bonds with the peptide N-terminus, adopts the same conformation as molecules loaded with full-length peptide. HLA-DR1:peptide combinations that were unable to engage up to four key hydrogen bonds were also unable to bind HLA-DM, while those truncated to the P2 residue bound well. These results indicate that the conformational changes in MHC class II molecules that are recognized by HLA-DM occur after disengagement of the P1 anchor residue.

  2. The N-terminus region of the putative C2H2 transcription factor Ada1 harbors a species-specific activation motif that regulates asexual reproduction in Fusarium verticillioides.

    PubMed

    Malapi-Wight, Martha; Kim, Jung-Eun; Shim, Won-Bo

    2014-01-01

    Fusarium verticillioides is an important plant pathogenic fungus causing maize ear and stalk rots. In addition, the fungus is directly associated with fumonisin contamination of food and feeds. Here, we report the functional characterization of Ada1, a putative Cys2-His2 zinc finger transcription factor with a high level of similarity to Aspergillus nidulans FlbC, which is required for the activation of the key regulator of conidiation brlA. ADA1 is predicted to encode a protein with two DNA binding motifs at the C terminus and a putative activator domain at the N terminus region. Deletion of the flbC gene in A. nidulans results in "fluffy" cotton-like colonies, with a defect in transition from vegetative growth to asexual development. In this study we show that Ada1 plays a key role in asexual development in F. verticillioides. Conidia production was significantly reduced in the knockout mutant (Δada1), in which aberrant conidia and conidiophores were also observed. We identified genes that are predicted to be downstream of ADA1, based on A. nidulans conidiation signaling pathway. Among them, the deletion of stuA homologue, FvSTUA, resulted in near absence of conidia production. To further investigate the functional conservation of this transcription factor, we complemented the Δada1 strain with A. nidulans flbC, F. verticillioides ADA1, and chimeric constructs. A. nidulans flbC failed to restore conidia production similar to the wild-type level. However, the Ada1N-terminal domain, which contains a putative activator, fused to A. nidulans FlbC C-terminal motif successfully complemented the Δada1 mutant. Taken together, Ada1 is an important transcriptional regulator of asexual development in F. verticillioides and that the N-terminus domain is critical for proper function of this transcription factor.

  3. Variability of CAG tandem repeats in exon 1 of the androgen receptor gene is not related with dog intersexuality.

    PubMed

    Nowacka-Woszuk, J; Switonski, M

    2010-02-01

    Numerous mutations of the human androgen receptor (AR) gene cause an intersexual phenotype, called the androgen insensitivity syndrome. The intersexual phenotype is also quite often diagnosed in dogs. The aim of this study was to conduct a comparative analysis of the entire coding sequence (eight exons) of the AR gene in healthy and four intersex dogs, as well as in three other canids (the red fox, arctic fox and Chinese raccoon dog). The coding sequence of the studied species appeared to be conserved (similarity above 97%) and polymorphism was found in exon 1 only. Altogether, 2 SNPs were identified in healthy dogs, 14 in red foxes, 16 in arctic foxes and 6 were found in Chinese raccoon dogs, respectively. Moreover, a variable number of tandem repeats (CAG and CAA), encoding an array of glutamines, was also observed in this exon. The CAA codon numbers were invariable within species, but the CAG repeats were polymorphic. The highest number of the CAG and CAA repeats was found in dogs (from 40 to 42) and the observed variability was similar in intersex and healthy dogs. In the other canids the variability fell within the following ranges: 29-37 (red fox), 37-39 (arctic fox) and 29-32 (Chinese raccoon dog). In addition, a polymorphic microsatellite marker in intron 2 was found in the dog, red fox and Chinese raccoon dog. It was concluded that the polymorphism level of the AR gene in the dog was lower than in the other canids and none of the detected polymorphisms, including variability of the CAG tandem repeats, could be related with the intersexual phenotype of the studied dogs.

  4. N-terminus of IpaB provides a potential anchor to the Shigella type III secretion system tip complex protein IpaD.

    PubMed

    Dickenson, Nicholas E; Arizmendi, Olivia; Patil, Mrinalini K; Toth, Ronald T; Middaugh, C Russell; Picking, William D; Picking, Wendy L

    2013-12-10

    The type III secretion system (T3SS) is an essential virulence factor for Shigella flexneri , providing a conduit through which host-altering effectors are injected directly into a host cell to promote uptake. The type III secretion apparatus (T3SA) is composed of a basal body, external needle, and regulatory tip complex. The nascent needle is a polymer of MxiH capped by a pentamer of invasion plasmid antigen D (IpaD). Exposure to bile salts (e.g., deoxycholate) causes a conformational change in IpaD and promotes recruitment of IpaB to the needle tip. It has been proposed that IpaB senses contact with host cell membranes, recruiting IpaC and inducing full secretion of T3SS effectors. Although the steps of T3SA maturation and their external triggers have been identified, details of specific protein interactions and mechanisms have remained difficult to study because of the hydrophobic nature of the IpaB and IpaC translocator proteins. Here, we explored the ability for a series of soluble N-terminal IpaB peptides to interact with IpaD. We found that DOC is required for the interaction and that a region of IpaB between residues 11-27 is required for maximum binding, which was confirmed in vivo. Furthermore, intramolecular FRET measurements indicated that movement of the IpaD distal domain away from the protein core accompanied the binding of IpaB11-226. Together, these new findings provide important new insight into the interactions and potential mechanisms that define the maturation of the Shigella T3SA needle tip complex and provide a foundation for further studies probing T3SS activation.

  5. Breed-Dependent Transcriptional Regulation of 5′-Untranslated GR (NR3C1) Exon 1 mRNA Variants in the Liver of Newborn Piglets

    PubMed Central

    Yang, Xiaojing; Ni, Yingdong; Cong, Rihua; Soloway, Paul D.; Zhao, Ruqian

    2012-01-01

    Glucocorticoids are vital for life and regulate an array of physiological functions by binding to the ubiquitously expressed glucocorticoid receptor (GR, also known as NR3C1). Previous studies demonstrate striking breed differences in plasma cortisol levels in pigs. However, investigation into the breed-dependent GR transcriptional regulation is hampered by lacking porcine GR promoter information. In this study, we sequenced 5.3 kb upstream of the translation start codon of the porcine GR gene, and identified seven alternative 5′-untranslated exons 1–4, 1–5, 1–6, 1–7, 1–8, 1–9,10 and 1–11. Among all these mRNA variants, exons 1–4 and 1–5, as well as the total GR were expressed significantly (P<0.05) higher in the liver of newborn piglets of Large White (LW) compared with Erhualian, a Chinese indigenous breed. Overall level of CpG methylation in the region flanking exons 1–4 and 1–5 did not show breed difference. However, nuclear content of Sp1, p-CREB and GR in the liver was significantly (P<0.05) higher in LW piglets, associated with enhanced binding of p-CREB, and higher level of histone H3 acetylation in 1–4 and 1–5 promoters. In contrast, GR binding to promoters of exons 1–4 and 1–5 was significantly diminished in LW piglets, implicating the presence of negative GREs. These results indicate that the difference in the hepatic expression of GR transcript variants between two breeds of pigs is determined, at least partly, by the disparity in the binding of transcription factors and the enrichment of histone H3 acetylation to the promoters. PMID:22792317

  6. Breed-dependent transcriptional regulation of 5'-untranslated GR (NR3C1) exon 1 mRNA variants in the liver of newborn piglets.

    PubMed

    Zou, Huafeng; Li, Runsheng; Jia, Yimin; Yang, Xiaojing; Ni, Yingdong; Cong, Rihua; Soloway, Paul D; Zhao, Ruqian

    2012-01-01

    Glucocorticoids are vital for life and regulate an array of physiological functions by binding to the ubiquitously expressed glucocorticoid receptor (GR, also known as NR3C1). Previous studies demonstrate striking breed differences in plasma cortisol levels in pigs. However, investigation into the breed-dependent GR transcriptional regulation is hampered by lacking porcine GR promoter information. In this study, we sequenced 5.3 kb upstream of the translation start codon of the porcine GR gene, and identified seven alternative 5'-untranslated exons 1-4, 1-5, 1-6, 1-7, 1-8, 1-9,10 and 1-11. Among all these mRNA variants, exons 1-4 and 1-5, as well as the total GR were expressed significantly (P<0.05) higher in the liver of newborn piglets of Large White (LW) compared with Erhualian, a Chinese indigenous breed. Overall level of CpG methylation in the region flanking exons 1-4 and 1-5 did not show breed difference. However, nuclear content of Sp1, p-CREB and GR in the liver was significantly (P<0.05) higher in LW piglets, associated with enhanced binding of p-CREB, and higher level of histone H3 acetylation in 1-4 and 1-5 promoters. In contrast, GR binding to promoters of exons 1-4 and 1-5 was significantly diminished in LW piglets, implicating the presence of negative GREs. These results indicate that the difference in the hepatic expression of GR transcript variants between two breeds of pigs is determined, at least partly, by the disparity in the binding of transcription factors and the enrichment of histone H3 acetylation to the promoters.

  7. Effect on HIV-1 Gene Expression, Tat-Vpr Interaction and Cell Apoptosis by Natural Variants of HIV-1 Tat Exon 1 and Vpr from Northern India

    PubMed Central

    Lata, Sneh; Ronsard, Larance; Sood, Vikas; Dar, Sajad A.; Ramachandran, Vishnampettai G.; Das, Shukla; Banerjea, Akhil C.

    2013-01-01

    Background Since HIV-1 Tat and Vpr genes are involved in promoter transactivation, apoptosis, etc, we carried out studies to find out nature and extent of natural variation in the two genes from seropositive patients from Northern India and determined their functional implications. Methods HIV-1 tat exon 1 and vpr were amplified from the genomic DNA isolated from the blood of HIV-1 infected individuals using specific primers by Polymerase Chain reaction (PCR) and subjected to extensive genetic analysis (CLUSTAL W, Simplot etc). Their expression was monitored by generating myc fusion clones. Tat exon 1 and Vpr variants were co-transfected with the reporter gene construct (LTR-luc) and their transactivation potential was monitored by measuring luciferase activity. Apoptosis and cell cycle analysis was done by Propidium Iodide (PI) staining followed by FACS. Results Exon 1 of tat was amplified from 21 samples and vpr was amplified from 16 samples. One of the Tat exon 1 variants showed phylogenetic relatedness to subtype B & C and turned out to be a unique recombinant. Two of the Vpr variants were B/C/D recombinants. These natural variations were found to have no impact on the stability of Tat and Vpr. These variants differed in their ability to transactivate B LTR and C LTR promoters. B/C recombinant Tat showed better co-operative interaction with Vpr. B/C/D recombination in Vpr was found to have no effect on its co-operativity with Tat. Recombinant Tat (B/C) induced more apoptosis than wild type B and C Tat. The B/C/D recombination in Vpr did not affect its G2 arrest induction potential but reduced its apoptosis induction ability. Conclusions Extensive sequence and region-specific variations were observed in Tat and Vpr genes from HIV-1 infected individuals from Northern India. These variations have functional implications & therefore important for the pathogenicity of virus. PMID:24367500

  8. Dynamic triggering

    USGS Publications Warehouse

    Hill, David P.; Prejean, Stephanie; Schubert, Gerald

    2015-01-01

    Dynamic stresses propagating as seismic waves from large earthquakes trigger a spectrum of responses at global distances. In addition to locally triggered earthquakes in a variety of tectonic environments, dynamic stresses trigger tectonic (nonvolcanic) tremor in the brittle–plastic transition zone along major plate-boundary faults, activity changes in hydrothermal and volcanic systems, and, in hydrologic domains, changes in spring discharge, water well levels, soil liquefaction, and the eruption of mud volcanoes. Surface waves with periods of 15–200 s are the most effective triggering agents; body-wave trigger is less frequent. Triggering dynamic stresses can be < 1 kPa.

  9. Isolation and expression of a novel chick G-protein cDNA coding for a G alpha i3 protein with a G alpha 0 N-terminus.

    PubMed Central

    Kilbourne, E J; Galper, J B

    1994-01-01

    We have cloned cDNAs coding for G-protein alpha subunits from a chick brain cDNA library. Based on sequence similarity to G-protein alpha subunits from other eukaryotes, one clone was designated G alpha i3. A second clone, G alpha i3-o, was identical to the G alpha i3 clone over 932 bases on the 3' end. The 5' end of G alpha i3-o, however, contained an alternative sequence in which the first 45 amino acids coded for are 100% identical to the conserved N-terminus of G alpha o from species such as rat, mouse, human, bovine and hamster. Both clones were found to be expressed in all tissues studied. The unusual alpha o-alpha i3-like G-protein chimera, G alpha i3-o, was found to be expressed at significantly lower levels than G alpha i3. In vitro transcription and translation of the G alpha i3-o cDNA clone gave a protein of approx. 41 kDa which stably bound guanosine 5'-[gamma-thio]triphosphate. G alpha i3-o appears to be the first G-protein alpha subunit cloned which contains ends that are homologous to two different alpha subunit isoforms, G alpha o and G alpha i3. Images Figure 4 Figure 5 Figure 6 Figure 7 PMID:8297335

  10. A Reduced Risk of Infection with Plasmodium vivax and Clinical Protection against Malaria Are Associated with Antibodies against the N Terminus but Not the C Terminus of Merozoite Surface Protein 1†

    PubMed Central

    Nogueira, Paulo Afonso; Piovesan Alves, Fabiana; Fernandez-Becerra, Carmen; Pein, Oliver; Rodrigues Santos, Neida; Pereira da Silva, Luiz Hildebrando; Plessman Camargo, Erney; del Portillo, Hernando A.

    2006-01-01

    Progress towards the development of a malaria vaccine against Plasmodium vivax, the most widely distributed human malaria parasite, will require a better understanding of the immune responses that confer clinical protection to patients in regions where malaria is endemic. The occurrence of clinical protection in P. vivax malaria in Brazil was first reported among residents of the riverine community of Portuchuelo, in Rondônia, western Amazon. We thus analyzed immune sera from this same human population to determine if naturally acquired humoral immune responses against the merozoite surface protein 1 of P. vivax, PvMSP1, could be associated with reduced risk of infection and/or clinical protection. Our results demonstrated that this association could be established with anti-PvMSP1 antibodies predominantly of the immunoglobulin G3 subclass directed against the N terminus but not against the C terminus, in spite of the latter being more immunogenic and capable of natural boosting. This is the first report of a prospective study of P. vivax malaria demonstrating an association of reduced risk of infection and clinical protection with antibodies against an antigen of this parasite. PMID:16622209

  11. Novel single base-pair deletion in exon 1 of XK gene leading to McLeod syndrome with chorea, muscle wasting, peripheral neuropathy, acanthocytosis and haemolysis.

    PubMed

    Wiethoff, Sarah; Xiromerisiou, Georgia; Bettencourt, Conceição; Kioumi, Anna; Tsiptsios, Iakovos; Tychalas, Athanasios; Evaggelia, Markousi; George, Kaltsounis; Makris, Vasileios; Hardy, John; Houlden, Henry

    2014-04-15

    We present a 70-year-old male patient of Greek origin with choreatic movements of the tongue and face, lower limb muscle weakness, peripheral neuropathy, elevated creatinephosphokinase (CPK), acanthocytosis and haemolysis in the absence of Kell RBC antigens with an additional Factor IX-deficiency. Genetic testing for mutations in the three exons of the XK gene revealed a previously unreported hemizygous single base-pair frameshift deletion at exon 1 (c.229delC, p.Leu80fs). In conclusion, we hereby describe a rare phenotype of a patient with McLeod syndrome which was discovered coincidentally during routine blood group testing and consecutively genetically confirmed.

  12. A novel SMAD family protein, SMAD9 is involved in follicular initiation and changes egg yield of geese via synonymous mutations in exon1 and intron2.

    PubMed

    Xu, Jun; Li, Jun; Wang, Haosen; Wang, Guanglin; Chen, Jie; Huang, Pin; Cheng, Jienan; Gan, Lu; Wang, Zhao; Cai, Yafei

    2015-01-01

    Elevation of egg performance is vital to goose farming. Many poultry scientists are seeking for efficient molecular genetic markers associated with egg yield. In this study, mRNA differential display was adopted to investigate gene expression profiling in the follicular development of goose. For the first time, a novel SMAD family protein SMAD9 (EST CJ111007) was found to be involved in follicular initiation and used to be a candidate gene. Functional regions analysis of Smad9 indicated that SMAD9 protein is highly conserved in MH1 and MH2 domains, and the connection area is highly variable region. 6 pairs of primers (p1-p6) were designed to detect the SNPs of Smad9 by PCR-SSCP method. The results revealed that polymorphisms were discovered in the PCR products amplified with P1 primers in exon1 and P3 primers in intron2. In Smad9 exon1, 5 genotypes were found: FK, FF, JJ, JK and KK, including 2 SNPs: 243 bp G → A, 309 bp T → G, the mutations did not result in amino acid mutations; In intron2, 3 genotypes were found: AA, BB and AB, only 1 SNP (C → T). The annual egg yield of FK genotype geese or allele gene A in intron2 are significantly more than those of other genotypes on the average (p < 0.05). Taken together, it is suggested that Smad9 is a promising candidate gene affecting egg performance in goose.

  13. The assessment of noncoding variant of PPOX gene in variegate porphyria reveals post-transcriptional role of the 5' untranslated exon 1.

    PubMed

    Fiorentino, Valeria; Brancaleoni, Valentina; Granata, Francesca; Graziadei, Giovanna; Di Pierro, Elena

    2016-10-01

    The PPOX gene encodes for the protoporphyrinogen oxidase, which is involved in heme production. The partial deficiency of protoporphyrinogen oxidase causes variegate porphyria. The tissue-specific regulation of other heme biosynthetic enzymes is extensively studied, but the information concerning transcriptional and post-transcriptional regulation of PPOX gene expression is scarcely available. In this study, we characterized functions of three variants identified in the regulatory regions of the PPOX gene, which show a novel role for the 5' untranslated exon 1. Using luciferase assays and RNA analysis, we demonstrated that only c.1-883G>C promoter variant causes a significant loss in the transcriptional activity of PPOX gene whereas c.1-413G>T 5' UTR variant inhibits translation of PPOX mRNA and c.1-176G>A splicing variant causes 4bp deletion in 5' UTR of PPOX mRNA variant 2. These observations indicate that the regulation of PPOX gene expression can also occur through a post-transcriptional modulation of the amount of gene product and that this modulation can be mediated by 5' untranslated exon 1. Moreover this study confirms that these regulatory regions represent an important molecular target for the pathogenesis of variegate porphyria. PMID:27667166

  14. A/G Gln20Arg (exon 1) and G/A Val156Met (exon 5) polymorphisms of the human orosomucoid 1 gene in Mexico.

    PubMed

    García-Ortiz, L; Vargas-Alarcón, G; Fragoso, J M; Granados, J; Maldonado Noriega, L; Navas Pérez, A; Huerta Reyes, E; Zenteno-Ruiz, J C; Martínez-Cordero, E

    2008-01-08

    The human orosomucoid 1 gene (ORM1) codes an alpha-1-acid glycoprotein that has been classified as an acute-phase reactive protein, and a major drug-binding serum component, as well as an immunomodulatory protein with genetic polymorphisms. Evaluation of ORM variation through isoelectric focusing and immunobloting has revealed a world-wide distribution of the ORM1 F and ORM1 S alleles. We evaluated and examined the genetic characteristics of two Mexican populations that have different anthropological and cultural antecedents, examining two ORM1 genotypes (exon 1 - A/G (Gln20Arg) and exon 5 G/A (Val156Met)) in 145 individuals, using nested polymerase chain reaction, sequencing, and restricted fragment length polymorphism. Mexican Mestizos had higher frequencies of the exon 1 A allele (P = 0.020) and AA genotype (P = 0.018) and lower frequency of the G allele (P = 0.020) when compared to Teenek Amerindians. When we examined exon 5 G/A (Val156Met) polymorphisms, we found significantly higher frequencies of the G allele (P = 0.0007) and the GG genotype (P = 0.0003) in the Mexican Mestizo population. The Teenek population had a significantly higher frequency of the A allele than has been reported for Chinese and African (P < 0.05) populations, and the G/A genotype was more frequently found in this Mexican population than in Chinese, African and European populations (P < 0.05).

  15. Detection of TMPRSS2-ERG translocations in human prostate cancer by expression profiling using GeneChip Human Exon 1.0 ST arrays.

    PubMed

    Jhavar, Sameer; Reid, Alison; Clark, Jeremy; Kote-Jarai, Zsofia; Christmas, Timothy; Thompson, Alan; Woodhouse, Christopher; Ogden, Christopher; Fisher, Cyril; Corbishley, Cathy; De-Bono, Johann; Eeles, Rosalind; Brewer, Daniel; Cooper, Colin

    2008-01-01

    Translocation of TMPRSS2 to the ERG gene, found in a high proportion of human prostate cancer, results in overexpression of the 3'-ERG sequences joined to the 5'-TMPRSS2 promoter. The studies presented here were designed to test the ability of expression analysis on GeneChip Human Exon 1.0 ST arrays to detect 5'-TMPRSS2-ERG-3' hybrid transcripts encoded by this translocation. Monitoring the relative expression of each ERG exon revealed altered transcription of the ERG gene in 15 of a series of 27 prostate cancer samples. In all cases, exons 4 to 11 exhibited enhanced expression compared with exons 2 and 3. This pattern of expression indicated that the most abundant hybrid transcripts involve fusions to ERG exon 4, and RT-PCR analyses confirmed the joining of TMPRSS2 exon 1 to ERG exon 4 in all 15 cases. The exon expression patterns also indicated that TMPRSS2-ERG fusion transcripts commonly contain deletion of ERG exon 8. Analysis of gene-level data from the arrays allowed the identification of genes whose expression levels significantly correlated with the presence of the translocation. These studies demonstrate that expression analyses using exon arrays represent a valuable approach for detecting ETS gene translocation in prostate cancer, in parallel with analyses of gene expression profiles.

  16. Severe acute respiratory syndrome coronavirus 3C-like proteinase N terminus is indispensable for proteolytic activity but not for enzyme dimerization. Biochemical and thermodynamic investigation in conjunction with molecular dynamics simulations.

    PubMed

    Chen, Shuai; Chen, Lili; Tan, Jinzhi; Chen, Jing; Du, Li; Sun, Tao; Shen, Jianhua; Chen, Kaixian; Jiang, Hualiang; Shen, Xu

    2005-01-01

    Severe acute respiratory syndrome (SARS) coronavirus is a novel human coronavirus and is responsible for SARS infection. SARS coronavirus 3C-like proteinase (SARS 3CL(pro)) plays key roles in viral replication and transcription and is an attractive target for anti-SARS drug discovery. In this report, we quantitatively characterized the dimerization features of the full-length and N-terminal residues 1-7 deleted SARS 3CL(pro)s by using glutaraldehyde cross-linking SDS-PAGE, size-exclusion chromatography, and isothermal titration calorimeter techniques. Glutaraldehyde cross-linking SDS-PAGE and size-exclusion chromatography results show that, similar to the full-length SARS 3CL(pro), the N-terminal deleted SARS 3CL(pro) still remains a dimer/monomer mixture within a wide range of protein concentrations. Isothermal titration calorimeter determinations indicate that the equilibrium dissociation constant (K(d)) of the N-terminal deleted proteinase dimer (262 microm) is very similar to that of the full-length proteinase dimer (227 microm). Enzymatic activity assay using the fluorescence resonance energy transfer method reveals that N-terminal deletion results in almost complete loss of enzymatic activity for SARS 3CL(pro). Molecular dynamics and docking simulations demonstrate the N-terminal deleted proteinase dimer adopts a state different from that of the full-length proteinase dimer, which increases the angle between the two protomers and reduces the binding pocket that is not beneficial to the substrate binding. This conclusion is verified by the surface plasmon resonance biosensor determination, indicating that the model substrate cannot bind to the N-terminal deleted proteinase. These results suggest the N terminus is not indispensable for the proteinase dimerization but may fix the dimer at the active state and is therefore vital to enzymatic activity.

  17. Mapping of the Tacaribe Arenavirus Z-Protein Binding Sites on the L Protein Identified both Amino Acids within the Putative Polymerase Domain and a Region at the N Terminus of L That Are Critically Involved in Binding▿

    PubMed Central

    Wilda, Maximiliano; Lopez, Nora; Casabona, Juan Cruz; Franze-Fernandez, Maria T.

    2008-01-01

    Tacaribe virus (TacV) is the prototype of the New World group of arenaviruses. The TacV genome encodes four proteins: the nucleoprotein (N), the glycoprotein precursor, the polymerase (L), and a RING finger protein (Z). Using a reverse genetics system, we demonstrated that TacV N and L are sufficient to drive transcription and replication mediated by TacV-like RNAs and that Z is a powerful inhibitor of these processes (Lopez et al., J. Virol. 65:12241-12251, 2001). More recently, we provided the first evidence of an interaction between Z and L and showed that Z's inhibitory activity was dependent on its ability to bind to L (Jácamo et al., J. Virol. 77:10383-10393, 2003). In the present study, we mapped the TacV Z-binding sites on the 2,210-amino-acid L polymerase. To that end, we performed deletion analysis and point mutations of L and studied the Z-L interaction by coimmunoprecipitation with specific sera. We found that the C-terminal region of L was not essential for the interaction and identified two noncontiguous regions that were critical for binding: one at the N-terminus of L between residues 156 and 292 and a second one in the polymerase domain (domain III). The importance of domain III in binding was revealed by substitutions in D1188 and H1189 within motif A and in each residue of the conserved SDD sequence (residues 1328, 1329, and 1330) within motif C. Our results showed that of the substituted residues, only H1189 and D1329 appeared to be critically involved in binding Z. PMID:18799569

  18. Fusion of an oligopeptide to the N terminus of an alkaline α-amylase from Alkalimonas amylolytica simultaneously improves the enzyme's catalytic efficiency, thermal stability, and resistance to oxidation.

    PubMed

    Yang, Haiquan; Lu, Xinyao; Liu, Long; Li, Jianghua; Shin, Hyun-dong; Chen, Rachel R; Du, Guocheng; Chen, Jian

    2013-05-01

    In this study, we constructed and expressed six fusion proteins composed of oligopeptides attached to the N terminus of the alkaline α-amylase (AmyK) from Alkalimonas amylolytica. The oligopeptides had various effects on the functional and structural characteristics of AmyK. AmyK-p1, the fusion protein containing peptide 1 (AEAEAKAKAEAEAKAK), exhibited improved specific activity, catalytic efficiency, alkaline stability, thermal stability, and oxidative stability compared with AmyK. Compared with AmyK, the specific activity and catalytic constant (kcat) of AmyK-p1 were increased by 4.1-fold and 3.5-fold, respectively. The following properties were also improved in AmyK-p1 compared with AmyK: kcat/Km increased from 1.8 liter/(g·min) to 9.7 liter/(g·min), stable pH range was extended from 7.0 to 11.0 to 7.0 to 12.0, optimal temperature increased from 50°C to 55°C, and the half-life at 60°C increased by ∼2-fold. Moreover, AmyK-p1 showed improved resistance to oxidation and retained 54% of its activity after incubation with H2O2, compared with 20% activity retained by AmyK. Finally, AmyK-p1 was more compatible than AmyK with the commercial solid detergents tested. The mechanisms responsible for these changes were analyzed by comparing the three-dimensional (3-D) structural models of AmyK and AmyK-p1. The significantly enhanced catalytic efficiency and stability of AmyK-p1 suggests its potential as a detergent ingredient. In addition, the oligopeptide fusion strategy described here may be useful for improving the catalytic efficiency and stability of other industrial enzymes.

  19. Folding of a beta-hairpin peptide derived from the N-terminus of ubiquitin. Conformational preferences of beta-turn residues dictate non-native beta-strand interactions.

    PubMed

    Jourdan, M; Griffiths-Jones, S R; Searle, M S

    2000-06-01

    The role of the non-native beta-turn sequence (NPDG) in nucleating the folding of a beta-hairpin peptide derived from the N-terminus of ubiquitin, has been examined by NMR and CD spectroscopy. The NPDG sequence, while representing a common two-residue type I turn sequence in proteins, folds to give a G1-bulged type I turn in the context of a beta-hairpin peptide, to the exclusion of other possible conformations. The turn conformation results in misalignment of the two beta strands and a beta hairpin with non-native side chain interactions. A truncated 12-residue analogue of the hairpin, in which the majority of residues in the N-terminal beta strand have been deleted, shows some weak propensity to fold into a G-bulged type I turn conformation in the absence of interstrand stabilizing interactions. The NPDG turn sequence pays some of the entropic cost in initiating folding allowing interstrand interactions, which in this case arise from the non-native pairing of residue side chains, to stabilize a significant population of the folded state. Examination of the relative abundance of the Pro-Asp type I turn, with G in the +B1 position, vs. the type I G-bulged turn PXG, in a database of high resolution structures, reveals 48 instances of PXG bulged turns for which X = Asp is by far the most common residue with 20 occurrences. Strikingly, there are no examples of a type I PD turn with G at the +B1 position, in good agreement with our experimental observations that the PDG G-bulged turn is populated preferentially in solution.

  20. A core activity associated with the N terminus of the yeast RAD52 protein is revealed by RAD51 overexpression suppression of C-terminal rad52 truncation alleles.

    PubMed Central

    Asleson, E N; Okagaki, R J; Livingston, D M

    1999-01-01

    C-terminal rad52 truncation and internal deletion mutants were characterized for their ability to repair MMS-induced double-strand breaks and to produce viable spores during meiosis. The rad52-Delta251 allele, encoding the N-terminal 251 amino acids of the predicted 504-amino-acid polypeptide, supports partial activity for both functions. Furthermore, RAD51 overexpression completely suppresses the MMS sensitivity of a rad52-Delta251 mutant. The absence of the C terminus in the truncated protein makes it likely that suppression occurs by bypassing the C-terminal functions of Rad52p. RAD51 overexpression does not suppress the low level of spore viability that the rad52-Delta251 allele causes and only partially suppresses the defect in rad52 alleles encoding the N-terminal 292 or 327 amino acids. The results of this study also show that intragenic complementation between rad52 alleles is governed by a complex relationship that depends heavily on the two alleles involved and their relative dosage. In heteroallelic rad52 diploids, the rad52-Delta251 allele does not complement rad52 missense mutations altering residues 61 or 64 in the N terminus. However, complementation is achieved with each of these missense alleles when the rad52-Delta251 allele is overexpressed. Complementation also occurs between rad52-Delta327 and an internal deletion allele missing residues 210 through 327. We suggest that the first 251 amino acids of Rad52p constitute a core domain that provides critical RAD52 activities. PMID:10511548

  1. Fusion of an Oligopeptide to the N Terminus of an Alkaline α-Amylase from Alkalimonas amylolytica Simultaneously Improves the Enzyme's Catalytic Efficiency, Thermal Stability, and Resistance to Oxidation

    PubMed Central

    Yang, Haiquan; Lu, Xinyao; Li, Jianghua; Shin, Hyun-dong; Chen, Rachel R.; Du, Guocheng

    2013-01-01

    In this study, we constructed and expressed six fusion proteins composed of oligopeptides attached to the N terminus of the alkaline α-amylase (AmyK) from Alkalimonas amylolytica. The oligopeptides had various effects on the functional and structural characteristics of AmyK. AmyK-p1, the fusion protein containing peptide 1 (AEAEAKAKAEAEAKAK), exhibited improved specific activity, catalytic efficiency, alkaline stability, thermal stability, and oxidative stability compared with AmyK. Compared with AmyK, the specific activity and catalytic constant (kcat) of AmyK-p1 were increased by 4.1-fold and 3.5-fold, respectively. The following properties were also improved in AmyK-p1 compared with AmyK: kcat/Km increased from 1.8 liter/(g·min) to 9.7 liter/(g·min), stable pH range was extended from 7.0 to 11.0 to 7.0 to 12.0, optimal temperature increased from 50°C to 55°C, and the half-life at 60°C increased by ∼2-fold. Moreover, AmyK-p1 showed improved resistance to oxidation and retained 54% of its activity after incubation with H2O2, compared with 20% activity retained by AmyK. Finally, AmyK-p1 was more compatible than AmyK with the commercial solid detergents tested. The mechanisms responsible for these changes were analyzed by comparing the three-dimensional (3-D) structural models of AmyK and AmyK-p1. The significantly enhanced catalytic efficiency and stability of AmyK-p1 suggests its potential as a detergent ingredient. In addition, the oligopeptide fusion strategy described here may be useful for improving the catalytic efficiency and stability of other industrial enzymes. PMID:23455344

  2. Trigger finger

    MedlinePlus

    ... Redness in your cut or hand Swelling or warmth in your cut or hand Yellow or green drainage from the cut Hand pain or discomfort Fever If your trigger finger returns, call your surgeon. You may need another surgery.

  3. Retention of heroin and morphine-6 beta-glucuronide analgesia in a new line of mice lacking exon 1 of MOR-1.

    PubMed

    Schuller, A G; King, M A; Zhang, J; Bolan, E; Pan, Y X; Morgan, D J; Chang, A; Czick, M E; Unterwald, E M; Pasternak, G W; Pintar, J E

    1999-02-01

    Morphine produces analgesia by activating mu opioid receptors encoded by the MOR-1 gene. Although morphine-6 beta-glucuronide (M6G), heroin and 6-acetylmorphine also are considered mu opioids, recent evidence suggests that they act through a distinct receptor mechanism. We examined this question in knockout mice containing disruptions of either the first or second coding exon of MOR-1. Mice homozygous for either MOR-1 mutation were insensitive to morphine. Heroin, 6-acetylmorphine and M6G still elicited analgesia in the exon-1 MOR-1 mutant, which also showed specific M6G binding, whereas M6G and 6-acetylmorphine were inactive in the exon-2 MOR-1 mutant. These results provide genetic evidence for a unique receptor site for M6G and heroin analgesia.

  4. Ethanol induced acetylation of histone at G9a exon1 and G9a-mediated histone H3 dimethylation leads to neurodegeneration in neonatal mice.

    PubMed

    Subbanna, S; Nagre, N N; Shivakumar, M; Umapathy, N S; Psychoyos, D; Basavarajappa, B S

    2014-01-31

    The transient exposure of immature rodents to ethanol during postnatal day 7 (P7), comparable to a time point within the third trimester of human pregnancy, induces neurodegeneration. However, the molecular mechanisms underlying the deleterious effects of ethanol on the developing brain are poorly understood. In our previous study, we showed that a high dose administration of ethanol at P7 enhances G9a and leads to caspase-3-mediated degradation of dimethylated H3 on lysine 9 (H3K9me2). In this study, we investigated the potential role of epigenetic changes at G9a exon1, G9a-mediated H3 dimethylation on neurodegeneration and G9a-associated proteins in the P7 brain following exposure to a low dose of ethanol. We found that a low dose of ethanol induces mild neurodegeneration in P7 mice, enhances specific acetylation of H3 on lysine 14 (H3K14ace) at G9a exon1, G9a protein levels, augments the dimethylation of H3K9 and H3 lysine 27 (H3K27me2). However, neither dimethylated H3K9 nor K27 underwent degradation. Pharmacological inhibition of G9a activity prior to ethanol treatment prevented H3 dimethylation and neurodegeneration. Further, our immunoprecipitation data suggest that G9a directly associates with DNA methyltransferase (DNMT3A) and methyl-CpG-binding protein 2 (MeCP2). In addition, DNMT3A and MeCP2 protein levels were enhanced by a low dose of ethanol that was shown to induce mild neurodegeneration. Collectively, these epigenetic alterations lead to association of G9a, DNMT3A and MeCP2 to form a larger repressive complex and have a significant role in low-dose ethanol-induced neurodegeneration in the developing brain.

  5. Protein Aggregation Formed by Recombinant cp19k Homologue of Balanus albicostatus Combined with an 18 kDa N-Terminus Encoded by pET-32a(+) Plasmid Having Adhesion Strength Comparable to Several Commercial Glues

    PubMed Central

    Liang, Chao; Li, Yunqiu; Liu, Zhiming; Wu, Wenjian; Hu, Biru

    2015-01-01

    The barnacle is well known for its tenacious and permanent attachment to a wide variety of underwater substrates, which is accomplished by synthesizing, secreting and curing a mixture of adhesive proteins termed “barnacle cement”. In order to evaluate interfacial adhesion abilities of barnacle cement proteins, the cp19k homologous gene in Balanus albicostatus (Balcp19k) was cloned and expressed in Escherichia coli. Here, we report an intriguing discovery of a gel-like super adhesive aggregation produced by Trx-Balcp19k, a recombinant Balcp19k fusion protein. The Trx-Balcp19k consists of an 18 kDa fragment at the N-terminus, which is encoded by pET-32a(+) plasmid and mainly comprised of a thioredoxin (Trx) tag, and Balcp19k at the C-terminus. The sticky aggregation was designated as “Trx-Balcp19k gel”, and the bulk adhesion strength, biochemical composition, as well as formation conditions were all carefully investigated. The Trx-Balcp19k gel exhibited strong adhesion strength of 2.10 ± 0.67 MPa, which was approximately fifty folds higher than that of the disaggregated Trx-Balcp19k (40 ± 8 kPa) and rivaled those of commercial polyvinyl acetate (PVA) craft glue (Mont Marte, Australia) and UHU glue (UHU GmbH & Co. KG, Germany). Lipids were absent from the Trx-Balcp19k gel and only a trace amount of carbohydrates was detected. We postulate that the electrostatic interactions play a key role in the formation of Trx-Balcp19k gel, by mediating self-aggregation of Trx-Balcp19k based on its asymmetric distribution pattern of charged amino acids. Taken together, we believe that our discovery not only presents a promising biological adhesive with potential applications in both biomedical and technical fields, but also provides valuable paradigms for molecular design of bio-inspired peptide- or protein-based materials. PMID:26317205

  6. Protein Aggregation Formed by Recombinant cp19k Homologue of Balanus albicostatus Combined with an 18 kDa N-Terminus Encoded by pET-32a(+) Plasmid Having Adhesion Strength Comparable to Several Commercial Glues.

    PubMed

    Liang, Chao; Li, Yunqiu; Liu, Zhiming; Wu, Wenjian; Hu, Biru

    2015-01-01

    The barnacle is well known for its tenacious and permanent attachment to a wide variety of underwater substrates, which is accomplished by synthesizing, secreting and curing a mixture of adhesive proteins termed "barnacle cement". In order to evaluate interfacial adhesion abilities of barnacle cement proteins, the cp19k homologous gene in Balanus albicostatus (Balcp19k) was cloned and expressed in Escherichia coli. Here, we report an intriguing discovery of a gel-like super adhesive aggregation produced by Trx-Balcp19k, a recombinant Balcp19k fusion protein. The Trx-Balcp19k consists of an 18 kDa fragment at the N-terminus, which is encoded by pET-32a(+) plasmid and mainly comprised of a thioredoxin (Trx) tag, and Balcp19k at the C-terminus. The sticky aggregation was designated as "Trx-Balcp19k gel", and the bulk adhesion strength, biochemical composition, as well as formation conditions were all carefully investigated. The Trx-Balcp19k gel exhibited strong adhesion strength of 2.10 ± 0.67 MPa, which was approximately fifty folds higher than that of the disaggregated Trx-Balcp19k (40 ± 8 kPa) and rivaled those of commercial polyvinyl acetate (PVA) craft glue (Mont Marte, Australia) and UHU glue (UHU GmbH & Co. KG, Germany). Lipids were absent from the Trx-Balcp19k gel and only a trace amount of carbohydrates was detected. We postulate that the electrostatic interactions play a key role in the formation of Trx-Balcp19k gel, by mediating self-aggregation of Trx-Balcp19k based on its asymmetric distribution pattern of charged amino acids. Taken together, we believe that our discovery not only presents a promising biological adhesive with potential applications in both biomedical and technical fields, but also provides valuable paradigms for molecular design of bio-inspired peptide- or protein-based materials. PMID:26317205

  7. Ubiquitin is conjugated by membrane ubiquitin ligase to three sites, including the N terminus, in transmembrane region of mammalian 3-hydroxy-3-methylglutaryl coenzyme A reductase: implications for sterol-regulated enzyme degradation.

    PubMed

    Doolman, Ram; Leichner, Gil S; Avner, Rachel; Roitelman, Joseph

    2004-09-10

    The stability of the endoplasmic reticulum (ER) glycoprotein 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), the key enzyme in cholesterol biosynthesis, is negatively regulated by sterols. HMGR is anchored in the ER via its N-terminal region, which spans the membrane eight times and contains a sterol-sensing domain. We have previously established that degradation of mammalian HMGR is mediated by the ubiquitin-proteasome system (Ravid, T., Doolman, R., Avner, R., Harats, D., and Roitelman, J. (2000) J. Biol. Chem. 275, 35840-35847). Here we expressed in HEK-293 cells an HA-tagged-truncated version of HMGR that encompasses all eight transmembrane spans (350 N-terminal residues). Similar to endogenous HMGR, degradation of this HMG(350)-3HA protein was accelerated by sterols, validating it as a model to study HMGR turnover. The degradation of HMG(240)-3HA, which lacks the last two transmembrane spans yet retains an intact sterol-sensing domain, was no longer accelerated by sterols. Using HMG(350)-3HA, we demonstrate that transmembrane region of HMGR is ubiquitinated in a sterol-regulated fashion. Through site-directed Lys --> Arg mutagenesis, we pinpoint Lys(248) and Lys(89) as the internal lysines for ubiquitin attachment, with Lys(248) serving as the major acceptor site for polyubiquitination. Moreover, the data indicate that the N terminus is also ubiquitinated. The degradation rates of the Lys --> Arg mutants correlates with their level of ubiquitination. Notably, lysine-less HMG(350)-3HA is degraded faster than wild-type protein, suggesting that lysines other than Lys(89) and Lys(248) attenuate ubiquitination at the latter residues. The ATP-dependent ubiquitination of HMGR in isolated microsomes requires E1 as the sole cytosolic protein, indicating that ER-bound E2 and E3 enzymes catalyze this modification. Polyubiquitination of HMGR is correlated with its extraction from the ER membrane, a process likely to be assisted by cytosolic p97/VCP/Cdc48p-Ufd1-Npl

  8. A novel motif in the NaTrxh N-terminus promotes its secretion, whereas the C-terminus participates in its interaction with S-RNase in vitro

    PubMed Central

    2014-01-01

    Background NaTrxh, a thioredoxin type h, shows differential expression between self-incompatible and self-compatible Nicotiana species. NaTrxh interacts in vitro with S-RNase and co-localizes with it in the extracellular matrix of the stylar transmitting tissue. NaTrxh contains N- and C-terminal extensions, a feature shared by thioredoxin h proteins of subgroup 2. To ascertain the function of these extensions in NaTrxh secretion and protein-protein interaction, we performed a deletion analysis on NaTrxh and fused the resulting variants to GFP. Results We found an internal domain in the N-terminal extension, called Nβ, that is essential for NaTrxh secretion but is not hydrophobic, a canonical feature of a signal peptide. The lack of hydrophobicity as well as the location of the secretion signal within the NaTrxh primary structure, suggest an unorthodox secretion route for NaTrxh. Notably, we found that the fusion protein NaTrxh-GFP(KDEL) is retained in the endoplasmic reticulum and that treatment of NaTrxh-GFP-expressing cells with Brefeldin A leads to its retention in the Golgi, which indicates that NaTrxh uses, to some extent, the endoplasmic reticulum and Golgi apparatus for secretion. Furthermore, we found that Nβ contributes to NaTrxh tertiary structure stabilization and that the C-terminus functions in the protein-protein interaction with S-RNase. Conclusions The extensions contained in NaTrxh sequence have specific functions on the protein. While the C-terminus directly participates in protein-protein interaction, particularly on its interaction with S-RNase in vitro; the N-terminal extension contains two structurally different motifs: Nα and Nβ. Nβ, the inner domain (Ala-17 to Pro-27), is essential and enough to target NaTrxh towards the apoplast. Interestingly, when it was fused to GFP, this protein was also found in the cell wall of the onion cells. Although the biochemical features of the N-terminus suggested a non-classical secretion pathway, our

  9. Triggering Klystrons

    SciTech Connect

    Stefan, Kelton D.; /Purdue U. /SLAC

    2010-08-25

    To determine if klystrons will perform to the specifications of the LCLS (Linac Coherent Light Source) project, a new digital trigger controller is needed for the Klystron/Microwave Department Test Laboratory. The controller needed to be programmed and Windows based user interface software needed to be written to interface with the device over a USB (Universal Serial Bus). Programming the device consisted of writing logic in VHDL (VHSIC (Very High Speed Integrated Circuits) hardware description language), and the Windows interface software was written in C++. Xilinx ISE (Integrated Software Environment) was used to compile the VHDL code and program the device, and Microsoft Visual Studio 2005 was used to compile the C++ based Windows software. The device was programmed in such a way as to easily allow read/write operations to it using a simple addressing model, and Windows software was developed to interface with the device over a USB connection. A method of setting configuration registers in the trigger device is absolutely necessary to the development of a new triggering system, and the method developed will fulfill this need adequately. More work is needed before the new trigger system is ready for use. The configuration registers in the device need to be fully integrated with the logic that will generate the RF signals, and this system will need to be tested extensively to determine if it meets the requirements for low noise trigger outputs.

  10. Methylation of Exons 1D, 1F, and 1H of the Glucocorticoid Receptor Gene Promoter and Exposure to Adversity in Pre-School Aged Children

    PubMed Central

    Tyrka, Audrey R.; Parade, Stephanie H.; Eslinger, Nicole M.; Marsit, Carmen J.; Lesseur, Corina; Armstrong, David A.; Philip, Noah S.; Josefson, Brittney; Seifer, Ronald

    2016-01-01

    Epigenetic modifications to the genome are a key mechanism involved in the biological encoding of experience. Animal studies and a growing body of literature in humans have shown that early adversity is linked to methylation of the gene for the glucocorticoid receptor (GR) which is a key regulator of the hypothalamic-pituitary-adrenal (HPA) axis as well as a broad range of physiological systems including metabolic and immune function. One hundred eighty-four families participated, including n=74 with child welfare documentation of moderate-severe maltreatment in the past six months. Children ranged in age from 3 to 5 years, and were racially and ethnically diverse. Structured record review and interviews in the home were used to assess a history of maltreatment, other traumas, and contextual life stressors, and a composite variable assessed the number exposures to these adversities. Methylation of regions 1D, 1F, and 1H of the GR gene was measured via sodium bisulfite pyrosequencing. The composite measure of adversity was positively correlated with methylation at exons 1D and 1F in the promoter of NR3C1. Individual stress measures were significantly associated with a several CpG sites in these regions. GR gene methylation may be a mechanism of the bio-behavioral effects of adverse exposures in young children. PMID:25997773

  11. The role of CTLA-4 exon-1 49 A/G polymorphism and soluble CTLA-4 protein level in egyptian patients with Behçet's disease.

    PubMed

    Abdel Galil, Sahar M; Hagrass, Hoda A

    2014-01-01

    This study analyzed the association of the A/G SNP at position +49 of exon-1 in the CTLA-4 gene to the susceptibility and clinical manifestations of Behcet's disease (BD). It was performed on 60 Egyptian BD patients and 95 age- and sex-matched healthy controls. The genotypes for the +49 A/G polymorphism of the CTLA-4 gene were determined by PCR-RFLP, while the serum level of CTLA-4 protein was measured by ELISA. CTLA-4 +49 A allele (P < 0.001, OR = 3.084, and CI (95%) = 1.90-4.99) and A/A genotype (P < 0.001, OR = 6.643, and CI (95%) = 2.58-17.10) frequency distribution was significantly more increased in patients than in the controls, with no significant differences between males and females with regard to the genotype or allele frequency distribution. A/A genotype was associated with a more reduced expression of sCTLA-4 protein in patients than in the controls (1.76 ± 0.19 versus 1.91 ± 0.30, resp; P < 0.0007). In addition, it is associated with the occurrence of ocular and vasculitic manifestations of BD in the patient group. The CTLA-4 gene could be considered as a susceptibility and a disease-modifying gene to BD in Egyptian population that needs further confirmatory studies on larger cohorts.

  12. Methods comparison for high-resolution transcriptional analysis of archival material on Affymetrix Plus 2.0 and Exon 1.0 microarrays.

    PubMed

    Linton, Kim; Hey, Yvonne; Dibben, Sian; Miller, Crispin; Freemont, Anthony; Radford, John; Pepper, Stuart

    2009-07-01

    Microarray gene expression profiling of formalin-fixed paraffin-embedded (FFPE) tissues is a new and evolving technique. This report compares transcript detection rates on Affymetrix U133 Plus 2.0 and Human Exon 1.0 ST GeneChips across several RNA extraction and target labeling protocols, using routinely collected archival FFPE samples. All RNA extraction protocols tested (Ambion-Optimum, Ambion-RecoverAll, and Qiagen-RNeasy FFPE) provided extracts suitable for microarray hybridization. Compared with Affymetrix One-Cycle labeled extracts, NuGEN system protocols utilizing oligo(dT) and random hexamer primers, and cDNA target preparations instead of cRNA, achieved percent present rates up to 55% on Plus 2.0 arrays. Based on two paired-sample analyses, at 90% specificity this equalled an average 30 percentage-point increase (from 50% to 80%) in FFPE transcript sensitivity relative to fresh frozen tissues, which we have assumed to have 100% sensitivity and specificity. The high content of Exon arrays, with multiple probe sets per exon, improved FFPE sensitivity to 92% at 96% specificity, corresponding to an absolute increase of ~600 genes over Plus 2.0 arrays. While larger series are needed to confirm high correspondence between fresh-frozen and FFPE expression patterns, these data suggest that both Plus 2.0 and Exon arrays are suitable platforms for FFPE microarray expression analyses.

  13. Non-covalent interactions of the carcinogen (+)-anti-BPDE with exon 1 of the human K-ras proto-oncogene

    NASA Astrophysics Data System (ADS)

    Rodriguez, Jorge H.; Deligkaris, Christos

    2013-03-01

    Investigating the complementary, but different, effects of physical (non-covalent) and chemical (covalent) mutagen-DNA and carcinogen-DNA interactions is important for understanding possible mechanisms of development and prevention of mutagenesis and carcinogenesis. A highly mutagenic and carcinogenic metabolite of the polycyclic aromatic hydrocarbon benzo[ α]pyrene, namely (+)-anti-BPDE, is known to undergo both physical and chemical complexation with DNA. The major covalent adduct, a promutagenic, is known to be an external (+)-trans-anti-BPDE-N2-dGuanosine configuration whose origins are not fully understood. Thus, it is desirable to study the mechanisms of external non-covalent BPDE-DNA binding and their possible relationships to external covalent trans adduct formation. We present a detailed codon-by-codon computational study of the non-covalent interactions of (+)-anti-BPDE with DNA which explains and correctly predicts preferential (+)-anti-BPDE binding at minor groove guanosines. Due to its relevance to carcinogenesis, the interaction of (+)-anti-BPDE with exon 1 of the human K-ras gene has been studied in detail. Present address: Department of Physics, Drury University

  14. Molecular and Genetic Characterization of HIV-1 Tat Exon-1 Gene from Cameroon Shows Conserved Tat HLA-Binding Epitopes: Functional Implications

    PubMed Central

    Teto, Georges; Fonsah, Julius Y.; Tagny, Claude T.; Mbanya, Dora; Nchindap, Emilienne; Kenmogne, Leopoldine; Fokam, Joseph; Njamnshi, Dora M.; Kouanfack, Charles; Njamnshi, Alfred K.; Kanmogne, Georgette D.

    2016-01-01

    HIV-1 Tat plays a critical role in viral transactivation. Subtype-B Tat has potential use as a therapeutic vaccine. However, viral genetic diversity and population genetics would significantly impact the efficacy of such a vaccine. Over 70% of the 37-million HIV-infected individuals are in sub-Saharan Africa (SSA) and harbor non-subtype-B HIV-1. Using specimens from 100 HIV-infected Cameroonians, we analyzed the sequences of HIV-1 Tat exon-1, its functional domains, post-translational modifications (PTMs), and human leukocyte antigens (HLA)-binding epitopes. Molecular phylogeny revealed a high genetic diversity with nine subtypes, CRF22_01A1/CRF01_AE, and negative selection in all subtypes. Amino acid mutations in Tat functional domains included N24K (44%), N29K (58%), and N40K (30%) in CRF02_AG, and N24K in all G subtypes. Motifs and phosphorylation analyses showed conserved amidation, N-myristoylation, casein kinase-2 (CK2), serine and threonine phosphorylation sites. Analysis of HLA allelic frequencies showed that epitopes for HLAs A*0205, B*5301, Cw*0401, Cw*0602, and Cw*0702 were conserved in 58%–100% of samples, with B*5301 epitopes having binding affinity scores > 100 in all subtypes. This is the first report of N-myristoylation, amidation, and CK2 sites in Tat; these PTMs and mutations could affect Tat function. HLA epitopes identified could be useful for designing Tat-based vaccines for highly diverse HIV-1 populations, as in SSA. PMID:27438849

  15. A platform to view huntingtin exon 1 aggregation flux in the cell reveals divergent influences from chaperones hsp40 and hsp70.

    PubMed

    Ormsby, Angelique R; Ramdzan, Yasmin M; Mok, Yee-Foong; Jovanoski, Kristijan D; Hatters, Danny M

    2013-12-27

    Our capacity for tracking how misfolded proteins aggregate inside a cell and how different aggregation states impact cell biology remains enigmatic. To address this, we built a new toolkit that enabled the high throughput tracking of individual cells enriched with polyglutamine-expanded Htt exon 1 (Httex1) monomers, oligomers, and inclusions using biosensors of aggregation state and flow cytometry pulse shape analysis. Supplemented with gel filtration chromatography and fluorescence-adapted sedimentation velocity analysis of cell lysates, we collated a multidimensional view of Httex1 aggregation in cells with respect to time, polyglutamine length, expression levels, cell survival, and overexpression of protein quality control chaperones hsp40 (DNAJB1) and hsp70 (HSPA1A). Cell death rates trended higher for Neuro2a cells containing Httex1 in inclusions than with Httex1 dispersed through the cytosol at time points of expression over 2 days. hsp40 stabilized monomers and suppressed inclusion formation but did not otherwise change Httex1 toxicity. hsp70, however, had no major effect on aggregation of Httex1 but increased the survival rate of cells with inclusions. hsp40 and hsp70 also increased levels of a second bicistronic reporter of Httex1 expression, mKate2, and increased total numbers of cells in culture, suggesting these chaperones partly rectify Httex1-induced deficiencies in quality control and growth rates. Collectively, these data suggest that Httex1 overstretches the protein quality control resources and that the defects can be partly rescued by overexpression of hsp40 and hsp70. Importantly, these effects occurred in a pronounced manner for soluble Httex1, which points to Httex1 aggregation occurring subsequently to more acute impacts on the cell. PMID:24196953

  16. A Platform to View Huntingtin Exon 1 Aggregation Flux in the Cell Reveals Divergent Influences from Chaperones hsp40 and hsp70*

    PubMed Central

    Ormsby, Angelique R.; Ramdzan, Yasmin M.; Mok, Yee-Foong; Jovanoski, Kristijan D.; Hatters, Danny M.

    2013-01-01

    Our capacity for tracking how misfolded proteins aggregate inside a cell and how different aggregation states impact cell biology remains enigmatic. To address this, we built a new toolkit that enabled the high throughput tracking of individual cells enriched with polyglutamine-expanded Htt exon 1 (Httex1) monomers, oligomers, and inclusions using biosensors of aggregation state and flow cytometry pulse shape analysis. Supplemented with gel filtration chromatography and fluorescence-adapted sedimentation velocity analysis of cell lysates, we collated a multidimensional view of Httex1 aggregation in cells with respect to time, polyglutamine length, expression levels, cell survival, and overexpression of protein quality control chaperones hsp40 (DNAJB1) and hsp70 (HSPA1A). Cell death rates trended higher for Neuro2a cells containing Httex1 in inclusions than with Httex1 dispersed through the cytosol at time points of expression over 2 days. hsp40 stabilized monomers and suppressed inclusion formation but did not otherwise change Httex1 toxicity. hsp70, however, had no major effect on aggregation of Httex1 but increased the survival rate of cells with inclusions. hsp40 and hsp70 also increased levels of a second bicistronic reporter of Httex1 expression, mKate2, and increased total numbers of cells in culture, suggesting these chaperones partly rectify Httex1-induced deficiencies in quality control and growth rates. Collectively, these data suggest that Httex1 overstretches the protein quality control resources and that the defects can be partly rescued by overexpression of hsp40 and hsp70. Importantly, these effects occurred in a pronounced manner for soluble Httex1, which points to Httex1 aggregation occurring subsequently to more acute impacts on the cell. PMID:24196953

  17. Firearm trigger assembly

    SciTech Connect

    Crandall, David L.; Watson, Richard W.

    2010-02-16

    A firearm trigger assembly for use with a firearm includes a trigger mounted to a forestock of the firearm so that the trigger is movable between a rest position and a triggering position by a forwardly placed support hand of a user. An elongated trigger member operatively associated with the trigger operates a sear assembly of the firearm when the trigger is moved to the triggering position. An action release assembly operatively associated with the firearm trigger assembly and a movable assembly of the firearm prevents the trigger from being moved to the triggering position when the movable assembly is not in the locked position.

  18. Inherited human complement C5 deficiency: Nonsense mutations in exons 1 (Gln{sup 1} to Stop) and 36 (Arg{sup 1458} to Stop) and compound heterozygosity in three African-American families

    SciTech Connect

    Wang, X.; Fleischer, D.T.; Whitehead, W.T.

    1995-05-15

    Hereditary C5 deficiency has been reported in several families of different ethnic backgrounds and from different geographic regions, but the molecular genetic defect causing C5 deficiency has not been delineated in any of them. To examine the molecular basis of C5 deficiency in the African-American population, the exons and intron/exon boundaries of the C5 structural genes from three C5-deficient (C5D) African-American families were sequenced, revealing two nonsense mutations. The nonsense mutations are located in exon 1 (C{sup 84}AG to TAG) in two of the C5D families (Rhode Island and North Carolina) and in exon 36 (C{sup 4521}GA to TGA) in the third C5D family (New York). The exon 1 and 36 mutations are contained in codons that encode the first amino acid of the C5 {beta}-chain (Gln{sup 1} to Stop) and residue 1458 in the {alpha}-chain (Arg{sup 1458} to Stop), respectively. Allele-specific PCR and sequence analyses demonstrated that the exon 1 mutation is present in only one of the C5 null genes in both the Rhode Island and North Carolina families, and the exon 36 mutation is contained in only one C5 null gene in the New York family. Neither of the nonsense mutations was found in the European or Caucasian-American C5D individuals examined. Collectively, these data indicate that: (1) C5 deficiency is caused by several different molecular genetic defects, (2) C5 deficiency in the African-American population can be explained in part by two distinct nonsense mutations in exons 1 and 36, and (3) compound heterozygosity exists in all of the reported African-American C5D families. 44 refs., 5 figs., 1 tab.

  19. Identifying asthma triggers.

    PubMed

    McCarty, Justin C; Ferguson, Berrylin J

    2014-02-01

    Asthma has many triggers including rhinosinusitis; allergy; irritants; medications (aspirin in aspirin-exacerbated respiratory disease); and obesity. Paradoxic vocal fold dysfunction mimics asthma and may be present along with asthma. This article reviews each of these triggers, outlining methods of recognizing the trigger and then its management. In many patients more than one trigger may be present. Full appreciation of the complexity of these relationships and targeted therapy to the trigger is needed to best care for the patient with asthma.

  20. p97 Homologs from Caenorhabditis elegans, CDC-48.1 and CDC-48.2, suppress the aggregate formation of huntingtin exon1 containing expanded polyQ repeat.

    PubMed

    Nishikori, Shingo; Yamanaka, Kunitoshi; Sakurai, Toshihiko; Esaki, Masatoshi; Ogura, Teru

    2008-08-01

    Polyglutamine (polyQ)-expanded proteins are associated with cytotoxicity in some neurodegenerative disorders such as Huntington's disease. We have reported that the aggregation of the polyQ-expanded protein is partially suppressed by co-expression of either of two homologs of an AAA chaperone p97, CDC-48.1 or CDC-48.2, in Caenorhabditis elegans, but how p97 regulates the aggregation of polyQ-expanded proteins remains unclear. Here we present direct evidence that CDC-48.1 and CDC-48.2 suppress the aggregation of a huntingtin (Htt) exon1 fragment containing an expanded polyQ repeat in vitro. CDC-48.1 and CDC-48.2 bound the Htt exon1 fragment directly, and suppressed the formation of SDS-insoluble aggregates of Htt fragments containing 53 glutamine residues (HttQ53) independently of nucleotides. CDC-48.1 and CDC-48.2 also modulated the oligomeric states of HttQ53 during the aggregate formation. In the absence of CDC-48.1 and CDC-48.2, HttQ53 formed 70-150 kDa oligomers, whereas 300-500 kDa oligomers as well as 70-150 kDa oligomers accumulated in the presence of CDC-48.1 and CDC-48.2. Taken together, these results suggest that p97 plays a protective role in neurodegenerative disorders by directly suppressing the protein aggregation as a molecular chaperone.

  1. The globoside receptor triggers structural changes in the B19 virus capsid that facilitate virus internalization.

    PubMed

    Bönsch, Claudia; Zuercher, Christoph; Lieby, Patricia; Kempf, Christoph; Ros, Carlos

    2010-11-01

    Globoside (Gb4Cer), Ku80 autoantigen, and α5β1 integrin have been identified as cell receptors/coreceptors for human parvovirus B19 (B19V), but their role and mechanism of interaction with the virus are largely unknown. In UT7/Epo cells, expression of Gb4Cer and CD49e (integrin alpha-5) was high, but expression of Ku80 was insignificant. B19V colocalized with Gb4Cer and, to a lesser extent, with CD49e. However, only anti-Gb4Cer antibodies could disturb virus attachment. Only a small proportion of cell-bound viruses were internalized, while the majority became detached from the receptor. When added to uninfected cells, the receptor-detached virus showed superior cell binding capacity and infectivity. Attachment of B19V to cells triggered conformational changes in the capsid leading to the accessibility of the N terminus of VP1 (VP1u) to antibodies, which was maintained in the receptor-detached virus. VP1u became similarly accessible to antibodies following incubation of B19V particles with increasing concentrations of purified Gb4Cer. The receptor-mediated exposure of VP1u is critical for virus internalization, since capsids lacking VP1 could bind to cells but were not internalized. Moreover, an antibody against the N terminus of VP1u disturbed virus internalization, but only when present during and not after virus attachment, indicating the involvement of this region in binding events required for internalization. These results suggest that Gb4Cer is not only the primary receptor for B19V attachment but also the mediator of capsid rearrangements required for subsequent interactions leading to virus internalization. The capacity of the virus to detach and reattach again would enhance the probability of productive infections.

  2. The Globoside Receptor Triggers Structural Changes in the B19 Virus Capsid That Facilitate Virus Internalization▿

    PubMed Central

    Bönsch, Claudia; Zuercher, Christoph; Lieby, Patricia; Kempf, Christoph; Ros, Carlos

    2010-01-01

    Globoside (Gb4Cer), Ku80 autoantigen, and α5β1 integrin have been identified as cell receptors/coreceptors for human parvovirus B19 (B19V), but their role and mechanism of interaction with the virus are largely unknown. In UT7/Epo cells, expression of Gb4Cer and CD49e (integrin alpha-5) was high, but expression of Ku80 was insignificant. B19V colocalized with Gb4Cer and, to a lesser extent, with CD49e. However, only anti-Gb4Cer antibodies could disturb virus attachment. Only a small proportion of cell-bound viruses were internalized, while the majority became detached from the receptor. When added to uninfected cells, the receptor-detached virus showed superior cell binding capacity and infectivity. Attachment of B19V to cells triggered conformational changes in the capsid leading to the accessibility of the N terminus of VP1 (VP1u) to antibodies, which was maintained in the receptor-detached virus. VP1u became similarly accessible to antibodies following incubation of B19V particles with increasing concentrations of purified Gb4Cer. The receptor-mediated exposure of VP1u is critical for virus internalization, since capsids lacking VP1 could bind to cells but were not internalized. Moreover, an antibody against the N terminus of VP1u disturbed virus internalization, but only when present during and not after virus attachment, indicating the involvement of this region in binding events required for internalization. These results suggest that Gb4Cer is not only the primary receptor for B19V attachment but also the mediator of capsid rearrangements required for subsequent interactions leading to virus internalization. The capacity of the virus to detach and reattach again would enhance the probability of productive infections. PMID:20826697

  3. Asthma triggers (image)

    MedlinePlus

    ... common asthma triggers are mold, pets, dust, grasses, pollen, cockroaches, odors from chemicals, and smoke from cigarettes. ... common asthma triggers are mold, pets, dust, grasses, pollen, cockroaches, odors from chemicals, and smoke from cigarettes.

  4. Mutation of single hydrophobic residue I27, L35, F39, L58, L65, L67, or L71 in the N terminus of VP5 abolishes interaction with the scaffold protein and prevents closure of herpes simplex virus type 1 capsid shells.

    PubMed

    Walters, Jewell N; Sexton, Gerry L; McCaffery, J Michael; Desai, Prashant

    2003-04-01

    Protein-protein interactions drive the assembly of the herpes simplex virus type 1 (HSV-1) capsid. A key interaction occurs between the C-terminal tail of the scaffold protein (pre-22a) and the major capsid protein (VP5). Previously (Z. Hong, M. Beaudet-Miller, J. Durkin, R. Zhang, and A. D. Kwong, J. Virol. 70:533-540, 1996) it was shown that the minimal domain in the scaffold protein necessary for this interaction was composed of a hydrophobic amphipathic helix. The goal of this study was to identify the hydrophobic residues in VP5 important for this bimolecular interaction. Results from the genetic analysis of second-site revertant virus mutants identified the importance of the N terminus of VP5 for the interaction with the scaffold protein. This allowed us to focus our efforts on a small region of this large polypeptide. Twenty-four hydrophobic residues, starting at L23 and ending at F84, were mutated to alanine. All the mutants were first screened for interaction with pre-22a in the yeast two-hybrid assay. From this in vitro assay, seven residues, I27, L35, F39, L58, L65, L67, and L71, that eliminated the interaction when mutated were identified. All 24 mutants were introduced into the virus genome with a genetic marker rescue/marker transfer system. For this system, viruses and cell lines that greatly facilitated the introduction of the mutants into the genome were made. The same seven mutants that abolished interaction of VP5 with pre-22a resulted in an absolute requirement for wild-type VP5 for growth of the viruses. The viruses encoding these mutations in VP5 were capable of forming capsid shells comprised of VP5, VP19C, VP23, and VP26, but the closure of these shells into an icosahedral structure was prevented. Mutation at L75 did not affect the ability of this protein to interact with pre-22a, as judged from the in vitro assay, but this mutation specified a lethal effect for virus growth and abolished the formation of any detectable assembled structure

  5. Myofascial trigger points.

    PubMed

    Lavelle, Elizabeth Demers; Lavelle, William; Smith, Howard S

    2007-03-01

    Painful conditions of the musculoskeletal system, including myofascial pain syndrome, constitute some of the most important chronic problems encountered in a clinical practice. A myofascial trigger points is a hyperirritable spot, usually within a taut band of skeletal muscle, which is painful on compression and can give rise to characteristic referred pain, motor dysfunction, and autonomic phenomena. Trigger points may be relieved through noninvasive measures, such as spray and stretch, transcutaneous electrical stimulation, physical therapy, and massage. Invasive treatments for myofascial trigger points include injections with local anesthetics, corticosteroids, or botulism toxin or dry needling. The etiology, pathophysiology, and treatment of myofascial trigger points are addressed in this article.

  6. Lessons from (triggered) tremor

    USGS Publications Warehouse

    Gomberg, Joan

    2010-01-01

    I test a “clock-advance” model that implies triggered tremor is ambient tremor that occurs at a sped-up rate as a result of loading from passing seismic waves. This proposed model predicts that triggering probability is proportional to the product of the ambient tremor rate and a function describing the efficacy of the triggering wave to initiate a tremor event. Using data mostly from Cascadia, I have compared qualitatively a suite of teleseismic waves that did and did not trigger tremor with ambient tremor rates. Many of the observations are consistent with the model if the efficacy of the triggering wave depends on wave amplitude. One triggered tremor observation clearly violates the clock-advance model. The model prediction that larger triggering waves result in larger triggered tremor signals also appears inconsistent with the measurements. I conclude that the tremor source process is a more complex system than that described by the clock-advance model predictions tested. Results of this and previous studies also demonstrate that (1) conditions suitable for tremor generation exist in many tectonic environments, but, within each, only occur at particular spots whose locations change with time; (2) any fluid flow must be restricted to less than a meter; (3) the degree to which delayed failure and secondary triggering occurs is likely insignificant; and 4) both shear and dilatational deformations may trigger tremor. Triggered and ambient tremor rates correlate more strongly with stress than stressing rate, suggesting tremor sources result from time-dependent weakening processes rather than simple Coulomb failure.

  7. AMY trigger system

    SciTech Connect

    Sakai, Yoshihide

    1989-04-01

    A trigger system of the AMY detector at TRISTAN e{sup +}e{sup -} collider is described briefly. The system uses simple track segment and shower cluster counting scheme to classify events to be triggered. It has been operating successfully since 1987.

  8. Increased Levels of β-catenin, LEF-1, and HPA-1 Correlate with Poor Prognosis for Acral Melanoma with Negative BRAF and NRAS Mutation in BRAF Exons 11 and 15 and NRAS Exons 1 and 2

    PubMed Central

    Xu, Sanxiong; Zhang, Jinyu; Jiang, Yongxin; Chen, Yongbin; Li, Hongjun; Liu, Xuefeng; Xu, Da; Chen, Yanjin; Yang, Yihao; Zhang, Ya; Li, Dongxu; Xia, Junfeng

    2015-01-01

    To determine the expression of β-catenin, lymphoid enhancer-binding protein-1 (LEF-1), and heparanase-1 (HPA-1) and to evaluate these proteins' potential prognostic values in malignant acral melanoma without mutations in BRAF exons 11 and 15 and NRAS exons 1 and 2, specimens from 90 patients with wild-type BRAF and NRAS were assessed and analyzed by immunohistochemistry and western blotting. The positive expression of β-catenin, lymphoid enhancer-binding protein-1, and heparanase-1 was observed in 36 (72%), 31 (62%), and 32 (64%) of the detected acral melanomas, respectively. The expression of β-catenin, lymphoid enhancer-binding protein-1, and heparanase-1 was not correlated with gender, age, or diseased body parts (p>0.05), but was significantly positively correlated with the tumor node metastasis (TNM) stage and metastasis (correlation=0.406 and 0.716, 0.397 and 0.582, 0.353 and 0.579; p=0.040 and 0.0001, 0.0040 and 0.0001, 0.0120 and 0.0001, respectively). We also observed that the increased expression of β-catenin, lymphoid enhancer-binding protein-1, and heparanase-1 was significantly correlated with decreased survival and poor prognosis (p=0.001, 0.010, and 0.023, respectively). A multifactorial analysis using Cox's regression model revealed that β-catenin, lymphoid enhancer-binding protein-1, heparanase-1, and the TNM stage were all independent factors in malignant melanoma (risk ratios were 7.294, 5.550, 5.622, and 4.794; p-values were 0.007, 0.018, 0.018, and 0.029, respectively). This study may provide the basis for the use of β-catenin, lymphoid enhancer-binding protein-1, and heparanase-1 as novel targets in the treatment of malignant invasion and metastasis in acral melanoma cancer. The expression of β-catenin, LEF-1, and HPA-1 was assessed and compared in malignant melanoma with that of peritumoral tissue and benign nevus in the patients with negative mutations in BRAF exons 11 and 15 and NRAS exons 1 and 2. The study may provide the basis for

  9. LHCb Topological Trigger Reoptimization

    NASA Astrophysics Data System (ADS)

    Likhomanenko, Tatiana; Ilten, Philip; Khairullin, Egor; Rogozhnikov, Alex; Ustyuzhanin, Andrey; Williams, Michael

    2015-12-01

    The main b-physics trigger algorithm used by the LHCb experiment is the so- called topological trigger. The topological trigger selects vertices which are a) detached from the primary proton-proton collision and b) compatible with coming from the decay of a b-hadron. In the LHC Run 1, this trigger, which utilized a custom boosted decision tree algorithm, selected a nearly 100% pure sample of b-hadrons with a typical efficiency of 60-70%; its output was used in about 60% of LHCb papers. This talk presents studies carried out to optimize the topological trigger for LHC Run 2. In particular, we have carried out a detailed comparison of various machine learning classifier algorithms, e.g., AdaBoost, MatrixNet and neural networks. The topological trigger algorithm is designed to select all ’interesting” decays of b-hadrons, but cannot be trained on every such decay. Studies have therefore been performed to determine how to optimize the performance of the classification algorithm on decays not used in the training. Methods studied include cascading, ensembling and blending techniques. Furthermore, novel boosting techniques have been implemented that will help reduce systematic uncertainties in Run 2 measurements. We demonstrate that the reoptimized topological trigger is expected to significantly improve on the Run 1 performance for a wide range of b-hadron decays.

  10. A novel stop codon mutation in exon 1 (558C>A) of the UGT1A1 gene in a Thai neonate with Crigler-Najjar syndrome type I.

    PubMed

    Wanlapakorn, N; Nilyanimit, P; Vorawandthanachai, T; Deesudjit, T; Dumrongpisutikul, N; Poovorawan, Y

    2015-01-01

    Human uridine 5'-diphosphate-glucuronosyltransferases play a critical role in detoxification by conjugating bilirubin with glucoronic acid. Impaired or reduced enzymatic activity causes a spectrum of clinical disorders such as Crigler-Najjar syndrome type I (CN1), Crigler-Najjar syndrome type II, and Gilbert's syndrome. CN1 is a severe form of unconjugated hyperbilirubinemia caused by homozygous or compound heterozygous mutations in the gene for uridine 5'-diphosphate glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1), resulting in complete loss of enzyme function. Here, we report a novel homozygous mutation of UGT1A1 in a female Thai infant who was diagnosed with CN1, and her parents were found to be heterozygous carriers. The patient was homozygous for the c.558C>A mutation, which resulted in a premature stop codon in exon 1. Her asymptomatic parents were carriers of the nonsense c.558C>A mutation. Our result suggests an important role for homozygous c.558C>A mutations in the UGT1A1 gene in the development of severe unconjugated hyperbilirubinemia. PMID:25729974

  11. Common Asthma Triggers

    MedlinePlus

    ... your bedding on the hottest water setting. Outdoor Air Pollution Outdoor air pollution can trigger an asthma attack. This pollution can ... your newspaper to plan your activities for when air pollution levels will be low. Cockroach Allergen Cockroaches and ...

  12. Dealing with Asthma Triggers

    MedlinePlus

    ... smell given off by paint or gas, and air pollution. If you notice that an irritant triggers your ... or other tobacco products around you. If outdoor air pollution is a problem, running the air conditioner or ...

  13. ELECTRONIC TRIGGER CIRCUIT

    DOEpatents

    Russell, J.A.G.

    1958-01-01

    An electronic trigger circuit is described of the type where an output pulse is obtained only after an input voltage has cqualed or exceeded a selected reference voltage. In general, the invention comprises a source of direct current reference voltage in series with an impedance and a diode rectifying element. An input pulse of preselected amplitude causes the diode to conduct and develop a signal across the impedance. The signal is delivered to an amplifier where an output pulse is produced and part of the output is fed back in a positive manner to the diode so that the amplifier produces a steep wave front trigger pulsc at the output. The trigger point of the described circuit is not subject to variation due to the aging, etc., of multi-electrode tabes, since the diode circuit essentially determines the trigger point.

  14. The LHCb Trigger System

    NASA Astrophysics Data System (ADS)

    Rodrigues, E.; LHCb Collaboration

    2007-08-01

    The LHCb detector has been conceived to study with high precision CP violation and rare decays of b-flavoured hadrons produced at the LHC. The LHCb trigger is of crucial importance in selecting the collisions of interest for b-physics studies. The trigger is based on a two-level system. The first level, Level-0, is implemented in hardware and uses information from the calorimeter, muon and pile-up systems to select events containing particles with relatively large transverse momentum, typically above 1-2 GeV. The Level-0 trigger accepts events at a rate of 1 MHz. All the detector information is then read out and fed into the High Level Trigger. This software trigger runs in the event-filter farm composed of about 1800 CPU nodes. Events are selected at a rate of 2 kHz and sent for mass storage and subsequent offline reconstruction and analysis. The current status and expected performance of the trigger system are described.

  15. Trigger mechanism for engines

    SciTech Connect

    Clark, L.R.

    1989-02-28

    A trigger mechanism is described for a blower-vacuum apparatus having a trigger mounted within a handle and a small engine comprising: a throttle; a ''L'' shaped lever having first and second legs mounted for rotation about an intermediate pivot within the handle when the trigger is depressed, interconnecting the trigger and the throttle, the second leg having first teeth defined therein, the lever further having idle, full throttle and stop positions; a normally raised latch means adapted to be rotated and axially depressed, the latch means having second teeth situated on a cam to engage the first teeth for holding the lever in an intermediate position between the idle and full throttle positions when the latch means is rotated. The latch means further are cam teeth into potential engagement with the lever teeth when the trigger is depressed, lever is biased to the stop position; and idle adjusting means means for intercepting the second leg for preventing the second leg from reaching the stop position when the latch means is raised.

  16. Cygnus Trigger System

    SciTech Connect

    G. Corrow, M. Hansen, D. Henderson, C. Mitton

    2008-02-01

    The Cygnus Dual Beam Radiographic Facility consists of two radiographic sources (Cygnus 1, Cygnus 2) each with a dose rating of 4 rads at 1 m, and a 1-mm diameter spot size. The electrical specifications are: 2.25 MV, 60 kA, 60 ns. This facility is located in an underground environment at the Nevada Test Site (NTS). These sources were developed as a primary diagnostic for subcritical tests, which are single-shot, high-value events. In such an application there is an emphasis on reliability and reproducibility. A robust, low-jitter trigger system is a key element for meeting these goals. The trigger system was developed with both commercial and project-specific equipment. In addition to the traditional functions of a trigger system there are novel features added to protect the investment of a high-value shot. Details of the trigger system, including elements designed specifically for a subcritical test application, will be presented. The individual electronic components have their nominal throughput, and when assembled have a system throughput with a measured range of jitter. The shot-to-shot jitter will be assessed both individually and in combination. Trigger reliability and reproducibility results will be presented for a substantial number of shots executed at the NTS.

  17. Androgen Receptor Exon 1 Mutation Causes Androgen Insensitivity by Creating Phosphorylation Site and Inhibiting Melanoma Antigen-A11 Activation of NH2- and Carboxyl-terminal Interaction-dependent Transactivation*

    PubMed Central

    Lagarde, William H.; Blackwelder, Amanda J.; Minges, John T.; Hnat, Andrew T.; French, Frank S.; Wilson, Elizabeth M.

    2012-01-01

    Naturally occurring germ line mutations in the X-linked human androgen receptor (AR) gene cause incomplete masculinization of the external genitalia by disrupting AR function in males with androgen insensitivity syndrome. Almost all AR missense mutations that cause androgen insensitivity syndrome are located in the highly structured DNA and ligand binding domains. In this report we investigate the functional defect associated with an AR exon 1 missense mutation, R405S, that caused partial androgen insensitivity. The 46,XX heterozygous maternal carrier had a wild-type Arg-405 CGC allele but transmitted an AGC mutant allele coding for Ser-405. At birth, the 46,XY proband had a bifid scrotum, hypospadias, and micropenis consistent with clinical stage 3 partial androgen insensitivity. Androgen-dependent transcriptional activity of AR-R405S expressed in CV1 cells was less than wild-type AR and refractory in androgen-dependent AR NH2- and carboxyl interaction transcription assays that depend on the coregulator effects of melanoma antigen-A11. This mutation created a Ser-405 phosphorylation site evident by the gel migration of an AR-R405S NH2-terminal fragment as a double band that converted to the wild-type single band after treatment with λ-phosphatase. Detrimental effects of the R405S mutation were related to the proximity of the AR WXXLF motif 433WHTLF437 required for melanoma antigen-A11 and p300 to stimulate transcriptional activity associated with the AR NH2- and carboxyl-terminal interaction. We conclude that the coregulator effects of melanoma antigen-A11 on the AR NH2- and carboxyl-terminal interaction amplify the androgen-dependent transcriptional response to p300 required for normal human male sex development in utero. PMID:22334658

  18. Microfabricated triggered vacuum switch

    DOEpatents

    Roesler, Alexander W.; Schare, Joshua M.; Bunch, Kyle

    2010-05-11

    A microfabricated vacuum switch is disclosed which includes a substrate upon which an anode, cathode and trigger electrode are located. A cover is sealed over the substrate under vacuum to complete the vacuum switch. In some embodiments of the present invention, a metal cover can be used in place of the trigger electrode on the substrate. Materials used for the vacuum switch are compatible with high vacuum, relatively high temperature processing. These materials include molybdenum, niobium, copper, tungsten, aluminum and alloys thereof for the anode and cathode. Carbon in the form of graphitic carbon, a diamond-like material, or carbon nanotubes can be used in the trigger electrode. Channels can be optionally formed in the substrate to mitigate against surface breakdown.

  19. Video Event Trigger

    NASA Technical Reports Server (NTRS)

    Williams, Glenn L.; Lichter, Michael J.

    1994-01-01

    Video event trigger (VET) processes video image data to generate trigger signal when image shows significant change like motion or appearance, disappearance, change in color, change in brightness, or dilation of object. System aids in efficient utilization of image-data-storage and image-data-processing equipment in applications in which many video frames show no changes and are wasteful to record and analyze all frames when only relatively few frames show changes of interest. Applications include video recording of automobile crash tests, automated video monitoring of entrances, exits, parking lots, and secure areas.

  20. Neutrophil Elastase and Proteinase-3 Trigger G Protein-biased Signaling through Proteinase-activated Receptor-1 (PAR1)*

    PubMed Central

    Mihara, Koichiro; Ramachandran, Rithwik; Renaux, Bernard; Saifeddine, Mahmoud; Hollenberg, Morley D.

    2013-01-01

    Neutrophil proteinases released at sites of inflammation can affect tissue function by either activating or disarming signal transduction mediated by proteinase-activated receptors (PARs). Because PAR1 is expressed at sites where abundant neutrophil infiltration occurs, we hypothesized that neutrophil-derived enzymes might also regulate PAR1 signaling. We report here that both neutrophil elastase and proteinase-3 cleave the human PAR1 N terminus at sites distinct from the thrombin cleavage site. This cleavage results in a disarming of thrombin-activated calcium signaling through PAR1. However, the distinct non-canonical tethered ligands unmasked by neutrophil elastase and proteinase-3, as well as synthetic peptides with sequences derived from these novel exposed tethered ligands, selectively stimulated PAR1-mediated mitogen-activated protein kinase activation. This signaling was blocked by pertussis toxin, implicating a Gαi-triggered signal pathway. We conclude that neutrophil proteinases trigger biased PAR1 signaling and we describe a novel set of tethered ligands that are distinct from the classical tethered ligand revealed by thrombin. We further demonstrate the function of this biased signaling in regulating endothelial cell barrier integrity. PMID:24052258

  1. Triggered plasma opening switch

    DOEpatents

    Mendel, Clifford W.

    1988-01-01

    A triggerable opening switch for a very high voltage and current pulse includes a transmission line extending from a source to a load and having an intermediate switch section including a plasma for conducting electrons between transmission line conductors and a magnetic field for breaking the plasma conduction path and magnetically insulating the electrons when it is desired to open the switch.

  2. Disambiguating Syntactic Triggers

    ERIC Educational Resources Information Center

    Sakas, William Gregory; Fodor, Janet Dean

    2012-01-01

    We present data from an artificial language domain that suggest new contributions to the theory of syntactic triggers. Whether a learning algorithm is capable of matching the achievements of child learners depends in part on how much parametric ambiguity there is in the input. For practical reasons this cannot be established for the domain of all…

  3. Triggered plasma opening switch

    SciTech Connect

    Mendel, C W

    1988-02-23

    A triggerable opening switch for a very high voltage and current pulse includes a transmission line extending from a source to a load and having an intermediate switch section including a plasma for conducting electrons between transmission line conductors and a magnetic field for breaking the plasma conduction path and magnetically insulating the electrons when it is desired to open the switch.

  4. Optically triggered infrared photodetector.

    PubMed

    Ramiro, Íñigo; Martí, Antonio; Antolín, Elisa; López, Esther; Datas, Alejandro; Luque, Antonio; Ripalda, José M; González, Yolanda

    2015-01-14

    We demonstrate a new class of semiconductor device: the optically triggered infrared photodetector (OTIP). This photodetector is based on a new physical principle that allows the detection of infrared light to be switched ON and OFF by means of an external light. Our experimental device, fabricated using InAs/AlGaAs quantum-dot technology, demonstrates normal incidence infrared detection in the 2-6 μm range. The detection is optically triggered by a 590 nm light-emitting diode. Furthermore, the detection gain is achieved in our device without an increase of the noise level. The novel characteristics of OTIPs open up new possibilities for third generation infrared imaging systems ( Rogalski, A.; Antoszewski, J.; Faraone, L. J. Appl. Phys. 2009, 105 (9), 091101). PMID:25490236

  5. Optically triggered infrared photodetector.

    PubMed

    Ramiro, Íñigo; Martí, Antonio; Antolín, Elisa; López, Esther; Datas, Alejandro; Luque, Antonio; Ripalda, José M; González, Yolanda

    2015-01-14

    We demonstrate a new class of semiconductor device: the optically triggered infrared photodetector (OTIP). This photodetector is based on a new physical principle that allows the detection of infrared light to be switched ON and OFF by means of an external light. Our experimental device, fabricated using InAs/AlGaAs quantum-dot technology, demonstrates normal incidence infrared detection in the 2-6 μm range. The detection is optically triggered by a 590 nm light-emitting diode. Furthermore, the detection gain is achieved in our device without an increase of the noise level. The novel characteristics of OTIPs open up new possibilities for third generation infrared imaging systems ( Rogalski, A.; Antoszewski, J.; Faraone, L. J. Appl. Phys. 2009, 105 (9), 091101).

  6. Neural networks for triggering

    SciTech Connect

    Denby, B. ); Campbell, M. ); Bedeschi, F. ); Chriss, N.; Bowers, C. ); Nesti, F. )

    1990-01-01

    Two types of neural network beauty trigger architectures, based on identification of electrons in jets and recognition of secondary vertices, have been simulated in the environment of the Fermilab CDF experiment. The efficiencies for B's and rejection of background obtained are encouraging. If hardware tests are successful, the electron identification architecture will be tested in the 1991 run of CDF. 10 refs., 5 figs., 1 tab.

  7. Dopamine triggers heterosynaptic plasticity.

    PubMed

    Ishikawa, Masago; Otaka, Mami; Huang, Yanhua H; Neumann, Peter A; Winters, Bradley D; Grace, Anthony A; Schlüter, Oliver M; Dong, Yan

    2013-04-17

    As a classic neuromodulator, dopamine has long been thought to modulate, rather than trigger, synaptic plasticity. In contrast, our present results demonstrate that within the parallel projections of dopaminergic and GABAergic terminals from the ventral tegmental area to the nucleus accumbens core (NAcCo), action-potential-activated release of dopamine heterosynaptically triggers LTD at GABAergic synapses, which is likely mediated by activating presynaptically located dopamine D1 class receptors and expressed by inhibiting presynaptic release of GABA. Moreover, this dopamine-mediated heterosynaptic LTD is abolished after withdrawal from cocaine exposure. These results suggest that action-potential-dependent dopamine release triggers very different cellular consequences from those induced by volume release or pharmacological manipulation. Activation of the ventral tegmental area to NAcCo projections is essential for emotional and motivational responses. This dopamine-mediated LTD allows a flexible output of NAcCo neurons, whereas disruption of this LTD may contribute to the rigid emotional and motivational state observed in addicts during cocaine withdrawal.

  8. Isolating Triggered Star Formation

    SciTech Connect

    Barton, Elizabeth J.; Arnold, Jacob A.; Zentner, Andrew R.; Bullock, James S.; Wechsler, Risa H.; /KIPAC, Menlo Park /SLAC

    2007-09-12

    Galaxy pairs provide a potentially powerful means of studying triggered star formation from galaxy interactions. We use a large cosmological N-body simulation coupled with a well-tested semi-analytic substructure model to demonstrate that the majority of galaxies in close pairs reside within cluster or group-size halos and therefore represent a biased population, poorly suited for direct comparison to 'field' galaxies. Thus, the frequent observation that some types of galaxies in pairs have redder colors than 'field' galaxies is primarily a selection effect. We use our simulations to devise a means to select galaxy pairs that are isolated in their dark matter halos with respect to other massive subhalos (N= 2 halos) and to select a control sample of isolated galaxies (N= 1 halos) for comparison. We then apply these selection criteria to a volume-limited subset of the 2dF Galaxy Redshift Survey with M{sub B,j} {le} -19 and obtain the first clean measure of the typical fraction of galaxies affected by triggered star formation and the average elevation in the star formation rate. We find that 24% (30.5 %) of these L* and sub-L* galaxies in isolated 50 (30) h{sup -1} kpc pairs exhibit star formation that is boosted by a factor of {approx}> 5 above their average past value, while only 10% of isolated galaxies in the control sample show this level of enhancement. Thus, 14% (20 %) of the galaxies in these close pairs show clear triggered star formation. Our orbit models suggest that 12% (16%) of 50 (30) h{sup -1} kpc close pairs that are isolated according to our definition have had a close ({le} 30 h{sup -1} kpc) pass within the last Gyr. Thus, the data are broadly consistent with a scenario in which most or all close passes of isolated pairs result in triggered star formation. The isolation criteria we develop provide a means to constrain star formation and feedback prescriptions in hydrodynamic simulations and a very general method of understanding the importance of

  9. Regulation of insulin-like growth factor I transcription by cyclic adenosine 3',5'-monophosphate (cAMP) in fetal rat bone cells through an element within exon 1: protein kinase A-dependent control without a consensus AMP response element

    NASA Technical Reports Server (NTRS)

    McCarthy, T. L.; Thomas, M. J.; Centrella, M.; Rotwein, P.

    1995-01-01

    Insulin-like growth factor I (IGF-I) is a locally synthesized anabolic growth factor for bone. IGF-I synthesis by primary fetal rat osteoblasts (Ob) is stimulated by agents that increase the intracellular cAMP concentration, including prostaglandin E2 (PGE2). Previous studies with Ob cultures demonstrated that PGE2 enhanced IGF-I transcription through selective use of IGF-I promoter 1, with little effect on IGF-I messenger RNA half-life. Transient transfection of Ob cultures with an array of promoter 1-luciferase reporter fusion constructs has now allowed localization of a potential cis-acting promoter element(s) responsible for cAMP-stimulated gene expression to the 5'-untranslated region (5'-UTR) of IGF-I exon 1, within a segment lacking a consensus cAMP response element. Our evidence derives from three principal observations: 1) a transfection construct containing only 122 nucleotides (nt) of promoter 1 and 328 nt of the 5'-UTR retained full PGE2-stimulated reporter expression; 2) maximal PGE2-driven reporter expression required the presence of nt 196 to 328 of exon 1 when tested within the context of IGF-I promoter 1; 3) cotransfection of IGF-I promoter-luciferase-reporter constructs with a plasmid encoding the alpha-isoform of the catalytic subunit of murine cAMP-dependent protein kinase (PKA) produced results comparable to those seen with PGE2 treatment, whereas cotransfection with a plasmid encoding a mutant regulatory subunit of PKA that cannot bind cAMP blocked PGE2-induced reporter expression. Deoxyribonuclease I footprinting of the 5'-UTR of exon 1 demonstrated protected sequences at HS3A, HS3B, and HS3D, three of six DNA-protein binding sites previously characterized with rat liver nuclear extracts. Of these three regions, only the HS3D binding site is located within the functionally identified hormonally responsive segment of IGF-I exon 1. These results directly implicate PKA in the control of IGF-I gene transcription by PGE2 and identify a segment of

  10. Triggering filamentation using turbulence

    NASA Astrophysics Data System (ADS)

    Eeltink, D.; Berti, N.; Marchiando, N.; Hermelin, S.; Gateau, J.; Brunetti, M.; Wolf, J. P.; Kasparian, J.

    2016-09-01

    We study the triggering of single filaments due to turbulence in the beam path for a laser of power below the filamenting threshold. Turbulence can act as a switch between the beam not filamenting and producing single filaments. This positive effect of turbulence on the filament probability, combined with our observation of off-axis filaments, suggests the underlying mechanism is modulation instability caused by transverse perturbations. We hereby experimentally explore the interaction of modulation instability and turbulence, commonly associated with multiple filaments, in the single-filament regime.

  11. Subnanosecond trigger system for ETA

    SciTech Connect

    Cook, E.G.; Lauer, E.J.; Reginato, L.L.; Rogers D.; Schmidt, J.A.

    1980-05-30

    A high-voltage trigger system capable of triggering 30, 250 kV spark gaps; each with less than +- 1 ns jitter has been constructed. In addition to low jitter rates, the trigger system must be capable of delivering the high voltage pulses to the spark gaps either simultaneously or sequentially as determined by other system requirements. The trigger system consists of several stages of pulse amplification culminating in 160 kV pulses having 30 ns risetime. The trigger system is described and test data provided.

  12. Trigger point therapy.

    PubMed

    Janssens, L A

    1992-03-01

    Trigger points (TP) are objectively demonstrable foci in muscles. They are painful on compression and trigger pain in a referred area. This area may be the only locus of complaint in humans. In dogs we cannot prove the existence of referred zones of pain. Therefore, we can only diagnose a TP-induced claudication if we cannot find bone, joint, or neurologic abnormalities, and we do find TP that disappear after treatment together with the original lameness. Several methods have been developed to demonstrate TP existence objectively. These are pressure algometry, pressure threshold measurements, magnetic resonance thermography, and histology. In humans, 71% of the TP described are acupuncture points. TP treatment consists of TP stimulation with non-invasive or invasive methods such as dry needling or injections. In the dog, ten TP are described in two categories of clinical patients. First, those with one or few TP reacting favorably on treatment (+/- 80% success in +/- 2-3 weeks). Second, those with many TPs reacting badly on treatment. Most probably the latter group are fibromyalgia patients.

  13. Latent myofascial trigger points.

    PubMed

    Ge, Hong-You; Arendt-Nielsen, Lars

    2011-10-01

    A latent myofascial trigger point (MTP) is defined as a focus of hyperirritability in a muscle taut band that is clinically associated with local twitch response and tenderness and/or referred pain upon manual examination. Current evidence suggests that the temporal profile of the spontaneous electrical activity at an MTP is similar to focal muscle fiber contraction and/or muscle cramp potentials, which contribute significantly to the induction of local tenderness and pain and motor dysfunctions. This review highlights the potential mechanisms underlying the sensory-motor dysfunctions associated with latent MTPs and discusses the contribution of central sensitization associated with latent MTPs and the MTP network to the spatial propagation of pain and motor dysfunctions. Treating latent MTPs in patients with musculoskeletal pain may not only decrease pain sensitivity and improve motor functions, but also prevent latent MTPs from transforming into active MTPs, and hence, prevent the development of myofascial pain syndrome.

  14. Gravity triggered neutrino condensates

    SciTech Connect

    Barenboim, Gabriela

    2010-11-01

    In this work we use the Schwinger-Dyson equations to study the possibility that an enhanced gravitational attraction triggers the formation of a right-handed neutrino condensate, inducing dynamical symmetry breaking and generating a Majorana mass for the right-handed neutrino at a scale appropriate for the seesaw mechanism. The composite field formed by the condensate phase could drive an early epoch of inflation. We find that to the lowest order, the theory does not allow dynamical symmetry breaking. Nevertheless, thanks to the large number of matter fields in the model, the suppression by additional powers in G of higher order terms can be compensated, boosting them up to their lowest order counterparts. This way chiral symmetry can be broken dynamically and the infrared mass generated turns out to be in the expected range for a successful seesaw scenario.

  15. The CMS high level trigger

    NASA Astrophysics Data System (ADS)

    Gori, Valentina

    2014-05-01

    The CMS experiment has been designed with a 2-level trigger system: the Level 1 Trigger, implemented on custom-designed electronics, and the High Level Trigger (HLT), a streamlined version of the CMS offline reconstruction software running on a computer farm. A software trigger system requires a tradeoff between the complexity of the algorithms running on the available computing power, the sustainable output rate, and the selection efficiency. Here we will present the performance of the main triggers used during the 2012 data taking, ranging from simpler single-object selections to more complex algorithms combining different objects, and applying analysis-level reconstruction and selection. We will discuss the optimisation of the triggers and the specific techniques to cope with the increasing LHC pile-up, reducing its impact on the physics performance.

  16. The CMS High Level Trigger

    NASA Astrophysics Data System (ADS)

    Trocino, Daniele

    2014-06-01

    The CMS experiment has been designed with a two-level trigger system: the Level-1 Trigger, implemented in custom-designed electronics, and the High-Level Trigger (HLT), a streamlined version of the CMS offline reconstruction software running on a computer farm. A software trigger system requires a tradeoff between the complexity of the algorithms running with the available computing power, the sustainable output rate, and the selection efficiency. We present the performance of the main triggers used during the 2012 data taking, ranging from simple single-object selections to more complex algorithms combining different objects, and applying analysis-level reconstruction and selection. We discuss the optimisation of the trigger and the specific techniques to cope with the increasing LHC pile-up, reducing its impact on the physics performance.

  17. The NA62 trigger system

    NASA Astrophysics Data System (ADS)

    Krivda, M.; NA62 Collaboration

    2013-08-01

    The main aim of the NA62 experiment (NA62 Technical Design Report, [1]) is to study ultra-rare Kaon decays. In order to select rare events over the overwhelming background, central systems with high-performance, high bandwidth, flexibility and configurability are necessary, that minimize dead time while maximizing data collection reliability. The NA62 experiment consists of 12 sub-detector systems and several trigger and control systems, for a total channel count of less than 100,000. The GigaTracKer (GTK) has the largest number of channels (54,000), and the Liquid Krypton (LKr) calorimeter shares with it the largest raw data rate (19 GB/s). The NA62 trigger system works with 3 trigger levels. The first trigger level is based on a hardware central trigger unit, so-called L0 Trigger Processor (L0TP), and Local Trigger Units (LTU), which are all located in the experimental cavern. Other two trigger levels are based on software, and done with a computer farm located on surface. The L0TP receives information from triggering sub-detectors asynchronously via Ethernet; it processes the information, and then transmits a final trigger decision synchronously to each sub-detector through the Trigger and Timing Control (TTC) system. The interface between L0TP and the TTC system, which is used for trigger and clock distribution, is provided by the Local Trigger Unit board (LTU). The LTU can work in two modes: global and stand-alone. In the global mode, the LTU provides an interface between L0TP and TTC system. In the stand-alone mode, the LTU can fully emulate L0TP and so provides an independent way for each sub-detector for testing or calibration purposes. In addition to the emulation functionality, a further functionality is implemented that allows to synchronize the clock of the LTU with the L0TP and the TTC system. For testing and debugging purposes, a Snap Shot Memory (SSM) interface is implemented, that can work

  18. Triggering requirements for SSC physics

    SciTech Connect

    Gilchriese, M.G.D.

    1989-04-01

    Some aspects of triggering requirements for high P{sub T} physics processes at the Superconducting Super Collider (SSC) are described. A very wide range of trigger types will be required to enable detection of the large number of potential physics signatures possible at the SSC. Although in many cases trigger rates are not now well understood, it is possible to conclude that the ability to trigger on transverse energy, number and energy of jets, number and energy of leptons (electrons and muons), missing energy and combinations of these will be required. An SSC trigger system must be both highly flexible and redundant to ensure reliable detection of many new physics processes at the SSC.

  19. International evaluation of unrecognizably uglifying human faces in late and severe secondary hyperparathyroidism in chronic kidney disease. Sagliker syndrome. A unique catastrophic entity, cytogenetic studies for chromosomal abnormalities, calcium-sensing receptor gene and GNAS1 mutations. Striking and promising missense mutations on the GNAS1 gene exons 1, 4, 10, 4.

    PubMed

    Yildiz, Ismail; Sagliker, Yahya; Demirhan, Osman; Tunc, Erdal; Inandiklioglu, Nihal; Tasdemir, Deniz; Acharya, Vidya; Zhang, Ling; Golea, Ovidia; Sabry, Alaa; Ookalkar, Dhananjay S; Capusa, Cristina; Radulescu, Dana; Garneata, Liliana; Mircescu, Gabriel; Ben Maiz, Hedi; Chen, Cheng Hsu; Prado Rome, Jorge; Benzegoutta, Mansour; Paylar, Nuray; Eyuboglu, Kamil; Karatepe, Ersin; Esenturk, Mustafa; Yavascan, Onder; Grzegorzevska, Alicza; Shilo, Valery; Mazdeh, Mitra Mahdavi; Francesco, Ramos Carillo; Gouda, Zaghloul; Adam, Siddik Momin; Emir, Idris; Ocal, Faith; Usta, Erol; Kiralp, Necati; Sagliker, Cemal; Ozkaynak, Piril Sagliker; Sagliker, Hasan Sabit; Bassuoni, Mahmoud; Sekin, Oktay

    2012-01-01

    Hypotheses explaining pathogenesis of secondary hyperparathyroidism (SH) in late and severe CKD as a unique entity called Sagliker syndrome (SS) are still unclear. This international study contains 60 patients from Turkey, India, Malaysia, China, Romania, Egypt, Tunisia, Taiwan, Mexico, Algeria, Poland, Russia, and Iran. We examined patients and first degree relatives for cytogenetic chromosomal abnormalities, calcium sensing receptor (Ca SR) genes in exons 2 and 3 abnormalities and GNAS1 genes mutations in exons 1, 4, 5, 7, 10, 13. Our syndrome could be a new syndrome in between SH, CKD, and hereditary bone dystrophies. We could not find chromosomal abnormalities in cytogenetics and on Ca SR gene exons 2 and 3. Interestingly, we did find promising missense mutations on the GNAS1 gene exons 1, 4, 10, 4. We finally thought that those catastrophic bone diseases were severe SH and its late treatments due to monetary deficiencies and iatrogenic mistreatments not started as early as possible. This was a sine qua non humanity task. Those brand new striking GNAS1 genes missense mutations have to be considered from now on for the genesis of SS. PMID:22200434

  20. Seismology: dynamic triggering of earthquakes.

    PubMed

    Gomberg, Joan; Johnson, Paul

    2005-10-01

    After an earthquake, numerous smaller shocks are triggered over distances comparable to the dimensions of the mainshock fault rupture, although they are rare at larger distances. Here we analyse the scaling of dynamic deformations (the stresses and strains associated with seismic waves) with distance from, and magnitude of, their triggering earthquake, and show that they can cause further earthquakes at any distance if their amplitude exceeds several microstrain, regardless of their frequency content. These triggering requirements are remarkably similar to those measured in the laboratory for inducing dynamic elastic nonlinear behaviour, which suggests that the underlying physics is similar.

  1. Pulsed thyristor trigger control circuit

    NASA Technical Reports Server (NTRS)

    Nola, F. J. (Inventor)

    1984-01-01

    A trigger control circuit is provided for producing firing pulses for the thyristor of a thyristor control system such as a power factor controller. The control circuit overcomes thyristor triggering problems involved with the current lag associated with controlling inductive loads and utilizes a phase difference signal, already present in the power factor controller, in deriving a signal for inhibiting generation of a firing pulse until no load current is flowing from the preceding half cycle and thereby ensuring that the thyristor is triggered on during each half cycle.

  2. Triggered Release from Polymer Capsules

    SciTech Connect

    Esser-Kahn, Aaron P.; Odom, Susan A.; Sottos, Nancy R.; White, Scott R.; Moore, Jeffrey S.

    2011-07-06

    Stimuli-responsive capsules are of interest in drug delivery, fragrance release, food preservation, and self-healing materials. Many methods are used to trigger the release of encapsulated contents. Here we highlight mechanisms for the controlled release of encapsulated cargo that utilize chemical reactions occurring in solid polymeric shell walls. Triggering mechanisms responsible for covalent bond cleavage that result in the release of capsule contents include chemical, biological, light, thermal, magnetic, and electrical stimuli. We present methods for encapsulation and release, triggering methods, and mechanisms and conclude with our opinions on interesting obstacles for chemically induced activation with relevance for controlled release.

  3. Landslide triggering modeling in Switzerland

    NASA Astrophysics Data System (ADS)

    Jafari Manesh, Ahoura; Mignan, Arnaud; Giardini, Domenico

    2016-04-01

    Switzerland is prone to hazard interactions due to its mountainous landscape. Historical earthquakes are known to have triggered aftershocks, landslides, rock falls and avalanches, as well as lake tsunamis. Here we present a simple cellular automaton to simulate landslide footprints triggered by both rain and earthquakes. The method is based on the Sandpile model, which dynamics is controlled by the ground slope. Rain levels are approximated by ground water saturation and earthquake-landslide triggering is evaluated using the concept of Newmark displacement. That concept is then modified to estimate stable slopes during shaking at which locations the landslide stops. The cellular automaton is first tested in a virtual region where a parameter sensitivity analysis is made. Then it is tested in a region of Switzerland, where historic landslides triggered by earthquakes are known to have occurred.

  4. Stimuli triggering violence in psychoses.

    PubMed

    Pontius, A A

    1981-01-01

    Various behavioral and neurophysiological models are suggested to objectify and quantify the defense of insanity and to assess dangerousness in someone who is being considered for release from custody. Two cases are presented that show a pattern of specific relationships between traumatic experiences in youth and a later trigger stimulus that releases homicidal action. Until a refined classification system and neurophysiological understanding of sudden aggression can be achieved, forensic psychiatrists should be aware of the psychotic trigger reaction within a clinical psychiatric model.

  5. Anthropogenic triggering of large earthquakes.

    PubMed

    Mulargia, Francesco; Bizzarri, Andrea

    2014-01-01

    The physical mechanism of the anthropogenic triggering of large earthquakes on active faults is studied on the basis of experimental phenomenology, i.e., that earthquakes occur on active tectonic faults, that crustal stress values are those measured in situ and, on active faults, comply to the values of the stress drop measured for real earthquakes, that the static friction coefficients are those inferred on faults, and that the effective triggering stresses are those inferred for real earthquakes. Deriving the conditions for earthquake nucleation as a time-dependent solution of the Tresca-Von Mises criterion applied in the framework of poroelasticity yields that active faults can be triggered by fluid overpressures < 0.1 MPa. Comparing this with the deviatoric stresses at the depth of crustal hypocenters, which are of the order of 1-10 MPa, we find that injecting in the subsoil fluids at the pressures typical of oil and gas production and storage may trigger destructive earthquakes on active faults at a few tens of kilometers. Fluid pressure propagates as slow stress waves along geometric paths operating in a drained condition and can advance the natural occurrence of earthquakes by a substantial amount of time. Furthermore, it is illusory to control earthquake triggering by close monitoring of minor "foreshocks", since the induction may occur with a delay up to several years.

  6. Anthropogenic triggering of large earthquakes.

    PubMed

    Mulargia, Francesco; Bizzarri, Andrea

    2014-01-01

    The physical mechanism of the anthropogenic triggering of large earthquakes on active faults is studied on the basis of experimental phenomenology, i.e., that earthquakes occur on active tectonic faults, that crustal stress values are those measured in situ and, on active faults, comply to the values of the stress drop measured for real earthquakes, that the static friction coefficients are those inferred on faults, and that the effective triggering stresses are those inferred for real earthquakes. Deriving the conditions for earthquake nucleation as a time-dependent solution of the Tresca-Von Mises criterion applied in the framework of poroelasticity yields that active faults can be triggered by fluid overpressures < 0.1 MPa. Comparing this with the deviatoric stresses at the depth of crustal hypocenters, which are of the order of 1-10 MPa, we find that injecting in the subsoil fluids at the pressures typical of oil and gas production and storage may trigger destructive earthquakes on active faults at a few tens of kilometers. Fluid pressure propagates as slow stress waves along geometric paths operating in a drained condition and can advance the natural occurrence of earthquakes by a substantial amount of time. Furthermore, it is illusory to control earthquake triggering by close monitoring of minor "foreshocks", since the induction may occur with a delay up to several years. PMID:25156190

  7. Anthropogenic Triggering of Large Earthquakes

    PubMed Central

    Mulargia, Francesco; Bizzarri, Andrea

    2014-01-01

    The physical mechanism of the anthropogenic triggering of large earthquakes on active faults is studied on the basis of experimental phenomenology, i.e., that earthquakes occur on active tectonic faults, that crustal stress values are those measured in situ and, on active faults, comply to the values of the stress drop measured for real earthquakes, that the static friction coefficients are those inferred on faults, and that the effective triggering stresses are those inferred for real earthquakes. Deriving the conditions for earthquake nucleation as a time-dependent solution of the Tresca-Von Mises criterion applied in the framework of poroelasticity yields that active faults can be triggered by fluid overpressures < 0.1 MPa. Comparing this with the deviatoric stresses at the depth of crustal hypocenters, which are of the order of 1–10 MPa, we find that injecting in the subsoil fluids at the pressures typical of oil and gas production and storage may trigger destructive earthquakes on active faults at a few tens of kilometers. Fluid pressure propagates as slow stress waves along geometric paths operating in a drained condition and can advance the natural occurrence of earthquakes by a substantial amount of time. Furthermore, it is illusory to control earthquake triggering by close monitoring of minor “foreshocks”, since the induction may occur with a delay up to several years. PMID:25156190

  8. Relationships between age and epi-genotype of the FMR1 exon 1/intron 1 boundary are consistent with non-random X-chromosome inactivation in FM individuals, with the selection for the unmethylated state being most significant between birth and puberty.

    PubMed

    Godler, David E; Inaba, Yoshimi; Shi, Elva Z; Skinner, Cindy; Bui, Quang M; Francis, David; Amor, David J; Hopper, John L; Loesch, Danuta Z; Hagerman, Randi J; Schwartz, Charles E; Slater, Howard R

    2013-04-15

    Methylation of the fragile X-related epigenetic element 2 (FREE2) located on the exon 1/intron 1 boundary of the FMR1 gene is related to FMRP expression and cognitive impairment in full mutation (FM; CGG>200) individuals. We examined the relationship between age, the size of the FMR1 CGG expansion and the methylation output ratio (MOR) at 12 CpG sites proximal to the exon 1/intron 1 boundary using FREE2 MALDI-TOF MS. The patient cohort included 119 males and 368 females, i.e. 121 healthy controls (CGG<40), 176 premutation (CGG 55-170) and 190 FM (CGG 213-2000). For all CpG units examined, FM males showed a significantly elevated MOR compared with that in hypermethylated FM females. In FM males the MOR for most CpG units significantly positively correlated with both age and CGG size (P< 0.05). In FM females the skewing towards the unmethylated state was significant for half of the units between birth and puberty (P < 0.05). The methylation status of intron 1 CpG10-12 that was most significantly related to cognitive impairment in our earlier study, did not change significantly with age in FM females. These results challenge the concept of fragile X syndrome (FXS)-related methylation being static over time, and suggest that due to the preference for the unmethylated state in FM females, X-inactivation at this locus is not random. The findings also highlight that the prognostic value of FXS methylation testing is not uniform between all CpG sites, and thus may need to be evaluated on a site-by-site basis.

  9. Integral magnetic ignition pickup trigger

    SciTech Connect

    King, R.

    1992-10-27

    This patent describes a trigger system for the ignition system of an internal combustion engine having a crankcase with a rotatable crankshaft therein, and a flywheel on one end of the crankcase connected to an end of the crankshaft. It comprises: a nonferromagnetic disk-shaped hub for connection to the crankshaft and rotatable therewith on the end opposite the flywheel; and a stationary sensor mounted adjacent the hub for detecting impulses from the magnetically responsive elements as the hub rotates and utilizing the impulses to trigger the ignition system.

  10. Know Your Smoking Triggers | Smokefree.gov

    Cancer.gov

    Triggers are the things that make you want to smoke. Different people have different triggers, like a stressful situation, sipping coffee, going to a party, or smelling cigarette smoke. Most triggers fall into one of these four categories: Emotional Pattern Social Withdrawal Knowing your triggers and understanding the best way to deal with them is your first line of defense.

  11. A New Look at Trigger Point Injections

    PubMed Central

    Wong, Clara S. M.; Wong, Steven H. S.

    2012-01-01

    Trigger point injections are commonly practised pain interventional techniques. However, there is still lack of objective diagnostic criteria for trigger points. The mechanisms of action of trigger point injection remain obscure and its efficacy remains heterogeneous. The advent of ultrasound technology in the noninvasive real-time imaging of soft tissues sheds new light on visualization of trigger points, explaining the effect of trigger point injection by blockade of peripheral nerves, and minimizing the complications of blind injection. PMID:21969825

  12. Environmental Triggers of Autoimmune Thyroiditis

    PubMed Central

    Burek, C. Lynne; Talor, Monica V.

    2009-01-01

    Autoimmune thyroiditis is among the most prevalent of all the autoimmunities. Autoimmune thyroiditis is multifactorial with contributions from genetic and environmental factors. Much information has been published about the genetic predisposition to autoimmune thyroiditis both in experimental animals and humans. There is, in contrast, very little data on environmental agents that can serve as the trigger or autoimmunity in a genetically predisposed host. The best-established environmental factor is excess dietary iodine. Increased iodine consumption is strongly implicated as a trigger for thyroiditis, but only in genetically susceptible individuals. However, excess iodine is not the only environmental agent implicated as a trigger leading to autoimmune thyroiditis. There are a wide variety of other synthetic chemicals that affect the thyroid gland or have the ability to promote immune dysfunction in the host. These chemicals are released into the environment by design, such as in pesticides, or as a by-product of industry. Candidate pollutants include polyaromatic hydrocarbons, polybrominated biphenols, and polychlorinated biphenols, among others. Infections are also reputed to trigger autoimmunity and may act alone or in concert with environmental chemicals. We have utilized a unique animal model, the NOD.H2h4 mouse to explore the influence of iodine and other environmental factors on autoimmune thyroiditis. PMID:19818584

  13. Environmental triggers of autoimmune thyroiditis.

    PubMed

    Burek, C Lynne; Talor, Monica V

    2009-01-01

    Autoimmune thyroiditis is among the most prevalent of all the autoimmunities. Autoimmune thyroiditis is multifactorial with contributions from genetic and environmental factors. Much information has been published about the genetic predisposition to autoimmune thyroiditis both in experimental animals and humans. There is, in contrast, very little data on environmental agents that can serve as the trigger for autoimmunity in a genetically predisposed host. The best-established environmental factor is excess dietary iodine. Increased iodine consumption is strongly implicated as a trigger for thyroiditis, but only in genetically susceptible individuals. However, excess iodine is not the only environmental agent implicated as a trigger leading to autoimmune thyroiditis. There are a wide variety of other synthetic chemicals that affect the thyroid gland or have the ability to promote immune dysfunction in the host. These chemicals are released into the environment by design, such as in pesticides, or as a by-product of industry. Candidate pollutants include polyaromatic hydrocarbons, polybrominated biphenols, and polychlorinated biphenols, among others. Infections are also reputed to trigger autoimmunity and may act alone or in concert with environmental chemicals. We have utilized a unique animal model, the NOD.H2(h4) mouse to explore the influence of iodine and other environmental factors on autoimmune thyroiditis. PMID:19818584

  14. Suicide Triggers Described by Herodotus

    PubMed Central

    Auchincloss, Stephane; Ahmadi, Jamshid

    2016-01-01

    Objective: The aim of this study was to better understand the triggers of suicide, particularly among the ancient Greek and Persian soldiers and commanders. Method: ‘Herodotus:TheHistories’ is a history of the rulers and soldiery who participated in the Greco-Persian wars (492-449 BCE). A new translation (2013) of this manuscript was studied. Accounts of suicide were collected and collated, with descriptions of circumstances, methods, and probable triggers. Results: Nine accounts of suicide were identified. Eight of these were named individuals (4 Greeks and 4 Persians); of whom, seven were male. Only one (not the female) appeared to act in response to a mental disorder. Other triggers of suicide included guilt, avoidance of dishonour/punishment and altruism. Cutting/ stabbing was the most common method; others included hanging, jumping, poison, and burning (the single female). Conclusion: While soldiers at a time of war do not reflect the general community, they are nevertheless members of their society. Thus, this evidence demonstrates that suicide triggered by burdensome circumstances (in addition to mental disorder) was known to the Greek and Persian people more than two millennia ago. PMID:27437010

  15. Triggering Reform at Public Schools

    ERIC Educational Resources Information Center

    Kelly, Andrew P.

    2012-01-01

    An intriguing experiment is afoot in some of the nation's struggling public schools. New "Parent Trigger" laws passed in California and on the agenda in New York, Ohio, Colorado, and Chicago, allow parents of chronically failing schools to unseat the schools' leadership and staff. But the initiative has pitfalls. It's easy to mobilize parents to…

  16. Host defenses trigger salmonella's arsenal.

    PubMed

    Keestra, A Marijke; Bäumler, Andreas J

    2011-03-17

    Salmonella survives in macrophages by using a molecular syringe to deliver proteins into the host-cell cytosol where they manipulate phagocyte physiology. Arpaia and colleagues (Arpaia et al., 2011) show that deployment of this virulence factor is triggered by the very responses that are intended to confer host resistance. PMID:21402352

  17. Trigger Finger: Adult and Pediatric Treatment Strategies.

    PubMed

    Giugale, Juan M; Fowler, John R

    2015-10-01

    Trigger fingers are common tendinopathies representing a stenosing flexor tenosynovitis of the fingers. Adult trigger finger can be treated nonsurgically using activity modification, splinting, and/or corticosteroid injections. Surgical treatment options include percutaneous A1 pulley release and open A1 pulley release. Excision of a slip of the flexor digitorum superficialis is reserved for patients with persistent triggering despite A1 release or patients with persistent flexion contracture. Pediatric trigger thumb is treated with open A1 pulley release. Pediatric trigger finger is treated with release of the A1 pulley with excision of a slip or all of the flexor digitorum superficialis if triggering persists. PMID:26410644

  18. Method for triggering an action

    DOEpatents

    Hall, David R.; Bartholomew, David B.; Johnson, Monte L.; Moon, Justin; Koehler, Roger O.

    2006-10-17

    A method for triggering an action of at least one downhole device on a downhole network integrated into a downhole tool string synchronized to an event comprises determining latency, sending a latency adjusted signal, and performing the action. The latency is determined between a control device and the at least one downhole device. The latency adjusted signal for triggering an action is sent to the downhole device. The action is performed downhole synchronized to the event. A preferred method for determining latency comprises the steps: a control device sends a first signal to the downhole device; after receiving the signal, the downhole device sends a response signal to the control device; and the control device analyzes the time from sending the signal to receiving the response signal.

  19. The CDF silicon vertex trigger

    SciTech Connect

    B. Ashmanskas; A. Barchiesi; A. Bardi

    2003-06-23

    The CDF experiment's Silicon Vertex Trigger is a system of 150 custom 9U VME boards that reconstructs axial tracks in the CDF silicon strip detector in a 15 {mu}sec pipeline. SVT's 35 {mu}m impact parameter resolution enables CDF's Level 2 trigger to distinguish primary and secondary particles, and hence to collect large samples of hadronic bottom and charm decays. We review some of SVT's key design features. Speed is achieved with custom VLSI pattern recognition, linearized track fitting, pipelining, and parallel processing. Testing and reliability are aided by built-in logic state analysis and test-data sourcing at each board's input and output, a common inter-board data link, and a universal ''Merger'' board for data fan-in/fan-out. Speed and adaptability are enhanced by use of modern FPGAs.

  20. Stimulus conflict triggers behavioral avoidance.

    PubMed

    Dignath, David; Eder, Andreas B

    2015-12-01

    According to a recent extension of the conflict-monitoring theory, conflict between two competing response tendencies is registered as an aversive event and triggers a motivation to avoid the source of conflict. In the present study, we tested this assumption. Over five experiments, we examined whether conflict is associated with an avoidance motivation and whether stimulus conflict or response conflict triggers an avoidance tendency. Participants first performed a color Stroop task. In a subsequent motivation test, participants responded to Stroop stimuli with approach- and avoidance-related lever movements. These results showed that Stroop-conflict stimuli increased the frequency of avoidance responses in a free-choice motivation test, and also increased the speed of avoidance relative to approach responses in a forced-choice test. High and low proportions of response conflict in the Stroop task had no effect on avoidance in the motivation test. Avoidance of conflict was, however, obtained even with new conflict stimuli that had not been presented before in a Stroop task, and when the Stroop task was replaced with an unrelated filler task. Taken together, these results suggest that stimulus conflict is sufficient to trigger avoidance.

  1. Stimulus conflict triggers behavioral avoidance.

    PubMed

    Dignath, David; Eder, Andreas B

    2015-12-01

    According to a recent extension of the conflict-monitoring theory, conflict between two competing response tendencies is registered as an aversive event and triggers a motivation to avoid the source of conflict. In the present study, we tested this assumption. Over five experiments, we examined whether conflict is associated with an avoidance motivation and whether stimulus conflict or response conflict triggers an avoidance tendency. Participants first performed a color Stroop task. In a subsequent motivation test, participants responded to Stroop stimuli with approach- and avoidance-related lever movements. These results showed that Stroop-conflict stimuli increased the frequency of avoidance responses in a free-choice motivation test, and also increased the speed of avoidance relative to approach responses in a forced-choice test. High and low proportions of response conflict in the Stroop task had no effect on avoidance in the motivation test. Avoidance of conflict was, however, obtained even with new conflict stimuli that had not been presented before in a Stroop task, and when the Stroop task was replaced with an unrelated filler task. Taken together, these results suggest that stimulus conflict is sufficient to trigger avoidance. PMID:25931151

  2. Setting the Triggering Thresholds on Swift

    SciTech Connect

    McLean, Kassandra M.; Fenimore, E.E.; Palmer, David; Barthelmy, S.; Gehrels, N.; Krimm, H.; Markwardt, C.; Parsons, A.

    2004-09-28

    The Burst Alert Telescope (BAT) on Swift has two main types of 'rate' triggers: short and long. Short trigger time scales range from 4ms to 64ms, while long triggers are 64ms to {approx_equal} 16 seconds. While both short and long trigger have criteria with one background sample (traditional 'one-sided' triggers), the long triggers can also have criteria with two background samples ('bracketed' triggers) which remove trends in the background. Both long and short triggers can select energy ranges of 15-25, 15-50, 25-100 and 50-350 KeV. There are more than 180 short triggering criteria and approximately 500 long triggering criteria used to detect gamma ray bursts. To fully utilize these criteria, the thresholds must be set correctly. The optimum thresholds are determined by a tradeoff between avoiding false triggers and capturing as many bursts as possible. We use realistic simulated orbital variations, which are the prime cause of false triggers.

  3. Pluripotent stem cells reveal erythroid-specific activities of the GATA1 N-terminus

    PubMed Central

    Byrska-Bishop, Marta; VanDorn, Daniel; Campbell, Amy E.; Betensky, Marisol; Arca, Philip R.; Yao, Yu; Gadue, Paul; Costa, Fernando F.; Nemiroff, Richard L.; Blobel, Gerd A.; French, Deborah L.; Hardison, Ross C.; Weiss, Mitchell J.; Chou, Stella T.

    2015-01-01

    Germline GATA1 mutations that result in the production of an amino-truncated protein termed GATA1s (where s indicates short) cause congenital hypoplastic anemia. In patients with trisomy 21, similar somatic GATA1s-producing mutations promote transient myeloproliferative disease and acute megakaryoblastic leukemia. Here, we demonstrate that induced pluripotent stem cells (iPSCs) from patients with GATA1-truncating mutations exhibit impaired erythroid potential, but enhanced megakaryopoiesis and myelopoiesis, recapitulating the major phenotypes of the associated diseases. Similarly, in developmentally arrested GATA1-deficient murine megakaryocyte-erythroid progenitors derived from murine embryonic stem cells (ESCs), expression of GATA1s promoted megakaryopoiesis, but not erythropoiesis. Transcriptome analysis revealed a selective deficiency in the ability of GATA1s to activate erythroid-specific genes within populations of hematopoietic progenitors. Although its DNA-binding domain was intact, chromatin immunoprecipitation studies showed that GATA1s binding at specific erythroid regulatory regions was impaired, while binding at many nonerythroid sites, including megakaryocytic and myeloid target genes, was normal. Together, these observations indicate that lineage-specific GATA1 cofactor associations are essential for normal chromatin occupancy and provide mechanistic insights into how GATA1s mutations cause human disease. More broadly, our studies underscore the value of ESCs and iPSCs to recapitulate and study disease phenotypes. PMID:25621499

  4. Nonenzymatic glycation at the N terminus of pathogenic prion protein in transmissible spongiform encephalopathies.

    PubMed

    Choi, Yeong-Gon; Kim, Jae-Il; Jeon, Yong-Chul; Park, Seok-Joo; Choi, Eun-Kyoung; Rubenstein, Richard; Kascsak, Richard J; Carp, Richard I; Kim, Yong-Sun

    2004-07-16

    Transmissible spongiform encephalopathies (TSEs) are transmissible neurodegenerative diseases characterized by the accumulation of an abnormally folded prion protein, termed PrPSc, and the development of pathological features of astrogliosis, vacuolation, neuronal cell loss, and in some cases amyloid plaques. Although considerable structural characterization of prion protein has been reported, neither the method of conversion of cellular prion protein, PrPC, into the pathogenic isoform nor the post-translational modification processes involved is known. We report that in animal and human TSEs, one or more lysines at residues 23, 24, and 27 of PrPSc are covalently modified with advanced glycosylation end products (AGEs), which may be carboxymethyl-lysine (CML), one of the structural varieties of AGEs. The arginine residue at position 37 may also be modified with AGE, but not the arginine residue at position 25. This result suggests that nonenzymatic glycation is one of the post-translational modifications of PrP(Sc). Furthermore, immunostaining studies indicate that, at least in clinically affected hamsters, astrocytes are the first site of this glycation process. PMID:15084583

  5. Flexibility of the alpha-spectrin N-terminus by EPR and fluorescence polarization.

    PubMed Central

    Cherry, L; Fung, L W; Menhart, N

    2000-01-01

    The structure and flexibility of the biologically important alpha-spectrin amino terminal region was examined by the use of fluorescence and EPR spectroscopy. The region studied has been previously demonstrated to be essential for the alpha-spectrin:beta-spectrin association of the tetramerization site. Appropriate spectroscopic probe moieties were coupled to this region in a recombinant fragment of human erythroid alpha-spectrin. There was good agreement between the EPR and fluorescence techniques in most of this region. Mobility determinations indicated that a portion of the region was relatively immobilized. This is significant, since although predictive methods have indicated that this region should be alpha-helical, previous experimental evidence obtained on smaller synthetic peptides had indicated that this region was disordered. Observed rigidity appears to be incompatible with such a disordered state, and has important ramifications for the flexibility of this molecule that is so integral to its role in stabilizing erythrocyte membranes. PMID:10866978

  6. The N-terminus of apolipoprotein A-V adopts a helix bundle molecular architecture.

    PubMed

    Wong, Kasuen; Beckstead, Jennifer A; Lee, Dustin; Weers, Paul M M; Guigard, Emmanuel; Kay, Cyril M; Ryan, Robert O

    2008-08-19

    Previous studies of recombinant full-length human apolipoprotein A-V (apoA-V) provided evidence of the presence of two independently folded structural domains. Computer-assisted sequence analysis and limited proteolysis studies identified an N-terminal fragment as a candidate for one of the domains. C-Terminal truncation variants in this size range, apoA-V(1-146) and apoA-V(1-169), were expressed in Escherichia coli and isolated. Unlike full-length apoA-V or apoA-V(1-169), apoA-V(1-146) was soluble in neutral-pH buffer in the absence of lipid. Sedimentation equilibrium analysis yielded a weight-average molecular weight of 18811, indicating apoA-V(1-146) exists as a monomer in solution. Guanidine HCl denaturation experiments at pH 3.0 yielded a one-step native to unfolded transition that corresponds directly with the more stable component of the two-stage denaturation profile exhibited by full-length apoA-V. On the other hand, denaturation experiments conducted at pH 7.0 revealed a less stable structure. In a manner similar to that of known helix bundle apolipoproteins, apoA-V(1-146) induced a relatively small enhancement in 8-anilino-1-naphthalenesulfonic acid fluorescence intensity. Quenching studies with single-Trp apoA-V(1-146) variants revealed that a unique site predicted to reside on the nonpolar face of an amphipathic alpha-helix was protected from quenching by KI. Taken together, the data suggest the 146 N-terminal residues of human apoA-V adopt a helix bundle molecular architecture in the absence of lipid and, thus, likely exist as an independently folded structural domain within the context of the intact protein.

  7. Infrasonic Observations from Triggered Lightning

    NASA Astrophysics Data System (ADS)

    Arechiga, R. O.; Johnson, J. B.; Edens, H. E.; Rison, W.; Thomas, R. J.; Eack, K.; Eastvedt, E. M.

    2009-12-01

    We measured acoustic signals during both triggered and natural lightning. A comparative analysis of simultaneous data from the Lightning Mapping Array (LMA), acoustic measurements and digital high-speed photography operating in the same area was made. Acoustic emissions, providing quantitative estimates of acoustic power and spectral content, will complement coincident investigations, such as X-ray emissions. Most cloud-to-ground lightning flashes lower negative charge to ground, but flashes that lower positive charge to ground are often unusually destructive and are less understood. The New Mexico Tech Lightning Mapping Array (LMA) locates the sources of impulsive RF radiation produced by lightning flashes in three spatial dimensions and time, operating in the 60 - 66 MHz television band. However, positive breakdown is rarely detected by the LMA and positive leader channels are outlined only by recoil events. Positive cloud-to-ground (CG) channels are usually not mapped (or partially mapped because they may have recoil events). Acoustic and electric field instruments are a good complement to the LMA, since they can detect both negative and positive leaders. An array of five stations was deployed during the Summer of 2009 (July 20 to August 13) in the Magdalena mountains of New Mexico, to monitor infrasound (below 20 Hz) and audio range sources due to natural and triggered lightning. The stations were located at close (57 m), medium (303 and 537 m) and far (1403 and 2556 m) distances surrounding the triggering site. Each station consisted of five sensors, one infrasonic and one in the audio range at the center, and three infrasonic in a triangular configuration. This research will provide a more complete picture, and provide further insight into the nature of lightning.

  8. Laser-triggered vacuum switch

    DOEpatents

    Brannon, Paul J.; Cowgill, Donald F.

    1990-01-01

    A laser-triggered vacuum switch has a material such as a alkali metal halide on the cathode electrode for thermally activated field emission of electrons and ions upon interaction with a laser beam, the material being in contact with the cathode with a surface facing the discharge gap. The material is preferably a mixture of KCl and Ti powders. The laser may either shine directly on the material, preferably through a hole in the anode, or be directed to the material over a fiber optic cable.

  9. Star formation and its triggers

    NASA Astrophysics Data System (ADS)

    Combes, F.

    2016-06-01

    The relation between star formation and gas density appears linear for galaxies on the main sequence, and when the molecular gas is considered. However, the star formation efficiency (SFE) defined as the ratio of SFR to gas surface densities, can be much higher when SF is triggered by a dynamical process such as galaxy interaction or mergers, or even secular evolution and cold gas accretion. I review recent work showing how the SFE can vary as a function of morphological type, environment, or redshift. Physical processes able to explain positive and negative feedback from supernovae or AGN are discussed.

  10. Dynamic Triggering of Microseismic Events

    NASA Astrophysics Data System (ADS)

    Lu, H.; Van der Baan, M.

    2015-12-01

    Microseismic events are commonly recorded during hydraulic fracturing experiments. In microseismic interpretations, each event is often regarded as independent and uncorrelated to neighboring ones. In reality, both the rock deformation (static stresses) and transient wave motion (dynamic stresses) associated with microseismic events add to the stress field together with the external loading (fluid injection). We believe the resulting static and dynamic stress perturbations will influence both the timing and spatial evolution of the microseismic cloud. We study the dynamic triggering of microseismicity using numerical simulations of a biaxial deformation test by means of a bonded particle method (Potyondy and Cundall, 2004), where crack development can be tracked and analyzed independently. Our methodology is to compare the stress changes due to one specific event with the occurrence of the next few events in the numerical simulations. In addition, we compute the dynamic stress perturbations for recorded large events analytically given their (non-double couple) failure mechanisms. Our results show that cracks following a major event tend to form in zones affected by the dynamic stresses by promoting new failure in areas that are critically stressed. This confirms that dynamic triggering during hydraulic fracturing operations but also larger scale seismicity is likely. It also demonstrates the often complex interplay between the dynamic and static stress changes and their effect on the temporal and spatial evolution of rock deformation at all scales.

  11. XI UV Laser Trigger System

    SciTech Connect

    Brickeen, B.K.; Morelli, G.L.; Paiva, R.A.; Powell, C.A.; Sundvold, P.D.

    1999-01-26

    The X1 accelerator project at Sandia National Laboratory/New Mexico utilizes SF6 insulated, multi-stage, UV laser triggered gas switches. A 265 nm UV laser system was designed and built to generate eight simultaneous output pulses of 10 mJ each with a 13 nsec pulse width. A 1061 nm solid-state Nd:Cr:GSGG laser was frequency quadrupled using a two-stage doubling process. The 1061 nm fundamental laser energy was frequency doubled with a KTP crystal to 530 nm, achieving 65% conversion efficiency. The 530 nm output was frequency doubled with KD*P crystal to 265 nm, achieving conversion efficiency of 31%. The 265 nm beam pulse was split into eight parallel channels with a system of partially reflecting mirrors. Low timing jitter and stable energy output were achieved. The entire optical system was packaged into a rugged, o-ring sealed, aluminum structure 10''x19''x2.75''. The size of the electronics was 12''x8''x8''. Subsequent accelerator system requirements dictated a redesign of the triggering system for an output beam with less angular divergence. An unstable, crossed porro prism resonator was designed and incorporated into the system. The beam divergence of the redesigned system was successfully decreased to 0.97 mrad in the UV. The resulting frequency doubling efficiencies were 55% to 530 nm and 25% to 265 nm. The optical output remained at 10 mJ in each channel with an 11 nsec pulse width.

  12. Landslides triggered by the earthquake

    SciTech Connect

    Harp, E.L.; Keefer, D.K.

    1990-01-01

    The May 2 earthquake triggered landslides numbering in the thousands. Most numerous were rockfalls and rockslides that occurred mainly on slopes steeper than 60{degree} within sandstone, siltstone, and shale units of Upper Cretaceous and Tertiary strata. Soil falls from cutbank slopes along streams were also numerous. Seven slumps in natural slopes were triggered, and minor liquefaction-induced lateral-spread failures occurred along Los Gatos Creek. Rockfalls and rockslides occurred as far as 34 km northwest, 15 km south, and 26 km southwest of the epicenter. There were few slope failures to the east of the epicenter, owing to the absence of steep slopes in that direction. Throughout the area affected, rockfalls and rockslides were concentrated on southwest-facing slopes; the failures on slopes facing in the southwest quadrant accounted for as much as 93% of all failures in some areas. Rockfalls and rockslides from ridge crests were predominantly from sandstone units. Along steeply incised canyons, however, failures in shale and siltstone units were also common. Small rockslides and soil slides occurred from cut slopes above oil-well pump pads in the oil fields; slumps were common in the outer parts of steep fill slopes of the pump pads. The distribution of seismically induced landslides throughout the entire earthquake-affected area was mapped from true-color airphotos taken on May 3, 1985.

  13. Antiviral immune responses: triggers of or triggered by autoimmunity?

    PubMed Central

    Münz, Christian; Lünemann, Jan D.; Getts, Meghann Teague; Miller, Stephen D.

    2010-01-01

    Several common autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus (SLE) and multiple sclerosis, are genetically linked to distinct human MHC class II molecules and other immune modulators. However, genetic predisposition is only one risk factor for the development of these diseases, and low concordance rates in monozygotic twins as well as geographical distribution of disease risk point towards environmental factors in the genesis of these diseases. Among these environmental factors, infections have been implicated in the onset and/or promotion of autoimmunity. In this review, we outline mechanisms by which pathogens can trigger autoimmune disease, and also pathways by which infection and immune control of infectious disease might be dysregulated during autoimmunity. PMID:19319143

  14. What triggers coronal mass ejections ?

    NASA Astrophysics Data System (ADS)

    Aulanier, Guillaume

    Coronal mass ejections (CMEs) are large clouds of highly magnetized plasma. They are ac-celerated from the solar atmosphere into interplanetary space by the Lorentz force, which is associated to their strong current-carrying magnetic fields. Both theory and observations lead to the inevitable conclusion that the launch of a CME must result from the sudden release of free magnetic energy, which has slowly been accumulated in the corona for a long time before the eruption. Since the incomplete, but seminal, loss-of-equilibrium model was proposed by van Tend and Kuperus (1978), a large variety of analytical and numerical storage-and-release MHD models has been put forward in the past 20 years or so. All these models rely on the slow increase of currents and/or the slow decrease of the restraining magnetic tension preceding the eruption. But they all put the emphazis on different physical mechanisms to achieve this preeruptive evolution, and to suddenly trigger and later drive a CME. Nevertheless, all these models actually share many common features, which all describe many individual observed aspects of solar eruptions. It is therefore not always clear which of all the suggested mecha-nisms do really account for the triggering of observed CMEs in general. Also, these mechanisms should arguably not be as numerous as the models themselves, owing to the common occurence of CMEs. In order to shed some light on this challenging, but unripe, topic, I will attempt to rediscuss the applicability of the models to the Sun, and to rethink the most sensitive ones in a common frame, so as to find their common denominator. I will elaborate on the idea that many of the proposed triggering mechanisms may actually only be considered as different ways to apply a "last push", which puts the system beyond its eruptive threshold. I will argue that, in most cases, the eruptive threshold is determined by the vertical gradient of the magnetic field in the low-β corona, just like the usual

  15. Episodic tremor triggers small earthquakes

    NASA Astrophysics Data System (ADS)

    Balcerak, Ernie

    2011-08-01

    It has been suggested that episodic tremor and slip (ETS), the weak shaking not associated with measurable earthquakes, could trigger nearby earthquakes. However, this had not been confirmed until recently. Vidale et al. monitored seismicity in the 4-month period around a 16-day episode of episodic tremor and slip in March 2010 in the Cascadia region. They observed five small earthquakes within the subducting slab during the ETS episode. They found that the timing and locations of earthquakes near the tremor suggest that the tremor and earthquakes are related. Furthermore, they observed that the rate of earthquakes across the area was several times higher within 2 days of tremor activity than at other times, adding to evidence of a connection between tremor and earthquakes. (Geochemistry, Geophysics, Geosystems, doi:10.1029/2011GC003559, 2011)

  16. Earthquake Simulator Finds Tremor Triggers

    SciTech Connect

    Johnson, Paul

    2015-03-27

    Using a novel device that simulates earthquakes in a laboratory setting, a Los Alamos researcher has found that seismic waves-the sounds radiated from earthquakes-can induce earthquake aftershocks, often long after a quake has subsided. The research provides insight into how earthquakes may be triggered and how they recur. Los Alamos researcher Paul Johnson and colleague Chris Marone at Penn State have discovered how wave energy can be stored in certain types of granular materials-like the type found along certain fault lines across the globe-and how this stored energy can suddenly be released as an earthquake when hit by relatively small seismic waves far beyond the traditional “aftershock zone” of a main quake. Perhaps most surprising, researchers have found that the release of energy can occur minutes, hours, or even days after the sound waves pass; the cause of the delay remains a tantalizing mystery.

  17. Tail reconnection triggering substorm onset.

    PubMed

    Angelopoulos, Vassilis; McFadden, James P; Larson, Davin; Carlson, Charles W; Mende, Stephen B; Frey, Harald; Phan, Tai; Sibeck, David G; Glassmeier, Karl-Heinz; Auster, Uli; Donovan, Eric; Mann, Ian R; Rae, I Jonathan; Russell, Christopher T; Runov, Andrei; Zhou, Xu-Zhi; Kepko, Larry

    2008-08-15

    Magnetospheric substorms explosively release solar wind energy previously stored in Earth's magnetotail, encompassing the entire magnetosphere and producing spectacular auroral displays. It has been unclear whether a substorm is triggered by a disruption of the electrical current flowing across the near-Earth magnetotail, at approximately 10 R(E) (R(E): Earth radius, or 6374 kilometers), or by the process of magnetic reconnection typically seen farther out in the magnetotail, at approximately 20 to 30 R(E). We report on simultaneous measurements in the magnetotail at multiple distances, at the time of substorm onset. Reconnection was observed at 20 R(E), at least 1.5 minutes before auroral intensification, at least 2 minutes before substorm expansion, and about 3 minutes before near-Earth current disruption. These results demonstrate that substorms are likely initiated by tail reconnection. PMID:18653845

  18. Bars Triggered By Galaxy Flybys

    NASA Astrophysics Data System (ADS)

    Holley-Bockelmann, Kelly; Lang, Meagan; Sinha, Manodeep

    2015-05-01

    Galaxy mergers drive galaxy evolution and are a key mechanism by which galaxies grow and transform. Unlike galaxy mergers where two galaxies combine into one remnant, galaxy flybys occur when two independent galaxy halos interpenetrate but detach at a later time; these one-time events are surprisingly common and can even out-number galaxy mergers at low redshift for massive halos. Although these interactions are transient and occur far outside the galaxy disk, flybys can still drive a rapid and large pertubations within both the intruder and victim halos. We explored how flyby encounters can transform each galaxy using a suite of N-body simulations. We present results from three co-planar flybys between disk galaxies, demonstrating that flybys can both trigger strong bar formation and can spin-up dark matter halos.

  19. A Mechanochemically Triggered "Click" Catalyst.

    PubMed

    Michael, Philipp; Binder, Wolfgang H

    2015-11-16

    "Click" chemistry represents one of the most powerful approaches for linking molecules in chemistry and materials science. Triggering this reaction by mechanical force would enable site- and stress-specific "click" reactions--a hitherto unreported observation. We introduce the design and realization of a homogeneous Cu catalyst able to activate through mechanical force when attached to suitable polymer chains, acting as a lever to transmit the force to the central catalytic system. Activation of the subsequent copper-catalyzed "click" reaction (CuAAC) is achieved either by ultrasonication or mechanical pressing of a polymeric material, using a fluorogenic dye to detect the activation of the catalyst. Based on an N-heterocyclic copper(I) carbene with attached polymeric chains of different flexibility, the force is transmitted to the central catalyst, thereby activating a CuAAC in solution and in the solid state. PMID:26420664

  20. CDF level 2 trigger upgrade

    SciTech Connect

    Anikeev, K.; Bogdan, M.; DeMaat, R.; Fedorko, W.; Frisch, H.; Hahn, K.; Hakala, M.; Keener, P.; Kim, Y.; Kroll, J.; Kwang, S.; Lewis, J.; Lin, C.; Liu, T.; Marjamaa, F.; Mansikkala, T.; Neu, C.; Pitkanen, S.; Reisert, B.; Rusu, V.; Sanders, H.; /Fermilab /Chicago U. /Pennsylvania U.

    2006-01-01

    We describe the new CDF Level 2 Trigger, which was commissioned during Spring 2005. The upgrade was necessitated by several factors that included increased bandwidth requirements, in view of the growing instantaneous luminosity of the Tevatron, and the need for a more robust system, since the older system was reaching the limits of maintainability. The challenges in designing the new system were interfacing with many different upstream detector subsystems, processing larger volumes of data at higher speed, and minimizing the impact on running the CDF experiment during the system commissioning phase. To meet these challenges, the new system was designed around a general purpose motherboard, the PULSAR, which is instrumented with powerful FPGAs and modern SRAMs, and which uses mezzanine cards to interface with upstream detector components and an industry standard data link (S-LINK) within the system.

  1. Landslide triggering by rain infiltration

    USGS Publications Warehouse

    Iverson, Richard M.

    2000-01-01

    Landsliding in response to rainfall involves physical processes that operate on disparate timescales. Relationships between these timescales guide development of a mathematical model that uses reduced forms of Richards equation to evaluate effects of rainfall infiltration on landslide occurrence, timing, depth, and acceleration in diverse situations. The longest pertinent timescale is A/D0, where D0 is the maximum hydraulic diffusivity of the soil and A is the catchment area that potentially affects groundwater pressures at a prospective landslide slip surface location with areal coordinates x, y and depth H. Times greater than A/D0 are necessary for establishment of steady background water pressures that develop at (x, y, H) in response to rainfall averaged over periods that commonly range from days to many decades. These steady groundwater pressures influence the propensity for landsliding at (x, y, H), but they do not trigger slope failure. Failure results from rainfall over a typically shorter timescale H2/D0 associated with transient pore pressure transmission during and following storms. Commonly, this timescale ranges from minutes to months. The shortest timescale affecting landslide responses to rainfall is √(H/g), where g is the magnitude of gravitational acceleration. Postfailure landslide motion occurs on this timescale, which indicates that the thinnest landslides accelerate most quickly if all other factors are constant. Effects of hydrologic processes on landslide processes across these diverse timescales are encapsulated by a response function, R(t*) = √(t*/π) exp (-1/t*) - erfc (1/√t*), which depends only on normalized time, t*. Use of R(t*) in conjunction with topographic data, rainfall intensity and duration information, an infinite-slope failure criterion, and Newton's second law predicts the timing, depth, and acceleration of rainfall-triggered landslides. Data from contrasting landslides that exhibit rapid, shallow motion and slow, deep

  2. Disaster triggers disaster: Earthquake triggering by tropical cyclones

    NASA Astrophysics Data System (ADS)

    Wdowinski, S.; Tsukanov, I.

    2011-12-01

    Three recent devastating earthquakes, the 1999 M=7.6 Chi-Chi (Taiwan), 2010 M=7.0 Leogane (Haiti), 2010 M=6.4 Kaohsiung (Taiwan), and additional three moderate size earthquakes (66 earthquake that occurred in the central mountainous area of Taiwan within three years after the typhoon. The 2009 Morakot typhoon was followed by 2009 M=6.2 Nantou and 2010 M=6.4 Kaohsiung earthquakes; the 1969 Flossie typhoon was followed by an M=6.3 earthquake in 1972; and the 1996 Herb typhoon by the 1998 M=6.2 Rueyli and 1999 M=7.6 Chi-Chi earthquakes. The earthquake catalog of Taiwan lists only two other M>6 main-shocks that occurred in Taiwan's central mountainous belt, one of them was in 1964 only four months after the wet Typhoon Gloria poured heavy rain in the same area. We suggest that the close proximity in time and space between wet tropical cyclones and earthquakes reflects a physical link between the two hazard types in which these earthquakes were triggered by rapid erosion induced by tropical cyclone's heavy rain. Based on remote sensing observations, meshfree finite element modeling, and Coulomb failure stress analysis, we show that the

  3. Architecture of the MEGA detector trigger

    NASA Astrophysics Data System (ADS)

    Chen, Y. K.; Cooper, M. D.; Cooper, P. S.; Dzemidzic, M.; Gagliardi, C. A.; Hogan, G. E.; Hungerford, E. V.; Kim, G. J.; Knott, J. E.; Lan, K. J.; Liu, F.; Mayes, B. W.; Mischke, R. E.; Phelps, R.; Pinsky, L. S.; Stantz, K. M.; Szymanski, J. J.; Tang, L. G.; Tribble, R. E.; Tu, X. L.; Van Ausdeln, L. A.; Von Witsch, W.; Wright, C. S.

    The trigger for the MEGA detector system is based on signals from single, high-energy photons interacting in one of the three MEGA pair spectrometers. The trigger is divided into a fast and a slow stage. The first stage produces a fast output if a specific pattern of detector hits is observed in the scintillators and high-speed wire chambers of a pair spectrometer. The second, slow-stage interrogates drift chamber hit patterns and provides a veto when the pattern fails a minimal requirement for reconstruction of the hits into a pair of circular orbits. The trigger interacts with the photon detector electronics by gating limited sections of the detector during the read-out of an event. This paper describes the two stage trigger system, the photon detector electronics, and the implementation of the trigger outputs to strobe the data acquisition system. The performance of the trigger is compared to Monte Carlo simulations of the photon detector response.

  4. Smart trigger logic for focal plane arrays

    DOEpatents

    Levy, James E; Campbell, David V; Holmes, Michael L; Lovejoy, Robert; Wojciechowski, Kenneth; Kay, Randolph R; Cavanaugh, William S; Gurrieri, Thomas M

    2014-03-25

    An electronic device includes a memory configured to receive data representing light intensity values from pixels in a focal plane array and a processor that analyzes the received data to determine which light values correspond to triggered pixels, where the triggered pixels are those pixels that meet a predefined set of criteria, and determines, for each triggered pixel, a set of neighbor pixels for which light intensity values are to be stored. The electronic device also includes a buffer that temporarily stores light intensity values for at least one previously processed row of pixels, so that when a triggered pixel is identified in a current row, light intensity values for the neighbor pixels in the previously processed row and for the triggered pixel are persistently stored, as well as a data transmitter that transmits the persistently stored light intensity values for the triggered and neighbor pixels to a data receiver.

  5. A muon trigger for the MACRO apparatus

    NASA Astrophysics Data System (ADS)

    Barbarito, E.; Bellotti, R.; Calicchio, M.; Castellano, M.; DeCataldo, G.; DeMarzo, C.; Erriquez, O.; Favuzzi, C.; Giglietto, N.; Liuzzi, R.; Spinelli, P.

    1991-02-01

    A trigger circuit based on EPROM components, able to manage up to 30 lines from independent counters, is described. The circuit has been designed and used in the MACRO apparatus at the Gran Sasso Laboratory for triggering on fast particles. The circuit works with standard TTL positive logic and is assembled in a double standard CAMAC module. It has a high triggering capacity and a high flexibility.

  6. The BTeV trigger: Recent developments

    SciTech Connect

    Kasper, Penelope; /Fermilab

    2003-12-01

    BTeV is a collider experiment at the Fermilab Tevatron dedicated to precision measurements of CP violation, mixing and rare decays of beauty and charm hadrons. The detector is a forward spectrometer with a pixel vertex detector inside a dipole magnet. A unique feature of BTeV is the trigger, which reconstructs tracks and vertices in every beam crossing. They present here an overview of the BTeV trigger and a description of recent improvements in trigger timing.

  7. Remote hydraulic ocean instrument trigger: DIRECTS

    SciTech Connect

    Jordan, M.

    1993-05-01

    A robust, reliable, inexpensive, easily operated, remote acting, deep ocean triggering system called DIRECTS (depth-indexed remote-equipment-commanding trigger system) is designed to initiate and power the operation of generic instrumentation at specific depths in the sea. The triggers, hydraulically actuated, are accurate within a few meters of depth and provide important post-retrieval confirmation of depth at the time of operation. The majority of research and commercial endeavors in the sea depend on the ability to accuratesly initiate subsea activities at specifically determined depths. Chemical, physical, and biological oceanographic sampling, commercial fishing, and offshore petroleum resource assessment are among operations requiring depth-accurate triggering capabilities.

  8. Ischemic Compression After Trigger Point Injection Affect the Treatment of Myofascial Trigger Points

    PubMed Central

    Kim, Soo A; Oh, Ki Young; Choi, Won Hyuck

    2013-01-01

    Objective To investigate the effects of trigger point injection with or without ischemic compression in treatment of myofascial trigger points in the upper trapezius muscle. Methods Sixty patients with active myofascial trigger points in upper trapezius muscle were randomly divided into three groups: group 1 (n=20) received only trigger point injections, group 2 (n=20) received trigger point injections with 30 seconds of ischemic compression, and group 3 (n=20) received trigger point injections with 60 seconds of ischemic compression. The visual analogue scale, pressure pain threshold, and range of motion of the neck were assessed before treatment, immediately after treatment, and 1 week after treatment. Korean Neck Disability Indexes were assessed before treatment and 1 week after treatment. Results We found a significant improvement in all assessment parameters (p<0.05) in all groups. But, receiving trigger point injections with ischemic compression group showed significant improvement as compared with the receiving only trigger point injections group. And no significant differences between receiving 30 seconds of ischemic compression group and 60 seconds of ischemic compression group. Conclusion This study demonstrated the effectiveness of ischemic compression for myofascial trigger point. Trigger point injections combined with ischemic compression shows better effects on treatment of myofascial trigger points in the upper trapezius muscle than the only trigger point injections therapy. But the duration of ischemic compression did not affect treatment of myofascial trigger point. PMID:24020035

  9. Nonlinear dynamical triggering of slow slip

    SciTech Connect

    Johnson, Paul A; Knuth, Matthew W; Kaproth, Bryan M; Carpenter, Brett; Guyer, Robert A; Le Bas, Pierre - Yves; Daub, Eric G; Marone, Chris

    2010-12-10

    Among the most fascinating, recent discoveries in seismology have been the phenomena of triggered slip, including triggered earthquakes and triggered-tremor, as well as triggered slow, silent-slip during which no seismic energy is radiated. Because fault nucleation depths cannot be probed directly, the physical regimes in which these phenomena occur are poorly understood. Thus determining physical properties that control diverse types of triggered fault sliding and what frictional constitutive laws govern triggered faulting variability is challenging. We are characterizing the physical controls of triggered faulting with the goal of developing constitutive relations by conducting laboratory and numerical modeling experiments in sheared granular media at varying load conditions. In order to simulate granular fault zone gouge in the laboratory, glass beads are sheared in a double-direct configuration under constant normal stress, while subject to transient perturbation by acoustic waves. We find that triggered, slow, silent-slip occurs at very small confining loads ({approx}1-3 MPa) that are smaller than those where dynamic earthquake triggering takes place (4-7 MPa), and that triggered slow-slip is associated with bursts of LFE-like acoustic emission. Experimental evidence suggests that the nonlinear dynamical response of the gouge material induced by dynamic waves may be responsible for the triggered slip behavior: the slip-duration, stress-drop and along-strike slip displacement are proportional to the triggering wave amplitude. Further, we observe a shear-modulus decrease corresponding to dynamic-wave triggering relative to the shear modulus of stick-slips. Modulus decrease in response to dynamical wave amplitudes of roughly a microstrain and above is a hallmark of elastic nonlinear behavior. We believe that the dynamical waves increase the material non-affine elastic deformation during shearing, simultaneously leading to instability and slow-slip. The inferred

  10. Global Trigger Upgrade firmware architecture for the level-1 Trigger of the CMS experiment

    NASA Astrophysics Data System (ADS)

    Rahbaran, B.; Arnold, B.; Bergauer, H.; Wittmann, J.; Matsushita, T.

    2015-02-01

    The Global Trigger (GT) is the final step of the CMS Level-1 Trigger and implements the ``menu'' of triggers, which is a set of selection requirements applied to the final list of objects (such as muons, electrons or jets) to trigger the readout of the detector and serve as basis for further calculations by the High Level Trigger. Operational experience in developing trigger menus from the first LHC run has shown that the requirements increased as the luminosity and pile-up increased. The new GT (μGT) is designed based on Xilinx Virtex-7 FPGAs, which combine unsurpassed flexibility with regard to scalability and high robustness. Furthermore, a custom board which receives signals from legacy electronics and basic binary inputs from less complex trigger sources is presented. Additionally, this paper describes the architecture of a distributed testing framework and the Trigger Menu Editor.

  11. Trigger Points: An Anatomical Substratum

    PubMed Central

    Akamatsu, Flávia Emi; Ayres, Bernardo Rodrigues; Saleh, Samir Omar; Hojaij, Flávio; Andrade, Mauro; Hsing, Wu Tu; Jacomo, Alfredo Luiz

    2015-01-01

    This study aimed to bring the trapezius muscle knowledge of the locations where the accessory nerve branches enter the muscle belly to reach the motor endplates and find myofascial trigger points (MTrPs). Although anatomoclinical correlations represent a major feature of MTrP, no previous reports describing the distribution of the accessory nerve branches and their anatomical relationship with MTrP are found in the literature. Both trapezius muscles from twelve adult cadavers were carefully dissected by the authors (anatomy professors and medical graduate students) to observe the exact point where the branches of the spinal accessory nerve entered the muscle belly. Dissection was performed through stratigraphic layers to preserve the motor innervation of the trapezius muscle, which is located deep in the muscle. Seven points are described, four of which are motor points: in all cases, these locations corresponded to clinically described MTrPs. The four points were common in these twelve cadavers. This type of clinical correlation between spinal accessory nerve branching and MTrP is useful to achieve a better understanding of the anatomical correlation of MTrP and the physiopathology of these disorders and may provide a scientific basis for their treatment, rendering useful additional information to therapists to achieve better diagnoses and improve therapeutic approaches. PMID:25811029

  12. Fluid pressure waves trigger earthquakes

    NASA Astrophysics Data System (ADS)

    Mulargia, Francesco; Bizzarri, Andrea

    2015-03-01

    Fluids-essentially meteoric water-are present everywhere in the Earth's crust, occasionally also with pressures higher than hydrostatic due to the tectonic strain imposed on impermeable undrained layers, to the impoundment of artificial lakes or to the forced injections required by oil and gas exploration and production. Experimental evidence suggests that such fluids flow along preferred paths of high diffusivity, provided by rock joints and faults. Studying the coupled poroelastic problem, we find that such flow is ruled by a nonlinear partial differential equation amenable to a Barenblatt-type solution, implying that it takes place in form of solitary pressure waves propagating at a velocity which decreases with time as v ∝ t [1/(n - 1) - 1] with n ≳ 7. According to Tresca-Von Mises criterion, these waves appear to play a major role in earthquake triggering, being also capable to account for aftershock delay without any further assumption. The measure of stress and fluid pressure inside active faults may therefore provide direct information about fault potential instability.

  13. Interaction with glycosaminoglycans is required for cyclophilin B to trigger integrin-mediated adhesion of peripheral blood T lymphocytes to extracellular matrix.

    PubMed

    Allain, Fabrice; Vanpouille, Christophe; Carpentier, Mathieu; Slomianny, Marie-Christine; Durieux, Sandrine; Spik, Geneviève

    2002-03-01

    Cyclophilins A and B (CyPA and CyPB) are cyclosporin A-binding proteins that are involved in inflammatory events. We have reported that CyPB interacts with two types of cell-surface-binding sites. The first site corresponds to a functional receptor and requires interaction with the central core of CyPB. This region is highly conserved in cyclophilins, suggesting that CyPA and CyPB might share biological activities mediated by interaction with this receptor. The second site is identified with glycosaminoglycans (GAGs), the binding region located in the N terminus of CyPB. The difference in the N-terminal extensions of CyPA and CyPB suggests that a unique interaction with GAGs might account for selective activity of CyPB. To explore this hypothesis, we analyzed the lymphocyte responses triggered by CyPA, CyPB, and CyPB(KKK-), a mutant unable to interact with GAGs. The three ligands seemed capable enough to elicit calcium signal and chemotaxis by binding to the same signaling receptor. In contrast, only CyPB enhanced firm adhesion of T cells to the extracellular matrix. This activity depended on the interactions with GAGs and signaling receptor. CyPB-mediated adhesion required CD147 presumably because it was a costimulatory molecule and was related to an activation of alpha4beta1 and alpha4beta7 integrins. Finally, we showed that CyPB was capable mainly to enhance T cell adhesion of the CD4+CD45RO+ subset. The present data indicate that CyPB rather than CyPA is a proinflammatory factor for T lymphocytes and highlight the crucial role of CyPB-GAG interaction in the chemokine-like activity of this protein.

  14. Hierarchical Trigger of the ALICE Calorimeters

    SciTech Connect

    Muller, Hans; Awes, Terry C

    2010-05-01

    The trigger of the ALICE electromagnetic calorimeters is implemented in 2 hierarchically connected layers of electronics. In the lower layer, level-0 algorithms search shower energy above threshold in locally confined Trigger Region Units (TRU). The top layer is implemented as a single, global trigger unit that receives the trigger data from all TRUs as input to the level-1 algorithm. This architecture was first developed for the PHOS high p{sub T} photon trigger before it was adopted by EMCal also for the jet trigger. TRU units digitize up to 112 analogue input signals from the Front End Electronics (FEE) and concentrate their digital stream in a single FPGA. A charge and time summing algorithm is combined with a peakfinder that suppresses spurious noise and is precise to single LHC bunches. With a peak-to-peak noise level of 150 MeV the linear dynamic range above threshold spans from MIP energies at 215 up to 50 GeV. Local level-0 decisions take less than 600 ns after LHC collisions, upon which all TRUs transfer their level-0 trigger data to the upstream global trigger module which searches within the remaining level-1 latency for high p{sub T} gamma showers (PHOS) and/or for Jet cone areas (EMCaL).

  15. Hierarchical trigger of the ALICE calorimeters

    NASA Astrophysics Data System (ADS)

    Muller, Hans; Awes, Terry C.; Novitzky, Norbert; Kral, Jiri; Rak, Jan; Schambach, Jo; Wang, Yaping; Wang, Dong; Zhou, Daicui

    2010-05-01

    The trigger of the ALICE electromagnetic calorimeters is implemented in 2 hierarchically connected layers of electronics. In the lower layer, level-0 algorithms search shower energy above threshold in locally confined Trigger Region Units (TRU). The top layer is implemented as a single, global trigger unit that receives the trigger data from all TRUs as input to the level-1 algorithm. This architecture was first developed for the PHOS high pT photon trigger before it was adopted by EMCal also for the jet trigger. TRU units digitize up to 112 analogue input signals from the Front End Electronics (FEE) and concentrate their digital stream in a single FPGA. A charge and time summing algorithm is combined with a peakfinder that suppresses spurious noise and is precise to single LHC bunches. With a peak-to-peak noise level of 150 MeV the linear dynamic range above threshold spans from MIP energies at 215 up to 50 GeV. Local level-0 decisions take less than 600 ns after LHC collisions, upon which all TRUs transfer their level-0 trigger data to the upstream global trigger module which searches within the remaining level-1 latency for high pT gamma showers (PHOS) and/or for Jet cone areas (EMCaL).

  16. Aspirin-triggered metabolites of EFAs.

    PubMed

    Makriyannis, Alexandros; Nikas, Spyros P

    2011-10-28

    Aspirin triggers the biosynthesis of oxygenated metabolites from arachidonic, eicosapentaenoic, and docosahexaenoic (DHA) acids. In a preceding issue, Serhan et al. (2011) describe a novel aspirin-triggered DHA pathway for the biosynthesis of a potent anti-inflammatory and proresolving molecule. PMID:22035788

  17. Methods for automatic trigger threshold adjustment

    DOEpatents

    Welch, Benjamin J; Partridge, Michael E

    2014-03-18

    Methods are presented for adjusting trigger threshold values to compensate for drift in the quiescent level of a signal monitored for initiating a data recording event, thereby avoiding false triggering conditions. Initial threshold values are periodically adjusted by re-measuring the quiescent signal level, and adjusting the threshold values by an offset computation based upon the measured quiescent signal level drift. Re-computation of the trigger threshold values can be implemented on time based or counter based criteria. Additionally, a qualification width counter can be utilized to implement a requirement that a trigger threshold criterion be met a given number of times prior to initiating a data recording event, further reducing the possibility of a false triggering situation.

  18. The LHCb trigger and its upgrade

    NASA Astrophysics Data System (ADS)

    Dziurda, A.

    2016-07-01

    The current LHCb trigger system consists of a hardware level, which reduces the LHC inelastic collision rate of 30 MHz, at which the entire detector is read out. In a second level, implemented in a farm of 20 k parallel-processing CPUs, the event rate is reduced to about 5 kHz. We review the performance of the LHCb trigger system during Run I of the LHC. Special attention is given to the use of multivariate analyses in the High Level Trigger. The major bottleneck for hadronic decays is the hardware trigger. LHCb plans a major upgrade of the detector and DAQ system in the LHC shutdown of 2018, enabling a purely software based trigger to process the full 30 MHz of inelastic collisions delivered by the LHC. We demonstrate that the planned architecture will be able to meet this challenge.

  19. An empirical profile of VLF triggered emissions

    NASA Astrophysics Data System (ADS)

    Li, J. D.; Spasojevic, M.; Inan, U. S.

    2015-08-01

    The Siple Transmitter Experiment operated from 1973 to 1988 and generated a wealth of observations of nonlinear wave-particle interactions including extensive recordings of triggered emissions generated by VLF signals injected into the magnetosphere from the transmitter at Siple Station, Antarctica. Due to their complex appearance and immensely varied behavior, triggered emissions remain poorly described and understood. This work provides a comprehensive statistical description of observed triggered emissions and establishes statistical bounds on triggered emission type (fallers, risers, and positive and negative hooks) and behavior (frequency changes between 1 kHz and 2.5 kHz with initial sweep rates between -2.5 kHz/s and 2.5 kHz/s, with risers undergoing a median frequency change of 556 Hz and fallers a median frequency change of -198 Hz). The statistical study also reveals an apparent dependence of the triggered emission behavior on the transmitted signal itself. Long tones and rising ramps generate more risers and positive hooks, while short tones and falling ramps produce more fallers and negative hooks. Triggered emissions also appear to favorably initiate with sweep rates similar to that of the triggering element, with the 1 kHz/s rising ramps triggering initial risers with a median sweep rate of 1.03 kHz/s and -1 kHz/s triggering initial fallers with a median sweep rate of -0.73 kHz/s. These results improve observations of wave modification resulting from wave-particle interactions in the radiation belts and can be used to validate numerical simulations of triggered emissions.

  20. JASMONATE-TRIGGERED PLANT IMMUNITY

    PubMed Central

    Campos, Marcelo L.; Kang, Jin-Ho; Howe, Gregg A.

    2014-01-01

    The plant hormone jasmonate (JA) exerts direct control over the production of chemical defense compounds that confer resistance to a remarkable spectrum of plant-associated organisms, ranging from microbial pathogens to vertebrate herbivores. The underlying mechanism of JA-triggered immunity (JATI) can be conceptualized as a multi-stage signal transduction cascade involving: i) pattern recognition receptors (PRRs) that couple the perception of danger signals to rapid synthesis of bioactive JA; ii) an evolutionarily conserved JA signaling module that links fluctuating JA levels to changes in the abundance of transcriptional repressor proteins; and iii) activation (de-repression) of transcription factors that orchestrate the expression of myriad chemical and morphological defense traits. Multiple negative feedback loops act in concert to restrain the duration and amplitude of defense responses, presumably to mitigate potential fitness costs of JATI. The convergence of diverse plant- and non-plant-derived signals on the core JA module indicates that JATI is a general response to perceived danger. However, the modular structure of JATI may accommodate attacker-specific defense responses through evolutionary innovation of PRRs (inputs) and defense traits (outputs). The efficacy of JATI as a defense strategy is highlighted by its capacity to shape natural populations of plant attackers, as well as the propensity of plant-associated organisms to subvert or otherwise manipulate JA signaling. As both a cellular hub for integrating informational cues from the environment and a common target of pathogen effectors, the core JA module provides a focal point for understanding immune system networks and the evolution of chemical diversity in the plant kingdom. PMID:24973116

  1. Triggered tremor sweet spots in Alaska

    USGS Publications Warehouse

    Gomberg, Joan; Prejean, Stephanie

    2013-01-01

    To better understand what controls fault slip along plate boundaries, we have exploited the abundance of seismic and geodetic data available from the richly varied tectonic environments composing Alaska. A search for tremor triggered by 11 large earthquakes throughout all of seismically monitored Alaska reveals two tremor “sweet spots”—regions where large-amplitude seismic waves repeatedly triggered tremor between 2006 and 2012. The two sweet spots locate in very different tectonic environments—one just trenchward and between the Aleutian islands of Unalaska and Akutan and the other in central mainland Alaska. The Unalaska/Akutan spot corroborates previous evidence that the region is ripe for tremor, perhaps because it is located where plate-interface frictional properties transition between stick-slip and stably sliding in both the dip direction and laterally. The mainland sweet spot coincides with a region of complex and uncertain plate interactions, and where no slow slip events or major crustal faults have been noted previously. Analyses showed that larger triggering wave amplitudes, and perhaps lower frequencies (<~0.03 Hz), may enhance the probability of triggering tremor. However, neither the maximum amplitude in the time domain or in a particular frequency band, nor the geometric relationship of the wavefield to the tremor source faults alone ensures a high probability of triggering. Triggered tremor at the two sweet spots also does not occur during slow slip events visually detectable in GPS data, although slow slip below the detection threshold may have facilitated tremor triggering.

  2. Performance of the ATLAS trigger system

    NASA Astrophysics Data System (ADS)

    Casadei, Diego

    2012-12-01

    The ATLAS trigger has been used very successfully to collect collision data during 2009-2011 LHC running at centre of mass energies between 900 GeV and 7 TeV. The three-level trigger system reduces the event rate from the design bunch-crossing rate of 40 MHz to an average recording rate of about 300 Hz. The first level uses custom electronics to reject most background events, in less than 2.5 μs, using information from the calorimeter and muon detectors. The upper two trigger levels are software-based triggers. The trigger system selects events by identifying signatures of muon, electron, photon, tau lepton, jet, and B meson candidates, as well as using global event signatures, such as missing transverse energy. We give an overview of the performance of these trigger selections based on extensive online running during the 2011 LHC run and discuss issues encountered during 2011 operations. We describe how the trigger has evolved with increasing LHC luminosity coping with pile-up conditions close to LHC design luminosity.

  3. The magnitude distribution of dynamically triggered earthquakes

    NASA Astrophysics Data System (ADS)

    Hernandez, Stephen

    Large dynamic strains carried by seismic waves are known to trigger seismicity far from their source region. It is unknown, however, whether surface waves trigger only small earthquakes, or whether they can also trigger large, societally significant earthquakes. To address this question, we use a mixing model approach in which total seismicity is decomposed into 2 broad subclasses: "triggered" events initiated or advanced by far-field dynamic strains, and "untriggered" spontaneous events consisting of everything else. The b-value of a mixed data set, b MIX, is decomposed into a weighted sum of b-values of its constituent components, bT and bU. For populations of earthquakes subjected to dynamic strain, the fraction of earthquakes that are likely triggered, f T, is estimated via inter-event time ratios and used to invert for bT. The confidence bounds on b T are estimated by multiple inversions of bootstrap resamplings of bMIX and fT. For Californian seismicity, data are consistent with a single-parameter Gutenberg-Richter hypothesis governing the magnitudes of both triggered and untriggered earthquakes. Triggered earthquakes therefore seem just as likely to be societally significant as any other population of earthquakes.

  4. Intraplate triggered earthquakes: Observations and interpretation

    USGS Publications Warehouse

    Hough, S.E.; Seeber, L.; Armbruster, J.G.

    2003-01-01

    We present evidence that at least two of the three 1811-1812 New Madrid, central United States, mainshocks and the 1886 Charleston, South Carolina, earthquake triggered earthquakes at regional distances. In addition to previously published evidence for triggered earthquakes in the northern Kentucky/southern Ohio region in 1812, we present evidence suggesting that triggered events might have occurred in the Wabash Valley, to the south of the New Madrid Seismic Zone, and near Charleston, South Carolina. We also discuss evidence that earthquakes might have been triggered in northern Kentucky within seconds of the passage of surface waves from the 23 January 1812 New Madrid mainshock. After the 1886 Charleston earthquake, accounts suggest that triggered events occurred near Moodus, Connecticut, and in southern Indiana. Notwithstanding the uncertainty associated with analysis of historical accounts, there is evidence that at least three out of the four known Mw 7 earthquakes in the central and eastern United States seem to have triggered earthquakes at distances beyond the typically assumed aftershock zone of 1-2 mainshock fault lengths. We explore the possibility that remotely triggered earthquakes might be common in low-strain-rate regions. We suggest that in a low-strain-rate environment, permanent, nonelastic deformation might play a more important role in stress accumulation than it does in interplate crust. Using a simple model incorporating elastic and anelastic strain release, we show that, for realistic parameter values, faults in intraplate crust remain close to their failure stress for a longer part of the earthquake cycle than do faults in high-strain-rate regions. Our results further suggest that remotely triggered earthquakes occur preferentially in regions of recent and/or future seismic activity, which suggests that faults are at a critical stress state in only some areas. Remotely triggered earthquakes may thus serve as beacons that identify regions of

  5. Remotely triggered earthquakes following moderate main shocks

    USGS Publications Warehouse

    Hough, S.E.

    2007-01-01

    Since 1992, remotely triggered earthquakes have been identified following large (M > 7) earthquakes in California as well as in other regions. These events, which occur at much greater distances than classic aftershocks, occur predominantly in active geothermal or volcanic regions, leading to theories that the earthquakes are triggered when passing seismic waves cause disruptions in magmatic or other fluid systems. In this paper, I focus on observations of remotely triggered earthquakes following moderate main shocks in diverse tectonic settings. I summarize evidence that remotely triggered earthquakes occur commonly in mid-continent and collisional zones. This evidence is derived from analysis of both historic earthquake sequences and from instrumentally recorded M5-6 earthquakes in eastern Canada. The latter analysis suggests that, while remotely triggered earthquakes do not occur pervasively following moderate earthquakes in eastern North America, a low level of triggering often does occur at distances beyond conventional aftershock zones. The inferred triggered events occur at the distances at which SmS waves are known to significantly increase ground motions. A similar result was found for 28 recent M5.3-7.1 earthquakes in California. In California, seismicity is found to increase on average to a distance of at least 200 km following moderate main shocks. This supports the conclusion that, even at distances of ???100 km, dynamic stress changes control the occurrence of triggered events. There are two explanations that can account for the occurrence of remotely triggered earthquakes in intraplate settings: (1) they occur at local zones of weakness, or (2) they occur in zones of local stress concentration. ?? 2007 The Geological Society of America.

  6. Revisiting Pneumatic Nail Gun Trigger Recommendations

    PubMed Central

    Albers, James; Lipscomb, Hester; Hudock, Stephen; Dement, John; Evanoff, Bradley; Fullen, Mark; Gillen, Matt; Kaskutas, Vicki; Nolan, James; Patterson, Dennis; Platner, James; Pompeii, Lisa; Schoenfisch, Ashley

    2015-01-01

    Summary Use of a pneumatic nail gun with a sequential actuation trigger (SAT) significantly diminishes the risk for acute traumatic injury compared to use of a contact actuation trigger (CAT) nail gun. A theoretically-based increased risk of work-related musculoskeletal disorders from use of a SAT nail gun, relative to CAT, appears unlikely and remains unproven. Based on current knowledge, the use of CAT nail guns cannot be justified as a safe alternative to SAT nail guns. This letter provides a perspective of ergonomists and occupational safety researchers recommending the use of the sequential actuation trigger for all nail gun tasks in the construction industry. PMID:26366020

  7. The ATLAS level 2 trigger supervisor.

    SciTech Connect

    Abolins, M.; Blair, R. E.; Dawson, J. W.; Owen, D.; Pope, B. G.; Schlereth, J. L.; Weber dos Santos, R.

    1997-04-03

    This paper presents an overview of the hardware and software proposed for the ATLAS level 2 Trigger ROI Builder/Supervisor. The essential requirements of this system are that it operate at the design Level 1 Trigger rate of 100kHz and that it support the technical requirements of the architectures suggested for the ATLAS Level 2 Trigger. Commercial equipment and software support are used to the maximum extent possible, with support from dedicated hardware. Timing requirements and latencies are discussed and simulation results are presented.

  8. Introduction to myofascial trigger points in dogs.

    PubMed

    Wall, Rick

    2014-06-01

    In dogs, muscles make up 44%-57% of total body weight and can serve as source of both pain and dysfunction when myofascial trigger points are present. However, rarely is muscle mentioned as a generator of pain in dogs, and even less mentioned is muscle dysfunction. The veterinary practitioner with interest in pain management, rehabilitation, orthopedics, and sports medicine must be familiar with the characteristics, etiology, and precipitating factors of myofascial trigger points. Additionally, the development of examination and treatment skill is needed to effectively manage myofascial trigger points in dogs. PMID:25454375

  9. Attempted Suicide Triggers in Thai Adolescent Perspectives.

    PubMed

    Sukhawaha, Supattra; Arunpongpaisal, Suwanna; Rungreangkulkij, Somporn

    2016-06-01

    The study goal was to describe attempted suicide triggers in Thai adolescents. A descriptive exploratory qualitative study approach was used utilizing in-depth interviews with twelve adolescents who had attempted suicide and six of their parents. Content analysis was conducted. Attempted suicide triggers were (1) severe verbal criticisms and expulsion to die by a significant family member, (2) disappointed and unwanted by boyfriend in first serious relationship, (3) unwanted pregnancy, and (4) mental illness leading to intense emotions and irresistible impulses. These attempted suicide triggers should be of concern and brought into suicide prevention management programs such as emotional management, effective communication for adolescents and family. PMID:27256938

  10. Electronic trigger for the ASP experiment

    SciTech Connect

    Wilson, R.J.

    1985-11-01

    The Anomalous Single Photon (ASP) electronic trigger is described. The experiments is based on an electromagnetic calorimeter composed of arrays of lead glass blocks, read out with photo-multiplier tubes, surrounding the interaction point at the PEP storage ring. The primary requirement of the trigger system is to be sensitive to low energy (approx. =0.5 GeV and above) photons whilst discriminating against high backgrounds at PEP. Analogue summing of the PMT signals and a sequence of programmable digital look-up tables produces a ''dead-timeless'' trigger for the beam collision rate of 408 kHz. 6 refs., 6 figs.

  11. Introduction to myofascial trigger points in dogs.

    PubMed

    Wall, Rick

    2014-06-01

    In dogs, muscles make up 44%-57% of total body weight and can serve as source of both pain and dysfunction when myofascial trigger points are present. However, rarely is muscle mentioned as a generator of pain in dogs, and even less mentioned is muscle dysfunction. The veterinary practitioner with interest in pain management, rehabilitation, orthopedics, and sports medicine must be familiar with the characteristics, etiology, and precipitating factors of myofascial trigger points. Additionally, the development of examination and treatment skill is needed to effectively manage myofascial trigger points in dogs.

  12. Triggered creep as a possible mechanism for delayed dynamic triggering of tremor and earthquakes

    USGS Publications Warehouse

    Shelly, D.R.; Peng, Z.; Hill, D.P.; Aiken, C.

    2011-01-01

    The passage of radiating seismic waves generates transient stresses in the Earth's crust that can trigger slip on faults far away from the original earthquake source. The triggered fault slip is detectable in the form of earthquakes and seismic tremor. However, the significance of these triggered events remains controversial, in part because they often occur with some delay, long after the triggering stress has passed. Here we scrutinize the location and timing of tremor on the San Andreas fault between 2001 and 2010 in relation to distant earthquakes. We observe tremor on the San Andreas fault that is initiated by passing seismic waves, yet migrates along the fault at a much slower velocity than the radiating seismic waves. We suggest that the migrating tremor records triggered slow slip of the San Andreas fault as a propagating creep event. We find that the triggered tremor and fault creep can be initiated by distant earthquakes as small as magnitude 5.4 and can persist for several days after the seismic waves have passed. Our observations of prolonged tremor activity provide a clear example of the delayed dynamic triggering of seismic events. Fault creep has been shown to trigger earthquakes, and we therefore suggest that the dynamic triggering of prolonged fault creep could provide a mechanism for the delayed triggering of earthquakes. ?? 2011 Macmillan Publishers Limited. All rights reserved.

  13. Software for implementing trigger algorithms on the upgraded CMS Global Trigger System

    NASA Astrophysics Data System (ADS)

    Matsushita, Takashi; Arnold, Bernhard

    2015-12-01

    The Global Trigger is the final step of the CMS Level-1 Trigger and implements a trigger menu, a set of selection requirements applied to the final list of trigger objects. The conditions for trigger object selection, with possible topological requirements on multiobject triggers, are combined by simple combinatorial logic to form the algorithms. The LHC has resumed its operation in 2015, the collision-energy will be increased to 13 TeV with the luminosity expected to go up to 2x1034 cm-2s-1. The CMS Level-1 trigger system will be upgraded to improve its performance for selecting interesting physics events and to operate within the predefined data-acquisition rate in the challenging environment expected at LHC Run 2. The Global Trigger will be re-implemented on modern FPGAs on an Advanced Mezzanine Card in MicroTCA crate. The upgraded system will benefit from the ability to process complex algorithms with DSP slices and increased processing resources with optical links running at 10 Gbit/s, enabling more algorithms at a time than previously possible and allowing CMS to be more flexible in how it handles the trigger bandwidth. In order to handle the increased complexity of the trigger menu implemented on the upgraded Global Trigger, a set of new software has been developed. The software allows a physicist to define a menu with analysis-like triggers using intuitive user interface. The menu is then realised on FPGAs with further software processing, instantiating predefined firmware blocks. The design and implementation of the software for preparing a menu for the upgraded CMS Global Trigger system are presented.

  14. The dangers of being trigger-happy

    NASA Astrophysics Data System (ADS)

    Dale, J. E.; Haworth, T. J.; Bressert, E.

    2015-06-01

    We examine the evidence offered for triggered star formation against the backdrop provided by recent numerical simulations of feedback from massive stars at or below giant molecular cloud sizescales. We compile a catalogue of 67 observational papers, mostly published over the last decade, and examine the signposts most commonly used to infer the presence of triggered star formation. We then determine how well these signposts perform in a recent suite of hydrodynamic simulations of star formation including feedback from O-type stars performed by Dale et al. We find that none of the observational markers improve the chances of correctly identifying a given star as triggered by more than factors of 2 at most. This limits the fidelity of these techniques in interpreting star formation histories. We therefore urge caution in interpreting observations of star formation near feedback-driven structures in terms of triggering.

  15. The new UA1 calorimeter trigger processor

    SciTech Connect

    Baird, S.A.; Campbell, D.; Cawthraw, M.; Coughlan, J.; Flynn, P.; Galagadera, S.; Grayer, G.; Halsall, R.; Shah, T.P.; Stephens, R.

    1989-02-01

    The UA1 First Level Trigger Processor (TP) is a fast digital machine with a highly parallel pipelined architecture of fast TTL combinational and programmable logic controlled by programmable microsequencers. The TP uses 100,000 IC's housed in 18 crates each containing 21 fastbus sized modules. It is hardwired with a very high level of interconnection. The energy deposited in the upgraded calorimeter is digitised into 1700 bytes of input data every beam crossing. The Processor selects in 1.5 microseconds events for further processing. The new electron trigger has improved hadron jet rejection, achieved by requiring low energy deposition around the electro-magnetic cluster. A missing transverse energy trigger and a total energy trigger have also been implemented.

  16. A hypothesis for delayed dynamic earthquake triggering

    USGS Publications Warehouse

    Parsons, T.

    2005-01-01

    It's uncertain whether more near-field earthquakes are triggered by static or dynamic stress changes. This ratio matters because static earthquake interactions are increasingly incorporated into probabilistic forecasts. Recent studies were unable to demonstrate all predictions from the static-stress-change hypothesis, particularly seismicity rate reductions. However, current dynamic stress change hypotheses do not explain delayed earthquake triggering and Omori's law. Here I show numerically that if seismic waves can alter some frictional contacts in neighboring fault zones, then dynamic triggering might cause delayed triggering and an Omori-law response. The hypothesis depends on faults following a rate/state friction law, and on seismic waves changing the mean critical slip distance (Dc) at nucleation zones.

  17. Graphics Processing Units for HEP trigger systems

    NASA Astrophysics Data System (ADS)

    Ammendola, R.; Bauce, M.; Biagioni, A.; Chiozzi, S.; Cotta Ramusino, A.; Fantechi, R.; Fiorini, M.; Giagu, S.; Gianoli, A.; Lamanna, G.; Lonardo, A.; Messina, A.; Neri, I.; Paolucci, P. S.; Piandani, R.; Pontisso, L.; Rescigno, M.; Simula, F.; Sozzi, M.; Vicini, P.

    2016-07-01

    General-purpose computing on GPUs (Graphics Processing Units) is emerging as a new paradigm in several fields of science, although so far applications have been tailored to the specific strengths of such devices as accelerator in offline computation. With the steady reduction of GPU latencies, and the increase in link and memory throughput, the use of such devices for real-time applications in high-energy physics data acquisition and trigger systems is becoming ripe. We will discuss the use of online parallel computing on GPU for synchronous low level trigger, focusing on CERN NA62 experiment trigger system. The use of GPU in higher level trigger system is also briefly considered.

  18. Trigger System Upgrades for the SNO+ Experiment

    NASA Astrophysics Data System (ADS)

    Marzec, Eric; Sno+ Collaboration

    2015-04-01

    The SNO+ experiment will explore many topics in neutrino physics including neutrino-less double beta decay, low-energy solar neutrinos, antineutrinos from reactors and natural sources, nucleon decay, and potentially supernova neutrinos. The SNO+ trigger and readout system consists of electronics both inherited from the SNO detector and newly created specifically to address the challenges presented by the addition of scintillation light. Addition of new utilities to the SNO+ trigger system will allow for a flexible calibration interface, more sophisticated use of the existing trigger system, and new, more targeted, background cuts that will improve physics sensitivity. These utilities will largely be orchestrated by a MicroZed System on Chip (SoC), micro-controller. Their range of application includes automatic fault detection, upgrades of SNO utilities, noise reduction, and interfacing between components of the trigger system.

  19. Remotely triggered nonvolcanic tremor in Sumbawa, Indonesia

    NASA Astrophysics Data System (ADS)

    Fuchs, F.; Lupi, M.; Miller, S. A.

    2014-06-01

    We present, for the first time, evidence for triggered tremor beneath the island of Sumbawa, Indonesia. We show triggered tremor in response to three teleseismic earthquakes: the Mw9.0 2011 Tohoku earthquake and two oceanic strike-slip earthquakes (Mw 8.6 and Mw8.2) offshore of Sumatra in 2012. We constrain an apparent triggering threshold of 1 mm/s ground velocity that corresponds to about 8 kPa dynamic stress. Peak tremor amplitudes of about 180 nm/s are observed, and scale with the ground velocity induced by the remote earthquakes. Triggered tremor responds to 45-65 s period surface waves and predominantly correlates with Rayleigh waves, even though the 2012 oceanic events have stronger Love wave amplitudes. We could not locate the tremor because of minimal station coverage, but data indicate several potential source volumes including the Flores Thrust, the Java subduction zone, or Tambora volcano.

  20. Sensor-trigger device for explosion barrier.

    PubMed

    Liebman, I; Duda, F; Conti, R

    1979-11-01

    A flame sensor-trigger device was developed for use with barriers to suppress coal dust explosions in undergound mines. Principal feature of the device is a dual infrared flame sensor combined with a pressure-arming element. This combination prevents false and premature triggering of the barrier. With minor modifications, the device can also be used with barriers for protection in other facilities against gas explosions and explosions involving dusts other than coal.

  1. Dynamic stresses, Coulomb failure, and remote triggering

    USGS Publications Warehouse

    Hill, D.P.

    2008-01-01

    Dynamic stresses associated with crustal surface waves with 15-30-sec periods and peak amplitudes 5 km). The latter is consistent with the observation that extensional or transtensional tectonic regimes are more susceptible to remote triggering by Rayleigh-wave dynamic stresses than compressional or transpressional regimes. Locally elevated pore pressures may have a role in the observed prevalence of dynamic triggering in extensional regimes and geothermal/volcanic systems.

  2. Decision-making triggers in adaptive management.

    PubMed

    Nie, Martin A; Schultz, Courtney A

    2012-12-01

    We analyzed whether decision-making triggers increase accountability of adaptive-management plans. Triggers are prenegotiated commitments in an adaptive-management plan that specify what actions are to be taken and when on the basis of information obtained from monitoring. Triggers improve certainty that particular actions will be taken by agencies in the future. We conducted an in-depth, qualitative review of the political and legal contexts of adaptive management and its application by U.S. federal agencies. Agencies must satisfy the judiciary that adaptive-management plans meet substantive legal standards and comply with the U.S. National Environmental Policy Act. We examined 3 cases in which triggers were used in adaptive-management plans: salmon (Oncorhynchus spp.) in the Columbia River, oil and gas development by the Bureau of Land Management, and a habitat conservation plan under the U.S. Endangered Species Act. In all the cases, key aspects of adaptive management, including controls and preidentified feedback loops, were not incorporated in the plans. Monitoring and triggered mitigation actions were limited in their enforceability, which was contingent on several factors, including which laws applied in each case and the degree of specificity in how triggers were written into plans. Other controversial aspects of these plans revolved around who designed, conducted, interpreted, and funded monitoring programs. Additional contentious issues were the level of precaution associated with trigger mechanisms and the definition of ecological baselines used as points of comparison. Despite these challenges, triggers can be used to increase accountability, by predefining points at which an adaptive management plan will be revisited and reevaluated, and thus improve the application of adaptive management in its complicated political and legal context. PMID:22891956

  3. Trigger finger, tendinosis, and intratendinous gene expression.

    PubMed

    Lundin, A-C; Aspenberg, P; Eliasson, P

    2014-04-01

    The pathogenesis of trigger finger has generally been ascribed to primary changes in the first annular ligament. In contrast, we recently found histological changes in the tendons, similar to the findings in Achilles tendinosis or tendinopathy. We therefore hypothesized that trigger finger tendons would show differences in gene expression in comparison to normal tendons in a pattern similar to what is published for Achilles tendinosis. We performed quantitative real-time polymerase chain reaction on biopsies from finger flexor tendons, 13 trigger fingers and 13 apparently healthy control tendons, to assess the expression of 10 genes which have been described to be differently expressed in tendinosis (collagen type 1a1, collagen 3a1, MMP-2, MMP-3, ADAMTS-5, TIMP-3, aggrecan, biglycan, decorin, and versican). In trigger finger tendons, collagen types 1a1 and 3a1, aggrecan and biglycan were all up-regulated, and MMP-3and TIMP-3 were down-regulated. These changes were statistically significant and have been previously described for Achilles tendinosis. The remaining four genes were not significantly altered. The changes in gene expression support the hypothesis that trigger finger is a form of tendinosis. Because trigger finger is a common condition, often treated surgically, it could provide opportunities for clinical research on tendinosis. PMID:22882155

  4. The CDF level 2 calorimetric trigger upgrade

    SciTech Connect

    Bhatti, A.; Canepa, A.; Casarsa, M.; Convery, M.; Cortiana, G.; Dell'Orso, M.; Donati, S.; Flanagan, G.; Frisch, H.; Fukun, T.; Krop, D.; /Chicago U., EFI /INFN, Pisa /Pisa U. /Pisa, Scuola Normale Superiore

    2009-01-01

    CDF II upgraded the calorimeter trigger to cope with the higher detector occupancy due to the increased Tevatron instantaneous luminosity ({approx} 2.8 x 10{sup 32} cm{sup -2} s{sup -1}). While the original system was implemented in custom hardware and provided to the L2 trigger a limited-quality jet clustering performed using a reduced resolution measurement of the transverse energy in the calorimeter trigger towers, the upgraded system provides offline-quality jet reconstruction of the full resolution calorimeter data. This allows to keep better under control the dependence of the trigger rates on the instantaneous luminosity and to improve the efficiency and purity of the trigger selections. The upgraded calorimeter trigger uses the general purpose VME board Pulsar, developed at CDF II and already widely used to upgrade the L2 tracking and L2 decision systems. A battery of Pulsars is used to merge and send the calorimeter data to the L2 CPUs, where software-implemented algorithms perform offline-like clustering. In this paper we review the design and the performance of the upgraded system.

  5. The Zeus calorimeter first level trigger

    SciTech Connect

    Smith, W.J.

    1989-04-01

    The design of the Zeus Detector Calorimeter Level Trigger is presented. The Zeus detector is being built for operation at HERA, a new storage ring that will provide collisions between 820 GeV protons and 30 GeV electrons in 1990. The calorimeter is made of depleted uranium plates and plastic scintillator read out by wavelength shifter bars into 12,864 photomultiplier tubes. These signals are combined into 974 trigger towers with separate electromagnetic and hadronic sums. The calorimeter first level trigger is pipelined with a decision provided 5 {mu}sec after each beam crossing, occurring every 96 nsec. The trigger determines the total energy, the total transverse energy, the missing energy, and the energy and number of isolated electrons and muons. It also provides information on the number and energy of clusters. The trigger rate needs to be held to 1 kHz against a rate of proton-beam gas interactions of approximately 500 kHz. The summed trigger tower pulseheights are digitized by flash ADC`s. The digital values are linearized, stored and used for sums and pattern tests.

  6. Commissioning of the CMS High Level Trigger

    SciTech Connect

    Agostino, Lorenzo; et al.

    2009-08-01

    The CMS experiment will collect data from the proton-proton collisions delivered by the Large Hadron Collider (LHC) at a centre-of-mass energy up to 14 TeV. The CMS trigger system is designed to cope with unprecedented luminosities and LHC bunch-crossing rates up to 40 MHz. The unique CMS trigger architecture only employs two trigger levels. The Level-1 trigger is implemented using custom electronics, while the High Level Trigger (HLT) is based on software algorithms running on a large cluster of commercial processors, the Event Filter Farm. We present the major functionalities of the CMS High Level Trigger system as of the starting of LHC beams operations in September 2008. The validation of the HLT system in the online environment with Monte Carlo simulated data and its commissioning during cosmic rays data taking campaigns are discussed in detail. We conclude with the description of the HLT operations with the first circulating LHC beams before the incident occurred the 19th September 2008.

  7. The Topo-trigger: a new concept of stereo trigger system for imaging atmospheric Cherenkov telescopes

    NASA Astrophysics Data System (ADS)

    López-Coto, R.; Mazin, D.; Paoletti, R.; Blanch Bigas, O.; Cortina, J.

    2016-04-01

    Imaging atmospheric Cherenkov telescopes (IACTs) such as the Major Atmospheric Gamma-ray Imaging Cherenkov (MAGIC) telescopes endeavor to reach the lowest possible energy threshold. In doing so the trigger system is a key element. Reducing the trigger threshold is hampered by the rapid increase of accidental triggers generated by ambient light (the so-called Night Sky Background NSB). In this paper we present a topological trigger, dubbed Topo-trigger, which rejects events on the basis of their relative orientation in the telescope cameras. We have simulated and tested the trigger selection algorithm in the MAGIC telescopes. The algorithm was tested using MonteCarlo simulations and shows a rejection of 85% of the accidental stereo triggers while preserving 99% of the gamma rays. A full implementation of this trigger system would achieve an increase in collection area between 10 and 20% at the energy threshold. The analysis energy threshold of the instrument is expected to decrease by ~ 8%. The selection algorithm was tested on real MAGIC data taken with the current trigger configuration and no γ-like events were found to be lost.

  8. Transient triggering of near and distant earthquakes

    USGS Publications Warehouse

    Gomberg, J.; Blanpied, M.L.; Beeler, N.M.

    1997-01-01

    We demonstrate qualitatively that frictional instability theory provides a context for understanding how earthquakes may be triggered by transient loads associated with seismic waves from near and distance earthquakes. We assume that earthquake triggering is a stick-slip process and test two hypotheses about the effect of transients on the timing of instabilities using a simple spring-slider model and a rate- and state-dependent friction constitutive law. A critical triggering threshold is implicit in such a model formulation. Our first hypothesis is that transient loads lead to clock advances; i.e., transients hasten the time of earthquakes that would have happened eventually due to constant background loading alone. Modeling results demonstrate that transient loads do lead to clock advances and that the triggered instabilities may occur after the transient has ceased (i.e., triggering may be delayed). These simple "clock-advance" models predict complex relationships between the triggering delay, the clock advance, and the transient characteristics. The triggering delay and the degree of clock advance both depend nonlinearly on when in the earthquake cycle the transient load is applied. This implies that the stress required to bring about failure does not depend linearly on loading time, even when the fault is loaded at a constant rate. The timing of instability also depends nonlinearly on the transient loading rate, faster rates more rapidly hastening instability. This implies that higher-frequency and/or longer-duration seismic waves should increase the amount of clock advance. These modeling results and simple calculations suggest that near (tens of kilometers) small/moderate earthquakes and remote (thousands of kilometers) earthquakes with magnitudes 2 to 3 units larger may be equally effective at triggering seismicity. Our second hypothesis is that some triggered seismicity represents earthquakes that would not have happened without the transient load (i

  9. The ATLAS trigger - commissioning with cosmic rays

    NASA Astrophysics Data System (ADS)

    Boyd, J.

    2008-07-01

    The ATLAS detector at CERN's LHC will be exposed to proton-proton collisions from beams crossing at 40 MHz. At the design luminosity there are roughly 23 collisions per bunch crossing. ATLAS has designed a three-level trigger system to select potentially interesting events. The first-level trigger, implemented in custom-built electronics, reduces the incoming rate to less than 100 kHz with a total latency of less than 2.5μs. The next two trigger levels run in software on commercial PC farms. They reduce the output rate to 100-200 Hz. In preparation for collision data-taking which is scheduled to commence in May 2008, several cosmic-ray commissioning runs have been performed. Among the first sub-detectors available for commissioning runs are parts of the barrel muon detector including the RPC detectors that are used in the first-level trigger. Data have been taken with a full slice of the muon trigger and readout chain, from the detectors in one sector of the RPC system, to the second-level trigger algorithms and the data-acquisition system. The system is being prepared to include the inner-tracking detector in the readout and second-level trigger. We will present the status and results of these cosmic-ray based commissioning activities. This work will prove to be invaluable not only during the commissioning phase but also for cosmic-ray data-taking during the normal running for detector performance studies.

  10. The D/Ø Silicon Track Trigger

    NASA Astrophysics Data System (ADS)

    Steinbrück, Georg

    2003-09-01

    We describe a trigger preprocessor to be used by the D Ø experiment for selecting events with tracks from the decay of long-lived particles. This Level 2 impact parameter trigger utilizes information from the Silicon Microstrip Tracker to reconstruct tracks with improved spatial and momentum resolutions compared to those obtained by the Level 1 tracking trigger. It is constructed of VME boards with much of the logic existing in programmable processors. A common motherboard provides the I/O infrastructure and three different daughter boards perform the tasks of identifying the roads from the tracking trigger data, finding the clusters in the roads in the silicon detector, and fitting tracks to the clusters. This approach provides flexibility for the design, testing and maintenance phases of the project. The track parameters are provided to the trigger framework in 25 μs. The effective impact parameter resolution for high-momentum tracks is 35 μm, dominated by the size of the Tevatron beam.

  11. Dietary aspects of migraine trigger factors.

    PubMed

    Rockett, Fernanda C; de Oliveira, Vanessa R; Castro, Kamila; Chaves, Márcia L F; Perla, Alexandre da S; Perry, Ingrid D S

    2012-06-01

    The significance of dietary factors as triggers for migraines is controversial, and the assessment of this topic is complex and inconclusive. In order to evaluate the published evidence on dietary triggers, a critical review of the literature was performed by conducting a search for food item descriptors linked to migraines in the PubMed and SciELO databases. Reviews and relevant references cited within the articles that resulted from the search were also included. Of the 45 studies reviewed, 16 were population studies that involved the association between migraines and eating habits or the prevalence of related dietary factors; 12 involved interventions or analyzed observational prospective cohorts; and 17 were retrospective studies. Approximately 30 dietary triggers were explored in total, although only seven of these were addressed experimentally. In the prospective studies, patients were instructed to keep a diary; two of these studies involved dietary interventions. Conclusions that are based on nonpharmacological prophylactic strategies with a scientific basis and that show an association between certain dietary factors and the triggering of migraines are limited by the lack of prospective studies with clear experimental designs. Nevertheless, the high frequency of possible specific dietary triggers validates efforts to elucidate the involvement of food-related factors in precipitating migraines.

  12. CMS muon detector and trigger performance

    NASA Astrophysics Data System (ADS)

    Piccolo, Davide; CMS Collaboration

    2011-02-01

    In the CMS experiment at the LHC proton-proton collider, a key role will be played by the muon system that is embedded inside the iron yoke used to close the magnetic flux of the CMS solenoid. The muon system of the CMS experiment performs three main tasks: triggering of muons, identifying muons, and assisting the central tracker in order to measure the momentum and charge of high-pt muons in the pseudorapidity region |η|≤2.4. The system is composed by a central barrel and two closing endcaps. Three independent technologies are used to reconstruct and trigger muons: Drift Tubes (DT) in the barrel, Cathode Strips Chambers (CSC) in the endcaps and Resistive Plate Chambers (RPC) in both barrel and endcap regions. All the detectors will contribute to the tracking and triggering of muons. Towards the end of 2008 and in 2009 the CMS experiment was commissioned with many millions of cosmic rays. These data have been fundamental to check the performance of the three sub-detectors and of the trigger response. In this paper the results in terms of the detection and trigger performance at the level of each sub-detector and at the level of the full muon system will be reported.

  13. Tau Trigger at the ATLAS Experiment

    SciTech Connect

    Benslama, K.; Kalinowski, A.; Belanger-Champange, C.; Brenner, R.; Bosman, M.; Casado, P.; Osuna, C.; Perez, E.; Vorwerk, V.; Czyczula, Z.; Dam, M.; Xella, S.; Demers, S.; Farrington, S.; Igonkina, O.; Kanaya, N.; Tsuno, S.; Ptacek, E.; Reinsch, A.; Strom, David M.; Torrence, E.; /Oregon U. /Sydney U. /Lancaster U. /Birmingham U.

    2011-11-09

    Many theoretical models, like the Standard Model or SUSY at large tan({beta}), predict Higgs bosons or new particles which decay more abundantly to final states including tau leptons than to other leptons. At the energy scale of the LHC, the identification of tau leptons, in particular in the hadronic decay mode, will be a challenging task due to an overwhelming QCD background which gives rise to jets of particles that can be hard to distinguish from hadronic tau decays. Equipped with excellent tracking and calorimetry, the ATLAS experiment has developed tau identification tools capable of working at the trigger level. This contribution presents tau trigger algorithms which exploit the main features of hadronic tau decays and describes the current tau trigger commissioning activities. Many of the SM processes being investigated at ATLAS, as well as numerous BSM searches, contain tau leptons in their final states. Being able to trigger effectively on the tau leptons in these events will contribute to the success of the ATLAS experiment. The tau trigger algorithms and monitoring infrastructure are ready for the first data, and are being tested with the data collected with cosmic muons. The development of efficiency measurements methods using QCD and Z {yields} {tau}{tau} events is well advanced.

  14. Explosively triggered gas-dielectric crowbar switch.

    PubMed

    Higgins, P B; Mathews, F H

    1979-04-01

    A gas-insulated gap switch with an unusually high standoff-to-trigger voltage ratio is described. Designed to standoff 500 kV when pressurized with SF(6) at 1.5 MPa (212 psi), the switch was triggered with as little as 19.3 kV across the gap by firing a shaped charge from one electrode toward the opposite electrode. Similar air-insulated and SF(6)-insulated gaps pressurized to 83 kPa (12 psi) and designed to standoff 50 and 150 kV, respectively, were triggered with 15.4 kV across the gap by firing an ordinary RP-2 detonator from one electrode toward the other.

  15. Self-triggering superconducting fault current limiter

    DOEpatents

    Yuan, Xing; Tekletsadik, Kasegn

    2008-10-21

    A modular and scaleable Matrix Fault Current Limiter (MFCL) that functions as a "variable impedance" device in an electric power network, using components made of superconducting and non-superconducting electrically conductive materials. The matrix fault current limiter comprises a fault current limiter module that includes a superconductor which is electrically coupled in parallel with a trigger coil, wherein the trigger coil is magnetically coupled to the superconductor. The current surge doing a fault within the electrical power network will cause the superconductor to transition to its resistive state and also generate a uniform magnetic field in the trigger coil and simultaneously limit the voltage developed across the superconductor. This results in fast and uniform quenching of the superconductors, significantly reduces the burnout risk associated with non-uniformity often existing within the volume of superconductor materials. The fault current limiter modules may be electrically coupled together to form various "n" (rows).times."m" (columns) matrix configurations.

  16. Use of GPUs in Trigger Systems

    NASA Astrophysics Data System (ADS)

    Lamanna, Gianluca

    In recent years the interest for using graphics processor (GPU) in general purpose high performance computing is constantly rising. In this paper we discuss the possible use of GPUs to construct a fast and effective real time trigger system, both in software and hardware levels. In particular, we study the integration of such a system in the NA62 trigger. The first application of GPUs for rings pattern recognition in the RICH will be presented. The results obtained show that there are not showstoppers in trigger systems with relatively low latency. Thanks to the use of off-the-shelf technology, in continous development for purposes related to video game and image processing market, the architecture described would be easily exported to other experiments, to build a versatile and fully customizable online selection.

  17. Paroxysmal discharges triggered by hearing spoken language.

    PubMed

    Tsuzuki, H; Kasuga, I

    1978-04-01

    We examined the modality of EEG activation by various kinds of acoustic stimulation in a middle-aged Japanese female with epilepsy. Paroxysmal discharges were triggered in the right frontal area (F4) by verval stimulation. For the activation of EEG, concentration of attention on the stimulation was essential; therefore paroxysmal discharges were triggered most easily by verbal stimuli when someone spoke to the patient directly. Stronger responses than usual were triggered by specific words, and apparently reflected the interest and concern of the patient. The latency from stimulation to paroxysmal discharges ranged from 230 to 1,300 msec, suggesting that the responses may have been a function of the perception and recognition of acoustic stimuli. "Heard-word epilepsy" or "Angesprochene Epilepsie" is suggested in this case.

  18. BTeV trigger/DAQ innovations

    SciTech Connect

    Votava, Margaret; /Fermilab

    2005-05-01

    BTeV was a proposed high-energy physics (HEP) collider experiment designed for the study of B-physics and CP Violation at the Tevatron at Fermilab. BTeV included a large-scale, high-speed trigger and data acquisition (DAQ) system, reading data from the detector at 500 Gbytes/sec and writing data to mass storage at a rate of 200 Mbytes/sec. The design of the trigger/DAQ system was innovative while remaining realistic in terms of technical feasibility, schedule and cost. This paper will give an overview of the BTeV trigger/DAQ architecture, highlight some of the technical challenges, and describe the approach that was used to solve these challenges.

  19. BTeV level 1 vertex trigger

    SciTech Connect

    Michael H.L.S. Wang

    2001-11-05

    BTeV is a B-physics experiment that expects to begin collecting data at the C0 interaction region of the Fermilab Tevatron in the year 2006. Its primary goal is to achieve unprecedented levels of sensitivity in the study of CP violation, mixing, and rare decays in b and c quark systems. In order to realize this, it will employ a state-of-the-art first-level vertex trigger (Level 1) that will look at every beam crossing to identify detached secondary vertices that provide evidence for heavy quark decays. This talk will briefly describe the BTeV detector and trigger, focus on the software and hardware aspects of the Level 1 vertex trigger, and describe work currently being done in these areas.

  20. Earthquake triggering by transient and static deformations

    USGS Publications Warehouse

    Gomberg, J.; Beeler, N.M.; Blanpied, M.L.; Bodin, P.

    1998-01-01

    Observational evidence for both static and transient near-field and far-field triggered seismicity are explained in terms of a frictional instability model, based on a single degree of freedom spring-slider system and rate- and state-dependent frictional constitutive equations. In this study a triggered earthquake is one whose failure time has been advanced by ??t (clock advance) due to a stress perturbation. Triggering stress perturbations considered include square-wave transients and step functions, analogous to seismic waves and coseismic static stress changes, respectively. Perturbations are superimposed on a constant background stressing rate which represents the tectonic stressing rate. The normal stress is assumed to be constant. Approximate, closed-form solutions of the rate-and-state equations are derived for these triggering and background loads, building on the work of Dieterich [1992, 1994]. These solutions can be used to simulate the effects of static and transient stresses as a function of amplitude, onset time t0, and in the case of square waves, duration. The accuracies of the approximate closed-form solutions are also evaluated with respect to the full numerical solution and t0. The approximate solutions underpredict the full solutions, although the difference decreases as t0, approaches the end of the earthquake cycle. The relationship between ??t and t0 differs for transient and static loads: a static stress step imposed late in the cycle causes less clock advance than an equal step imposed earlier, whereas a later applied transient causes greater clock advance than an equal one imposed earlier. For equal ??t, transient amplitudes must be greater than static loads by factors of several tens to hundreds depending on t0. We show that the rate-and-state model requires that the total slip at failure is a constant, regardless of the loading history. Thus a static load applied early in the cycle, or a transient applied at any time, reduces the stress

  1. More About The Video Event Trigger

    NASA Technical Reports Server (NTRS)

    Williams, Glenn L.

    1996-01-01

    Report presents additional information about system described in "Video Event Trigger" (LEW-15076). Digital electronic system processes video-image data to generate trigger signal when image shows significant change, such as motion, or appearance, disappearance, change in color, brightness, or dilation of object. Potential uses include monitoring of hallways, parking lots, and other areas during hours when supposed unoccupied, looking for fires, tracking airplanes or other moving objects, identification of missing or defective parts on production lines, and video recording of automobile crash tests.

  2. THE HIGH ENERGY TRANSIENT EXPLORER TRIGGERING ALGORITHM

    SciTech Connect

    E. FENIMORE; M. GALASSI

    2001-05-01

    The High Energy Transient Explorer uses a triggering algorithm for gamma-ray bursts that can achieve near the statistical limit by fitting to several background regions to remove trends. Dozens of trigger criteria run simultaneously covering time scales from 80 msec to 10.5 sec or longer. Each criteria is controlled by about 25 constants which gives the flexibility to search wide parameter spaces. On orbit, we have been able to operate at 6{sigma}, a factor of two more sensitive than previous experiments.

  3. The ZEUS calorimeter first level trigger

    SciTech Connect

    Foudas, C.; Dawson, J.; Krakauer, D.; Talaga, R.; Ali, I.; Behrens, B.; Fordham, C.; Goussiou, A.; Jaworski, M.; Lackey, J.

    1994-12-31

    The authors present results on the efficiency and performance of the ZEUS detector Calorimeter First Level Trigger (CFLT) using data taken during the 1993 HERA physics run. The CFLT is designed to process events in a digital pipeline applying pattern recognition algorithms and fast digital summation techniques in order to collect interesting physics events and reduce background from beam gas interactions. The total FLT efficiency was 98% for neutral current events and 85% for charged current events above Q{sup 2} of 10 GeV{sup 2}. The introduction of the isolated electron trigger increases the CFLT beam gas rejection by a factor of two.

  4. Remotely triggered nonvolcanic tremor in Sumbawa, Indonesia

    NASA Astrophysics Data System (ADS)

    Fuchs, Florian; Lupi, Matteo; Miller, Stephen

    2015-04-01

    Nonvolcanic (or tectonic) tremor is a seismic phenomenom which can provide important information about dynamics of plate boundaries but the underlying mechanisms are not well understood. Tectonic tremor is often associated with slow-slip (termed episodic tremor and slip) and understanding the mechanisms driving tremor presents an important challenge because it is likely a dominant aspect of the evolutionary processes leading to tsunamigenic, megathrust subduction zone earthquakes. Tectonic tremor is observed worldwide, mainly along major subduction zones and plate boundaries such as in Alaska/Aleutians, Cascadia, the San Andreas Fault, Japan or Taiwan. We present, for the first time, evidence for triggered tremor beneath the island of Sumbawa, Indonesia. The island of Sumbawa, Indonesia, is part of the Lesser Sunda Group about 250 km north of the Australian/Eurasian plate collision at the Java Trench with a convergence rate of approximately 70 mm/yr. We show surface wave triggered tremor beneath Sumbawa in response to three teleseismic earthquakes: the Mw9.0 2011 Tohoku earthquake and two oceanic strike-slip earthquakes (Mw 8.6 and Mw8.2) offshore of Sumatra in 2012. Tremor amplitudes scale with ground motion and peak at 180 nm/s ground velocity on the horizontal components. A comparison of ground motion of the three triggering events and a similar (nontriggering) Mw7.6 2012 Philippines event constrains an apparent triggering threshold of approximately 1 mm/s ground velocity or 8 kPa dynamic stress. Surface wave periods of 45-65 s appear optimal for triggering tremor at Sumbawa which predominantly correlates with Rayleigh waves, even though the 2012 oceanic events have stronger Love wave amplitudes and triggering potential. Rayleigh wave triggering, low-triggering amplitudes, and the tectonic setting all favor a model of tremor generated by localized fluid transport. We could not locate the tremor because of minimal station coverage, but data indicate several

  5. Perceived triggers of asthma: key to symptom perception and management.

    PubMed

    Janssens, T; Ritz, T

    2013-09-01

    Adequate asthma management depends on an accurate identification of asthma triggers. A review of the literature on trigger perception in asthma shows that individuals vary in their perception of asthma triggers and that the correlation between self-reported asthma triggers and allergy tests is only modest. In this article, we provide an overview of psychological mechanisms involved in the process of asthma triggers identification. We identify sources of errors in trigger identification and targets for behavioural interventions that aim to improve the accuracy of asthma trigger identification and thereby enhance asthma control.

  6. Thermally triggered degradation of transient electronic devices.

    PubMed

    Park, Chan Woo; Kang, Seung-Kyun; Hernandez, Hector Lopez; Kaitz, Joshua A; Wie, Dae Seung; Shin, Jiho; Lee, Olivia P; Sottos, Nancy R; Moore, Jeffrey S; Rogers, John A; White, Scott R

    2015-07-01

    Thermally triggered transient electronics using wax-encapsulated acid, which enable rapid device destruction via acidic degradation of the metal electronic components are reported. Using a cyclic poly(phthalaldehyde) (cPPA) substrate affords a more rapid destruction of the device due to acidic depolymerization of cPPA.

  7. Osmotic pressure-triggered cavitation in microcapsules.

    PubMed

    Shang, Luoran; Cheng, Yao; Wang, Jie; Yu, Yunru; Zhao, Yuanjin; Chen, Yongping; Gu, Zhongze

    2016-01-21

    A cavitation system was found in solid microcapsules with a membrane shell and a liquid core. By simply treating these microcapsules with hypertonic solutions, cavitation could be controllably triggered without special equipment or complex operations. A cavitation-formed vapor bubble was fully entrapped within the microcapsules, thus providing an advantageous method for fabricating encapsulated microbubbles with controllable dimensions and functional components. PMID:26659708

  8. Triggering of earthquake aftershocks by dynamic stresses

    USGS Publications Warehouse

    Kilb, Debi; Gomberg, J.; Bodin, P.

    2000-01-01

    It is thought that small 'static' stress changes due to permanent fault displacement can alter the likelihood of, or trigger, earthquakes on nearby faults. Many studies of triggering in the nearfield, particularly of aftershocks, rely on these static changes as the triggering agent and consider them only in terms of equivalent changes in the applied load on the fault. Here we report a comparison of the aftershock pattern of the moment magnitude MW = 7.3 Landers earthquake, not only with static stress changes but also with transient, oscillatory stress changes transmitted as seismic waves (that is, 'dynamic' stresses). Dynamic stresses do not permanently change the applied load and thus can trigger earthquakes only by altering the mechanical state or properties of the fault zone. These dynamically weakened faults may fail after the seismic waves have passed by, and might even cause earthquakes that would not otherwise have occurred. We find similar asymmetries in the aftershock and dynamic stress patterns, the latter being due to rupture propagation, whereas the static stress changes lack this asymmetry. Previous studies have shown that dynamic stresses can promote failure at remote distances, but here we show that they can also do so nearby.

  9. Event reconstruction algorithms for the ATLAS trigger

    NASA Astrophysics Data System (ADS)

    F-Martin, T.; Abolins, M.; Adragna, P.; Aleksandrov, E.; Aleksandrov, I.; Amorim, A.; Anderson, K.; Anduaga, X.; Aracena, I.; Asquith, L.; Avolio, G.; Backlund, S.; Badescu, E.; Baines, J.; Barria, P.; Bartoldus, R.; Batreanu, S.; Beck, H. P.; Bee, C.; Bell, P.; Bell, W. H.; Bellomo, M.; Benslama, K.; Berge, D.; Berger, N.; Berry, T.; Biglietti, M.; Blair, R. R.; Bogaerts, A.; Bold, T.; Bosman, M.; Boyd, J.; Brelier, B.; Burckhart, C. D.; Buttar, C.; Campanelli, M.; Caprini, M.; Carlino, G.; Casadei, D.; Casado, P.; Cataldi, G.; Cimino, D.; Ciobotaru, M.; Clements, D.; Coccaro, A.; Conde, M. P.; Conventi, F.; Corso, R. A.; Costa, M. J.; Coura, T. R.; Cranfield, R.; Cranmer, K.; Crone, G.; Dam, M.; Damazio, D.; Dawson, I.; Dawson, J.; DeAlmeida Simoes, A. J.; DeCecco, S.; DeSanto, A.; Della Pietra, M.; Delsart, P.-A.; Demers, S.; Demirkoz, B.; Di Mattia, A.; Dionisi, C.; Djilkibaev, R.; Dobinson, R.; Dobson, M.; Dotti, A.; Dova, M.; Drake, G.; Dufour, M.-A.; Eckweiler, S.; Ehrenfeld, W.; Eifert, T.; Ellis, N.; Emeliyanov, D.; Enoque Ferreira de Lima, D.; Ermoline, Y.; Eschrich, I.; Facius, K.; Falciano, S.; Farthouat, P.; Feng, E.; Ferland, J.; Ferrari, R.; Ferrer, M. L.; Fischer, G.; Francis, D.; Gadomski, S.; Garitaonandia, E. H.; Gaudio, G.; Gaumer, O.; George, S.; Giagu, S.; Goncalo, R.; Gorini, B.; Gorini, E.; Gowdy, S.; Grabowska, B. I.; Grancagnolo, S.; Green, B.; Haas, S.; Haberichter, W.; Hadavand, H.; Haeberli, C.; Haller, J.; Hamilton, A.; Hansen, J. R.; Hauschild, M.; Hauser, R.; Head, S.; Hillier, S.; Hoecker, A.; Hryn'ova, T.; Hughes, J. R.; Huston, J.; Idarraga, J.; Igonkina, O.; Inada, M.; Jain, V.; Johns, K.; Joos, M.; Kama, S.; Kanaya, N.; Kazarov, A.; Kehoe, R.; Khoriauli, G.; Kieft, G.; Kilvington, G.; Kirk, J.; Kiyamura, H.; Kolos, S.; Kono, T.; Konstantinidis, N.; Korcyl, K.; Kordas, K.; Kotov, V.; Krasznahorkay, A.; Kubota, T.; Kugel, A.; Kuhn, D.; Kurasige, H.; Kuwabara, T.; Kwee, R.; Lankford, A.; LeCompte, T.; Leahu, L.; Leahu, M.; Ledroit, F.; Lehmann, M. G.; Lei, X.; Lellouch, D.; Leyton, M.; Li, S.; Lim, H.; Lohse, T.; Losada, M.; Luci, C.; Luminari, L.; Mapelli, L.; Martin, B.; Martin, B. T.; Marzano, F.; Masik, J.; McMahon, T.; Mcpherson, R.; Medinnis, M.; Meessen, C.; Meirosu, C.; Messina, A.; Mincer, A.; Mineev, M.; Misiejuk, A.; Moenig, K.; Monticelli, F.; Moraes, A.; Moreno, D.; Morettini, P.; Murillo, G. R.; Nagano, K.; Nagasaka, Y.; Negri, A.; Nemethy, P.; Neusiedl, A.; Nisati, A.; Nozicka, M.; Omachi, C.; Osculati, B.; Osuna, C.; Padilla, C.; Panikashvili, N.; Parodi, F.; Pasqualucci, E.; Pauly, T.; Perera, V.; Perez, E.; Perez Reale, V.; Petersen, J.; Piegaia, R.; Pilcher, J.; Pinzon, G.; Pope, B.; Potter, C.; Primavera, M.; Radescu, V.; Rajagopalan, S.; Renkel, P.; Rescigno, M.; Rieke, S.; Risler, C.; Riu, I.; Robertson, S.; Roda, C.; Rodriguez, D.; Rogriquez, Y.; Ryabov, Y.; Ryan, P.; Salvatore, D.; Santamarina, C.; Santamarina, R. C.; Scannicchio, D.; Scannicchio, D. A.; Schiavi, C.; Schlereth, J.; Scholtes, I.; Schooltz, D.; Scott, W.; Segura, E.; Shimbo, N.; Sidoti, A.; Siragusa, G.; Sivoklokov, S.; Sloper, J. E.; Smizanska, M.; Soloviev, I.; Soluk, R.; Spagnolo, S.; Spiwoks, R.; Stancu, S.; Steinberg, P.; Stelzer, J.; Stradling, A.; Strom, D.; Strong, J.; Su, D.; Sushkov, S.; Sutton, M.; Szymocha, T.; Tapprogge, S.; Tarem, S.; Tarem, Z.; Teixeira, D. P.; Tokoshuku, K.; Torrence, E.; Touchard, F.; Tremblet, L.; Tripiana, M.; Usai, G.; Vachon, B.; Vandelli, W.; Ventura, A.; Vercesi, V.; Vermeulen, J.; Von Der Schmitt, J.; Wang, M.; Watson, A.; Wengler, T.; Werner, P.; Wheeler, E. S.; Wickens, F.; Wiedenmann, W.; Wielers M, M.; Wilkens, H.; Winklmeier, F.; Woehrling, E.-E.; Wu, S.-L.; Wu, X.; Xella, S.; Yamazaki, Y.; Yu, M.; Zema, F.; Zhang, J.; Zhao, L.; Zobernig, H.; dos Anjos, A.; zur Nedden, M.; zcan, E.; nel, G.

    2008-07-01

    The ATLAS experiment under construction at CERN is due to begin operation at the end of 2007. The detector will record the results of proton-proton collisions at a center-of-mass energy of 14 TeV. The trigger is a three-tier system designed to identify in real-time potentially interesting events that are then saved for detailed offline analysis. The trigger system will select approximately 200 Hz of potentially interesting events out of the 40 MHz bunch-crossing rate (with 109 interactions per second at the nominal luminosity). Algorithms used in the trigger system to identify different event features of interest will be described, as well as their expected performance in terms of selection efficiency, background rejection and computation time per event. The talk will concentrate on recent improvements and on performance studies, using a very detailed simulation of the ATLAS detector and electronics chain that emulates the raw data as it will appear at the input to the trigger system.

  10. Performance of the CMS High Level Trigger

    NASA Astrophysics Data System (ADS)

    Perrotta, Andrea

    2015-12-01

    The CMS experiment has been designed with a 2-level trigger system. The first level is implemented using custom-designed electronics. The second level is the so-called High Level Trigger (HLT), a streamlined version of the CMS offline reconstruction software running on a computer farm. For Run II of the Large Hadron Collider, the increases in center-of-mass energy and luminosity will raise the event rate to a level challenging for the HLT algorithms. The increase in the number of interactions per bunch crossing, on average 25 in 2012, and expected to be around 40 in Run II, will be an additional complication. We present here the expected performance of the main triggers that will be used during the 2015 data taking campaign, paying particular attention to the new approaches that have been developed to cope with the challenges of the new run. This includes improvements in HLT electron and photon reconstruction as well as better performing muon triggers. We will also present the performance of the improved tracking and vertexing algorithms, discussing their impact on the b-tagging performance as well as on the jet and missing energy reconstruction.

  11. Histopathology of tenosynovium in trigger fingers.

    PubMed

    Uchihashi, Kazuyoshi; Tsuruta, Toshiyuki; Mine, Hiroko; Aoki, Shigehisa; Nishijima-Matsunobu, Aki; Yamamoto, Mihoko; Kuraoka, Akio; Toda, Shuji

    2014-06-01

    Stenosing flexor tenosynovitis, trigger finger, is a common clinical disorder causing painful locking or contracture of the involved digits, and most instances are idiopathic. This problem is generally caused by a size mismatch between the swollen flexor tendon and the thickened first annular pulley. Although hypertrophic pulleys have been histologically and ultrasonographically detected, little is known about the histopathology of the tenosynovium covering the tendons of trigger fingers. We identified chondrocytoid cells that produced hyaluronic acid in 23 (61%) fingers and hypocellular collagen matrix in 32 (84%) fingers around the tenosynovium among 38 specimens of tenosynovium from patients with trigger fingers. These chondrocytoid cells expressed the synovial B cell marker CD44, but not the chondrocyte marker S-100 protein. The incidence of these findings was much higher than that of conventional findings of synovitis, such as inflammatory infiltrate (37%), increased vascularity (37%), hyperplasia of synovial lining cells (21%), or fibrin exudation (5%). We discovered the following distinctive histopathological features of trigger finger: hyaluronic acid-producing chondrocytoid cells originated from fibroblastic synovial B cells, and a hypocellular collagen matrix surrounding the tenosynovium. Thus, an edematous extracellular matrix with active hyaluronic acid synthesis might increase pressure under the pulley and contribute to the progression of stenosis. PMID:24965110

  12. THE STAR LEVEL-3 TRIGGER SYSTEM.

    SciTech Connect

    LANGE, J.S.; ADLER, C.; BERGER, J.; DEMELLO, M.; FLIERL, D.; ET AL

    1999-11-15

    The STAR level-3 trigger is a MYRINET interconnected ALPHA processor farm, performing online tracking of N{sub track} {ge} 8000 particles (N{sub point} {le} 45 per track) with a design input rate of R=100 Hz. A large scale prototype system was tested in 12/99 with laser and cosmic particle events.

  13. Triggered earthquakes and deep well activities

    USGS Publications Warehouse

    Nicholson, C.; Wesson, R.L.

    1992-01-01

    Earthquakes can be triggered by any significant perturbation of the hydrologic regime. In areas where potentially active faults are already close to failure, the increased pore pressure resulting from fluid injection, or, alternatively, the massive extraction of fluid or gas, can induce sufficient stress and/or strain changes that, with time, can lead to sudden catastrophic failure in a major earthquake. Injection-induced earthquakes typically result from the reduction in frictional strength along preexisting, nearby faults caused by the increased formation fluid pressure. Earthquakes associated with production appear to respond to more complex mechanisms of subsidence, crustal unloading, and poroelastic changes in response to applied strains induced by the massive withdrawal of subsurface material. As each of these different types of triggered events can occur up to several years after well activities have begun (or even several years after all well activities have stopped), this suggests that the actual triggering process may be a very complex combination of effects, particularly if both fluid extraction and injection have taken place locally. To date, more than thirty cases of earthquakes triggered by well activities can be documented throughout the United States and Canada. Based on these case histories, it is evident that, owing to preexisting stress conditions in the upper crust, certain areas tend to have higher probabilities of exhibiting such induced seismicity. ?? 1992 Birkha??user Verlag.

  14. Triggering of earthquake aftershocks by dynamic stresses.

    PubMed

    Kilb, D; Gomberg, J; Bodin, P

    2000-11-30

    It is thought that small 'static' stress changes due to permanent fault displacement can alter the likelihood of, or trigger, earthquakes on nearby faults. Many studies of triggering in the near-field, particularly of aftershocks, rely on these static changes as the triggering agent and consider them only in terms of equivalent changes in the applied load on the fault. Here we report a comparison of the aftershock pattern of the moment magnitude Mw = 7.3 Landers earthquake, not only with static stress changes but also with transient, oscillatory stress changes transmitted as seismic waves (that is, 'dynamic' stresses). Dynamic stresses do not permanently change the applied load and thus can trigger earthquakes only by altering the mechanical state or properties of the fault zone. These dynamically weakened faults may fail after the seismic waves have passed by, and might even cause earthquakes that would not otherwise have occurred. We find similar asymmetries in the aftershock and dynamic stress patterns, the latter being due to rupture propagation, whereas the static stress changes lack this asymmetry. Previous studies have shown that dynamic stresses can promote failure at remote distances, but here we show that they can also do so nearby.

  15. Multiple output timing and trigger generator

    SciTech Connect

    Wheat, Robert M.; Dale, Gregory E

    2009-01-01

    In support of the development of a multiple stage pulse modulator at the Los Alamos National Laboratory, we have developed a first generation, multiple output timing and trigger generator. Exploiting Commercial Off The Shelf (COTS) Micro Controller Units (MCU's), the timing and trigger generator provides 32 independent outputs with a timing resolution of about 500 ns. The timing and trigger generator system is comprised of two MCU boards and a single PC. One of the MCU boards performs the functions of the timing and signal generation (the timing controller) while the second MCU board accepts commands from the PC and provides the timing instructions to the timing controller. The PC provides the user interface for adjusting the on and off timing for each of the output signals. This system provides 32 output or timing signals which can be pre-programmed to be in an on or off state for each of 64 time steps. The width or duration of each of the 64 time steps is programmable from 2 {micro}s to 2.5 ms with a minimum time resolution of 500 ns. The repetition rate of the programmed pulse train is only limited by the time duration of the programmed event. This paper describes the design and function of the timing and trigger generator system and software including test results and measurements.

  16. FPGA Trigger System to Run Klystrons

    SciTech Connect

    Gray, Darius; /Texas A-M /SLAC

    2010-08-25

    The Klystron Department is in need of a new trigger system to update the laboratory capabilities. The objective of the research is to develop the trigger system using Field Programmable Gate Array (FPGA) technology with a user interface that will allow one to communicate with the FPGA via a Universal Serial Bus (USB). This trigger system will be used for the testing of klystrons. The key materials used consists of the Xilinx Integrated Software Environment (ISE) Foundation, a Programmable Read Only Memory (Prom) XCF04S, a Xilinx Spartan 3E 35S500E FPGA, Xilinx Platform Cable USB II, a Printed Circuit Board (PCB), a 100 MHz oscillator, and an oscilloscope. Key considerations include eight triggers, two of which have variable phase shifting capabilities. Once the project was completed the output signals were able to be manipulated via a Graphical User Interface by varying the delay and width of the signal. This was as planned; however, the ability to vary the phase was not completed. Future work could consist of being able to vary the phase. This project will give the operators in the Klystron Department more flexibility to run various tests.

  17. Cough in asthma triggered by reflux episodes.

    PubMed

    Mehta, Devendra; He, Zhaoping; Padman, Raj

    2014-05-01

    With combined pH and impedance monitoring, non-acid, as well as acid reflux episodes, are more commonly detected immediately prior to cough in asthma in children. Gastroesophageal reflux should be evaluated as a trigger for cough in difficult childhood asthma.

  18. Myofacial Trigger Points in Advanced Cancer Patients

    PubMed Central

    Hasuo, Hideaki; Ishihara, Tatsuhiko; Kanbara, Kenji; Fukunaga, Mikihiko

    2016-01-01

    Myofascial pain syndrome is started to be recognized as one of important factors of pain in cancer patients. However, no reports on features of myofascial trigger points were found in terminally-ill cancer populations. This time, we encountered 5 patients with myofascial pain syndrome and terminal cancer in whom delirium developed due to increased doses of opioid without a diagnosis of myofascial pain syndrome on initial presentation. The delirium subsided with dose reductions of opioid and treatment of myofascial pain syndrome. The common reason for a delayed diagnosis among the patients included an incomplete palpation of the painful sites, which led to unsuccessful myofascial trigger points identification. The features of myofascial trigger points included single onset in the cancer pain management site with opioid and the contralateral abdominal side muscles of the non-common sites. Withdrawal reflexes associated with cancer pain in the supine position, which are increasingly seen in the terminal cancer patients, were considered to have contributed to this siuation. We consider that careful palpation of the painful site is important, in order to obtain greater knowledge and understanding of the features of myofascial trigger points. PMID:26962285

  19. Event Reconstruction Algorithms for the ATLAS Trigger

    SciTech Connect

    Fonseca-Martin, T.; Abolins, M.; Adragna, P.; Aleksandrov, E.; Aleksandrov, I.; Amorim, A.; Anderson, K.; Anduaga, X.; Aracena, I.; Asquith, L.; Avolio, G.; Backlund, S.; Badescu, E.; Baines, J.; Barria, P.; Bartoldus, R.; Batreanu, S.; Beck, H.P.; Bee, C.; Bell, P.; Bell, W.H.; /more authors..

    2011-11-09

    The ATLAS experiment under construction at CERN is due to begin operation at the end of 2007. The detector will record the results of proton-proton collisions at a center-of-mass energy of 14 TeV. The trigger is a three-tier system designed to identify in real-time potentially interesting events that are then saved for detailed offline analysis. The trigger system will select approximately 200 Hz of potentially interesting events out of the 40 MHz bunch-crossing rate (with 10{sup 9} interactions per second at the nominal luminosity). Algorithms used in the trigger system to identify different event features of interest will be described, as well as their expected performance in terms of selection efficiency, background rejection and computation time per event. The talk will concentrate on recent improvements and on performance studies, using a very detailed simulation of the ATLAS detector and electronics chain that emulates the raw data as it will appear at the input to the trigger system.

  20. Natural and unnatural triggers of myocardial infarction.

    PubMed

    Kloner, Robert A

    2006-01-01

    Previous analyses have suggested that factors that stimulate the sympathetic nervous system and catecholamine release can trigger acute myocardial infarction. The wake-up time, Mondays, winter season, physical exertion, emotional upset, overeating, lack of sleep, cocaine, marijuana, anger, and sexual activity are some of the more common triggers. Certain natural disasters such as earthquakes and blizzards have also been associated with an increase in cardiac events. Certain unnatural triggers may play a role including the Holiday season. Holiday season cardiac events peak on Christmas and New Year. A number of hypotheses have been raised to explain the increase in cardiac events during the holidays, including overeating, excessive use of salt and alcohol, exposure to particulates, from fireplaces, a delay in seeking medical help, anxiety or depression related to the holidays, and poorer staffing of health care facilities at this time. War has been associated with an increase in cardiac events. Data regarding an increase in cardiac events during the 9/11 terrorist attack have been mixed. Understanding the cause of cardiovascular triggers will help in developing potential therapies.

  1. On near-source earthquake triggering

    USGS Publications Warehouse

    Parsons, T.; Velasco, A.A.

    2009-01-01

    When one earthquake triggers others nearby, what connects them? Two processes are observed: static stress change from fault offset and dynamic stress changes from passing seismic waves. In the near-source region (r ??? 50 km for M ??? 5 sources) both processes may be operating, and since both mechanisms are expected to raise earthquake rates, it is difficult to isolate them. We thus compare explosions with earthquakes because only earthquakes cause significant static stress changes. We find that large explosions at the Nevada Test Site do not trigger earthquakes at rates comparable to similar magnitude earthquakes. Surface waves are associated with regional and long-range dynamic triggering, but we note that surface waves with low enough frequency to penetrate to depths where most aftershocks of the 1992 M = 5.7 Little Skull Mountain main shock occurred (???12 km) would not have developed significant amplitude within a 50-km radius. We therefore focus on the best candidate phases to cause local dynamic triggering, direct waves that pass through observed near-source aftershock clusters. We examine these phases, which arrived at the nearest (200-270 km) broadband station before the surface wave train and could thus be isolated for study. Direct comparison of spectral amplitudes of presurface wave arrivals shows that M ??? 5 explosions and earthquakes deliver the same peak dynamic stresses into the near-source crust. We conclude that a static stress change model can readily explain observed aftershock patterns, whereas it is difficult to attribute near-source triggering to a dynamic process because of the dearth of aftershocks near large explosions.

  2. A large aperture laser triggered intensified charge coupled device using second-harmonic laser light triggering

    NASA Astrophysics Data System (ADS)

    Yamauchi, Toshihiko; Dimock, Dirck

    1997-06-01

    For application to a ruby laser Thomson scattering system, we have developed a laser triggered intensified charge coupled device (CCD) with 80 mm aperture, two stages of intensification, and 80 ns gating. To improve the dynamic range, the CCD is cooled and read out slowly (1 s). To obtain a good extinction ratio (>1.1×107), the zoom electrode of the first intensifier is gated using a ˜10 kV laser triggered spark gap. The stability of this spark gap has been greatly improved by frequency doubling the laser trigger light.

  3. AMPLITUDE DISCRIMINATOR HAVING SEPARATE TRIGGERING AND RECOVERY CONTROLS UTILIZING AUTOMATIC TRIGGERING

    DOEpatents

    Chase, R.L.

    1962-01-23

    A transistorized amplitude discriminator circuit is described in which the initial triggering sensitivity and the recovery threshold are separately adjustable in a convenient manner. The discriminator is provided with two independent bias components, one of which is for circuit hysteresis (recovery) and one of which is for trigger threshold level. A switching circuit is provided to remove the second bias component upon activation of the trigger so that the recovery threshold is always at the point where the trailing edge of the input signal pulse goes through zero or other desired value. (AEC)

  4. Photoconductive semiconductor switches: Laser Q-switch trigger and switch-trigger laser integration

    SciTech Connect

    Loubriel, G.M.; Mar, A.; Hamil, R.A.; Zutavern, F.J.; Helgeson, W.D.

    1997-12-01

    This report provides a summary of the Pulser In a Chip 9000-Discretionary LDRD. The program began in January of 1997 and concluded in September of 1997. The over-arching goal of this LDRD is to study whether laser diode triggered photoconductive semiconductor switches (PCSS) can be used to activate electro-optic devices such as Q-switches and Pockels cells and to study possible laser diode/switch integration. The PCSS switches we used were high gain GaAs switches because they can be triggered with small amounts of laser light. The specific goals of the LDRD were to demonstrate: (1) that small laser diode arrays that are potential candidates for laser-switch integration will indeed trigger the PCSS switch, and (2) that high gain GaAs switches can be used to trigger optical Q-switches in lasers such as the lasers to be used in the X-1 Advanced Radiation Source and the laser used for direct optical initiation (DOI) of explosives. The technology developed with this LDRD is now the prime candidate for triggering the Q switch in the multiple lasers in the laser trigger system of the X-1 Advanced Radiation Source and may be utilized in other accelerators. As part of the LDRD we developed a commercial supplier. To study laser/switch integration we tested triggering the high gain GaAs switches with: edge emitting laser diodes, vertical cavity surface emitting lasers (VCSELs), and transverse junction stripe (TJS) lasers. The first two types of lasers (edge emitting and VCSELs) did activate the PCSS but are harder to integrate with the PCSS for a compact package. The US lasers, while easier to integrate with the switch, did not trigger the PCSS at the US laser power levels we used. The PCSS was used to activate the Q-switch of the compact laser to be used in the X-1 Advanced Radiation Source.

  5. The BTeV trigger architecture

    SciTech Connect

    Michael H.L.S. Wang

    2003-08-21

    BTeV is a high-statistics B-physics experiment that will achieve new levels of sensitivity in testing the Standard Model explanation of CP violation, mixing, and rare decays in the b and c quark systems by operating in the unique environment of a hadron collider. In order to achieve its goals, it will make use of a state-of-the-art Si-pixel vertex detector and a novel 3-level hierarchical trigger that will look at every single beam crossing to detect the presence of heavy quark decays. This talk will describe the trigger architecture focusing on key design aspects that allow the use of commercially available technology in a highly feasible and practical solution that meets the demanding physics requirements of the BTeV experiment.

  6. GLAST Burst Monitor Trigger Classification Algorithm

    NASA Technical Reports Server (NTRS)

    Perrin, D. J.; Sidman, E. D.; Meegan, C. A.; Briggs, M. S.; Connaughton, V.

    2004-01-01

    The Gamma Ray Large Area Space Telescope (GLAST), currently set for launch in the first quarter of 2007, will consist of two instruments, the GLAST Burst Monitor (GBM) and the Large Area Telescope (LAT). One of the goals of the GBM is to identify and locate gamma-ray bursts using on-board software. The GLAST observatory can then be re-oriented to allow observations by the LAT. A Bayesian analysis will be used to distinguish gamma-ray bursts from other triggering events, such as solar flares, magnetospheric particle precipitation, soft gamma repeaters (SGRs), and Cygnus X-1 flaring. The trigger parameters used in the analysis are the burst celestial coordinates, angle from the Earth's horizon, spectral hardness, and the spacecraft geomagnetic latitude. The algorithm will be described and the results of testing will be presented.

  7. A light-triggered protein secretion system.

    PubMed

    Chen, Daniel; Gibson, Emily S; Kennedy, Matthew J

    2013-05-13

    Optical control of protein interactions has emerged as a powerful experimental paradigm for manipulating and studying various cellular processes. Tools are now available for controlling a number of cellular functions, but some fundamental processes, such as protein secretion, have been difficult to engineer using current optical tools. Here we use UVR8, a plant photoreceptor protein that forms photolabile homodimers, to engineer the first light-triggered protein secretion system. UVR8 fusion proteins were conditionally sequestered in the endoplasmic reticulum, and a brief pulse of light triggered robust forward trafficking through the secretory pathway to the plasma membrane. UVR8 was not responsive to excitation light used to image cyan, green, or red fluorescent protein variants, allowing multicolor visualization of cellular markers and secreted protein cargo as it traverses the cellular secretory pathway. We implemented this novel tool in neurons to demonstrate restricted, local trafficking of secretory cargo near dendritic branch points.

  8. Level-2 Calorimeter Trigger Upgrade at CDF

    SciTech Connect

    Flanagan, G.U.; /Purdue U.

    2007-04-01

    The CDF Run II Level-2 calorimeter trigger is implemented in hardware and is based on an algorithm used in Run I. This system insured good performance at low luminosity obtained during the Tevatron Run II. However, as the Tevatron instantaneous luminosity increases, the limitations of the current system due to the algorithm start to become clear. In this paper, we will present an upgrade of the Level-2 calorimeter trigger system at CDF. The upgrade is based on the Pulsar board, a general purpose VME board developed at CDF and used for upgrading both the Level-2 tracking and the Level-2 global decision crate. This paper will describe the design, hardware and software implementation, as well as the advantages of this approach over the existing system.

  9. Checkpoint triggering in a computer system

    DOEpatents

    Cher, Chen-Yong

    2016-09-06

    According to an aspect, a method for triggering creation of a checkpoint in a computer system includes executing a task in a processing node of the computer system and determining whether it is time to read a monitor associated with a metric of the task. The monitor is read to determine a value of the metric based on determining that it is time to read the monitor. A threshold for triggering creation of the checkpoint is determined based on the value of the metric. Based on determining that the value of the metric has crossed the threshold, the checkpoint including state data of the task is created to enable restarting execution of the task upon a restart operation.

  10. Does low atmospheric pressure independently trigger migraine?

    PubMed

    Bolay, Hayrunnisa; Rapoport, Alan

    2011-10-01

    Although atmospheric weather changes are often listed among the common migraine triggers, studies to determine the specific weather component(s) responsible have yielded inconsistent results. Atmospheric pressure change produces air movement, and low pressure in particular is associated with warm weather, winds, clouds, dust, and precipitation, but how this effect might generate migraine is not immediately obvious. Humans are exposed to low atmospheric pressure in situations such as ascent to high altitude or traveling by airplane in a pressurized cabin. In this brief overview, we consider those conditions and experimental data delineating other elements in the atmosphere potentially related to migraine (such as Saharan dust). We conclude that the available data suggest low atmospheric pressure unaccompanied by other factors does not trigger migraine.

  11. Insignificant solar-terrestrial triggering of earthquakes

    USGS Publications Warehouse

    Love, Jeffrey J.; Thomas, Jeremy N.

    2013-01-01

    We examine the claim that solar-terrestrial interaction, as measured by sunspots, solar wind velocity, and geomagnetic activity, might play a role in triggering earthquakes. We count the number of earthquakes having magnitudes that exceed chosen thresholds in calendar years, months, and days, and we order these counts by the corresponding rank of annual, monthly, and daily averages of the solar-terrestrial variables. We measure the statistical significance of the difference between the earthquake-number distributions below and above the median of the solar-terrestrial averages by χ2 and Student's t tests. Across a range of earthquake magnitude thresholds, we find no consistent and statistically significant distributional differences. We also introduce time lags between the solar-terrestrial variables and the number of earthquakes, but again no statistically significant distributional difference is found. We cannot reject the null hypothesis of no solar-terrestrial triggering of earthquakes.

  12. Correlated observations of three triggered lightning flashes

    NASA Technical Reports Server (NTRS)

    Idone, V. P.; Orville, R. E.; Hubert, P.; Barret, L.; Eybert-Berard, A.

    1984-01-01

    Three triggered lightning flashes, initiated during the Thunderstorm Research International Program (1981) at Langmuir Laboratory, New Mexico, are examined on the basis of three-dimensional return stroke propagation speeds and peak currents. Nonlinear relationships result between return stroke propagation speed and stroke peak current for 56 strokes, and between return stroke propagation speed and dart leader propagation speed for 32 strokes. Calculated linear correlation coefficients include dart leader propagation speed and ensuing return stroke peak current (32 strokes; r = 0.84); and stroke peak current and interstroke interval (69 strokes; r = 0.57). Earlier natural lightning data do not concur with the weak positive correlation between dart leader propagation speed and interstroke interval. Therefore, application of triggered lightning results to natural lightning phenomena must be made with certain caveats. Mean values are included for the three-dimensional return stroke propagation speed and for the three-dimensional dart leader propagation speed.

  13. The ALICE Central Trigger Processor (CTP) upgrade

    NASA Astrophysics Data System (ADS)

    Krivda, M.; Alexandre, D.; Barnby, L. S.; Evans, D.; Jones, P. G.; Jusko, A.; Lietava, R.; Pospíšil, J.; Villalobos Baillie, O.

    2016-03-01

    The ALICE Central Trigger Processor (CTP) at the CERN LHC has been upgraded for LHC Run 2, to improve the Transition Radiation Detector (TRD) data-taking efficiency and to improve the physics performance of ALICE. There is a new additional CTP interaction record sent using a new second Detector Data Link (DDL), a 2 GB DDR3 memory and an extension of functionality for classes. The CTP switch has been incorporated directly onto the new LM0 board. A design proposal for an ALICE CTP upgrade for LHC Run 3 is also presented. Part of the development is a low latency high bandwidth interface whose purpose is to minimize an overall trigger latency.

  14. CNS disease triggering Takotsubo stress cardiomyopathy.

    PubMed

    Finsterer, Josef; Wahbi, Karim

    2014-12-15

    There are a number of hereditary and non-hereditary central nervous system (CNS) disorders, which directly or indirectly affect the heart (brain-heart disorders). The most well-known of these CNS disorders are epilepsy, stroke, infectious or immunological encephalitis/meningitis, migraine, and traumatic brain injury. In addition, a number of hereditary and non-hereditary neurodegenerative disorders may impair cardiac functions. Affection of the heart may manifest not only as arrhythmias, myocardial infarction, autonomic impairment, systolic dysfunction/heart failure, arterial hypertension, or pulmonary hypertension, but also as stress cardiomyopathy (Takotsubo syndrome, TTS). CNS disease triggering TTS includes subarachnoid bleeding, epilepsy, ischemic stroke, intracerebral bleeding, migraine, encephalitis, traumatic brain injury, PRES syndrome, or ALS. Usually, TTS is acutely precipitated by stress triggered by various different events. TTS is one of the cardiac abnormalities most frequently induced by CNS disorders. Appropriate management of TTS from CNS disorders is essential to improve the outcome of affected patients. PMID:25213573

  15. Does low atmospheric pressure independently trigger migraine?

    PubMed

    Bolay, Hayrunnisa; Rapoport, Alan

    2011-10-01

    Although atmospheric weather changes are often listed among the common migraine triggers, studies to determine the specific weather component(s) responsible have yielded inconsistent results. Atmospheric pressure change produces air movement, and low pressure in particular is associated with warm weather, winds, clouds, dust, and precipitation, but how this effect might generate migraine is not immediately obvious. Humans are exposed to low atmospheric pressure in situations such as ascent to high altitude or traveling by airplane in a pressurized cabin. In this brief overview, we consider those conditions and experimental data delineating other elements in the atmosphere potentially related to migraine (such as Saharan dust). We conclude that the available data suggest low atmospheric pressure unaccompanied by other factors does not trigger migraine. PMID:21906054

  16. Modeling seismic swarms triggered by aseismic transients

    NASA Astrophysics Data System (ADS)

    Llenos, Andrea L.; McGuire, Jeffrey J.; Ogata, Yosihiko

    2009-04-01

    The rate of earthquake occurrence varies by many orders of magnitude in a given region due to variations in the stress state of the crust. Our focus here is on variations in seismicity rate triggered by transient aseismic processes such as fluid flow, fault creep or magma intrusion. While these processes have been shown to trigger earthquakes, converting observed seismicity variations into estimates of stress rate variations has been challenging. Essentially aftershock sequences often obscure changes in the background seismicity rate resulting from aseismic processes. Two common approaches for estimating the time dependence of the underlying driving mechanisms are the stochastic Epidemic Type Aftershock Sequence model (ETAS) [Ogata, Y., (1988), Statistical models for earthquake occurrences and residual analysis for point processes, J. Am. Stat. Assoc., 83, 9-27.] and a physical approach based on the rate- and state-model of fault friction [Dieterich, J., (1994), A constitutive law for rate of earthquake production and its application to earthquake clustering, J. Geophys. Res., 99, 2601-2618.]. The models have different strengths that could be combined to allow more quantitative studies of earthquake triggering. To accomplish this, we identify the parameters that relate to one another in the two models and examine their dependence on stressing rate. A particular conflict arises because the rate-state model predicts that aftershock productivity scales with stressing rate while the ETAS model assumes that it is time independent. To resolve this issue, we estimate triggering parameters for 4 earthquake swarms contemporaneous with geodetically observed deformation transients in various tectonic environments. We find that stressing rate transients increase the background seismicity rate without affecting aftershock productivity. We then specify a combined model for seismicity rate variations that will allow future studies to invert seismicity catalogs for variations in

  17. Moon origin - The impact-trigger hypothesis

    NASA Technical Reports Server (NTRS)

    Hartmann, William K.

    1986-01-01

    Arguments in favor of the impact-trigger model of lunar origin are presented. Lunar properties favoring this hypothesis include: (1) lunar iron and volatile deficiency; (2) angular momentum of the earth-moon system; and (3) similar O isotopes, bulk iron contents, and densities of earth's mantle and the moon. It is shown that the intense early bombardment averaged during earth's formation was several billion times the present meteoritic mass flux, consistent with a giant impact.

  18. Acoustic Manifestations of Natural versus Triggered Lightning

    NASA Astrophysics Data System (ADS)

    Arechiga, R. O.; Johnson, J. B.; Edens, H. E.; Rison, W.; Thomas, R. J.; Eack, K.; Eastvedt, E. M.; Aulich, G. D.; Trueblood, J.

    2010-12-01

    Positive leaders are rarely detected by VHF lightning detection systems; positive leader channels are usually outlined only by recoil events. Positive cloud-to-ground (CG) channels are usually not mapped. The goal of this work is to study the types of thunder produced by natural versus triggered lightning and to assess which types of thunder signals have electromagnetic activity detected by the lightning mapping array (LMA). Towards this end we are investigating the lightning detection capabilities of acoustic techniques, and comparing them with the LMA. In a previous study we used array beam forming and time of flight information to locate acoustic sources associated with lightning. Even though there was some mismatch, generally LMA and acoustic techniques saw the same phenomena. To increase the database of acoustic data from lightning, we deployed a network of three infrasound arrays (30 m aperture) during the summer of 2010 (August 3 to present) in the Magdalena mountains of New Mexico, to monitor infrasound (below 20 Hz) and audio range sources due to natural and triggered lightning. The arrays were located at a range of distances (60 to 1400 m) surrounding the triggering site, called the Kiva, used by Langmuir Laboratory to launch rockets. We have continuous acoustic measurements of lightning data from July 20 to September 18 of 2009, and from August 3 to September 1 of 2010. So far, lightning activity around the Kiva was higher during the summer of 2009. We will present acoustic data from several interesting lightning flashes including a comparison between a natural and a triggered one.

  19. CMS muon detector and trigger performance

    NASA Astrophysics Data System (ADS)

    Park, Sung Keun; CMS Collaboration

    2011-06-01

    The CMS muon system has been in full operation since its commissioning with several million events of cosmic ray data. The muon system of the CMS experiment consists of three independent detectors: Resistive Plate Chambers (RPCs) both in the barrel and the endcap, Drift Tubes (DTs) in the barrel, and Cathode Strip Chambers (CSCs) in the endcap region. In this report, the performance of each of these muon detectors and their trigger response are presented.

  20. On the complexity of triggering evolutionary radiations.

    PubMed

    Bouchenak-Khelladi, Yanis; Onstein, Renske E; Xing, Yaowu; Schwery, Orlando; Linder, H Peter

    2015-07-01

    Recent developments in phylogenetic methods have made it possible to reconstruct evolutionary radiations from extant taxa, but identifying the triggers of radiations is still problematic. Here, we propose a conceptual framework to explore the role of variables that may impact radiations. We classify the variables into extrinsic conditions vs intrinsic traits, whether they provide background conditions, trigger the radiation, or modulate the radiation. We used three clades representing angiosperm phylogenetic and structural diversity (Ericaceae, Fagales and Poales) as test groups. We located radiation events, selected variables potentially associated with diversification, and inferred the temporal sequences of evolution. We found 13 shifts in diversification regimes in the three clades. We classified the associated variables, and determined whether they originated before the relevant radiation (backgrounds), originated simultaneously with the radiations (triggers), or evolved later (modulators). By applying this conceptual framework, we establish that radiations require both extrinsic conditions and intrinsic traits, but that the sequence of these is not important. We also show that diversification drivers can be detected by being more variable within a radiation than conserved traits that only allow occupation of a new habitat. This framework facilitates exploration of the causative factors of evolutionary radiations.

  1. Transdermal anaesthesia for percutaneous trigger finger release.

    PubMed

    Yiannakopoulos, Christos K; Ignatiadis, Ioannis A

    2006-01-01

    The purpose of this study was to evaluate the safety and efficiency of transdermal anaesthesia using eutectic mixture of lidocaine and prilocaine (EMLA) in patients undergoing percutaneous trigger finger release and to compare it with lidocaine infiltration. In this prospective, randomised study percutaneous release of the A1 annular pulley was performed to treat stenosing tenosynovitis (trigger finger syndrome) in 50 patients (50 fingers). The procedure was performed either under transdermal anaesthesia using EMLA applied transcutaneously 120 minutes prior to the operation (Group A, n = 25) or using local infiltration anaesthesia using lidocaine (Group B, n = 25). Pain experienced during administration of anaesthesia and during the operation was assessed using a 10-point Visual Analogue Pain Scale (VAPS), while all patients rated the effectiveness of anaesthesia with a 5-point scale. There were no significant differences between the two groups in the VAPS during the operation (1.33 +/- 0.52 versus 1.59 +/- 0.87) and the satisfaction scores (4.6 +/- 0.2 versus 4.4 +/- 0.3). The VAPS score during the administration of anaesthesia was statistically significantly less in the EMLA group (0 versus 5.96 +/- 2.41). All patients were satisfied with the final result of the operation. Percutaneous trigger finger release can be performed as an office procedure with the use of EMLA avoiding the use of injectable local infiltration anaesthesia. PMID:17405199

  2. ENSO-triggered floods in South America

    NASA Astrophysics Data System (ADS)

    Isla, Federico Ignacio

    2016-04-01

    ENSO-triggered floods altered completely the annual discharge of most watersheds of South America. Anomalous years as 1941, 1982-83 and 1997-98 signified enormous discharges of rivers draining toward the Pacific but also to the Atlantic Ocean. These floods affected large cities as Porto Alegre, Blumenau, Curitiba, Asunción, Santa Fe and Buenos Aires. Maximum discharge months are particular and easily distinguished at those watersheds located at the South American Arid Diagonal. At watersheds conditioned by precipitations delivered from the Atlantic or Pacific anticyclonic centers the ENSO-triggered floods are difficult to discern. The floods of 1941 affected 70,000 inhabitants in Porto Alegre. In 1983, Blumenau city was flooded during several days; and the Paraná River multiplied 15 times the width of its middle floodplain. The Colorado River in Northern Patagonia connected for the last time to the Desaguadero-Chadileuvú-Curacó system and therefore received saline water. ENSO years modify also the water balance of certain piedmont lakes of Southern Patagonia: the increases in snow accumulations cause high water levels with a lag of 13 months. The correlation between the maximum monthly discharges of 1982-83 and 1997-98 at different regions and watersheds indicates they can be forecasted for future floods triggered by same phenomena. South American rivers can be classified therefore into ENSO-affected, and ENSO-dominated, for those within the Arid Diagonal that are exclusively subject to high discharges during these years.

  3. CMS High Level Trigger Timing Measurements

    NASA Astrophysics Data System (ADS)

    Richardson, Clint

    2015-12-01

    The two-level trigger system employed by CMS consists of the Level 1 (L1) Trigger, which is implemented using custom-built electronics, and the High Level Trigger (HLT), a farm of commercial CPUs running a streamlined version of the offline CMS reconstruction software. The operational L1 output rate of 100 kHz, together with the number of CPUs in the HLT farm, imposes a fundamental constraint on the amount of time available for the HLT to process events. Exceeding this limit impacts the experiment's ability to collect data efficiently. Hence, there is a critical need to characterize the performance of the HLT farm as well as the algorithms run prior to start up in order to ensure optimal data taking. Additional complications arise from the fact that the HLT farm consists of multiple generations of hardware and there can be subtleties in machine performance. We present our methods of measuring the timing performance of the CMS HLT, including the challenges of making such measurements. Results for the performance of various Intel Xeon architectures from 2009-2014 and different data taking scenarios are also presented.

  4. Another look at aircraft-triggered lightning

    NASA Technical Reports Server (NTRS)

    Clifford, D. W.

    1980-01-01

    There is positive evidence that a rapidly moving aircraft charged to high potentials by triboelectric processes can trigger lightning discharges by passage through freezing precipitation. The freezing zone in a nonstormy rain cloud is shown to be an electrically volatile region because of the potent charge exchange mechanisms which are active in agitated mixtures of supercooled water droplet and ice. Several intensifying effects are suggested which can be produced by the passage of an aircraft through this precipitation, resulting in a highly-ionized wake which acts like a trailing conductor. If weak charge centers are present in the cloud, the ionized wake acts to short out the gradient field resulting in very high potentials at the aircraft. The high potentials explain the electrical activity at the aircraft described by pilots, including intense corona, sparks and radio interference terminating in a loud discharge. Lightning strikes to naval aircraft towing gunnery targets at the end of long steel cables are described, showing that the same triggering mechanism may be involved in those cases. Recommendations are made to include triggering experiments in government flight programs now in progress.

  5. ATP-triggered anticancer drug delivery

    NASA Astrophysics Data System (ADS)

    Mo, Ran; Jiang, Tianyue; Disanto, Rocco; Tai, Wanyi; Gu, Zhen

    2014-03-01

    Stimuli-triggered drug delivery systems have been increasingly used to promote physiological specificity and on-demand therapeutic efficacy of anticancer drugs. Here we utilize adenosine-5'-triphosphate (ATP) as a trigger for the controlled release of anticancer drugs. We demonstrate that polymeric nanocarriers functionalized with an ATP-binding aptamer-incorporated DNA motif can selectively release the intercalating doxorubicin via a conformational switch when in an ATP-rich environment. The half-maximal inhibitory concentration of ATP-responsive nanovehicles is 0.24 μM in MDA-MB-231 cells, a 3.6-fold increase in the cytotoxicity compared with that of non-ATP-responsive nanovehicles. Equipped with an outer shell crosslinked by hyaluronic acid, a specific tumour-targeting ligand, the ATP-responsive nanocarriers present an improvement in the chemotherapeutic inhibition of tumour growth using xenograft MDA-MB-231 tumour-bearing mice. This ATP-triggered drug release system provides a more sophisticated drug delivery system, which can differentiate ATP levels to facilitate the selective release of drugs.

  6. Clinical implication of latent myofascial trigger point.

    PubMed

    Celik, Derya; Mutlu, Ebru Kaya

    2013-08-01

    Myofascial trigger points (MTrPs) are hyperirritable points located within a taut band of skeletal muscle or fascia, which cause referred pain, local tenderness and autonomic changes when compressed. There are fundamental differences between the effects produced by the two basic types of MTrPs (active and latent). Active trigger points (ATrPs) usually produce referred pain and tenderness. In contrast, latent trigger points (LTrPs) are foci of hyperirritability in a taut band of muscle, which are clinically associated with a local twitch response, tenderness and/or referred pain upon manual examination. LTrPs may be found in many pain-free skeletal muscles and may be "activated" and converted to ATrPs by continuous detrimental stimuli. ATrPs can be inactivated by different treatment strategies; however, they never fully disappear but rather convert to the latent form. Therefore, the diagnosis and treatment of LTrPs is important. This review highlights the clinical implication of LTrPs.

  7. Aspartame as a dietary trigger of headache.

    PubMed

    Lipton, R B; Newman, L C; Cohen, J S; Solomon, S

    1989-02-01

    Many dietary factors have been implicated as possible precipitants of headache. There have been recent differences of opinion with regard to the effect of the artificial sweetener aspartame as a precipitant of headache. To assess the importance of aspartame as a dietary factor in headache, 190 consecutive patients of the Montefiore Medical Center Headache Unit were questioned about the effect of alcohol, carbohydrates and aspartame in triggering their headaches. Of the 171 patients who fully completed the survey, 49.7 percent reported alcohol as a precipitating factor, compared to 8.2 percent reporting aspartame and 2.3 percent reporting carbohydrates. Patients with migraine were significantly more likely to report alcohol as a triggering factor and also reported aspartame as a precipitant three times more often than those having other types of headache. The conflicting results of two recent placebo-control studies of aspartame and headache are discussed. We conclude that aspartame may be an important dietary trigger of headache in some people.

  8. The Sandia transportable triggered lightning instrumentation facility

    NASA Technical Reports Server (NTRS)

    Schnetzer, George H.; Fisher, Richard J.

    1991-01-01

    Development of the Sandia Transportable Triggered Lightning Instrumentation Facility (SATTLIF) was motivated by a requirement for the in situ testing of a munitions storage bunker. Transfer functions relating the incident flash currents to voltages, currents, and electromagnetic field values throughout the structure will be obtained for use in refining and validating a lightning response computer model of this type of structure. A preliminary shakedown trial of the facility under actual operational conditions was performed during summer of 1990 at the Kennedy Space Center's (KSC) rocket-triggered lightning test site. A description is given of the SATTLIF, which is readily transportable on a single flatbed truck of by aircraft, and its instrumentation for measuring incident lightning channel currents and the responses of the systems under test. Measurements of return-stroke current peaks obtained with the SATTLIF are presented. Agreement with data acquired on the same flashes with existing KSC instrumentation is, on average, to within approximately 7 percent. Continuing currents were measured with a resolution of approximately 2.5 A. This field trial demonstrated the practicality of using a transportable triggered lightning facility for specialized test applications.

  9. Predicting asthma control: the role of psychological triggers.

    PubMed

    Ritz, Thomas; Bobb, Carol; Griffiths, Chris

    2014-01-01

    Asthma triggers have been linked to adverse health outcomes in asthma, but little is known about their association with asthma control. Because trigger avoidance is an integral part of successful asthma management, psychological triggers in particular may be associated with suboptimal asthma control, given the difficulty of controlling them. We examined cross-sectional and longitudinal associations of perceived asthma triggers with self-report of asthma control impairment, symptoms, and spirometric lung function (forced expiratory volume in the 1st second, [FEV1]) in 179 adult primary care asthma patients. Perceived asthma triggers explained up to 42.5% of the variance in asthma control and symptoms, but not in FEV1 alone. Allergic triggers explained up to 12.1% of the asthma control and symptom variance, three nonallergic trigger types, air pollution/irritants, physical activity, and infection, explained up to 26.2% over and above allergic triggers, and psychological triggers up to 9.5% over and above all other triggers. Psychological triggers alone explained up to 33.9% of the variance and were the only trigger class that was consistently significant in all final multiple regression models predicting control and symptoms. Psychological triggers also predicted lower asthma control 3-6 months later, although controlling for initial asthma control eliminated this association. In free reports of individually relevant triggers, only psychological triggers were associated with suboptimal asthma control. Trigger factors are important predictors of self-reported asthma control and symptoms but not actual lung function. Particular attention should be directed to psychological triggers as indicators of patients' perceptions of suboptimal asthma control.

  10. Oracle Database Y2K Protection Triggers Generators

    SciTech Connect

    Cribbs, C.A.

    1999-06-02

    I developed PL/SQL code that generates or modifies PL/SQL �BEFORE EACH ROW� triggers to protect database date columns from Y2K non-compliant date input (from all sources) into the database. A function is imbedded in the triggers that uses the �RR� year formatted date conversion. For each table with at least one date column and with INSERT/UPDATE/DELETE trigger(s), my code inserts date conversion code into the existing trigger(s). For INSERT/UPDATE not in a trigger(s), my code creates a trigger for the absent DML command(s). Designed to be: Transferable to other servers with minimum effort; A uniform and consistent problem solution with easy implementation, testing, and configuration management. No need to manually code and edit SQL trigger files: Modifies existing triggers; Creates needed triggers; Self documented (output comments with code); SQL files configuration management ready. Can customize the: Date conversion function; Code modifications for the trigger; Universal lookup/key; �

  11. Compact SCR trigger circuit for ignitron switch operates efficiently

    NASA Technical Reports Server (NTRS)

    Foster, L. E.

    1965-01-01

    Trigger circuit with two series-connected SCR triggers an ignitron switch used to discharge high-energy capacitor banks. It does not require a warmup period and operates at relatively high efficiency.

  12. New shower maximum trigger for electrons and photons at CDF

    SciTech Connect

    Amidei, D.; Burkett, K.; Gerdes, D.; Miao, C.; Wolinski, D.; Byrum, K.; Dawson, J.; Nodulman, L.; Wicklund, A.B.

    1994-07-28

    For the 1994 Tevatron collider run, CDF has upgraded the electron and photo trigger hardware to make use of shower position and size information from the central shower maximum detector. For electrons, the upgrade has resulted in a 50% reduction in backgrounds while retaining approximately 90% of the signal. The new trigger also eliminates the background to photon triggers from single-phototube spikes.

  13. Rational engineering of a virulence gene from Mycobacterium tuberculosis facilitates proteomic analysis of a natural protein N-terminus

    PubMed Central

    Reyna, Cristal; Mba Medie, Felix; Champion, Matthew M.; Champion, Patricia A.

    2016-01-01

    Mass spectrometry (MS) for the detection of proteins is an indispensable tool for evaluating the biological processes of the proteome. Proteomics frequently requires proteolysis of proteins into peptide fragments. Proteins can be refractory to ideal proteolysis at the sequence level rendering them difficult to analyze by routine proteomics methods. EsxA (ESAT-6, Early Secreted Antigen, 6kDa) is a major virulence determinant of Mycobacterium tuberculosis, the cause of human tuberculosis. EsxA is routinely used to evaluate mycobacterial virulence in the laboratory and as a biomarker for tuberculosis in humans. The sequence of EsxA hinders deeper MS analysis beyond routine detection. Here we engineer the sequence of EsxA to add desirable tryptic properties aimed at improving complex MS analysis. We demonstrate that EsxA variants are amenable to MS analysis and remain functional in established in vitro and ex vivo assays of Esx-1-function. We provide the first demonstration of molecular engineering to specifically improve MS analysis of individual microbial proteins. PMID:27625110

  14. The role of MscL amphipathic N terminus indicates a blueprint for bilayer-mediated gating of mechanosensitive channels

    PubMed Central

    Bavi, Navid; Cortes, D. Marien; Cox, Charles D.; Rohde, Paul R.; Liu, Weihong; Deitmer, Joachim W.; Bavi, Omid; Strop, Pavel; Hill, Adam P.; Rees, Douglas; Corry, Ben; Perozo, Eduardo; Martinac, Boris

    2016-01-01

    The bacterial mechanosensitive channel MscL gates in response to membrane tension as a result of mechanical force transmitted directly to the channel from the lipid bilayer. MscL represents an excellent model system to study the basic biophysical principles of mechanosensory transduction. However, understanding of the essential structural components that transduce bilayer tension into channel gating remains incomplete. Here using multiple experimental and computational approaches, we demonstrate that the amphipathic N-terminal helix of MscL acts as a crucial structural element during tension-induced gating, both stabilizing the closed state and coupling the channel to the membrane. We propose that this may also represent a common principle in the gating cycle of unrelated mechanosensitive ion channels, allowing the coupling of channel conformation to membrane dynamics. PMID:27329693

  15. EFHC1, a protein mutated in juvenile myoclonic epilepsy, associates with the mitotic spindle through its N-terminus

    SciTech Connect

    Nijs, Laurence de; Lakaye, Bernard; Coumans, Bernard; Leon, Christine; Ikeda, Takashi; Delgado-Escueta, Antonio V.; Chanas, Grazyna . E-mail: G.Chanas@ulg.ac.be

    2006-09-10

    A novel gene, EFHC1, mutated in juvenile myoclonic epilepsy (JME) encodes a protein with three DM10 domains of unknown function and one putative EF-hand motif. To study the properties of EFHC1, we expressed EGFP-tagged protein in various cell lines. In interphase cells, the fusion protein was present in the cytoplasm and in the nucleus with specific accumulation at the centrosome. During mitosis EGFP-EFHC1 colocalized with the mitotic spindle, especially at spindle poles and with the midbody during cytokinesis. Using a specific antibody, we demonstrated the same distribution of the endogenous protein. Deletion analyses revealed that the N-terminal region of EFHC1 is crucial for the association with the mitotic spindle and the midbody. Our results suggest that EFHC1 could play an important role during cell division.

  16. N-terminus conservation in the terminal pigment of phycobilisomes from a prokaryotic and eukaryotic alga. [Porphyridium cruentum; Nostoc

    SciTech Connect

    Gantt, E.; Cunningham, F.X. Jr.; Lipschultz, C.A.; Mimuro, M. )

    1988-04-01

    High molecular weight polypeptides from phycobilisomes, believed to be involved in facilitating the energy flow from phycobilisomes to thylakoids, are conserved in the prokaryote Nostoc sp. and the eukaryote Porphyridium cruentum. Partial N-terminal sequence analysis of the phycobilisome-polypeptides of Nostoc (94 kilodalton) and Porphyridium (92 kilodalton) revealed 55% identity in the first 20 residues, but no significant homology with sequences of other phycobiliproteins or phycobilisome-linkers. Polypeptides (94 and 92 kilodalton) from Nostoc thylakoids free of phycobilisomes, previously presumed to be involved in the phycobilisome-thylakoid linkage exhibit the same immunocrossreactivity but are different from the 94 kilodalton-phycobilisome polypeptide by having blocked N-termini and a different amino acid composition.

  17. Rational engineering of a virulence gene from Mycobacterium tuberculosis facilitates proteomic analysis of a natural protein N-terminus.

    PubMed

    Reyna, Cristal; Mba Medie, Felix; Champion, Matthew M; Champion, Patricia A

    2016-01-01

    Mass spectrometry (MS) for the detection of proteins is an indispensable tool for evaluating the biological processes of the proteome. Proteomics frequently requires proteolysis of proteins into peptide fragments. Proteins can be refractory to ideal proteolysis at the sequence level rendering them difficult to analyze by routine proteomics methods. EsxA (ESAT-6, Early Secreted Antigen, 6kDa) is a major virulence determinant of Mycobacterium tuberculosis, the cause of human tuberculosis. EsxA is routinely used to evaluate mycobacterial virulence in the laboratory and as a biomarker for tuberculosis in humans. The sequence of EsxA hinders deeper MS analysis beyond routine detection. Here we engineer the sequence of EsxA to add desirable tryptic properties aimed at improving complex MS analysis. We demonstrate that EsxA variants are amenable to MS analysis and remain functional in established in vitro and ex vivo assays of Esx-1-function. We provide the first demonstration of molecular engineering to specifically improve MS analysis of individual microbial proteins. PMID:27625110

  18. pH-dependent channel gating in connexin26 hemichannels involves conformational changes in N-terminus.

    PubMed

    Wang, Xia; Xu, Xue; Ma, Ming; Zhou, Wei; Wang, Yonghua; Yang, Ling

    2012-05-01

    Connexin (Cx) hemichannels controlling an exchange of ions and metabolites between the cytoplasm and extracellular milieu can be modulated by the variation of intracellular pH during physiological and pathological conditions. To address the mechanism by which the pH exerts its effect on hemichannels, we have performed two 100-ns molecular dynamics simulations of the Cx26 channel in both acidic and neutral states. The results show that: 1) transmembrane domains undergo clockwise motions around the pore axis under both acidic and neutral conditions, while extracellular segments keep stable. 2) Under neutral condition, Cx26 has a tightly closed configuration that occurs through the assembly of N-terminal helix (NTH) region. This shows a constriction formed by the interhelical interactions of Asp2 and Met1 from neighboring NTH, which shapes the narrowest segment (pore radius<2Å) of the pore, preventing the passage of ions from the extracellular side. This indicates that Asp2 may act as a channel gate. 3) Under the acidic condition, the constriction is relieved by the protonation of Asp2 causing interruption of interhelical interactions, Cx26 has a flexibly opening pore (pore radius>4.5Å) around NTH region, allowing the passage of chloride ions unimpeded by the side-chain Asp2. While in the extracellular part two chloride ions interact with the side-chain Lys41 from three subunits. Finally, we provide a plausible mechanism of pH-dependent gating of hemichannel that involves protonation of the aspartic residues, suggesting that the pH sensitivity of hemichannel permeability is a sophisticated mechanism for cell regulating ion permeation. PMID:22285739

  19. The N-terminus of porcine circovirus type 2 replication protein is required for nuclear localization and ori binding activities

    SciTech Connect

    Lin, W.-L.; Chien, M.-S.; Du, Y.-W.; Wu, P.-C.; Huang Chienjin

    2009-02-20

    Porcine circovirus type 2 possesses a circular, single-stranded DNA genome that requires the replication protein (Rep) for virus replication. To characterize the DNA binding potential and the significant region that confers the nuclear localization of the Rep protein, the defined coding regions of rep gene were cloned and expressed. All of the recombinant proteins except for the N-terminal 110 residues deletion mutant could bind to the double-stranded minimal binding site of replication origin (ori). In addition, the N-terminal deletion mutant lacking 110 residues exhibited mainly cytoplasmic staining in the transfected cells in contrast to the others, which localized dominantly in the nucleus, suggesting that this N-terminal domain is essential for nuclear localization. Furthermore, a series of green fluorescence proteins (GFP) containing potential nuclear localization signal (NLS) sequences were tested for their cellular distribution. The ability of the utmost 20 residues of the N-terminal region to target the GFP to the nucleus confirmed its role as a functional NLS.

  20. Human Islet Amyloid Polypeptide N-Terminus Fragment Self-Assembly: Effect of Conserved Disulfide Bond on Aggregation Propensity

    NASA Astrophysics Data System (ADS)

    Ilitchev, Alexandre I.; Giammona, Maxwell J.; Do, Thanh D.; Wong, Amy G.; Buratto, Steven K.; Shea, Joan-Emma; Raleigh, Daniel P.; Bowers, Michael T.

    2016-06-01

    Amyloid formation by human islet amyloid polypeptide (hIAPP) has long been implicated in the pathogeny of type 2 diabetes mellitus (T2DM) and failure of islet transplants, but the mechanism of IAPP self-assembly is still unclear. Numerous fragments of hIAPP are capable of self-association into oligomeric aggregates, both amyloid and non-amyloid in structure. The N-terminal region of IAPP contains a conserved disulfide bond between cysteines at position 2 and 7, which is important to hIAPP's in vivo function and may play a role in in vitro aggregation. The importance of the disulfide bond in this region was probed using a combination of ion mobility-based mass spectrometry experiments, molecular dynamics simulations, and high-resolution atomic force microscopy imaging on the wildtype 1-8 hIAPP fragment, a reduced fragment with no disulfide bond, and a fragment with both cysteines at positions 2 and 7 mutated to serine. The results indicate the wildtype fragment aggregates by a different pathway than either comparison peptide and that the intact disulfide bond may be protective against aggregation due to a reduction of inter-peptide hydrogen bonding.

  1. Tooth Enamel Protein Amelogenin Binds to Ameloblast Cell Membrane-Mimicking Vesicles via its N-terminus

    PubMed Central

    LOKAPPA, SOWMYA BEKSHE; CHANDRABABU, KARTHIK BALAKRISHNA; MORADIAN-OLDAK, JANET

    2015-01-01

    We have recently reported that the extracellular enamel protein amelogenin has affinity to interact with phospholipids and proposed that such interactions may play key roles in enamel biomineralization as well as reported amelogenin signaling activities. Here, in order to identify the liposome-interacting domains of amelogenin we designed four different amelogenin mutants containing only a single tryptophan at positions 25, 45, 112 and 161. Circular dichroism studies of the mutants confirmed that they are structurally similar to the wild-type amelogenin. Utilizing the intrinsic fluorescence of single tryptophan residues and fluorescence resonance energy transfer FRET, we analyzed the accessibility and strength of their binding with an ameloblast cell membrane-mimicking model membrane (ACML) and a negatively charged liposome used as a membrane model. We found that amelogenin has membrane-binding ability mainly via its N-terminal, close to residues W25 and W45. Significant blue shift was also observed in the fluorescence of a N-terminal peptide following addition of liposomes. We suggest that, among other mechanisms, enamel malformation in cases of Amelogenesis Imperfecta (AI) with mutations at the N-terminal may be the result of defective amelogenin-cell interactions. PMID:26188506

  2. pH-dependent channel gating in connexin26 hemichannels involves conformational changes in N-terminus.

    PubMed

    Wang, Xia; Xu, Xue; Ma, Ming; Zhou, Wei; Wang, Yonghua; Yang, Ling

    2012-05-01

    Connexin (Cx) hemichannels controlling an exchange of ions and metabolites between the cytoplasm and extracellular milieu can be modulated by the variation of intracellular pH during physiological and pathological conditions. To address the mechanism by which the pH exerts its effect on hemichannels, we have performed two 100-ns molecular dynamics simulations of the Cx26 channel in both acidic and neutral states. The results show that: 1) transmembrane domains undergo clockwise motions around the pore axis under both acidic and neutral conditions, while extracellular segments keep stable. 2) Under neutral condition, Cx26 has a tightly closed configuration that occurs through the assembly of N-terminal helix (NTH) region. This shows a constriction formed by the interhelical interactions of Asp2 and Met1 from neighboring NTH, which shapes the narrowest segment (pore radius<2Å) of the pore, preventing the passage of ions from the extracellular side. This indicates that Asp2 may act as a channel gate. 3) Under the acidic condition, the constriction is relieved by the protonation of Asp2 causing interruption of interhelical interactions, Cx26 has a flexibly opening pore (pore radius>4.5Å) around NTH region, allowing the passage of chloride ions unimpeded by the side-chain Asp2. While in the extracellular part two chloride ions interact with the side-chain Lys41 from three subunits. Finally, we provide a plausible mechanism of pH-dependent gating of hemichannel that involves protonation of the aspartic residues, suggesting that the pH sensitivity of hemichannel permeability is a sophisticated mechanism for cell regulating ion permeation.

  3. The role of the N-terminus of the myosin essential light chain in cardiac muscle contraction

    PubMed Central

    Kazmierczak, Katarzyna; Xu, Yuanyuan; Jones, Michelle; Guzman, Georgianna; Hernandez, Olga M.; Kerrick, W. Glenn L.; Szczesna-Cordary, Danuta

    2011-01-01

    Summary To study the regulation of cardiac muscle contraction by the myosin essential light chain (ELC) and the physiological significance of its N-terminal extension, we generated transgenic (Tg) mice partially replacing the endogenous mouse ventricular ELC with either the human ventricular ELC wild type (Tg-WT) or its 43 amino acid N-terminal truncation mutant (Tg-Δ43) in the murine hearts. The mutant protein is similar in sequence to the short ELC variant present in skeletal muscle and the ELC protein distribution in Tg-Δ43 ventricles resembles that of fast skeletal muscle. Cardiac muscle preparations from Tg-Δ43 mice demonstrate reduced force per cross-sectional area of muscle, which is likely caused by a reduced number of force generating myosin cross-bridges and/or by decreased force per cross-bridge. As the mice grow older, the contractile force per cross-sectional area further decreases in Tg-Δ43 mice and the mutant hearts develop a phenotype of non-pathologic hypertrophy while still maintaining normal cardiac performance. The myocardium of older Tg-Δ43 mice also exhibits reduced myosin content. Our results suggest that the role of the N-terminal ELC extension is to maintain the integrity of myosin and to modulate force generation by decreasing myosin neck region compliance and promoting strong cross-bridge formation and/or by enhancing myosin attachment to actin. PMID:19361417

  4. Plasticity in Interactions of Fibroblast Growth Factor 1 (FGF1) N Terminus with FGF Receptors Underlies Promiscuity of FGF1*

    PubMed Central

    Beenken, Andrew; Eliseenkova, Anna V.; Ibrahimi, Omar A.; Olsen, Shaun K.; Mohammadi, Moosa

    2012-01-01

    Tissue-specific alternative splicing in the second half of Ig-like domain 3 (D3) of fibroblast growth factor receptors 1–3 (FGFR1 to -3) generates epithelial FGFR1b-FGFR3b and mesenchymal FGFR1c-FGFR3c splice isoforms. This splicing event establishes a selectivity filter to restrict the ligand binding specificity of FGFRb and FGFRc isoforms to mesenchymally and epithelially derived fibroblast growth factors (FGFs), respectively. FGF1 is termed the “universal FGFR ligand” because it overrides this specificity barrier. To elucidate the molecular basis for FGF1 cross-reactivity with the “b” and “c” splice isoforms of FGFRs, we determined the first crystal structure of FGF1 in complex with an FGFRb isoform, FGFR2b, at 2.1 Å resolution. Comparison of the FGF1-FGFR2b structure with the three previously published FGF1-FGFRc structures reveals that plasticity in the interactions of the N-terminal region of FGF1 with FGFR D3 is the main determinant of FGF1 cross-reactivity with both isoforms of FGFRs. In support of our structural data, we demonstrate that substitution of three N-terminal residues (Gly-19, His-25, and Phe-26) of FGF2 (a ligand that does not bind FGFR2b) for the corresponding residues of FGF1 (Phe-16, Asn-22, and Tyr-23) enables the FGF2 triple mutant to bind and activate FGFR2b. These findings taken together with our previous structural data on receptor binding specificity of FGF2, FGF8, and FGF10 conclusively show that sequence divergence at the N termini of FGFs is the primary regulator of the receptor binding specificity and promiscuity of FGFs. PMID:22057274

  5. Cutting Edge: Novel Tmem173 Allele Reveals Importance of STING N Terminus in Trafficking and Type I IFN Production.

    PubMed

    Surpris, Guy; Chan, Jennie; Thompson, Mikayla; Ilyukha, Vladimir; Liu, Beiyun C; Atianand, Maninjay; Sharma, Shruti; Volkova, Tatyana; Smirnova, Irina; Fitzgerald, Katherine A; Poltorak, Alexander

    2016-01-15

    With the stimulator of IFN genes (STING) C terminus being extensively studied, the role of the N-terminal domain (NTD) of STING remains an important subject of investigation. In this article, we identify novel mutations in NTD of Sting of the MOLF strain in response to HSV and Listeria monocytogenes both in vitro and in vivo. These mutations are responsible for low levels of IFN-β caused by failure of MOLF STING to translocate from the endoplasmic reticulum. These data provide evidence that the NTD of STING affects DNA responses via control of trafficking. They also show that the genetic diversity of wild-derived mice resembles the diversity observed in humans. Several human alleles of STING confer attenuated IFN-I production similar to what we observe with the MOLF Sting allele, a crucial functional difference not apparent in classical inbred mice. Thus, understanding the functional significance of polymorphisms in MOLF STING can provide basic mechanistic insights relevant to humans.

  6. Ca2+ and membrane binding to annexin 3 modulate the structure and dynamics of its N terminus and domain III

    PubMed Central

    Sopkova, Jana; Raguenes-Nicol, Céline; Vincent, Michel; Chevalier, Anne; Lewit-Bentley, Anita; Russo-Marie, Françoise; Gallay, Jacques

    2002-01-01

    Annexin 3 (ANX A3) represents ∼1% of the total protein of human neutrophils and promotes tight contact between membranes of isolated specific granules in vitro leading to their aggregation. Like for other annexins, the primary molecular events of the action of this protein is likely its binding to negatively charged phospholipid membranes in a Ca2+-dependent manner, via Ca2+-binding sites located on the convex side of the highly conserved core of the molecule. The conformation and dynamics of domain III can be affected by this process, as it was shown for other members of the family. The 20 amino-acid, N-terminal segment of the protein also could be affected and also might play a role in the modulation of its binding to the membranes. The structure and dynamics of these two regions were investigated by fluorescence of the two tryptophan residues of the protein (respectively, W190 in domain III and W5 in the N-terminal segment) in the wild type and in single-tryptophan mutants. By contrast to ANX A5, which shows a closed conformation and a buried W187 residue in the absence of Ca2+, domain III of ANX A3 exhibits an open conformation and a widely solvent-accessible W190 residue in the same conditions. This is in agreement with the three-dimensional structure of the ANX A3-E231A mutant lacking the bidentate Ca2+ ligand in domain III. Ca2+ in the millimolar concentration range provokes nevertheless a large mobility increase of the W190 residue, while interaction with the membranes reduces it slightly. In the N-terminal region, the W5 residue, inserted in the central pore of the protein, is weakly accessible to the solvent and less mobile than W190. Its amplitude of rotation increases upon binding of Ca2+ and returns to its original value when interacting with membranes. Ca2+ concentration for half binding of the W5A mutant to negatively charged membranes is ∼0.5 mM while it increases to ∼1 mM for the ANX A3 wild type and to ∼3 mM for the W190 ANX A3 mutant. In addition to the expected perturbation of the W190 environment at the contact surface between the protein and the membrane bilayer, binding of the protein to Ca2+ and to membranes modulates the flexibility of the ANX A3 hinge region at the opposite of this interface and might affect its membrane permeabilizing properties. PMID:12070314

  7. Critical residues in the PMEL/Pmel17 N-terminus direct the hierarchical assembly of melanosomal fibrils

    PubMed Central

    Leonhardt, Ralf M.; Vigneron, Nathalie; Hee, Jia Shee; Graham, Morven; Cresswell, Peter

    2013-01-01

    PMEL (also called Pmel17 or gp100) is a melanocyte/melanoma-specific glycoprotein that plays a critical role in melanosome development by forming a fibrillar amyloid matrix in the organelle for melanin deposition. Although ultimately not a component of mature fibrils, the PMEL N-terminal region (NTR) is essential for their formation. By mutational analysis we establish a high-resolution map of this domain in which sequence elements and functionally critical residues are assigned. We show that the NTR functions in cis to drive the aggregation of the downstream polycystic kidney disease (PKD) domain into a melanosomal core matrix. This is essential to promote in trans the stabilization and terminal proteolytic maturation of the repeat (RPT) domain–containing MαC units, precursors of the second fibrillogenic fragment. We conclude that during melanosome biogenesis the NTR controls the hierarchical assembly of melanosomal fibrils. PMID:23389629

  8. The role of MscL amphipathic N terminus indicates a blueprint for bilayer-mediated gating of mechanosensitive channels.

    PubMed

    Bavi, Navid; Cortes, D Marien; Cox, Charles D; Rohde, Paul R; Liu, Weihong; Deitmer, Joachim W; Bavi, Omid; Strop, Pavel; Hill, Adam P; Rees, Douglas; Corry, Ben; Perozo, Eduardo; Martinac, Boris

    2016-01-01

    The bacterial mechanosensitive channel MscL gates in response to membrane tension as a result of mechanical force transmitted directly to the channel from the lipid bilayer. MscL represents an excellent model system to study the basic biophysical principles of mechanosensory transduction. However, understanding of the essential structural components that transduce bilayer tension into channel gating remains incomplete. Here using multiple experimental and computational approaches, we demonstrate that the amphipathic N-terminal helix of MscL acts as a crucial structural element during tension-induced gating, both stabilizing the closed state and coupling the channel to the membrane. We propose that this may also represent a common principle in the gating cycle of unrelated mechanosensitive ion channels, allowing the coupling of channel conformation to membrane dynamics. PMID:27329693

  9. Structural remodeling of the N-terminus tunes TRPA1 channel activation and regulates behavioral responses in Drosophila.

    PubMed

    Braun, Andrew P

    2012-01-01

    Our bodies are constantly bombarded by a diversity of environmental stimuli, such as touch, taste, sound, smell, light, etc. To detect and process this broad array of signals, nature has evolved a variety of cellular sensory mechanisms and pathways that interface with the environment and transmit neural signals back to the CNS where they are translated into behavioral decisions. Transient Response Potential (TRP) cation channels were first identified in invertebrates (i.e., Drosophila) and represent a sizeable receptor/channel family in mammals, consisting of 28 individual members grouped into subclasses denoted TRPC, TRPV, TRPM, TRPML, TRPP and TRPA (for a recent review, see ref. 1). Although originally described as ion channels, we now know that many members of the TRP family also function as receptors for a range of stimuli, including temperature, pH, chemical compounds and membrane voltage. In fact, several TRP isoforms display multimodal sensitivity, meaning that they can respond to more than one stimulus. For example, TRPV1, or the capcaisin receptor, displays both thermal and chemical sensitivity, and the two stimuli may act synergistically to increase channel activity. Physiologically, TRP family members are expressed in a variety of sensory afferent nerves that feed environmental information to the CNS, and also in smaller C-type afferent fibers responsible for peripheral pain sensation and transmission. Therapeutically, manipulation of TRP channel activity may represent an effective strategy to treat peripheral pain associated with inflammation and chronic tissue injury. PMID:22388005

  10. The N Terminus of the Retinoblastoma Protein Inhibits DNA Replication via a Bipartite Mechanism Disrupted in Partially Penetrant Retinoblastomas

    PubMed Central

    Borysov, Sergiy I.; Nepon-Sixt, Brook S.

    2015-01-01

    The N-terminal domain of the retinoblastoma (Rb) tumor suppressor protein (RbN) harbors in-frame exon deletions in partially penetrant hereditary retinoblastomas and is known to impair cell growth and tumorigenesis. However, how such RbN deletions contribute to Rb tumor- and growth-suppressive functions is unknown. Here we establish that RbN directly inhibits DNA replication initiation and elongation using a bipartite mechanism involving N-terminal exons lost in cancer. Specifically, Rb exon 7 is necessary and sufficient to target and inhibit the replicative CMG helicase, resulting in the accumulation of inactive CMGs on chromatin. An independent N-terminal loop domain, which forms a projection, specifically blocks DNA polymerase α (Pol-α) and Ctf4 recruitment without affecting DNA polymerases ε and δ or the CMG helicase. Individual disruption of exon 7 or the projection in RbN or Rb, as occurs in inherited cancers, partially impairs the ability of Rb/RbN to inhibit DNA replication and block G1-to-S cell cycle transit. However, their combined loss abolishes these functions of Rb. Thus, Rb growth-suppressive functions include its ability to block replicative complexes via bipartite, independent, and additive N-terminal domains. The partial loss of replication, CMG, or Pol-α control provides a potential molecular explanation for how N-terminal Rb loss-of-function deletions contribute to the etiology of partially penetrant retinoblastomas. PMID:26711265

  11. Missing Transverse Momentum Trigger Performance Studies for the ATLAS Calorimeter Trigger Upgrades

    NASA Astrophysics Data System (ADS)

    Stamas, Brianna; Parrish, Elliot; Lisi, Luc; Dudley, Christopher; Majewski, Stephanie

    2016-03-01

    The ATLAS Experiment is one of two general purpose detectors at the Large Hadron Collider at CERN in Geneva, Switzerland. In anticipation of discovering new physics, the detector will undergo numerous hardware upgrades including improvements to the Liquid Argon Calorimeter trigger electronics. For the upgrade, one component of the Level-1 trigger system will be the global feature extractor, gFEX, which will house three field programmable gate arrays (FPGAs). Specifically, in order to improve the missing transverse energy (ETmiss)trigger, an adapted topological clustering algorithm is being investigated for implementation on the FPGAs for reconstruction of proton-proton interactions in the ATLAS detector. Using simulated data, this study analyzes the performance of the adapted algorithm in software.

  12. Interfacing Detectors to Triggers And DAQ Electronics

    SciTech Connect

    Crosetto, Dario B.

    1999-05-03

    The complete design of the front-end electronics interfacing LHCb detectors, Level-0 trigger and higher levels of trigger with flexible configuration parameters has been made for (a) ASIC implementation, and (b) FPGA implementation. The importance of approaching designs in technology-independent form becomes essential with the actual rapid electronics evolution. Being able to constrain the entire design to a few types of replicated components: (a) the fully programmable 3D-Flow system, and (b) the configurable front-end circuit described in this article, provides even further advantages because only one or two types of components will need to migrate to the newer technologies. To base on today's technology the design of a system such as the LHCb project that is to begin working in 2006 is not cost-effective. The effort required to migrate to a higher-performance will, in that case, be almost equivalent to completely redesigning the architecture from scratch. The proposed technology independent design with the current configurable front-end module described in this article and the scalable 3D-Flow fully programmable system described elsewhere, based on the study of the evolution of electronics during the past few years and the forecasted advances in the years to come, aims to provide a technology-independent design which lends itself to any technology at any time. In this case, technology independence is based mainly on generic-HDL reusable code which allows a very rapid realization of the state-of-the-art circuits in terms of gate density, power dissipation, and clock frequency. The design of four trigger towers presently fits into an OR3T30 FPGA. Preliminary test results (provided in this paper) meet the functional requirements of LHCb and provide sufficient flexibility to introduce future changes. The complete system design is also provided along with the integration of the front-end design in the entire system and the cost and dimension of the electronics.

  13. Triggered Star Formation From Shock to Disk

    NASA Astrophysics Data System (ADS)

    Blackman, Eric

    2014-10-01

    Triggered star formation {TSF} occurs when supersonic flows generated by distant supernova blast waves, stellar winds {wind blown bubbles} or ionization fronts {D-type fronts in HII regions} sweep over a stable cloud. TSF may play a role in massive regions of star formation where winds, HII regions and, eventually, blast-waves sweep through dense, heterogeneous molecular material. In addition TSF has played an important role in discussions of the formation of our own solar system because it offers a natural way of injecting short lived radioactive isotopes {SLRI's} like 26^Al into material which will then form planetary bodies.The purpose of this proposal is to use advanced numerical tools to explore the physics of TSF in greater detail than has been attempted before. Previous studies have not been able to follow triggering past the early stages before a star forms. Our 3-D Adaptive Mesh Refinement {AMR} MHD code contains well tested physics modules which will allow us to track the influence of self-gravity, radiation-transport, cooling by molecules/neutrals/atoms and, finally, the collapse of gas into stars {i.e.condensed gravitating point-like objects or "sink-particles"}. With this tool we will follow triggering well past the formation of the star to explore the creation of accretion disks and their properties. In addition the microphysics routines in the code allow us to make detailed contact with HST observations such as the pillars in the Carina nebula via synthetic observations of line profiles, proper motions, Position-Velocity diagrams and statistics.

  14. Frontal cortex mediates unconsciously triggered inhibitory control.

    PubMed

    van Gaal, Simon; Ridderinkhof, K Richard; Fahrenfort, Johannes J; Scholte, H Steven; Lamme, Victor A F

    2008-08-01

    To further our understanding of the function of conscious experience we need to know which cognitive processes require awareness and which do not. Here, we show that an unconscious stimulus can trigger inhibitory control processes, commonly ascribed to conscious control mechanisms. We combined the metacontrast masking paradigm and the Go/No-Go paradigm to study whether unconscious No-Go signals can actively trigger high-level inhibitory control processes, strongly associated with the prefrontal cortex (PFC). Behaviorally, unconscious No-Go signals sometimes triggered response inhibition to the level of complete response termination and yielded a slow down in the speed of responses that were not inhibited. Electroencephalographic recordings showed that unconscious No-Go signals elicit two neural events: (1) an early occipital event and (2) a frontocentral event somewhat later in time. The first neural event represents the visual encoding of the unconscious No-Go stimulus, and is also present in a control experiment where the masked stimulus has no behavioral relevance. The second event is unique to the Go/No-Go experiment, and shows the subsequent implementation of inhibitory control in the PFC. The size of the frontal activity pattern correlated highly with the impact of unconscious No-Go signals on subsequent behavior. We conclude that unconscious stimuli can influence whether a task will be performed or interrupted, and thus exert a form of cognitive control. These findings challenge traditional views concerning the proposed relationship between awareness and cognitive control and stretch the alleged limits and depth of unconscious information processing. PMID:18685030

  15. Aspects of earthquake triggering and seismicity clustering

    NASA Astrophysics Data System (ADS)

    Chen, Xiaowei

    Earthquakes strongly cluster in space and time, driven both by earthquake-to-earthquake triggering and underlying physical processes, such as tectonic stress loading, increased pore pressure, etc. I explore both global and regional datasets to understand characteristics of these processes in different tectonic environments. I study global seismicity using intermediate-period (35--70 s) Rayleigh waves recorded by the global seismic network. Applying a surface wave detect method identifies about 1000 previously un-cataloged earthquakes from 1997 to 2009, most of which are located in the southern ocean. I further analyze a small number of these events that are located in Antarctica to understand glacial-related triggering processes. Absolute and differential travel-times measured from waveform cross-correlation are used to obtain refined locations. A single-force model is applied to the observed amplitudes at 50~Hz to obtain best-fitting force directions. Additionally, possible glacial calving events are identified from MODIS images. The combined results suggest that events on Vanderford and Ninnis glaciers are a result of calving processes. To understand the general characteristics of earthquake clustering from a large dataset of earthquakes, I analyze seismicity in southern California. I use a high-resolution earthquake catalog based on waveform cross-correlation to study the spatial-temporal distribution of earthquakes. Parameters based on event location, magnitude and occurrence time are computed for isolated seismicity clusters. Spatial migration behavior is modeled using a weighted-least-squares method. Aftershock-like event clusters do not exhibit significant spatial migration compared with earthquake swarms. Two triggering processes are considered for swarms: slow slip and fluid diffusion, which are distinguished based on a statistical analysis of event migration. The results suggest fluid-induced seismicity is found across southern California, particularly

  16. Simple multifunction discriminator for multichannel triggers

    SciTech Connect

    Maier, M.R.

    1982-10-01

    A simple version of a multifunction timing discriminator using only two integrated circuits is presented. It can be configured as a leading edge, a constant fraction, a zero cross or a dual threshold timing discriminator. Since so few parts are used, it is well suited for building multichannel timing discriminators. Two versions of this circuit are described: a quadruple multifunction discriminator and an octal constant fraction trigger. The different compromises made in these units are discussed. Results for walk and jitter obtained with these are presented and possible improvements are disussed.

  17. Pulsed laser triggered high speed microfluidic switch

    NASA Astrophysics Data System (ADS)

    Wu, Ting-Hsiang; Gao, Lanyu; Chen, Yue; Wei, Kenneth; Chiou, Pei-Yu

    2008-10-01

    We report a high-speed microfluidic switch capable of achieving a switching time of 10 μs. The switching mechanism is realized by exciting dynamic vapor bubbles with focused laser pulses in a microfluidic polydimethylsiloxane (PDMS) channel. The bubble expansion deforms the elastic PDMS channel wall and squeezes the adjacent sample channel to control its fluid and particle flows as captured by the time-resolved imaging system. A switching of polystyrene microspheres in a Y-shaped channel has also been demonstrated. This ultrafast laser triggered switching mechanism has the potential to advance the sorting speed of state-of-the-art microscale fluorescence activated cell sorting devices.

  18. Hydrodynamical trigger mechanism for pulsar glitches.

    PubMed

    Glampedakis, Kostas; Andersson, Nils

    2009-04-10

    We describe a new instability that may trigger the global unpinning of vortices in a spinning neutron star, leading to the transfer of angular momentum from the superfluid component to the star's crust. The instability, which is associated with the inertial r modes of a superfluid neutron star, sets in once the rotational lag in the system reaches a critical level. We demonstrate that our simple model agrees well with the observed glitch data. This new idea should stimulate work on more detailed neutron star models, which would account for the crustal shear stresses and magnetic field effects we have ignored. PMID:19392421

  19. Widespread triggering of nonvolcanic tremor in California.

    PubMed

    Gomberg, Joan; Rubinstein, Justin L; Peng, Zhigang; Creager, Kenneth C; Vidale, John E; Bodin, Paul

    2008-01-11

    We identified seven locations on or near the transform plate boundary in California where nonvolcanic tremor was triggered by the 2002 Denali earthquake. This result implies that the conditions essential for nonvolcanic tremor exist in a range of tectonic environments. Models explaining tremor typically require conditions endemic to subduction zones, that is, high temperatures and fluid pressures, because previously tremor was nearly exclusively documented in subduction zones. The absence of tremor in geothermal areas is inconsistent with such models. Additionally, we found no correlation between creeping or locked faults and tremor, contrary to predictions of frictional models of tremor.

  20. Inflammation: a trigger for acute coronary syndrome.

    PubMed

    Sager, Hendrik B; Nahrendorf, Matthias

    2016-09-01

    Atherosclerosis is a chronic inflammatory disease of the vessel wall and a major cause of death worldwide. One of atherosclerosis' most dreadful complications are acute coronary syndromes that comprise ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, and unstable angina. We now understand that inflammation substantially contributes to the initiation, progression, and destabilization of atherosclerosis. In this review, we will focus on the role of inflammatory leukocytes, which are the cellular protagonists of vascular inflammation, in triggering disease progression and, ultimately, the destabilization that causes acute coronary syndromes. PMID:27273431

  1. Extremely Intense Magnetospheric Substorms : External Triggering? Preconditioning?

    NASA Astrophysics Data System (ADS)

    Tsurutani, Bruce; Echer, Ezequiel; Hajra, Rajkumar

    2016-07-01

    We study particularly intense substorms using a variety of near-Earth spacecraft data and ground observations. We will relate the solar cycle dependences of events, determine whether the supersubstorms are externally or internally triggered, and their relationship to other factors such as magnetospheric preconditioning. If time permits, we will explore the details of the events and whether they are similar to regular (Akasofu, 1964) substorms or not. These intense substorms are an important feature of space weather since they may be responsible for power outages.

  2. Childhood Asthma Management and Environmental Triggers.

    PubMed

    Hollenbach, Jessica P; Cloutier, Michelle M

    2015-10-01

    Asthma is the most common chronic disease among children. It cannot be prevented but can be controlled. Industrialized countries experience high lifetime asthma prevalence that has increased over recent decades. Asthma has a complex interplay of genetic and environmental triggers. Studies have revealed complex interactions of lung structure and function genes with environmental exposures such as environmental tobacco smoke and vitamin D. Home environmental strategies can reduce asthma morbidity in children but should be tailored to specific allergens. Coupled with education and severity-specific asthma therapy, tailored interventions may be the most effective strategy to manage childhood asthma.

  3. Statistics of Static Stress Earthquake Triggering

    NASA Astrophysics Data System (ADS)

    Nandan, S.; Ouillon, G.; Woessner, J.; Sornette, D.; Wiemer, S.

    2014-12-01

    A likely source of earthquake clustering is static and/or dynamic stresses transferred by individual events. Previous attempts to quantify the role of static stress generally considered only the stress changes caused by large events, and often discarded data uncertainties. We test the static stress change hypothesis empirically by considering all events of magnitude M≥ 2.1 and the uncertainties in location and focal mechanism in the focal mechanism catalog for Southern California between 1981 and 2010 (Yang et al., 2011). We quantify: How the waiting time between earthquakes (1) relates to the Coulomb stress change (2) induced by event Ei at the location of Ej; How significant is the Coulomb Index (CI), fraction of source-receiver pairs with positive ∆CFS interactions, conditioned on time and amplitude of ∆CFS, compared to a mean-field CI derived from the time-independent structure of the fault network. We approximate the waiting time distributions empirically by (3), which respectively consists of triggering and background rate components, tapered by an exponential term to model the finiteness of the catalog. We observe that K/(Bc^p ) (the ratio of the triggering to the background rates at t=0), the exponent p, and the Maxwell time τ all increase with |∆CFS| and are significantly larger for positive than for negative ∆CFS's. τ varies between ~90 days and ~150 days (approximately 0.3 decades over 6 decades of variation in stress). It defines the time beyond which the memory of stress is overprinted by occurrence of other events. The CI values become significant above a threshold |∆CFS|. The mean-field CI is 52%, while the maximum observed CI value is ~60%. Correcting for the focal plane ambiguity, those values become respectively ~55% and ~72%. Lastly, the CI values decrease with the waiting time and converge to the mean-field CI value. The increase of p-value and K/(Bc^p ) with |∆CFS| contradicts the prediction of stress shadow regions where

  4. New methods for trigger electronics development

    SciTech Connect

    Cleland, W.E.; Stern, E.G.

    1991-12-31

    The large and complex nature of RHIC experiments and the tight time schedule for their construction requires that new techniques for designing the electronics should be employed. This is particularly true of the trigger and data acquisition electronics which has to be ready for turn-on of the experiment. We describe the use of the Workview package from VIEWlogic Inc. for design, simulation, and verification of a flash ADC readout system. We also show how field-programmable gate arrays such as the Xilinx 4000 might be employed to construct or prototype circuits with a large number of gates while preserving flexibility.

  5. Mitochondrial Retrograde Signaling: Triggers, Pathways, and Outcomes

    PubMed Central

    da Cunha, Fernanda Marques; Torelli, Nicole Quesada; Kowaltowski, Alicia J.

    2015-01-01

    Mitochondria are essential organelles for eukaryotic homeostasis. Although these organelles possess their own DNA, the vast majority (>99%) of mitochondrial proteins are encoded in the nucleus. This situation makes systems that allow the communication between mitochondria and the nucleus a requirement not only to coordinate mitochondrial protein synthesis during biogenesis but also to communicate eventual mitochondrial malfunctions, triggering compensatory responses in the nucleus. Mitochondria-to-nucleus retrograde signaling has been described in various organisms, albeit with differences in effector pathways, molecules, and outcomes, as discussed in this review. PMID:26583058

  6. Fingerprint on trigger: A real case.

    PubMed

    Amata, B; Aprea, G M; Chiuri, A; Zampa, F

    2015-08-01

    The results obtained by employing a usual technique for latent prints development on firearms are presented. A fingermark on a trigger was enhanced and this print was used to identify the person who handled the firearm. Indeed, it is not usual to find a useful fingermark in that position and, more in general, on firearms because of many different factors described in the following sections. The uniqueness of the results reported in this paper allow to consider the present casework as very interesting for the forensic community.

  7. Upgrade of the ATLAS Central Trigger for LHC Run-2

    NASA Astrophysics Data System (ADS)

    Artz, S.; Bauss, B.; Boterenbrood, H.; Buescher, V.; Degele, R.; Dhaliwal, S.; Ellis, N.; Farthouat, P.; Galster, G.; Ghibaudi, M.; Glatzer, J.; Haas, S.; Igonkina, O.; Jakobi, K.; Jansweijer, P.; Kahra, C.; Kaluza, A.; Kaneda, M.; Marzin, A.; Ohm, C.; Silva Oliveira, M. V.; Pauly, T.; Pöttgen, R.; Reiss, A.; Schäfer, U.; Schäffer, J.; Schipper, J. D.; Schmieden, K.; Schreuder, F.; Simioni, E.; Simon, M.; Spiwoks, R.; Stelzer, J.; Tapprogge, S.; Vermeulen, J.; Vogel, A.; Zinser, M.

    2015-02-01

    The increased energy and luminosity of the LHC in the run-2 data taking period requires a more selective trigger menu in order to satisfy the physics goals of ATLAS. Therefore the electronics of the central trigger system is upgraded to allow for a larger variety and more sophisticated trigger criteria. In addition, the software controlling the central trigger processor (CTP) has been redesigned to allow the CTP to accommodate three freely configurable and separately operating sets of sub detectors, each independently using the almost full functionality of the trigger hardware. This new approach and its operational advantages are discussed as well as the hardware upgrades.

  8. The VME-based D0 muon trigger electronics

    SciTech Connect

    Fortner, M; Green, J; Hedin, D; Morphis, R; Repond, S; Willis, S; Zazula, R; Johns, K; Bazizi, K; Fahland, T; Hall, R E; Jerger, S; Lietzke, C; Smith, D; Butler, J M; Diehl, H T; Eartly, D; Fitzpatrick, T; Green, D; Haggerty, H; Hansen, S; Hawkins, J; Igarashi, S; Joestlein, H

    1990-11-01

    The trigger electronics for the muon system of the Fermilab D0 detector is described. The hardware trigger consists of VME-based cards designed to find probable tracks in individual chambers and then match these track segments. The fast trigger is highly parallel and able to discern probable tracks from about 15,000 trigger cells in under 200 ns from receipt of all bits in the counting house. There is a parallel confirmation trigger with a response time of 1--5 microseconds that provides a crude calculation of the momentum and charge of the muon. 6 refs., 7 figs.

  9. Note: A novel trigger generator for a pseudospark switch.

    PubMed

    Chatzakis, J; Hassan, S M; Clark, E L; Lee, P; Tatarakis, M

    2015-01-01

    A novel trigger generator for operating a pseudospark switch has been developed based on a series connection of several insulated gate bipolar transistors. The trigger generator can be operated in single shot mode up to a repetition rate of 1 kHz. It is characterized by a fast rise time and low jitter between the output trigger pulses of less than 1 ns. It produces 3 kV, 1 μs pulses into a 50 Ω load that can trigger a pseudospark switch. By eliminating bulkier, slower high voltage components, the overall volume of the trigger generator is reduced. This allows for faster, high voltage switching to take place and thereby increasing the power density of the unit. Using this pseudospark trigger generator, it is possible to trigger single or multiple pseudospark gaps without the requirement to use a pulse shaping circuit.

  10. Triggering of repeating earthquakes in central California

    USGS Publications Warehouse

    Wu, Chunquan; Gomberg, Joan; Ben-Naim, Eli; Johnson, Paul

    2014-01-01

    Dynamic stresses carried by transient seismic waves have been found capable of triggering earthquakes instantly in various tectonic settings. Delayed triggering may be even more common, but the mechanisms are not well understood. Catalogs of repeating earthquakes, earthquakes that recur repeatedly at the same location, provide ideal data sets to test the effects of transient dynamic perturbations on the timing of earthquake occurrence. Here we employ a catalog of 165 families containing ~2500 total repeating earthquakes to test whether dynamic perturbations from local, regional, and teleseismic earthquakes change recurrence intervals. The distance to the earthquake generating the perturbing waves is a proxy for the relative potential contributions of static and dynamic deformations, because static deformations decay more rapidly with distance. Clear changes followed the nearby 2004 Mw6 Parkfield earthquake, so we study only repeaters prior to its origin time. We apply a Monte Carlo approach to compare the observed number of shortened recurrence intervals following dynamic perturbations with the distribution of this number estimated for randomized perturbation times. We examine the comparison for a series of dynamic stress peak amplitude and distance thresholds. The results suggest a weak correlation between dynamic perturbations in excess of ~20 kPa and shortened recurrence intervals, for both nearby and remote perturbations.

  11. Triggered self-assembly of magnetic nanoparticles

    PubMed Central

    Ye, L.; Pearson, T.; Cordeau, Y.; Mefford, O. T.; Crawford, T. M.

    2016-01-01

    Colloidal magnetic nanoparticles are candidates for application in biology, medicine and nanomanufac-turing. Understanding how these particles interact collectively in fluids, especially how they assemble and aggregate under external magnetic fields, is critical for high quality, safe, and reliable deployment of these particles. Here, by applying magnetic forces that vary strongly over the same length scale as the colloidal stabilizing force and then varying this colloidal repulsion, we can trigger self-assembly of these nanoparticles into parallel line patterns on the surface of a disk drive medium. Localized within nanometers of the medium surface, this effect is strongly dependent on the ionic properties of the colloidal fluid but at a level too small to cause bulk colloidal aggregation. We use real-time optical diffraction to monitor the dynamics of self-assembly, detecting local colloidal changes with greatly enhanced sensitivity compared with conventional light scattering. Simulations predict the triggering but not the dynamics, especially at short measurement times. Beyond using spatially-varying magnetic forces to balance interactions and drive assembly in magnetic nanoparticles, future measurements leveraging the sensitivity of this approach could identify novel colloidal effects that impact real-world applications of these nanoparticles. PMID:26975332

  12. Triggered self-assembly of magnetic nanoparticles

    NASA Astrophysics Data System (ADS)

    Ye, L.; Pearson, T.; Cordeau, Y.; Mefford, O. T.; Crawford, T. M.

    2016-03-01

    Colloidal magnetic nanoparticles are candidates for application in biology, medicine and nanomanufac-turing. Understanding how these particles interact collectively in fluids, especially how they assemble and aggregate under external magnetic fields, is critical for high quality, safe, and reliable deployment of these particles. Here, by applying magnetic forces that vary strongly over the same length scale as the colloidal stabilizing force and then varying this colloidal repulsion, we can trigger self-assembly of these nanoparticles into parallel line patterns on the surface of a disk drive medium. Localized within nanometers of the medium surface, this effect is strongly dependent on the ionic properties of the colloidal fluid but at a level too small to cause bulk colloidal aggregation. We use real-time optical diffraction to monitor the dynamics of self-assembly, detecting local colloidal changes with greatly enhanced sensitivity compared with conventional light scattering. Simulations predict the triggering but not the dynamics, especially at short measurement times. Beyond using spatially-varying magnetic forces to balance interactions and drive assembly in magnetic nanoparticles, future measurements leveraging the sensitivity of this approach could identify novel colloidal effects that impact real-world applications of these nanoparticles.

  13. Triggering of Erythrocyte Death by Triparanol

    PubMed Central

    Officioso, Arbace; Manna, Caterina; Alzoubi, Kousi; Lang, Florian

    2015-01-01

    The cholesterol synthesis inhibitor Triparanol has been shown to trigger apoptosis in several malignancies. Similar to the apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include oxidative stress which may activate erythrocytic Ca2+ permeable unselective cation channels with subsequent Ca2+ entry and increase of cytosolic Ca2+ activity ([Ca2+]i). The present study explored whether and how Triparanol induces eryptosis. To this end, phosphatidylserine exposure at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, hemolysis from hemoglobin release, [Ca2+]i from Fluo3-fluorescence, and ROS formation from 2’,7’-dichlorodihydrofluorescein diacetate (DCFDA) dependent fluorescence. As a result, a 48 h exposure of human erythrocytes to Triparanol (20 µM) significantly increased DCFDA fluorescence and significantly increased Fluo3-fluorescence. Triparanol (15 µM) significantly increased the percentage of annexin-V-binding cells, and significantly decreased the forward scatter. The effect of Triparanol on annexin-V-binding was significantly blunted, but not abolished by removal of extracellular Ca2+. In conclusion, Triparanol leads to eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane. Triparanol is at least in part effective by stimulating ROS formation and Ca2+ entry. PMID:26305256

  14. Neurobiology of the myofascial trigger point.

    PubMed

    Gerwin, R D

    1994-11-01

    The clinical phenomenon of the MTrP is accessible to any clinician who takes the time to learn to palpate skeletal muscle gently and carefully, and who is willing to learn the functional anatomy necessary to understand the regional spread of MTrPs through functional muscle units (Travell and Simons, 1992). Yet despite the years of clinical study of MPS, the pathophysiology of the central feature, the trigger point, has remained elusive. Many investigators have contributed to the general understanding of the mechanisms of pain perception, but we owe a particular debt of gratitude to Dr Seigfried Mense of Heidelberg for his pursuit of the study of pain originating in muscle lesions. However, Dr Mense would be the first to caution us against the direct transference of the results obtained with an inflammatory lesion produced in the experimental animal to the pain of MTrPs in the clinic patient. Notwithstanding that, researchers in the field of pain have given us an understanding of the basis for the hyperalgesia, allodynia and the previously difficult-to-understand finding of referred pain zones that we see daily in our patients. Finally, the interesting initial observations of Hubbard and Berkoff (1993), suggesting that the muscle spindle may be associated with the trigger point, open yet another door in our understanding of the nature of MPS. PMID:7850878

  15. Vaccines as a trigger for myopathies.

    PubMed

    Orbach, H; Tanay, A

    2009-11-01

    Vaccines are considered to be among the greatest medical discoveries, credited with the virtual eradication of some diseases and the consequent improved survival and quality of life of the at-risk population. With that, vaccines are among the environmental factors implicated as triggers for the development of inflammatory myopathies. The sporadic reports on vaccine-induced inflammatory myopathies include cases of hepatitis B virus, bacillus Calmette-Guérin, tetanus, influenza, smallpox, polio, diphtheria, diphtheria-pertussis-tetanus, combination of diphtheria with scarlet fever and diphtheria-pertussis-tetanus with polio vaccines. However, a significant increase in the incidence of dermatomyositis or polymyositis after any massive vaccination campaign has not been reported in the literature. In study patients with inflammatory myopathies, no recent immunization was recorded in any of the patients. Moreover, after the 1976 mass flu vaccination, no increase in the incidence of inflammatory myopathies was observed. Although rare, macrophagic myofasciitis has been reported following vaccination and is attributed to the aluminium hydroxide used as an adjuvant in some vaccines. Prospective multicenter studies are needed to identify potential environmental factors, including vaccines, as potential triggers for inflammatory myopathies.

  16. Programmable pH-triggered DNA nanoswitches.

    PubMed

    Idili, Andrea; Vallée-Bélisle, Alexis; Ricci, Francesco

    2014-04-23

    We have designed programmable DNA-based nanoswitches whose closing/opening can be triggered over specific different pH windows. These nanoswitches form an intramolecular triplex DNA structure through pH-sensitive parallel Hoogsteen interactions. We demonstrate that by simply changing the relative content of TAT/CGC triplets in the switches, we can rationally tune their pH dependence over more than 5 pH units. The ability to design DNA-based switches with tunable pH dependence provides the opportunity to engineer pH nanosensors with unprecedented wide sensitivity to pH changes. For example, by mixing in the same solution three switches with different pH sensitivity, we developed a pH nanosensor that can precisely monitor pH variations over 5.5 units of pH. With their fast response time (<200 ms) and high reversibility, these pH-triggered nanoswitches appear particularly suitable for applications ranging from the real-time monitoring of pH changes in vivo to the development of pH sensitive smart nanomaterials. PMID:24716858

  17. Engineering Challenges in Antiproton Triggered Fusion Propulsion

    SciTech Connect

    Cassenti, Brice; Kammash, Terry

    2008-01-21

    During the last decade antiproton triggered fusion propulsion has been investigated as a method for achieving high specific impulse, high thrust in a nuclear pulse propulsion system. In general the antiprotons are injected into a pellet containing fusion fuel with a small amount of fissionable material (i.e., an amount less than the critical mass) where the products from the fission are then used to trigger a fusion reaction. Initial calculations and simulations indicate that if magnetically insulated inertial confinement fusion is used that the pellets should result in a specific impulse of between 100,000 and 300,000 seconds at high thrust. The engineering challenges associated with this propulsion system are significant. For example, the antiprotons must be precisely focused. The pellet must be designed to contain the fission and initial fusion products and this will require strong magnetic fields. The fusion fuel must be contained for a sufficiently long time to effectively release the fusion energy, and the payload must be shielded from the radiation, especially the excess neutrons emitted, in addition to many other particles. We will review the recent progress, possible engineering solutions and the potential performance of these systems.

  18. Assessment of Myofascial Trigger Points Using Ultrasound.

    PubMed

    Kumbhare, Dinesh A; Elzibak, Alyaa H; Noseworthy, Michael D

    2016-01-01

    Myofascial pain syndrome is a common musculoskeletal pain disorder characterized by the presence of myofascial trigger points (MTrPs). The diagnosis of myofascial pain syndrome is currently made on clinical grounds. Numerous diagnostic criteria are used to identify myofascial pain syndrome, including the localization of MTrPs. Identifying the presence of MTrPs currently requires the physician to palpate the symptomatic region. Because the interrater reliability of the palpation technique has been found to be poor, numerous groups have been interested in finding objective imaging measures to localize the MTrP. This comprehensive review focuses on summarizing ultrasound imaging techniques that have shown promise in visually localizing the trigger point. The authors' literature search identified three sonographic approaches that have been used in MTrP localization: conventional gray-scale imaging, Doppler imaging, and elastographic ultrasound imaging. This review article explains the basic physics behind the imaging methods and summarizes the characteristics of the MTrP as identified by the ultrasonic techniques.

  19. How cold pool triggers deep convection?

    NASA Astrophysics Data System (ADS)

    Yano, Jun-Ichi

    2014-05-01

    The cold pool in the boundary layer is often considered a major triggering mechanism of convection. Here, presented are basic theoretical considerations on this issue. Observations suggest that cold pool-generated convective cells is available for shallow maritime convection (Warner et al. 1979; Zuidema et al. 2012), maritime deep convection (Barnes and Garstang 1982; Addis et al. 1984; Young et al. 1995) and continental deep convection (e.g., Lima and Wilson 2008; Flamant 2009; Lothon et al. 2011; Dione et al. 2013). Moreover, numerical studies appear to suggest that cold pools promote the organization of clouds into larger structures and thereby aid the transition from shallow to deep convection (Khairoutdinov and Randall 2006, Boing et al. 2012, Schlemmer and Hohenegger, 2014). Even a cold--pool parameterization coupled with convection is already proposed (Grandpeix and Lafore 2010: but see also Yano 2012). However, the suggested link between the cold pool and deep convection so far is phenomenological at the best. A specific process that the cold pool leads to a trigger of deep convection must still to be pinned down. Naively, one may imagine that a cold pool lifts up the air at the front as it propagates. Such an uplifting leads to a trigger of convection. However, one must realize that a shift of air along with its propagation does not necessarily lead to an uplifting, and even if it may happen, it would not far exceed a depth of the cold pool itself. Thus, the uplifting can never be anything vigorous. Its thermodynamic characteristics do help much either for inducing convection. The cold-pool air is rather under rapid recovering process before it can induce convection under a simple parcel-lifting argument. The most likely reason that the cold pool may induce convection is its gust winds that may encounter an air mass from an opposite direction. This induces a strong convergence, also leading to a strong uplifting. This is an argument essentially developed

  20. An 'Anomalous' Triggered Lightning Flash in Florida

    NASA Astrophysics Data System (ADS)

    Gamerota, W. R.; Uman, M. A.; Hill, J. D.; Pilkey, J. T.; Ngin, T.; Jordan, D. M.; Mata, C.; Mata, A.

    2012-12-01

    Classical (grounded wire) rocket-and-wire triggered lightning flashes whose leaders do not traverse the path of the wire remnants are sometimes referred to as 'anomalous'. We present high-speed video images captured at 10 kilo-frames per second (kfps), with supporting data, to characterize an 'anomalous' rocket-triggered lightning flash that occurred on 15 May 2012 at the International Center for Lightning Research and Testing (ICLRT) in north-central Florida. The event begins as a classical rocket-triggered lightning flash with an upward positive leader (UPL) initiating from the tip of the wire at a height of about 280 m above ground level. The top 259 m of the trailing wire explodes 2.7 s after the rocket exits the launch tube, while the bottom 17 m of the wire does not explode (does not become luminous). Approximately 1.4 ms after wire explosion, a stepped leader initiates a few meters above the top of the wire remnants and propagates downward, attaching to the top of a grounded utility pole 2.1 ms after initiation and 117 m southwest of the launching facility. Beginning 600 μs prior to this sustained stepped leader development, attempted stepped leaders (luminous steps emanating from the UPL channel above the wire remnants) are observed in three locations: 20 m and 5 m above the top of the wire remnants and at the top of the wire remnants. Correlated electric field derivative (dE/dt), channel-base current, and high-speed video captured at 300 kfps reveal an electrical discharge of peak current 365 A initiating from about 17 m above the launching facility, apparently the top of the unexploded triggering wire, when the stepped leader is no more than 60 m above ground level. There are significant differences between the 'anomalous' triggered lightning flash described here and those observed in New Mexico and in France in the late 1970s and early 1980s: First, the time duration between explosion of our wire and the sustained stepped leader development a few meters

  1. B7H6-derived peptides trigger TNF-α-dependent immunostimulatory activity of lymphocytic NK92-MI cells.

    PubMed

    Phillips, Mariana; Romeo, Francesca; Bitsaktsis, Constantine; Sabatino, David

    2016-09-01

    The rise of biologics that can stimulate immune responses towards the eradication of tumors has led to the evolution of cancer-based immunotherapy. Representatively, B7H6 has been recently identified as a protein ligand on tumor cells that binds specifically to the NKp30 receptor and triggers NK cell-derived cytokine production, which ultimately leads to tumor cell lysis and death. In an effort to develop effective immunotherapy approaches, the rational design of a novel class of immunostimulatory peptides (IPs) derived from the binding interface of B7H6:NKp30 is described in this study. The IPs comprised the B7H6 active site sequence for NKp30 binding and immunostimulatory activity. An aminohexanoic acid linker was also introduced at the N-terminus of the peptides for FITC-labeling by Fmoc-solid phase peptide synthesis. The peptides were characterized by LCMS to confirm identities and purities >95%. The secondary structures of the peptides were examined by CD spectroscopy in H2 O, PBS and a H2 O:TFE mixture which demonstrated versatile peptide structures which transitioned from random coil (H2 O) to α-helical (PBS) and turn-type (H2 O:TFE) conformations. Their biological properties were then evaluated by flow cytometry, enzyme-linked immunosorbent assays (ELISAs), and cell death assays. The occupancy of the synthetic peptides to a human NK cell line demonstrated comparable binding relative to the natural NKp30 ligand, B7H6, and the human anti-NKp30 monoclonal antibody (mAb), in a concentration dependent manner. A competitive binding assay between the human anti-NKp30 mAb or B7H6, and the synthetic peptides, demonstrated partial displacement of the ligands upon anti-NKp30 mAb treatment, suggesting NKp30 receptor specificities by the synthetic peptides. Moreover, the immunostimulatory activity of B7H6 was demonstrated by the secretion of the pro-inflammatory cytokines tumor necrosis factor-alfa (TNF-α) and interferon gamma (IFN-γ) by the human NK cell line. The

  2. Baseflow as the trigger of intraplate earthquakes

    NASA Astrophysics Data System (ADS)

    Costain, J. K.

    2012-12-01

    Intraplate earthquakes can be triggered by small changes in crustal loading, unloading, or pore-fluid pressure. A self-organized crust appears to be remarkably sensitive to extremely small changes in either pore-fluid pressure diffusion or stress loading, implying that these small changes in stress do not cause earthquakes, but only trigger them. Baseflow is commonly assumed to be equivalent to recharge. Groundwater recharge can trigger seismicity by reducing the effective normal stress on fractures. Intervals of higher groundwater recharge can be identified by determining when a stream is in baseflow recession, which is accccomplished by a hydrograph separation. Using the central Virginia seismic zone as an example, intraplate earthquakes tend to follow intervals of higher baseflow, i.e., recharge. A finite element model (FEM) of pore-fluid pressure diffusion for which the diffusion is within intersecting and hydraulically transmissive fracture zones allows comparisons to be made between 1) times of maxima in baseflow as determined for stream gaging station 02.0350.00 on the James River in the central Virginia seismic zone (CVSZ) and the time of occurrence of the Virginia 5.8 earthquake of August 23, 2010, and between 2) theoretical times of maxima in pore-fluid pressure diffusion from impulsive surface sources applied to exposed fracture zones as computed from the FEM simulation. The CVSZ, the New Madrid seismic zone, and the central Oklahoma seismic zone (COSZ) are all bisected by major river systems. Preliminary analysis of the stream gaging stations on rivers in and near the COSZ suggests that the earthquakes may be associated with the Canadian River system. The Meers fault does not seem to be involved. There is a slight correlation between the duration of baseflow and earthquake magnitude in the COSZ. The magnitude 5.6 earthquake of November 5, 2011 occurred about 200 days after a prolonged period of relatively high baseflow (recharge) as determined at stream

  3. Premonitory slip and tidal triggering of earthquakes

    USGS Publications Warehouse

    Lockner, D.A.; Beeler, N.M.

    1999-01-01

    Earth tides. Triggered seismicity has been reported resulting from the passage of surface waves excited by the Landers earthquake. These transient waves had measured amplitudes in excess of 0.1 MPa at frequencies of 0.05 to 0.2 Hz in regions of notable seismicity increase. Similar stress oscillations in our laboratory experiments produced strongly correlated stick-slip events. We suggest that seemingly inconsistent natural observations of triggered seismicity and absence of tidal triggering indicate that failure is amplitude and frequency dependent. This is the expected result if, as in our laboratory experiments, the rheology of the Earth's crust permits delayed failure.

  4. Investigation of Remotely Triggered Tremor and Earthquakes in Latin America

    NASA Astrophysics Data System (ADS)

    Gonzalez-Huizar, H.; Velasco, A. A.

    2014-12-01

    It has been shown that non-volcanic tremor (NVT) as well as small to moderate size earthquakes can be triggered by the seismic waves from distant earthquakes; however, little is understood about the triggering mechanisms. Investigating cases of remote triggering offers the opportunity to improve our knowledge about the physical mechanisms of earthquake interaction and nucleation. Furthermore, the similarities observed between remotely triggered NVT and those related to slow slip events, suggest that investigating triggered NVT may give us important insights into the mechanisms involved in slow slip events and their potential role in the earthquake cycle. In this work we present new results and the techniques we employ in identifying, locating and modeling cases of triggered earthquakes and NVT in Latin America and the Caribbean. In particular, we use global and regional seismic networks to perform an intensive search for triggered seismicity in Mexico, Cuba, Nicaragua, Costa Rica, Colombia, Ecuador, Peru, Bolivia, and Chile. Our results suggest that seismicity can be triggered in a broad variety of tectonic environments, depending strongly on the triggering dynamic stress amplitude and orientation. This investigation will help to define the regions where remote triggering occurs and their susceptibility to undergo an important increase in seismicity after the occurrence of a distant large earthquake.

  5. Peptides as triggers of plant defence.

    PubMed

    Albert, Markus

    2013-12-01

    Plants are confronted with several biotic stresses such as microbial pathogens and other herbivores. To defend against such attackers, plants possess an array of pattern recognition receptors (PRRs) that sense the danger and consequently initiate a defence programme that prevents further damage and spreading of the pest. Characteristic pathogenic structures, so-called microbe-associated molecular patterns (MAMPs), serve as signals that allow the plant to sense invaders. Additionally, pathogens wound or damage the plant and the resulting release of damage-associated molecular patterns (DAMPs) serves as a warning signal. This review focuses on peptides that serve as triggers or amplifiers of plant defence and thus follow the definition of a MAMP or a DAMP. PMID:24014869

  6. Simulation of rockfalls triggered by earthquakes

    USGS Publications Warehouse

    Kobayashi, Y.; Harp, E.L.; Kagawa, T.

    1990-01-01

    A computer program to simulate the downslope movement of boulders in rolling or bouncing modes has been developed and applied to actual rockfalls triggered by the Mammoth Lakes, California, earthquake sequence in 1980 and the Central Idaho earthquake in 1983. In order to reproduce a movement mode where bouncing predominated, we introduced an artificial unevenness to the slope surface by adding a small random number to the interpolated value of the mid-points between the adjacent surveyed points. Three hundred simulations were computed for each site by changing the random number series, which determined distances and bouncing intervals. The movement of the boulders was, in general, rather erratic depending on the random numbers employed, and the results could not be seen as deterministic but stochastic. The closest agreement between calculated and actual movements was obtained at the site with the most detailed and accurate topographic measurements. ?? 1990 Springer-Verlag.

  7. Using fixed financial triggers for incentive plans.

    PubMed

    Bjork, D A; Fairley, D J

    2000-03-01

    Of course, some organizations are making no changes at all, because they don't believe that financial performance will justify paying even small awards. Healthcare organizations with executive incentive compensation plans need to review existing plans with their compensation committees. Merely leaving in place incentive plans developed prior to BBA may be doing a dis-service to the executive teams, the hospital, and the board. Using the incentive plan to focus management's attention on a few key areas is still relevant, maybe more so than ever. A complete review of incentive plans--participation, opportunity levels, financial triggers, performance measures, and other factors--is an important element of total executive compensation, probably now more than ever. PMID:11183296

  8. Synchronization trigger control system for flow visualization

    NASA Technical Reports Server (NTRS)

    Chun, K. S.

    1987-01-01

    The use of cinematography or holographic interferometry for dynamic flow visualization in an internal combustion engine requires a control device that globally synchronizes camera and light source timing at a predefined shaft encoder angle. The device is capable of 0.35 deg resolution for rotational speeds of up to 73 240 rpm. This was achieved by implementing the shaft encoder signal addressed look-up table (LUT) and appropriate latches. The developed digital signal processing technique achieves 25 nsec of high speed triggering angle detection by using direct parallel bit comparison of the shaft encoder digital code with a simulated angle reference code, instead of using angle value comparison which involves more complicated computation steps. In order to establish synchronization to an AC reference signal whose magnitude is variant with the rotating speed, a dynamic peak followup synchronization technique has been devised. This method scrutinizes the reference signal and provides the right timing within 40 nsec. Two application examples are described.

  9. Starvation drives a threshold triggering communication.

    PubMed

    Mailleux, Anne-Catherine; Detrain, Claire; Deneubourg, Jean-Louis

    2006-11-01

    The decision for an ant forager to launch recruitment is governed by an internal response threshold. Here, we demonstrate that this threshold (the desired volume) triggering trail-laying increases under starvation. As a consequence, highly starved foragers lay a recruitment trail and bring back to the nest higher quantities of food from large unlimited resources. In contrast, when the volume of the food source is under their crop capacity, the percentage of trail-communicating foragers is lower following a prolonged period of starvation. Such starvation-dependent changes in the "desired volume" threshold explain how ants optimize recruitment and select liquid food resources in order to prevent collective exploitation of low profitability. PMID:17050837

  10. Aftershock triggering by complete Coulomb stress changes

    USGS Publications Warehouse

    Kilb, Debi; Gomberg, J.; Bodin, P.

    2002-01-01

    We examine the correlation between seismicity rate change following the 1992, M7.3, Landers, California, earthquake and characteristics of the complete Coulomb failure stress (CFS) changes (??CFS(t)) that this earthquake generated. At close distances the time-varying "dynamic" portion of the stress change depends on how the rupture develops temporally and spatially and arises from radiated seismic waves and from permanent coseismic fault displacement. The permanent "static" portion (??CFS) depends only on the final coseismic displacement. ??CFS diminishes much more rapidly with distance than the transient, dynamic stress changes. A common interpretation of the strong correlation between ??CFS and aftershocks is that load changes can advance or delay failure. Stress changes may also promote failure by physically altering properties of the fault or its environs. Because it is transient, ??CFS(t) can alter the failure rate only by the latter means. We calculate both ??CFS and the maximum positive value of ??CFS(t) (peak ??CFS(t)) using a reflectivity program. Input parameters are constrained by modeling Landers displacement seismograms. We quantify the correlation between maps of seismicity rate changes and maps of modeled ??CFS and peak ??CFS(t) and find agreement for both models. However, rupture directivity, which does not affect ??CFS, creates larger peak ??CFS(t) values northwest of the main shock. This asymmetry is also observed in seismicity rate changes but not in ??CFS. This result implies that dynamic stress changes are as effective as static stress changes in triggering aftershocks and may trigger earthquakes long after the waves have passed.

  11. A solar tornado triggered by flares?

    NASA Astrophysics Data System (ADS)

    Panesar, N. K.; Innes, D. E.; Tiwari, S. K.; Low, B. C.

    2013-01-01

    Context. Solar tornados are dynamical, conspicuously helical magnetic structures that are mainly observed as a prominence activity. Aims: We investigate and propose a triggering mechanism for the solar tornado observed in a prominence cavity by SDO/AIA on September 25, 2011. Methods: High-cadence EUV images from the SDO/AIA and the Ahead spacecraft of STEREO/EUVI are used to correlate three flares in the neighbouring active-region (NOAA 11303) and their EUV waves with the dynamical developments of the tornado. The timings of the flares and EUV waves observed on-disk in 195 Å are analysed in relation to the tornado activities observed at the limb in 171 Å. Results: Each of the three flares and its related EUV wave occurred within ten hours of the onset of the tornado. They have an observed causal relationship with the commencement of activity in the prominence where the tornado develops. Tornado-like rotations along the side of the prominence start after the second flare. The prominence cavity expands with the accelerating tornado motion after the third flare. Conclusions: Flares in the neighbouring active region may have affected the cavity prominence system and triggered the solar tornado. A plausible mechanism is that the active-region coronal field contracted by the "Hudson effect" through the loss of magnetic energy as flares. Subsequently, the cavity expanded by its magnetic pressure to fill the surrounding low corona. We suggest that the tornado is the dynamical response of the helical prominence field to the cavity expansion. Movies are available in electronic form at http://www.aanda.org

  12. Note: Triggering behavior of a vacuum arc plasma source

    NASA Astrophysics Data System (ADS)

    Lan, C. H.; Long, J. D.; Zheng, L.; Dong, P.; Yang, Z.; Li, J.; Wang, T.; He, J. L.

    2016-08-01

    Axial symmetry of discharge is very important for application of vacuum arc plasma. It is discovered that the triggering method is a significant factor that would influence the symmetry of arc discharge at the final stable stage. Using high-speed multiframe photography, the transition processes from cathode-trigger discharge to cathode-anode discharge were observed. It is shown that the performances of the two triggering methods investigated are quite different. Arc discharge triggered by independent electric source can be stabilized at the center of anode grid, but it is difficult to achieve such good symmetry through resistance triggering. It is also found that the triggering process is highly correlated to the behavior of emitted electrons.

  13. Burst mode trigger of STEREO in situ measurements

    NASA Astrophysics Data System (ADS)

    Jian, L. K.; Russell, C. T.; Luhmann, J. G.; Curtis, D.; Schroeder, P.

    2013-06-01

    Since the launch of the STEREO spacecraft, the in situ instrument suites have continued to modify their burst mode trigger in order to optimize the collection of high-cadence magnetic field, solar wind, and suprathermal electron data. This report reviews the criteria used for the burst mode trigger and their evolution with time. From 2007 to 2011, the twin STEREO spacecraft observed 236 interplanetary shocks, and 54% of them were captured by the burst mode trigger. The capture rate increased remarkably with time, from 30% in 2007 to 69% in 2011. We evaluate the performance of multiple trigger criteria and investigate why some of the shocks were missed by the trigger. Lessons learned from STEREO are useful for future missions, because the telemetry bandwidth needed to capture the waveforms of high frequency but infrequent events would be unaffordable without an effective burst mode trigger.

  14. Robotically assisted velocity-sensitive triggered focused ultrasound surgery

    NASA Astrophysics Data System (ADS)

    Maier, Florian; Brunner, Alexander; Jenne, Jürgen W.; Krafft, Axel J.; Semmler, Wolfhard; Bock, Michael

    2012-11-01

    Magnetic Resonance (MR) guided Focused Ultrasound Surgery (FUS) of abdominal organs is challenging due to breathing motion and limited patient access in the MR environment. In this work, an experimental robotically assisted FUS setup was combined with a MR-based navigator technique to realize motion-compensated sonications and online temperature imaging. Experiments were carried out in a static phantom, during periodic manual motion of the phantom without triggering, and with triggering to evaluate the triggering method. In contrast to the non-triggered sonication, the results of the triggered sonication show a confined symmetric temperature distribution. In conclusion, the velocity sensitive navigator can be employed for triggered FUS to compensate for periodic motion. Combined with the robotic FUS setup, flexible treatment of abdominal targets might be realized.

  15. Performance and upgrade plans of the LHCb trigger system

    NASA Astrophysics Data System (ADS)

    Gligorov, V. V.; LHCb Collaboration

    2013-08-01

    The trigger of the LHCb experiment consists of two stages: an initial hardware trigger, and a high-level trigger implemented in a farm of parallel-processing CPUs. It reduces the event rate from an input of 15 MHz to an output rate of around 4 kHz. In order to maximize efficiencies and minimize biases, the trigger is designed around inclusive selection algorithms, culminating in a novel boosted decision tree which enables the efficient selection of beauty hadron decays based on a robust partial reconstruction of their decay products. In order to improve performance, the LHCb upgrade aims to significantly increase the rate at which the detector will be read out, and hence shift more of the workload onto the high-level trigger. It is demonstrated that the current high-level trigger architecture will be able to meet this challenge, and the expected efficiencies in several key channels are discussed in context of the LHCb upgrade.

  16. Note: Triggering behavior of a vacuum arc plasma source.

    PubMed

    Lan, C H; Long, J D; Zheng, L; Dong, P; Yang, Z; Li, J; Wang, T; He, J L

    2016-08-01

    Axial symmetry of discharge is very important for application of vacuum arc plasma. It is discovered that the triggering method is a significant factor that would influence the symmetry of arc discharge at the final stable stage. Using high-speed multiframe photography, the transition processes from cathode-trigger discharge to cathode-anode discharge were observed. It is shown that the performances of the two triggering methods investigated are quite different. Arc discharge triggered by independent electric source can be stabilized at the center of anode grid, but it is difficult to achieve such good symmetry through resistance triggering. It is also found that the triggering process is highly correlated to the behavior of emitted electrons. PMID:27587176

  17. The Time-of-Flight trigger at CDF

    SciTech Connect

    Bauer, G.; Mulhearn, M.J.; Paus, Ch.; Schieferdecker, P.; Tether, S.; Lewis, J.D.; Shaw, T.; Acosta, D.; Konigsberg, J.; Madorsky, A.; /Florida U.

    2006-05-01

    The Time-of-Flight (TOF) detector measures the arrival time and deposited energy of charged particles reaching scintillator bars surrounding the central tracking region of the CDF detector. Requiring high ionization in the TOF system provides a unique trigger capability, which has been used for a magnetic monopole search. Other uses, with smaller pulse height thresholds, include a high-multiplicity charged-particle trigger useful for QCD studies and a much improved cosmic ray trigger for calibrating other detector components. Although not designed as input to CDF's global Level 1 trigger, the TOF system has been easily adapted to this role by the addition of 24 cables, new firmware, and four custom TOF trigger boards (TOTRIBs). This article describes the TOF trigger.

  18. Mark-II Data Acquisition and Trigger system

    SciTech Connect

    Breidenbach, M.

    1984-06-01

    The Mark-II Data Acquisition and Trigger system requirements and general solution are described. The solution takes advantage of the synchronous crossing times and low event rates of an electron positron collider to permit a very highly multiplexed analog scheme to be effective. The system depends on a two level trigger to operate with acceptable dead time. The trigger, multiplexing, data reduction, calibration, and CAMAC systems are described.

  19. Whistler-triggered emissions observed by ISIS satellites

    NASA Technical Reports Server (NTRS)

    Nakamura, Y.; Ondoh, T.

    1989-01-01

    A statistical examination has been conducted of the ducted and nonducted whistler-triggered emissions (WTEs) observed by the ISIS satellites in the 1979-1981 period. Most WTEs are observed with simultaneous lower hybrid resonance in the topside ionosphere. The VLF emissions triggered by ducted whistlers frequently occur at L of 2-3, while those triggered by nonducted whistlers occur in the wider latitudinal regions at L of 2.2-4.3.

  20. Trigger and Readout System for the Ashra-1 Detector

    NASA Astrophysics Data System (ADS)

    Aita, Y.; Aoki, T.; Asaoka, Y.; Morimoto, Y.; Motz, H. M.; Sasaki, M.; Abiko, C.; Kanokohata, C.; Ogawa, S.; Shibuya, H.; Takada, T.; Kimura, T.; Learned, J. G.; Matsuno, S.; Kuze, S.; Binder, P. M.; Goldman, J.; Sugiyama, N.; Watanabe, Y.

    Highly sophisticated trigger and readout system has been developed for All-sky Survey High Resolution Air-shower (Ashra) detector. Ashra-1 detector has 42 degree diameter field of view. Detection of Cherenkov and fluorescence light from large background in the large field of view requires finely segmented and high speed trigger and readout system. The system is composed of optical fiber image transmission system, 64 × 64 channel trigger sensor and FPGA based trigger logic processor. The system typically processes the image within 10 to 30 ns and opens the shutter on the fine CMOS sensor. 64 × 64 coarse split image is transferred via 64 × 64 precisely aligned optical fiber bundle to a photon sensor. Current signals from the photon sensor are discriminated by custom made trigger amplifiers. FPGA based processor processes 64 × 64 hit pattern and correspondent partial area of the fine image is acquired. Commissioning earth skimming tau neutrino observational search was carried out with this trigger system. In addition to the geometrical advantage of the Ashra observational site, the excellent tau shower axis measurement based on the fine imaging and the night sky background rejection based on the fine and fast imaging allow zero background tau shower search. Adoption of the optical fiber bundle and trigger LSI realized 4k channel trigger system cheaply. Detectability of tau shower is also confirmed by simultaneously observed Cherenkov air shower. Reduction of the trigger threshold appears to enhance the effective area especially in PeV tau neutrino energy region. New two dimensional trigger LSI was introduced and the trigger threshold was lowered. New calibration system of the trigger system was recently developed and introduced to the Ashra detector

  1. Method for modifying trigger level for adsorber regeneration

    DOEpatents

    Ruth, Michael J.; Cunningham, Michael J.

    2010-05-25

    A method for modifying a NO.sub.x adsorber regeneration triggering variable. Engine operating conditions are monitored until the regeneration triggering variable is met. The adsorber is regenerated and the adsorbtion efficiency of the adsorber is subsequently determined. The regeneration triggering variable is modified to correspond with the decline in adsorber efficiency. The adsorber efficiency may be determined using an empirically predetermined set of values or by using a pair of oxygen sensors to determine the oxygen response delay across the sensors.

  2. A VXIbus based trigger for the CLAS detector at CEBAF

    SciTech Connect

    D.C. Doughty, Jr.; J. Englert; R. Hale; S. Lemon; P. Leung; C. Cuevas; D. Joyce

    1992-04-01

    A VXIbus based first level triggering system for the CLAS detector at CEBAF has been designed and prototyped. It uses pipelining and a triple memory lookup to produce a dead-timeless trigger decision with an average latency of 110 nS and a jitter of 20 nS. The VXIbus Extended Start/Stop triggering protocols allow sub-nanosecond time synchronization.

  3. A VXIbus based trigger for the CLAS detector at CEBAF

    SciTech Connect

    Doughty, D.C. Jr.; Englert, J.; Hale, R.; Lemon, S. ); Leung, P. ); Cuevas, C.; Joyce, D. )

    1992-04-01

    This paper discusses a VXIbus based first level triggering system for the CLAS detector at CEBAF which has been designed and prototyped. It uses pipelining and a triple memory lookup to produce a dead-timeless trigger decision with an average latency of 110 ns and a jitter of 20 ns. The VXIbus Extended Start/Stop triggering protocols allow sub-nanosecond time synchronization.

  4. The Level 0 Trigger Processor for the NA62 experiment

    NASA Astrophysics Data System (ADS)

    Chiozzi, S.; Gamberini, E.; Gianoli, A.; Mila, G.; Neri, I.; Petrucci, F.; Soldi, D.

    2016-07-01

    In the NA62 experiment at CERN, the intense flux of particles requires a high-performance trigger for the data acquisition system. A Level 0 Trigger Processor (L0TP) was realized, performing the event selection based on trigger primitives coming from sub-detectors and reducing the trigger rate from 10 to 1 MHz. The L0TP is based on a commercial FPGA device and has been implemented in two different solutions. The performance of the two systems are highlighted and compared.

  5. The digital trigger system for the RED-100 detector

    SciTech Connect

    Naumov, P. P. Akimov, D. Yu.; Belov, V. A.; Bolozdynya, A. I.; Efremenko, Yu. V.; Kaplin, V. A.

    2015-12-15

    The system for forming a trigger for the liquid xenon detector RED-100 is developed. The trigger can be generated for all types of events that the detector needs for calibration and data acquisition, including the events with a single electron of ionization. In the system, a mechanism of event detection is implemented according to which the timestamp and event type are assigned to each event. The trigger system is required in the systems searching for rare events to select and keep only the necessary information from the ADC array. The specifications and implementation of the trigger unit which provides a high efficiency of response even to low-energy events are considered.

  6. The upgrade of the ATLAS first-level calorimeter trigger

    NASA Astrophysics Data System (ADS)

    Yamamoto, Shimpei

    2016-07-01

    The first-level calorimeter trigger (L1Calo) had operated successfully through the first data taking phase of the ATLAS experiment at the CERN Large Hadron Collider. Towards forthcoming LHC runs, a series of upgrades is planned for L1Calo to face new challenges posed by the upcoming increases of the beam energy and the luminosity. This paper reviews the ATLAS L1Calo trigger upgrade project that introduces new architectures for the liquid-argon calorimeter trigger readout and the L1Calo trigger processing system.

  7. Migraine triggered by sucralose--a case report.

    PubMed

    Bigal, Marcelo E; Krymchantowski, Abouch V

    2006-03-01

    Sucralose is the active compound of the most commonly sold sweetener in the United States. Different than aspartame, sucralose is not considered to be a migraine trigger. Herein we report a patient with attacks of migraine consistently triggered by sucralose. She also suffers from menstrually related migraine that had been well-controlled for several months since she switched her contraceptive from fixed estrogen to triphasic contraceptive pills. Some attacks triggered by sucralose were preceded by aura, and she had never experienced migraine with aura before. Withdrawal of the compound was associated with complete resolution of the attacks. Single-blind exposure (vs. sugar) triggered the attacks, after an attack-free period.

  8. Upgrade of the ALICE muon trigger electronics

    NASA Astrophysics Data System (ADS)

    Dupieux, P.; Joly, B.; Jouve, F.; Manen, S.; Vandaële, R.

    2014-09-01

    The ALICE muon trigger is a large scale detector based on single gap bakelite RPCs. An upgrade of the electronics is needed in order to withstand the increase of luminosity after the LHC Long Shutdown-2 in 2018-2019. The detector will be read out at the minimum bias rate of 100 kHz in Pb-Pb collisions (including a safety factor of 2), two orders of magnitude above the present design. For the most exposed RPCs and in the present conditions of operation, the total integrated charge could be as high as 100 mC/cm2 with rates up to 100 Hz/cm2, which is above the present limit for safe operation. In order to overcome these limitations, upgrade projects of the Front-End (FE) and Readout Electronics are scheduled. The readout upgrade at high rate with low dead time requires changing most of the present electronics. It involves a new design for the 234 Local cards receiving the LVDS signals from the FE electronics and the 16 Regional concentrator cards. The readout chain is completed by a single Common Readout Unit developed for most ALICE sub-detectors. The new architecture of the muon trigger readout will be briefly presented. The present FE electronics, designed for the streamer mode, must be replaced to prevent ageing of the RPCs in the future operating conditions. The new FE called FEERIC (for Front-End Electronics Rapid Integrated Circuit) will have to perform amplification of the analog input signals. This will allow for RPC operation in a low-gain avalanche mode, with a much smaller charge deposit (factor 3-5) in the detector as compared to the present conditions. The purpose is to discriminate RPC signals with a charge threshold around 100 fC, in both polarities, and with a time jitter below 1 ns. We will describe the FE card and FEERIC ASIC features and first prototype performance, report on test results obtained on a cosmic test bench and discuss ongoing developments.

  9. Finger Tendon Travel Associated with Sequential Trigger Nail Gun Use

    PubMed Central

    Lowe, Brian; Albers, James; Hudock, Stephen; Krieg, Edward

    2015-01-01

    TECHNICAL ABSTRACT Background Pneumatic nail guns used in wood framing are equipped with one of two triggering mechanisms. Sequential actuation triggers have been shown to be a safer alternative to contact actuation triggers because they reduce traumatic injury risk. However, the sequential actuation trigger must be depressed for each individual nail fired as opposed to the contact actuation trigger, which allows the trigger to be held depressed as nails are fired repeatedly by bumping the safety tip against the workpiece. As such, concerns have been raised about risks for cumulative trauma injury, and reduced productivity, due to repetitive finger motion with the sequential actuation trigger. Purpose This study developed a method to predict cumulative finger flexor tendon travel associated with the sequential actuation trigger nail gun from finger joint kinematics measured in the trigger actuation and productivity standards for wood-frame construction tasks. Methods Finger motions were measured from six users wearing an instrumented electrogoniometer glove in a simulation of two common framing tasks–wall building and flat nailing of material. Flexor tendon travel was calculated from the ensemble average kinematics for an individual nail fired. Results Finger flexor tendon travel was attributable mostly to proximal interphalangeal and distal interphalangeal joint motion. Tendon travel per nail fired appeared to be slightly greater for a wall-building task than a flat nailing task. The present study data, in combination with construction industry productivity standards, suggest that a high-production workday would be associated with less than 60 m/day cumulative tendon travel per worker (based on 1700 trigger presses/day). Conclusion and Applications These results suggest that exposure to finger tendon travel from sequential actuation trigger nail gun use may be below levels that have been previously associated with high musculoskeletal disorder risk. PMID

  10. Triggered infrared spectroscopy for investigating metalloprotein chemistry.

    PubMed

    Vincent, Kylie A

    2010-08-13

    Recent developments in infrared (IR) spectroscopic time resolution, sensitivity and sample manipulation make this technique a powerful addition to the suite of complementary approaches for the study of time-resolved chemistry at metal centres within proteins. Application of IR spectroscopy to proteins has often targeted the amide bands as probes for gross structural change. This article focuses on the possibilities arising from recent IR technical developments for studies that monitor localized vibrational oscillators in proteins--native or exogenous ligands such as NO, CO, SCN(-) or CN(-), or genetically or chemically introduced probes with IR-active vibrations. These report on the electronic and coordination state of metals, the kinetics, intermediates and reaction pathways of ligand release, hydrogen-bonding interactions between the protein and IR probe, and the electrostatic character of sites in a protein. Metalloprotein reactions can be triggered by light/dark transitions, an electrochemical step, a change in solute composition or equilibration with a new gas atmosphere, and spectra can be obtained over a range of time domains as far as the sub-picosecond level. We can expect to see IR spectroscopy exploited, alongside other spectroscopies, and crystallography, to elucidate reactions of a wide range of metalloprotein chemistry with relevance to cell metabolism, health and energy catalysis.

  11. Submarine landslides: processes, triggers and hazard prediction.

    PubMed

    Masson, D G; Harbitz, C B; Wynn, R B; Pedersen, G; Løvholt, F

    2006-08-15

    Huge landslides, mobilizing hundreds to thousands of km(3) of sediment and rock are ubiquitous in submarine settings ranging from the steepest volcanic island slopes to the gentlest muddy slopes of submarine deltas. Here, we summarize current knowledge of such landslides and the problems of assessing their hazard potential. The major hazards related to submarine landslides include destruction of seabed infrastructure, collapse of coastal areas into the sea and landslide-generated tsunamis. Most submarine slopes are inherently stable. Elevated pore pressures (leading to decreased frictional resistance to sliding) and specific weak layers within stratified sequences appear to be the key factors influencing landslide occurrence. Elevated pore pressures can result from normal depositional processes or from transient processes such as earthquake shaking; historical evidence suggests that the majority of large submarine landslides are triggered by earthquakes. Because of their tsunamigenic potential, ocean-island flank collapses and rockslides in fjords have been identified as the most dangerous of all landslide related hazards. Published models of ocean-island landslides mainly examine 'worst-case scenarios' that have a low probability of occurrence. Areas prone to submarine landsliding are relatively easy to identify, but we are still some way from being able to forecast individual events with precision. Monitoring of critical areas where landslides might be imminent and modelling landslide consequences so that appropriate mitigation strategies can be developed would appear to be areas where advances on current practice are possible.

  12. Can ice sheets trigger abrupt climatic change?

    SciTech Connect

    Hughes, T.

    1996-11-01

    The discovery in recent years of abrupt climatic changes in climate proxy records from Greenland ice cores and North Atlantic sediment cores, and from other sites around the world, has diverted attention from gradual insolation changes caused by Earth`s orbital variations to more rapid processes on Earth`s surface as forcing Quaternary climatic change. In particular, forcing by ice sheets has been quantified for a major ice stream that drained the Laurentide Ice Sheet along Hudson Strait. The history of these recent discoveries leading to an interest in ice sheets is reviewed, and a case is made that ice sheets may drive abrupt climatic change that is virtually synchronous worldwide. Attention is focused on abrupt inception and termination of a Quaternary glaciation cycle, abrupt changes recorded as stadials and interstadials within the cycle, abrupt changes in ice streams that trigger stadials and interstadials, and abrupt changes in the Laurentide Ice Sheet linked to effectively simultaneous abrupt changes in its ice streams. Remaining work needed to quantify further these changes is discussed. 90 refs., 14 figs.

  13. ULF Waves Triggered By An Ssc Onset

    NASA Astrophysics Data System (ADS)

    Laakso, H.; Glassmeier, K. H.; Andre, M.; Balogh, A.; Dunlop, M.; Gustafsson, G.; Mozer, F.; Pedersen, A.

    One of typical consequences of storm sudden commencements (SSC) is the occur- rence of large-amplitude wave activities, such as low-frequency field line resonances (FLR). They are triggered by compressional waves generated at the magnetopause by fast moving solar wind disturbances. In this paper we investigate FLRs after one SSC onset on August 30, 2001, 14:11 UT, using multi-point electric and magnetic field measurements from the Cluster satellites. At the moment of the onset, the quartet was in the inner magnetosphere near 12 MLT. Cluster 1, 2 and 4 were separated by a few thousand km at L = 4.3-4.5 whereas Cluster 3 was almost 2 RE away at L = 5.4. The SSC onset was immediately followed by strong field line resonances as detected by all four satellites; the amplitude of electric field fluctuations was 2 mV/m in the be- ginning, but it decreased during the first oscillation period. The waves persisted for an hour. During this time, Cluster 3 moved towards the perigee near L = 4, whereas the other three moved to higher L shells up to L = 7. This study will present details of the electric and magnetic field oscillations and the Poynting vector during the event. We particularly compare wave characteristics at four points as well as their L shell dependence.

  14. Polar domain walls trigger magnetoelectric coupling

    PubMed Central

    Fontcuberta, Josep; Skumryev, Vassil; Laukhin, Vladimir; Granados, Xavier; Salje, Ekhard K. H.

    2015-01-01

    Interface physics in oxides heterostructures is pivotal in material’s science. Domain walls (DWs) in ferroic systems are examples of naturally occurring interfaces, where order parameter of neighboring domains is modified and emerging properties may develop. Here we show that electric tuning of ferroelastic domain walls in SrTiO3 leads to dramatic changes of the magnetic domain structure of a neighboring magnetic layer (La1/2Sr1/2MnO3) epitaxially clamped on a SrTiO3 substrate. We show that the properties of the magnetic layer are intimately connected to the existence of polar regions at twin boundaries of SrTiO3, developing at , that can be electrically modulated. These findings illustrate that by exploiting the responsiveness of DWs nanoregions to external stimuli, even in absence of any domain contribution, prominent and adjustable macroscopic reactions of neighboring layers can be obtained. We conclude that polar DWs, known to exist in other materials, can be used to trigger tunable responses and may lead to new ways for the manipulation of interfacial emerging properties. PMID:26387597

  15. Coinfection can trigger multiple pandemic waves.

    PubMed

    Merler, Stefano; Poletti, Piero; Ajelli, Marco; Caprile, Bruno; Manfredi, Piero

    2008-09-21

    Sequences of epidemic waves have been observed in past influenza pandemics, such as the Spanish influenza. Possible explanations may be sought either in mechanisms altering the structure of the network of contacts, such as those induced by changes in the rates of movement of people or by public health measures, or in the genetic drift of the influenza virus, since the appearance of new strains can reduce or eliminate herd immunity. The pandemic outbreaks may also be influenced by coinfection with other acute respiratory infections (ARI) that increase transmissibility of influenza virus (by coughing, sneezing, running nose). In fact, some viruses (e.g., Rhinovirus and Adenovirus) have been found to induce "clouds" of bacteria and increase the transmissibility of Staphylococcus aureus. Moreover, Rhinovirus and Adenovirus were detected in patients during past pandemics, and their presence is linked to superspreading events. In this paper, by assuming increased transmissibility in coinfected individuals, we propose and study a model where multiple pandemic waves are triggered by coinfection with ARI. The model agrees well with mortality excess data during the 1918 pandemic influenza, thereby providing indications for potential pandemic mitigation.

  16. Featured Image: A Bubble Triggering Star Formation

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-05-01

    This remarkable false-color, mid-infrared image (click for the full view!) was produced by the Wide-field Infrared Survey Explorer (WISE). It captures a tantalizing view of Sh 2-207 and Sh 2-208, the latter of which is one of the lowest-metallicity star-forming regions in the Galaxy. In a recent study led by Chikako Yasui (University of Tokyo and the Koyama Astronomical Observatory), a team of scientists has examined this region to better understand how star formation in low-metallicity environments differs from that in the solar neighborhood. The authors analysis suggests that sequential star formation is taking place in these low-metallicity regions, triggered by an expanding bubble (the large dashed oval indicated in the image) with a ~30 pc radius. You can find out more about their study by checking out the paper below!CitationChikako Yasui et al 2016 AJ 151 115. doi:10.3847/0004-6256/151/5/115

  17. Competition for Trophies Triggers Male Generosity

    PubMed Central

    Pan, Xiaofei Sophia; Houser, Daniel

    2011-01-01

    Background Cooperation is indispensable in human societies, and much progress has been made towards understanding human pro-social decisions. Formal incentives, such as punishment, are suggested as potential effective approaches despite the fact that punishment can crowd out intrinsic motives for cooperation and detrimentally impact efficiency. At the same time, evolutionary biologists have long recognized that cooperation, especially food sharing, is typically efficiently organized in groups living on wild foods, even absent formal economic incentives. Despite its evident importance, the source of this voluntary compliance remains largely uninformed. Drawing on costly signaling theory, and in light of the widely established competitive nature of males, we hypothesize that unique and displayable rewards (trophies) out of competition may trigger male generosity in competitive social environments. Principal Findings Here, we use a controlled laboratory experiment to show that cooperation is sustained in a generosity competition with trophy rewards, but breaks down in the same environment with equally valuable but non-unique and non-displayable rewards. Further, we find that males' competition for trophies is the driving force behind treatment differences. In contrast, it appears that female competitiveness is not modulated by trophy rewards. Significance Our results suggest new approaches to promoting cooperation in human groups that, unlike punishment mechanisms, do not sacrifice efficiency. This could have important implications in any domain where voluntary compliance matters — including relations between spouses, employers and employees, market transactions, and conformity to legal standards. PMID:21494668

  18. Submarine landslides: processes, triggers and hazard prediction.

    PubMed

    Masson, D G; Harbitz, C B; Wynn, R B; Pedersen, G; Løvholt, F

    2006-08-15

    Huge landslides, mobilizing hundreds to thousands of km(3) of sediment and rock are ubiquitous in submarine settings ranging from the steepest volcanic island slopes to the gentlest muddy slopes of submarine deltas. Here, we summarize current knowledge of such landslides and the problems of assessing their hazard potential. The major hazards related to submarine landslides include destruction of seabed infrastructure, collapse of coastal areas into the sea and landslide-generated tsunamis. Most submarine slopes are inherently stable. Elevated pore pressures (leading to decreased frictional resistance to sliding) and specific weak layers within stratified sequences appear to be the key factors influencing landslide occurrence. Elevated pore pressures can result from normal depositional processes or from transient processes such as earthquake shaking; historical evidence suggests that the majority of large submarine landslides are triggered by earthquakes. Because of their tsunamigenic potential, ocean-island flank collapses and rockslides in fjords have been identified as the most dangerous of all landslide related hazards. Published models of ocean-island landslides mainly examine 'worst-case scenarios' that have a low probability of occurrence. Areas prone to submarine landsliding are relatively easy to identify, but we are still some way from being able to forecast individual events with precision. Monitoring of critical areas where landslides might be imminent and modelling landslide consequences so that appropriate mitigation strategies can be developed would appear to be areas where advances on current practice are possible. PMID:16844646

  19. Triggering of Programmed Erythrocyte Death by Alantolactone

    PubMed Central

    Alzoubi, Kousi; Calabrò, Salvatrice; Egler, Jasmin; Faggio, Caterina; Lang, Florian

    2014-01-01

    The sesquiterpene alantolactone counteracts malignancy, an effect at least in part due to stimulation of suicidal death or apoptosis of tumor cells. Signaling of alantolactone induced apoptosis involves altered gene expression and mitochondrial depolarization. Erythrocytes lack mitochondria and nuclei but may enter suicidal death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine exposure at the erythrocyte surface. Cellular mechanisms involved in triggering of eryptosis include increase of cytosolic Ca2+-activity ([Ca2+]i) and oxidative stress. The present study explored, whether alantolactone stimulates eryptosis. To this end, erythrocyte volume was estimated from forward scatter, phosphatidylserine-exposure at the erythrocyte surface from FITC-annexin-V-binding, [Ca2+]i from Fluo3-fluorescence, ceramide abundance from binding of fluorescent antibodies, and oxidative stress from 2',7'-dichlorodihydrofluorescein-diacetate (DCFDA) fluorescence. As a result, a 48 h exposure of human erythrocytes to alantolactone (≥20 μM) significantly decreased erythrocyte forward scatter and increased the percentage of annexin-V-binding cells. Alantolactone significantly increased Fluo3 fluorescence (60 μM), ceramide abundance (60 μM) and DCFDA fluorescence (≥40 μM). The effect of alantolactone (60 μM) on annexin-V-binding was not significantly modified by removal of extracellular Ca2+. In conclusion, alantolactone stimulates suicidal erythrocyte death or eryptosis, an effect paralleled by increase of [Ca2+]i, ceramide abundance and oxidative stress. PMID:25533522

  20. Trigger point needling: techniques and outcome.

    PubMed

    Vulfsons, Simon; Ratmansky, Motti; Kalichman, Leonid

    2012-10-01

    In this review we provide the updates on last years' advancements in basic science, imaging methods, efficacy, and safety of dry needling of myofascial trigger points (MTrPs). The latest studies confirmed that dry needling is an effective and safe method for the treatment of MTrPs when provided by adequately trained physicians or physical therapists. Recent basic studies have confirmed that at the site of an active MTrP there are elevated levels of inflammatory mediators, known to be associated with persistent pain states and myofascial tenderness and that this local milieu changes with the occurrence of local twitch response. Two new modalities, sonoelastography and magnetic resonance elastography, were recently introduced allowing noninvasive imaging of MTrPs. MTrP dry needling, at least partially, involves supraspinal pain control via midbrain periaqueductal gray matter activation. A recent study demonstrated that distal muscle needling reduces proximal pain by means of the diffuse noxious inhibitory control. Therefore, in a patient too sensitive to be needled in the area of the primary pain source, the treatment can be initiated with distal needling.

  1. Using Reflection Triggers while Learning in an Online Course

    ERIC Educational Resources Information Center

    Verpoorten, Dominique; Westera, Wim; Specht, Marcus

    2012-01-01

    This paper reports on a controlled experiment on the effects of three types of reflection triggers in an online course. Fifty-four volunteers, distributed in five groups, used these structured opportunities for reflection during learning. Results show that reflection triggers were extensively employed by the test persons and were perceived as…

  2. Inconsistency with Prior Knowledge Triggers Children's Causal Explanatory Reasoning

    ERIC Educational Resources Information Center

    Legare, Cristine H.; Gelman, Susan A.; Wellman, Henry M.

    2010-01-01

    What events trigger causal explanatory reasoning in young children? Children's explanations could be triggered by either consistent events (suggesting that explanations serve a confirmatory function) or inconsistent events (suggesting that they promote discovery of new information). In 2 studies with preschool children (N = 80), events that were…

  3. Triggering Death of Adherent Cells with Ultraviolet Radiation.

    PubMed

    Crowley, Lisa C; Waterhouse, Nigel J

    2016-01-01

    Ultraviolet (UV) radiation is a convenient stimulus for triggering cell death that is available in most laboratories. We use a Stratalinker UV cross-linker because it is a safe, cheap, reliable, consistent, and easily controlled source of UV irradiation. This protocol describes using a Stratalinker to trigger UV-induced death of HeLa cells. PMID:27371593

  4. 76 FR 31295 - WTO Agricultural Safeguard Trigger Levels

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-31

    ... Secretary of Agriculture in Presidential Proclamation No. 6763, dated December 23, 1994, 60 FR 1005 (Jan. 4... Trigger Levels, published in the Federal Register at 60 FR 427 (Jan. 4, 1995). Notice: As provided in... Round Agricultural Safeguard Trigger Levels published in the Federal Register, at 60 FR 427 (Jan....

  5. Could Stroke Trigger Be Prevented by Healthy Family Relationships?

    ERIC Educational Resources Information Center

    Rochette, Annie; Gaulin, Philippe; Tellier, Myriam

    2009-01-01

    Although major stroke risk factors are well documented, little is known about which life circumstances are perceived to be related to the actual triggering of a first stroke. The purpose was to explore self-perceived spontaneously related life circumstances surrounding the trigger of a first stroke. A qualitative design with a phenomenological…

  6. Triggering for Magnetic Field Measurements of the LCLS Undulators

    SciTech Connect

    Hacker, Kirsten

    2010-12-13

    A triggering system for magnetic field measurements of the LCLS undulators has been built with a National Instruments PXI-1002 and a Xylinx FPGA board. The system generates single triggers at specified positions, regardless of encoder sensor jitter about a linear scale.

  7. The ATLAS Data Acquisition and Trigger: concept, design and status

    NASA Astrophysics Data System (ADS)

    Kordas, K.; Abolins, M.; Alexandrov, I.; Amorim, A.; Aracena, I.; Armstrong, S.; Badescu, E.; Baines, J. T. M.; Barros, N.; Beck, H. P.; Bee, C.; Bellomo, M.; Biglietti, M.; Blair, R.; Bogaerts, J. A. C.; Bold, T.; Bosman, M.; Burckhart-Chromek, D.; Caprini, M.; Caramarcu, C.; Carlino, G.; Caron, B.; Casado, M. P.; Cataldi, G.; Ciobotaru, M.; Comune, G.; Conde-Muino, P.; Conventi, F.; Corso-Radu, A.; Cranfield, R.; Cranmer, K.; Crone, G.; Damazio, D.; Dawson, J.; De Santo, A.; Del Prete, T.; Della Pietra, M.; Di Mattia, A.; Diaz-Gomaz, M.; Dobinson, R. W.; Dobson, M.; Dos Anjos, A.; Dotti, A.; Drake, G.; Ellis, N.; Emeliyanov, D.; Ermoline, Y.; Ertorer, E.; Falciano, S.; Ferrari, R.; Ferrer, M. L.; Francis, D.; Gadomski, S.; Gameiro, S.; Garitaonandia, H.; Gaudio, G.; Gaumer, O.; George, S.; Gesualdi-Mello, A.; Goncalo, R.; Gorini, B.; Gorini, E.; Green, B.; Haas, S.; Haberichter, W. N.; Hadavand, H.; Haeberli, C.; Haller, J.; Hansen, J.; Hauser, R.; Hillier, S. J.; Höcker, A.; Hughes-Jones, R. E.; Joos, M.; Kabana, S.; Kazarov, A.; Khomich, A.; Kieft, G.; Kilvington, G.; Kirk, J.; Klous, S.; Kohno, T.; Kolos, S.; Konstantinidis, N.; Kootz, A.; Korcyl, K.; Kotov, V.; Kugel, A.; Landon, M.; Lankford, A.; Leahu, L.; Leahu, M.; Lehmann-Miotto, G.; Le Vine, M. J.; Liu, W.; Lowe, C.; Luminari, L.; Maeno, T.; Männer, R.; Mapelli, L.; Martin, B.; Marzano, F.; Masik, J.; McLaren, R.; McMahon, T.; Meessen, C.; Meirosu, C.; Mineev, M.; Misiejuk, A.; Moore, R.; Morettini, P.; Mornacchi, G.; Müller, M.; Murillo-García, R.; Nagasaka, Y.; Negri, A.; Nisati, A.; Osuna, C.; Padilla, C.; Panikashvili, N.; Parodi, F.; Pasqualucci, E.; Pauly, T.; Perera, V.; Pérez-Réale, V.; Petersen, J.; Pinfold, J. L.; Pope, B.; Portes de Albuquerque, M.; Potter, C.; Pretzl, K.; Prigent, D.; Primavera, M.; Rheaum, P.; Robertson, S.; Roda, C.; Ryabov, Y.; Salvatore, D.; Santamarina-Rios, C.; Scannicchio, D. A.; Schiavi, C.; Schlereth, J. L.; Scholtes, I.; Seixas, M.; Sidoti, A.; Sivoklokov, S.; Sloper, J.; Sole-Segura, E.; Soloviev, I.; Soluk, R.; Spagnolo, S.; Spiwoks, R.; Stamen, R.; Stancu, S.; Stefanidis, E.; Strong, J.; Sushkov, S.; Sutton, M.; Szymocha, T.; Tapprogge, S.; Tarem, S.; Tarem, Z.; Teixeira-Dias, P.; Thomas, E.; Torres, R.; Touchard, F.; Tremblet, L.; Unel, N. G.; Usai, G.; Vachon, B.; Van Wasen, J.; Vandelli, W.; Vaz Gil Lopes, L.; Ventura, A.; Vercesi, V.; Vermeulen, J.; von der Schmitt, H.; Warburton, A.; Watson, A.; Wengler, T.; Werner, P.; Wheeler, S.; Wickens, F.; Wiedenmann, W.; Wielers, M.; Wiesmann, M.; Woehrling, E. E.; Wu, X.; Yasu, Y.; Yu, M.; Zema, F.; Zobernig, H.

    2007-10-01

    This article presents the base-line design and implementation of the ATLAS Trigger and Data Acquisition system, in particular the Data Flow and High Level Trigger components. The status of the installation and commissioning of the system is also presented.

  8. Evaluation of triggering functions in convective parameterization schemes using observations

    NASA Astrophysics Data System (ADS)

    Ettammal, S.; Zhang, G. J.

    2013-12-01

    Realistic simulation of different modes of atmospheric variability ranging from the diurnal cycle to inter-annual variability in global climate models (GCMs) depends crucially on the convection triggering criteria. In this study, using the data from constrained variational analysis by the Atmospheric System Research program for single column models (SCM), the performance of the commonly used convective triggering functions in GCMs is evaluated, based on the equitable threat score (ETS) value, a widely used forecast verification metric. From the ETS score, four consistently better performing triggering functions were identified. They are based on dilute dCAPE, parcel buoyancy at the lifting condensation level (Bechtold scheme), undilute dCAPE and dilute CAPE triggering functions. The key variables used to define these triggering functions were examined in detail. It was found that the skill score value of the dilute dCAPE triggering function does not show much variation among different data sets. Analysis of the composite fields and probability distributions of key variables of the triggering functions, based on the correct-prediction, over-prediction, under-prediction of convection and correct prediction of no convection cases for convection onset, brings to light some critical factors responsible for the performance of the trigger functions.

  9. Parent Trigger Policies, Representation, and the Public Good

    ERIC Educational Resources Information Center

    Allen, Ann; Saultz, Andrew

    2015-01-01

    Using theories of representation and democratic education, this article examines the impetus of parent trigger policies in the United States and their potential effects on public good goals for public education. The article also uses theories of representation and responsible democratic governance to assess the parent trigger policies, or what are…

  10. Local near instantaneously dynamically triggered aftershocks of large earthquakes

    NASA Astrophysics Data System (ADS)

    Fan, Wenyuan; Shearer, Peter M.

    2016-09-01

    Aftershocks are often triggered by static- and/or dynamic-stress changes caused by mainshocks. The relative importance of the two triggering mechanisms is controversial at near-to-intermediate distances. We detected and located 48 previously unidentified large early aftershocks triggered by earthquakes with magnitudes between ≥7 and 8 within a few fault lengths (approximately 300 kilometers), during times that high-amplitude surface waves arrive from the mainshock (less than 200 seconds). The observations indicate that near-to-intermediate-field dynamic triggering commonly exists and fundamentally promotes aftershock occurrence. The mainshocks and their nearby early aftershocks are located at major subduction zones and continental boundaries, and mainshocks with all types of faulting-mechanisms (normal, reverse, and strike-slip) can trigger early aftershocks.

  11. Local near instantaneously dynamically triggered aftershocks of large earthquakes.

    PubMed

    Fan, Wenyuan; Shearer, Peter M

    2016-09-01

    Aftershocks are often triggered by static- and/or dynamic-stress changes caused by mainshocks. The relative importance of the two triggering mechanisms is controversial at near-to-intermediate distances. We detected and located 48 previously unidentified large early aftershocks triggered by earthquakes with magnitudes between ≥7 and 8 within a few fault lengths (approximately 300 kilometers), during times that high-amplitude surface waves arrive from the mainshock (less than 200 seconds). The observations indicate that near-to-intermediate-field dynamic triggering commonly exists and fundamentally promotes aftershock occurrence. The mainshocks and their nearby early aftershocks are located at major subduction zones and continental boundaries, and mainshocks with all types of faulting-mechanisms (normal, reverse, and strike-slip) can trigger early aftershocks.

  12. Innovative Techniques for Teaching about Landslides and Triggered Landslide Events

    NASA Astrophysics Data System (ADS)

    Taylor, F. E.; Malamud, B. D.

    2014-12-01

    When we think of a landslide (mass wasting), both the public and scientists often envisage an individual movement of earth material down a slope. Yet, landslides often occur not as individuals, but as parts of a triggered landslide event. This is where a trigger (e.g., an earthquake or heavy rainfall) results in up to tens of thousands of landslides in a region in the minutes to days after the trigger. In this paper, we will present ideas for innovative demonstrations, teaching practicals and projects, ranging from low-cost low-tech to more advanced digital methods, to communicate the ideas of landslides and triggered landslide events to the public and students. This paper is aimed at those in secondary school/university education and the public sector looking for examples to interest and inform their respective audiences about landslides, triggered landslide events, and the importance and implications of considering landslides not just as individuals, but as populations.

  13. Local near instantaneously dynamically triggered aftershocks of large earthquakes.

    PubMed

    Fan, Wenyuan; Shearer, Peter M

    2016-09-01

    Aftershocks are often triggered by static- and/or dynamic-stress changes caused by mainshocks. The relative importance of the two triggering mechanisms is controversial at near-to-intermediate distances. We detected and located 48 previously unidentified large early aftershocks triggered by earthquakes with magnitudes between ≥7 and 8 within a few fault lengths (approximately 300 kilometers), during times that high-amplitude surface waves arrive from the mainshock (less than 200 seconds). The observations indicate that near-to-intermediate-field dynamic triggering commonly exists and fundamentally promotes aftershock occurrence. The mainshocks and their nearby early aftershocks are located at major subduction zones and continental boundaries, and mainshocks with all types of faulting-mechanisms (normal, reverse, and strike-slip) can trigger early aftershocks. PMID:27609887

  14. The Current Means for Detection of Migraine Headache Trigger Sites.

    PubMed

    Guyuron, Bahman; Nahabet, Edward; Khansa, Ibrahim; Reed, Deborah; Janis, Jeffrey E

    2015-10-01

    The authors' 15-year experience with migraine surgery has led them to believe that the most common reasons for incomplete response are failure to detect all of the trigger sites or, on rare occasions, inadequate surgery on the trigger sites. Thus, accurate identification of trigger sites is essential. The purpose of this article is to share the authors' current stepwise algorithm for accurately detecting the migraine trigger sites, which has evolved through surgery on nearly 1000 patients. To begin, a thorough history is taken. Each patient's constellation of symptoms can point toward one or multiple trigger points. The patient is asked to point to the most frequent site from which migraine headaches originate with one fingertip, and then the site is explored with a Doppler. If an arterial Doppler signal is identified at the site, it is considered an active arterial trigger site. Response to a nerve block with a local anesthetic in a patient with an active migraine headache confirms the presence of a trigger site. If the patient does not have pain at the time of the office visit, an injection of botulinum toxin A at the suspected trigger site may be considered. Although positive responses to botulinum toxin A and nerve block are very helpful and reliable in confirming the trigger sites, negative responses must be interpreted with extreme caution. In patients with a migraine headache starting from the retrobulbar site, a computed tomography scan of the paranasal sinuses is obtained to look for contact points and other pathology that would confirm rhinogenic trigger sites.

  15. Operation of the Upgraded ATLAS Level-1 Central Trigger System

    NASA Astrophysics Data System (ADS)

    Glatzer, Julian

    2015-12-01

    The ATLAS Level-1 Central Trigger (L1CT) system is a central part of ATLAS data-taking and has undergone a major upgrade for Run 2 of the LHC, in order to cope with the expected increase of instantaneous luminosity of a factor of two with respect to Run 1. The upgraded hardware offers more flexibility in the trigger decisions due to the factor of two increase in the number of trigger inputs and usable trigger channels. It also provides an interface to the new topological trigger system. Operationally - particularly useful for commissioning, calibration and test runs - it allows concurrent running of up to three different subdetector combinations. An overview of the operational software framework of the L1CT system with particular emphasis on the configuration, controls and monitoring aspects is given. The software framework allows a consistent configuration with respect to the ATLAS experiment and the LHC machine, upstream and downstream trigger processors, and the data acquisition system. Trigger and dead-time rates are monitored coherently at all stages of processing and are logged by the online computing system for physics analysis, data quality assurance and operational debugging. In addition, the synchronisation of trigger inputs is watched based on bunch-by-bunch trigger information. Several software tools allow for efficient display of the relevant information in the control room in a way useful for shifters and experts. The design of the framework aims at reliability, flexibility, and robustness of the system and takes into account the operational experience gained during Run 1. The Level-1 Central Trigger was successfully operated with high efficiency during the cosmic-ray, beam-splash and first Run 2 data taking with the full ATLAS detector.

  16. Ecdysis triggering hormone signaling in arthropods.

    PubMed

    Roller, Ladislav; Zitnanová, Inka; Dai, Li; Simo, Ladislav; Park, Yoonseong; Satake, Honoo; Tanaka, Yoshiaki; Adams, Michael E; Zitnan, Dusan

    2010-03-01

    Ecdysis triggering hormones (ETHs) from endocrine Inka cells initiate the ecdysis sequence through action on central neurons expressing ETH receptors (ETHR) in model moth and dipteran species. We used various biochemical, molecular and BLAST search techniques to detect these signaling molecules in representatives of diverse arthropods. Using peptide isolation from tracheal extracts, cDNA cloning or homology searches, we identified ETHs in a variety of hemimetabolous and holometabolous insects. Most insects produce two related ETHs, but only a single active peptide was isolated from the cricket and one peptide is encoded by the eth gene of the honeybee, parasitic wasp and aphid. Immunohistochemical staining with antiserum to Manduca PETH revealed Inka cells on tracheal surface of diverse insects. In spite of conserved ETH sequences, comparison of natural and the ETH-induced ecdysis sequence in the honeybee and beetle revealed considerable species-specific differences in pre-ecdysis and ecdysis behaviors. DNA sequences coding for putative ETHR were deduced from available genomes of several hemimetabolous and holometabolous insects. In all insects examined, the ethr gene encodes two subtypes of the receptor (ETHR-A and ETHR-B). Phylogenetic analysis showed that these receptors fall into a family of closely related GPCRs. We report for the first time the presence of putative ETHs and ETHRs in genomes of other arthropods, including the tick (Arachnida) and water flea (Crustacea). The possible source of ETH in ticks was detected in paired cells located in all pedal segments. Our results provide further evidence of structural and functional conservation of ETH-ETHR signaling.

  17. A FLUX ROPE ERUPTION TRIGGERED BY JETS

    SciTech Connect

    Guo Juan; Zhang Hongqi; Deng Yuanyong; Lin Jiaben; Su Jiangtao; Liu Yu

    2010-03-10

    We present an observation of a filament eruption caused by recurrent chromospheric plasma injections (surges/jets) on 2006 July 6. The filament eruption was associated with an M2.5 two-ribbon flare and a coronal mass ejection (CME). There was a light bridge in the umbra of the main sunspot of NOAA 10898; one end of the filament was terminated at the region close to the light bridge, and recurrent surges were observed to be ejected from the light bridge. The surges occurred intermittently for about 8 hr before the filament eruption, and finally a clear jet was found at the light bridge to trigger the filament eruption. We analyzed the evolutions of the relative darkness of the filament and the loaded mass by the continuous surges quantitatively. It was found that as the occurrence of the surges, the relative darkness of the filament body continued growing for about 3-4 hr, reached its maximum, and kept stable for more than 2 hr until it erupted. If suppose 50% of the ejected mass by the surges could be trapped by the filament channel, then the total loaded mass into the filament channelwill be about 0.57x10{sup 16} g with a momentum of 0.57x10{sup 22} g cm s{sup -1} by 08:08 UT, which is a non-negligible effect on the stability of the filament. Based on the observations, we present a model showing the important role that recurrent chromospheric mass injection play in the evolution and eruption of a flux rope. Our study confirms that the surge activities can efficiently supply the necessary material for some filament formation. Furthermore, our study indicates that the continuous mass with momentum loaded by the surge activities to the filament channel could make the filament unstable and cause it to erupt.

  18. Dynamic triggering during rupture nucleation in sandstone

    NASA Astrophysics Data System (ADS)

    Schubnel, Alexandre; Chanard, Kristel; Latour, Soumaya; Petrelis, François; Hatano, Takahiro; Mair, Karen; Vinciguerra, Sergio

    2016-04-01

    Fluid induced stress perturbations in the crust at seismogenic depths can be caused by various sources, such as deglaciation unloading, magmatic intrusion or fluid injection and withdrawal. Numbers of studies have robustly shown their link to earthquake triggering. However, the role of small periodic stress variations induced by solid earth and oceanic tides or seasonal hydrology in the seismic cycle, of the order of a few kPa, remains unclear. Indeed, the existence or absence of correlation between these loading phenomena and earthquakes have been equally proposed in the literature. To investigate this question, we performed a set of triaxial deformation experiments on porous water-saturated Fontainebleau sandstones. Rock samples were loaded by the combined action of steps of constant stress (creep), intended to simulate tectonic loading and small sinusoidal pore pressure variations with a range of amplitudes, analogous to tides or seasonal loading. All tests were conducted at a regulated temperature of 35C and a constant 35 MPa confining pressure. Our experimental results show that (1) pore pressure oscillations do not seem to influence the deformation rate at which the rock fails, (2) they correlate with acoustic emissions. Even more interestingly, we observe a progressive increase of the correlation coefficient in time as the rock approaches failure. The correlation coefficient is also sensitive to the amplitude of pore pressure oscillations as larger oscillations produce higher correlation levels. Finally, we show that, in the last hours of creep before failure, acoustic emissions occur significantly more when the pore pressure is at its lowest. This suggest that the correlation of small stress perturbations and acoustic emissions depend on the state stress of a rock and the amplitude of the perturbations and that emissions occur more likely when cracks are unclamped.

  19. Dynamic triggering of Lusi, East Java Basin

    NASA Astrophysics Data System (ADS)

    Lupi, Matteo; Saenger, Erik H.; Fuchs, Florian; Miller, Steve

    2016-04-01

    On the 27th of May 2006, a M6.3 strike slip earthquake struck beneath Yogyakarta, Java. Forty-seven hours later a mixture of mud, breccia, and gas reached the surface near Sidoarjo, 250 km far from the epicenter, creating several mud vents aligned along a NW-SE direction. The mud eruption reached a peak of 180.000 km3 of erupted material per day and it is still ongoing. The major eruption crater was named Lusi and represents the surface expression of a newborn sedimentary-hosted hydrothermal system. Lusi flooded several villages causing a loss of approximately 4 billions to Indonesia. Previous geochemical and geological data suggest that the Yogyakarta earthquake may have reactivated parts of the Watukosek fault system, a strike slip structure upon which Lusi resides. The Watukosek fault systems connects the East Java basin to the volcanic arc, which may explain the presence of both biogenic and thermogenic fluids. To quantify the effects of incoming seismic energy at Lusi we conducted a seismic wave propagation study on a geological model of Lusi's structure. A key feature of our model is a low velocity shear zone in the Kalibeng formation caused by elevated pore pressures, which is often neglected in other studies. Our analysis highlights the importance of the overall geological structure that focused the seismic energy causing elevated strain rates at depth. In particular, we show that body waves generated by the Yogyakarta earthquake may have induced liquefaction of the Kalibeng formation. As consequence, the liquefied mud injected and reactivated parts of the Watukosek fault system. Our findings are in agreement with previous studies suggesting that Lusi was an unfortunate case of dynamic triggering promoted by the Yogyakarta earthquake.

  20. Study of Tectonic Tremor in Depth: Triggering Stress Observation and Model of the Triggering Mechanism

    NASA Astrophysics Data System (ADS)

    Wang, Tien-Huei

    Non-volcanic tremor (NVT) has been discovered in recent years due to advances in seismic instruments and increased density of seismic networks. The NVT is a special kind of seismic signal indicative of the physical conditions and the failure mechanism on the source on the fault where NVT occurs. The detection methods used and the sensitivity of them relies on the density, distance and instrumentation of the station network available. How accurately the tremor is identified in different regions varies greatly among different studies. Therefore, there has not been study that rigorously documents tectonic tremors in different regions under limited methods and data. Meanwhile, many incidences of NVTs are observed during or after small but significant strain change induced by teleseismic, regional or local earthquake. The understanding of the triggering mechanisms critical for tremor remains unclear. In addition, characteristics of the triggering of NVT in different regions are rarely compared because of the short time frame after the discovery of the triggered NVTs. We first explore tectonic tremor based on observations to learn about its triggering, frequency of occurrence, location and spectral characteristics. Then, we numerically model the triggering of instability on the estimated tremor-source, under assumptions fine-tuned according to previous studies (Thomas et al., 2009; Miyazawa et al., 2005; Hill, 2008; Ito, 2009; Rubinstein et al., 2007; Peng and Chao, 2008). The onset of the slip reveals that how and when the external loading triggers tremor. It also holds the information to the background stress conditions under which tremor source starts with. We observe and detect tremor in two regions: Anza and Cholame, along San Jacinto Fault (SJF) and San Andreas Fault (SAF) respectively. These two sections of the faults, relative to general fault zone on which general earthquakes occur, are considered transition zones where slip of slow rates occurs. Slip events

  1. Switch performance in peripherally and centrally triggered saccades.

    PubMed

    Vermeiren, Astrid; Liefooghe, Baptist; Vandierendonck, André

    2010-10-01

    A common hypothesis is that the switch cost measured when switching between prosaccades and antisaccades mainly reflects the inhibition of the saccadic system after the execution of an antisaccade, which requires the inhibition of a gaze response. The present study further tested this hypothesis by comparing switch performance between peripherally triggered saccades and centrally triggered saccades with the latter type of saccades not requiring inhibition of a gaze response. For peripherally triggered saccades, a switch cost was present for prosaccades but not for antisaccades. For centrally triggered saccades, a switch cost was present both for prosaccades and for antisaccades. The difference between both saccade tasks further supports the hypothesis that the switch performance observed for peripherally triggered saccades is related to the inhibition of a gaze response that is required when executing a peripherally triggered antisaccade and the persisting inhibition in the saccadic system this entails. Furthermore, the switch costs observed for centrally triggered saccades indicate that more general processes besides the persisting inhibition in the saccadic system, such as reconfiguration and interference control, also contribute to the switch performance in saccades.

  2. Preliminary on-orbit results of trigger system for DAMPE

    NASA Astrophysics Data System (ADS)

    Zhang, Yongqiang; Chang, Jin; Guo, Jian hua; Dong, TieKuang; Liu, Yang

    2016-07-01

    The Dark Matter Particle Explorer (DAMPE), Chinese first high energy cosmic ray explorer in space, has been successfully launched at Jiuquan Satellite Launch Center, with the mission of searching dark matter particle. Large energy range for electron/gamma, good energy resolution, and excellent PID ability, make DAMPE to be the most promising detector so far to find the signal of dark matter. DAMPE consists of four sub-detectors: Plastic Scintillation detector, Silicon-Tungsten tracker, BGO calorimeter and Neutron detector. The hit signals generated by the BGO calorimeter and the trigger board (in DAQ) constitute the trigger system of DAMPE, which will generate trigger signals for the four sub-detectors to start data acquisition. The trigger system reduces the trigger rates on orbit from about 1kHz to 70~100Hz, that releases the stress of DAQ transmitting data to ground. In this paper, we will introduce the trigger system of DAMPE, and present some preliminary on-orbit results e.g. trigger efficiency, together with the beam test results at CERN and the simulation results as comparison.

  3. Mirror-image trigger thumb in dichorionic identical twins.

    PubMed

    Wang, Eric D; Xu, Xiaoti; Dagum, Alexander B

    2012-06-01

    The congenital vs acquired etiology of pediatric trigger thumb is the subject of considerable debate. Existing case reports of bilateral presentation in identical twins and first-degree familial association support the congenital hypothesis. However, prospective studies have yet to report a neonate presenting with this anomaly at birth. This article describes the first known set of dichorionic, monozygotic identical twins with unilateral trigger thumbs, affecting contralateral (mirror-image) hands and with asynchronous age at presentation (11 months and 18 months, respectively).Pediatric trigger thumb is caused by a mismatch between the flexor pollicis longus tendon and its A1 synovial pulley. Four sets of twins have been previously reported in the literature with trigger thumb. Of these, 3 sets were monozygotic twins who had bilaterally affected thumbs. Together with the absence of trauma, a congenital etiology was suggested. The fact that pediatric trigger thumb is generally seen several months after birth was felt to be due to infants holding their thumbs clutched in their palms until 6 months. However, no confirmed cases of trigger thumb have been diagnosed at birth in several large prospective studies of newborns.In the current case, the asynchronous presentation of unilateral trigger thumbs in identical twins does not support a solely congenital cause. Furthermore, the mirror-image presentation contradicts current embryological understanding of the temporal course of twinning and the determination of laterality. Thus, a multifactorial etiology is supported with both a genetic and acquired component affecting the development of this condition. PMID:22691680

  4. Electrophysiological characteristics according to activity level of myofascial trigger points.

    PubMed

    Yu, Seong Hun; Kim, Hyun Jin

    2015-09-01

    [Purpose] This study compared the differences in electrophysiological characteristics of normal muscles versus muscles with latent or active myofascial trigger points, and identified the neuromuscular physiological characteristics of muscles with active myofascial trigger points, thereby providing a quantitative evaluation of myofascial pain syndrome and clinical foundational data for its diagnosis. [Subjects] Ninety adults in their 20s participated in this study. Subjects were equally divided into three groups: the active myofascial trigger point group, the latent myofascial trigger point group, and the control group. [Methods] Maximum voluntary isometric contraction (MVIC), endurance, median frequency (MDF), and muscle fatigue index were measured in all subjects. [Results] No significant differences in MVIC or endurance were revealed among the three groups. However, the active trigger point group had significantly different MDF and muscle fatigue index compared with the control group. [Conclusion] Given that muscles with active myofascial trigger points had an increased MDF and suffered muscle fatigue more easily, increased recruitment of motor unit action potential of type II fibers was evident. Therefore, electrophysiological analysis of these myofascial trigger points can be applied to evaluate the effect of physical therapy and provide a quantitative diagnosis of myofascial pain syndrome.

  5. Performance evaluation of trigger algorithm for the MACE telescope

    NASA Astrophysics Data System (ADS)

    Yadav, Kuldeep; Yadav, K. K.; Bhatt, N.; Chouhan, N.; Sikder, S. S.; Behere, A.; Pithawa, C. K.; Tickoo, A. K.; Rannot, R. C.; Bhattacharyya, S.; Mitra, A. K.; Koul, R.

    The MACE (Major Atmospheric Cherenkov Experiment) telescope with a light collector diameter of 21 m, is being set up at Hanle (32.80 N, 78.90 E, 4200m asl) India, to explore the gamma-ray sky in the tens of GeV energy range. The imaging camera of the telescope comprises 1088 pixels covering a total field-of-view of 4.30 × 4.00 with trigger field-of-view of 2.60 × 3.00 and an uniform pixel resolution of 0.120. In order to achieve low energy trigger threshold of less than 30 GeV, a two level trigger scheme is being designed for the telescope. The first level trigger is generated within 16 pixels of the Camera Integrated Module (CIM) based on 4 nearest neighbour (4NN) close cluster configuration within a coincidence gate window of 5 ns while the second level trigger is generated by combining the first level triggers from neighbouring CIMs. Each pixel of the telescope is expected to operate at a single pixel threshold between 8-10 photo-electrons where the single channel rate dominated by the after- pulsing is expected to be ˜500 kHz. The hardware implementation of the trigger logic is based on complex programmable logic devices (CPLD). The basic design concept, hardware implementation and performance evaluation of the trigger system in terms of threshold energy and trigger rate estimates based on Monte Carlo data for the MACE telescope will be presented in this meeting.

  6. Dynamic stresses, coulomb failure, and remote triggering: corrected

    USGS Publications Warehouse

    Hill, David P.

    2012-01-01

    Dynamic stresses associated with crustal surface waves with 15–30 s periods and peak amplitudes <1  MPa are capable of triggering seismicity at sites remote from the generating mainshock under appropriate conditions. Coulomb failure models based on a frictional strength threshold offer one explanation for instances of rapid‐onset triggered seismicity that develop during the surface‐wave peak dynamic stressing. Evaluation of the triggering potential of surface‐wave dynamic stresses acting on critically stressed faults using a Mohr’s circle representation together with the Coulomb failure criteria indicates that Love waves should have a higher triggering potential than Rayleigh waves for most fault orientations and wave incidence angles. That (1) the onset of triggered seismicity often appears to begin during the Rayleigh wave rather than the earlier arriving Love wave, and (2) Love‐wave amplitudes typically exceed those for Rayleigh waves suggests that the explanation for rapid‐onset dynamic triggering may not reside solely with a simple static‐threshold friction mode. The results also indicate that normal faults should be more susceptible to dynamic triggering by 20‐s Rayleigh‐wave stresses than thrust faults in the shallow seismogenic crust (<10  km) while the advantage tips in favor of reverse faults greater depths. This transition depth scales with wavelength and coincides roughly with the transition from retrograde‐to‐prograde particle motion. Locally elevated pore pressures may have a role in the observed prevalence of dynamic triggering in extensional regimes and geothermal/volcanic systems. The result is consistent with the apparent elevated susceptibility of extensional or transtensional tectonic regimes to remote triggering by Rayleigh‐wave dynamic stresses than compressional or transpressional regimes.

  7. Low-power triggered data acquisition system and method

    NASA Technical Reports Server (NTRS)

    Champaigne, Kevin (Inventor); Sumners, Jonathan (Inventor)

    2012-01-01

    A low-power triggered data acquisition system and method utilizes low-powered circuitry, comparators, and digital logic incorporated into a miniaturized device interfaced with self-generating transducer sensor inputs to detect, identify and assess impact and damage to surfaces and structures wherein, upon the occurrence of a triggering event that produces a signal greater than a set threshold changes the comparator output and causes the system to acquire and store digital data representative of the incoming waveform on at least one triggered channel. The sensors may be disposed in an array to provide triangulation and location of the impact.

  8. Development of a Low-energy Trigger for VERITAS

    SciTech Connect

    Kildea, J.

    2008-12-24

    During the 2007/2008 observing season a low-energy trigger configuration was developed and tested for VERITAS. The configuration makes uses of the small ({approx}35 m) baseline between two of the VERITAS telescopes and employs a much lower discriminator threshold and tighter coincidence window compared to the standard VERITAS trigger. Five hours of Crab Nebula ON/OFF observations were obtained in low-energy mode and were used to test new low-energy analysis algorithms. We present some details of the VERITAS low-energy trigger and the associated data analysis.

  9. On the proposed triggering of Jovian radio emissions

    NASA Technical Reports Server (NTRS)

    Desch, M. D.; Kaiser, M. L.

    1985-01-01

    Calvert (1985) has proposed that a solar type III radio bursts can trigger the onset of certain Jovian hectometer wavelength emissions. It is shown, using the data obtained by the Voyager Planetary Radio Astronomy experiment, that this triggering hypothesis is not supported statistically. Furthermore, the causality of this proposed triggering is questioned because much of the Jovian hectometer emission is due to a quasi-continuous radio source rotating, in lighthouse fashion, with Jupiter. Thus, an observed 'onset' of emission is simply a function of the observer's position in local time around Jupiter.

  10. CO2-Triggered Switchable Solvents, Surfactants, and Other Materials

    SciTech Connect

    Jessop, Philip G.; Mercer, Sean; Heldebrant, David J.

    2012-06-14

    Waste CO2 at atmospheric pressure can be used to trigger dramatic changes in the properties of certain switchable materials. Compared to other triggers such as light, acids, oxidants, CO2 has the advantages that it is inexpensive, nonhazardous, non-accumulating in the system, easily removed, and it does not require the material to be transparent. Known CO2-triggered switchable materials 10 now include solvents, surfactants, solutes, catalysts, particles, polymers, and gels. The added flexibility of switchable materials represents a new strategy for minimizing energy and material consumption in process and product design.

  11. Method and apparatus to trigger superconductors in current limiting devices

    DOEpatents

    Yuan, Xing; Hazelton, Drew Willard; Walker, Michael Stephen

    2004-10-26

    A method and apparatus for magnetically triggering a superconductor in a superconducting fault current limiter to transition from a superconducting state to a resistive state. The triggering is achieved by employing current-carrying trigger coil or foil on either or both the inner diameter and outer diameter of a superconductor. The current-carrying coil or foil generates a magnetic field with sufficient strength and the superconductor is disposed within essentially uniform magnetic field region. For superconductor in a tubular-configured form, an additional magnetic field can be generated by placing current-carrying wire or foil inside the tube and along the center axial line.

  12. Advanced integrated safeguards using front-end-triggering devices

    SciTech Connect

    Howell, J.A.; Whitty, W.J.

    1995-12-01

    This report addresses potential uses of front-end-triggering devices for enhanced safeguards. Such systems incorporate video surveillance as well as radiation and other sensors. Also covered in the report are integration issues and analysis techniques.

  13. Can Trauma Trigger Violent Crime in Mentally Ill?

    MedlinePlus

    ... gov/news/fullstory_159859.html Can Trauma Trigger Violent Crime in Mentally Ill? Short-term risk was ... events are more likely to engage in a violent crime in the week following the trauma, a ...

  14. Resident-to-resident violence triggers in nursing homes.

    PubMed

    Snellgrove, Susan; Beck, Cornelia; Green, Angela; McSweeney, Jean C

    2013-11-01

    Certified nurses' assistants (CNAs) employed by a rural nursing home in Northeast Arkansas described their perceptions of resident-to-resident violence in order to provide insight on factors, including unmet needs, that may trigger the phenomenon. Semistructured interviews were conducted with 11 CNAs. Data were analyzed using content analysis and constant comparison. Two categories of triggers emerged from the data-active and passive. Active triggers involved the actions of other residents that were intrusive in nature, such as wandering into a residents' personal space, taking a resident's belongings, and so forth. Passive triggers did not involve the actions of residents but related to the internal and external environment of the residents. Examples were factors such as boredom, competition for attention and communication difficulties. Results indicate that there are factors, including unmet needs within the nursing home environment that may be identified and altered to prevent violence between residents.

  15. The CMS Level-1 Trigger Barrel Track Finder

    NASA Astrophysics Data System (ADS)

    Ero, J.; Evangelou, I.; Flouris, G.; Foudas, C.; Guiducci, L.; Loukas, N.; Manthos, N.; Papadopoulos, I.; Paradas, E.; Sotiropoulos, S.; Sphicas, P.; Triossi, A.; Wulz, C.

    2016-03-01

    The design and performance of the upgraded CMS Level-1 Trigger Barrel Muon Track Finder (BMTF) is presented. Monte Carlo simulation data as well as cosmic ray data from a CMS muon detector slice test have been used to study in detail the performance of the new track finder. The design architecture is based on twelve MP7 cards each of which uses a Xilinx Virtex-7 FPGA and can receive and transmit data at 10 Gbps from 72 input and 72 output fibers. According to the CMS Trigger Upgrade TDR the BMTF receives trigger primitive data which are computed using both RPC and DT data and transmits data from a number of muon candidates to the upgraded Global Muon Trigger. Results from detailed studies of comparisons between the BMTF algorithm results and the results of a C++ emulator are also presented. The new BMTF will be commissioned for data taking in 2016.

  16. LIF bio-aerosol threat triggers: then and now

    NASA Astrophysics Data System (ADS)

    DeFreez, Richard

    2009-09-01

    Bio-aerosol terrorist attacks have been carried out against civilians in the United States and elsewhere. Unfortunately, recurrence appears inevitable. A fast, reliable, and inexpensive bioaerosol threat detection trigger can be an important tool for detect-to-protect and detect-to-treat countermeasure scenarios. Bio-aerosol threat detection triggers employing light, historically laser light but recently LED light, for induced native- or auto-fluorescence (LIF) have been developed for well over a decade without a generally accepted solution being found. This paper presents a brief history of LIF triggers and reviews many vendor efforts, past and current. Various technical approaches and design considerations are discussed. Triggers from ICx technology, currently available or in development, are also discussed.

  17. Resident-to-Resident Violence Triggers in Nursing Homes

    PubMed Central

    Snellgrove, Susan; Beck, Cornelia; Green, Angela; McSweeney, Jean C.

    2014-01-01

    Certified nurses’ assistants (CNAs) employed by a rural nursing home in Northeast Arkansas described their perceptions of resident-to-resident violence in order to provide insight on factors, including unmet needs, that may trigger the phenomenon. Semistructured interviews were conducted with 11 CNAs. Data were analyzed using content analysis and constant comparison. Two categories of triggers emerged from the data—active and passive. Active triggers involved the actions of other residents that were intrusive in nature, such as wandering into a residents’ personal space, taking a resident’s belongings, and so forth. Passive triggers did not involve the actions of residents but related to the internal and external environment of the residents. Examples were factors such as boredom, competition for attention and communication difficulties. Results indicate that there are factors, including unmet needs within the nursing home environment that may be identified and altered to prevent violence between residents. PMID:23447361

  18. L0 trigger unit prototype for BM@N setup

    NASA Astrophysics Data System (ADS)

    Batenkov, O. I.; Bogoslovski, D. N.; Rogov, V. Y.; Sergeev, S. V.; Yurevich, V. I.

    2016-09-01

    The BM@N facility is a fixed target experiment based on heavy ion beams of the Nuclotron-M accelerator. The aim of the BM@N is to study nucleus - nucleus collisions at energies up to 4.5 GeV per nucleon. A level 0 trigger processor unit (Trigger L0 unit, T0U) for the BM@N deuterons and carbon ions at Run'2015 has been developed. The T0U is used to generate a BM@N zero level trigger and a TOF detector precise start.T0U generates trigger signal based on beam line and target area detector signals. This module also provides both control and monitoring of the detector front-end electronics power supplies. This article presents a concept, characteristics and test results of the T0U module during the Run 2015.

  19. Engineered biological nanofactories trigger quorum sensing response in targeted bacteria

    NASA Astrophysics Data System (ADS)

    Fernandes, Rohan; Roy, Varnika; Wu, Hsuan-Chen; Bentley, William E.

    2010-03-01

    Biological nanofactories, which are engineered to contain modules that can target, sense and synthesize molecules, can trigger communication between different bacterial populations. These communications influence biofilm formation, virulence, bioluminescence and many other bacterial functions in a process called quorum sensing. Here, we show the assembly of a nanofactory that can trigger a bacterial quorum sensing response in the absence of native quorum molecules. The nanofactory comprises an antibody (for targeting) and a fusion protein that produces quorum molecules when bound to the targeted bacterium. Our nanofactory selectively targets the appropriate bacteria and triggers a quorum sensing response when added to two populations of bacteria. The nanofactories also trigger communication between two bacterial populations that are otherwise non-communicating. We envision the use of these nanofactories in generating new antimicrobial treatments that target the communication networks of bacteria rather than their viability.

  20. Spatial Distributions of Foreshocks and Aftershocks: Static or Dynamic Triggering

    NASA Astrophysics Data System (ADS)

    Werner, M. J.; Rubin, A. M.

    2012-04-01

    In recent years, the spatial distributions of foreshocks and aftershocks have been scrutinized for evidence supporting either triggering by static stress changes induced by the permanent deformation from prior earthquakes or triggering by the dynamic stresses from seismic waves. Felzer & Brodsky (2006) identified small (m<4) mainshocks and triggered aftershocks, stacked the distances between these pairs and observed a single power-law decay with distance that extends beyond the zone traditionally thought to be affected by static stress changes. On this basis, they argued that dynamic stresses are responsible for triggering earthquakes. Richards-Dinger et al. (2010) and other studies, however, have presented several lines of evidence that suggest otherwise. One crucial question is whether the stacked distances of pairs of earthquakes, representing either mainshock-aftershock or foreshock-mainshock pairs, are in fact correctly identified and not misattributed, unrelated earthquakes. This question is especially important in the critical distance range of several to tens of earthquake radii, over which static stresses are thought to be too small to affect seismicity. If earthquake pairs in this range are not causally related, then the histogram of foreshock-mainshock and mainshock-aftershock pairs should be identical, and the difference between the two histograms can be used to identify remote triggering. Results based on southern Californian seismicity suggest that (1) the existence of a single power-law with a particular exponent may not be a robust observation, (2) geothermal regions seem to play an important role over the relevant distances, (3) remote triggering seems to exist beyond the classical static stress influence zone (perhaps out to 15 km after mainshocks with magnitudes between 3 and 4), (4) simple ETAS model simulations cannot reproduce all observations, and (5) at most one-third of the remote aftershocks had received significant static Coulomb stress

  1. Skier triggering of backcountry avalanches with skilled route selection

    NASA Astrophysics Data System (ADS)

    Sinickas, Alexandra; Haegeli, Pascal; Jamieson, Bruce

    2015-04-01

    Jamieson (2009) provided numerical estimates for the baseline probabilities of triggering an avalanche by a backcountry skier making fresh tracks without skilled route selection as a function of the North American avalanche danger scale (i.e., hazard levels Low, Moderate, Considerable, High and Extreme). Using the results of an expert survey, he showed that triggering probabilities while skiing directly up, down or across a trigger zone without skilled route selection increase roughly by a factor of 10 with each step of the North American avalanche danger scale (i.e. hazard level). The objective of the present study is to examine the effect of skilled route selection on the relationship between triggering probability and hazard level. To assess the effect of skilled route selection on triggering probability by hazard level, we analysed avalanche hazard assessments as well as reports of skiing activity and triggering of avalanches from 11 Canadian helicopter and snowcat operations during two winters (2012-13 and 2013-14). These reports were submitted to the daily information exchange among Canadian avalanche safety operations, and reflect professional decision-making and route selection practices of guides leading groups of skiers. We selected all skier-controlled or accidentally triggered avalanches with a destructive size greater than size 1 according to the Canadian avalanche size classification, triggered by any member of a guided group (guide or guest). These operations forecast the avalanche hazard daily for each of three elevation bands: alpine, treeline and below treeline. In contrast to the 2009 study, an exposure was defined as a group skiing within any one of the three elevation bands, and consequently within a hazard rating, for the day (~4,300 ratings over two winters). For example, a group that skied below treeline (rated Moderate) and treeline (rated Considerable) in one day, would receive one count for exposure to Moderate hazard, and one count for

  2. Human-Gyrovirus-Apoptin Triggers Mitochondrial Death Pathway—Nur77 is Required for Apoptosis Triggering

    PubMed Central

    Chaabane, Wiem; Cieślar-Pobuda, Artur; El-Gazzah, Mohamed; Jain, Mayur V.; Rzeszowska-Wolny, Joanna; Rafat, Mehrdad; Stetefeld, Joerg; Ghavami, Saeid; Łos, Marek J.

    2014-01-01

    The human gyrovirus derived protein Apoptin (HGV-Apoptin) a homologue of the chicken anemia virus Apoptin (CAV-Apoptin), a protein with high cancer cells selective toxicity, triggers apoptosis selectively in cancer cells. In this paper, we show that HGV-Apoptin acts independently from the death receptor pathway as it induces apoptosis in similar rates in Jurkat cells deficient in either FADD (fas-associated death domain) function or caspase-8 (key players of the extrinsic pathway) and their parental clones. HGV-Apoptin induces apoptosis via the activation of the mitochondrial intrinsic pathway. It induces both mitochondrial inner and outer membrane permebilization, characterized by the loss of the mitochondrial potential and the release into cytoplasm of the pro-apoptotic molecules including apoptosis inducing factor and cytochrome c. HGV-Apoptin acts via the apoptosome, as lack of expression of apoptotic protease-activating factor 1 in murine embryonic fibroblast strongly protected the cells from HGV-Apoptin–induced apoptosis. Moreover, QVD-oph a broad-spectrum caspase inhibitor delayed HGV-Apoptin–induced death. On the other hand, overexpression of the anti-apoptotic BCL-XL confers resistance to HGV-Apoptin–induced cell death. In contrast, cells that lack the expression of the pro-apoptotic BAX and BAK are protected from HGV-Apoptin induced apoptosis. Furthermore, HGV-Apoptin acts independently from p53 signal but triggers the cytoplasmic translocation of Nur77. Taking together these data indicate that HGV-Apoptin acts through the mitochondrial pathway, in a caspase-dependent manner but independently from the death receptor pathway. PMID:25246270

  3. Triggered Swarms and Induced Aftershock Sequences in Geothermal Systems

    NASA Astrophysics Data System (ADS)

    Shcherbakov, R.; Turcotte, D. L.; Yikilmaz, M. B.; Kellogg, L. H.; Rundle, J. B.

    2015-12-01

    Natural geothermal systems, which are used for energy generation, are usually associated with high seismic activity. This can be related to the large-scale injection and extraction of fluids to enhance geothermal recovery. This results in the changes of the pore pressure and pore-elastic stress field and can stimulate the occurrence of earthquakes. These systems are also prone to triggering of seismicity by the passage of seismic waves generated by large distant main shocks. In this study, we analyze clustering and triggering of seismicity at several geothermal fields in California. Particularly, we consider the seismicity at the Geysers, Coso, and Salton Sea geothermal fields. We analyze aftershock sequences generated by local large events with magnitudes greater than 4.0 and earthquake swarms generated by several significant long distant main shocks. We show that the rate of the aftershock sequences generated by the local large events in the two days before and two days after the reference event can be modelled reasonably well by the time dependent Epidemic Type Aftershock Sequence (ETAS) model. On the other hand, the swarms of activity triggered by large distant earthquakes cannot be described by the ETAS model. To model the increase in the rate of seismicity associated with triggering by large distant main shocks we introduce an additional time-dependent triggering mechanism into the ETAS model. In almost all cases the frequency-magnitude statistics of triggered sequences follow Gutenberg-Richter scaling to a good approximation. The analysis indicates that the seismicity triggered by relatively large local events can initiate sequences similar to regular aftershock sequences. In contrast, the distant main shocks trigger swarm like activity with faster decaying rates.

  4. Effect of Trigger Point Injection on Lumbosacral Radiculopathy Source

    PubMed Central

    Saeidian, Seyed Reza; Pipelzadeh, Mohammad Reza; Rasras, Saleh; Zeinali, Masud

    2014-01-01

    Background: Active muscular trigger points (aMTPs) presenting with radiating pain can interfere in diagnosis and treatment of patients suffering from lumbosacral radiculopathy. Objectives: We aimed to diagnose and evaluate the trigger point therapy on the outcome of pain in patients with lumbosacral radiculopathy. Materials and Methods: A total of 98 patients were enrolled suffered with chronic pain andlumbosacral radiculopathy at L4-L5 and L5-S1 who were candidates of non-surgical management. All patients received conservative modalities, including bed rest, non-steroidal anti-inflammatory agents (NSAID), and physiotherapy. These treatments continued for a week. Patients were examined for the presence of trigger points in their lower extremities. Those who had trigger points were divided into 2 groups (TP and N). Patients in TP group underwent trigger point injection therapy. No further therapy was done for the N group. Pain scores and straight leg raise (SLR) test in both groups were collected and analyzed on the seventh and 10th days of the therapy. Results were analyzed by paired t test and chi-square test. Results: Out of 98 patients, 64 had trigger points. Thirty-two patients were assigned to each group. Pain scores (Mean ± SD) in TP group was 7.12 ± 1.13 and in N group was 6.7 ± 1.16, P = 0.196. Following the treatment, pain scores were 2.4 ± 1.5 in TP group and 4.06 ± 1.76 in N group P = 0.008. SLR test became negative in all patients in TP group but only in 6 (19%) patients in N group, P = 0.001. Conclusions: Results show that trigger point injection therapy in patients suffering from chronic lumbosacral radiculopathy with trigger points can significantly improve their recovery, and conservative therapy may not be adequate. PMID:25337469

  5. Intrasynovial lipoma causing trigger wrist and carpal tunnel syndrome.

    PubMed

    Imai, Shinji; Kodama, Narihito; Matsusue, Yoshitaka

    2008-01-01

    Triggering of the flexor tendon at the wrist is rare. We report a case of intrasynovial lipoma that caused a trigger wrist. As far as we know it is unique in that the intrasynovial lipoma simultaneously caused carpal tunnel syndrome. The massive tenosynovitis and adhesion of flexors tendons after the locking of the intrasynovial lipoma may have resulted from inflammation caused by attrition within the carpal tunnel.

  6. A neural network z-vertex trigger for Belle II

    NASA Astrophysics Data System (ADS)

    Neuhaus, S.; Skambraks, S.; Abudinen, F.; Chen, Y.; Feindt, M.; Frühwirth, R.; Heck, M.; Kiesling, C.; Knoll, A.; Paul, S.; Schieck, J.

    2015-05-01

    We present the concept of a track trigger for the Belle II experiment, based on a neural network approach, that is able to reconstruct the z (longitudinal) position of the event vertex within the latency of the first level trigger. The trigger will thus be able to suppress a large fraction of the dominating background from events outside of the interaction region. The trigger uses the drift time information of the hits from the Central Drift Chamber (CDC) of Belle II within narrow cones in polar and azimuthal angle as well as in transverse momentum (sectors), and estimates the z-vertex without explicit track reconstruction. The preprocessing for the track trigger is based on the track information provided by the standard CDC trigger. It takes input from the 2D (r — φ) track finder, adds information from the stereo wires of the CDC, and finds the appropriate sectors in the CDC for each track in a given event. Within each sector, the z-vertex of the associated track is estimated by a specialized neural network, with a continuous output corresponding to the scaled z-vertex. The input values for the neural network are calculated from the wire hits of the CDC.

  7. Influence of supraliminal reward information on unconsciously triggered response inhibition.

    PubMed

    Diao, Liuting; Ding, Cody; Qi, Senqing; Zeng, Qinghong; Huang, Bo; Xu, Mengsi; Fan, Lingxia; Yang, Dong

    2014-01-01

    Although executive functions (e.g., response inhibition) are often thought to interact consciously with reward, recent studies have demonstrated that they can also be triggered by unconscious stimuli. Further research has suggested a close relationship between consciously and unconsciously triggered response inhibition. To date, however, the effect of reward on unconsciously triggered response inhibition has not been explored. To address this issue, participants in this study performed runs of a modified Go/No-Go task during which they were exposed to both high and low value monetary rewards presented both supraliminally and subliminally. Participants were informed that they would earn the reward displayed if they responded correctly to each trial of the run. According to the results, when rewards were presented supraliminally, a greater unconsciously triggered response inhibition was observed for high-value rewards than for low-value rewards. In contrast, when rewards were presented subliminally, no enhanced unconsciously triggered response inhibition was observed. Results revealed that supraliminal and subliminal rewards have distinct effects on unconsciously triggered response inhibition. These findings have important implications for extending our understanding of the relationship between reward and response inhibition. PMID:25268227

  8. L1 track finding for a time multiplexed trigger

    NASA Astrophysics Data System (ADS)

    Cieri, D.; Brooke, J.; Grimes, M.; Newbold, D.; Harder, K.; Shepherd-Themistocleous, C.; Tomalin, I.; Vichoudis, P.; Reid, I.; Iles, G.; Hall, G.; James, T.; Pesaresi, M.; Rose, A.; Tapper, A.; Uchida, K.

    2016-07-01

    At the HL-LHC, proton bunches will cross each other every 25 ns, producing an average of 140 pp-collisions per bunch crossing. To operate in such an environment, the CMS experiment will need a L1 hardware trigger able to identify interesting events within a latency of 12.5 μs. The future L1 trigger will make use also of data coming from the silicon tracker to control the trigger rate. The architecture that will be used in future to process tracker data is still under discussion. One interesting proposal makes use of the Time Multiplexed Trigger concept, already implemented in the CMS calorimeter trigger for the Phase I trigger upgrade. The proposed track finding algorithm is based on the Hough Transform method. The algorithm has been tested using simulated pp-collision data. Results show a very good tracking efficiency. The algorithm will be demonstrated in hardware in the coming months using the MP7, which is a μTCA board with a powerful FPGA capable of handling data rates approaching 1 Tb/s.

  9. Review of trigger and on-line processors at SLAC

    SciTech Connect

    Lankford, A.J.

    1984-07-01

    The role of trigger and on-line processors in reducing data rates to manageable proportions in e/sup +/e/sup -/ physics experiments is defined not by high physics or background rates, but by the large event sizes of the general-purpose detectors employed. The rate of e/sup +/e/sup -/ annihilation is low, and backgrounds are not high; yet the number of physics processes which can be studied is vast and varied. This paper begins by briefly describing the role of trigger processors in the e/sup +/e/sup -/ context. The usual flow of the trigger decision process is illustrated with selected examples of SLAC trigger processing. The features are mentioned of triggering at the SLC and the trigger processing plans of the two SLC detectors: The Mark II and the SLD. The most common on-line processors at SLAC, the BADC, the SLAC Scanner Processor, the SLAC FASTBUS Controller, and the VAX CAMAC Channel, are discussed. Uses of the 168/E, 3081/E, and FASTBUS VAX processors are mentioned. The manner in which these processors are interfaced and the function they serve on line is described. Finally, the accelerator control system for the SLC is outlined. This paper is a survey in nature, and hence, relies heavily upon references to previous publications for detailed description of work mentioned here. 27 references, 9 figures, 1 table.

  10. Influence of Supraliminal Reward Information on Unconsciously Triggered Response Inhibition

    PubMed Central

    Diao, Liuting; Ding, Cody; Qi, Senqing; Zeng, Qinghong; Huang, Bo; Xu, Mengsi; Fan, Lingxia; Yang, Dong

    2014-01-01

    Although executive functions (e.g., response inhibition) are often thought to interact consciously with reward, recent studies have demonstrated that they can also be triggered by unconscious stimuli. Further research has suggested a close relationship between consciously and unconsciously triggered response inhibition. To date, however, the effect of reward on unconsciously triggered response inhibition has not been explored. To address this issue, participants in this study performed runs of a modified Go/No-Go task during which they were exposed to both high and low value monetary rewards presented both supraliminally and subliminally. Participants were informed that they would earn the reward displayed if they responded correctly to each trial of the run. According to the results, when rewards were presented supraliminally, a greater unconsciously triggered response inhibition was observed for high-value rewards than for low-value rewards. In contrast, when rewards were presented subliminally, no enhanced unconsciously triggered response inhibition was observed. Results revealed that supraliminal and subliminal rewards have distinct effects on unconsciously triggered response inhibition. These findings have important implications for extending our understanding of the relationship between reward and response inhibition. PMID:25268227

  11. Darwin's triggering mechanism of volcano eruptions

    NASA Astrophysics Data System (ADS)

    Galiev, Shamil

    2010-05-01

    Charles Darwin wrote that ‘… the elevation of many hundred square miles of territory near Concepcion is part of the same phenomenon, with that splashing up, if I may so call it, of volcanic matter through the orifices in the Cordillera at the moment of the shock;…' and ‘…a power, I may remark, which acts in paroxysmal upheavals like that of Concepcion, and in great volcanic eruptions,…'. Darwin reports that ‘…several of the great chimneys in the Cordillera of central Chile commenced a fresh period of activity ….' In particular, Darwin reported on four-simultaneous large eruptions from the following volcanoes: Robinson Crusoe, Minchinmavida, Cerro Yanteles and Peteroa (we cite the Darwin's sentences following his The Voyage of the Beagle and researchspace. auckland. ac. nz/handle/2292/4474). Let us consider these eruptions taking into account the volcano shape and the conduit. Three of the volcanoes (Minchinmavida (2404 m), Cerro Yanteles (2050 m), and Peteroa (3603 m)) are stratovolcanos and are formed of symmetrical cones with steep sides. Robinson Crusoe (922 m) is a shield volcano and is formed of a cone with gently sloping sides. They are not very active. We may surmise, that their vents had a sealing plug (vent fill) in 1835. All these volcanoes are conical. These common features are important for Darwin's triggering model, which is discussed below. The vent fill material, usually, has high level of porosity and a very low tensile strength and can easily be fragmented by tension waves. The action of a severe earthquake on the volcano base may be compared with a nuclear blast explosion of the base. It is known, that after a underground nuclear explosion the vertical motion and the surface fractures in a tope of mountains were observed. The same is related to the propagation of waves in conical elements. After the explosive load of the base. the tip may break and fly off at high velocity. Analogous phenomenon may be generated as a result of a

  12. Darwin's triggering mechanism of volcano eruptions

    NASA Astrophysics Data System (ADS)

    Galiev, Shamil

    2010-05-01

    Charles Darwin wrote that ‘… the elevation of many hundred square miles of territory near Concepcion is part of the same phenomenon, with that splashing up, if I may so call it, of volcanic matter through the orifices in the Cordillera at the moment of the shock;…' and ‘…a power, I may remark, which acts in paroxysmal upheavals like that of Concepcion, and in great volcanic eruptions,…'. Darwin reports that ‘…several of the great chimneys in the Cordillera of central Chile commenced a fresh period of activity ….' In particular, Darwin reported on four-simultaneous large eruptions from the following volcanoes: Robinson Crusoe, Minchinmavida, Cerro Yanteles and Peteroa (we cite the Darwin's sentences following his The Voyage of the Beagle and researchspace. auckland. ac. nz/handle/2292/4474). Let us consider these eruptions taking into account the volcano shape and the conduit. Three of the volcanoes (Minchinmavida (2404 m), Cerro Yanteles (2050 m), and Peteroa (3603 m)) are stratovolcanos and are formed of symmetrical cones with steep sides. Robinson Crusoe (922 m) is a shield volcano and is formed of a cone with gently sloping sides. They are not very active. We may surmise, that their vents had a sealing plug (vent fill) in 1835. All these volcanoes are conical. These common features are important for Darwin's triggering model, which is discussed below. The vent fill material, usually, has high level of porosity and a very low tensile strength and can easily be fragmented by tension waves. The action of a severe earthquake on the volcano base may be compared with a nuclear blast explosion of the base. It is known, that after a underground nuclear explosion the vertical motion and the surface fractures in a tope of mountains were observed. The same is related to the propagation of waves in conical elements. After the explosive load of the base. the tip may break and fly off at high velocity. Analogous phenomenon may be generated as a result of a

  13. Mafic intrusions triggering eruptions in Iceland

    NASA Astrophysics Data System (ADS)

    Sigmarsson, O.

    2012-04-01

    . Earlier gabbroic fractionation of plagioclase, clinopyroxene and rare olivine crystals led to more evolved compositions and saturation of iron-titanium oxides. Significant variations in glass compositions indicate several liquid-lines-of-descent, possibly at somewhat different pressure, with MgO and K2O concentrations ranging from 4.6-5.7% and 0.46 to 0.60%, respectively. These variable magma differentiation trends and the abundant microlites suggest degassing over a considerable depth range and remobilizing of magma pockets at different depths with somewhat variable compositions. This is coherent with the magma plumbing system beneath Grímsvötn being recently recharged with a deeper-derived and gas-rich basaltic melt. This basaltic intrusion resulted in mingled basaltic magma with higher gas content than before and the sub-plinian character of the last Grímsvötn eruption. The last two eruptions in Iceland therefore were both triggered by an injection of more mafic magma 1)rapidly into a solidifying silicic intrusion beneath Eyjafjallajökull and 2) more slowly disrupting a closed-system magma chamber behaviour beneath Grímsvötn volcano.

  14. Remotely Triggered Seismicity in Volcanic and Hydrothermal Environments - Which Processes?

    NASA Astrophysics Data System (ADS)

    Hill, D. P.

    2001-12-01

    The abrupt increase in seismicity rates at sites throughout much of the western United States immediately following the 1992 M=7.4 Landers earthquake provided compelling evidence that large regional earthquakes can trigger local earthquake activity at sites many source dimensions removed from the mainshock epicenter. Remotely triggered seismicity has since been documented for a number of other large earthquakes including the 1999 M=7.1 Hector Mine earthquake. Well-documented instances of remotely triggered seismicity are largely confined to transtensional or extensional tectonic regimes with a large fraction of these closely associated with hydrothermal and/or young volcanic systems. In the case of Long Valley caldera in eastern California, which responded to both the Landers and Hector Mines earthquakes, the triggered seismicity appears to be secondary to a larger, aseismic deformation transient. Because this is the only remotely triggered site with continuous deformation monitoring, however, it remains unclear whether a deformation transient is fundamental component of the remote triggering process. Fluids, either aqueous or magmatic, play a central role in most models for the triggering process in hydrothermal and/or young magmatic systems. These models span a range of intriguing (and sometimes counter-intuitive) physical processes including pressure increases associated with advective overpressure and rectified diffusion in bubbly fluids, hydraulic surges resulting from rupturing of compartments of super-hydrostatic fluids in the brittle-plastic transition zone, hydraulic pumping of near-surface pore fluids by surface waves, disruption of fine sediment accumulations (dams) in confined aquifers, local stress changes in the brittle crust associated with relaxation or mobilization of a partially crystallized magma body. All appeal to the dynamic stresses from the mainshock triggering a non-linear response in a crustal volume that is in some sense in a near

  15. Observing earthquakes triggered in the near field by dynamic deformations

    USGS Publications Warehouse

    Gomberg, J.; Bodin, P.; Reasenberg, P.A.

    2003-01-01

    We examine the hypothesis that dynamic deformations associated with seismic waves trigger earthquakes in many tectonic environments. Our analysis focuses on seismicity at close range (within the aftershock zone), complementing published studies of long-range triggering. Our results suggest that dynamic triggering is not confined to remote distances or to geothermal and volcanic regions. Long unilaterally propagating ruptures may focus radiated dynamic deformations in the propagation direction. Therefore, we expect seismicity triggered dynamically by a directive rupture to occur asymmetrically, with a majority of triggered earthquakes in the direction of rupture propagation. Bilaterally propagating ruptures also may be directive, and we propose simple criteria for assessing their directivity. We compare the inferred rupture direction and observed seismicity rate change following 15 earthquakes (M 5.7 to M 8.1) that occured in California and Idaho in the United States, the Gulf of Aqaba, Syria, Guatemala, China, New Guinea, Turkey, Japan, Mexico, and Antarctica. Nine of these mainshocks had clearly directive, unilateral ruptures. Of these nine, seven apparently induced an asymmetric increase in seismicity rate that correlates with the rupture direction. The two exceptions include an earthquake preceded by a comparable-magnitude event on a conjugate fault and another for which data limitations prohibited conclusive results. Similar (but weaker) correlations were found for the bilaterally rupturing earthquakes we studied. Although the static stress change also may trigger seismicity, it and the seismicity it triggers are expected to be similarly asymmetric only if the final slip is skewed toward the rupture terminus. For several of the directive earthquakes, we suggest that the seismicity rate change correlates better with the dynamic stress field than the static stress change.

  16. Ryanodine receptor dysfunction and triggered activity in the heart.

    PubMed

    Katra, Rodolphe P; Oya, Toshiyuki; Hoeker, Gregory S; Laurita, Kenneth R

    2007-05-01

    Arrhythmogenesis has been increasingly linked to cardiac ryanodine receptor (RyR) dysfunction. However, the mechanistic relationship between abnormal RyR function and arrhythmogenesis in the heart is not clear. We hypothesize that, under abnormal RyR conditions, triggered activity will be caused by spontaneous calcium release (SCR) events that depend on transmural heterogeneities of calcium handling. We performed high-resolution optical mapping of intracellular calcium and transmembrane potential in the canine left ventricular wedge preparation (n = 28). Rapid pacing was used to initiate triggered activity under normal and abnormal RyR conditions induced by FKBP12.6 dissociation and beta-adrenergic stimulation (20-150 microM rapamycin, 0.2 microM isoproterenol). Under abnormal RyR conditions, almost all preparations experienced SCRs and triggered activity, in contrast to control, rapamycin, or isoproterenol conditions alone. Furthermore, under abnormal RyR conditions, complex arrhythmias (monomorphic and polymorphic tachycardia) were commonly observed. After washout of rapamycin and isoproterenol, no triggered activity was observed. Surprisingly, triggered activity and SCRs occurred preferentially near the epicardium but not the endocardium (P < 0.01). Interestingly, the occurrence of triggered activity and SCR events could not be explained by cytoplasmic calcium levels, but rather by fast calcium reuptake kinetics. These data suggest that, under abnormal RyR conditions, triggered activity is caused by multiple SCR events that depend on the faster calcium reuptake kinetics near the epicardium. Furthermore, multiple regions of SCR may be a mechanism for multifocal arrhythmias associated with RyR dysfunction. PMID:17189349

  17. Effects of triggering mechanism on snow avalanche slope angles and slab depths from field data

    NASA Astrophysics Data System (ADS)

    McClung, David M.

    2013-04-01

    Field data from snow avalanche fracture lines for slope angle and slab depth (measured perpendicular to the weak layer) were analyzed for different triggering mechanisms. For slope angle, the results showed that the same probability density function (pdf) (of log-logistic type) and range (25 - 55 degrees) apply independent of triggering mechanism. For slab depth, the same pdf (generalized extreme value) applies independent of triggering mechanism. For both slope angle and slab depth, the data skewness differentiated between triggering mechanism and increased with applied triggering load. For slope angle, skewness is lowest for natural triggering by snow loads and highest for triggering from human intervention. For slab depth, the skewness is lowest for natural triggering and highest for a mix of triggers including explosive control with skier triggering being intermediate. The results reveal the effects of triggering mechanism which are important for risk analyses and to guide avalanche forecasting.

  18. An experimental comparison of triggered and random pulse train uncertainties

    SciTech Connect

    Henzlova, Daniela; Menlove, Howard O; Swinhoe, Martyn T

    2010-01-01

    In this paper we present an experimental comparison of signal-triggered and randomly triggered based analysis algorithms of neutron multiplicity data. Traditional shift register type signal-triggered multiplicity analysis of singles, doubles and triples rates is compared with analysis using randomly triggered gates. Two methods of random gate generation are explored - non-overlapping gates (Feyrunan approach) and periodic overlapping gates (fast accidentals). Using californium sources with low, medium and high rate in combination with AmLi sources (as a surrogate for plutonium) we investigate relative standard deviation (RSD) of data in order to determine if there are parameter spaces in which one of the measurement methods should be preferred. Neutron correlation analysis is a commonly used NDA technique to assay plutonium mass. The data can be collected in two distinct ways: using signal-triggered or randomly triggered counting gates. Analysis algorithms were developed for both approaches to determine singles (S), doubles (D) and triples (7) rates from the measured sample. Currently the most commonly implemented technique to collect neutron coincidence data utilizes shift register based electronics. Shift register uses signal-triggered counting gates to generate foreground multiplicity distribution of correlated+accidental events and a random gate (opened after a predefined long delay following the signal trigger) to generate background multiplicity distribution of accidental events. Modern shift registers include fast accidental option to sample data with a fixed clock frequency. This way a set of overlapping gates is used to generate background multiplicity distributions in order to improve the measurement precision. In parallel to shift register approach the Feynman variance technique is frequently used, which utilizes set of consecutive non-overlapping gates. In general, different user communities (e.g. safeguards, nuclear material accountancy, emergency

  19. Interactive Teaching about Landslides and Triggered Landslide Events

    NASA Astrophysics Data System (ADS)

    Taylor, Faith E.; Malamud, Bruce D.

    2015-04-01

    When we think of a landslide (mass wasting), both the public and scientists often envisage an individual movement of earth material down a slope. Yet, landslides often occur not as individuals, but as parts of a triggered landslide event. This is where a trigger (e.g., an earthquake or heavy rainfall) results in up to tens of thousands of landslides in a region in the minutes to days after the trigger. The sum of the impacts of these landslides may be greater than individual parts. This interactive Prezi poster will present ideas for innovative demonstrations, teaching practicals and projects, ranging from low-cost low-tech to more advanced digital methods, to communicate the ideas of landslides and triggered landslide events to the public and students. We will give live hands-on demonstrations and welcome discussions with other scientists to share ideas and best practices. This paper is aimed at those in secondary school/university education and the public sector looking for examples to interest and inform their respective audiences about landslides, triggered landslide events, and the importance and implications of considering landslides not just as individuals, but as populations.

  20. Integration of the trigger and data acquisition systems in ATLAS

    NASA Astrophysics Data System (ADS)

    Abolins, M.; Adragna, P.; Aleksandrov, E.; Aleksandrov, I.; Amorim, A.; Anderson, K.; Anduaga, X.; Aracena, I.; Asquith, L.; Avolio, G.; Backlund, S.; Badescu, E.; Baines, J.; Barria, P.; Bartoldus, R.; Batreanu, S.; Beck, H. P.; Bee, C.; Bell, P.; Bell, W. H.; Bellomo, M.; Benslama, K.; Berge, D.; Berger, N.; Berry, T.; Biglietti, M.; Blair, R. E.; Bogaerts, A.; Bold, T.; Bosman, M.; Boyd, J.; Brelier, B.; B-Chromek, D.; Buttar, C.; Campanelli, M.; Caprini, M.; Carlino, G.; Casadei, D.; Casado, P.; Cataldi, G.; Cimino, D.; Ciobotaru, M; . Clements, D.; Coccaro, A.; Muino, P. C.; Conventi, F.; C-Radu, A.; Costa, M. J.; Torres, R. C.; Cranfield, R.; Cranmer, K.; Crone, G.; Dam, M.; Damazio, D.; Dawson, I.; Dawson, J.; Simoes, J. D. A.; Cecco, S. D.; Santo, A. D.; Della Pietra, M.; Delsart, P.-A.; Demers, S.; Demirkoz, B.; Mattia, A. D.; Dionisi, C.; Djilkibaev, R.; Dobinson, R.; Dobson, M.; Dotti, A.; Dova, M.; Drake, G.; Dufour, M.-A.; Eckweiler, S.; Ehrenfeld, W.; Eifert, T.; Ellis, N.; Emeliyanov, D.; Lima, D. E. F. d.; Ermoline, Y.; Eschrich, I.; Facius, K.; Falciano, S.; Farthouat, P.; Feng, E.; Ferland, J.; Ferrari, R.; Ferrer, M. L.; Fischer, G.; F-Martin, T.; Francis, D.; Gadomski, S.; Elejabarrieta, H. G.; Gaudio, G.; Gaumer, O.; George, S.; Giagu, S.; Goncalo, R.; Gorini, B.; Gorini, E.; Gowdy, S.; G-Bold, I.; Grancagnolo, S.; Green, B.; Haas, S.; Haberichter, W.; Hadavand, H.; Haeberli, C.; Haller, J.; Hamilton, A.; Hansen, J. R.; Hauschild, M.; Hauser, R.; Head, S.; Hillier, S.; Hoecker, A.; Hryn'ova, T.; H-Jones, R.; Huston, J.; Idarraga, J.; Igonkina, O.; Inada, M.; Jain, V.; Johns, K.; Joos, M.; Kama, S.; Kanaya, N.; Kazarov, A.; Kehoe, R.; Khoriauli, G.; Kieft, G.; Kilvington, G.; Kirk, J.; Kiyamura, H.; Klous, S.; Kolos, S.; Kono, T.; Konstantinidis, N.; Korcyl, K.; Kordas, K.; Kotov, V.; Krasznahorkay, A.; Kubota, T.; Kugel, A.; Kuhn, D.; Kurasige, H.; Kuwabara, T.; Kwee, R.; Lankford, A.; LeCompte, T.; Leahu, L.; Leahu, M.; Ledroit, F.; Miotto, G. L.; Lei, X.; Lellouch, D.; Leyton, M.; Li, S.; Lim, H.; Lohse, T.; Losada, M.; Luci, C.; Luminari, L.; Mapelli, L.; Martin, B.; Martin, B. T.; Marzano, F.; Masik, J.; McMahon, T.; McPherson, R.; Medinnis, M.; Meessen, C.; Meirosu, C.; Messina, A.; Mincer, A.; Mineev, M.; Misiejuk, A.; Moenig, K.; Monticelli, F.; Moraes, A.; Moreno, D.; Morettini, P.; Garcia, R. M.; Nagano, K.; Nagasaka, Y.; Negri, A.; Nemethy, P.; Neusiedl, A.; Nisati, A.; Nozicka, M.; Omachi, C.; Osculati, B.; Osuna, C.; Padilla, C.; Panikashvili, N.; Parodi, F.; Pasqualucci, E.; Pauly, T.; Perera, V.; Perez, E.; Reale, V. P.; Petersen, J.; Piegaia, R.; Pilcher, J.; Pinzon, G.; Pope, B.; Potter, C.; Primavera, M.; Radescu, V.; Rajagopalan, S.; Renkel, P.; Rescigno, M.; Rieke, S.; Risler, C.; Riu, I.; Robertson, S.; Roda, C.; Rodriguez, D.; Rogriquez, Y.; Ryabov, Y.; Ryan, P.; Salvatore, D.; Santamarina, C.; Rios, C. S.; Scannicchio, D.; Scannicchio, D. A.; Schiavi, C.; Schlereth, J.; Scholtes, I.; Schooltz, D.; Scott, W.; Segura, E.; Shimbo, N.; Sidoti, A.; Siragusa, G.; Sivoklokov, S.; Sloper, J. E.; Smizanska, M.; Soloviev, I.; Soluk, R.; Spagnolo, S.; Spiwoks, R.; Stancu, S.; Steinberg, P.; Stelzer, J.; Stradling, A.; Strom, D.; Strong, J.; Su, D.; Sushkov, S.; Sutton, M.; Szymocha, T.; Tapprogge, S.; Tarem, S.; Tarem, Z.; T-Dias, P.; Tokoshuku, K.; Torrence, E.; Touchard, F.; Tremblet, L.; Tripiana, M.; Usai, G.; Vachon, B.; Vandelli, W.; Ventura, A.; Vercesi, V.; Vermeulen, J.; Schmitt, J. V. D.; Wang, M.; Watson, A.; Wengler, T.; Werner, P.; W-Ellis, S.; Wickens, F.; Wiedenmann, W.; Wielers, M.; Wilkens, H.; Winklmeier, F.; Woehrling, E.-E.; Wu, S.-L.; Wu, X.; Xella, S.; Yamazaki, Y.; Yu, M.; Zema, F.; Zhang, J.; Zhao, L.; Zobernig, H.; dos Anjos, A.; zur Nedden, M.; Özcan, E.; Ünel, G.

    2008-07-01

    During 2006 and the first half of 2007, the installation, integration and commissioning of trigger and data acquisition (TDAQ) equipment in the ATLAS experimental area have progressed. There have been a series of technical runs using the final components of the system already installed in the experimental area. Various tests have been run including ones where level 1 preselected simulated proton-proton events have been processed in a loop mode through the trigger and dataflow chains. The system included the readout buffers containing the events, event building, level 2 and event filter trigger algorithms. The scalability of the system with respect to the number of event building nodes used has been studied and quantities critical for the final system, such as trigger rates and event processing times, have been measured using different trigger algorithms as well as different TDAQ components. This paper presents the TDAQ architecture, the current status of the installation and commissioning and highlights the main test results that validate the system.

  1. The LUX experiment - trigger and data acquisition systems

    NASA Astrophysics Data System (ADS)

    Druszkiewicz, Eryk

    2013-04-01

    The Large Underground Xenon (LUX) detector is a two-phase xenon time projection chamber designed to detect interactions of dark matter particles with the xenon nuclei. Signals from the detector PMTs are processed by custom-built analog electronics which provide properly shaped signals for the trigger and data acquisition (DAQ) systems. During calibrations, both systems must be able to handle high rates and have large dynamic ranges; during dark matter searches, maximum sensitivity requires low thresholds. The trigger system uses eight-channel 64-MHz digitizers (DDC-8) connected to a Trigger Builder (TB). The FPGA cores on the digitizers perform real-time pulse identification (discriminating between S1 and S2-like signals) and event localization. The TB uses hit patterns, hit maps, and maximum response detection to make trigger decisions, which are reached within few microseconds after the occurrence of an event of interest. The DAQ system is comprised of commercial digitizers with customized firmware. Its real-time baseline suppression allows for a maximum event acquisition rate in excess of 1.5 kHz, which results in virtually no deadtime. The performance of the trigger and DAQ systems during the commissioning runs of LUX will be discussed.

  2. Effectiveness of splinting for the treatment of trigger finger.

    PubMed

    Colbourn, Julie; Heath, Noel; Manary, Sherry; Pacifico, Denette

    2008-01-01

    The purpose of this study was to evaluate the efficacy of custom thermoplastic splinting designed to limit metacarpalphalangeal (MCP) joint flexion for trigger finger as a first treatment option. This study was a single group, prepost design with 28 participants fit with a low-profile custom thermoplastic MCP blocking (ring) splint. The pre- and post outcome measures included: stages of stenosing tenosynovitis (SST), grip strength, Numeric Pain Rating Scale (NPRS), the number of triggering events in ten active fists, and participant perceived improvement in symptoms. These measures were taken at the time of initial assessment before splint fabrication and after six weeks of continuous splint wear. Participants were given an educational handout on trigger finger and exercises to complete independently. After the use of a splint, there were statistically significant improvements in the SST, NPRS, the number of triggering events in ten active fists, and in the participant perceived improvement in symptoms. Grip strength did not significantly change. This study demonstrated a benefit from the use of a custom thermoplastic splint for an isolated incidence of trigger finger based on chosen outcome measures. PMID:19006759

  3. A Parameterization for the Triggering of Landscape Generated Moist Convection

    NASA Technical Reports Server (NTRS)

    Lynn, Barry H.; Tao, Wei-Kuo; Abramopoulos, Frank

    1998-01-01

    A set of relatively high resolution three-dimensional (3D) simulations were produced to investigate the triggering of moist convection by landscape generated mesoscale circulations. The local accumulated rainfall varied monotonically (linearly) with the size of individual landscape patches, demonstrating the need to develop a trigger function that is sensitive to the size of individual patches. A new triggering function that includes the effect of landscapes generated mesoscale circulations over patches of different sizes consists of a parcel's perturbation in vertical velocity (nu(sub 0)), temperature (theta(sub 0)), and moisture (q(sub 0)). Each variable in the triggering function was also sensitive to soil moisture gradients, atmospheric initial conditions, and moist processes. The parcel's vertical velocity, temperature, and moisture perturbation were partitioned into mesoscale and turbulent components. Budget equations were derived for theta(sub 0) and q(sub 0). Of the many terms in this set of budget equations, the turbulent, vertical flux of the mesoscale temperature and moisture contributed most to the triggering of moist convection through the impact of these fluxes on the parcel's temperature and moisture profile. These fluxes needed to be parameterized to obtain theta(sub 0) and q(sub 0). The mesoscale vertical velocity also affected the profile of nu(sub 0). We used similarity theory to parameterize these fluxes as well as the parcel's mesoscale vertical velocity.

  4. Absence of remotely triggered large earthquakes beyond the mainshock region

    USGS Publications Warehouse

    Parsons, T.; Velasco, A.A.

    2011-01-01

    Large earthquakes are known to trigger earthquakes elsewhere. Damaging large aftershocks occur close to the mainshock and microearthquakes are triggered by passing seismic waves at significant distances from the mainshock. It is unclear, however, whether bigger, more damaging earthquakes are routinely triggered at distances far from the mainshock, heightening the global seismic hazard after every large earthquake. Here we assemble a catalogue of all possible earthquakes greater than M 5 that might have been triggered by every M 7 or larger mainshock during the past 30 years. We compare the timing of earthquakes greater than M 5 with the temporal and spatial passage of surface waves generated by large earthquakes using a complete worldwide catalogue. Whereas small earthquakes are triggered immediately during the passage of surface waves at all spatial ranges, we find no significant temporal association between surface-wave arrivals and larger earthquakes. We observe a significant increase in the rate of seismic activity at distances confined to within two to three rupture lengths of the mainshock. Thus, we conclude that the regional hazard of larger earthquakes is increased after a mainshock, but the global hazard is not.

  5. Triggering on B-jets at CDF II

    SciTech Connect

    Amerio, Silvia; Casarsa, Massimo; Cortiana, Giorgio; Donini, Julien; Lucchesi, Donatella; Pagan Griso, Simone; /Padua U. /INFN, Padua

    2009-01-01

    In this paper we present a trigger algorithm able to select online events enriched of b-jets. This feature is of central interest in order to extend the physics reach for standard model and minimal super symmetric model Higgs decaying into a pair of b-quarks. The algorithm fully exploits the recently upgraded CDFII tracking system and Level 2 CALorimeter cluster finder. These upgrades are necessary to cope with Tevatron increasing luminosity and provide new and refined trigger primitives that are the key elements of our algorithm together with the already existing silicon vertex trigger. A b-hadron can travel some millimeters before decaying and the trigger algorithm exploits this characteristic by searching for tracks displaced with respect to the primary vertex and matched to energetic jets of particles. We discuss the study and the optimization of the algorithm, its technical implementation as well as its performance. The new trigger provides an efficient selection for Higgs decaying into a pair of b-quarks and runs up to high luminosity with an acceptable occupancy of the available bandwidth.

  6. The triggers or precipitants of the acute migraine attack.

    PubMed

    Kelman, L

    2007-05-01

    The aim of this study was to evaluate and define the triggers of the acute migraine attack. Patients rated triggers on a 0-3 scale for the average headache. Demographics, prodrome, aura, headache characteristics, postdrome, medication responsiveness, acute and chronic disability, sleep characteristics and social and personal characteristics were also recorded. One thousand two hundred and seven International Classification of Headache Disorders-2 (1.1-1.2, and 1.5.1) patients were evaluated, of whom 75.9% reported triggers (40.4% infrequently, 26.7% frequently and 8.8% very frequently). The trigger frequencies were stress (79.7%), hormones in women (65.1%), not eating (57.3%), weather (53.2%), sleep disturbance (49.8%), perfume or odour (43.7%), neck pain (38.4%), light(s) (38.1%), alcohol (37.8%), smoke (35.7%), sleeping late (32.0%), heat (30.3%), food (26.9%), exercise (22.1%) and sexual activity (5.2%). Triggers were more likely to be associated with a more florid acute migraine attack. Differences were seen between women and men, aura and no aura, episodic and chronic migraine, and between migraine and probable migraine.

  7. eXtremely Fast Tracker trigger upgrade at CDF

    SciTech Connect

    Abulencia, A.; Azzurri, P.; Cochran, E.; Cox, C.; Cox, D.; Dittmann, J.; Donati, S.; Efron, J.; Erbacher, R.; Errede, D.; Fedorko, I.; /INFN, Pisa /Pisa U. /Pisa, Scuola Normale Superiore /Purdue U.

    2009-01-01

    The CDF II eXtremely Fast Tracker (XFT) is a trigger processor which reconstructs charged particle tracks in the transverse plane of the central tracking chamber. The XFT tracks are also extrapolated to the electromagnetic calorimeter and muon chambers to generate trigger electron and muon candidates. The XFT is crucial for the entire CDF II physics program: it detects high P{sub t} lepton from W/Z and heavy flavors decay and, in conjunction with the level 2 processor, it identifies secondary vertices from beauty decay. The XFT has thus been crucial for the recent measurement of the B{sub s}{sup 0} oscillation and {Sigma}{sub b}. The increase of the Tevatron instantaneous luminosity demanded an upgrade of the system to cope with the higher occupancy of the chamber. In the upgraded XFT, three-dimensional tracking reduces the level of fake tracks and measures the longitudinal track parameters, which strongly reinforce the trigger selection. This allows to maintain the trigger perfectly efficient at the record luminosities 2-3 x 10{sup 32} cm{sup -2} s{sup -1} and to maintain intact the CDF II high luminosity physics program, which includes the Higgs search. In this paper we review the architecture, the used technology, the performance and the impact of the upgraded XFT on the entire CDF II trigger strategy.

  8. Integration of the Trigger and Data Acquisition Systems in ATLAS

    SciTech Connect

    Abolins, M.; Adragna, P.; Aleksandrov, E.; Aleksandrov, I.; Amorim, A.; Anderson, K.; Anduaga, X.; Aracena, I.; Asquith, L.; Avolio, G.; Backlund, S.; Badescu, E.; Baines, J.; Barria, P.; Bartoldus, R.; Batreanu, S.; Beck, H.P.; Bee, C.; Bell, P.; Bell, W.H.; Bellomo, M.; /more authors..

    2011-11-09

    During 2006 and the first half of 2007, the installation, integration and commissioning of trigger and data acquisition (TDAQ) equipment in the ATLAS experimental area have progressed. There have been a series of technical runs using the final components of the system already installed in the experimental area. Various tests have been run including ones where level 1 preselected simulated proton-proton events have been processed in a loop mode through the trigger and dataflow chains. The system included the readout buffers containing the events, event building, level 2 and event filter trigger algorithms. The scalability of the system with respect to the number of event building nodes used has been studied and quantities critical for the final system, such as trigger rates and event processing times, have been measured using different trigger algorithms as well as different TDAQ components. This paper presents the TDAQ architecture, the current status of the installation and commissioning and highlights the main test results that validate the system.

  9. Ribonucleotide triggered DNA damage and RNA-DNA damage responses

    PubMed Central

    Wallace, Bret D; Williams, R Scott

    2014-01-01

    Research indicates that the transient contamination of DNA with ribonucleotides exceeds all other known types of DNA damage combined. The consequences of ribose incorporation into DNA, and the identity of protein factors operating in this RNA-DNA realm to protect genomic integrity from RNA-triggered events are emerging. Left unrepaired, the presence of ribonucleotides in genomic DNA impacts cellular proliferation and is associated with chromosome instability, gross chromosomal rearrangements, mutagenesis, and production of previously unrecognized forms of ribonucleotide-triggered DNA damage. Here, we highlight recent findings on the nature and structure of DNA damage arising from ribonucleotides in DNA, and the identification of cellular factors acting in an RNA-DNA damage response (RDDR) to counter RNA-triggered DNA damage. PMID:25692233

  10. VLSI-based video event triggering for image data compression

    NASA Astrophysics Data System (ADS)

    Williams, Glenn L.

    1994-02-01

    Long-duration, on-orbit microgravity experiments require a combination of high resolution and high frame rate video data acquisition. The digitized high-rate video stream presents a difficult data storage problem. Data produced at rates of several hundred million bytes per second may require a total mission video data storage requirement exceeding one terabyte. A NASA-designed, VLSI-based, highly parallel digital state machine generates a digital trigger signal at the onset of a video event. High capacity random access memory storage coupled with newly available fuzzy logic devices permits the monitoring of a video image stream for long term (DC-like) or short term (AC-like) changes caused by spatial translation, dilation, appearance, disappearance, or color change in a video object. Pre-trigger and post-trigger storage techniques are then adaptable to archiving only the significant video images.

  11. Dynamic triggering of small local earthquakes in the central Himalaya

    NASA Astrophysics Data System (ADS)

    Mendoza, Manuel M.; Ghosh, Abhijit; Rai, Shyam S.

    2016-09-01

    We present the first observation of remote dynamic triggering of local microearthquakes in central Himalaya caused by the teleseismic waves from the 2007 Mw 8.5 Sumatra earthquake that occurs ~4500 km away. We find small local earthquakes in the Kumaon-Garhwal Himalaya triggered by teleseismic long-period surface waves. Interestingly, an elevated level of seismicity persists for a week or so after the arrival of the teleseismic waves. The teleseismic waves impart ~9 kPa of peak dynamic stresses, suggesting that the Himalayan faults in this area are sensitive to small stress changes. This heightened and protracted seismicity indicates that the transient dynamic stresses may have triggered secondary processes, such as slow slip, that may be responsible for the persistence of this earthquake sequence. The region is thought to be close to a large damaging earthquake in the near future. This study provides improved constraints on the factors controlling the earthquake cycle.

  12. VLSI-based Video Event Triggering for Image Data Compression

    NASA Technical Reports Server (NTRS)

    Williams, Glenn L.

    1994-01-01

    Long-duration, on-orbit microgravity experiments require a combination of high resolution and high frame rate video data acquisition. The digitized high-rate video stream presents a difficult data storage problem. Data produced at rates of several hundred million bytes per second may require a total mission video data storage requirement exceeding one terabyte. A NASA-designed, VLSI-based, highly parallel digital state machine generates a digital trigger signal at the onset of a video event. High capacity random access memory storage coupled with newly available fuzzy logic devices permits the monitoring of a video image stream for long term (DC-like) or short term (AC-like) changes caused by spatial translation, dilation, appearance, disappearance, or color change in a video object. Pre-trigger and post-trigger storage techniques are then adaptable to archiving only the significant video images.

  13. Triggered Observations of a new VHE Gamma-ray Blazar

    NASA Astrophysics Data System (ADS)

    Boettcher, Markus

    2011-10-01

    We propose triggered observations of a new VHE blazar. Observations will be triggered following the detection of a flaring state by VERITAS. Simultaneous radio, near-IR, and optical coverage by the GLAST-AGILE Support Program (GASP) will be arranged, and we will include Fermi MeV -- GeV gamma-ray data. The proposed campaign aims at the study of new TeV blazars with data to allow meaningful studies of their broadband spectral and variability properties, and ultimately understand the mechanisms of particle acceleration and emission of radiation in TeV blazars. This proposal follows the same strategy as a predecessor proposal in AO-6 which was triggered and led to a highly successful multiwavelength campaign on W~Comae in June 2008.

  14. Digital self-triggered robust control of nonlinear systems

    NASA Astrophysics Data System (ADS)

    Di Benedetto, M. D.; Di Gennaro, S.; D'Innocenzo, A.

    2013-09-01

    In this paper, we develop novel results on self-triggered control of nonlinear systems, subject to perturbations, and sensing/computation/actuation delays. First, considering an unperturbed nonlinear system with bounded delays, we provide conditions that guarantee the existence of a self-triggered control strategy stabilizing the closed-loop system. Then, considering parameter uncertainties, disturbances and bounded delays, we provide conditions guaranteeing the existence of a self-triggered strategy that keeps the state arbitrarily close to the equilibrium point. In both cases, we provide a methodology for the computation of the next execution time. We show on an example the relevant benefits obtained with this approach in terms of energy consumption with respect to control algorithms based on a constant sampling with a sensible reduction of the average sampling time.

  15. Accelerative propagation and explosion triggering by expanding turbulent premixed flames.

    PubMed

    Akkerman, V'yacheslav; Chaudhuri, Swetaprovo; Law, Chung K

    2013-02-01

    The dynamics and morphology of outwardly propagating, accelerating turbulent premixed flames and the effect of flame acceleration on explosion triggering are analyzed. Guided by recent theoretical results and substantiated by experiments, we find that an expanding flame front in an externally forced, near-isotropic turbulent environment exhibits accelerative propagation given by a well-defined power law based on the average global flame radius. In this context the limits of the power-law exponent and the effective turbulence intensity experienced by the flame are derived. The power-law exponent is found to be substantially larger than that for the hydrodynamically unstable cellular laminar flames, hence facilitating the possibility of detonation triggering in turbulent environments. For large length scales, hydrodynamic instability is expected to provide additional acceleration, thus further favoring the attainment of detonation triggering.

  16. Triggered-release nanocapsules for drug delivery to the lungs.

    PubMed

    Chana, Jasminder; Forbes, Ben; Jones, Stuart A

    2015-01-01

    This study demonstrated the feasibility of trigger-responsive inhaled delivery of medicines using soft solid shelled nanocapsules. The delivery system was a 50nm sized lipid rich capsule carrier that distended rapidly when mixed with an exogenous non-ionic surfactant trigger, Pluronic® L62D. Capsule distension was accompanied by solid shell permeabilisation which resulted in payload release from the carrier; 63.9±16.3% within 1h. In electrolyte rich aqueous fluids Pluronic® L62D was loosely aggregated, which we suggest to be the cause of its potency in lipid nanocapsule permeabilisation compared to other structurally similar molecules. The specificity of the interaction between L62D and the nanocapsule resulted in carrier payload delivery into human epithelial cells without any adverse effects on metabolic activity or barrier function. This effective, biocompatible, trigger-responsive delivery system provides a versatile platform technology for inhaled medicines.

  17. Development and Applications of Photo-triggered Theranostic Agents

    PubMed Central

    Rai, Prakash; Mallidi, Srivallesha; Zheng, Xiang; Rahmanzadeh, Ramtin; Mir, Youssef; Elrington, Stefan; Khurshid, Ahmat; Hasan, Tayyaba

    2010-01-01

    Theranostics, the fusion of therapy and diagnostics for optimizing efficacy and safety of therapeutic regimes, is a growing field that is paving the way towards the goal of personalized medicine for the benefit of patients. The use of light as a remote-activation mechanism for drug delivery has received increased attention due to its advantages in highly specific spatial and temporal control of compound release. Photo-triggered theranostic constructs could facilitate an entirely new category of clinical solutions which permit early recognition of the disease by enhancing contrast in various imaging modalities followed by the tailored guidance of therapy. Finally, such theranostic agents could aid imaging modalities in monitoring response to therapy. This article reviews recent developments in the use of light-triggered theranostic agents for simultaneous imaging and photoactivation of therapeutic agents. Specifically, we discuss recent developments in the use of theranostic agents for photodynamic-, photothermal- or photo-triggered chemo-therapy for several diseases. PMID:20858520

  18. Surface-wave potential for triggering tectonic (nonvolcanic) tremor

    USGS Publications Warehouse

    Hill, D.P.

    2010-01-01

    Source processes commonly posed to explain instances of remote dynamic triggering of tectonic (nonvolcanic) tremor by surface waves include frictional failure and various modes of fluid activation. The relative potential for Love- and Rayleigh-wave dynamic stresses to trigger tectonic tremor through failure on critically stressed thrust and vertical strike-slip faults under the Coulomb-Griffith failure criteria as a function of incidence angle is anticorrelated over the 15- to 30-km-depth range that hosts tectonic tremor. Love-wave potential is high for strike-parallel incidence on low-angle reverse faults and null for strike-normal incidence; the opposite holds for Rayleigh waves. Love-wave potential is high for both strike-parallel and strike-normal incidence on vertical, strike-slip faults and minimal for ~45?? incidence angles. The opposite holds for Rayleigh waves. This pattern is consistent with documented instances of tremor triggered by Love waves incident on the Cascadia mega-thrust and the San Andreas fault (SAF) in central California resulting from shear failure on weak faults (apparent friction, ????? 0.2). However, documented instances of tremor triggered by surface waves with strike-parallel incidence along the Nankai megathrust beneath Shikoku, Japan, is associated primarily with Rayleigh waves. This is consistent with the tremor bursts resulting from mixed-mode failure (crack opening and shear failure) facilitated by near-lithostatic ambient pore pressure, low differential stress, with a moderate friction coefficient (?? ~ 0.6) on the Nankai subduction interface. Rayleigh-wave dilatational stress is relatively weak at tectonic tremor source depths and seems unlikely to contribute significantly to the triggering process, except perhaps for an indirect role on the SAF in sustaining tremor into the Rayleigh-wave coda that was initially triggered by Love waves.

  19. FPGA based triggers in the Pierre Auger Observatory

    NASA Astrophysics Data System (ADS)

    Szadkowski, Z.

    2008-01-01

    The Pierre Auger Observatory is an international project for research on ultra-high energy cosmic rays (UHECR) above 10 19 eV and currently the world largest "hybrid" experiment. The hybrid technique uses both the detection of particles at the ground in water Cherenkov detectors (WCD) and measurements of fluorescence light generated in the atmosphere by the extensive air showers. This technique offers unique possibilities for cross-calibration and reduction of measurement uncertainties. The surface array will contain 1600 surface detector stations distributed over 3000 km2 in the Southern Hemisphere (under construction in Argentina) and 4000 WCD distributed over 10000 km2 at a Northern Hemisphere site in Colorado (deployment planned for 2008). Four fluorescence stations each containing 6 wide-angle Schmidt telescopes and each equipped with 440 PMTs with 1.5° angle resolution and 30 • 30° of field of view are located on the border of the surface array in the Southern Site. The paper presents implementations of the FPGA used for triggering. The use is illustrated with currently working schemes as well as other possible ideas especially promising for the surface detector in which currently used triggers seems to be not effective enough for very inclined and horizontal showers. Proposed new triggers enlarge a simple 1-bit threshold detection to the online analysis of a FADC trace shape. This corresponds to a charge from PMTs or signal power estimation. The next category is spectral triggers analyzing sequential samples in the frequency domain. Digital sigma-delta filters immunize the trigger circuitry on the pedestal variation as results of huge temperature swings. Presented DCT trigger provides native pedestal independence.

  20. Pregnancy as a possible trigger for heritable pulmonary arterial hypertension.

    PubMed

    Limoges, Maude; Langleben, David; Fox, Benjamin D; Shear, Roberta; Wieczorek, Paul; Rudski, Lawrence G; Hirsch, Andrew M; Schlesinger, Robert D; Lesenko, Lyda

    2016-09-01

    It is unclear whether pregnancy is a trigger or accelerant for idiopathic pulmonary arterial hypertension (PAH). Alternatively, its frequency close to the onset of symptoms and diagnosis in the idiopathic PAH population may represent a coincidence in a disease that predominates in young women. We describe a carrier of a BMPR2 gene mutation who had an uneventful first pregnancy but had aggressive PAH during her second pregnancy and now has ongoing heritable PAH. The possible role of pregnancy as a trigger in this vulnerable patient is discussed. Databases of patients with heritable PAH should be explored to see whether pregnancy is related to overt manifestation of the disease. PMID:27683615