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Sample records for exon1 n-terminus triggers

  1. Polyglutamine disruption of the huntingtin exon1 N-terminus triggers a complex aggregation mechanism

    PubMed Central

    Thakur, Ashwani K.; Jayaraman, Murali; Mishra, Rakesh; Thakur, Monika; Chellgren, Veronique M.; Byeon, In-Ja; Anjum, Dalaver H.; Kodali, Ravindra; Creamer, Trevor P.; Conway, James F.; M.Gronenborn, Angela; Wetzel, Ronald

    2009-01-01

    Simple polyglutamine (polyQ) peptides aggregate in vitro via a nucleated growth pathway directly yielding amyloid-like aggregates. We show here that the 17 amino acid flanking sequence (httNT) N-terminal to the polyQ in the toxic huntingtin exon1 fragment imparts onto this peptide a complex alternative aggregation mechanism. In isolation the httNT peptide is a compact coil that resists aggregation. When polyQ is fused to this sequence, it induces in httNT, in a repeat-length dependent fashion, a more extended conformation that greatly enhances its aggregation into globular oligomers with httNT cores and exposed polyQ. In a second step, a new, amyloid-like aggregate is formed with a core composed of both httNT and polyQ. The results indicate unprecedented complexity in how primary sequence controls aggregation within a substantially disordered peptide, and have implications for the molecular mechanism of Huntington's disease. PMID:19270701

  2. Phosphorylation of SDT repeats in the MDC1 N terminus triggers retention of NBS1 at the DNA damage–modified chromatin

    PubMed Central

    Melander, Fredrik; Bekker-Jensen, Simon; Falck, Jacob; Bartek, Jiri; Mailand, Niels; Lukas, Jiri

    2008-01-01

    DNA double-strand breaks (DSBs) trigger accumulation of the MRE11–RAD50–Nijmegen breakage syndrome 1 (NBS1 [MRN]) complex, whose retention on the DSB-flanking chromatin facilitates survival. Chromatin retention of MRN requires the MDC1 adaptor protein, but the mechanism behind the MRN–MDC1 interaction is unknown. We show that the NBS1 subunit of MRN interacts with the MDC1 N terminus enriched in Ser-Asp-Thr (SDT) repeats. This interaction was constitutive and mediated by binding between the phosphorylated SDT repeats of MDC1 and the phosphate-binding forkhead-associated domain of NBS1. Phosphorylation of the SDT repeats by casein kinase 2 (CK2) was sufficient to trigger MDC1–NBS1 interaction in vitro, and MDC1 associated with CK2 activity in cells. Inhibition of CK2 reduced SDT phosphorylation in vivo, and disruption of the SDT-associated phosphoacceptor sites prevented the retention of NBS1 at DSBs. Together, these data suggest that phosphorylation of the SDT repeats in the MDC1 N terminus functions to recruit NBS1 and, thereby, increases the local concentration of MRN at the sites of chromosomal breakage. PMID:18411307

  3. Aberrant splicing of HTT generates the pathogenic exon 1 protein in Huntington disease.

    PubMed

    Sathasivam, Kirupa; Neueder, Andreas; Gipson, Theresa A; Landles, Christian; Benjamin, Agnesska C; Bondulich, Marie K; Smith, Donna L; Faull, Richard L M; Roos, Raymund A C; Howland, David; Detloff, Peter J; Housman, David E; Bates, Gillian P

    2013-02-01

    Huntington disease (HD) is a devastating, late-onset, inherited neurodegenerative disorder that manifests with personality changes, movement disorders, and cognitive decline. It is caused by a CAG repeat expansion in exon 1 of the HTT gene that translates to a polyglutamine tract in the huntingtin protein (HTT). The formation of HTT fragments has been implicated as an essential step in the molecular pathogenesis of HD and several proteases that cleave HTT have been identified. However, the importance of smaller N-terminal fragments has been highlighted by their presence in HD postmortem brains and by the fact that nuclear inclusions are only detected by antibodies to the N terminus of HTT. Despite an intense research effort, the precise length of these fragments and the mechanism by which they are generated remains unknown. Here we show that CAG repeat length-dependent aberrant splicing of exon 1 HTT results in a short polyadenylated mRNA that is translated into an exon 1 HTT protein. Given that mutant exon 1 HTT proteins have consistently been shown to be highly pathogenic in HD mouse models, the aberrant splicing of HTT mRNA provides a mechanistic basis for the molecular pathogenesis of HD. RNA-targeted therapeutic strategies designed to lower the levels of HTT are under development. Many of these approaches would not prevent the production of exon 1 HTT and should be reviewed in light of our findings. PMID:23341618

  4. 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.

  5. Novel Archaeal Adhesion Pilins with a Conserved N Terminus

    PubMed Central

    Esquivel, Rianne N.; Xu, Rachel

    2013-01-01

    Type IV pili play important roles in a wide array of processes, including surface adhesion and twitching motility. Although archaeal genomes encode a diverse set of type IV pilus subunits, the functions for most remain unknown. We have now characterized six Haloferax volcanii pilins, PilA[1-6], each containing an identical 30-amino-acid N-terminal hydrophobic motif that is part of a larger highly conserved domain of unknown function (Duf1628). Deletion mutants lacking up to five of the six pilin genes display no significant adhesion defects; however, H. volcanii lacking all six pilins (ΔpilA[1-6]) does not adhere to glass or plastic. Consistent with these results, the expression of any one of these pilins in trans is sufficient to produce functional pili in the ΔpilA[1-6] strain. PilA1His and PilA2His only partially rescue this phenotype, whereas ΔpilA[1-6] strains expressing PilA3His or PilA4His adhere even more strongly than the parental strain. Most surprisingly, expressing either PilA5His or PilA6His in the ΔpilA[1-6] strain results in microcolony formation. A hybrid protein in which the conserved N terminus of the mature PilA1His is replaced with the corresponding N domain of FlgA1 is processed by the prepilin peptidase, but it does not assemble functional pili, leading us to conclude that Duf1628 can be annotated as the N terminus of archaeal PilA adhesion pilins. Finally, the pilin prediction program, FlaFind, which was trained primarily on archaeal flagellin sequences, was successfully refined to more accurately predict pilins based on the in vivo verification of PilA[1-6]. PMID:23794623

  6. 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.

  7. Solid Phase Formylation of N-Terminus Peptides.

    PubMed

    Tornesello, Anna Lucia; Sanseverino, Marina; Buonaguro, Franco Maria

    2016-01-01

    Formylation of amino groups is a critical reaction involved in several biological processes including post-translational modification of histones. The addition of a formyl group (CHO) to the N-terminal end of a peptide chain generates biologically active molecules. N-formyl-peptides can be produced by different methods. We performed the N-formylation of two chemotactic hexapetides, Met1-Leu2-Lys3-Leu4-Ile5-Val6 and Met1-Met2-Tyr3-Ala4-Leu5-Phe6, carrying out the reaction directly on peptidyl-resin following pre-activation of formic acid with N,N-dicyclohexylcarbodiimmide (DCC) in liquid phase. The overnight incubation at 4 °C resulted in a significant increase in production yields of formylated peptides compared to the reaction performed at room temperature. The method is consistently effective, rapid, and inexpensive. Moreover, the synthetic strategy can be applied for the formylation of all primary amines at N-terminus of peptide chains or amino groups of lysine side-chains in solid phase. PMID:27271589

  8. Acetylation within the First 17 Residues of Huntingtin Exon 1 Alters Aggregation and Lipid Binding.

    PubMed

    Chaibva, Maxmore; Jawahery, Sudi; Pilkington, Albert W; Arndt, James R; Sarver, Olivia; Valentine, Stephen; Matysiak, Silvina; Legleiter, Justin

    2016-07-26

    Huntington's disease (HD) is a genetic neurodegenerative disorder caused by an expanded polyglutamine (polyQ) domain near the N-terminus of the huntingtin (htt) protein. Expanded polyQ leads to htt aggregation. The first 17 amino acids (Nt(17)) in htt comprise a lipid-binding domain that undergoes a number of posttranslational modifications that can modulate htt toxicity and subcellular localization. As there are three lysines within Nt(17), we evaluated the impact of lysine acetylation on htt aggregation in solution and on model lipid bilayers. Acetylation of htt-exon1(51Q) and synthetic truncated htt-exon 1 mimicking peptides (Nt(17)-Q35-P10-KK) was achieved using a selective covalent label, sulfo-N-hydroxysuccinimide (NHSA). With this treatment, all three lysine residues (K6, K9, and K15) in Nt(17) were significantly acetylated. N-terminal htt acetylation retarded fibril formation in solution and promoted the formation of larger globular aggregates. Acetylated htt also bound lipid membranes and disrupted the lipid bilayer morphology less aggressively compared with the wild-type. Computational studies provided mechanistic insights into how acetylation alters the interaction of Nt(17) with lipid membranes. Our results highlight that N-terminal acetylation influences the aggregation of htt and its interaction with lipid bilayers. PMID:27463137

  9. 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.

  10. N-terminus regulation of VMAT2 mediates methamphetamine stimulated efflux

    PubMed Central

    Torres, Brian; Ruoho, Arnold E.

    2014-01-01

    The 20 amino acid N-terminus of the vesicular monoamine transporter 2 (VMAT2) was examined as a regulator of VMAT2 function. Removal of the first 16 or 19 amino acids of the N-terminus resulted in a molecule with reduced ability to sequester [3H]-5HT. A GST-construct of the N-terminus underwent phosphorylation in the presence of PKC at serines 15 and 18. These putative phosphorylation sites were examined for effects on function. Phospho-mimetic substitution of serines 15 and 18 with aspartate in the full-length VMAT2 resulted in reduced [3H]-5HT sequestration and reduced methamphetamine-stimulated efflux of preloaded [3H]-5HT. In contrast, mutation of serines 15 and 18 to alanines maintained intact net substrate sequestration but eliminated methamphetamine-stimulated efflux of pre-accumulated [3H]-5HT. In summary, these data suggest a model in which the VMAT2 N-terminus regulates monoamine sequestration. PMID:24321511

  11. Identification of Novel Potentially Toxic Oligomers Formed in Vitro from Mammalian-derived Expanded huntingtin Exon-1 Protein*

    PubMed Central

    Nucifora, Leslie G.; Burke, Kathleen A.; Feng, Xia; Arbez, Nicolas; Zhu, Shanshan; Miller, Jason; Yang, Guocheng; Ratovitski, Tamara; Delannoy, Michael; Muchowski, Paul J.; Finkbeiner, Steven; Legleiter, Justin; Ross, Christopher A.; Poirier, Michelle A.

    2012-01-01

    Huntington disease is a genetic neurodegenerative disorder that arises from an expanded polyglutamine region in the N terminus of the HD gene product, huntingtin. Protein inclusions comprised of N-terminal fragments of mutant huntingtin are a characteristic feature of disease, though are likely to play a protective role rather than a causative one in neurodegeneration. Soluble oligomeric assemblies of huntingtin formed early in the aggregation process are candidate toxic species in HD. In the present study, we established an in vitro system to generate recombinant huntingtin in mammalian cells. Using both denaturing and native gel analysis, we have identified novel oligomeric forms of mammalian-derived expanded huntingtin exon-1 N-terminal fragment. These species are transient and were not previously detected using bacterially expressed exon-1 protein. Importantly, these species are recognized by 3B5H10, an antibody that recognizes a two-stranded hairpin conformation of expanded polyglutamine believed to be associated with a toxic form of huntingtin. Interestingly, comparable oligomeric species were not observed for expanded huntingtin shortstop, a 117-amino acid fragment of huntingtin shown previously in mammalian cell lines and transgenic mice, and here in primary cortical neurons, to be non-toxic. Further, we demonstrate that expanded huntingtin shortstop has a reduced ability to form amyloid-like fibrils characteristic of the aggregation pathway for toxic expanded polyglutamine proteins. Taken together, these data provide a possible candidate toxic species in HD. In addition, these studies demonstrate the fundamental differences in early aggregation events between mutant huntingtin exon-1 and shortstop proteins that may underlie the differences in toxicity. PMID:22433867

  12. 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.

  13. Cadherin adhesion depends on a salt bridge at the N-terminus.

    PubMed

    Harrison, Oliver J; Corps, Elaine M; Kilshaw, Peter J

    2005-09-15

    There is now considerable evidence that cell adhesion by cadherins requires a strand exchange process in which the second amino acid at the N-terminus of the cadherin molecule, Trp2, docks into a hydrophobic pocket in the domain fold of the opposing cadherin. Here we show that strand exchange depends on a salt bridge formed between the N-terminal amino group of one cadherin molecule and the acidic side chain of Glu89 of the other. Prevention of this bond in N-cadherin by introducing the mutation Glu89Ala or by extending the N-terminus with additional amino acids strongly inhibited strand exchange. But when the two modifications were present in opposing cadherin molecules respectively, they acted in a complementary manner, lowering activation energy for strand exchange and greatly increasing the strength of the adhesive interaction. N-cadherin that retained an uncleaved prodomain or lacked Trp2 adhered strongly to the Glu89Ala mutant but not to wild-type molecules. Similarly, N-cadherin in which the hydrophobic acceptor pocket was blocked by an isoleucine side chain adhered to a partner that had an extended N-terminus. We explain these results in terms of the free energy changes that accompany strand exchange. Our findings provide new insight into the mechanism of adhesion and demonstrate the feasibility of greatly increasing cadherin affinity. PMID:16118243

  14. 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.

  15. A molecular genetic dissection of the evolutionarily conserved N terminus of yeast Rad52.

    PubMed Central

    Mortensen, Uffe H; Erdeniz, Naz; Feng, Qi; Rothstein, Rodney

    2002-01-01

    Rad52 is a DNA-binding protein that stimulates the annealing of complementary single-stranded DNA. Only the N terminus of Rad52 is evolutionarily conserved; it contains the core activity of the protein, including its DNA-binding activity. To identify amino acid residues that are important for Rad52 function(s), we systematically replaced 76 of 165 amino acid residues in the N terminus with alanine. These substitutions were examined for their effects on the repair of gamma-ray-induced DNA damage and on both interchromosomal and direct repeat heteroallelic recombination. This analysis identified five regions that are required for efficient gamma-ray damage repair or mitotic recombination. Two regions, I and II, also contain the classic mutations, rad52-2 and rad52-1, respectively. Interestingly, four of the five regions contain mutations that impair the ability to repair gamma-ray-induced DNA damage yet still allow mitotic recombinants to be produced at rates that are similar to or higher than those obtained with wild-type strains. In addition, a new class of separation-of-function mutation that is only partially deficient in the repair of gamma-ray damage, but exhibits decreased mitotic recombination similar to rad52 null strains, was identified. These results suggest that Rad52 protein acts differently on lesions that occur spontaneously during the cell cycle than on those induced by gamma-irradiation. PMID:12072453

  16. 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

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

    PubMed

    Dunajová, Lucia; Cash, Emily; Markus, Robert; Rochette, Sophie; Townley, Amelia R; Wheatley, Sally P

    2016-07-15

    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

  18. 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

  19. Mutational analysis of the N terminus of the protein of maize transposable element Ac.

    PubMed Central

    Li, M G; Starlinger, P

    1990-01-01

    Mutations of transposable element Ac were tested for their capability to excise themselves from their location autonomously, to be excised by an active Ac, or to act in trans in the excision of an Ac delta element. Removal of 101 amino acids from the N terminus of the Ac protein does not decrease excision. A cis-acting site between base pairs 186 and 207 is important for excision by the wild-type protein but is not necessary for excision by the truncated protein. Improvement of the sequence context of the first AUG does not have a significant effect. Mutations in a small open reading frame of Ac encoding a 102-amino acid protein do not visibly alter excision frequency. Images PMID:2166942

  20. An autophosphorylating but not transphosphorylating activity is associated with the unique N terminus of the herpes simplex virus type 1 ribonucleotide reductase large subunit.

    PubMed Central

    Conner, J; Cooper, J; Furlong, J; Clements, J B

    1992-01-01

    We report on a protein kinase function encoded by the unique N terminus of the herpes simplex virus type 1 (HSV-1) ribonucleotide reductase large subunit (R1). R1 expressed in Escherichia coli exhibited autophosphorylation activity in a reaction which depended on the presence of the unique N terminus. When the N terminus was separately expressed in E. coli and partially purified, a similar autophosphorylation reaction was observed. Importantly, transphosphorylation of histones and of proteins in HSV-1-infected cell extracts was also observed with purified R1 and with truncated R1 mutants in which most of the N terminus was deleted. Ion-exchange chromatography was used to separate the autophosphorylating activity of the N terminus from the transphosphorylating activity of an E. coli contaminant protein kinase. We propose a putative function for this activity of the HSV-1 R1 N terminus during the immediate-early phase of virus replication. Images PMID:1331536

  1. N-terminus-mediated dimerization of ROCK-I is required for RhoE binding and actin reorganization.

    PubMed

    Garg, Ritu; Riento, Kirsi; Keep, Nicholas; Morris, Jonathan D H; Ridley, Anne J

    2008-04-15

    ROCK-I (Rho-associated kinase 1) is a serine/threonine kinase that can be activated by RhoA and inhibited by RhoE. ROCK-I has an N-terminal kinase domain, a central coiled-coil region and a RhoA-binding domain near the C-terminus. We have previously shown that RhoE binds to the N-terminal 420 amino acids of ROCK-I, which includes the kinase domain as well as N-terminal and C-terminal extensions. In the present study, we show that N-terminus-mediated dimerization of ROCK-I is required for RhoE binding. The central coiled-coil domain can also dimerize ROCK-I in cells, but this is insufficient in the absence of the N-terminus to allow RhoE binding. The kinase activity of ROCK-I(1-420) is required for dimerization and RhoE binding; however, inclusion of part of the coiled-coil domain compensates for lack of kinase activity, allowing RhoE to bind. N-terminus-mediated dimerization is also required for ROCK-I to induce the formation of stellate actin stress fibres in cells. These results indicate that dimerization via the N-terminus is critical for ROCK-I function in cells and for its regulation by RhoE. PMID:18215121

  2. Effects of N-terminus modifications on the conformation and permeation activities of the synthetic peptide L1A.

    PubMed

    Zanin, Luciana Puia Moro; de Araujo, Alexandre Suman; Juliano, Maria Aparecida; Casella, Tiago; Nogueira, Mara Correa Lelles; Ruggiero Neto, João

    2016-06-01

    We investigate the effect of the N-terminus modification of the L1A, a synthetic octadecapeptide, on its helical content, affinity and lytic action in model membranes and on its hemolytic and antibacterial activities. L1A and its acetylated analog displayed a selective antibacterial activity to Gram-negative bacteria without being hemolytic. The covalently linked 2-aminobezoic acid to the N-terminus impaired the antibacterial efficacy and increased hemolysis. Despite their lower net charge (+2), N-terminus modifications resulted in enhanced affinity and improved lytic efficiency in anionic vesicles. The analogs also showed higher helical content and consequently higher amphipathicity in these vesicles. The conformational analysis by molecular dynamics simulations in 30 % of TFE/water showed that the hydrophobic faces of the peptides are in close contact with CF3 groups of TFE while the hydrophilic faces with water molecules. Due to the loss of the amino charge, the N-termini of the analogs are buried in TFE molecules. The analysis of the pair distribution functions, obtained for the center of mass of the charged groups, has evidenced that the state of the N-terminus has influenced the possibility of different ion-pairing. The higher complexity of the bacterial cells compared with anionic vesicles hampers to establish correlations structure-function for the analogs. PMID:26920749

  3. Differences in activity of actinoporins are related with the hydrophobicity of their N-terminus.

    PubMed

    Ros, Uris; Rodríguez-Vera, Wendy; Pedrera, Lohans; Valiente, Pedro A; Cabezas, Sheila; Lanio, María E; García-Sáez, Ana J; Alvarez, Carlos

    2015-09-01

    Actinoporins are pore-forming toxins (PFT) produced by sea anemones with molecular mass around 20 kDa and high affinity for sphingomyelin. The most studied atinoporins are sticholysins I and II (StI/StII) from Stichodactyla helianthus, equinatoxin II (EqtII) from Actinia equina, and fragaceatoxin C (FraC) from Actinia fragacea. Their N-terminal sequences encompassing residues 1-30 seem to be the best candidates for pore formation. This segment comprises an amphipathic α-helix preceded by a more or less hydrophobic segment, depending on the toxin, of around 10 amino acid residues. Although it is clear that the N-terminal is the most variable sequence in this protein family, the role of their hydrophobic segment in not fully understood. Here we show a comparison of StI, StII, EqtII, and FraC activities with that of their respective N-terminal synthetic peptides. The hemolytic and permeabilizing activity of the peptides reproduce qualitatively the behavior of their respective parental proteins and are particularly related to the hydrophobicity of the corresponding 1-10 segment. Furthermore, the dendrogram analysis of actinoporins' N-terminal sequence allows relating differences in alignment with differences in activity among the four toxins. We have also evaluated the penetration depth of the N-terminal segment of StI and StII by using Trp-containing peptide-analogs. Our data suggest that the N-terminus of StII is more deeply buried into the hydrophobic core of the bilayer than that of StI. We hypothesize that the highest activity of StII could be ascribed to a larger hydrophobic continuum, an uninterrupted sequence of non-charged mainly hydrophobic amino acid residues, of its N-terminus promoting a highest ability to partially insert in the membrane core. Moreover, as we show for four related peptides that a higher hydrophobicity contributes to increase the activity, we reinforce the notion that this property must be taken into account to design new potent

  4. 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

  5. Specificity studies on enteropeptidase substrates related to the N-terminus of trypsinogen.

    PubMed Central

    Jenö, P; Green, J R; Lentze, M J

    1987-01-01

    The specificity of the synthetic substrate Gly-[L-Asp]4-L-Lys 2-naphthylamide originally developed for the assay of enteropeptidase (EC 3.4.21.9), was investigated with partially purified aminopeptidase. Our results indicate that, not only enteropeptidase, but also the concerted action of the aminopeptidases of the rat small intestine, can rapidly release 2-naphthylamine from the substrate. A previously undescribed, highly active, dipeptidylaminopeptidase, which hydrolyses a Gly-Asp dipeptide from the N-terminus of the substrate, was detected in rat small intestine. The resulting [L-Asp]3-L-Lys 2-naphthylamide fragment is then degraded by a combination of aminopeptidase A and N to yield free 2-naphthylamine. Thus the present substrate cannot be regarded as being specific for enteropeptidase, and its use leads to an over-estimation of enteropeptidase activity in homogenates and extracts of intestinal tissue. In order to prevent this non-specific hydrolysis by aminopeptidases, stereoisomeric substrates with the sequence L-Ala-D-Asp-[L-Asp]3-L-Lys methyl ester, D-Ala-[L-Asp]4-L-Lys methyl ester and L-Ala-[Asp]4-L-Lys methyl ester were synthesized and tested as alternative substrates by their ability to inhibit the enteropeptidase-catalysed activation of trypsinogen. PMID:3297038

  6. 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

  7. Structural studies of the tethered N-terminus of the Alzheimer's disease amyloid-β peptide.

    PubMed

    Nisbet, Rebecca M; Nuttall, Stewart D; Robert, Remy; Caine, Joanne M; Dolezal, Olan; Hattarki, Meghan; Pearce, Lesley A; Davydova, Natalia; Masters, Colin L; Varghese, Jose N; Streltsov, Victor A

    2013-10-01

    Alzheimer's disease is the most common form of dementia in humans and is related to the accumulation of the amyloid-β (Aβ) peptide and its interaction with metals (Cu, Fe, and Zn) in the brain. Crystallographic structural information about Aβ peptide deposits and the details of the metal-binding site is limited owing to the heterogeneous nature of aggregation states formed by the peptide. Here, we present a crystal structure of Aβ residues 1-16 fused to the N-terminus of the Escherichia coli immunity protein Im7, and stabilized with the fragment antigen binding fragment of the anti-Aβ N-terminal antibody WO2. The structure demonstrates that Aβ residues 10-16, which are not in complex with the antibody, adopt a mixture of local polyproline II-helix and turn type conformations, enhancing cooperativity between the two adjacent histidine residues His13 and His14. Furthermore, this relatively rigid region of Aβ (residues, 10-16) appear as an almost independent unit available for trapping metal ions and provides a rationale for the His13-metal-His14 coordination in the Aβ1-16 fragment implicated in Aβ metal binding. This novel structure, therefore, has the potential to provide a foundation for investigating the effect of metal ion binding to Aβ and illustrates a potential target for the development of future Alzheimer's disease therapeutics aimed at stabilizing the N-terminal monomer structure, in particular residues His13 and His14, and preventing Aβ metal-binding-induced neurotoxicity. PMID:23609990

  8. 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

  9. Deconstructing honeybee vitellogenin: novel 40 kDa fragment assigned to its N terminus

    PubMed Central

    Havukainen, Heli; Halskau, Øyvind; Skjaerven, Lars; Smedal, Bente; Amdam, Gro V.

    2011-01-01

    Vitellogenin, an egg-yolk protein precursor common to oviparous animals, is found abundantly in honeybee workers – a caste of helpers that do not usually lay eggs. Instead, honeybee vitellogenin (180 kDa) participates in processes other than reproduction: it influences hormone signaling, food-related behavior, immunity, stress resistance and longevity. The molecular basis of these functions is largely unknown. Here, we establish and compare the molecular properties of vitellogenin from honeybee hemolymph (blood) and abdominal fat body, two compartments that are linked to vitellogenin functions. Our results reveal a novel 40 kDa vitellogenin fragment in abdominal fat body tissue, the main site for vitellogenin synthesis and storage. Using MALDI-TOF combined with MS/MS mass-spectroscopy, we assign the 40 kDa fragment to the N terminus of vitellogenin, whereas a previously observed 150 kDa fragment corresponded to the remainder of the protein. We show that both protein units are N glycosylated and phosphorylated. Focusing on the novel 40 kDa fragment, we present a homology model based on the structure of lamprey lipovitellin that includes a conserved β-barrel-like shape, with a lipophilic cavity in the interior and two insect-specific loops that have not been described before. Our data indicate that the honeybee fat body vitellogenin experiences cleavage unlike hemolymph vitellogenin, a pattern that can suggest a tissue-specific role. Our experiments advance the molecular understanding of vitellogenin, of which the multiple physiological and behavioral effects in honeybees are well established. PMID:21270306

  10. 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. PMID

  11. The N-terminus of VDAC: Structure, mutational analysis, and a potential role in regulating barrel shape.

    PubMed

    Shuvo, Sabbir R; Ferens, Fraser G; Court, Deborah A

    2016-06-01

    A novel feature of the voltage-dependent anion channel (VDAC, mitochondrial porin), is the barrel, comprising an odd number of β-strands and closed by parallel strands. Recent research has focused on the N-terminal segment, which in the available structures, resides in the lumen and is not part of the barrel. In this review, the structural data obtained from vertebrate VDAC are integrated with those from VDAC in artificial bilayers, emphasizing the array of native and tagged versions of VDAC used. The data are discussed with respect to a recent gating model (Zachariae et al. (2012) Structure 20:1-10), in which the N-terminus acts not as a gate on a stable barrel, but rather stabilizes the barrel, preventing its shift into a partially collapsed, low-conductance, closed state. Additionally, the role of the N-terminus in VDAC oligomerization, apoptosis through interactions with hexokinase and its interaction with ATP are discussed briefly. PMID:26997586

  12. The dual functions of the extreme N-terminus of TDP-43 in regulating its biological activity and inclusion formation.

    PubMed

    Zhang, Yong-Jie; Caulfield, Thomas; Xu, Ya-Fei; Gendron, Tania F; Hubbard, Jaime; Stetler, Caroline; Sasaguri, Hiroki; Whitelaw, Ena C; Cai, Shuyi; Lee, Wing Cheung; Petrucelli, Leonard

    2013-08-01

    TAR DNA-binding protein-43 (TDP-43) is the principal component of ubiquitinated inclusions in amyotrophic lateral sclerosis (ALS) and the most common pathological subtype of frontotemporal dementia-frontotemporal lobar degeneration with TDP-43-positive inclusions (FTLD-TDP). To date, the C-terminus of TDP-43, which is aggregation-prone and contains almost all ALS-associated mutations, has garnered much attention while the functions of the N-terminus of TDP-43 remain largely unknown. To bridge this gap in our knowledge, we utilized novel cell culture and computer-assisted models to evaluate which region(s) of TDP-43 regulate its folding, self-interaction, biological activity and aggregation. We determined that the extreme N-terminus of TDP-43, specifically the first 10 residues, regulates folding of TDP-43 monomers necessary for proper homodimerization and TDP-43-regulated splicing. Despite such beneficial functions, we discovered an interesting dichotomy: full-length TDP-43 aggregation, which is believed to be a pathogenic process, also requires the extreme N-terminus of TDP-43. As such, we provide new insight into the structural basis for TDP-43 function and aggregation, and we suggest that stabilization of TDP-43 homodimers, the physiologically active form of TDP-43, may be a promising therapeutic strategy for ALS and FTLD-TDP. PMID:23575225

  13. 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

  14. 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

  15. A model for the function of the bisphosphorylated heart-specific troponin-I N-terminus.

    PubMed

    Jaquet, K; Lohmann, K; Czisch, M; Holak, T; Gulati, J; Jaquet, R

    1998-08-01

    Bisphosphorylation of two adjacently located serine residues in the heart-specific N-terminus of the cTnl subunit reduces calcium affinity of the cTnC subunit. An interaction of the phosphorylation region of cTnI with acidic residues of another cTn subunit has been proposed formerly based on 31P nuclear magnetic resonance (NMR) data. A possible candidate is cTnC. Thus, an interaction model of cTnC with the bisphosphorylated cTnI N-terminus has been built using a homology model of hcTnC based on the crystal structure of tusTnC and the structure of the phosphorylation region of cTnI determined by 2D NMR. By computational search, five cluster of acidic residues of cTnC might interact with the cTnI phosphorylation region. Three sites could be excluded by 31P-NMR experiments. The two remaining sites are located in the N-terminal helix of cTnC and between calcium binding sites III and IV. Reorientation of the arginine and phosphoserine sidechains within the phosphorylation region as proposed by refined docking could explain the formerly measured changes in pKaapp values. Thus, local pKa changes might lead to the reduction of calcium affinity observed upon cTnI bisphosphorylation. PMID:9742449

  16. 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.

  17. The role of N-terminus of Plasmodium falciparum ORC1 in telomeric localization and var gene silencing

    PubMed Central

    Deshmukh, Abhijit S.; Srivastava, Sandeep; Herrmann, Susann; Gupta, Ashish; Mitra, Pallabi; Gilberger, Tim Wolf; Dhar, Suman Kumar

    2012-01-01

    Plasmodium falciparum origin recognition complex 1 (ORC1) protein has been implicated in DNA replication and silencing var gene family. However, the mechanism and the domain structure of ORC1 related to the regulation of var gene family are unknown. Here we show that the unique N-terminus of PfORC1 (PfORC1N1–238) is targeted to the nuclear periphery in vivo and this region binds to the telomeric DNA in vitro due to the presence of a leucine heptad repeats. Like PfORC1N1–238, endogenous full length ORC1, was found to be associated with sub telomeric repeat regions and promoters of various var genes. Additionally, binding and propagation of ORC1 to telomeric and subtelomeric regions was severely compromised in PfSir2 deficient parasites suggesting the dependence of endogenous ORC1 on Sir2 for var gene regulation. This feature is not previously described for Plasmodium ORC1 and contrary to yeast Saccharomyces cerevisiae where ORC function as a landing pad for Sir proteins. Interestingly, the overexpression of ORC1N1–238 compromises the binding of Sir2 at the subtelomeric loci and var gene promoters consistent with de-repression of some var genes. These results establish role of the N-terminus of PfORC1 in heterochromatin formation and regulation of var gene expression in co-ordination with Sir2 in P. falciparum. PMID:22379140

  18. 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

  19. Mechanical ventilation with positive end-expiratory pressure decreases the circulating concentrations of the N-terminus and C-terminus of the atrial natriuretic factor prohormone.

    PubMed

    Vesely, D L; Salmon, J S

    1990-01-01

    Mechanical ventilation with positive end-expiratory pressure (PEEP) decreases urine output and urinary sodium excretion. The influence of PEEP during controlled mechanical ventilation on the circulating concentrations of the N-terminus and C-terminus of the atrial natriuretic factor (ANF) prohormone which both contain natriuretic and diuretic peptides was investigated in 7 patients with acute respiratory failure. The 98 amino acid (aa) N-terminus, the midportion of the N-terminus consisting of aa 31-67 of the 126 aa ANF prohormone (i.e., pro ANF 31-67) and the C-terminus (aa 99-126; ANF) were found to be significantly (p less than 0.05; ANOVA) elevated compared to 54 healthy volunteers during acute respiratory failure prior to institution of PEEP. With institution of 10 cm of H2O of PEEP all 7 patients had a significant (p less than 0.05) decrease in the circulating concentrations of pro ANFs 1-98, 31-67 and ANF. These findings suggest that the increased thoracic pressure secondary to PEEP which reduces venous return and lowers atrial filling pressure results in a decreased release of the N-terminus and C-terminus of the ANF prohormone. This decrease in the N-terminus and C-terminus of the ANF prohormone appears to represent a physiologic mechanism for restoration of intravascular volume, secondary to decreased sodium excretion. PMID:2151585

  20. 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. PMID:25499885

  1. The N Terminus and C Terminus of Herpes Simplex Virus 1 ICP4 Cooperate To Activate Viral Gene Expression

    PubMed Central

    Wagner, Lauren M.; Lester, Jonathan T.; Sivrich, Frances L.

    2012-01-01

    Infected cell polypeptide 4 (ICP4) activates transcription from most viral promoters. Two transactivation domains, one N-terminal and one C terminal, are largely responsible for the activation functions of ICP4. A mutant ICP4 molecule lacking the C-terminal activation domain (n208) efficiently activates many early genes, whereas late genes are poorly activated, and virus growth is severely impaired. The regions within the N terminus of ICP4 (amino acids 1 to 210) that contribute to activation were investigated by analysis of deletion mutants in the presence or absence of the C-terminal activation domain. The mutants were assessed for their abilities to support viral replication and to regulate gene expression. Several deletions in regions conserved in other alphaherpesviruses resulted in impaired activation and viral growth, without affecting DNA binding. The single small deletion that had the greatest effect on activation in the absence of the C terminus corresponded to a highly conserved stretch of amino acids between 81 and 96, rendering the molecule nonfunctional. However, when the C terminus was present, the same deletion had a minimal effect on activity. The amino terminus of ICP4 was predicted to be relatively disordered compared to the DNA-binding domain and the C-terminal 500 amino acids. Moreover, the amino terminus appears to be in a relatively extended conformation as determined by the hydrodynamic properties of several mutants. The data support a model where the amino terminus is an extended and possibly flexible region of the protein, allowing it to efficiently interact with multiple transcription factors at a distance from where it is bound to DNA, thereby enabling ICP4 to function as a general activator of polymerase II transcription. The C terminus of ICP4 can compensate for some of the mutations in the N terminus, suggesting that it either specifies redundant interactions or enables the amino terminus to function more efficiently. PMID:22496239

  2. The N Terminus of Andes Virus L Protein Suppresses mRNA and Protein Expression in Mammalian Cells

    PubMed Central

    Heinemann, Patrick; Schmidt-Chanasit, Jonas

    2013-01-01

    Little is known about the structure and function of the 250-kDa L protein of hantaviruses, although it plays a central role in virus genome transcription and replication. When attempting to study Andes virus (ANDV) L protein in mammalian cells, we encountered difficulties. Even in a strong overexpression system, ANDV L protein could not be detected by immunoblotting. Deletion analysis revealed that the 534 N-terminal amino acid residues determine the low-expression phenotype. Inhibition of translation due to RNA secondary structures around the start codon, rapid proteasomal degradation, and reduced half-life time were excluded. However, ANDV L protein expression could be rescued upon mutation of the catalytic PD-E-K motif and further conserved residues of the putative endonuclease at the N terminus of the protein. In addition, wild-type ANDV L rather than expressible L mutants suppressed the level of L mRNA, as well as reporter mRNAs. Wild-type L protein also reduced the synthesis of cellular proteins in the high-molecular-weight range. Using expressible ANDV L mutants as a tool for localization studies, we show that L protein colocalizes with ANDV N and NSs but not Gc protein. A fraction of L protein also colocalized with the cellular processing (P) body component DCP1a. Overall, these data suggest that ANDV L protein possesses a highly active endonuclease at the N terminus suppressing the level of its own as well as heterologous mRNAs upon recombinant expression in mammalian cells. PMID:23576516

  3. Phosphorylation and Cellular Function of the Human Rpa2 N-Terminus in the Budding Yeast Saccharomyces cerevisiae

    PubMed Central

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

    2015-01-01

    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. PMID:25499885

  4. The N-terminus of Prp1 (Prp6/U5-102 K) is essential for spliceosome activation in vivo

    PubMed Central

    Lützelberger, Martin; Bottner, Claudia A.; Schwelnus, Wiebke; Zock-Emmenthal, Susanne; Razanau, Aleh; Käufer, Norbert F.

    2010-01-01

    The spliceosomal protein Prp1 (Prp6/U5-102 K) is necessary for the integrity of pre-catalytic spliceosomal complexes. We have identified a novel regulatory function for Prp1. Expression of mutations in the N-terminus of Prp1 leads to the accumulation of pre-catalytic spliceosomal complexes containing the five snRNAs U1, U2, U5 and U4/U6 and pre-mRNAs. The mutations in the N-terminus, which prevent splicing to occur, include in vitro and in vivo identified phosphorylation sites of Prp4 kinase. These sites are highly conserved in the human ortholog U5-102 K. The results presented here demonstrate that structural integrity of the N-terminus is required to mediate a splicing event, but is not necessary for the assembly of spliceosomes. PMID:20007600

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. Native N-terminus nitrophorin 2 from the kissing bug: similarities to and differences from NP2(D1A).

    PubMed

    Berry, Robert E; Muthu, Dhanasekaran; Shokhireva, Tatiana K; Garrett, Sarah A; Zhang, Hongjun; Walker, F Ann

    2012-09-01

    The first amino acid of mature native nitrophorin 2 is aspartic acid, and when expressed in E. coli, the wild-type gene of the mature protein retains the methionine-0, which is produced by translation of the start codon. This form of NP2, (M0)NP2, has been found to have different properties from its D1A mutant, for which the Met0 is cleaved by the methionine aminopeptidase of E. coli (R. E. Berry, T. K. Shokhireva, I. Filippov, M. N. Shokhirev, H. Zhang, F. A. Walker, Biochemistry 2007, 46, 6830). Native N-terminus nitrophorin 2 ((ΔM0)NP2) has been prepared by employing periplasmic expression of NP2 in E. coli using the pelB leader sequence from Erwinia carotovora, which is present in the pET-26b expression plasmid (Novagen). This paper details the similarities and differences between the three different N-terminal forms of nitrophorin 2, (M0)NP2, NP2(D1A), and (ΔM0)NP2. It is found that the NMR spectra of high- and low-spin (ΔM0)NP2 are essentially identical to those of NP2(D1A), but the rate and equilibrium constants for histamine and NO dissociation/association of the two are different. PMID:22976966

  11. The biliverdin chromophore binds covalently to a conserved cysteine residue in the N-terminus of Agrobacterium phytochrome Agp1.

    PubMed

    Lamparter, Tilman; Carrascal, Montserrat; Michael, Norbert; Martinez, Enriqueta; Rottwinkel, Gregor; Abian, Joaquin

    2004-03-30

    Phytochromes are widely distributed biliprotein photoreceptors. Typically, the chromophore becomes covalently linked to the protein during an autocatalytic lyase reaction. Plant and cyanobacterial phytochromes incorporate bilins with a ring A ethylidene side chain, whereas other bacterial phytochromes utilize biliverdin as chromophore, which has a vinyl ring A side chain. For Agrobacterium phytochrome Agp1, site-directed mutagenesis provided evidence that biliverdin is bound to cysteine 20. This cysteine is highly conserved within bacterial homologues, but its role as attachment site has as yet not been proven. We therefore performed mass spectrometry studies on proteolytic holopeptide fragments. For that purpose, an Agp1 expression vector was re-engineered to produce a protein with an N-terminal affinity tag. Following proteolysis, the chromophore co-purified with a ca. 5 kDa fragment during affinity chromatography, showing that the attachment site is located close to the N-terminus. Mass spectrometry analyses performed with the purified chromopeptide confirmed the role of the cysteine 20 as biliverdin attachment site. We also analyzed the role of the highly conserved histidine 250 by site-directed mutagenesis. The homologous amino acid plays an important but yet undefined role in plant phytochromes and has been proposed as chromophore attachment site of Deinococcus phytochrome. We found that in Agp1, this amino acid is dispensable for covalent attachment, but required for tight chromophore-protein interaction. PMID:15035636

  12. 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

  13. Regulation of Estrogen Receptor α N-Terminus Conformation and Function by Peptidyl Prolyl Isomerase Pin1

    PubMed Central

    Rajbhandari, Prashant; Finn, Greg; Solodin, Natalia M.; Singarapu, Kiran K.; Sahu, Sarata C.; Markley, John L.; Kadunc, Kelley J.; Ellison-Zelski, Stephanie J.; Kariagina, Anastasia; Haslam, Sandra Z.; Lu, Kun Ping

    2012-01-01

    Estrogen receptor alpha (ERα), a key driver of growth in the majority of breast cancers, contains an unstructured transactivation domain (AF1) in its N terminus that is a convergence point for growth factor and hormonal activation. This domain is controlled by phosphorylation, but how phosphorylation impacts AF1 structure and function is unclear. We found that serine 118 (S118) phosphorylation of the ERα AF1 region in response to estrogen (agonist), tamoxifen (antagonist), and growth factors results in recruitment of the peptidyl prolyl cis/trans isomerase Pin1. Phosphorylation of S118 is critical for Pin1 binding, and mutation of S118 to alanine prevents this association. Importantly, Pin1 isomerizes the serine118-proline119 bond from a cis to trans isomer, with a concomitant increase in AF1 transcriptional activity. Pin1 overexpression promotes ligand-independent and tamoxifen-inducible activity of ERα and growth of tamoxifen-resistant breast cancer cells. Pin1 expression correlates with proliferation in ERα-positive rat mammary tumors. These results establish phosphorylation-coupled proline isomerization as a mechanism modulating AF1 functional activity and provide insight into the role of a conformational switch in the functional regulation of the intrinsically disordered transactivation domain of ERα. PMID:22064478

  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. 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

  16. 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

  17. Crystal structures of tubulin acetyltransferase reveal a conserved catalytic core and the plasticity of the essential N terminus.

    PubMed

    Kormendi, Vasilisa; Szyk, Agnieszka; Piszczek, Grzegorz; Roll-Mecak, Antonina

    2012-12-01

    Tubulin acetyltransferase (TAT) acetylates Lys-40 of α-tubulin in the microtubule lumen. TAT is inefficient, and its activity is enhanced when tubulin is incorporated in microtubules. Acetylation is associated with stable microtubules and regulates the binding of microtubule motors and associated proteins. TAT is important in neuronal polarity and mechanosensation, and decreased tubulin acetylation levels are associated with axonal transport defects and neurodegeneration. We present the first structure of TAT in complex with acetyl-CoA (Ac-CoA) at 2.7 Å resolution. The structure reveals a conserved stable catalytic core shared with other GCN5 superfamily acetyltransferases consisting of a central β-sheet flanked by α-helices and a C-terminal β-hairpin unique to TAT. Structure-guided mutagenesis establishes the molecular determinants for Ac-CoA and tubulin substrate recognition. The wild-type TAT construct is a monomer in solution. We identify a metastable interface between the conserved core and N-terminal domain that modulates the oligomerization of TAT in solution and is essential for activity. The 2.45 Å resolution structure of an inactive TAT construct with an active site point mutation near this interface reveals a domain-swapped dimer in which the functionally essential N terminus shows evidence of marked structural plasticity. The sequence segment corresponding to this structurally plastic region in TAT has been implicated in substrate recognition in other GCN5 superfamily acetyltransferases. Our structures provide a rational platform for the mechanistic dissection of TAT activity and the design of TAT inhibitors with therapeutic potential in neuronal regeneration. PMID:23105108

  18. 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

  19. 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

  20. Differential activation of yeast adenylyl cyclase by Ras1 and Ras2 depends on the conserved N terminus.

    PubMed

    Hurwitz, N; Segal, M; Marbach, I; Levitzki, A

    1995-11-21

    Although both Ras1 and Ras2 activate adenylyl cyclase in yeast, a number of differences can be observed regarding their function in the cAMP pathway. To explore the relative contribution of conserved and variable domains in determining these differences, chimeric RAS1-RAS2 or RAS2-RAS1 genes were constructed by swapping the sequences encoding the variable C-terminal domains. These constructs were expressed in a cdc25ts ras1 ras2 strain. Biochemical data show that the difference in efficacy of adenylyl cyclase activation between the two Ras proteins resides in the highly conserved N-terminal domain. This finding is supported by the observation that Ras2 delta, in which the C-terminal domain of Ras2 has been deleted, is a more potent activator of the yeast adenylyl cyclase than Ras1 delta, in which the C-terminal domain of Ras1 has been deleted. These observations suggest that amino acid residues other than the highly conserved residues of the effector domain within the N terminus may determine the efficiency of functional interaction with adenylyl cyclase. Similar levels of intracellular cAMP were found in Ras1, Ras1-Ras2, Ras1 delta, Ras2, and Ras2-Ras1 strains throughout the growth curve. This was found to result from the higher expression of Ras1 and Ras1-Ras2, which compensate for their lower efficacy in activating adenylyl cyclase. These results suggest that the difference between the Ras1 and the Ras2 phenotype is not due to their different efficacy in activating the cAMP pathway and that the divergent C-terminal domains are responsible for these differences, through interaction with other regulatory elements. PMID:7479926

  1. Effects of residue 5-point mutation and N-terminus hydrophobic residues on temporin-SHc physicochemical and biological properties.

    PubMed

    Abbassi, Feten; Piesse, Christophe; Foulon, Thierry; Nicolas, Pierre; Ladram, Ali

    2014-09-01

    Temporin-SHc (FLSHIAGFLSNLFamide) first isolated from skin extraction of the Tunisian frog Pelophylax saharica, which shows potent antimicrobial activity against Gram-positive bacteria and is highly active against yeasts and fungi without hemolytic activity at antimicrobial concentrations. The peptide adopts well-defined α-helical conformation when bound to SDS micelles. In this study, we explored the effects of residue at position 5 and the N-terminus hydrophobic character on the hydrophilic/polar face of temp-SHc, on its biological activities (antimicrobial and hemolytic) and biophysical properties (hydrophobicity, amphipathicity and helicity). Antibacterial and hemolytic properties of temporin-SHc derivatives depend strongly on physicochemical properties. Therefore, slight decreasing amphipathicity together with hydrophobicity and helicity by the substitution Ile(5) → Leu decreased antimicrobial potency approximately twofold without changing of hemolytic activity. It is noteworthy that a conservative amino acid substitution decreases the antimicrobial activity, underlining the differences between Leu/Ile side chains insertion into the lipid bilayer. While the modification of N-terminal hydrophobic character by four residue inversion decreased amphipathicity (twofold) of (4-1)L5temp-SHc and resulted in an increase in antibacterial activity against E. coli, E. faecalis and C. parapsilosis of at least fourfold, its therapeutic potential is limited by its drastic increase of hemolysis (LC₅₀ = 2 μM). We found that the percentage of helicity of temp-SHc analog is directly correlated to its hemolytic activity. Last, the hydrophobic N-terminal character is an important determinant of antimicrobial activity. PMID:24842084

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

    PubMed

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

    2015-05-01

    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

  3. 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

  4. Determinant for beta-subunit regulation in high-conductance voltage-activated and Ca(2+)-sensitive K+ channels: an additional transmembrane region at the N terminus.

    PubMed

    Wallner, M; Meera, P; Toro, L

    1996-12-10

    The pore-forming alpha subunit of large conductance voltage- and Ca(2+)-sensitive K (MaxiK) channels is regulated by a beta subunit that has two membrane-spanning regions separated by an extracellular loop. To investigate the structural determinants in the pore-forming alpha subunit necessary for beta-subunit modulation, we made chimeric constructs between a human MaxiK channel and the Drosophila homologue, which we show is insensitive to beta-subunit modulation, and analyzed the topology of the alpha subunit. A comparison of multiple sequence alignments with hydrophobicity plots revealed that MaxiK channel alpha subunits have a unique hydrophobic segment (S0) at the N terminus. This segment is in addition to the six putative transmembrane segments (S1-S6) usually found in voltage-dependent ion channels. The transmembrane nature of this unique S0 region was demonstrated by in vitro translation experiments. Moreover, normal functional expression of signal sequence fusions and in vitro N-linked glycosylation experiments indicate that S0 leads to an exoplasmic N terminus. Therefore, we propose a new model where MaxiK channels have a seventh transmembrane segment at the N terminus (S0). Chimeric exchange of 41 N-terminal amino acids, including S0, from the human MaxiK channel to the Drosophila homologue transfers beta-subunit regulation to the otherwise unresponsive Drosophila channel. Both the unique S0 region and the exoplasmic N terminus are necessary for this gain of function. PMID:8962157

  5. Lost in translation: translational interference from a recurrent mutation in exon 1 of MECP2

    PubMed Central

    Saxena, A; de Lagarde, D; Leonard, H; Williamson, S L; Vasudevan, V; Christodoulou, J; Thompson, E; MacLeod, P; Ravine, D

    2006-01-01

    Background Rett syndrome (RTT) is an X linked neuro‐developmental disorder affecting mostly girls. Mutations in the coding region of MECP2 are found in 80% of classic RTT patients. Until recently, the region encoding MECP2 was believed to comprise exons 2, 3, and 4 with the ATG start site located at the end of exon 2 (MeCP2_e2). Methods Recent reports of another mRNA transcript transcribed from exon 1 (MeCP2_e1) prompted us to screen exon 1 among RNA samples from 20 females with classic or atypical RTT. Results A previously reported 11 base pair deletion in exon 1 was detected in one subject with a milder phenotype. Although RNA expression for both protein isoforms was detected from the mutant allele, evaluation of MeCP2 protein in uncultured patient lymphocytes by immunocytochemistry revealed that MeCP2 protein production was restricted to only 74–76% of lymphocytes. X chromosome inactivation studies of genomic DNA revealed similar XCI ratios at the HUMARA locus (73:27 with HpaII and 74:26 with McrBC). We have demonstrated that translation but not transcription of the MeCP2_e2 isoform is ablated by the 11 nucleotide deletion, 103 nucleotides upstream of the e2 translation start site. Conclusions These findings reveal that nucleotides within the deleted sequence in the 5′‐UTR of the MeCP2_e2 transcript, while not required for transcription, are essential for translation. PMID:16155192

  6. Novel alleles of the transforming growth factor β-1 regulatory region and exon 1.

    PubMed

    Arrieta-Bolaños, E; Madrigal, J A; Shaw, B E

    2015-06-01

    Transforming growth factor β-1, encoded by the TGFB1 gene, is a cytokine that plays a central role in many physiologic and pathogenic processes with pleiotropic effects. Regulatory activity for this gene has been shown for 3.0 kb between positions -2665 and +423 from its translational start site. At least 17 TGFB1 regulatory region and exon 1 alleles have been defined on the basis of 18 polymorphic sites. Polymorphisms in TGFB1's regulatory region have been associated with differential levels of expression of this cytokine and to genetic risk in cancer and transplantation. In this report, we present 19 novel TGFB1 regulatory region and exon 1 alleles: p018-p036. Amplification of TGFB1's regulatory region was performed with an in-house protocol, and novel alleles were defined by either allele-specific amplification and/or molecular cloning of the amplicons, followed by sequencing in isolation. Three of these novel alleles (p018, p019, and p020) are shown to be formed by novel combinations of the aforementioned known polymorphic positions. Another 16 novel alleles are shown to carry additional known and unknown single-nucleotide polymorphisms. Polymorphism in TGFB1's regulatory region could have an impact on important processes, including embryogenesis, hematopoiesis, carcinogenesis, angiogenesis, fibrosis, immune responses, and transplantation, making its characterization necessary. PMID:25808355

  7. α-Synuclein and huntingtin exon 1 amyloid fibrils bind laterally to the cellular membrane

    PubMed Central

    Monsellier, Elodie; Bousset, Luc; Melki, Ronald

    2016-01-01

    Fibrillar aggregates involved in neurodegenerative diseases have the ability to spread from one cell to another in a prion-like manner. The underlying molecular mechanisms, in particular the binding mode of the fibrils to cell membranes, are poorly understood. In this work we decipher the modality by which aggregates bind to the cellular membrane, one of the obligatory steps of the propagation cycle. By characterizing the binding properties of aggregates made of α-synuclein or huntingtin exon 1 protein displaying similar composition and structure but different lengths to mammalian cells we demonstrate that in both cases aggregates bind laterally to the cellular membrane, with aggregates extremities displaying little or no role in membrane binding. Lateral binding to artificial liposomes was also observed by transmission electron microscopy. In addition we show that although α-synuclein and huntingtin exon 1 fibrils bind both laterally to the cellular membrane, their mechanisms of interaction differ. Our findings have important implications for the development of future therapeutic tools that aim to block protein aggregates propagation in the brain. PMID:26757959

  8. TDP-43 N terminus encodes a novel ubiquitin-like fold and its unfolded form in equilibrium that can be shifted by binding to ssDNA.

    PubMed

    Qin, Haina; Lim, Liang-Zhong; Wei, Yuanyuan; Song, Jianxing

    2014-12-30

    Transactivation response element (TAR) DNA-binding protein 43 (TDP-43) is the principal component of ubiquitinated inclusions characteristic of most forms of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia-frontotemporal lobar degeneration with TDP-43-positive inclusions (FTLD-TDP), as well as an increasing spectrum of other neurodegenerative diseases. Previous structural and functional studies on TDP-43 have been mostly focused on its recognized domains. Very recently, however, its extreme N terminus was identified to be a double-edged sword indispensable for both physiology and proteinopathy, but thus far its structure remains unknown due to the severe aggregation. Here as facilitated by our previous discovery that protein aggregation can be significantly minimized by reducing salt concentrations, by circular dichroism and NMR spectroscopy we revealed that the TDP-43 N terminus encodes a well-folded structure in concentration-dependent equilibrium with its unfolded form. Despite previous failure in detecting any sequence homology to ubiquitin, the folded state was determined to adopt a novel ubiquitin-like fold by the CS-Rosetta program with NMR chemical shifts and 78 unambiguous long-range nuclear Overhauser effect (NOE) constraints. Remarkably, this ubiquitin-like fold could bind ssDNA, and the binding shifted the conformational equilibrium toward reducing the unfolded population. To the best of our knowledge, the TDP-43 N terminus represents the first ubiquitin-like fold capable of directly binding nucleic acid. Our results provide a molecular mechanism rationalizing the functional dichotomy of TDP-43 and might also shed light on the formation and dynamics of cellular ribonucleoprotein granules, which have been recently linked to ALS pathogenesis. As a consequence, one therapeutic strategy for TDP-43-causing diseases might be to stabilize its ubiquitin-like fold by ssDNA or designed molecules. PMID:25503365

  9. The long N-terminus of the human monocarboxylate transporter 8 is a target of ubiquitin-dependent proteasomal degradation which regulates protein expression and oligomerization capacity.

    PubMed

    Zwanziger, Denise; Schmidt, Mathias; Fischer, Jana; Kleinau, Gunnar; Braun, Doreen; Schweizer, Ulrich; Moeller, Lars Christian; Biebermann, Heike; Fuehrer, Dagmar

    2016-10-15

    Monocarboxylate transporter 8 (MCT8) equilibrates thyroid hormones between the extra- and the intracellular sides. MCT8 exists either with a short or a long N-terminus, but potential functional differences between both variants are yet not known. We, therefore, generated MCT8 constructs which are different in N-terminal length: MCT8(1-613), MCT8(25-613), MCT8(49-613) and MCT8(75-613). The M75G substitution prevents translation of MCT8(75-613) and ensures expression of full-length MCT8 protein. The K56G substitution was made to prevent ubiquitinylation. Cell-surface expression, localization and proteasomal degradation were investigated using C-terminally GFP-tagged MCT8 constructs (HEK293 and MDCK1 cells) and oligomerization capacity was determined using N-terminally HA- and C-terminally FLAG-tagged MCT8 constructs (COS7 cells). MCT8(1-613)-GFP showed a lower protein expression than the shorter MCT8(75-613)-GFP protein. The proteasome inhibitor lactacystin increased MCT8(1-613)-GFP protein amount, suggesting proteasomal degradation of MCT8 with the long N-terminus. Ubiquitin conjugation of MCT8(1-613)-GFP was found by immuno-precipitation. A diminished ubiquitin conjugation caused by K56G substitution resulted in increased MCT8(1-613)-GFP protein expression. Sandwich ELISA was performed to investigate if the bands at higher molecular weight observed in Western blot analysis are due to MCT8 oligomerization, which was indeed shown. Our data imply a role of the long N-terminus of MCT8 as target of ubiquitin-dependent proteasomal degradation affecting MCT8 amount and subsequently oligomerization capacity. PMID:27222294

  10. Barbiturates require the N terminus and first transmembrane domain of the delta subunit for enhancement of alpha1beta3delta GABAA receptor currents.

    PubMed

    Feng, Hua-Jun; Macdonald, Robert L

    2010-07-30

    GABA(A) receptors are composed predominantly of alphabetagamma receptors, which mediate primarily synaptic inhibition, and alphabetadelta receptors, which mediate primarily extrasynaptic inhibition. At saturating GABA concentrations, the barbiturate pentobarbital substantially increased the amplitude and desensitization of the alpha1beta3delta receptor but not the alpha1beta3gamma2L receptor currents. To explore the structural domains of the delta subunit that are involved in pentobarbital potentiation and increased desensitization of alpha1beta3delta currents, chimeric cDNAs were constructed by progressive replacement of gamma2L subunit sequence with a delta subunit sequence or a delta subunit sequence with a gamma2L subunit sequence, and HEK293T cells were co-transfected with alpha1 and beta3 subunits or alpha1 and beta3 subunits and a gamma2L, delta, or chimeric subunit. Currents evoked by a saturating concentration of GABA or by co-application of GABA and pentobarbital were recorded using the patch clamp technique. By comparing the extent of enhancement and changes in kinetic properties produced by pentobarbital among chimeric and wild type receptors, we concluded that although potentiation of alpha1beta3delta currents by pentobarbital required the delta subunit sequence from the N terminus to proline 241 in the first transmembrane domain (M1), increasing desensitization of alpha1beta3delta currents required a delta subunit sequence from the N terminus to isoleucine 235 in M1. These findings suggest that the delta subunit N terminus and N-terminal portion of the M1 domain are, at least in part, involved in transduction of the allosteric effect of pentobarbital to enhance alpha1beta3delta currents and that this effect involves a distinct but overlapping structural domain from that involved in altering desensitization. PMID:20525684

  11. Insight into the structural and biological relevance of the T/R transition of the N-terminus of the B-chain in human insulin.

    PubMed

    Kosinová, Lucie; Veverka, Václav; Novotná, Pavlína; Collinsová, Michaela; Urbanová, Marie; Moody, Nicholas R; Turkenburg, Johan P; Jiráček, Jiří; Brzozowski, Andrzej M; Žáková, Lenka

    2014-06-01

    The N-terminus of the B-chain of insulin may adopt two alternative conformations designated as the T- and R-states. Despite the recent structural insight into insulin-insulin receptor (IR) complexes, the physiological relevance of the T/R transition is still unclear. Hence, this study focused on the rational design, synthesis, and characterization of human insulin analogues structurally locked in expected R- or T-states. Sites B3, B5, and B8, capable of affecting the conformation of the N-terminus of the B-chain, were subjects of rational substitutions with amino acids with specific allowed and disallowed dihedral φ and ψ main-chain angles. α-Aminoisobutyric acid was systematically incorporated into positions B3, B5, and B8 for stabilization of the R-state, and N-methylalanine and d-proline amino acids were introduced at position B8 for stabilization of the T-state. IR affinities of the analogues were compared and correlated with their T/R transition ability and analyzed against their crystal and nuclear magnetic resonance structures. Our data revealed that (i) the T-like state is indeed important for the folding efficiency of (pro)insulin, (ii) the R-state is most probably incompatible with an active form of insulin, (iii) the R-state cannot be induced or stabilized by a single substitution at a specific site, and (iv) the B1-B8 segment is capable of folding into a variety of low-affinity T-like states. Therefore, we conclude that the active conformation of the N-terminus of the B-chain must be different from the "classical" T-state and that a substantial flexibility of the B1-B8 segment, where GlyB8 plays a key role, is a crucial prerequisite for an efficient insulin-IR interaction. PMID:24819248

  12. Insight into the Structural and Biological Relevance of the T/R Transition of the N-Terminus of the B-Chain in Human Insulin

    PubMed Central

    2014-01-01

    The N-terminus of the B-chain of insulin may adopt two alternative conformations designated as the T- and R-states. Despite the recent structural insight into insulin–insulin receptor (IR) complexes, the physiological relevance of the T/R transition is still unclear. Hence, this study focused on the rational design, synthesis, and characterization of human insulin analogues structurally locked in expected R- or T-states. Sites B3, B5, and B8, capable of affecting the conformation of the N-terminus of the B-chain, were subjects of rational substitutions with amino acids with specific allowed and disallowed dihedral φ and ψ main-chain angles. α-Aminoisobutyric acid was systematically incorporated into positions B3, B5, and B8 for stabilization of the R-state, and N-methylalanine and d-proline amino acids were introduced at position B8 for stabilization of the T-state. IR affinities of the analogues were compared and correlated with their T/R transition ability and analyzed against their crystal and nuclear magnetic resonance structures. Our data revealed that (i) the T-like state is indeed important for the folding efficiency of (pro)insulin, (ii) the R-state is most probably incompatible with an active form of insulin, (iii) the R-state cannot be induced or stabilized by a single substitution at a specific site, and (iv) the B1–B8 segment is capable of folding into a variety of low-affinity T-like states. Therefore, we conclude that the active conformation of the N-terminus of the B-chain must be different from the “classical” T-state and that a substantial flexibility of the B1–B8 segment, where GlyB8 plays a key role, is a crucial prerequisite for an efficient insulin–IR interaction. PMID:24819248

  13. Immunochemical detection of proteins related to the human c-myc exon 1.

    PubMed Central

    Gazin, C; Rigolet, M; Briand, J P; Van Regenmortel, M H; Galibert, F

    1986-01-01

    Published sequence data of the human c-myc gene indicate the presence of a coding capacity for a polypeptide of 188 residues within the first exon. Using antibodies raised against five synthetic peptides corresponding to different non-over-lapping parts of this polypeptide, two proteins of 32 kd and 58 kd antigenically related to the synthetic peptides have been detected in extracts of human cells. The confidence of this detection has been reinforced by showing that epitopes corresponding to different peptides were indeed located on the same molecule and that the 58 kd protein appears to be a dimeric form of the 32 kd protein. That these proteins originate from the first exon was indicated by: hybrid-arrested translation experiments followed by immunodetection of the translation products; in vitro translation of messenger RNA derived from cloned exon 1 by SP6 polymerase transcription. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. PMID:2430795

  14. Anionic Phospholipid Interactions of the Prion Protein N Terminus Are Minimally Perturbing and Not Driven Solely by the Octapeptide Repeat Domain*

    PubMed Central

    Boland, Martin P.; Hatty, Claire R.; Separovic, Frances; Hill, Andrew F.; Tew, Deborah J.; Barnham, Kevin J.; Haigh, Cathryn L.; James, Michael; Masters, Colin L.; Collins, Steven J.

    2010-01-01

    Although the N terminus of the prion protein (PrPC) has been shown to directly associate with lipid membranes, the precise determinants, biophysical basis, and functional implications of such binding, particularly in relation to endogenously occurring fragments, are unresolved. To better understand these issues, we studied a range of synthetic peptides: specifically those equating to the N1 (residues 23–110) and N2 (23–89) fragments derived from constitutive processing of PrPC and including those representing arbitrarily defined component domains of the N terminus of mouse prion protein. Utilizing more physiologically relevant large unilamellar vesicles, fluorescence studies at synaptosomal pH (7.4) showed absent binding of all peptides to lipids containing the zwitterionic headgroup phosphatidylcholine and mixtures containing the anionic headgroups phosphatidylglycerol or phosphatidylserine. At pH 5, typical of early endosomes, quartz crystal microbalance with dissipation showed the highest affinity binding occurred with N1 and N2, selective for anionic lipid species. Of particular note, the absence of binding by individual peptides representing component domains underscored the importance of the combination of the octapeptide repeat and the N-terminal polybasic regions for effective membrane interaction. In addition, using quartz crystal microbalance with dissipation and solid-state NMR, we characterized for the first time that both N1 and N2 deeply insert into the lipid bilayer with minimal disruption. Potential functional implications related to cellular stress responses are discussed. PMID:20679345

  15. 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.

  16. 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. PMID:24655510

  17. Exploring the Structure of the 100 Amino-Acid Residue Long N-Terminus of the Plant Antenna Protein CP29

    PubMed Central

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

    2014-01-01

    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. PMID:24655510

  18. Peptide vaccine against canine parvovirus: identification of two neutralization subsites in the N terminus of VP2 and optimization of the amino acid sequence.

    PubMed

    Casal, J I; Langeveld, J P; Cortés, E; Schaaper, W W; van Dijk, E; Vela, C; Kamstrup, S; Meloen, R H

    1995-11-01

    The N-terminal domain of the major capsid protein VP2 of canine parvovirus was shown to be an excellent target for development of a synthetic peptide vaccine, but detailed information about number of epitopes, optimal length, sequence choice, and site of coupling to the carrier protein was lacking. Therefore, several overlapping peptides based on this N terminus were synthesized to establish conditions for optimal and reproducible induction of neutralizing antibodies in rabbits. The specificity and neutralizing ability of the antibody response for these peptides were determined. Within the N-terminal 23 residues of VP2, two subsites able to induce neutralizing antibodies and which overlapped by only two glycine residues at positions 10 and 11 could be discriminated. The shortest sequence sufficient for neutralization induction was nine residues. Peptides longer than 13 residues consistently induced neutralization, provided that their N termini were located between positions 1 and 11 of VP2. The orientation of the peptides at the carrier protein was also of importance, being more effective when coupled through the N terminus than through the C terminus to keyhole limpet hemocyanin. The results suggest that the presence of amino acid residues 2 to 21 (and probably 3 to 17) of VP2 in a single peptide is preferable for a synthetic peptide vaccine. PMID:7474152

  19. The N-terminus zinc finger domain of Xenopus SIP1 is important for neural induction, but not for suppression of Xbra expression.

    PubMed

    Nitta, Kazuhiro R; Takahashi, Shuji; Haramoto, Yoshikazu; Fukuda, Masakazu; Tanegashima, Kousuke; Onuma, Yasuko; Asashima, Makoto

    2007-01-01

    Smad-interacting protein-1 (SIP1), also known as deltaEF2, ZEB2 and zfhx1b, is essential for the formation of the neural tube and the somites. Overexpression of Xenopus SIP1 causes ectopic neural induction via inhibition of bone morphogenetic protein (BMP) signaling and inhibition of Xbra expression. Here, we report the functional analyses of 4 domain-deletion mutants of XSIP1. Deletion of the N-terminus zinc finger domain suppressed neural induction and BMP inhibition, but these were not affected by deletion of the other domains (the Smad binding domain, the DNA-binding homeodomain together with the CtBP binding site and the C-terminus zinc finger). Therefore SIP1 does not inhibit BMP signaling by binding to Smad proteins. In contrast, all of the deletion constructs inhibited Xbra expression. These results suggest that the N-terminus zinc finger domain of XSIP1 has an important role in neural induction and that Xbra suppression occurs via a mechanism separate from the neural inducing activity. PMID:17554684

  20. Characterization of 5' promoter and exon 1-3 polymorphism of the RAET1E gene.

    PubMed

    Cox, Steven T; Pearson, Hayley; Laza-Briviesca, Raquel; Pesoa, Susanna; Vullo, Carlos; Madrigal, J Alejandro; Saudemont, Aurore

    2016-01-01

    NKG2D is an activating receptor utilized by natural killer (NK) cells that recognizes upregulated ligands on infected, tumorigenic and damaged cells, leading to their cytolysis. However, the NKG2D ligand (NKG2DL) system is very complex with eight known gene loci encoding slightly different molecules. Furthermore, most NKG2DL gene loci such as MICA and MICB are highly polymorphic with potential for functional differences. NKG2DL expression on tumors varies depending on the malignancy and tumors can also release soluble NKG2DL that exert anergic effects on NK cells when engagement with NKG2D occurs, allowing escape from NK cell immunosurveillance. We carried out RAET1E typing of IHW cell line DNA, including a 580 bp proximal promoter fragment and exons 1-3 identifying 13 of 15 known RAET1E alleles. We determined 7 polymorphisms within the promoter region, including 2 already known that contributed to 9 promoter types. RAET1E alleles with variability in the extracellular region also differed with respect to promoter type and one allele, RAET1E(∗)003, associated with 5 promoter types. We then identified putative transcription factor binding sites for RAET1E, and found 5 of the 7 promoter polymorphisms may disrupt these sites, abrogating binding of transcription factors and varying the potential level of expression. PMID:26519211

  1. Rapid molecular diagnosis of the Gilbert's syndrome-associated exon 1 mutation within the UGT1A1 gene.

    PubMed

    Hsieh, T-Y; Shiu, T-Y; Chu, N-F; Chao, T-Y; Chu, H-C; Chang, W-K; Chao, Y-C; Huang, H-H

    2014-01-01

    Gilbert's syndrome is suspected in patients with unconjugated hyperbilirubinemia caused by decreased activity of the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene in the absence of abnormal liver function and hemolysis. The major genetic variants underlying Gilbert's syndrome are TATA-box repeats of the promoter region and exon 1 G211A of the coding region, particularly in Asians. The efficacy of DNA melting curve analysis, however, has not been established for the G211A mutation. For rapid and accurate molecular diagnosis of Gilbert's syndrome, DNA melting curve analysis was evaluated for its genotyping capability not only for TATA-box repeats of the UGT1A1 promoter, but also for G211A of UGT1A1 exon 1. TA repeats within the TATA-box sequence and the exon 1 G211A mutation of the UGT1A1 gene were analyzed by DNA melting curve analysis. To evaluate the assay reliability, direct sequencing or polyacrylamide gel electrophoresis was used as a comparative method. All homozygous and heterozygous polymorphisms of A(TA)7TAA within the TATA-box allele and of exon 1 G211A mutants of the UGT1A1 gene were successfully identified with DNA melting curve analysis. DNA melting curve analysis is, therefore, an effective molecular method for the rapid diagnosis of Gilbert's syndrome, as it detects not only TATA-box polymorphisms but also the exon 1 G211A mutation located within the UGT1A1 gene. PMID:24615032

  2. 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

  3. Cauliflower mosaic virus gene VI product N-terminus contains regions involved in resistance-breakage, self-association and interactions with movement protein

    PubMed Central

    Hapiak, Michael; Li, Yongzhong; Agama, Keli; Swade, Shaddy; Okenka, Genevieve; Falk, Jessica; Khandekar, Sushant; Raikhy, Gaurav; Anderson, Alisha; Pollock, Justin; Zellner, Wendy; Schoelz, James; Leisner, Scott M.

    2008-01-01

    Cauliflower mosaic virus (CaMV) gene VI encodes a multifunctional protein (P6) involved in the translation of viral RNA, the formation of inclusion bodies, and the determination of host range. Arabidopsis thaliana ecotype Tsu-0 prevents the systemic spread of most CaMV isolates, including CM1841. However, CaMV isolate W260 overcomes this resistance. In this paper, the N-terminal 110 amino acids of P6 (termed D1) were identified as the resistance-breaking region. D1 also bound full-length P6. Furthermore, binding of W260 D1 to P6 induced higher β-galactosidase activity and better leucine-independent growth in the yeast two-hybrid system than its CM1841 counterpart. Thus, W260 may evade Tsu-0 resistance by mediating P6 self-association in a manner different from that of CM1841. Because Tsu-0 resistance prevents virus movement, interaction of P6 with P1 (CaMV movement protein) was investigated. Both yeast two-hybrid analyses and maltose-binding protein pull-down experiments show that P6 interacts with P1. Although neither half of P1 interacts with P6, the N-terminus of P6 binds P1. Interestingly, D1 by itself does not interact with P1, indicating that different portions of the P6 N-terminus are involved in different activities. The P1-P6 interactions suggest a role for P6 in virus transport, possibly by regulating P1 tubule formation or the assembly of movement complexes. PMID:18851998

  4. Conserved Residues in the N Terminus of Lipin-1 Are Required for Binding to Protein Phosphatase-1c, Nuclear Translocation, and Phosphatidate Phosphatase Activity*

    PubMed Central

    Kok, Bernard P. C.; Skene-Arnold, Tamara D.; Ling, Ji; Benesch, Matthew G. K.; Dewald, Jay; Harris, Thurl E.; Holmes, Charles F. B.; Brindley, David N.

    2014-01-01

    Lipin-1 is a phosphatidate phosphatase in glycerolipid biosynthesis and signal transduction. It also serves as a transcriptional co-regulator to control lipid metabolism and adipogenesis. These functions are controlled partly by its subcellular distribution. Hyperphosphorylated lipin-1 remains sequestered in the cytosol, whereas hypophosphorylated lipin-1 translocates to the endoplasmic reticulum and nucleus. The serine/threonine protein phosphatase-1 catalytic subunit (PP-1c) is a major protein dephosphorylation enzyme. Its activity is controlled by interactions with different regulatory proteins, many of which contain conserved RVXF binding motifs. We found that lipin-1 binds to PP-1cγ through a similar HVRF binding motif. This interaction depends on Mg2+ or Mn2+ and is competitively inhibited by (R/H)VXF-containing peptides. Mutating the HVRF motif in the highly conserved N terminus of lipin-1 greatly decreases PP-1cγ interaction. Moreover, mutations of other residues in the N terminus of lipin-1 also modulate PP-1cγ binding. PP-1cγ binds poorly to a phosphomimetic mutant of lipin-1 and binds well to the non-phosphorylatable lipin-1 mutant. This indicates that lipin-1 is dephosphorylated before PP-1cγ binds to its HVRF motif. Importantly, mutating the HVRF motif also abrogates the nuclear translocation and phosphatidate phosphatase activity of lipin-1. In conclusion, we provide novel evidence of the importance of the lipin-1 N-terminal domain for its catalytic activity, nuclear localization, and binding to PP-1cγ. PMID:24558042

  5. 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

  6. The N terminus of SKAP55 enables T cell adhesion to TCR and integrin ligands via distinct mechanisms

    PubMed Central

    Ophir, Michael J.; Liu, Beiyun C.

    2013-01-01

    The T cell receptor (TCR) triggers the assembly of “SLP-76 microclusters,” which mediate signals required for T cell activation. In addition to regulating integrin activation, we show that Src kinase–associated phosphoprotein of 55 kD (SKAP55) is required for microcluster persistence and movement, junctional stabilization, and integrin-independent adhesion via the TCR. These functions require the dimerization of SKAP55 and its interaction with the adaptor adhesion and degranulation-promoting adaptor protein (ADAP). A “tandem dimer” containing two ADAP-binding SKAP55 Src homology 3 (SH3) domains stabilized SLP-76 microclusters and promoted T cell adhesion via the TCR, but could not support adhesion to integrin ligands. Finally, the SKAP55 dimerization motif (DM) enabled the coimmunoprecipitation of the Rap1-dependent integrin regulator Rap1-GTP–interacting adaptor molecule (RIAM), the recruitment of talin into TCR-induced adhesive junctions, and “inside-out” signaling to β1 integrins. Our data indicate that SKAP55 dimers stabilize SLP-76 microclusters, couple SLP-76 to the force-generating systems responsible for microcluster movement, and enable adhesion via the TCR by mechanisms independent of RIAM, talin, and β1 integrins. PMID:24368808

  7. C11449. Native N-Terminus Nitrophorin 2 from the Kissing Bug: Similarities to and Differences from NP2(D1A)

    PubMed Central

    Berry, Robert E.; Muthu, Dhanasekaran; Shokhireva, Tatiana K.; Garrett, Sarah A.; Zhang, Hongjun; Walker, F. Ann

    2012-01-01

    The first amino acid of mature native nitrophorin 2 is aspartic acid, and when expressed in E. coli the wild-type gene of the mature protein retains the methionine-0 which is produced by translation of the start codon. This form of NP2, (M0)NP2, has been found to have different properties from its D1A mutant, for which the Met0 is cleaved by the methionine aminopeptidase of E. coli [R. E. Berry, T. K. Shokhireva, I. Filippov, M. N. Shokhirev, H. Zhang, F. A. Walker, Biochemistry 2007, 46, 6830]. Native N-terminus nitrophorin 2 ((ΔM0)NP2) has been prepared by employing periplasmic expression of NP2 in E. coli using the pelB leader sequence from Erwinia carotovora, which is present in the pET-26b expression plasmid (Novagen). This paper details the similarities and differences between the three different N-terminal forms of nitrophorin 2, (M0)NP2, NP2(D1A), and (ΔM0)NP2. It is found that the NMR spectra of high- and low-spin (ΔM0)NP2 are essentially identical to those of NP2(D1A), but the rate and equilibrium constants for histamine and NO dissociation/association of the two are different. PMID:22976966

  8. The structural organization of the N-terminus domain of SopB, a virulence factor of Salmonella, depends on the nature of its protein partners.

    PubMed

    Roblin, Pierre; Lebrun, Pierre; Rucktooa, Prakash; Dewitte, Frederique; Lens, Zoe; Receveur-Brechot, Véronique; Raussens, Vincent; Villeret, Vincent; Bompard, Coralie

    2013-12-01

    The TTSS is used by Salmonella and many bacterial pathogens to inject virulence factors directly into the cytoplasm of target eukaryotic cells. Once translocated these so-called effector proteins hijack a vast array of crucial cellular functions to the benefit of the bacteria. In the bacterial cytoplasm, some effectors are stabilized and maintained in a secretion competent state by interaction with specific type III chaperones. In this work we studied the conformation of the Chaperone Binding Domain of the effector named Salmonella Outer protein B (SopB) alone and in complex with its cognate chaperone SigE by a combination of biochemical, biophysical and structural approaches. Our results show that the N-terminus part of SopB is mainly composed by α-helices and unfolded regions whose organization/stabilization depends on their interaction with the different partners. This suggests that the partially unfolded state of this N-terminal region, which confers the adaptability of the effector to bind very different partners during the infection cycle, allows the bacteria to modulate numerous host cells functions limiting the number of translocated effectors. PMID:24075929

  9. 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

  10. The RZZ complex requires the N-terminus of KNL1 to mediate optimal Mad1 kinetochore localization in human cells.

    PubMed

    Caldas, Gina V; Lynch, Tina R; Anderson, Ryan; Afreen, Sana; Varma, Dileep; DeLuca, Jennifer G

    2015-11-01

    The spindle assembly checkpoint is a surveillance mechanism that blocks anaphase onset until all chromosomes are properly attached to microtubules of the mitotic spindle. Checkpoint activity requires kinetochore localization of Mad1/Mad2 to inhibit activation of the anaphase promoting complex/cyclosome in the presence of unattached kinetochores. In budding yeast and Caenorhabditis elegans, Bub1, recruited to kinetochores through KNL1, recruits Mad1/Mad2 by direct linkage with Mad1. However, in human cells it is not yet established which kinetochore protein(s) function as the Mad1/Mad2 receptor. Both Bub1 and the RZZ complex have been implicated in Mad1/Mad2 kinetochore recruitment; however, their specific roles remain unclear. Here, we investigate the contributions of Bub1, RZZ and KNL1 to Mad1/Mad2 kinetochore recruitment. We find that the RZZ complex localizes to the N-terminus of KNL1, downstream of Bub1, to mediate robust Mad1/Mad2 kinetochore localization. Our data also point to the existence of a KNL1-, Bub1-independent mechanism for RZZ and Mad1/Mad2 kinetochore recruitment. Based on our results, we propose that in humans, the primary mediator for Mad1/Mad2 kinetochore localization is the RZZ complex. PMID:26581576

  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. Vaccination of Cattle with the N Terminus of LppQ of Mycoplasma mycoides subsp. mycoides Results in Type III Immune Complex Disease upon Experimental Infection

    PubMed Central

    Frey, Joachim; Smith, Ken; Schnier, Christian; Wesonga, Hezron; Naessens, Jan; McKeever, Declan

    2015-01-01

    Contagious bovine pleuropneumonia (CBPP) is a serious respiratory disease of cattle caused by Mycoplasma mycoides subsp. mycoides. Current vaccines against CBPP induce short-lived immunity and can cause severe postvaccine reactions. Previous studies have identified the N terminus of the transmembrane lipoprotein Q (LppQ-N′) of M. mycoides subsp. mycoides as the major antigen and a possible virulence factor. We therefore immunized cattle with purified recombinant LppQ-N′ formulated in Freund's adjuvant and challenged them with M. mycoides subsp. mycoides. Vaccinated animals showed a strong seroconversion to LppQ, but they exhibited significantly enhanced postchallenge glomerulonephritis compared to the placebo group (P = 0.021). Glomerulonephritis was characterized by features that suggested the development of antigen-antibody immune complexes. Clinical signs and gross pathological scores did not significantly differ between vaccinated and placebo groups. These findings reveal for the first time the pathogenesis of enhanced disease as a result of antibodies against LppQ during challenge and also argue against inclusion of LppQ-N′ in a future subunit vaccine for CBPP. PMID:25733516

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

    PubMed Central

    MACBETH, MARK R.; LINGAM, ARUNTH T.; BASS, BRENDA L.

    2004-01-01

    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. PMID:15383678

  15. Vaccination of cattle with the N terminus of LppQ of Mycoplasma mycoides subsp. mycoides results in type III immune complex disease upon experimental infection.

    PubMed

    Mulongo, Musa; Frey, Joachim; Smith, Ken; Schnier, Christian; Wesonga, Hezron; Naessens, Jan; McKeever, Declan

    2015-05-01

    Contagious bovine pleuropneumonia (CBPP) is a serious respiratory disease of cattle caused by Mycoplasma mycoides subsp. mycoides. Current vaccines against CBPP induce short-lived immunity and can cause severe postvaccine reactions. Previous studies have identified the N terminus of the transmembrane lipoprotein Q (LppQ-N') of M. mycoides subsp. mycoides as the major antigen and a possible virulence factor. We therefore immunized cattle with purified recombinant LppQ-N' formulated in Freund's adjuvant and challenged them with M. mycoides subsp. mycoides. Vaccinated animals showed a strong seroconversion to LppQ, but they exhibited significantly enhanced postchallenge glomerulonephritis compared to the placebo group (P = 0.021). Glomerulonephritis was characterized by features that suggested the development of antigen-antibody immune complexes. Clinical signs and gross pathological scores did not significantly differ between vaccinated and placebo groups. These findings reveal for the first time the pathogenesis of enhanced disease as a result of antibodies against LppQ during challenge and also argue against inclusion of LppQ-N' in a future subunit vaccine for CBPP. PMID:25733516

  16. 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

  17. Heat stability of maize endosperm ADP-glucose pyrophosphorylase is enhanced by insertion of a cysteine in the N terminus of the small subunit.

    PubMed

    Linebarger, Carla R Lyerly; Boehlein, Susan K; Sewell, Aileen K; Shaw, Janine; Hannah, L Curtis

    2005-12-01

    ADP-glucose pyrophosphorylase (AGPase) is a key regulatory enzyme in starch biosynthesis. However, plant AGPases differ in several parameters, including spatial and temporal expression, allosteric regulation, and heat stability. AGPases of cereal endosperms are heat labile, while those in other tissues, such as the potato (Solanum tuberosum) tuber, are heat stable. Sequence comparisons of heat-stable and heat-labile AGPases identified an N-terminal motif unique to heat-stable enzymes. Insertion of this motif into recombinant maize (Zea mays) endosperm AGPase increased the half-life at 58 degrees C more than 70-fold. Km values for physiological substrates were unaffected, although Kcat was doubled. A cysteine within the inserted motif gives rise to small subunit homodimers not found in the wild-type maize enzyme. Placement of this N-terminal motif into a mosaic small subunit containing the N terminus from maize endosperm and the C terminus from potato tuber AGPase increases heat stability more than 300-fold. PMID:16299180

  18. 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

  19. 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. PMID:27339139

  20. The RZZ complex requires the N-terminus of KNL1 to mediate optimal Mad1 kinetochore localization in human cells

    PubMed Central

    Caldas, Gina V.; Lynch, Tina R.; Anderson, Ryan; Afreen, Sana; Varma, Dileep; DeLuca, Jennifer G.

    2015-01-01

    The spindle assembly checkpoint is a surveillance mechanism that blocks anaphase onset until all chromosomes are properly attached to microtubules of the mitotic spindle. Checkpoint activity requires kinetochore localization of Mad1/Mad2 to inhibit activation of the anaphase promoting complex/cyclosome in the presence of unattached kinetochores. In budding yeast and Caenorhabditis elegans, Bub1, recruited to kinetochores through KNL1, recruits Mad1/Mad2 by direct linkage with Mad1. However, in human cells it is not yet established which kinetochore protein(s) function as the Mad1/Mad2 receptor. Both Bub1 and the RZZ complex have been implicated in Mad1/Mad2 kinetochore recruitment; however, their specific roles remain unclear. Here, we investigate the contributions of Bub1, RZZ and KNL1 to Mad1/Mad2 kinetochore recruitment. We find that the RZZ complex localizes to the N-terminus of KNL1, downstream of Bub1, to mediate robust Mad1/Mad2 kinetochore localization. Our data also point to the existence of a KNL1-, Bub1-independent mechanism for RZZ and Mad1/Mad2 kinetochore recruitment. Based on our results, we propose that in humans, the primary mediator for Mad1/Mad2 kinetochore localization is the RZZ complex. PMID:26581576

  1. 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.

  2. 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

  3. 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

  4. 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

  5. Harvey ras genes transform without mutant codons, apparently activated by truncation of a 5' exon (exon -1).

    PubMed Central

    Cichutek, K; Duesberg, P H

    1986-01-01

    The hypothesis is tested that the ras gene of Harvey sarcoma virus (Ha-SV) and the proto-ras DNAs from certain tumor cells derive transforming function from specific codons in which they differ from normal proto-ras genes. Molecularly cloned Harvey proviral vectors carrying viral ras, normal rat proto-ras, and recombinant ras genes in which the virus-specific ras codons 12 and 59 were replaced by proto-ras equivalents each transformed aneuploid mouse 3T3 cells after latent periods that ranged from 4 to 10 days. Viruses with or without virus-specific ras codons all transformed diploid rat cells in 3-5 days equally well. However, in the absence of virus replication, mutant codons were beneficial for transforming function. Deletion of non-ras regions of Ha-SV did not affect transforming function. We conclude that specific ras codons are not necessary for transforming function. Comparisons of the ras sequences of Ha-SV, BALB SV, and Rasheed SV with sequences of proto-ras genes from rat and man revealed an upstream proto-ras exon, termed exon -1. The 3' end of this exon is present in all three viruses and in a ras pseudogene of the rat. Since ras genes transform without mutation and since exon -1 is truncated in viral ras genes and all transforming proto-ras DNAs of the Harvey and the Kirsten ras family, we propose that ras genes are activated by truncation of exon -1 either via viral transduction or artificially via cloning and transfection. The proposal implies that untruncated proto-ras genes with point mutations may not be cellular cancer genes. Images PMID:3517865

  6. Association between CTLA-4 exon-1 +49A/G polymorphism and asthma: an updated meta-analysis.

    PubMed

    Yao, Ying-Shui; Wang, Lin-Hong; Chang, Wei-Wei; He, Lian-Ping; Li, Jie; Jin, Yue-Long; Li, Chao-Pin

    2015-01-01

    The results of studies on association between CTLA-4 exon-1 +49A/G (rs231775) polymorphism and susceptibility to asthma are controversial. To derive a more precise estimation of the relationship between the CTLA-4 exon-1 +49A/G polymorphism and asthma, a meta-analysis of 15 published case-control studies was performed. 15 studies meeting our inclusion criteria comprising 4006 asthma cases and 3729 controls were included. The effect summary odds ratio (OR) and 95% confidence intervals were obtained. Publication bias was tested by funnel plot, Egger's test and heterogeneity was assessed. The combined results showed that there were significant differences in genotype distribution between asthma cases and control on the basis of all studies, GG + GA versus AA (OR = 0.76, 95% CI: 0.62-0.93; P = 0.008). When stratifying for the race, the phenomenon was found that asthma cases had a significantly higher frequency of GG/GA versus AA (OR = 0.71; 95% CI: 0.51-0.99; P = 0.04) than control in Caucasian. Stratifying subjects by age indicated an association between CTLA-4 +49 GG + GA genotype and asthma in children (OR = 0.75; 95% CI: 0.62-0.90; P = 0.002), but no association in adults (OR = 0.93; 95% CI: 0.76-1.14; P = 0.48). Furthermore, significant association was observed in atopic asthma under the fixed-effects model (GG + GA vs. AA: P = 0.03, OR = 0.81, 95% CI = 0.67-0.98, P heterogeneity = 0.22). Our meta-analysis results suggest that CTLA-4 exon-1 +49A/G polymorphism might be a risk factor for asthma susceptibility, at least in Caucasian, children, and patients with atopy status. PMID:26064199

  7. 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.

  8. A Nonviral Peptide Can Replace the Entire N Terminus of Zucchini Yellow Mosaic Potyvirus Coat Protein and Permits Viral Systemic Infection

    PubMed Central

    Arazi, T.; Shiboleth, Y. M.; Gal-On, A.

    2001-01-01

    Systematic deletion and peptide tagging of the amino-terminal domain (NT, ∼43 amino acids) of an attenuated zucchini yellow mosaic potyvirus (ZYMV-AGII) coat protein (CP) were used to elucidate its role in viral systemic infection. Deletion mutants truncated by 8, 13, and 33 amino acid residues from the CP-NT 5′ end were systemically infectious and produced symptoms similar to those of the AGII virus. Tagging these deletion mutants with either human c-Myc (Myc) or hexahistidine peptides maintained viral infectivity. Similarly, addition of these peptides to the intact AGII CP-NT did not affect viral life cycle. To determine which parts, if any, of the CP-NT are essential for viral systemic infection, a series of Myc-tagged mutants with 8 to 43 amino acids removed from the CP-NT were constructed. All Myc-tagged CP-NT deletion mutants, including those from which virtually all the viral CP-NT had been eliminated, were able to encapsidate and cause systemic infection. Furthermore, chimeric viruses with deletions of up to 33 amino acids from CP-NT produced symptoms indistinguishable from those caused by the parental AGII virus. In contrast to CP-NT Myc fusion, addition of the foot-and-mouth disease virus (FMDV) immunogenic epitope to AGII CP-NT did not permit systemic infection. However, fusion of the Myc peptide to the N terminus of the FMDV peptide restored the capability of the virus to spread systemically. We have demonstrated that all CP-NT fused peptides were exposed on the virion surface, masking natural CP immunogenic determinants. Our findings demonstrate that CP-NT is not essential for ZYMV spread and that it can be replaced by an appropriate foreign peptide while maintaining systemic infectivity. PMID:11413299

  9. 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

  10. Structure–activity relationships of the N-terminus of calcitonin gene-related peptide: key roles of alanine-5 and threonine-6 in receptor activation

    PubMed Central

    Hay, Debbie L; Harris, Paul WR; Kowalczyk, Renata; Brimble, Margaret A; Rathbone, Dan L; Barwell, James; Conner, Alex C; Poyner, David R

    2014-01-01

    Background and Purpose: The N-terminus of calcitonin gene-related peptide (CGRP) is important for receptor activation, especially the disulphide-bonded ring (residues 1–7). However, the roles of individual amino acids within this region have not been examined and so the molecular determinants of agonism are unknown. This study has examined the role of residues 1, 3–6 and 8–9, excluding Cys-2 and Cys-7. Experimental Approach: CGRP derivatives were substituted with either cysteine or alanine; further residues were introduced at position 6. Their affinity was measured by radioligand binding and their efficacy by measuring cAMP production in SK-N-MC cells and β-arrestin 2 translocation in CHO-K1 cells at the CGRP receptor. Key Results: Substitution of Ala-5 by cysteine reduced affinity 270-fold and reduced efficacy for production of cAMP in SK-N-MCs. Potency at β-arrestin translocation was reduced by ninefold. Substitution of Thr-6 by cysteine destroyed all measurable efficacy of both cAMP and β-arrestin responses; substitution with either alanine or serine impaired potency. Substitutions at positions 1, 4, 8 and 9 resulted in approximately 10-fold reductions in potency at both responses. Similar observations were made at a second CGRP-activated receptor, the AMY1(a) receptor. Conclusions and Implications: Ala-5 and Thr-6 are key determinants of agonist activity for CGRP. Ala-5 is also very important for receptor binding. Residues outside of the 1–7 ring also contribute to agonist activity. PMID:24125506

  11. 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

  12. Identification of an epitope in the C terminus of normal prion protein whose expression is modulated by binding events in the N terminus.

    PubMed

    Li, R; Liu, T; Wong, B S; Pan, T; Morillas, M; Swietnicki, W; O'Rourke, K; Gambetti, P; Surewicz, W K; Sy, M S

    2000-08-18

    We have characterized the epitopes of a panel of 12 monoclonal antibodies (Mabs) directed to normal human cellular prion protein (PrP(C)) using ELISA and Western blotting of recombinant PrP or synthetic peptide fragments of PrP. The first group of antibodies, which is represented by Mabs 5B2 and 8B4, reacts with PrP(23-145), indicating that the epitopes for these Mabs are located in the 23 to 145 N-terminal region of human PrP. The second group includes Mabs 1A1, 6H3, 7A9, 8C6, 8H4, 9H7 and 2G8. These antibodies bind to epitopes localized within N-terminally truncated recombinant PrP(90-231). Finally, Mabs 5C3, 2C9 and 7A12 recognize both PrP(23-145) and PrP(90-231), suggesting that the epitopes for this group are located in the region encompassing residues 90 to 145. By Western blotting with PepSpot(TM), only three of Mabs studied (5B2, 8B4 and 2G8) bind to linear epitopes that are present in 13-residue long synthetic peptides corresponding to human PrP fragments. The remaining nine Mabs appear to recognize conformational epitopes. Two N terminus-specific Mabs were found to prevent the binding of the C terminus-specific Mab 6H3. This observation suggests that the unstructured N-terminal region may influence the local conformation within the folded C-terminal domain of prion protein. PMID:10966770

  13. The N Terminus of the Vaccinia Virus Protein F1L Is an Intrinsically Unstructured Region That Is Not Involved in Apoptosis Regulation.

    PubMed

    Caria, Sofia; Marshall, Bevan; Burton, Robyn-Lee; Campbell, Stephanie; Pantaki-Eimany, Delara; Hawkins, Christine J; Barry, Michele; Kvansakul, Marc

    2016-07-01

    Subversion of host cell apoptotic responses is a prominent feature of viral immune evasion strategies to prevent premature clearance of infected cells. Numerous poxviruses encode structural and functional homologs of the Bcl-2 family of proteins, and vaccinia virus harbors antiapoptotic F1L that potently inhibits the mitochondrial apoptotic checkpoint. Recently F1L has been assigned a caspase-9 inhibitory function attributed to an N-terminal α helical region of F1L spanning residues 1-15 (1) preceding the domain-swapped Bcl-2-like domains. Using a reconstituted caspase inhibition assay in yeast we found that unlike AcP35, a well characterized caspase-9 inhibitor from the insect virus Autographa californica multiple nucleopolyhedrovirus, F1L does not prevent caspase-9-mediated yeast cell death. Furthermore, we found that deletion of the F1L N-terminal region does not impede F1L antiapoptotic activity in the context of a viral infection. Solution analysis of the F1L N-terminal regions using small angle x-ray scattering indicates that the region of F1L spanning residues 1-50 located N-terminally from the Bcl-2 fold is an intrinsically unstructured region. We conclude that the N terminus of F1L is not involved in apoptosis inhibition and may act as a regulatory element in other signaling pathways in a manner reminiscent of other unstructured regulatory elements commonly found in mammalian prosurvival Bcl-2 members including Bcl-xL and Mcl-1. PMID:27151220

  14. 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

  15. 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

  16. The unique Leishmania EIF4E4 N-terminus is a target for multiple phosphorylation events and participates in critical interactions required for translation initiation.

    PubMed

    de Melo Neto, Osvaldo P; da Costa Lima, Tamara D C; Xavier, Camila C; Nascimento, Larissa M; Romão, Tatiany P; Assis, Ludmila A; Pereira, Mariana M C; Reis, Christian R S; Papadopoulou, Barbara

    2015-01-01

    The eukaryotic initiation factor 4E (eIF4E) recognizes the mRNA cap structure and, together with eIF4G and eIF4A, form the eIF4F complex that regulates translation initiation in eukaryotes. In trypanosomatids, 2 eIF4E homologues (EIF4E3 and EIF4E4) have been shown to be part of eIF4F-like complexes with presumed roles in translation initiation. Both proteins possess unique N-terminal extensions, which can be targeted for phosphorylation. Here, we provide novel insights on the Leishmania infantum EIF4E4 function and regulation. We show that EIF4E4 is constitutively expressed throughout the parasite development but is preferentially phosphorylated in exponentially grown promastigote and amastigote life stages, hence correlating with high levels of translation. Phosphorylation targets multiple serine-proline or threonine-proline residues within the N-terminal extension of EIF4E4 but does not require binding to the EIF4E4's partner, EIF4G3, or to the cap structure. We also report that EIF4E4 interacts with PABP1 through 3 conserved boxes at the EIF4E4 N-terminus and that this interaction is a prerequisite for efficient EIF4E4 phosphorylation. EIF4E4 is essential for Leishmania growth and an EIF4E4 null mutant was only obtained in the presence of an ectopically provided wild type gene. Complementation for the loss of EIF4E4 with several EIF4E4 mutant proteins affecting either phosphorylation or binding to mRNA or to EIF4E4 protein partners revealed that, in contrast to other eukaryotes, only the EIF4E4-PABP1 interaction but neither the binding to EIF4G3 nor phosphorylation is essential for translation. These studies also demonstrated that the lack of both EIF4E4 phosphorylation and EIF4G3 binding leads to a non-functional protein. Altogether, these findings further highlight the unique features of the translation initiation process in trypanosomatid protozoa. PMID:26338184

  17. Interaction of a synthetic peptide corresponding to the N-terminus of canine distemper virus fusion protein with phospholipid vesicles: a biophysical study.

    PubMed

    Aranda, Francisco J; Teruel, José A; Ortiz, Antonio

    2003-12-01

    The F protein of canine distemper virus (CDV) is a classic type I glycoprotein formed by two polypeptides, F1 and F2. The N-terminal regions of the F1 polypeptides of CDV, measles virus and other paramyxoviruses present moderate to high homology, supporting the existence of a high conservation within these structures, which emphasises its role in viral-host cell membrane fusion. This N-terminal polypeptide is usually termed the fusion peptide. The fusion peptides of most viral fusion-mediating glycoproteins contain a high proportion of hydrophobic amino acids, which facilitates its insertion into target membranes during fusion. In this work we report on the interaction of a 31-residue synthetic peptide (FP31) corresponding to the N terminus of CDV F1 protein with phospholipid membranes composed of various phospholipids, as studied by means of various biophysical techniques. FTIR investigation of FP31 secondary structure in aqueous medium and in membranes resulted in a major proportion of alpha-helical structure which increased upon membrane insertion. Differential scanning calorimetry (DSC) showed that the presence of concentrations of FP31 as low as 0.1 mol%, in mixtures with L-alpha-dimyristoylphosphatidylcholine (DMPC), L-alpha-dipalmitoylphosphatidylcholine (DPPC) and L-alpha-distearoylphosphatidylcholine (DSPC), already affected the thermotropic properties of the gel to liquid-crystalline phase transition. In mixtures with the three lipids, increasing the concentration of peptide made the pretransition to disappear, and lowered and broadened the main transition. This effect was slightly stronger as the acyl chain length of the phospholipid grew larger. In the corresponding partial phase diagrams, no immiscibilities or critical points were observed. FTIR showed that incorporation of 1 mol% of peptide in DPPC shifted the antisymmetric and symmetric CH2 stretching bands to higher values, indicating the existence of an additional disordering of the acyl chain

  18. Novel exon 1 protein-coding regions N-terminally extend human KCNE3 and KCNE4.

    PubMed

    Abbott, Geoffrey W

    2016-08-01

    The 5 human (h)KCNE β subunits each regulate various cation channels and are linked to inherited cardiac arrhythmias. Reported here are previously undiscovered protein-coding regions in exon 1 of hKCNE3 and hKCNE4 that extend their encoded extracellular domains by 44 and 51 residues, which yields full-length proteins of 147 and 221 residues, respectively. Full-length hKCNE3 and hKCNE4 transcript and protein are expressed in multiple human tissues; for hKCNE4, only the longer protein isoform is detectable. Two-electrode voltage-clamp electrophysiology revealed that, when coexpressed in Xenopus laevis oocytes with various potassium channels, the newly discovered segment preserved conversion of KCNQ1 by hKCNE3 to a constitutively open channel, but prevented its inhibition of Kv4.2 and KCNQ4. hKCNE4 slowing of Kv4.2 inactivation and positive-shifted steady-state inactivation were also preserved in the longer form. In contrast, full-length hKCNE4 inhibition of KCNQ1 was limited to 40% at +40 mV vs. 80% inhibition by the shorter form, and augmentation of KCNQ4 activity by hKCNE4 was entirely abolished by the additional segment. Among the genome databases analyzed, the longer KCNE3 is confined to primates; full-length KCNE4 is widespread in vertebrates but is notably absent from Mus musculus Findings highlight unexpected KCNE gene diversity, raise the possibility of dynamic regulation of KCNE partner modulation via splice variation, and suggest that the longer hKCNE3 and hKCNE4 proteins should be adopted in future mechanistic and genetic screening studies.-Abbott, G. W. Novel exon 1 protein-coding regions N-terminally extend human KCNE3 and KCNE4. PMID:27162025

  19. Effective quantitative real-time polymerase chain reaction analysis of the parkin gene (PARK2) exon 1–12 dosage

    PubMed Central

    Shadrina, Maria I; Semenova, Elena V; Slominsky, Petr A; Bagyeva, Gulbahar H; Illarioshkin, Sergei N; Ivanova-Smolenskaia, Irina I; Limborska, Svetlana A

    2007-01-01

    Background One of the causes of Parkinson's disease is mutations in the PARK2 gene. Deletions and duplications of single exons or exon groups account for a large proportion of the gene mutations. Direct detection of these mutations can be used for the diagnosis of Parkinson's disease. Methods To detect these mutations, we developed an effective technique based on the real-time TaqMan PCR system, which allows us to evaluate the copynumbers of the PARK2 gene exons by comparing the intensity of the amplification signals from some exon of this gene with that of the β-globin gene (the internal control). Results We analyzed rearrangements in exons 1–12 of the PARK2 gene in 64 patients from Russia with early-onset Parkinson's disease. The frequency of these mutations in our patients was 14%. Conclusion We have developed a simple, accurate, and reproducible method applicable to the rapid detection of exon rearrangements in the PARK2 gene. It is suitable for the analysis of large patient groups, and it may become the basis for a diagnostic test. PMID:17324265

  20. Association of GCN1–GCN20 regulatory complex with the N-terminus of eIF2α kinase GCN2 is required for GCN2 activation

    PubMed Central

    Garcia-Barrio, Minerva; Dong, Jinsheng; Ufano, Sandra; Hinnebusch, Alan G.

    2000-01-01

    Stimulation of GCN4 mRNA translation due to phosphorylation of the α-subunit of initiation factor 2 (eIF2) by its specific kinase, GCN2, requires binding of uncharged tRNA to a histidyl-tRNA synthetase (HisRS)-like domain in GCN2. GCN2 function in vivo also requires GCN1 and GCN20, but it was unknown whether these latter proteins act directly to promote the stimulation of GCN2 by uncharged tRNA. We found that the GCN1–GCN20 complex physically interacts with GCN2, binding to the N-terminus of the protein. Overexpression of N-terminal GCN2 segments had a dominant-negative phenotype that correlated with their ability to interact with GCN1–GCN20 and impede association between GCN1 and native GCN2. Consistently, this Gcn– phenotype was suppressed by overexpressing GCN2, GCN1–GCN20 or tRNAHis. The requirement for GCN1 was also reduced by overexpressing tRNAHis in a gcn1Δ strain. We conclude that binding of GCN1–GCN20 to GCN2 is required for its activation by uncharged tRNA. The homologous N-terminus of Drosophila GCN2 interacted with yeast GCN1–GCN20 and had a dominant Gcn– phenotype, suggesting evolutionary conservation of this interaction. PMID:10775272

  1. Solid-State Nuclear Magnetic Resonance on the Static and Dynamic Domains of Huntingtin Exon-1 Fibrils

    PubMed Central

    Isas, J. Mario; Langen, Ralf; Siemer, Ansgar B.

    2016-01-01

    Amyloid-like fibrils formed by huntingtin exon-1 (httex1) are a hallmark of Huntington's Disease (HD). The structure of these fibrils is unknown and determining their structure is an important step towards understanding the misfolding processes that cause HD. In HD a polyglutamine (polyQ) domain in httex1 is expanded to a degree that it gains the ability to form aggregates comprising the core of the resulting fibrils. Despite the simplicity of this polyQ sequence the structure of httex1 fibrils has been difficult to determine. The current study provides a detailed structural investigation of fibrils formed by httex1 using solid-state NMR spectroscopy. We show that the polyQ domain of httex1 forms the static amyloid core similar to polyQ model peptides. The Gln residues of this domain exist in two distinct conformations that are found in separate domains or monomers but are relatively close in space. The rest of httex1 is relatively dynamic on an NMR time scale, especially the proline-rich C-terminus, which we found to be in a polyproline II helical and random coil conformation. We observed a similar dynamic C-terminus in a soluble form of (httex1 indicating that the conformation of this part of httex1 is not changed when aggregating into an amyloid fibril. From these data we propose a bottlebrush model for the fibrils formed by httex1. In this model, the polyQ domains form the center and the proline-rich domains the bristles of the bottlebrush. PMID:26020223

  2. Identification of a novel heterozygous truncation mutation in exon 1 of ARHGAP29 in an Indian subject with nonsyndromic cleft lip with cleft palate

    PubMed Central

    Chandrasekharan, Deepak; Ramanathan, Arvind

    2014-01-01

    Objective: Mutations in exon 1 of ARHGAP29, a RhoA specific GTPase have been identified in North American and Filipino subjects with nonsyndromic cleft palate and cleft lip with or without cleft palate. Since the genetic status of ARHGAP29 in Indian subjects with nonsyndromic oral clefts is not known, we designed the present study to investigate the occurrence of the above mutations in them. Materials and Methods: Total genomic DNA extracted from peripheral blood of 60 subjects with nonsyndromic cleft palate and cleft lip with or without cleft palate, and equal number of control healthy subjects were amplified with primers flanking exon 1 of ARHGAP29 gene and subjected to direct sequencing. Results: Sequencing analysis identified a nonsense mutation in exon 1 of ARHGAP29 that caused substitution of lysine to stop codon at codon position 32 in a subject with nonsyndromic cleft lip with cleft palate. The mutation, however, occurred in heterozygous condition. None of the other subjects carried mutation in this region. Conclusion: The study has thus identified a rare but novel truncation mutation in ARHGAP29 gene for the first time in nonsyndromic oral clefts. PMID:25512736

  3. Functional and topological studies with Trp-containing analogs of the peptide StII(1-30) derived from the N-terminus of the pore forming toxin sticholysin II: contribution to understand its orientation in membrane.

    PubMed

    Ros, Uris; Souto, Ana Lucia C F; de Oliveira, Felipe J; Crusca, Edson; Pazos, Fabiola; Cilli, Eduardo M; Lanio, Maria E; Schreier, Shirley; Alvarez, Carlos

    2013-07-01

    Sticholysin II (St II) is the most potent cytolysin produced by the sea anemone Stichodactyla helianthus, exerting hemolytic activity via pore formation in membranes. The toxin's N-terminus contains an amphipathic α-helix that is very likely involved in pore formation. We have previously demonstrated that the synthetic peptide StII(1-30) encompassing the 1-30 segment of St II forms pores of similar radius to that of the protein (around 1 nm), being a good model of toxin functionality. Here we have studied the functional and conformational properties of fluorescent analogs of StII(1-30) in lipid membranes. The analogs were obtained by replacing Leu residues at positions 2, 12, 17, and 24 with the intrinsically fluorescent amino acid Trp (StII(1-30L2W), StII(1-30L12W), StII(1-30L17W), or StII(1-30L24W), respectively). The exchange by Trp did not significantly modify the activity and conformation of the parent peptide. The blue-shift and intensity enhancement of fluorescence in the presence of membrane indicated that Trp at position 2 is more deeply buried in the hydrophobic region of the bilayer. These experiments, as well as assays with water-soluble or spin-labeled lipid-soluble fluorescence quenchers suggest an orientation of StII(1-30) with its N-terminus oriented towards the hydrophobic core of the bilayer while the rest of the peptide is more exposed to the aqueous environment, as hypothesized for sticholysins. PMID:23868208

  4. 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. PMID:24161731

  5. 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 Central

    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. PMID:23976922

  6. 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. PMID:24529944

  7. 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

  8. A transient α-helical molecular recognition element in the disordered N-terminus of the Sgs1 helicase is critical for chromosome stability and binding of Top3/Rmi1

    PubMed Central

    Kennedy, Jessica A.; Daughdrill, Gary W.; Schmidt, Kristina H.

    2013-01-01

    The RecQ-like DNA helicase family is essential for the maintenance of genome stability in all organisms. Sgs1, a member of this family in Saccharomyces cerevisiae, regulates early and late steps of double-strand break repair by homologous recombination. Using nuclear magnetic resonance spectroscopy, we show that the N-terminal 125 residues of Sgs1 are disordered and contain a transient α-helix that extends from residue 25 to 38. Based on the residue-specific knowledge of transient secondary structure, we designed proline mutations to disrupt this α-helix and observed hypersensitivity to DNA damaging agents and increased frequency of genome rearrangements. In vitro binding assays show that the defects of the proline mutants are the result of impaired binding of Top3 and Rmi1 to Sgs1. Extending mutagenesis N-terminally revealed a second functionally critical region that spans residues 9–17. Depending on the position of the proline substitution in the helix functional impairment of Sgs1 function varied, gradually increasing from the C- to the N-terminus. The multiscale approach we used to interrogate structure/function relationships in the long disordered N-terminal segment of Sgs1 allowed us to precisely define a functionally critical region and should be generally applicable to other disordered proteins. PMID:24038467

  9. A transient α-helical molecular recognition element in the disordered N-terminus of the Sgs1 helicase is critical for chromosome stability and binding of Top3/Rmi1.

    PubMed

    Kennedy, Jessica A; Daughdrill, Gary W; Schmidt, Kristina H

    2013-12-01

    The RecQ-like DNA helicase family is essential for the maintenance of genome stability in all organisms. Sgs1, a member of this family in Saccharomyces cerevisiae, regulates early and late steps of double-strand break repair by homologous recombination. Using nuclear magnetic resonance spectroscopy, we show that the N-terminal 125 residues of Sgs1 are disordered and contain a transient α-helix that extends from residue 25 to 38. Based on the residue-specific knowledge of transient secondary structure, we designed proline mutations to disrupt this α-helix and observed hypersensitivity to DNA damaging agents and increased frequency of genome rearrangements. In vitro binding assays show that the defects of the proline mutants are the result of impaired binding of Top3 and Rmi1 to Sgs1. Extending mutagenesis N-terminally revealed a second functionally critical region that spans residues 9-17. Depending on the position of the proline substitution in the helix functional impairment of Sgs1 function varied, gradually increasing from the C- to the N-terminus. The multiscale approach we used to interrogate structure/function relationships in the long disordered N-terminal segment of Sgs1 allowed us to precisely define a functionally critical region and should be generally applicable to other disordered proteins. PMID:24038467

  10. A noncoding melanophilin gene (MLPH) SNP at the splice donor of exon 1 represents a candidate causal mutation for coat color dilution in dogs.

    PubMed

    Drögemüller, Cord; Philipp, Ute; Haase, Bianca; Günzel-Apel, Anne-Rose; Leeb, Tosso

    2007-01-01

    Coat color dilution in several breeds of dog is characterized by a specific pigmentation phenotype and sometimes accompanied by hair loss and recurrent skin inflammation, the so-called color dilution alopecia or black hair follicular dysplasia. Coat color dilution (d) is inherited as a Mendelian autosomal recessive trait. In a previous study, MLPH polymorphisms showed perfect cosegregation with the dilute phenotype within breeds. However, different dilute haplotypes were found in different breeds, and no single polymorphism was identified in the coding sequence that was likely to be causative for the dilute phenotype. We resequenced the 5'-region of the canine MLPH gene and identified a strong candidate single nucleotide polymorphism within the nontranslated exon 1, which showed perfect association to the dilute phenotype in 65 dilute dogs from 7 different breeds. The A/G polymorphism is located at the last nucleotide of exon 1 and the mutant A-allele is predicted to reduce splicing efficiency 8-fold. An MLPH mRNA expression study using quantitative reverse transcriptase-polymerase chain reaction confirmed that dd animals had only about approximately 25% of the MLPH transcript compared with DD animals. These results provide preliminary evidence that the reported regulatory MLPH mutation might represent a causal mutation for coat color dilution in dogs. PMID:17519392

  11. Calpastatin exon 1B-derived peptide, a selective inhibitor of calpain: enhancing cell permeability by conjugation with penetratin.

    PubMed

    Gil-Parrado, Shirley; Assfalg-Machleidt, Irmgard; Fiorino, Ferdinando; Deluca, Dominga; Pfeiler, Dietmar; Schaschke, Norbert; Moroder, Luis; Machleidt, Werner

    2003-03-01

    The ubiquitous calpains, mu- and m-calpain, have been implicated in essential physiological processes and various pathologies. Cell-permeable specific inhibitors are important tools to elucidate the roles of calpains in cultivated cells and animal models. The synthetic N-acetylated 27-mer peptide derived from exon B of the inhibitory domain 1 of human calpastatin (CP1B) is unique as a potent and highly selective reversible calpain inhibitor, but is poorly cell-permeant. By addition of N-terminal cysteine residues we have generated a disulfide-conjugated CP1B with the cell-penetrating 16-mer peptide penetratin derived from the third helix of the Antennapedia homeodomain protein. The inhibitory potency and selectivity of CP1B for calpain versus cathepsin B and L, caspase 3 and the proteasome was not affected by the conjugation with penetratin. The conjugate was shown to efficiently penetrate into living LCLC 103H cells, since it prevents ionomycin-induced calpain activation at 200-fold lower concentration than the non-conjugated inhibitor and is able to reduce calpain-triggered apoptosis of these cells. Penetratin-conjugated CP1B seems to be a promising alternative to the widely used cell-permeable peptide aldehydes (e.g. calpain inhibitor 1) which inhibit the lysosomal cathepsins and partially the proteasome as well or even better than the calpains. PMID:12715890

  12. 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

  13. Fluorescent tagging of VP22 in N-terminus reveals that VP22 favors Marek’s disease virus (MDV) virulence in chickens and allows morphogenesis study in MD tumor cells

    PubMed Central

    2013-01-01

    Marek’s disease virus (MDV) is an alpha-herpesvirus causing Marek’s disease in chickens, mostly associated with T-cell lymphoma. VP22 is a tegument protein abundantly expressed in cells during the lytic cycle, which is essential for MDV spread in culture. Our aim was to generate a pathogenic MDV expressing a green fluorescent protein (EGFP) fused to the N-terminus of VP22 to better decipher the role of VP22 in vivo and monitor MDV morphogenesis in tumors cells. In culture, rRB-1B EGFP22 led to 1.6-fold smaller plaques than the parental virus. In chickens, the rRB-1B EGFP22 virus was impaired in its ability to induce lymphoma and to spread in contact birds. The MDV genome copy number in blood and feathers during the time course of infection indicated that rRB-1B EGFP22 reached its two major target cells, but had a growth defect in these two tissues. Therefore, the integrity of VP22 is critical for an efficient replication in vivo, for tumor formation and horizontal transmission. An examination of EGFP fluorescence in rRB-1B EGFP22-induced tumors showed that about 0.1% of the cells were in lytic phase. EGFP-positive tumor cells were selected by cytometry and analyzed for MDV morphogenesis by transmission electron microscopy. Only few particles were present per cell, and all types of virions (except mature enveloped virions) were detected unequivocally inside tumor lymphoid cells. These results indicate that MDV morphogenesis in tumor cells is more similar to the morphorgenesis in fibroblastic cells in culture, albeit poorly efficient, than in feather follicle epithelial cells. PMID:24359464

  14. Fluorescent tagging of VP22 in N-terminus reveals that VP22 favors Marek's disease virus (MDV) virulence in chickens and allows morphogenesis study in MD tumor cells.

    PubMed

    Rémy, Sylvie; Blondeau, Caroline; Le Vern, Yves; Lemesle, Monique; Vautherot, Jean-François; Denesvre, Caroline

    2013-01-01

    Marek's disease virus (MDV) is an alpha-herpesvirus causing Marek's disease in chickens, mostly associated with T-cell lymphoma. VP22 is a tegument protein abundantly expressed in cells during the lytic cycle, which is essential for MDV spread in culture. Our aim was to generate a pathogenic MDV expressing a green fluorescent protein (EGFP) fused to the N-terminus of VP22 to better decipher the role of VP22 in vivo and monitor MDV morphogenesis in tumors cells. In culture, rRB-1B EGFP22 led to 1.6-fold smaller plaques than the parental virus. In chickens, the rRB-1B EGFP22 virus was impaired in its ability to induce lymphoma and to spread in contact birds. The MDV genome copy number in blood and feathers during the time course of infection indicated that rRB-1B EGFP22 reached its two major target cells, but had a growth defect in these two tissues. Therefore, the integrity of VP22 is critical for an efficient replication in vivo, for tumor formation and horizontal transmission. An examination of EGFP fluorescence in rRB-1B EGFP22-induced tumors showed that about 0.1% of the cells were in lytic phase. EGFP-positive tumor cells were selected by cytometry and analyzed for MDV morphogenesis by transmission electron microscopy. Only few particles were present per cell, and all types of virions (except mature enveloped virions) were detected unequivocally inside tumor lymphoid cells. These results indicate that MDV morphogenesis in tumor cells is more similar to the morphorgenesis in fibroblastic cells in culture, albeit poorly efficient, than in feather follicle epithelial cells. PMID:24359464

  15. A tumor of the uterine cervix with a complex histology in a Peutz-Jeghers syndrome patient with genomic deletion of the STK11 exon 1 region.

    PubMed

    Kobayashi, Yusuke; Masuda, Kenta; Kimura, Tokuhiro; Nomura, Hiroyuki; Hirasawa, Akira; Banno, Kouji; Susumu, Nobuyuki; Sugano, Kokichi; Aoki, Daisuke

    2014-02-01

    Patients with Peutz-Jeghers syndrome (PJS) have a risk of complicating malignant tumors, including cancer of the uterine cervix. Mutations in the STK11 gene have been identified as being responsible for PJS. However, the genotype-phenotype correlation in PJS is poorly understood, especially with respect to malignant tumors. Here, we report a detailed analysis of a case of a cervical tumor in a PJS patient showing a large genomic deletion in exon 1 of STK11 without human papillomavirus infection. Histological examination revealed a complex histology consisting of three components: lobular endocervical gland hyperplasia (LEGH), minimal deviation adenocarcinoma (MDA) and mucinous adenocarcinoma. Immunohistochemistry for STK11 was positive in the LEGH and MDA components, while that of the mucinous adenocarcinoma stained very faintly. These findings support a close relationship among LEGH, MDA and mucinous adenocarcinoma and imply that inactivation of STK11 may occur during progression from MDA to mucinous adenocarcinoma. PMID:24490603

  16. Site-specific methylation changes in the glucocorticoid receptor exon 1F promoter in relation to life adversity: systematic review of contributing factors

    PubMed Central

    Daskalakis, Nikolaos P.; Yehuda, Rachel

    2014-01-01

    There has been recent interest in epigenetics in psychiatry since it offers a means of understanding how stressful life experiences, in interaction with the genotype, result in epigenetic changes that result in altered gene expression, ultimately affecting the risk for mental disorders. Many studies focused on methylation of the glucocorticoid receptor exon 1F promoter following an initial observation that changes in this region could be modulated by the environment. This review examines all published studies that have attempted to measure methylation in this region using different techniques, several tissue types, populations at different behavioral state and stages of development. Methodological issues have been raised with the aim of attempting to understand methylation quantification and site of action. We propose that it is useful to examine whether methylation at specific sites within the promoter region may be particularly relevant to psychiatric vulnerability to stress-related outcomes. PMID:25484853

  17. Ethanol Induced Acetylation of Histone at G9a Exon1 and G9a-Mediated Histone H3 Dimethylation leads to Neurodegeneration in Neonatal Mice

    PubMed Central

    Subbanna, Shivakumar; Nagre, Nagaraja N.; Shivakumar, Madhu; Umapathy, Nagavedi S.; Psychoyos, Delphine; Basavarajappa, Balapal S.

    2014-01-01

    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. PMID:24300108

  18. 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.

  19. Large conductance voltage- and calcium-dependent K+ channel, a distinct member of voltage-dependent ion channels with seven N-terminal transmembrane segments (S0-S6), an extracellular N terminus, and an intracellular (S9-S10) C terminus.

    PubMed

    Meera, P; Wallner, M; Song, M; Toro, L

    1997-12-01

    Large conductance voltage- and Ca2+-dependent K+ (MaxiK) channels show sequence similarities to voltage-gated ion channels. They have a homologous S1-S6 region, but are unique at the N and C termini. At the C terminus, MaxiK channels have four additional hydrophobic regions (S7-S10) of unknown topology. At the N terminus, we have recently proposed a new model where MaxiK channels have an additional transmembrane region (S0) that confers beta subunit regulation. Using transient expression of epitope tagged MaxiK channels, in vitro translation, functional, and "in vivo" reconstitution assays, we now show that MaxiK channels have seven transmembrane segments (S0-S6) at the N terminus and a S1-S6 region that folds in a similar way as in voltage-gated ion channels. Further, our results indicate that hydrophobic segments S9-S10 in the C terminus are cytoplasmic and unequivocally demonstrate that S0 forms an additional transmembrane segment leading to an exoplasmic N terminus. PMID:9391153

  20. Large conductance voltage- and calcium-dependent K+ channel, a distinct member of voltage-dependent ion channels with seven N-terminal transmembrane segments (S0-S6), an extracellular N terminus, and an intracellular (S9-S10) C terminus

    PubMed Central

    Meera, Pratap; Wallner, Martin; Song, Min; Toro, Ligia

    1997-01-01

    Large conductance voltage- and Ca2+-dependent K+ (MaxiK) channels show sequence similarities to voltage-gated ion channels. They have a homologous S1-S6 region, but are unique at the N and C termini. At the C terminus, MaxiK channels have four additional hydrophobic regions (S7-S10) of unknown topology. At the N terminus, we have recently proposed a new model where MaxiK channels have an additional transmembrane region (S0) that confers β subunit regulation. Using transient expression of epitope tagged MaxiK channels, in vitro translation, functional, and “in vivo” reconstitution assays, we now show that MaxiK channels have seven transmembrane segments (S0-S6) at the N terminus and a S1-S6 region that folds in a similar way as in voltage-gated ion channels. Further, our results indicate that hydrophobic segments S9-S10 in the C terminus are cytoplasmic and unequivocally demonstrate that S0 forms an additional transmembrane segment leading to an exoplasmic N terminus. PMID:9391153

  1. Spectroscopic and Functional Characterization of Nitrophorin 7 from the Blood-Feeding Insect Rhodnius prolixus Reveals an Important Role of Its Isoform-Specific N-Terminus for Proper Protein Function†

    PubMed Central

    Knipp, Markus; Yang, Fei; Berry, Robert E.; Zhang, Hongjun; Shokhirev, Maxim N.; Walker, F. Ann

    2008-01-01

    Nitrophorins (NPs) are a class of NO transporting and histamine sequestering heme b proteins that occur in the saliva of the bloodsucking insect Rhodnius prolixus. A detailed study of the newly described member, NP7, is presented herein. NP7 NO association constants KeqIII(NO) reveal a drastic change when the pH is varied from 5.5 (reflecting the insect's saliva) to slightly above plasma pH (7.5) (>109 M−1 → 4.0 × 106 M−1); thus, the protein promotes the storage of NO in the insect's saliva and its release inside the victim's tissue. In contrast to the other nitrophorins NP1-4, histamine sequestering cannot be accomplished in vivo due to the low binding constant KeqIII(histamine) = 105 M−1 compared to [histamine] = 1 − 10 × 10−9 M in the blood. A major part of this study deals with the N-terminus 1Leu–Pro–Gly–Glu–Cys5 of NP7, which is not found in NP1-4. Since NP7 has not been isolated from the insects so far, but was recognized in a cDNA library instead, the N-terminal site of signal peptidase cleavage upon protein secretion was predicted by the program SignalP [Andersen, J.F., Gudderra, N.P., Francischetti, I.M.B., Valenzuela, J.G., Ribeiro, J.M.C. (2004) Biochemistry 43, 6987-6994]. In marked contrast to wild-type NP7, NP7(Δ1-3) shows a very high NO-affinity at pH 7.5 (KeqIII(NO)≈ 109 M−1), suggesting that the release of NO in the plasma cannot efficiently be accomplished by the truncated form. Comparison of the reduction potentials of both constructs by spectroelectrochemistry revealed an average increase of +85 mV for various distal ligands bound to the heme-iron when 1Leu–Pro–Gly3 was removed. However, 1H NMR and EPR spectroscopy show that the electronic properties of the FeIII cofactor are similar in both wild-type NP7 and NP7(Δ1-3). Further, thermal denaturation that revealed a higher stability of wild-type NP7 compared to NP7(Δ1-3), in combination with a homology model based on the NP2 crystal structure (RMSD = 0.39

  2. 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

  3. 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

  4. Cloning and expression of the liver and muscle isoforms of ovine carnitine palmitoyltransferase 1: residues within the N-terminus of the muscle isoform influence the kinetic properties of the enzyme.

    PubMed Central

    Price, Nigel T; Jackson, Vicky N; van der Leij, Feike R; Cameron, Jacqueline M; Travers, Maureen T; Bartelds, Beatrijs; Huijkman, Nicolette C; Zammit, Victor A

    2003-01-01

    The nucleotide sequence data reported will appear in DDBJ, EMBL, GenBank(R) and GSDB Nucleotide Sequence Databases; the sequences of ovine CPT1A and CPT1B cDNAs have the accession numbers Y18387 and AJ272435 respectively and the partial adipose tissue and liver CPT1A clones have the accession numbers Y18830 and Y18829 respectively. Fatty acid and ketone body metabolism differ considerably between monogastric and ruminant species. The regulation of the key enzymes involved may differ accordingly. Carnitine palmitoyltransferase 1 (CPT 1) is the key locus for the control of long-chain fatty acid beta-oxidation and liver ketogenesis. Previously we showed that CPT 1 kinetics in sheep and rat liver mitochondria differ. We cloned cDNAs for both isoforms [liver- (L-) and muscle- (M-)] of ovine CPT 1 in order to elucidate the structural features of these proteins and their genes ( CPT1A and CPT1B ). Their deduced amino acid sequences show a high degree of conservation compared with orthologues from other mammalian species, with the notable exception of the N-terminus of ovine M-CPT 1. These differences were also present in bovine M-CPT 1, whose N-terminal sequence we determined. In addition, the 5'-end of the sheep CPT1B cDNA suggested a different promoter architecture when compared with previously characterized CPT1B genes. Northern blotting revealed differences in tissue distribution for both CPT1A and CPT1B transcripts compared with other species. In particular, ovine CPT1B mRNA was less tissue restricted, and the predominant transcript in the pancreas was CPT1B. Expression in yeast allowed kinetic characterization of the two native enzymes, and of a chimaera in which the distinctive N-terminal segment of ovine M-CPT 1 was replaced with that from rat M-CPT 1. The ovine N-terminal segment influences the kinetics of the enzyme for both its substrates, such that the K (m) for palmitoyl-CoA is decreased and that for carnitine is increased for the chimaera, relative to the

  5. Cell type-restricted expression of erythrocyte tropomodulin Isoform41 in exon 1 knockout/LacZ knock-in heterozygous mice.

    PubMed

    Yao, Weijuan; Chu, Xin; Sung, Lanping Amy

    2015-01-01

    Full-length erythrocyte tropomodulin (E-Tmod or Tmod1) isoform of 41 kDa is an actin nucleation protein and caps the pointed end of tropomyosin-coated actin filaments. It participates in the length control of short actin protofilaments in the erythrocyte membrane skeletal network as well as the organization of microfilaments in non-erythroid cells. Recently we discovered and characterized a truncated isoform of 29 kDa, which lacks the N-terminal sequence encoded by exons 1 and 2 required for nucleation and capping. Thus, it is important to study the expression pattern of solely the E-Tmod41 isoform in tissues. We utilized our exon 1 knockout (KO) mouse model with a knock-in lacZ reporter gene which reports the expression of E-Tmod41, but not E-Tmod29. Because this homozygous isoform-specific KO is an embryonic lethal mutation, we used heterozygous mice. X-gal staining localized specific signals at the single cell level and revealed a timed expression during embryonic development and restricted expression in adult mice. Our results showed that E-Tmod41 expressing cells include developing and young erythroid cells, developing somites, young fiber cells in the lens, certain subtype(s) of tubular cells in the kidney, smooth muscle cells in various tissues, and horizontal cells in the retina. A comparison with previous studies revealed that most if not all tissues known to express E-Tmod contained lacZ-expressing cells. Interestingly, some tubular cells were lacZ-positive while others in the same renal tubule were not, indicating heterogeneity within the tubular cells. Combined with double immunocytochemistry, we further localized E-Tmod41 to dendritic spines of horizontal cells. These timed and cell-type restricted expressions of E-Tmod41 suggest a role of actin nucleation and/or short actin protofilaments in these cell types and sub-cellular structures. PMID:25721257

  6. 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

  7. 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

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

    PubMed

    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

  9. 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

  10. Mutation in Exon 1f of PLEC, Leading to Disruption of Plectin Isoform 1f, Causes Autosomal-Recessive Limb-Girdle Muscular Dystrophy

    PubMed Central

    Gundesli, Hulya; Talim, Beril; Korkusuz, Petek; Balci-Hayta, Burcu; Cirak, Sebahattin; Akarsu, Nurten A.; Topaloglu, Haluk; Dincer, Pervin

    2010-01-01

    Limb-girdle muscular dystrophy (LGMD) is a genetically heterogeneous group of inherited muscular disorders manifesting symmetric, proximal, and slowly progressive muscle weakness. Using Affymetrix 250K SNP Array genotyping and homozygosity mapping, we mapped an autosomal-recessive LGMD phenotype to the telomeric portion of chromosome 8q in a consanguineous Turkish family with three affected individuals. DNA sequence analysis of PLEC identified a homozygous c.1_9del mutation containing an initiation codon in exon 1f, which is an isoform-specific sequence of plectin isoform 1f. The same homozygous mutation was also detected in two additional families during the analysis of 72 independent LGMD2-affected families. Moreover, we showed that the expression of PLEC was reduced in the patient's muscle and that there was almost no expression for plectin 1f mRNA as a result of the mutation. In addition to dystrophic changes in muscle, ultrastructural alterations, such as membrane duplications, an enlarged space between the membrane and sarcomere, and misalignment of Z-disks, were observed by transmission electron microscopy. Unlike the control skeletal muscle, no sarcolemmal staining of plectin was detected in the patient's muscle. We conclude that as a result of plectin 1f deficiency, the linkage between the sarcolemma and sarcomere is broken, which could affect the structural organization of the myofiber. Our data show that one of the isoforms of plectin plays a key role in skeletal muscle function and that disruption of the plectin 1f can cause the LGMD2 phenotype without any dermatologic component as was previously reported with mutations in constant exons of PLEC. PMID:21109228

  11. 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

  12. 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

  13. Firearm trigger assembly

    DOEpatents

    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.

  14. Myofascial trigger point pain.

    PubMed

    Jaeger, Bernadette

    2013-01-01

    Myofascial trigger point pain is an extremely prevalent cause of persistent pain disorders in all parts of the body, not just the head, neck, and face. Features include deep aching pain in any structure, referred from focally tender points in taut bands of skeletal muscle (the trigger points). Diagnosis depends on accurate palpation with 2-4 kg/cm2 of pressure for 10 to 20 seconds over the suspected trigger point to allow the referred pain pattern to develop. In the head and neck region, cervical muscle trigger points (key trigger points) often incite and perpetuate trigger points (satellite trigger points) and referred pain from masticatory muscles. Management requires identification and control of as many perpetuating factors as possible (posture, body mechanics, psychological stress or depression, poor sleep or nutrition). Trigger point therapies such as spray and stretch or trigger point injections are best used as adjunctive therapy. PMID:24864393

  15. Novel NUP98-HOXC11 fusion gene resulted from a chromosomal break within exon 1 of HOXC11 in acute myeloid leukemia with t(11;12)(p15;q13).

    PubMed

    Taketani, Takeshi; Taki, Tomohiko; Shibuya, Noriko; Kikuchi, Akira; Hanada, Ryoji; Hayashi, Yasuhide

    2002-08-15

    The NUP98 gene has been reported to be fused to 11 partner genes in hematological malignancies with 11p15 translocations. Among NUP98 fusion partner genes, HOXA and HOXD clusters have been reported thus far; however, no HOXC or HOXB clusters have been reported. We identified a novel NUP98-HOXC11 fusion gene in a pediatric patient with de novo acute myeloid leukemia having t(11;12)(p15;q13). The breakpoint of NUP98 was located within a LINE repetitive sequence (HAL1) in intron 12, and the breakpoint of HOXC11 was located within exon 1, resulting in a NUP98-HOXC11 in-frame fusion transcript containing exon 12 of NUP98 fused to a part of exon 1 of HOXC11 with an 8-bp insertion derived from the intron sequence just 5' of the breakpoint of NUP98. The NUP98-HOXC11 fusion protein consists of the NH2-terminal phenylalanine-glycine repeat motif of NUP98 and the COOH-terminal homeodomain of HOXC11. Although the frequency of HOXC11 expression was not high in leukemia cell lines, its expression was significantly more frequent in myeloid than lymphoid leukemia cell lines. These data suggest that the NUP98-HOXC11 fusion protein plays a role in the pathogenesis of myeloid malignancies. PMID:12183408

  16. Asthma triggers (image)

    MedlinePlus

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

  17. 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.

  18. Triggered Jovian radio emissions

    NASA Technical Reports Server (NTRS)

    Calvert, W.

    1985-01-01

    Certain Jovian radio emissions seem to be triggered from outside, by much weaker radio waves from the sun. Recently found in the Voyager observations near Jupiter, such triggering occurs at hectometric wavelengths during the arrival of solar radio bursts, with the triggered emissions lasting sometimes more than an hour as they slowly drifted toward higher frequencies. Like the previous discovery of similar triggered emissions at the earth, this suggests that Jupiter's emissions might also originate from natural radio lasers.

  19. Ethanol Exposure Induces Neonatal Neurodegeneration by Enhancing CB1R Exon1 Histone H4K8 Acetylation and Up-regulating CB1R Function causing Neurobehavioral Abnormalities in Adult Mice

    PubMed Central

    Subbanna, Shivakumar; Nagre, Nagaraja N.; Umapathy, Nagavedi S.; Pace, Betty S.

    2015-01-01

    Background: Ethanol exposure to rodents during postnatal day 7 (P7), which is comparable to the third trimester of human pregnancy, induces long-term potentiation and memory deficits. However, the molecular mechanisms underlying these deficits are still poorly understood. Methods: In the present study, we explored the potential role of epigenetic changes at cannabinoid type 1 (CB1R) exon1 and additional CB1R functions, which could promote memory deficits in animal models of fetal alcohol spectrum disorder. Results: We found that ethanol treatment of P7 mice enhances acetylation of H4 on lysine 8 (H4K8ace) at CB1R exon1, CB1R binding as well as the CB1R agonist-stimulated GTPγS binding in the hippocampus and neocortex, two brain regions that are vulnerable to ethanol at P7 and are important for memory formation and storage, respectively. We also found that ethanol inhibits cyclic adenosine monophosphate response element-binding protein (CREB) phosphorylation and activity-regulated cytoskeleton-associated protein (Arc) expression in neonatal and adult mice. The blockade or genetic deletion of CB1Rs prior to ethanol treatment at P7 rescued CREB phosphorylation and Arc expression. CB1R knockout mice exhibited neither ethanol-induced neurodegeneration nor inhibition of CREB phosphorylation or Arc expression. However, both neonatal and adult mice did exhibit enhanced CREB phosphorylation and Arc protein expression. P7 ethanol-treated adult mice exhibited impaired spatial and social recognition memory, which were prevented by the pharmacological blockade or deletion of CB1Rs at P7. Conclusions: Together, these findings suggest that P7 ethanol treatment induces CB1R expression through epigenetic modification of the CB1R gene, and that the enhanced CB1R function induces pCREB, Arc, spatial, and social memory deficits in adult mice. PMID:25609594

  20. Stay away from asthma triggers

    MedlinePlus

    Asthma triggers - stay away from; Asthma triggers - avoiding; Reactive airway disease - triggers; Bronchial asthma - triggers ... to them. Have someone who does not have asthma cut the grass, or wear a facemask if ...

  1. Sequence analysis and structure prediction of 23S rRNA:m1G methyltransferases reveals a conserved core augmented with a putative Zn-binding domain in the N-terminus and family-specific elaborations in the C-terminus.

    PubMed

    Bujnicki, Janusz M; Blumenthal, Robert M; Rychlewski, Leszek

    2002-01-01

    N1-methylation of G748 within 23S ribosomal RNA results in resistance to the macrolide tylosin in Streptomyces. In contrast, the Escherichia coli mutant lacking N1-methylation of G745 exhibits increased resistance to viomycin, in addition to severe defects of growth characteristics. Both methylated guanines are located in hairpin 35, in domain II of prokaryotic 23S rRNA. G748 and G745 are modified by related S-adenosylmethionine-dependent methyltransferases (MTases), TlrB and RrmA respectively. Earlier sequence comparisons allowed identification of the AdoMet-binding site, however the catalytic site and the target-recognition region of these enzymes could not be delineated unambiguously. In this work, we carried out sequence-to-structure threading of the rRNA:m1G MTase family against the database of known structures to Identify those "missing regions". Our analysis confirms the earlier prediction of the AdoMet-binding site, but suggests a different location of the putative catalytic center than was previously postulated. We predict that RrmA and TlrB possess two regions that may be responsible for specific interactions with their target nucleic acid sequences: a putative Zn-finger domain in the N-terminus and the variable domain close to the C-terminus, which indicates that 23S rRNA MTases exhibit the primary structural organization distinct from other nucleic acid MTases, despite sharing the common catalytic domain. PMID:11763974

  2. Axon injury triggers EFA-6 mediated destabilization of axonal microtubules via TACC and doublecortin like kinase

    PubMed Central

    Chen, Lizhen; Chuang, Marian; Koorman, Thijs; Boxem, Mike; Jin, Yishi; Chisholm, Andrew D

    2015-01-01

    Axon injury triggers a series of changes in the axonal cytoskeleton that are prerequisites for effective axon regeneration. In Caenorhabditis elegans the signaling protein Exchange Factor for ARF-6 (EFA-6) is a potent intrinsic inhibitor of axon regrowth. Here we show that axon injury triggers rapid EFA-6-dependent inhibition of axonal microtubule (MT) dynamics, concomitant with relocalization of EFA-6. EFA-6 relocalization and axon regrowth inhibition require a conserved 18-aa motif in its otherwise intrinsically disordered N-terminal domain. The EFA-6 N-terminus binds the MT-associated proteins TAC-1/Transforming-Acidic-Coiled-Coil, and ZYG-8/Doublecortin-Like-Kinase, both of which are required for regenerative growth cone formation, and which act downstream of EFA-6. After injury TAC-1 and EFA-6 transiently relocalize to sites marked by the MT minus end binding protein PTRN-1/Patronin. We propose that EFA-6 acts as a bifunctional injury-responsive regulator of axonal MT dynamics, acting at the cell cortex in the steady state and at MT minus ends after injury. DOI: http://dx.doi.org/10.7554/eLife.08695.001 PMID:26339988

  3. Causality and headache triggers

    PubMed Central

    Turner, Dana P.; Smitherman, Todd A.; Martin, Vincent T.; Penzien, Donald B.; Houle, Timothy T.

    2013-01-01

    Objective The objective of this study was to explore the conditions necessary to assign causal status to headache triggers. Background The term “headache trigger” is commonly used to label any stimulus that is assumed to cause headaches. However, the assumptions required for determining if a given stimulus in fact has a causal-type relationship in eliciting headaches have not been explicated. Methods A synthesis and application of Rubin’s Causal Model is applied to the context of headache causes. From this application the conditions necessary to infer that one event (trigger) causes another (headache) are outlined using basic assumptions and examples from relevant literature. Results Although many conditions must be satisfied for a causal attribution, three basic assumptions are identified for determining causality in headache triggers: 1) constancy of the sufferer; 2) constancy of the trigger effect; and 3) constancy of the trigger presentation. A valid evaluation of a potential trigger’s effect can only be undertaken once these three basic assumptions are satisfied during formal or informal studies of headache triggers. Conclusions Evaluating these assumptions is extremely difficult or infeasible in clinical practice, and satisfying them during natural experimentation is unlikely. Researchers, practitioners, and headache sufferers are encouraged to avoid natural experimentation to determine the causal effects of headache triggers. Instead, formal experimental designs or retrospective diary studies using advanced statistical modeling techniques provide the best approaches to satisfy the required assumptions and inform causal statements about headache triggers. PMID:23534872

  4. 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.

  5. 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

  6. 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.

  7. 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 ...

  8. 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 ...

  9. 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.

  10. Calorimetry Triggering in ATLAS

    SciTech Connect

    Igonkina, O.; Achenbach, R.; Adragna, P.; Aharrouche, M.; Alexandre, G.; Andrei, V.; Anduaga, X.; Aracena, I.; Backlund, S.; Baines, J.; Barnett, B.M.; Bauss, B.; Bee, C.; Behera, P.; Bell, P.; Bendel, M.; Benslama, K.; Berry, T.; Bogaerts, A.; Bohm, C.; Bold, T.; /UC, Irvine /AGH-UST, Cracow /Birmingham U. /Barcelona, IFAE /CERN /Birmingham U. /Rutherford /Montreal U. /Santa Maria U., Valparaiso /DESY /DESY, Zeuthen /Geneva U. /City Coll., N.Y. /Barcelona, IFAE /CERN /Birmingham U. /Kirchhoff Inst. Phys. /Birmingham U. /Lisbon, LIFEP /Rio de Janeiro Federal U. /City Coll., N.Y. /Birmingham U. /Copenhagen U. /Copenhagen U. /Brookhaven /Rutherford /Royal Holloway, U. of London /Pennsylvania U. /Montreal U. /SLAC /CERN /Michigan State U. /Chile U., Catolica /City Coll., N.Y. /Oxford U. /La Plata U. /McGill U. /Mainz U., Inst. Phys. /Hamburg U. /DESY /DESY, Zeuthen /Geneva U. /Queen Mary, U. of London /CERN /Rutherford /Rio de Janeiro Federal U. /Birmingham U. /Montreal U. /CERN /Kirchhoff Inst. Phys. /Liverpool U. /Royal Holloway, U. of London /Pennsylvania U. /Kirchhoff Inst. Phys. /Geneva U. /Birmingham U. /NIKHEF, Amsterdam /Rutherford /Royal Holloway, U. of London /Rutherford /Royal Holloway, U. of London /AGH-UST, Cracow /Mainz U., Inst. Phys. /Mainz U., Inst. Phys. /Birmingham U. /Hamburg U. /DESY /DESY, Zeuthen /Geneva U. /Kirchhoff Inst. Phys. /Michigan State U. /Stockholm U. /Stockholm U. /Birmingham U. /CERN /Montreal U. /Stockholm U. /Arizona U. /Regina U. /Regina U. /Rutherford /NIKHEF, Amsterdam /Kirchhoff Inst. Phys. /DESY /DESY, Zeuthen /City Coll., N.Y. /University Coll. London /Humboldt U., Berlin /Queen Mary, U. of London /Argonne /LPSC, Grenoble /Arizona U. /Kirchhoff Inst. Phys. /Birmingham U. /Antonio Narino U. /Hamburg U. /DESY /DESY, Zeuthen /Kirchhoff Inst. Phys. /Birmingham U. /Chile U., Catolica /Indiana U. /Manchester U. /Kirchhoff Inst. Phys. /Rutherford /City Coll., N.Y. /Stockholm U. /La Plata U. /Antonio Narino U. /Queen Mary, U. of London /Kirchhoff Inst. Phys. /Antonio Narino U. /Pavia U. /City Coll., N.Y. /Mainz U., Inst. Phys. /Mainz U., Inst. Phys. /Pennsylvania U. /Barcelona, IFAE /Barcelona, IFAE /Chile U., Catolica /Genoa U. /INFN, Genoa /Rutherford /Barcelona, IFAE /Nevis Labs, Columbia U. /CERN /Antonio Narino U. /McGill U. /Rutherford /Santa Maria U., Valparaiso /Rutherford /Chile U., Catolica /Brookhaven /Oregon U. /Mainz U., Inst. Phys. /Barcelona, IFAE /McGill U. /Antonio Narino U. /Antonio Narino U. /Kirchhoff Inst. Phys. /Sydney U. /Rutherford /McGill U. /McGill U. /Pavia U. /Genoa U. /INFN, Genoa /Kirchhoff Inst. Phys. /Kirchhoff Inst. Phys. /Mainz U., Inst. Phys. /Barcelona, IFAE /SLAC /Stockholm U. /Moscow State U. /Stockholm U. /Birmingham U. /Kirchhoff Inst. Phys. /DESY /DESY, Zeuthen /Birmingham U. /Geneva U. /Oregon U. /Barcelona, IFAE /University Coll. London /Royal Holloway, U. of London /Birmingham U. /Mainz U., Inst. Phys. /Birmingham U. /Birmingham U. /Oregon U. /La Plata U. /Geneva U. /Chile U., Catolica /McGill U. /Pavia U. /Barcelona, IFAE /Regina U. /Birmingham U. /Birmingham U. /Kirchhoff Inst. Phys. /Oxford U. /CERN /Kirchhoff Inst. Phys. /UC, Irvine /UC, Irvine /Wisconsin U., Madison /Rutherford /Mainz U., Inst. Phys. /CERN /Geneva U. /Copenhagen U. /City Coll., N.Y. /Wisconsin U., Madison /Rio de Janeiro Federal U. /Wisconsin U., Madison /Stockholm U. /University Coll. London

    2011-12-08

    The ATLAS experiment is preparing for data taking at 14 TeV collision energy. A rich discovery physics program is being prepared in addition to the detailed study of Standard Model processes which will be produced in abundance. The ATLAS multi-level trigger system is designed to accept one event in 2/10{sup 5} to enable the selection of rare and unusual physics events. The ATLAS calorimeter system is a precise instrument, which includes liquid Argon electro-magnetic and hadronic components as well as a scintillator-tile hadronic calorimeter. All these components are used in the various levels of the trigger system. A wide physics coverage is ensured by inclusively selecting events with candidate electrons, photons, taus, jets or those with large missing transverse energy. The commissioning of the trigger system is being performed with cosmic ray events and by replaying simulated Monte Carlo events through the trigger and data acquisition system.

  11. Dynamic Triggering Stress Modeling

    NASA Astrophysics Data System (ADS)

    Gonzalez-Huizar, H.; Velasco, A. A.

    2008-12-01

    It has been well established that static (permanent) stress changes can trigger nearby earthquakes, within a few fault lengths from the causative event, whereas triggering by dynamic (transient) stresses carried by seismic waves both nearby and at remote distances has not been as well documented nor understood. An analysis of the change in the local stress caused by the passing of surfaces waves is important for the understanding of this phenomenon. In this study, we modeled the change in the stress that the passing of Rayleigh and Loves waves causes on a fault plane of arbitrary orientation, and applied a Coulomb failure criteria to calculate the potential of these stress changes to trigger reverse, normal or strike-slip failure. We preliminarily test these model results with data from dynamically triggering earthquakes in the Australian Bowen Basin. In the Bowen region, the modeling predicts a maximum triggering potential for Rayleigh waves arriving perpendicularly to the strike of the reverse faults present in the region. The modeled potentials agree with our observations, and give us an understanding of the dynamic stress orientation needed to trigger different type of earthquakes.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. TOTEM Trigger System Firmware

    NASA Astrophysics Data System (ADS)

    Kopal, Josef

    2014-06-01

    This paper describes the TOTEM Trigger System Firmware that is operational at LHC since 2009. The TOTEM experiment is devoted to the forward hadronic physics at collision energy from 2.7 to 14TeV. It is composed of three different subdetectors that are placed at 9, 13.5, and 220m from the Interaction Point 5. A time-critical-logic firmware is implemented inside FPGA circuits to review collisions and to select the relevant ones to be stored by the Data Acquisition (DAQ). The Trigger system has been modified in the 2012-2013 LHC runs allowing the experiment to take data in cooperation with CMS.

  17. 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…

  18. 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.

  19. 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.

  20. 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

  1. GLAST's GBM Burst Trigger

    NASA Technical Reports Server (NTRS)

    Band, D.; Briggs, M.; Connaughton, V.; Kippen, M.; Preece, R.

    2003-01-01

    The GLAST Burst Monitor (GBM) will detect and localize bursts for the GLAST mission, and provide the spectral and temporal context in the traditional 10 keV to 25 MeV band for the high energy observations by the Large Area Telescope (LAT). The GBM will use traditional rate triggers in up to three energy bands, and on a variety of timescales between 16 ms and 16 s.

  2. GLAST's GBM Burst Trigger

    SciTech Connect

    Band, D.; Kippen, M.

    2004-09-28

    The GLAST Burst Monitor (GBM) will detect and localize bursts for the GLAST mission, and provide the spectral and temporal context in the traditional 10 keV to 25 MeV band for the high energy observations by the Large Area Telescope (LAT). The GBM will use traditional rate triggers in up to three energy bands, and on a variety of timescales between 16 ms and 16 s.

  3. 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.

  4. 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

  5. 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

  6. Triggered Codeswitching between Cognate Languages

    ERIC Educational Resources Information Center

    Broersma, Mirjam

    2009-01-01

    This study shows further evidence for triggered codeswitching. In natural speech from a Dutch-English bilingual, codeswitches occurred more often directly next to a cognate (or "trigger word") than elsewhere. This evidence from typologically related, cognate languages extends previous evidence for triggering between typologically unrelated…

  7. 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.

  8. Protons Trigger Mitochondrial Flashes.

    PubMed

    Wang, Xianhua; Zhang, Xing; Huang, Zhanglong; Wu, Di; Liu, Beibei; Zhang, Rufeng; Yin, Rongkang; Hou, Tingting; Jian, Chongshu; Xu, Jiejia; Zhao, Yan; Wang, Yanru; Gao, Feng; Cheng, Heping

    2016-07-26

    Emerging evidence indicates that mitochondrial flashes (mitoflashes) are highly conserved elemental mitochondrial signaling events. However, which signal controls their ignition and how they are integrated with other mitochondrial signals and functions remain elusive. In this study, we aimed to further delineate the signal components of the mitoflash and determine the mitoflash trigger mechanism. Using multiple biosensors and chemical probes as well as label-free autofluorescence, we found that the mitoflash reflects chemical and electrical excitation at the single-organelle level, comprising bursting superoxide production, oxidative redox shift, and matrix alkalinization as well as transient membrane depolarization. Both electroneutral H(+)/K(+) or H(+)/Na(+) antiport and matrix proton uncaging elicited immediate and robust mitoflash responses over a broad dynamic range in cardiomyocytes and HeLa cells. However, charge-uncompensated proton transport, which depolarizes mitochondria, caused the opposite effect, and steady matrix acidification mildly inhibited mitoflashes. Based on a numerical simulation, we estimated a mean proton lifetime of 1.42 ns and diffusion distance of 2.06 nm in the matrix. We conclude that nanodomain protons act as a novel, to our knowledge, trigger of mitoflashes in energized mitochondria. This finding suggests that mitoflash genesis is functionally and mechanistically integrated with mitochondrial energy metabolism. PMID:27463140

  9. Effector triggered immunity

    PubMed Central

    Rajamuthiah, Rajmohan; Mylonakis, Eleftherios

    2014-01-01

    Pathogenic bacteria produce virulence factors called effectors, which are important components of the infection process. Effectors aid in pathogenesis by facilitating bacterial attachment, pathogen entry into or exit from the host cell, immunoevasion, and immunosuppression. Effectors also have the ability to subvert host cellular processes, such as hijacking cytoskeletal machinery or blocking protein translation. However, host cells possess an evolutionarily conserved innate immune response that can sense the pathogen through the activity of its effectors and mount a robust immune response. This “effector triggered immunity” (ETI) was first discovered in plants but recent evidence suggest that the process is also well conserved in metazoans. We will discuss salient points of the mechanism of ETI in metazoans from recent studies done in mammalian cells and invertebrate model hosts. PMID:25513770

  10. 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.

  11. 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.

  12. Triggering with the LHCb calorimeters

    NASA Astrophysics Data System (ADS)

    Lefevre, Regis; LHCb Collaboration

    2009-04-01

    The LHCb experiment at the LHC has been conceived to pursue high precision studies of CP violation and rare phenomena in b hadron decays. The online selection is crucial in LHCb and relies on the calorimeters to trigger on high transverse energy electrons, photons, π0 and hadrons. In this purpose a dedicated electronic has been realized. The calorimeter trigger system has been commissioned and is used to trigger on cosmic muons before beams start circulating in the LHC. When the LHC will start, it will also provide a very useful interaction trigger.

  13. 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

  14. Triggering of repeated earthquakes

    NASA Astrophysics Data System (ADS)

    Sobolev, G. A.; Zakrzhevskaya, N. A.; Sobolev, D. G.

    2016-03-01

    Based on the analysis of the world's earthquakes with magnitudes M ≥ 6.5 for 1960-2013, it is shown that they cause global-scale coherent seismic oscillations which most distinctly manifest themselves in the period interval of 4-6 min during 1-3 days after the event. After these earthquakes, a repeated shock has an increased probability to occur in different seismically active regions located as far away as a few thousand km from the previous event, i.e., a remote interaction of seismic events takes place. The number of the repeated shocks N( t) decreases with time, which characterizes the memory of the lithosphere about the impact that has occurred. The time decay N( t) can be approximated by the linear, exponential, and powerlaw dependences. No distinct correlation between the spatial locations of the initial and repeated earthquakes is revealed. The probable triggering mechanisms of the remote interaction between the earthquakes are discussed. Surface seismic waves traveling several times around the Earth's, coherent oscillations, and global source are the most preferable candidates. This may lead to the accumulation and coalescence of ruptures in the highly stressed or weakened domains of a seismically active region, which increases the probability of a repeated earthquake.

  15. Fermi GBM Early Trigger Characteristics

    SciTech Connect

    Connaughton, Valerie; Briggs, Michael; Paciesas, Bill; Meegan, Charles

    2009-05-25

    Since the launch of the Fermi observatory on June 11 2008, the Gamma-ray Burst Monitor (GBM) has seen approximately 250 triggers of which about 150 were cosmic gamma-ray bursts (GRBs). GBM operates dozens of trigger algorithms covering various energy bands and timescales and is therefore sensitive to a wide variety of phenomena, both astrophysical and not.

  16. 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.

  17. 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.

  18. 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.

  19. 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. PMID:16208360

  20. The D0 upgrade trigger

    SciTech Connect

    Eno, S.

    1994-09-01

    The current trigger system for the D0 detector at Fermilab`s Tevatron will need to be upgraded when the Min Injector is installed and the Tevatron can operate at luminosities exceeding 10{sup 32} cm{sup {minus}2}s{sup {minus}1} and with a crossing time of 132 ns. We report on preliminary designs for upgrades to the trigger system for the Main Injector era.

  1. Anthropogenic Triggering of Large Earthquakes

    NASA Astrophysics Data System (ADS)

    Mulargia, Francesco; Bizzarri, Andrea

    2014-08-01

    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.

  2. 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

  3. 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

  4. Slow earthquakes triggered by typhoons.

    PubMed

    Liu, ChiChing; Linde, Alan T; Sacks, I Selwyn

    2009-06-11

    The first reports on a slow earthquake were for an event in the Izu peninsula, Japan, on an intraplate, seismically active fault. Since then, many slow earthquakes have been detected. It has been suggested that the slow events may trigger ordinary earthquakes (in a context supported by numerical modelling), but their broader significance in terms of earthquake occurrence remains unclear. Triggering of earthquakes has received much attention: strain diffusion from large regional earthquakes has been shown to influence large earthquake activity, and earthquakes may be triggered during the passage of teleseismic waves, a phenomenon now recognized as being common. Here we show that, in eastern Taiwan, slow earthquakes can be triggered by typhoons. We model the largest of these earthquakes as repeated episodes of slow slip on a reverse fault just under land and dipping to the west; the characteristics of all events are sufficiently similar that they can be modelled with minor variations of the model parameters. Lower pressure results in a very small unclamping of the fault that must be close to the failure condition for the typhoon to act as a trigger. This area experiences very high compressional deformation but has a paucity of large earthquakes; repeating slow events may be segmenting the stressed area and thus inhibiting large earthquakes, which require a long, continuous seismic rupture. PMID:19516339

  5. Industrial accidents triggered by lightning.

    PubMed

    Renni, Elisabetta; Krausmann, Elisabeth; Cozzani, Valerio

    2010-12-15

    Natural disasters can cause major accidents in chemical facilities where they can lead to the release of hazardous materials which in turn can result in fires, explosions or toxic dispersion. Lightning strikes are the most frequent cause of major accidents triggered by natural events. In order to contribute towards the development of a quantitative approach for assessing lightning risk at industrial facilities, lightning-triggered accident case histories were retrieved from the major industrial accident databases and analysed to extract information on types of vulnerable equipment, failure dynamics and damage states, as well as on the final consequences of the event. The most vulnerable category of equipment is storage tanks. Lightning damage is incurred by immediate ignition, electrical and electronic systems failure or structural damage with subsequent release. Toxic releases and tank fires tend to be the most common scenarios associated with lightning strikes. Oil, diesel and gasoline are the substances most frequently released during lightning-triggered Natech accidents. PMID:20817399

  6. 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.

  7. 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.

  8. Detector array control and triggering

    SciTech Connect

    Aiello, S.; Anzalone, A.; Bartolucci, M. |

    1998-08-01

    A commercial DSP-based board installed in a host-PC was employed for the fast, on-line and real-time computation of special algorithms, in order to perform event selection and operate as a 2nd level trigger. Moreover an ad hoc build interface, realized using PLDs with a view to connecting the DSP-board to the ADCs and to the data acquisition system, has been tested in order to evaluate the performances of these programmable devices used as a look-up-table and as a decisional part of a 1st level trigger.

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. Soluble CD40 ligand induces β3 integrin tyrosine phosphorylation and triggers platelet activation by outside-in signaling

    PubMed Central

    Prasad, K. S. Srinivasa; Andre, Patrick; He, Ming; Bao, Ming; Manganello, Jeanne; Phillips, David R.

    2003-01-01

    We earlier reported that the soluble form of the CD40 ligand (sCD40L), is involved in thrombosis by stabilizing platelet thrombi. In this article, we have determined the mechanism by which this protein affects platelet biology. Addition of sCD40L to washed platelets was found to activate the receptor function of αIIbβ3 as measured by the induction of fibrinogen binding and the formation of platelet microparticles. Mutation in the KGD sequence (D117E) of sCD40L, the αIIbβ3-binding domain in the N terminus of the protein resulted in a loss of the platelet-stimulatory activity of this protein. Integrilin, a αIIbβ3 antagonist, but not an antibody to CD40 that blocked the ligand-binding activity, inhibited these platelet-stimulatory events. CD40-/- platelets bound fibrinogen and formed microparticles similar to WT platelets, again indicating that CD40 is not involved in sCD40L-induced platelet activation. Exposure of platelets to sCD40L, but not D117E-sCD40L-coated surfaces, induced platelet thrombi formation under arterial shear rate. sCD40L-induced platelet stimulation resulted in the phosphorylation of tyrosine-759 in the cytoplasmic domain of β3. Platelets from the diYF mouse strain, expressing β3 in which both cytoplasmic tyrosines are mutated to phenylalanine, were defective in sCD40L-induced platelet stimulation. These data indicate that sCD40L is a primary platelet agonist and that platelet stimulation is induced by the binding of the KGD domain of sCD40L to αIIbβ3, triggering outside-in signaling by tyrosine phosphorylation of β3. PMID:14519852

  15. 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.

  16. 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.

  17. The L3 energy trigger

    NASA Astrophysics Data System (ADS)

    Bizzarri, R.; Cesaroni, F.; Gentile, S.; Lunadei, G.; Fukushima, M.; Herten, G.; Hebbeker, T.

    1989-11-01

    The L3 first-level energy trigger is based on energy measurements in electromagnetic and hadronic calorimeters and in luminosity monitors. The information from these detectors is evaluated and a decision is taken in about 20 μs (the time between two bunch crossings in LEP is 22 μs). This trigger makes use of 300 CAMAC modules: an arithmetic logic unit (ALU), a BUS multiplexer (BS), a memory lookup table (MLU), a data stack (DS) and a fast encoding and readout ADC (FERA), each of them performing dedicated functions. The data are transmitted via front-panel ECL buses. The CAMAC data-way is used only for initialization and checking purposes. The system operates synchronously with a period of 60 ns.

  18. Optical Spectra of Triggered Lightning

    NASA Astrophysics Data System (ADS)

    Walker, T. D.; Biagi, C. J.; Hill, J. D.; Jordan, D. M.; Uman, M. A.; Christian, H. J., Jr.

    2009-12-01

    In August 2009, the first optical spectra of triggered lightning flashes were acquired. Data from two triggered lightning flashes were obtained at the International Center for Lightning Research and Testing in north-central Florida. The spectrometer that was used has an average dispersion of 260 Å/mm resulting in an average resolution of 5 Å when mated to a Photron (SA1.1) high-speed camera. The spectra captured with this system had a free spectral range of 3800-8000 Å. The spectra were captured at 300,000 frames per second. The spectrometer's vertical field of view was 3 m at an altitude 50 m above the launch tower, intended to view the middle of the triggering wire. Preliminary results show that the copper spectrum dominated the earliest part of the flash and copper lines persisted during the total lifetime of the detectable spectrum. Animations over the lifetime of the stroke from the initial wire illumination to multiple return strokes show the evolution of the spectrum. In addition, coordinated high speed channel base current, electric field and imagery measurements of the exploding wire, downward leaders, and return strokes were recorded. Quantitative analysis of the spectral evolution will be discussed in the context of the overall flash development.

  19. 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.

  20. 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.

  1. Triggering for charm, beauty, and truth

    SciTech Connect

    Appel, J.A.

    1982-02-01

    As the search for more and more rare processes accelerates, the need for more and more effective event triggers also accelerates. In the earliest experiments, a simple coincidence often sufficed not only as the event trigger, but as the complete record of an event of interest. In today's experiments, not only has the fast trigger become more sophisticated, but one or more additional level of trigger processing precedes writing event data to magnetic tape for later analysis. Further search experiments will certainly require further expansion in the number of trigger levels required to filter those rare events of particular interest.

  2. The Database Driven ATLAS Trigger Configuration System

    NASA Astrophysics Data System (ADS)

    Chavez, Carlos; Gianelli, Michele; Martyniuk, Alex; Stelzer, Joerg; Stockton, Mark; Vazquez, Will

    2015-12-01

    The ATLAS trigger configuration system uses a centrally provided relational database to store the configurations for all levels of the ATLAS trigger system. The configuration used at any point during data taking is maintained in this database. A interface to this database is provided by the TriggerTool, a Java-based graphical user interface. The TriggerTool has been designed to work as both a convenient browser and editor of configurations in the database for both general users and experts. The updates to the trigger system necessitated by the upgrades and changes in both hardware and software during the first long shut down of the LHC will be explored.

  3. 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.

  4. Membrane-triggered plant immunity

    PubMed Central

    Jung, Su-Jin; Lee, Hong Gil; Seo, Pil Joon

    2014-01-01

    Plants have evolved sophisticated defense mechanisms to resist pathogen invasion. Upon the pathogen recognition, the host plants activate a variety of signal transduction pathways, and one of representative defense responses is systemic acquired resistance (SAR) that provides strong immunity against secondary infections in systemic tissues. Accumulating evidence has demonstrated that modulation of membrane composition contributes to establishing SAR and disease resistance in Arabidopsis, but underlying molecular mechanisms remain to be elucidated. Here, we show that a membrane-bound transcription factor (MTF) is associated with plant responses to pathogen attack. The MTF is responsive to microbe-associated molecular pattern (MAMP)-triggered membrane rigidification at the levels of transcription and proteolytic processing. The processed nuclear transcription factor possibly regulates pathogen resistance by directly regulating PATHOGENESIS-RELATED (PR) genes. Taken together, our results suggest that pathogenic microorganisms trigger changes in physico-chemical properties of cellular membrane in plants, and the MTF conveys the membrane information to the nucleus to ensure prompt establishment of plant immunity. PMID:25763708

  5. 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.

  6. 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

  7. 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.

  8. Is osseointegration inflammation-triggered?

    PubMed

    Vitkov, Ljubomir; Hartl, Dominik; Hannig, Matthias

    2016-08-01

    Bioinert endosteal implants cause a foreign body reaction, whereas bioactive ones cause osseointegration. However, the mechanisms responsible for the two modi of host response remain unclear. COX-2(-/-) animal models showed the dependence of osseointegration on prostaglandins. PGE2, a product of COX-2, augments Wnt signalling, a pathway that promotes the regeneration in many types of tissues. Recently, we demonstrated the ability of bioactive implants to recruit neutrophils and to trigger neutrophil extracellular traps (NETs), which are a potent source of PGE2. In bioinert implants no PGE2 release has been ascertained. Collectively, these findings suggest that osseointegration might be the host response to bioactive implants, novel and quite different to the so-called foreign body reaction. PMID:27372846

  9. Acoustic properties of triggered lightning

    NASA Astrophysics Data System (ADS)

    Dayeh, M. A.; Evans, N.; Ramaekers, J.; Trevino, J.; Rassoul, H.; Lucia, R. J.; Dwyer, J. R.; Uman, M. A.; Jordan, D. M.

    2014-12-01

    Acoustic signatures from rocket-triggered lightning are measured by a 15m long, one-dimensional microphone array consisting of 16 receivers situated 90 meters from the lightning channel. Measurements were taken at the International Center for Lightning Research and Testing (ICLRT) in Camp Blanding, FL during the summer of 2014. The linear array was oriented in an end-fire position so that the peak acoustic reception pattern can be steered vertically along the channel with a frequency-dependent spatial resolution, enabling us to sample the acoustic signatures from different portions along the lightning channel. We report on the characteristics of acoustic signatures associated with several return strokes in 6 measured flashes (total of 29 return strokes). In addition, we study the relationship between the amplitude, peak frequency, and inferred energy input of each stroke acoustic signature and the associated measured lightning parameters. Furthermore, challenges of obtaining acoustic measurements in thunderstorm harsh conditions and their countermeasures will also be discussed.

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. Diet and Dermatitis: Food Triggers

    PubMed Central

    Schlichte, Megan

    2014-01-01

    Given increasing awareness of the link between diet and health, many patients are concerned that dietary factors may trigger dermatitis. Research has found that dietary factors can indeed exacerbate atopic dermatitis or cause dermatitis due to systemic contact dermatitis. In atopic dermatitis, dietary factors are more likely to cause an exacerbation among infants or children with moderate-to-severe atopic dermatitis relative to other populations. Foods may trigger rapid, immunoglobulin E-mediated hypersensitivity reactions or may lead to late eczematous reactions. While immediate reactions occur within minutes to hours of food exposure, late eczematous reactions may occur anywhere from hours to two days later. Screening methods, such as food allergen-specific serum immunoglobulin E tests or skin prick tests, can identify sensitization to specific foods, but a diagnosis of food allergy requires specific signs and symptoms that occur reproducibly upon food exposure. Many patients who are sensitized will not develop clinical findings upon food exposure; therefore, these tests may result in false-positive tests for food allergy. This is why the gold standard for diagnosis remains the double-blind, placebo-controlled food challenge. In another condition, systemic contact dermatitis, ingestion of a specific food can actually cause dermatitis. Systemic contact dermatitis is a distinct T-cell mediated immunological reaction in which dietary exposure to specific allergens results in dermatitis. Balsam of Peru and nickel are well-known causes of systemic contact dermatitis, and reports have implicated multiple other allergens. This review seeks to increase awareness of important food allergens, elucidate their relationship with atopic dermatitis and systemic contact dermatitis, and review available diagnostic and treatment strategies. PMID:24688624

  16. A novel calorimeter trigger concept: The jet trigger of the H1 experiment at HERA

    NASA Astrophysics Data System (ADS)

    Olivier, Bob; Dubak-Behrendt, Ana; Kiesling, Christian; Reisert, Burkard; Aktas, Adil; Antunovic, Biljana; Bracinik, Juraj; Braquet, Charles; Brettel, Horst; Dulny, Barbara; Fent, Jürgen; Fras, Markus; Fröchtenicht, Walter; Haberer, Werner; Hoffmann, Dirk; Modjesch, Miriam; Placakyte, Ringaile; Schörner-Sadenius, Thomas; Wassatsch, Andreas; Zimmermann, Jens

    2011-06-01

    We report on a novel trigger for the liquid argon calorimeter which was installed in the H1 Experiment at HERA. This trigger, called the "Jet Trigger", was running at level 1 and implemented a real-time cluster algorithm. Within only 800 ns, the Jet Trigger algorithm found local energy maxima in the calorimeter, summed their immediate neighbors, sorted the resulting jets by energy, and applied topological conditions for the final level 1 trigger decision. The Jet Trigger was in operation from the year 2006 until the end of the HERA running in the summer of 2007. With the Jet Trigger it was possible to substantially reduce the thresholds for triggering on electrons and jets, giving access to a largely extended phase space for physical observables which could not have been reached in H1 before. The concepts of the Jet Trigger may be an interesting upgrade option for the LHC experiments.

  17. 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

  18. Smart trigger logic for focal plane arrays

    SciTech Connect

    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.

  19. 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.

  20. Phosphorylation Interferes with Maturation of Amyloid-β Fibrillar Structure in the N Terminus.

    PubMed

    Rezaei-Ghaleh, Nasrollah; Kumar, Sathish; Walter, Jochen; Zweckstetter, Markus

    2016-07-29

    Neurodegeneration is characterized by the ubiquitous presence of modifications in protein deposits. Despite their potential significance in the initiation and progression of neurodegenerative diseases, the effects of posttranslational modifications on the molecular properties of protein aggregates are largely unknown. Here, we study the Alzheimer disease-related amyloid-β (Aβ) peptide and investigate how phosphorylation at serine 8 affects the structure of Aβ aggregates. Serine 8 is shown to be located in a region of high conformational flexibility in monomeric Aβ, which upon phosphorylation undergoes changes in local conformational dynamics. Using hydrogen-deuterium exchange NMR and fluorescence quenching techniques, we demonstrate that Aβ phosphorylation at serine 8 causes structural changes in the N-terminal region of Aβ aggregates in favor of less compact conformations. Structural changes induced by serine 8 phosphorylation can provide a mechanistic link between phosphorylation and other biological events that involve the N-terminal region of Aβ aggregates. Our data therefore support an important role of posttranslational modifications in the structural polymorphism of amyloid aggregates and their modulatory effect on neurodegeneration. PMID:27252381

  1. Cloning and bioinformatical analysis of the N-terminus of the sonic hedgehog gene.

    PubMed

    Zhang, Yi; Zhao, Shu; Dong, Weiren; He, Suifen; Wang, Haihong; Zhang, Lihua; Tang, Yinjuan; Guo, Jiasong; Guo, Suiqun

    2013-01-25

    The sonic hedgehog protein not only plays a key role in early embryonic development, but also has essential effects on the adult nervous system, including neural stem cell proliferation, differentiation, migration and neuronal axon guidance. The N-terminal fragment of sonic hedgehog is the key functional element in this process. Therefore, this study aimed to clone and analyze the N-terminal fragment of the sonic hedgehog gene. Total RNA was extracted from the notochord of a Sprague-Dawley rat at embryonic day 9 and the N-terminal fragment of sonic hedgehog was amplified by nested reverse transcription-PCR. The N-terminal fragment of the sonic hedgehog gene was successfully cloned. The secondary and tertiary structures of the N-terminal fragment of the sonic hedgehog protein were predicted using Jpred and Phyre online. PMID:25206596

  2. Structural and Functional Characterization of the N Terminus of Schizosaccharomyces pombe Cwf10

    PubMed Central

    Livesay, S. Brent; Collier, Scott E.; Bitton, Danny A.; Bähler, Jürg

    2013-01-01

    The spliceosome is a dynamic macromolecular machine that catalyzes the removal of introns from pre-mRNA, yielding mature message. Schizosaccharomyces pombe Cwf10 (homolog of Saccharomyces cerevisiae Snu114 and human U5-116K), an integral member of the U5 snRNP, is a GTPase that has multiple roles within the splicing cycle. Cwf10/Snu114 family members are highly homologous to eukaryotic translation elongation factor EF2, and they contain a conserved N-terminal extension (NTE) to the EF2-like portion, predicted to be an intrinsically unfolded domain. Using S. pombe as a model system, we show that the NTE is not essential, but cells lacking this domain are defective in pre-mRNA splicing. Genetic interactions between cwf10-ΔNTE and other pre-mRNA splicing mutants are consistent with a role for the NTE in spliceosome activation and second-step catalysis. Characterization of Cwf10-NTE by various biophysical techniques shows that in solution the NTE contains regions of both structure and disorder. The first 23 highly conserved amino acids of the NTE are essential for its role in splicing but when overexpressed are not sufficient to restore pre-mRNA splicing to wild-type levels in cwf10-ΔNTE cells. When the entire NTE is overexpressed in the cwf10-ΔNTE background, it can complement the truncated Cwf10 protein in trans, and it immunoprecipitates a complex similar in composition to the late-stage U5.U2/U6 spliceosome. These data show that the structurally flexible NTE is capable of independently incorporating into the spliceosome and improving splicing function, possibly indicating a role for the NTE in stabilizing conformational rearrangements during a splice cycle. PMID:24014766

  3. The mycobacterial Mpa–proteasome unfolds and degrades pupylated substrates by engaging Pup's N-terminus

    PubMed Central

    Striebel, Frank; Hunkeler, Moritz; Summer, Heike; Weber-Ban, Eilika

    2010-01-01

    Mycobacterium tuberculosis, along with other actinobacteria, harbours proteasomes in addition to members of the general bacterial repertoire of degradation complexes. In analogy to ubiquitination in eukaryotes, substrates are tagged for proteasomal degradation with prokaryotic ubiquitin-like protein (Pup) that is recognized by the N-terminal coiled-coil domain of the ATPase Mpa (also called ARC). Here, we reconstitute the entire mycobacterial proteasome degradation system for pupylated substrates and establish its mechanistic features with respect to substrate recruitment, unfolding and degradation. We show that the Mpa–proteasome complex unfolds and degrades Pup-tagged proteins and that this activity requires physical interaction of the ATPase with the proteasome. Furthermore, we establish the N-terminal region of Pup as the structural element required for engagement of pupylated substrates into the Mpa pore. In this process, Mpa pulls on Pup to initiate unfolding of substrate proteins and to drag them toward the proteasome chamber. Unlike the eukaryotic ubiquitin, Pup is not recycled but degraded with the substrate. This assigns a dual function to Pup as both the Mpa recognition element as well as the threading determinant. PMID:20203624

  4. N-Terminus of Cardiac Myosin Essential Light Chain Modulates Myosin Step-Size.

    PubMed

    Wang, Yihua; Ajtai, Katalin; Kazmierczak, Katarzyna; Szczesna-Cordary, Danuta; Burghardt, Thomas P

    2016-01-12

    Muscle myosin cyclically hydrolyzes ATP to translate actin. Ventricular cardiac myosin (βmys) moves actin with three distinct unitary step-sizes resulting from its lever-arm rotation and with step-frequencies that are modulated in a myosin regulation mechanism. The lever-arm associated essential light chain (vELC) binds actin by its 43 residue N-terminal extension. Unitary steps were proposed to involve the vELC N-terminal extension with the 8 nm step engaging the vELC/actin bond facilitating an extra ∼19 degrees of lever-arm rotation while the predominant 5 nm step forgoes vELC/actin binding. A minor 3 nm step is the unlikely conversion of the completed 5 to the 8 nm step. This hypothesis was tested using a 17 residue N-terminal truncated vELC in porcine βmys (Δ17βmys) and a 43 residue N-terminal truncated human vELC expressed in transgenic mouse heart (Δ43αmys). Step-size and step-frequency were measured using the Qdot motility assay. Both Δ17βmys and Δ43αmys had significantly increased 5 nm step-frequency and coincident loss in the 8 nm step-frequency compared to native proteins suggesting the vELC/actin interaction drives step-size preference. Step-size and step-frequency probability densities depend on the relative fraction of truncated vELC and relate linearly to pure myosin species concentrations in a mixture containing native vELC homodimer, two truncated vELCs in the modified homodimer, and one native and one truncated vELC in the heterodimer. Step-size and step-frequency, measured for native homodimer and at two or more known relative fractions of truncated vELC, are surmised for each pure species by using a new analytical method. PMID:26671638

  5. Immunization of N terminus of enterovirus 71 VP4 elicits cross-protective antibody responses

    PubMed Central

    2013-01-01

    Background Enterovirus 71 (EV71) is major cause of hand, foot and mouth disease. Large epidemics of EV71 infection have been recently reported in the Asian-Pacific region. Currently, no vaccine is available to prevent EV71 infection. Results The peptide (VP4N20) consisting of the first 20 amino acids at the N-terminal of VP4 of EV71 genotype C4 were fused to hepatitis B core (HBcAg) protein. Expression of fusion proteins in E. coli resulted in the formation of chimeric virus-like particles (VLPs). Mice immunized with the chimeric VLPs elicited anti-VP4N20 antibody response. In vitro microneutralization experiments showed that anti-chimeric VLPs sera were able to neutralize not only EV71 of genotype C4 but also EV71 of genotype A. Neonatal mice model confirmed the neutralizing ability of anti-chimeric VLPs sera. Eiptope mapping led to the identification of a “core sequence” responsible for antibody recognition within the peptide. Conclusions Immunization of chimeric VLPs is able to elicit antibodies displaying a broad neutralizing activity against different genotypes of EV71 in vitro. The “core sequence” of EV71-VP4 is highly conserved across EV71 genotypes. The chimeric VLPs have a great potential to be a novel vaccine candidate with a broad cross-protection against different EV71 genotypes. PMID:24320792

  6. Understanding dengue virus capsid protein disordered N-Terminus and pep14-23-based inhibition.

    PubMed

    Faustino, André F; Guerra, Gabriela M; Huber, Roland G; Hollmann, Axel; Domingues, Marco M; Barbosa, Glauce M; Enguita, Francisco J; Bond, Peter J; Castanho, Miguel A R B; Da Poian, Andrea T; Almeida, Fabio C L; Santos, Nuno C; Martins, Ivo C

    2015-02-20

    Dengue virus (DENV) infection affects millions of people and is becoming a major global disease for which there is no specific available treatment. pep14-23 is a recently designed peptide, based on a conserved segment of DENV capsid (C) protein. It inhibits the interaction of DENV C with host intracellular lipid droplets (LDs), which is crucial for viral replication. Combining bioinformatics and biophysics, here, we analyzed pep14-23 structure and ability to bind different phospholipids, relating that information with the full-length DENV C. We show that pep14-23 acquires α-helical conformation upon binding to negatively charged phospholipid membranes, displaying an asymmetric charge distribution structural arrangement. Structure prediction for the N-terminal segment reveals four viable homodimer orientations that alternatively shield or expose the DENV C hydrophobic pocket. Taken together, these findings suggest a new biological role for the disordered N-terminal region, which may function as an autoinhibitory domain mediating DENV C interaction with its biological targets. The results fit with our current understanding of DENV C and pep14-23 structure and function, paving the way for similar approaches to understanding disordered proteins and improved peptidomimetics drug development strategies against DENV and similar Flavivirus infections. PMID:25412346

  7. Function of the N-terminus of zizimin1: autoinhibition and membrane targeting

    PubMed Central

    Meller, Nahum; Westbrook, Marjorie W.; Shannon, John D.; Guda, Chittibabu; Schwartz, Martin Alexander

    2009-01-01

    SYNOPSIS Rho family small GTPases are critical regulators of multiple cellular functions. Dbl homology domain-containing proteins are the classical guanine nucleotide exchange factors (GEFs) responsible for activation of Rho proteins. Zizimin1 is a Cdc42-specific GEF that belongs to a second family of mammalian Rho-GEFs, CZH proteins, which possess a novel type of GEF Domain. CZH proteins can be divided into a subfamily related to DOCK180 and a subfamily related to zizimin1. The two groups share two conserved regions named the CZH1 (or DHR1) domain and the CZH2 (DHR2 or DOCKER) domains, the latter exhibiting GEF activity. We now show that limited proteolysis of zizimin1 suggests the existence of structural domains that do not correspond to those identified on the basis of homologies. We demonstrate that the N-terminal half binds to the GEF domain through three distinct areas, including the CZH1, to inhibit the interaction with Cdc42. The N-terminal Pleckstrin homology (PH) domain binds phosphoinositides and mediates zizimin1 membrane targeting. These data define two novel functions for the N-terminal region of zizimin1. PMID:17935486

  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. Prompt trigger primitives for a self-seeded track trigger

    NASA Astrophysics Data System (ADS)

    Dressanandt, N.; Halgeri, A.; Kamat, M.; Koppal, V.; Newcomer, M.

    2012-10-01

    A viable self-seeded track trigger for a high rate collider detector environment must have excellent angular precision, response times commensurate with beam crossing rate and low mass. We have designed a fast clustering block servicing 128 contiguous strips to be included in an LHC upgrade silicon strip front end ASIC (ABC130) with these objectives in mind. The block is based on the presence of an analog front end with binary (threshold determined) strip readout latched at each beam crossing. Combinatorial logic tests for the presence of one or two adjacent strips over threshold, a qualifying cluster, at each beam crossing and transmits up to two, eight bits clusters descriptors, specifying address and cluster width via a high speed LVDS output. It is envisioned that a correlator chip, presently in conception, receives this data and via look-up tables checks for coincident hits between silicon strip layers. Since the clustering output will report the presence of one or two hit strips, a half strip pitch ( ~ 40 um for the ATLAS detector) resolution may be possible for each cluster. Our timing results show that the combinatorial clustering logic will settle within 6 ns. Assuming a beam crossing rate of 40 MHz, 16 bits of serialized data can be shifted out at 640MHz each crossing. This will allow a beam synchronous update rate providing data for up to two clusters for each bank of 128 strips. The data latency into the correlator chip will be only two crossings. Present power estimates suggest that the fast cluster block with LVDS driver will consume less than 12 mW.

  12. Intrasaccadic perception triggers pupillary constriction.

    PubMed

    Mathôt, Sebastiaan; Melmi, Jean-Baptiste; Castet, Eric

    2015-01-01

    It is commonly believed that vision is impaired during saccadic eye movements. However, here we report that some visual stimuli are clearly visible during saccades, and trigger a constriction of the eye's pupil. Participants viewed sinusoid gratings that changed polarity 150 times per second (every 6.67 ms). At this rate of flicker, the gratings were perceived as homogeneous surfaces while participants fixated. However, the flickering gratings contained ambiguous motion: rightward and leftward motion for vertical gratings; upward and downward motion for horizontal gratings. When participants made a saccade perpendicular to the gratings' orientation (e.g., a leftward saccade for a vertical grating), the eye's peak velocity matched the gratings' motion. As a result, the retinal image was approximately stable for a brief moment during the saccade, and this gave rise to an intrasaccadic percept: A normally invisible stimulus became visible when eye velocity was maximal. Our results confirm and extend previous studies by demonstrating intrasaccadic perception using a reflexive measure (pupillometry) that does not rely on subjective report. Our results further show that intrasaccadic perception affects all stages of visual processing, from the pupillary response to visual awareness. PMID:26339536

  13. 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.

  14. 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

  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. 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.

  17. The H1 neural network trigger project

    NASA Astrophysics Data System (ADS)

    Kiesling, C.; Denby, B.; Fent, J.; Fröchtenicht, W.; Garda, P.; Granado, B.; Grindhammer, G.; Haberer, W.; Janauschek, L.; Kobler, T.; Koblitz, B.; Nellen, G.; Prevotet, J.-C.; Schmidt, S.; Tzamariudaki, E.; Udluft, S.

    2001-08-01

    We present a short overview of neuromorphic hardware and some of the physics projects making use of such devices. As a concrete example we describe an innovative project within the H1-Experiment at the electron-proton collider HERA, instrumenting hardwired neural networks as pattern recognition machines to discriminate between wanted physics and uninteresting background at the trigger level. The decision time of the system is less than 20 microseconds, typical for a modern second level trigger. The neural trigger has been successfully running for the past four years and has turned out new physics results from H1 unobtainable so far with other triggering schemes. We describe the concepts and the technical realization of the neural network trigger system, present the most important physics results, and motivate an upgrade of the system for the future high luminosity running at HERA. The upgrade concentrates on "intelligent preprocessing" of the neural inputs which help to strongly improve the networks' discrimination power.

  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. Dark matter triggers of supernovae

    NASA Astrophysics Data System (ADS)

    Graham, Peter W.; Rajendran, Surjeet; Varela, Jaime

    2015-09-01

    The transit of primordial black holes through a white dwarf causes localized heating around the trajectory of the black hole through dynamical friction. For sufficiently massive black holes, this heat can initiate runaway thermonuclear fusion causing the white dwarf to explode as a supernova. The shape of the observed distribution of white dwarfs with masses up to 1.25 M⊙ rules out primordial black holes with masses ˜1019- 1020 gm as a dominant constituent of the local dark matter density. Black holes with masses as large as 1024 gm will be excluded if recent observations by the NuStar Collaboration of a population of white dwarfs near the galactic center are confirmed. Black holes in the mass range 1020- 1022 gm are also constrained by the observed supernova rate, though these bounds are subject to astrophysical uncertainties. These bounds can be further strengthened through measurements of white dwarf binaries in gravitational wave observatories. The mechanism proposed in this paper can constrain a variety of other dark matter scenarios such as Q balls, annihilation/collision of large composite states of dark matter and models of dark matter where the accretion of dark matter leads to the formation of compact cores within the star. White dwarfs, with their astronomical lifetimes and sizes, can thus act as large spacetime volume detectors enabling a unique probe of the properties of dark matter, especially of dark matter candidates that have low number density. This mechanism also raises the intriguing possibility that a class of supernova may be triggered through rare events induced by dark matter rather than the conventional mechanism of accreting white dwarfs that explode upon reaching the Chandrasekhar mass.

  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. 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.

  2. Triggering at a high luminosity hadron collider

    SciTech Connect

    Price, L.E.; Wagner, R.G.; Abolins, M.A.

    1984-01-01

    The extreme interaction rate occurring at the SSC as described in the Reference Design Report poses the principal new challenge for the triggering system compared with detectors at previous accelerators. At SSC we must plan for about 10/sup 8/ interactions per second. If bunch crossings occur each 33 ns, there will be an average of 3 interactions in each bunch crossing. Potential problems for triggering are presented both by the high total rate and by the multiple interactions per bunch crossing, so that triggering events must be selected in the presence of other interactions independent of the inherent speed of either detector elements or triggering electronics. Three principal topics are considered in this report: (1) Practical selections to be made in a first-level trigger to reduce the rate by a factor of 1000. (2) Electronics expected to implement this first-level trigger, and (3) the ultimate trigger selections that must be used to select the approximately 1 Hz that can practically be recorded for detailed analysis. 11 references, 6 figures.

  3. 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.

  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. 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

  6. 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.

  7. The upgrade of the CMS Global Trigger

    NASA Astrophysics Data System (ADS)

    Wittmann, J.; Arnold, B.; Bergauer, H.; Jeitler, M.; Matsushita, T.; Rabady, D.; Rahbaran, B.; Wulz, C.-E.

    2016-02-01

    The Global Trigger is the final step of the CMS Level-1 Trigger. Previously implemented in VME, it has been redesigned and completely rebuilt in MicroTCA technology, using the Virtex-7 FPGA chip family. It will allow to implement trigger algorithms close to the final physics selection. The new system is presented, together with performance tests undertaken in parallel operation with the legacy system during the initial months of Run II of the LHC at a beam energy of 13 TeV.

  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. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  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. Trigger circuits for the PHENIX electromagnetic calorimeter

    SciTech Connect

    Frank, S.S.; Britton, C.L. Jr.; Winterberg, A.L.; Young, G.R.

    1997-11-01

    Monolithic and discrete circuits have been developed to provide trigger signals for the PHENIX electromagnetic calorimeter detector. These trigger circuits are deadtimeless and create overlapping 4 by 4 energy sums, a cosmic muon trigger, and a 144 channel energy sum. The front end electronics of the PHENIX system sample the energy and timing channels at each bunch crossing (BC) but it is not known immediately if this data is of interest. The information from the trigger circuits is used to determine if the data collected is of interest and should be digitized and stored or discarded. This paper presents details of the design, issues affecting circuit performance, characterization of prototypes fabricated in 1.2 {micro}m Orbit CMOS, and integration of the circuits into the EMCal electronics system.

  16. Session summary: Electronics, triggering and data acquisition

    SciTech Connect

    Rescia, S.

    1991-12-01

    The session focused on the requirements for calorimetry at the SSC/LHC. Results on new readout techniques, calibration, radiation hard electronics and semiconductor devices, analog and digital front and electronics, and trigger strategies are presented.

  17. The CDF L2 XFT Trigger Upgrade

    SciTech Connect

    Lister, Alison; /UC, Davis

    2008-10-01

    We briefly present the eXtremely Fast Tracker stereo track upgrade for the CDF Level 2 trigger system. This upgrade enabled full 3D track reconstruction at Level 2 of the 3-Level CDF online triggering system. Using information provided by the stereo layers of the Central Outer Tracker, we can decrease the trigger rate due to fake tracks by requiring the tracks to be consistent with a single vertex in all three dimensions but also by using the track information to 'point' to the various detector components. We will also discuss the effectiveness of the Level 2 stereo track algorithm at achieving reduced trigger rates with high efficiencies during high luminosity running.

  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. 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.

  20. 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

  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. Upgrade of the trigger system of CMS

    NASA Astrophysics Data System (ADS)

    Jeitler, Manfred; CMS Collaboration

    2013-08-01

    Various parts of the CMS trigger and in particular the Level-1 hardware trigger will be upgraded to cope with increasing luminosity, using more selective trigger conditions at Level 1 and improving the reliability of the system. Many trigger subsystems use FPGAs (Field Programmable Gate Arrays) in the electronics and will benefit from developments in this technology, allowing us to place much more logic into a single FPGA chip, thus reducing the number of chips, electronic boards and interconnections and in this way improving reliability. A number of subsystems plan to switch from the old VME bus to the new microTCA crate standard. Using similar approaches, identical modules and common software wherever possible will reduce costs and manpower requirements and improve the serviceability of the whole trigger system. The computer-farm based High-Level Trigger will not only be extended by using increasing numbers of more powerful PCs but there are also concepts for making it more robust and the software easier to maintain, which will result in better efficiency of the whole system.

  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 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.

  5. 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.

  6. Intraplate Triggered Earthquakes: Observations and Interpretation

    NASA Astrophysics Data System (ADS)

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

    2001-12-01

    We present evidence that at least two of the three principal 1811-1812 New Madrid, mainshocks and the 1886 Charleston, South Carolina, earthquake were associated with remotely triggered earthquakes. In addition to previously published results showing that the New Madrid sequence triggered earthquakes in the northern Kentucky/southern Ohio region, we present evidence suggesting that triggered events might have occurred in the Wabash Valley, to the south of the New Madrid Seismic Zone, and possibly near Charleston, South Carolina region as well. We also discuss evidence that earthquakes might have been triggered in northern Kentucky in the immediate wake of the strong ground motions associated with 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. Thus at least three out of the four known M>=7 earthquakes in the central and eastern United States seem to have triggered earthquakes outside their aftershock zones. 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, non-elastic deformation might play a relatively more important role in stress accumulation than it does in interplate crust. Using a simple model incorporating both elastic and anelastic strain release, we show that, for realistic parameter values, faults in intraplate crust might remain close to their failure stress for a longer part of the earthquake cycle than faults in high strain-rate regions. Our results furthermore reveal that remotely triggered earthquakes occur preferentially in regions of recent and/or future seismic activity, which suggests that faults tend to be at a critical stress state in only some areas. It is not surprising that triggered earthquakes would serve as beacons that identify regions that are approaching a critical stress state. Their

  7. Triggering the LBL time projection chamber

    SciTech Connect

    Ronan, M.; Millaud, J.; McGathen, T.

    1981-10-01

    A fast digital trigger was built for the LBL Time Projection Chamber (TPC) installed in the PEP-4 detector at SLAC. The TPC is an innovative High Energy Physics detector which will provide particle identification from dE/dx information within the tracking volume. The TPC trigger uses discriminator signals from 2220 dE/dx wire channels to require a track of ionization in the TPC which originates from the colliding beam intersection region. The trigger processing is performed as the ionization drifts onto the proportional wires and is completed 17 ..mu..s after beam crossing. This report describes the basic operation of the TPC detector and its trigger; a pretrigger which uses prompt TPC information from the endcap region; and the electronic implementation. The trigger can be tested with realistic simulated patterns of ionization deposits in the TPC which are stored in local memories. Test results from electronic simulations and first results of a test with cosmic rays are shown.

  8. 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.

  9. Trigger points – ultrasound and thermal findings

    PubMed Central

    Cojocaru, MC; Cojocaru, IM; Voiculescu, VM; Cojan-Carlea, NA; Dumitru, VL; Berteanu, M

    2015-01-01

    Rationale: Muscle pain can be elicited by any irritation of the nociceptors in the muscle or central sensitization in the central nervous system. The most frequently described muscle pain syndromes are myofascial pain syndrome and fibromyalgia syndrome. Myofascial pain syndrome has a more localized manifestation, the trigger points. Objective: If there is a correlation between the clinical findings, the ultrasound examination and the thermal pattern of trigger points exist. Material and method: The presence of trigger points can be identified by using clinical criteria. An ultrasound examination was performed to evaluate the trigger point dimensions. The ultrasound showed an ellipsoidal hypoechogenic area in the muscle. A thermography of the low back region was performed in order to observe the thermal pattern of the area. Results: Trigger points are represented by a higher temperature area surrounded by a cooler area, probably caused by a deficit in the blood flow around those points. Discussion: Infrared thermography could be a great asset for the monitoring of neuromusculoskeletal disorders and their dynamics, as well as an important aid for the initial diagnosis of conditions associated with tissue temperature alterations. PMID:26351532

  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. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Triggering of Aftershocks by Free Oscillations

    NASA Astrophysics Data System (ADS)

    Bufe, C. G.; Varnes, D. J.

    2001-12-01

    Periodicities observed in aftershock sequences may result from earthquake triggering by free oscillations of the Earth produced by the main shock. Using an algorithm we developed to compute spectra of inter-event times, we examine inter-event intervals of teleseismically recorded aftershock sequences from large (M>7.5) main shocks that occurred during 1980-2001. Observed periodicities may result from triggering at intervals that are multiples of normal mode periods. We have focussed our analysis of inter-event times on identification of triggering by free oscillations at periods in the range 6-60 minutes. In this paper we describe our most commonly observed aftershock inter-event times and the free oscillation modes most likely to be the triggers. Because of their separation, the longer period modes are easiest to identify in the aftershock data (0S2 at 53.9 minutes, 0S3 at 35.6 minutes, 0S4 at 25.8 minutes, and 0T2 at 43.9 minutes). Evidence of triggering by 0S2 and 0T2 was also found in the aftershocks of the 1989 Loma Prieta, CA (M 7) earthquake (Kamal and Mansinha, 1996). Because of the plethora of higher modes, shorter inter-event periods are more difficult to identify with a particular mode. Preliminary analysis of the 2001 Bhuj, India (M 7.7) earthquake sequence tentatively identifies a contribution to triggering of the first four large aftershocks by multiples of 0S12 (8.37 minutes).

  16. The CMS High-Level Trigger

    SciTech Connect

    Covarelli, R.

    2009-12-17

    At the startup of the LHC, the CMS data acquisition is expected to be able to sustain an event readout rate of up to 100 kHz from the Level-1 trigger. These events will be read into a large processor farm which will run the 'High-Level Trigger'(HLT) selection algorithms and will output a rate of about 150 Hz for permanent data storage. In this report HLT performances are shown for selections based on muons, electrons, photons, jets, missing transverse energy, {tau} leptons and b quarks: expected efficiencies, background rates and CPU time consumption are reported as well as relaxation criteria foreseen for a LHC startup instantaneous luminosity.

  17. 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.

  18. Subacute Cutaneous Lupus Erythematosus Triggered by Radiotherapy

    PubMed Central

    Kolm, I.; Pawlik, E.; Eggmann, N.; Kamarachev, J.; Kerl, K.; French, L.E.; Hofbauer, G.F.L.

    2013-01-01

    Background The origin of collagen autoimmune diseases is not fully understood. Some studies postulate a mechanism of molecular mimicry or heterologous immunity following viral infections triggering autoimmunity. Apart from infections, other exogenous factors such as visible light or X-rays have been reported to incite autoimmunity. Case Report We report a case of histologically and serologically confirmed subacute lupus erythematosus (SCLE) following radiotherapy for breast cancer. Discussion The close temporal and spatial correlation between radiotherapy and onset of SCLE in this patient suggests that an autoimmune reaction may have been triggered locally by functionally altering the immune system and breaking self-tolerance. PMID:24019776

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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. PMID:25991389

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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. PMID:11117741

  10. Laser trigger system for the Jupiter module

    SciTech Connect

    Paiva, R.; Sundvoid, S.; Morelli, G.; Powell, C.; Hamil, R.; Corley, J.; Pankuch, P.; Law, K.; Alexander, J.

    1995-10-01

    A UV laser trigger system has been designed to trigger the eight SF6 filled high voltage switches in the Jupiter module. The system is compact and modular, allowing for approximately thirty lasers to be triggered simultaneously in the full Jupiter design. The laser will be kinematically mounted near the high voltage section to minimize the path length to the high voltage switches and decrease the sensitivity to misalignment. The laser system is specifically built for the purpose of triggering the Jupiter module. It is a 265 nm UV laser system designed to generate eight simultaneous laser pulses of 10 mJ each with a 13 nsec pulsewidth. A 1061 nm solid-state Nd:Cr:GSGG laser is frequency quadrupled with a two stage doubling process. The 1061 nm fundamental laser energy is frequency doubled with a type II KTP crystal to generate 530 nm energy. The 530 nm output is frequency doubled with a type I KD*P crystal to generate 265 nm energy. The 265 nm pulse is split into eight parallel channels with a system of partially reflecting mirrors. Low timing jitter and a stable energy output level for the system were achieved. The entire optical system was packaged in a rugged, sealed aluminum structure 10 in. {times} 19 in. {times} 2.75 in. The size of the laser electronics unit is 7 in. {times} 8 in. {times} 8 in.

  11. Large Scale Impacts and Triggered Volcanism

    NASA Technical Reports Server (NTRS)

    Ivanov, B. A.; Melosh, H. J.

    2003-01-01

    The idea of impact induced volcanism continues to blossom ([1-3] and other references). However, this appealing idea is seldom supported with an appropriate physical mechanism. The aim of this publication is to critically examine some frequently cited mechanisms of impact energy transformation into a trigger for terrestrial volcanism and magmatism.

  12. 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)

  13. High Level Trigger Configuration and Handling of Trigger Tables in the CMS Filter Farm

    SciTech Connect

    Bauer, G; Behrens, U; Boyer, V; Branson, J; Brett, A; Cano, E; Carboni, A; Ciganek, M; Cittolin, S; O'dell, V; Erhan, S; Gigi, D; Glege, F; Gomez-Reino, R; Gulmini, M; Gutleber, J; Hollar, J; Lange, D; Kim, J C; Klute, M; Lipeles, E; Perez, J L; Maron, G; Meijers, F; Meschi, E; Moser, R; Mlot, E G; Murray, S; Oh, A; Orsini, L; Paus, C; Petrucci, A; Pieri, M; Pollet, L; Racz, A; Sakulin, H; Sani, M; Schieferdecker, P; Schwick, C; Sumorok, K; Suzuki, I; Tsirigkas, D; Varela, J

    2009-11-22

    The CMS experiment at the CERN Large Hadron Collider is currently being commissioned and is scheduled to collect the first pp collision data in 2008. CMS features a two-level trigger system. The Level-1 trigger, based on custom hardware, is designed to reduce the collision rate of 40 MHz to approximately 100 kHz. Data for events accepted by the Level-1 trigger are read out and assembled by an Event Builder. The High Level Trigger (HLT) employs a set of sophisticated software algorithms, to analyze the complete event information, and further reduce the accepted event rate for permanent storage and analysis. This paper describes the design and implementation of the HLT Configuration Management system. First experiences with commissioning of the HLT system are also reported.

  14. Pattern-Triggered Immunity Suppresses Programmed Cell Death Triggered by Fumonisin B1

    PubMed Central

    Igarashi, Daisuke; Bethke, Gerit; Xu, Yuan; Tsuda, Kenichi; Glazebrook, Jane; Katagiri, Fumiaki

    2013-01-01

    Programmed cell death (PCD) is a crucial process for plant innate immunity and development. In plant innate immunity, PCD is believed to prevent the spread of pathogens from the infection site. Although proper control of PCD is important for plant fitness, we have limited understanding of the molecular mechanisms regulating plant PCD. Plant innate immunity triggered by recognition of effectors (effector-triggered immunity, ETI) is often associated with PCD. However pattern-triggered immunity (PTI), which is triggered by recognition of elicitors called microbe-associated molecular patterns (MAMPs), is not. Therefore we hypothesized that PTI might suppress PCD. Here we report that PCD triggered by the mycotoxin fumonisin B1 (FB1) can be suppressed by PTI in Arabidopsis. FB1-triggered cell death was suppressed by treatment with the MAMPs flg22 (a part of bacterial flagellin) or elf18 (a part of the bacterial elongation factor EF-Tu) but not chitin (a component of fungal cell walls). Although plant hormone signaling is associated with PCD and PTI, both FB1-triggered cell death and suppression of cell death by flg22 treatment were still observed in mutants deficient in jasmonic acid (JA), ethylene (ET) and salicylic acid (SA) signaling. The MAP kinases MPK3 and MPK6 are transiently activated and inactivated within one hour during PTI. We found that FB1 activated MPK3 and MPK6 about 36–48 hours after treatment. Interestingly, this late activation was attenuated by flg22 treatment. These results suggest that PTI suppression of FB1-triggered cell death may involve suppression of MPK3/MPK6 signaling but does not require JA/ET/SA signaling. PMID:23560104

  15. 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.

  16. 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.

  17. 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.

  18. Gastroesophageal reflux: a potential asthma trigger.

    PubMed

    Harding, Susan M

    2005-02-01

    Gastroesophageal reflux (GER) is a potential trigger of asthma. Approximately 77% of asthmatics report heartburn. GER is a risk factor for asthma-related hospitalization and oral steroid burst use. Asthmatics may be predisposed to GER development because of a high prevalence of hiatal hernia and autonomic dysregulation and an increased pressure gradient between the abdominal cavity and the thorax, over-riding the lower esophageal sphincter pressure barrier. Asthma medications may potentiate GER. Potential mechanisms of esophageal acid-induced bronchoconstriction include a vagally mediated reflex, local axonal reflexes, heightened bronchial reactivity, and microaspiration, all resulting in neurogenic inflammation. Anti-reflux therapy improves asthma symptoms in approximately 70% of asthmatics with GER. A 3-month empiric trial of twice-daily proton pump inhibitor given 30 to 60 minutes before breakfast and dinner can identify asthmatics who have GER as a trigger of their asthma. PMID:15579368

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. A parallel pipelined dataflow trigger processor

    SciTech Connect

    Lee, C.; Miller, G.; Kaplan, D.M.; Sa, J. ); Hsiung, Y.B. ); Carey, T.; Jeppesen, R. )

    1991-04-01

    This paper describes a parallel pipelined data flow trigger processor which is used in Fermilab E789. E789 is an experiment to study low-multiplicity decays of particles containing b or c quarks. The processor consists of an upstream vertex processor and a downstream track processor. The algorithms which reconstruct the postulated particle paths and calculate particle origin are implemented via interconnected function-specific hardware modules. The algorithm is directly dependent upon the organization of the modules, the specific arrangement of the inter-module cabling, on-board memory data. The processor provides an indication of the presence of at least one interesting particle pair in the current event by asserting Read on its Read/Skip output. The Read assertion is then used as a trigger to capture all of the event's data for subsequent extensive off-line analysis.

  4. 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

  5. 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.

  6. 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.

  7. A light-triggered protein secretion system

    PubMed Central

    Chen, Daniel; Gibson, Emily S.

    2013-01-01

    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. PMID:23671313

  8. Triply triggered doxorubicin release from supramolecular nanocontainers.

    PubMed

    Loh, Xian Jun; del Barrio, Jesús; Toh, Pearl Pei Chern; Lee, Tung-Chun; Jiao, Dezhi; Rauwald, Urs; Appel, Eric A; Scherman, Oren A

    2012-01-01

    The synthesis of a supramolecular double hydrophilic block copolymer (DHBC) held together by cucurbit[8]uril (CB[8]) ternary complexation and its subsequent self-assembly into micelles is described. This system is responsive to multiple external triggers including temperature, pH and the addition of a competitive guest. The supramolecular block copolymer assembly consists of poly(N-isopropylacrylamide) (PNIPAAm) as a thermoresponsive block and poly(dimethylaminoethylmethacrylate) (PDMAEMA) as a pH-responsive block. Moreover, encapsulation and controlled drug release was demonstrated with this system using the chemotherapeutic drug doxorubicin (DOX). This triple stimuli-responsive DHBC micelle system represents an evolution over conventional double stimuli-responsive covalent diblock copolymer systems and displayed a significant reduction in the viability of HeLa cells upon triggered release of DOX from the supramolecular micellar nanocontainers. PMID:22148638

  9. I. Specific Nature of Triggering Events.

    PubMed

    Eckert, R

    1965-03-01

    The flash of Noctiluca miliaris occurs only in response to a characteristic all-or-none action potential, the polarity of which is opposite to that of metazoan action potentials, whether recorded internally or externally. Mechanical stimulation evokes a slow, generator-like graded potential which can give rise to the flash-triggering action potential. The flash is all-or-none; it facilitates, summates, and exhibits fatigue, each independently of changes in the amplitude of the action potential. PMID:17790656

  10. 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.

  11. 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.

  12. Trigger chemistries for better industrial formulations.

    PubMed

    Wang, Hsuan-Chin; Zhang, Yanfeng; Possanza, Catherine M; Zimmerman, Steven C; Cheng, Jianjun; Moore, Jeffrey S; Harris, Keith; Katz, Joshua S

    2015-04-01

    In recent years, innovations and consumer demands have led to increasingly complex liquid formulations. These growing complexities have provided industrial players and their customers access to new markets through product differentiation, improved performance, and compatibility/stability with other products. One strategy for enabling more complex formulations is the use of active encapsulation. When encapsulation is employed, strategies are required to effect the release of the active at the desired location and time of action. One particular route that has received significant academic research effort is the employment of triggers to induce active release upon a specific stimulus, though little has translated for industrial use to date. To address emerging industrial formulation needs, in this review, we discuss areas of trigger release chemistries and their applications specifically as relevant to industrial use. We focus the discussion on the use of heat, light, shear, and pH triggers as applied in several model polymeric systems for inducing active release. The goal is that through this review trends will emerge for how technologies can be better developed to maximize their value through industrial adaptation. PMID:25768973

  13. 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.

  14. 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.

  15. The Sandia Transportable Triggered Lightning Instrumentation Facility

    SciTech Connect

    Schnetzer, G.H.; Fisher, R.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 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 the summer of 1990 at the Kennedy Space Center's (KSC) rocket-triggered lightning test site in Florida. A description is given of the SATTLIF, which is readily transportable on a single flatbed truck or by aircraft, and its instrumentation for measuring incident lightning channel currents and the responses of systems under test. Measurements of return-stroke current peaks obtained with the SATLLIF 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. 5 refs., 12 figs., 1 tab.

  16. 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.

  17. Cancer exosomes trigger fibroblast to myofibroblast differentiation.

    PubMed

    Webber, Jason; Steadman, Robert; Mason, Malcolm D; Tabi, Zsuzsanna; Clayton, Aled

    2010-12-01

    There is a growing interest in the cell-cell communication roles in cancer mediated by secreted vesicles termed exosomes. In this study, we examined whether exosomes produced by cancer cells could transmit information to normal stromal fibroblasts and trigger a cellular response. We found that some cancer-derived exosomes could trigger elevated α-smooth muscle actin expression and other changes consistent with the process of fibroblast differentiation into myofibroblasts. We show that TGF-β is expressed at the exosome surface in association with the transmembrane proteoglycan betaglycan. Although existing in a latent state, this complex was fully functional in eliciting SMAD-dependent signaling. Inhibiting either signaling or betaglycan expression attenuated differentiation. While the kinetics and overall magnitude of the response were similar to that achieved with soluble TGF-β, we identified important qualitative differences unique to the exosomal route of TGF-β delivery, as exemplified by a significant elevation in fibroblast FGF2 production. This hitherto unknown trigger for instigating cellular differentiation in a distinctive manner has major implications for mechanisms underlying cancer-recruited stroma, fibrotic diseases, and wound-healing responses. PMID:21098712

  18. 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; �

  19. 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.

  20. The trigger system of the OPAL experiment at LEP

    NASA Astrophysics Data System (ADS)

    Arignon, M.; Ball, A. H.; Bell, K. W.; Bramhall, M.; Braun, A.; Carter, A. A.; Carter, J. R.; Charlton, D. G.; Dittmar, M.; Farthouat, P.; Feyt, J.; Gao, H.; Gary, J. W.; Gillies, J. D.; Greiner, C.; Hammarstroem, R.; Hart, J.; Heuer, R.-D.; Hill, J. C.; Hillier, S. J.; Hilse, T.; Humbert, R.; Jaroslawski, S.; Joos, D.; Jovanovic, P.; Kawamoto, T.; Kellogg, R. G.; Kobayashi, T.; Le Du, P.; Levinson, L. J.; Loebinger, F. K.; MacBeth, A. A.; Mikenberg, G.; Milborrow, R.; Pawley, S. J.; Penton, A.; Pritchard, T. W.; Quast, G.; Ricth, G.; Roach, C. M.; Runge, K.; Schaile, O.; Scherer, D.; Schuler, G.; Schwarz, J.; Springer, R. W.; Takeda, H.; Virtue, C. J.; Wagner, A.; Ward, D. R.; Watkins, P. M.; Webel, M.; Weber, C.; Weymann, M.; Wilson, G. W.; Wilson, J. A.

    1992-03-01

    This paper describes the trigger system of the OPAL detector at the e+e- collider LEP and its performance during the first year of data taking. A high level of redundancy and fine detector segmentation at the trigger level led to a high efficiency for all considered physics reactions while the trigger rates were kept low.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. Abdominal Trigger Points and Psychological Function.

    PubMed

    Reeves, Roy R; Ladner, Mark E

    2016-02-01

    Myofascial trigger points (TPs) are a poorly understood phenomenon involving the myofascial system and its related neural, lymphatic, and circulatory elements. Compression or massage of a TP causes localized pain and may cause referred pain and autonomic phenomena. The authors describe a 58-year-old woman who experienced precipitation of substantial psychological symptoms directly related to her treatment for a lower abdominal TP. Her symptoms resolved after 2 weeks of receiving high-velocity, low-amplitude manipulation and soft tissue massage. Particularly in the abdomen, TPs may be associated with psychological reactions as well as physical aspects of bodily function. PMID:26830528

  7. Optically Triggered Immune Response through Photocaged Oligonucleotides

    PubMed Central

    Govan, Jeane M.; Young, Douglas D.; Lively, Mark O.

    2015-01-01

    Bacterial and viral CpG oligonculeotides are unmethylated cytosine-phosphate-guanosine dinucleotide sequences and trigger an innate immune response through activation of the toll-like receptor 9 (TLR9). We have developed synthetic photocaged CpGs via site-specific incorporation of nitropiperonyloxymethyl (NPOM)-caged thymidine residues. These oligonucleotides enable the optical control of TLR9 function and thereby provide light-activation of an immune response. We provide a proof-of-concept model by applying a reporter assay in live cells and by quantification of endogenous production of interleukin 6. PMID:26034339

  8. 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

  9. 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.

  10. 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.

  11. Use of parallel counters for triggering

    NASA Astrophysics Data System (ADS)

    Nikityuk, N. M.

    1992-10-01

    The results of an investigation into using parallel counters, majority coincidence schemes and parallel compressors for triggering in multichannel high energy spectrometers are described. Concrete examples of methods of constructing fast and economical new devices used to determine multiplicity hits t > 900 registered in a hodoscopic plane and a pixel detector are given. For this purpose the author uses the syndrome coding method and cellular arrays. In addition, the author has created an effective coding matrix which can be used for light signal coding. For example, such signals are supplied from scintillators to photomultipliers. The investigation has been performed at the Laboratory of High Energies, JINR.

  12. Trigger Algorithm Design for a SUSY Lepton Trigger based on Forward Proton Tagging

    SciTech Connect

    Gronberg, J; Hollar, J

    2010-03-29

    At the Large Hadron Collider (LHC) pair production of SUSY leptons in gamma-gamma interactions will often include intact off-energy protons. Including detectors in the beampipe to measure these protons can give additional information to separate these events from background. We report on expected event rates and background rejection for a slepton trigger design in the Compact Muon Solenoid (CMS) experiment incorporating forward proton information. We conclude that a trigger that can observe an interesting number of events is feasible with the appropriate detector hardware.

  13. SQL Triggers Reacting on Time Events: An Extension Proposal

    NASA Astrophysics Data System (ADS)

    Behrend, Andreas; Dorau, Christian; Manthey, Rainer

    Being able to activate triggers at timepoints reached or after time intervals elapsed has been acknowledged by many authors as a valuable functionality of a DBMS. Recently, the interest in time-based triggers has been renewed in the context of data stream monitoring. However, up till now SQL triggers react to data changes only, even though research proposals and prototypes have been supporting several other event types, in particular time-based ones, since long. We therefore propose a seamless extension of the SQL trigger concept by time-based triggers, focussing on semantic issues arising from such an extension.

  14. Isomer Triggering via Nuclear Excitation by Electron Capture

    SciTech Connect

    Palffy, Adriana; Evers, Joerg; Keitel, Christoph H.

    2007-10-26

    Triggering of long-lived nuclear isomeric states via coupling to the atomic shells in the process of nuclear excitation by electron capture (NEEC) is studied. NEEC occurring in highly charged ions can excite the isomeric state to a triggering level that subsequently decays to the ground state. We present total cross sections for NEEC isomer triggering considering experimentally confirmed low-lying triggering levels and reaction rates based on realistic experimental parameters in ion storage rings. A comparison with other isomer triggering mechanisms shows that, among these, NEEC is the most efficient.

  15. Operation and modeling of the FORTE trigger box

    SciTech Connect

    Murphy, T.

    1996-06-01

    The fast on-orbit recording of transient events satellite (FORTE) will carry a multiple-narrow-band trigger designed to detect impulsive VHF signals embedded in a high-noise background. The FORTE trigger boxes consist of eight VHF channels spaced across twenty MHz of bandwidth. A trigger is generated when a sufficiently bright signal is seen in a user-defined number of these channels within a specified coincidence window. In addition, the trigger circuitry incorporates a feature to reject events caused by the actuation of narrow-band carriers. This report describes the trigger`s operating principles and their implementation in the satellite hardware. We then discuss a computer model which can be used to simulate the performance of the trigger circuit.

  16. Triggered self-assembly of magnetic nanoparticles.

    PubMed

    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 nanomanufacturing. 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

  17. Transient Rechargeable Batteries Triggered by Cascade Reactions.

    PubMed

    Fu, Kun; Liu, Zhen; Yao, Yonggang; Wang, Zhengyang; Zhao, Bin; Luo, Wei; Dai, Jiaqi; Lacey, Steven D; Zhou, Lihui; Shen, Fei; Kim, Myeongseob; Swafford, Laura; Sengupta, Louise; Hu, Liangbing

    2015-07-01

    Transient battery is a new type of technology that allows the battery to disappear by an external trigger at any time. In this work, we successfully demonstrated the first transient rechargeable batteries based on dissoluble electrodes including V2O5 as the cathode and lithium metal as the anode as well as a biodegradable separator and battery encasement (PVP and sodium alginate, respectively). All the components are robust in a traditional lithium-ion battery (LIB) organic electrolyte and disappear in water completely within minutes due to triggered cascade reactions. With a simple cut-and-stack method, we designed a fully transient device with an area of 0.5 cm by 1 cm and total energy of 0.1 J. A shadow-mask technique was used to demonstrate the miniature device, which is compatible with transient electronics manufacturing. The materials, fabrication methods, and integration strategy discussed will be of interest for future developments in transient, self-powered electronics. The demonstration of a miniature Li battery shows the feasibility toward system integration for all transient electronics. PMID:26083530

  18. 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.

  19. 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.

  20. 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

  1. 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

  2. Astrophysically Triggered Searches for Gravitational Waves

    NASA Astrophysics Data System (ADS)

    Marka, Zsuzsa

    2010-02-01

    Many expected sources of gravitational waves are observable in more traditional channels, via gamma rays, X-rays, optical, radio, or neutrino emission. Some of these channels are already being used in searches for gravitational waves with the LIGO-GEO600-Virgo interferometer network, and others are currently being incorporated into new or planned searches. Astrophysical targets include gamma-ray bursts, soft-gamma repeaters, supernovae, and glitching pulsars. The observation of electromagnetic or neutrino emission simultaneously with gravitational waves could be crucial for the first direct detection of gravitational waves. Information on the progenitor, such as trigger time, direction and expected frequency range, can enhance our ability to identify gravitational wave signatures with amplitude close to the noise floor of the detector. Furthermore, combining gravitational waves with electromagnetic and neutrino observations will enable the extraction of scientific insight that was hidden from us before. We will discuss the status for astrophysically triggered searches with the LIGO-GEO600-Virgo network and the science goals and outlook for the second and third generation gravitational wave detector era. )

  3. [The electrical conductivity of triggered lightning channel].

    PubMed

    Zhang, Hua-ming; Yuan, Ping; Su, Mao-gen; Lü, Shi-hua

    2007-10-01

    Spectra of return strokes for artificial triggered lightning were obtained by optical multi-channel analyzer (OMA) in Shandong region. Compared with previous spectra of natural lightning, additional lines of ArI 602.5 nm and ArII 666.5 nm were observed. Under the model of local thermodynamic equilibrium, electronic temperatures of the lightning channel plasma were obtained according to the relative line intensities. Meanwhile, with semi-empirical method the electron density was obtained by Halpha line Stark broadening. In combination with plasma theory, electrical conductivity of the lightning channel has been calculated for the first time, and the characteristic of conductivity for lightning channel was also discussed. The relation between the electrical conductivity of channel and the return stroke current was analyzed, providing reference data for further work on computing return stroke current. Results show that the lightning channel is a good conductor, and electrons are the main carrier of channel current. The brightness of artificial triggered lightning channel is usually higher than that of natural lightning, and its current is smaller than that of the natural lightning. PMID:18306764

  4. Series resonance inverter with triggered vacuum gaps

    NASA Astrophysics Data System (ADS)

    Damstra, Geert C.; Zhang, X.

    1994-05-01

    Series resonance inverters based on semi-conductor switching elements are well-known and have a wide range of application, mainly for lower voltages. For high voltage application many switching elements have to be put in series to obtain sufficient blocking voltage. Voltage grinding and multiple gate control elements are needed. There is much experience with the triggered vacuum gaps as high voltage/high current single shot elements, for example in reignition circuits for synthetic circuit breaker tests. These elements have a blocking voltage of 50 - 100 kV and are triggerable by a light fiber control device. A prototype inverter has been developed that generates 0.1 Hz, 30 kV AC voltages with a flat top for tests on cables and capacitors of many micro farads fed from a low voltage supply of about 600 V. Only two TVG elements are needed to switch the resonant circuit alternatively on the positive or negative supply. The resonant circuit itself consists of the capacitance of the testobject and a high quality inductor that determines the frequency and the peak current of the voltage reversing process.

  5. Testing atmospheric and tidal earthquake triggering

    NASA Astrophysics Data System (ADS)

    Hainzl, S.; Ben-Zion, Y.; Cattania, C.; Wassermann, J. M.

    2013-12-01

    Seismicity closely related to hydrological impacts has been observed in several locations worldwide; particularly in intraplate areas where tectonic stressing rates are small. The trigger mechanism is usually explained by a poroelastic response of the seismogenic crust to surface water flux, leading to pore pressure changes at depth. To explain the earthquake triggering in response of those small stress changes, however, the crust has to be near a critical state in which other transient processes might be significant such as thermoelastic stress changes induced by the surface temperature variations or tidal stresses. We aim at a systematic comparative testing of these processes for particular case studies by analyzing modeled seismicity rate changes based on rate- and state-dependent frictional nucleation. One of our examples is the Mt. Hochstaufen in SW Germany, where seismicity is known to vary seasonally. A previous analysis showed that the seismicity in 2002 was highly correlated to rainfall-induced seismicity changes based on pore pressure diffusion. We have revisited this case by accounting for additional poroelastic effects, as well as for thermoelastic and tidal stresses and tested whether the model can explain the observations of the subsequent eight years between 2003 and 2010. Our analysis confirms that rainfall is the dominant driving force in this region. The model not only fits the year 2002 activity very well, but provides with the same parameters a reasonable fit to the subsequent period, with a probability gain of about 4 per event in comparison to a time-independent Poisson model.

  6. 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

  7. 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

  8. Numerical modeling of shallow fault creep triggered by nearby earthquakes

    NASA Astrophysics Data System (ADS)

    Wei, M.; Liu, Y.; McGuire, J. J.

    2011-12-01

    The 2010 El Mayor-Cucapha Mw 7.2 earthquake is the largest earthquake that strikes southern California in the last 18 years. It has triggered shallow fault creep on many faults in Salton Trough, Southern California, making it at least the 8th time in the last 42 years that a local or regional earthquake has done so. However, the triggering mechanism of fault creep and its implications to seismic hazard and fault mechanics is still poorly understood. For example, what determines the relative importance of static triggering and dynamic triggering of fault creep? What can we learn about the local frictional properties and normal stress from the triggering of fault creep? To understand the triggering mechanism and constrain fault frictional properties, we simulate the triggered fault creep on the Superstition Hills Fault (SHF), Salton Trough, Southern California. We use realistic static and dynamic shaking due to nearby earthquakes as stress perturbations to a 2D (in a 3D medium) planar fault model with rate-and-state frictional property variations both in depth and along strike. Unlike many previous studies, we focus on the simulation of triggered shallow fault creep instead of earthquakes. Our fault model can reproduce the triggering process, by static, dynamic , and combined stress perturbation. Preliminary results show that the magnitude of perturbation relative to the original stress level is an important parameter. In the static case, perturbation of 1% of normal stress trigger delayed fault creep whereas 10% of normal stress generate instantaneous creep. In the dynamic case, a change of two times in magnitude of perturbation can result in difference of triggered creep in several orders of magnitude. We explore combined triggering with different ratio of static and dynamic perturbation. The timing of triggering in a earthquake cycle is also important. With measurements on triggered creep on the SHF, we constrain local stress level and frictional parameters, which

  9. Triggering the Formation of the Solar System

    NASA Astrophysics Data System (ADS)

    Taylor, G. J.

    2003-05-01

    One of the most amazing discoveries in space science is the unambiguous evidence from meteorites that the solar nebula (the cloud of gas and dust in which the Sun and planets formed) contained radioactive isotopes with half-lives so short that they no longer exist. These include isotopes with very short half-lives, such as calcium-41 (100,000 years) and aluminum-26 (740,000 years), and those with longer half-lives such as plutonium-244 (81 million years). The short-lived isotopes are particularly interesting. If they formed in an exploding star, that explosion might have triggered the collapse of the huge interstellar cloud in which the Sun formed. On the other hand, if they formed in the solar nebula by intense radiation close to the Sun, then it would prove some hypotheses about the young Sun and jets of radiation from it. As synthesized and lucidly explained by Ernst Zinner (Washington University in St. Louis), recent data from ancient objects in meteorites point strongly to the supernova trigger idea. K. K. Marhas and J. N. Goswami (Physical Research Laboratory, Ahmedabad, India), and A. M. Davis (University of Chicago) found clear evidence in meteorites that beryllium-10, the one isotope that everybody agrees can be produced by solar radiation, is not accompanied by other short-lived isotopes as it would be if they were all produced by radiation flowing from the young Sun. (Beryllium-10 can also be made by galactic cosmic rays in the interstellar molecular cloud from which the solar system formed.) Two other research groups reported at the Lunar and Planetary Science Conference (March, 2003) that unmetamorphosed ordinary chondrites contained iron-60, an extinct isotope with a half-life of 1.5 million years. Iron-60 cannot be produced by intense, energetic solar radiation, so it must have been made before the Solar System began to form. The best bet is that much of it was made during the supernova explosion that triggered the formation of the Solar System.

  10. Triggering of volcanic activity by large earthquakes

    NASA Astrophysics Data System (ADS)

    Avouris, D.; Carn, S. A.; Waite, G. P.

    2011-12-01

    Statistical analysis of temporal relationships between large earthquakes and volcanic eruptions suggests seismic waves may trigger eruptions even over great distances, although the causative mechanism is not well constrained. In this study the relationship between large earthquakes and subtle changes in volcanic activity was investigated in order to gain greater insight into the relationship between dynamic stress and volcanic response. Daily measurements from the Ozone Monitoring Instrument (OMI), onboard the Aura satellite, provide constraints on volcanic sulfur dioxide (SO2) emission rates as a measure of subtle changes in activity. An SO2 timeseries was produced from OMI data for thirteen persistently active volcanoes. Seismic surface-wave amplitudes were modeled from the source mechanisms of moment magnitude (Mw) ≥7 earthquakes, and peak dynamic stress (PDS) was calculated. The SO2 timeseries for each volcano was used to calculate a baseline threshold for comparison with post-earthquake emission. Delay times for an SO2 response following each earthquake at each volcano were analyzed and compared to a random catalog. The delay time analysis was inconclusive. However, an analysis based on the occurrence of large earthquakes showed a response at most volcanoes. Using the PDS calculations as a filtering criterion for the earthquake catalog, the SO2 mass for each volcano was analyzed in 28-day windows centered on the earthquake origin time. If the average SO2 mass after the earthquake was greater than an arbitrary percentage of pre-earthquake mass, we identified the volcano as having a response to the event. This window analysis provided insight on what type of volcanic activity is more susceptible to triggering by dynamic stress. The volcanoes with lava lakes included in this study, Ambrym, Gaua, Villarrica, and Erta Ale, showed a clear response to dynamic stress while the volcanoes with lava domes, Merapi, Semeru, and Bagana showed no response at all. Perhaps

  11. Remote triggering of deep earthquakes in the 2002 Tonga sequences.

    PubMed

    Tibi, Rigobert; Wiens, Douglas A; Inoue, Hiroshi

    2003-08-21

    It is well established that an earthquake in the Earth's crust can trigger subsequent earthquakes, but such triggering has not been documented for deeper earthquakes. Models for shallow fault interactions suggest that static (permanent) stress changes can trigger nearby earthquakes, within a few fault lengths from the causative earthquake, whereas dynamic (transient) stresses carried by seismic waves may trigger earthquakes both nearby and at remote distances. Here we present a detailed analysis of the 19 August 2002 Tonga deep earthquake sequences and show evidence for both static and dynamic triggering. Seven minutes after a magnitude 7.6 earthquake occurred at a depth of 598 km, a magnitude 7.7 earthquake (664 km depth) occurred 300 km away, in a previously aseismic region. We found that nearby aftershocks of the first mainshock are preferentially located in regions where static stresses are predicted to have been enhanced by the mainshock. But the second mainshock and other triggered events are located at larger distances where static stress increases should be negligible, thus suggesting dynamic triggering. The origin times of the triggered events do not correspond to arrival times of the main seismic waves from the mainshocks and the dynamically triggered earthquakes frequently occur in aseismic regions below or adjacent to the seismic zone. We propose that these events are triggered by transient effects in regions near criticality, but where earthquakes have difficulty nucleating without external influences. PMID:12931183

  12. 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.

  13. Synthesising periodic triggering signals with genetic oscillators.

    PubMed

    Lin, Chun-Liang; Chen, Po-Kuei

    2014-02-01

    The potential of the clock lies in its role of triggering logic reaction for sequential biological circuits. This research introduces an idea of designing a genetic clock generator by Fourier series based on the genetic oscillators. The authors generalise the design idea using a combination of fundamental sinusoidal signals. Since biochemical reaction of the biological system is extremely slow, however, transition between minimal and maximal levels is instantaneous for an ideal clock signal; it is thus not directly realisable in biological systems. That means it would be hard to directly synthesize a square wave generator for use as a genetic clock. They apply Fourier series to represent a square wave as a finite summation of sinusoidal waves generated by some genetic oscillators with different harmonic oscillating frequencies, in which the amplitude alternates at a constant frequency between the fixed minimal and maximal levels with the same duration of time. PMID:24451394

  14. Triggered Reconnection at 1 MA on COBRA

    NASA Astrophysics Data System (ADS)

    Greenly, John; Blesener, Kate; Seyler, Charles; Zhao, Xuan

    2013-10-01

    We present new results in the study of magnetic reconnection of flux generated by two parallel currents in exploding Al wires driven to 1 MA by the Cornell COBRA pulser. Magnetic and thermal energy are stored in the system as the current rises in 200 ns. The stored energy is then dissipated in reconnection and outflows triggered at the time of voltage reversal and the decline of external magnetic pressure. Data are presented from a new optical spectroscopy diagnostic with high spatial and spectral resolution. The flows are supersonic. Strongly radiating shocks are associated with the current sheet and outflow boundaries. PERSEUS MHD and XMHD simulations are presented to compare with experiment and characterize the reconnection regime. Work supported by US DOE.

  15. Scintillation fiber hodoscope for topological triggering

    SciTech Connect

    Ferro-Luzzi, M.; Gorin, A.; Korolev, V.; Kuznetsov, A.; Manuilov, I.; Riazantsev, A.; Sidorov, A.; Kobayashi, M.; Yoshimura, Y.; Maki, T.; Kuroda, K.-I.; Penzo, A.; Takeutchi, F.; Okada, K.

    1998-11-09

    A fast and precise scintillating fiber (SciFi) hodoscope based on KURARAY SciFi and HAMAMATSU multianode H6568 tubes was constructed to be used in DIRAC experiment (PS-212) at CERN for tracking and topological triggering information. The front-end electronics was custom developed to allow on-line discrimination after built-in dynamic cross-talk rejection. Preliminary tests of the detector using more than 300 read-out channels have shown an excellent stability and optimum performance for this system: a uniform detection efficiency of 98%, a 125 {mu}m single hit and {approx}0.5 mm two-hit space resolution, 0.6 ns time resolution.

  16. Tidal triggering effect on earthquakes occurrence

    NASA Astrophysics Data System (ADS)

    Contadakis, M. E.; Arabelos, D.; Spatalas, S. D.

    2016-01-01

    In this review we present the investigation for the tidal triggering evidence on the earthquakes at various seismic areas of Greece. The result of our analysis using the HiCum method, indicate that the monthly variation of the frequencies of earthquake occurrence is in accordance with the period of the tidal lunar monthly (Mm) variations. The same happens with the corresponding diurnal and semi-diurnal variations of the frequencies of earthquake occurrence with the diurnal (K1), (O1) and semi-diurnal solar (S2) and semidiurnal lunar (M2) tidal variations. The confidence level of the Tidal-Earthquake frequency period compliance is very sensitive to the seismicity of the area and we call it Tidal - Earthquake frequency compliance parameter. We suggest that this parameter may be used in earthquake risk evaluation.

  17. Trigger delay compensation of beam synchronous sampling

    SciTech Connect

    Steimel, J.

    1996-05-01

    One of the problems of providing beam feedback in a large accelerator is the lack of beam synchronous trigger signals far from the RF signal source. IF single bucket resolutions are required, a cable extending from the RF source to the other side of the accelerator will not provide a synchronous signal if the RF frequency changes significantly with respect to the cable delay. This paper offers a solution to this problem by locking to the RF, at the remote location, using a digital phase locked loop. Then, the digitized frequency value is used to calculate the phase shift required to remain synchronized to the beam. Results are shown for phase lock to the Fermilab Main Ring RF. 1 ref., 4 figs.

  18. Explosion triggering by an accelerating flame.

    PubMed

    Bychkov, Vitaly; Akkerman, V'yacheslav

    2006-06-01

    The analytical theory of explosion triggering by an accelerating flame is developed. The theory describes the structure of a one-dimensional isentropic compression wave pushed by the flame front. The condition of explosion in the gas mixture ahead of the flame front is derived; the instant of the explosion is determined provided that a mechanism of chemical kinetics is known. As an example, it is demonstrated how the problem is solved in the case of a single reaction of Arrhenius type, controlling combustion both inside the flame front and ahead of the flame. The model of an Arrhenius reaction with a cutoff temperature is also considered. The limitations of the theory due to the shock formation in the compression wave are found. Comparison of the theoretical results to the previous numerical simulations shows good agreement. PMID:16906974

  19. Scintillation fiber hodoscope for topological triggering

    NASA Astrophysics Data System (ADS)

    Ferro-Luzzi, M.; Gorin, A.; Kobayashi, M.; Korolev, V.; Kuznetsov, A.; Maki, T.; Manuilov, I.; Kuroda, K.-I.; Penzo, A.; Riazantsev, A.; Sidorov, A.; Takeutchi, F.; Okada, K.; Yoshimura, Y.

    1998-11-01

    A fast and precise scintillating fiber (SciFi) hodoscope based on KURARAY SciFi and HAMAMATSU multianode H6568 tubes was constructed to be used in DIRAC experiment (PS-212) at CERN for tracking and topological triggering information. The front-end electronics was custom developed to allow on-line discrimination after built-in dynamic cross-talk rejection. Preliminary tests of the detector using more than 300 read-out channels have shown an excellent stability and optimum performance for this system: a uniform detection efficiency of 98%, a 125 μm single hit and ˜0.5 mm two-hit space resolution, 0.6 ns time resolution.

  20. Gravitational wave triggered searches for failed supernovae

    NASA Astrophysics Data System (ADS)

    Annis, James; Dark Energy Survey Collaboration

    2016-03-01

    Stellar core collapses occur to all stars of sufficiently high mass and often result in supernovae. A small fraction of supergiant stars, however, are thought to collapse directly into black holes without producing supernovae. A survey of such ``failed'' supernovae would require monitoring millions of supergiants for several years. That is very challenging even for current surveys. With the start of the Advanced LIGO science run, we investigate the possibility of detecting failed supernovae by looking for missing supergiants associated with gravitational wave triggers. We use the Dark Energy Camera (DECam). Our project is a joint effort between the community and the Dark Energy Survey (DES) collaboration. In this talk we report on our ongoing efforts and discuss prospects for future searches.

  1. Solanidine and tomatidine trigger scar pruritus.

    PubMed

    Alonso, Pedro E; Rioja, Luis F

    2016-05-01

    Scar pruritus is frequently encountered in clinical practice (particularly in burn patients) owing to its poorly known pathogenesis and difficult treatment. In previous work, we demonstrated the usefulness of a diet excluding edible solanaceae (viz., potatoes, tomatoes, peppers and aubergines) in patients with antihistamine-resistant scar pruritus. We hypothesized that alkaloids in solanaceae (particularly their secondary metabolites or aglycones) might be the actual pruritogens. In order to test this hypothesis, we conducted a single-blind prospective study on patients responding favourably to a solanaceae-free diet whose scar pruritus could be ascribed to one of the four foods. The study involved applying the aglycones solanidine and tomatidine to each scar and checking whether, and which, had a pruritogenic effect. A total of 18 patients (90%) responded by developing pruritus; also, the triggering aglycone coincided with that prevailing in the pruritogenic food. We concluded that solanaceae aglycones are directly involved in the pathogenesis of scar pruritus. PMID:26777454

  2. 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.

  3. 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.

  4. 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

  5. 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.

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

    PubMed

    Borysov, Sergiy I; Nepon-Sixt, Brook S; Alexandrow, Mark G

    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

  7. N-terminus three residues deletion mutant of human beta-defensin 3 with remarkably enhanced salt-resistance.

    PubMed

    Li, Tao; Guo, Feng; Wang, Qin; Fang, Huali; Li, Zhan; Wang, Dehui; Wang, Hui

    2015-01-01

    In this study, we designed and synthesized three N-terminal deletion analogs of human beta-defensin 3 (hBD-3), namely, hBD-3Δ4, hBD-3Δ7, and hBD-3Δ10, to determine the effect of N-terminal residues on the antibacterial activity and salt resistance of these peptides. The antibacterial activities and salt resistance of hBD-3 and its analogs were tested against a broad range of standard and clinically isolated strains. The deletion of nine N-terminal residues significantly reduced the antibacterial activity of hBD-3 against most of tested strains, particularly Klebsiella pneumonia. Compared with hBD-3 and other analogs, the analog with a deletion of three residues, hBD-3Δ4, exhibited significantly higher antimicrobial activity against almost all the tested strains, especially Escherichia coli and Enterococcus faecium, at high NaCl concentrations. Given its broad spectrum of antimicrobial activity and high salt resistance, hBD-3Δ4 could serve as a promising template for new therapeutic antimicrobial agents. PMID:25706284

  8. ACC2 Is Expressed at High Levels Human White Adipose and Has an Isoform with a Novel N-Terminus

    PubMed Central

    Raymond, Christopher K.; Garrett-Engele, Philip; Ohwaki, Kenji; Kan, Zhengyan; Kusunoki, Jun; Johnson, Jason M.

    2009-01-01

    Acetyl-CoA carboxylases ACC1 and ACC2 catalyze the carboxylation of acetyl-CoA to malonyl-CoA, regulating fatty-acid synthesis and oxidation, and are potential targets for treatment of metabolic syndrome. Expression of ACC1 in rodent lipogenic tissues and ACC2 in rodent oxidative tissues, coupled with the predicted localization of ACC2 to the mitochondrial membrane, have suggested separate functional roles for ACC1 in lipogenesis and ACC2 in fatty acid oxidation. We find, however, that human adipose tissue, unlike rodent adipose, expresses more ACC2 mRNA relative to the oxidative tissues muscle and heart. Human adipose, along with human liver, expresses more ACC2 than ACC1. Using RT-PCR, real-time PCR, and immunoprecipitation we report a novel isoform of ACC2 (ACC2.v2) that is expressed at significant levels in human adipose. The protein generated by this isoform has enzymatic activity, is endogenously expressed in adipose, and lacks the N-terminal sequence. Both ACC2 isoforms are capable of de novo lipogenesis, suggesting that ACC2, in addition to ACC1, may play a role in lipogenesis. The results demonstrate a significant difference in ACC expression between human and rodents, which may introduce difficulties for the use of rodent models for development of ACC inhibitors. PMID:19190759

  9. 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

  10. Poliovirus Replication Requires the N-terminus but not the Catalytic Sec7 Domain of ArfGEF GBF1

    PubMed Central

    Belov, George A.; Kovtunovych, Gennadiy; Jackson, Catherine L.; Ehrenfeld, Ellie

    2010-01-01

    Viruses are intracellular parasites whose reproduction relies on factors provided by the host. The cellular protein GBF1 is critical for poliovirus replication. Here we show that the contribution of GBF1 to virus replication is different from its known activities in uninfected cells. Normally GBF1 activates the Arf GTPases necessary for formation of COPI transport vesicles. GBF1 function is modulated by p115 and Rab1b. However, in polio-infected cells, p115 is degraded and neither p115 nor Rab1b knock-down affects virus replication. Poliovirus infection is very sensitive to BFA, an inhibitor of Arf activation by GBF1. BFA targets the catalytic Sec7 domain of GBF1. Nevertheless the BFA block of polio replication is rescued by expression of only the N-terminal region of GBF1 lacking the Sec7 domain. Replication of BFA-resistant poliovirus in the presence of BFA is uncoupled from Arf activation but is dependent on GBF1. Thus the function(s) of this protein essential for viral replication can be separated from those required for cellular metabolism. PMID:20497182

  11. 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. PMID:26685207

  12. 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.

    2016-02-01

    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.

  13. Comparison of stability, cellular, glucose-lowering and appetite supressing effects of oxyntomodulin analogues modified at the N-terminus.

    PubMed

    Lynch, Aisling M; Pathak, Nupur; Flatt, Yasmin E; Gault, Victor A; O'Harte, Finbarr P M; Irwin, Nigel; Flatt, Peter R

    2014-11-15

    Oxyntomodulin (Oxm) possesses beneficial biological actions for the potential treatment of obesity-diabetes. However, rapid inactivation by dipeptidyl peptidase-4 (DPP-4) results in a short half-life, hindering therapeutic applicability. In the present study, six Oxm analogues namely, (Thr(2))Oxm, (Asp(3))Oxm, (Aib(2))Oxm, (d-Ser(2))Oxm, (N-acetyl)Oxm and (d-Ser(2))Oxm-Lys-γ-glutamyl-PAL were synthesised and tested for DPP-4 stability and biological activity. Native Oxm, (Thr(2))Oxm and (Asp(3))Oxm were rapidly degraded by DPP-4, while (Aib(2))Oxm, (d-Ser(2))Oxm, (N-acetyl)Oxm and (d-Ser(2))Oxm-Lys-γ-glutamyl-PAL were resistant to degradation. All peptides stimulated cAMP production (P<0.01 to P<0.001) in GLP-1-R, but not in GIP-R, transfected cells. In glucagon-R transfected cells, all peptides except (N-acetyl)Oxm and (Thr(2))Oxm evoked significant cAMP generation. Similarly, all analogues, except (N-acetyl)Oxm, exhibited prominent (P<0.05 to P<0.001) insulinotropic activity in BRIN BD11 cells. When administered in conjunction with glucose to normal mice only native Oxm, (Aib(2))Oxm and (d-Ser(2))Oxm significantly (P<0.05 to P<0.01) increased overall plasma insulin levels. The corresponding glycaemic excursion was significantly (P<0.05 to P<0.001) lowered by all Oxm peptides, barring (N-acetyl)Oxm. Further investigations revealed persistent glucose-lowering and insulin-releasing actions of (d-Ser(2))Oxm-Lys-γ-glutamyl-PAL. Studies in GIP- and GLP-1-receptor KO mice with (Aib(2))Oxm, (d-Ser(2))Oxm, and (d-Ser(2))Oxm-Lys-γ-glutamyl-PAL highlighted the importance of GLP-1 receptor signalling for the beneficial glucose homoeostatic actions of these analogues. All peptides, except (N-acetyl)Oxm, possessed significant appetite suppressive effects in mice. These data highlight the significant therapeutic promise of enzymatically stable Oxm-based peptides, particularly with position 2 modifications, for the treatment of obesity-diabetes. PMID:25246014

  14. 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.

  15. Characterization of continuous B-cell epitopes in the N-terminus of glutamate decarboxylase67 using monoclonal antibodies.

    PubMed

    Agca, Selin; Houen, Gunnar; Trier, Nicole Hartwig

    2014-12-01

    Glutamate decarboxylase (GAD) is an autoantigen associated with the autoimmune disorders Type-1 diabetes (T1D) and stiff-person syndrome (SPS). The protein, being an essential enzyme involved in the production of the inhibitory neurotransmitter γ-aminobutyric acid, exists in two isoforms, GAD67 and GAD65. Both isoforms may be targeted by autoantibodies in SPS and T1D patients, although SPS primarily is associated with the presence of GAD67 autoantibodies, whereas T1D mainly is associated with the presence of GAD65 autoantibodies. In this study, we describe antibody reactivity to overlapping GAD67 peptides covering the complete protein sequence by modified peptide enzyme-linked immunosorbent assay in order to identify potential GAD67 epitopes using two monoclonal antibodies (mAbs). Both GAD67 mAbs showed reactivity to linear epitopes located at the N-terminal end of GAD67. The epitopes of GAD mAb 1 and 2 were identified as the amino acid sequences NAGADPNTTN and TETDFSNLF, respectively, corresponding to amino acids 14-23 and 91-99. Fine mapping of the epitopes revealed that antibody reactivity was related to amino acid side-chain functionality, rather than amino acid side-chain specificity. Additionally, results suggested that non-contact amino acids in the epitope structure were essential for antibody reactivity. The exact role of these amino acids remains to be determined, but they are thought to be involved in backbone hydrogen bonds or stabilization of the epitope structure. As only limited knowledge is available in relation to antigenic regions of GAD67, this study contributes to characterization of GAD67 epitopes and may be a first step in the development of peptide-based therapeutics against SPS. PMID:25358241

  16. Localization of the major antigenic determinant of EDP208 pili at the N-terminus of the pilus protein.

    PubMed Central

    Worobec, E A; Taneja, A K; Hodges, R S; Paranchych, W

    1983-01-01

    Trypsin digestion of pilin monomers from EDP208 conjugative pili causes cleavage of Lys12 to yield an N-terminal dodecapeptide, ET1 (Mr approximately equal to 1,500), and the remaining C-terminal fragment, ER (Mr approximately equal to 10,000). Using the amino acid sequence for ET1 provided by Frost et al. (J. Bacteriol. 153:950-954), we synthesized the N-terminal dodecapeptide chemically, conjugated it to bovine serum albumin, and subjected it to immunological studies. Antisera prepared against intact EDP208 pili as well as against the synthetic ET1-BSA conjugate were used in experiments involving an enzyme-linked immunosorbant assay and electrophoretic transfer of proteins from sodium dodecyl sulfate-polyacrylamide gels to nitrocellulose sheets. Both experimental approaches showed strong reactivity between the synthetic dodecapeptide and antiserum raised against whole pili. It was also found that antiserum raised against the synthetic peptide was reactive against intact pilus protein, indicating that the N-terminal dodecapeptide is an important antigenic determinant of the EDP208 pilus protein. Additional studies showed that the C-terminal fragment, ER, may contain one or two additional antigenic sites. Images PMID:6185467

  17. 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.

  18. Nuclear localization of the Hermes transposase depends on basic amino acid residues at the N-terminus of the protein.

    PubMed

    Michel, K; Atkinson, P W

    2003-07-01

    For the Hermes transposable element to be mobilized in its eukaryotic host, the transposase, encoded by the element, must make contact with its DNA. After synthesis in the cytoplasm, the transposase has to be actively imported into the nucleus because its size of 70.1 kDa prevents passive diffusion through the nuclear pore. Studies in vitro using transient expression of a Hermes-EGFP fusion protein in Drosophila melanogaster Schneider 2 cells showed the transposase was located predominantly in the nucleus. In silico sequence analysis, however, did not reveal any nuclear localization signal (NLS). To identify the sequence(s) responsible for localization of Hermes transposase in the nucleus, truncated or mutated forms of the transposase were examined for their influence on sub-cellular localization of marker proteins fused to the transposase. Using the same expression system and a GFP-GUS fusion double marker, residues 1-110 were recognized as sufficient, and residues 1-32 as necessary, for nuclear localization. Amino acid K25 greatly facilitated nuclear localization, indicating that at least this basic amino acid plays a significant role in this process. This sequence overlaps the proposed DNA binding region of the Hermes transposase and is not necessarily conserved in all members of the hAT transposable element family. PMID:12858343

  19. 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.

  20. 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

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

    PubMed

    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. Graphical Abstract ᅟ. PMID:26894887

  2. Three Surface Layer Homology Domains at the N Terminus of the Clostridium cellulovorans Major Cellulosomal Subunit EngE

    PubMed Central

    Tamaru, Yutaka; Doi, Roy H.

    1999-01-01

    The gene engE, coding for endoglucanase E, one of the three major subunits of the Clostridium cellulovorans cellulosome, has been isolated and sequenced. engE is comprised of an open reading frame (ORF) of 3,090 bp and encodes a protein of 1,030 amino acids with a molecular weight of 111,796. The amino acid sequence derived from engE revealed a structure consisting of catalytic and noncatalytic domains. The N-terminal-half region of EngE consisted of a signal peptide of 31 amino acid residues and three repeated surface layer homology (SLH) domains, which were highly conserved and homologous to an S-layer protein from the gram-negative bacterium Caulobacter crescentus. The C-terminal-half region, which is necessary for the enzymatic function of EngE and for binding of EngE to the scaffolding protein CbpA, consisted of a catalytic domain homologous to that of family 5 of the glycosyl hydrolases, a domain of unknown function, and a duplicated sequence (DS or dockerin) at its C terminus. engE is located downstream of an ORF, ORF1, that is homologous to the Bacillus subtilis phosphomethylpyrimidine kinase (pmk) gene. The unique presence of three SLH domains and a DS suggests that EngE is capable of binding both to CbpA to form a CbpA-EngE cellulosome complex and to the surface layer of C. cellulovorans. PMID:10322032

  3. 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

  4. 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

  5. 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.

  6. 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

  7. Dimerization of the human papillomavirus type 16 E2 N terminus results in DNA looping within the upstream regulatory region.

    PubMed

    Hernandez-Ramon, Elena E; Burns, Julie E; Zhang, Wenke; Walker, Hannah F; Allen, Stephanie; Antson, Alfred A; Maitland, Norman J

    2008-05-01

    Papillomavirus E2 proteins play a central role in regulating viral gene expression and replication. DNA-binding activity is associated with the C-terminal domain of E2, which forms a stable dimer, while the N-terminal domain is responsible for E2's replication and transactivation functions. The crystal structure of the latter domain revealed a second dimerization interface on E2 which may be responsible for DNA loop formation in the regulatory region of the human papillomavirus (HPV) genome. We investigated the biological significance of the N-terminal dimerization by introducing single amino acid substitutions into the dimerization interface. As expected, these substitutions did not influence the C-terminal dimerization and DNA-binding functions of E2. However, the mutations led to reduced transactivation of a synthetic E2-responsive reporter gene, while HPV DNA replication was unaffected. The effect of the mutations on DNA looping was visualized by atomic force microscopy. While wild-type E2 was able to generate DNA loops, all three mutant E2 proteins were defective in this ability. Our results suggest that N-terminal dimerization plays a role in E2-mediated transactivation, probably via DNA looping, a common mechanism for remote regulation of gene transcription. PMID:18337573

  8. Degradation, Promoter Recruitment and Transactivation Mediated by the Extreme N-Terminus of MHC Class II Transactivator CIITA Isoform III

    PubMed Central

    Ethier, Sylvain; Gaudreau, Luc; Steimle, Viktor

    2016-01-01

    Multiple relationships between ubiquitin-proteasome mediated protein turnover and transcriptional activation have been well documented, but the underlying mechanisms are still poorly understood. One way to induce degradation is via ubiquitination of the N-terminal α-amino group of proteins. The major histocompatibility complex (MHC) class II transactivator CIITA is the master regulator of MHC class II gene expression and we found earlier that CIITA is a short-lived protein. Using stable and transient transfections of different CIITA constructs into HEK-293 and HeLa cell lines, we show here that the extreme N-terminal end of CIITA isoform III induces both rapid degradation and transactivation. It is essential that this sequence resides at the N-terminal end of the protein since blocking of the N-terminal end with an epitope-tag stabilizes the protein and reduces transactivation potential. The first ten amino acids of CIITA isoform III act as a portable degron and transactivation sequence when transferred as N-terminal extension to truncated CIITA constructs and are also able to destabilize a heterologous protein. The same is observed with the N-terminal ends of several known N-terminal ubiquitination substrates, such as Id2, Cdt1 and MyoD. Arginine and proline residues within the N-terminal ends contribute to rapid turnover. The N-terminal end of CIITA isoform III is responsible for efficient in vivo recruitment to the HLA-DRA promoter and increased interaction with components of the transcription machinery, such as TBP, p300, p400/Domino, the 19S ATPase S8, and the MHC-II promoter binding complex RFX. These experiments reveal a novel function of free N-terminal ends of proteins in degradation-dependent transcriptional activation. PMID:26871568

  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. Degradation, Promoter Recruitment and Transactivation Mediated by the Extreme N-Terminus of MHC Class II Transactivator CIITA Isoform III.

    PubMed

    Beaulieu, Yves B; Leon Machado, Jorge A; Ethier, Sylvain; Gaudreau, Luc; Steimle, Viktor

    2016-01-01

    Multiple relationships between ubiquitin-proteasome mediated protein turnover and transcriptional activation have been well documented, but the underlying mechanisms are still poorly understood. One way to induce degradation is via ubiquitination of the N-terminal α-amino group of proteins. The major histocompatibility complex (MHC) class II transactivator CIITA is the master regulator of MHC class II gene expression and we found earlier that CIITA is a short-lived protein. Using stable and transient transfections of different CIITA constructs into HEK-293 and HeLa cell lines, we show here that the extreme N-terminal end of CIITA isoform III induces both rapid degradation and transactivation. It is essential that this sequence resides at the N-terminal end of the protein since blocking of the N-terminal end with an epitope-tag stabilizes the protein and reduces transactivation potential. The first ten amino acids of CIITA isoform III act as a portable degron and transactivation sequence when transferred as N-terminal extension to truncated CIITA constructs and are also able to destabilize a heterologous protein. The same is observed with the N-terminal ends of several known N-terminal ubiquitination substrates, such as Id2, Cdt1 and MyoD. Arginine and proline residues within the N-terminal ends contribute to rapid turnover. The N-terminal end of CIITA isoform III is responsible for efficient in vivo recruitment to the HLA-DRA promoter and increased interaction with components of the transcription machinery, such as TBP, p300, p400/Domino, the 19S ATPase S8, and the MHC-II promoter binding complex RFX. These experiments reveal a novel function of free N-terminal ends of proteins in degradation-dependent transcriptional activation. PMID:26871568

  11. 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.

  12. 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

  13. 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.

  14. 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.

  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. Dynamic Triggering of Deep Earthquakes—a Global Perspective

    NASA Astrophysics Data System (ADS)

    Zhan, Z.; Shearer, P. M.

    2014-12-01

    Dynamic triggering has been robustly observed for shallow earthquakes and tremor. Understanding this phenomenon provides important constraints on earthquake dynamics, such as earthquake nucleation, fault frictional properties, slow slip, and stress distributions. Tibi et al. (2003) reported examples of dynamic triggering in deep earthquakes and pointed out their potential to constrain the still-enigmatic faulting mechanisms of deep earthquakes. Here we analyze global earthquake catalogs to systematically search for statistically significant dynamic triggering at depths greater than 300 km. We find that dynamic triggering of deep earthquakes is most pronounced within 3 hours after the master events, and is limited in depth (i.e., triggering of and by shallow earthquakes is not observed). We also observed a significant downward triggering bias. We suggest that these characteristics may be related to deep earthquake rupture directivity and meta-stable olivine wedge structures inside subducted slabs.

  17. 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.

  18. 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.

  19. 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.

  20. Low-cost trigger circuit for sampling oscilloscope

    NASA Astrophysics Data System (ADS)

    Burd, Aleksander; Opalska, Katarzyna

    2008-01-01

    The paper presents a low-cost trigger circuit for use in sampling oscilloscope with bandwidth in order of hundreds of MHz. The presented dual-step trigger circuit provides relatively high bandwidth because of significant reduction of possibility of incorrect turning on in trigger circuit flip-flop (caused by circuit instability called tremor or - describing the same phenomenon by other means - its metastability. The paper presents a circuit structure, principle of operation and its physical realization.

  1. 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

  2. Insight into the physics of rupture: Dynamic triggering seismicity

    NASA Astrophysics Data System (ADS)

    Gonzalez-Huizar, Hector

    2009-12-01

    Seismic waves can trigger earthquakes and tremor at large distances from the causable event. Dynamic triggering occurs when the surface waves from large earthquakes change the stresses conditions on previously overstressed faults, promoting failure. To understand the causative stresses and environments behind dynamic triggering, we model the change in the stress field that the passing of Rayleigh and Love waves cause on a fault plane of arbitrary orientation relative to the direction of propagation of the waves, and apply a Coulomb failure criterion to calculate the potential of these stress changes to trigger seismicity. We apply our model to three different study regions and compare with observations. In the first case, we compare our model results with data from dynamically triggered earthquakes in the Australian Bowen Basin, Our data analysis shows that for this region, surface waves arriving at 45 degrees from the average local stress field are the most likely to trigger local seismicity. This agrees with our observations. In the second study case, we show how the same model can be applied to dynamic triggering of Non-volcanic tremor (NVT). Our modeling predicts the potential of a seismic wave to trigger slip on a fault plane promoting NVT. We search for tremor in the Central Range in Taiwan triggered by surfaces waves and compare the observations with our modeling. In the last study case, we present our modeling of the dynamic stress that triggered two events in Utah, one triggered by the 1992 Landers earthquake and the other by the 2002 Denali Fault earthquake. We show how dynamic stress modeling can be used to discriminate between the two axial planes of a first motion focal mechanism of a dynamically triggered event.

  3. 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.

  4. The digital trigger system for the RED-100 detector

    NASA Astrophysics Data System (ADS)

    Naumov, P. P.; Akimov, D. Yu.; Belov, V. A.; Bolozdynya, A. I.; Efremenko, Yu. V.; Kaplin, V. A.

    2015-12-01

    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.

  5. The ATLAS Trigger System: Ready for Run-2

    NASA Astrophysics Data System (ADS)

    Nakahama, Yu

    2015-12-01

    The ATLAS trigger system has been used very successfully for the online event selection during the LHC's first run (Run-1) between 2009 and 2013 at centre-of-mass energies (√s) between 900 GeV and 8 TeV. The trigger system consists of a hardware Level-1 (L1) and a software-based high-level trigger (HLT) that reduces the event rate from the design bunch-crossing rate of 40 MHz to an average recording rate of a few hundred Hz. During the next data-taking period (Run-2) starting in early 2015, the LHC will operate at √s = 13 TeV, resulting in roughly five times higher trigger rates. We will review the upgrades to the ATLAS trigger system that have been implemented during the long shutdown and that will allow us to cope with these increased trigger rates while maintaining or even improving our efficiencies to select relevant physics processes. These include changes to the L1 calorimeter trigger, the introduction of new L1 topological trigger modules, improvements in the L1 muon system and the merging of the previous two-level HLT system into a single event-filter farm. Finally, we will summarize the commissioning status of the trigger system in view of the imminent restart of data-taking.

  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. 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.

  8. Video event trigger and tracking system using fuzzy comparators

    NASA Technical Reports Server (NTRS)

    Williams, Glenn L. (Inventor)

    1996-01-01

    A video observation method and apparatus, the apparatus having a frame storage mechanism, a dividing mechanism, a plurality of fuzzy comparators and a trigger signal mechanism. The frame storage mechanism stores at least one non-current video frame of a viewing field. The dividing mechanism divides a current video frame of the viewing field and the at least one non-current video frame into a plurality of corresponding trigger sections. The plurality of fuzzy comparators each compare and detect a fuzzy logic difference between one trigger section of the current video frame and the corresponding trigger sections of the at least one non-current video frame, the number of fuzzy comparators being selected so that every trigger section of the current video frame is compared. The trigger signal mechanism provides a trigger signal when a fuzzy logic difference is detected between any of the corresponding current and non-current trigger sections. A video observation mechanism and data reducing mechanism may be included with the above apparatus or alone with only a frame storage mechanism, a single generic comparator and a trigger signal mechanism. The video observation mechanism provides a video data stream, wherein each pixel of each frame of a viewing field is provided as multiple bits of data. The data reducing mechanism reduces each set of multiple bits of data which correspond to each pixel to one bit of binary data based on whether the pixel has a level of grey which is above or below a threshold level of grey.

  9. GPUs for real-time processing in HEP trigger systems

    NASA Astrophysics Data System (ADS)

    Ammendola, R.; Biagioni, A.; Deri, L.; Fiorini, M.; Frezza, O.; Lamanna, G.; Lo Cicero, F.; Lonardo, A.; Messina, A.; Sozzi, M.; Pantaleo, F.; Paolucci, Ps; Rossetti, D.; Simula, F.; Tosoratto, L.; Vicini, P.; Gap Collaboration

    2014-06-01

    We describe a pilot project (GAP - GPU Application Project) for the use of GPUs (Graphics processing units) for online triggering applications in High Energy Physics experiments. Two major trends can be identified in the development of trigger and DAQ systems for particle physics experiments: the massive use of general-purpose commodity systems such as commercial multicore PC farms for data acquisition, and the reduction of trigger levels implemented in hardware, towards a fully software data selection system ("trigger-less"). The innovative approach presented here aims at exploiting the parallel computing power of commercial GPUs to perform fast computations in software not only in high level trigger levels but also in early trigger stages. General-purpose computing on GPUs 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 accelerators in offline computation. With the steady reduction of GPU latencies, and the increase in link and memory throughputs, the use of such devices for real-time applications in high energy physics data acquisition and trigger systems is becoming relevant. We discuss in detail the use of online parallel computing on GPUs for synchronous low-level triggers with fixed latency. In particular we show preliminary results on a first test in the CERN NA62 experiment. The use of GPUs in high level triggers is also considered, the CERN ATLAS experiment being taken as a case study of possible applications.

  10. GPUs for real-time processing in HEP trigger systems

    NASA Astrophysics Data System (ADS)

    Lamanna, G.; Ammendola, R.; Bauce, M.; Biagioni, A.; Fantechi, R.; Fiorini, M.; Giagu, S.; Graverini, E.; Lamanna, G.; Lonardo, A.; Messina, A.; Pantaleo, F.; Paolucci, P. S.; Piandani, R.; Rescigno, M.; Simula, F.; Sozzi, M.; Vicini, P.

    2014-06-01

    We describe a pilot project for the use of Graphics Processing Units (GPUs) for online triggering applications in High Energy Physics (HEP) experiments. Two major trends can be identified in the development of trigger and DAQ systems for HEP experiments: the massive use of general-purpose commodity systems such as commercial multicore PC farms for data acquisition, and the reduction of trigger levels implemented in hardware, towards a pure software selection system (trigger-less). The very innovative approach presented here aims at exploiting the parallel computing power of commercial GPUs to perform fast computations in software both at low- and high-level trigger stages. General-purpose computing on GPUs 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 throughputs, the use of such devices for real-time applications in high-energy physics data acquisition and trigger systems is becoming very attractive. We discuss in details the use of online parallel computing on GPUs for synchronous low-level trigger with fixed latency. In particular we show preliminary results on a first test in the NA62 experiment at CERN. The use of GPUs in high-level triggers is also considered, the ATLAS experiment (and in particular the muon trigger) at CERN will be taken as a study case of possible applications.

  11. 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.

  12. 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

  13. The Extracellular Surface of the GLP-1 Receptor Is a Molecular Trigger for Biased Agonism.

    PubMed

    Wootten, Denise; Reynolds, Christopher A; Smith, Kevin J; Mobarec, Juan C; Koole, Cassandra; Savage, Emilia E; Pabreja, Kavita; Simms, John; Sridhar, Rohan; Furness, Sebastian G B; Liu, Mengjie; Thompson, Philip E; Miller, Laurence J; Christopoulos, Arthur; Sexton, Patrick M

    2016-06-16

    Ligand-directed signal bias offers opportunities for sculpting molecular events, with the promise of better, safer therapeutics. Critical to the exploitation of signal bias is an understanding of the molecular events coupling ligand binding to intracellular signaling. Activation of class B G protein-coupled receptors is driven by interaction of the peptide N terminus with the receptor core. To understand how this drives signaling, we have used advanced analytical methods that enable separation of effects on pathway-specific signaling from those that modify agonist affinity and mapped the functional consequence of receptor modification onto three-dimensional models of a receptor-ligand complex. This yields molecular insights into the initiation of receptor activation and the mechanistic basis for biased agonism. Our data reveal that peptide agonists can engage different elements of the receptor extracellular face to achieve effector coupling and biased signaling providing a foundation for rational design of biased agonists. PMID:27315480

  14. 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

  15. Early diabetic neuropathy: Triggers and mechanisms

    PubMed Central

    Dobretsov, Maxim; Romanovsky, Dmitry; Stimers, Joseph R

    2007-01-01

    Peripheral neuropathy, and specifically distal peripheral neuropathy (DPN), is one of the most frequent and troublesome complications of diabetes mellitus. It is the major reason for morbidity and mortality among diabetic patients. It is also frequently associated with debilitating pain. Unfortunately, our knowledge of the natural history and pathogenesis of this disease remains limited. For a long time hyperglycemia was viewed as a major, if not the sole factor, responsible for all symptomatic presentations of DPN. Multiple clinical observations and animal studies supported this view. The control of blood glucose as an obligatory step of therapy to delay or reverse DPN is no longer an arguable issue. However, while supporting evidence for the glycemic hypothesis has accumulated, multiple controversies accumulated as well. It is obvious now that DPN cannot be fully understood without considering factors besides hyperglycemia. Some symptoms of DPN may develop with little, if any, correlation with the glycemic status of a patient. It is also clear that identification of these putative non-glycemic mechanisms of DPN is of utmost importance for our understanding of failures with existing treatments and for the development of new approaches for diagnosis and therapy of DPN. In this work we will review the strengths and weaknesses of the glycemic hypothesis, focusing on clinical and animal data and on the pathogenesis of early stages and triggers of DPN other than hyperglycemia. PMID:17226897

  16. An enhanced multiwavelength ultraviolet biological trigger lidar

    NASA Astrophysics Data System (ADS)

    Achey, Alexander; Bufton, Jack; Dawson, Jeffrey; Huang, Wen; Lee, Sangmin; Mehta, Nikhil; Prasad, Coorg R.

    2004-12-01

    A compact Ultraviolet Biological Trigger Lidar (UBTL) instrument for detection and discrimination of bio-warfare-agent (BWA) simulant aerosol clouds was developed by us [Prasad, et al, 2004] using a 5mW, 375nm semiconductor UV optical source (SUVOS) laser diode. It underwent successful field tests at Dugway Proving Ground and demonstrated measurement ranges of over 300m for elastic scattering and >100m for fluorescence. The UBTL was modified during mid-2004 to enhance its detection and discrimination performance with increased range of operation and sensitivity. The major optical modifications were: 1. increase in telescope collection aperture to 200 mm diameter: 2. addition of 266nm and 977nm laser transmitters: 3. addition of three detection channels for 266nm and 977nm elastic backscatter and fluorescence centered at 330nm. Also the commercial electronics of the original UBTL were replaced with a multi-channel field programmable gate array (FPGA) chip for laser diode modulation and data acquisition that allowed simultaneous and continuous operation of the UBTL sensor on all of its transmitter and receiver wavelengths. A notebook computer was added for data display and storage. Field tests were performed during July 2004 at the Edgewood Chemical and Biological Center in Maryland to establish the enhanced performance of UBTL subsystems. Results of these tests are presented and discussed.

  17. 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

  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. High Resolution Spectroscopy of Rocket Triggered Lightning

    NASA Astrophysics Data System (ADS)

    Walker, T. D.; Christian, H. J.

    2012-12-01

    In the Summer of 2012, optical spectra of rocket triggered lightning return strokes were recorded at the International Center for Lightning Research and Testing in north-central Florida. The spectra were recorded with a Phantom v710 high speed CMOS camera running at 670 kfps (kiloframes per second) with a 1 microsecond exposure time and a Princeton ProEM high speed CCD camera running at over 1,000 kfps with a 0.5 microsecond exposure time. Three separate volume phase holographic grisms were used during the study and were sensitive in the spectral ranges of 3800-6200 Angstroms, 6400-6700 Angstroms, 7600-7900 Angstroms. The first had a spectral resolution of 5 Angstroms, allowing the separation of singly ionized nitrogen multiplets. These spectra were recorded 50m above the ground with 0.65 m vertical field of view. The second and third spectrometers were recorded with the Princeton ProEM camera and had a resolution of 0.5 Angstroms. These spectra were recorded 50m above ground with 0.06 m vertical field of view. The evolution of important lines in the spectral ranges such as singly ionized nitrogen lines (including spatially resolved 4630 Angstrom multiplet), H-alpha, and a resolved 7774 Angstrom Neutral oxygen triplet will all be presented. The opacity of the lightning channel as well as number density, temperature, and conductivity, will be discussed along with channel base current.

  20. 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

  1. Externally triggered dual function of complex microcapsules.

    PubMed

    Yi, Qiangying; Sukhorukov, Gleb B

    2013-10-22

    By introducing UV-sensitive chemical groups causing different potential response as building blocks, fabricated LbL capsules can be endowed with dual UV-responsive properties in specific layers. One block is responsible for fast capsule sealing and the other for longer term capsule swelling and rupture. Therefore, the multifunction of these capsules could be activated selectively when exposed to external UV light with suitable wavelengths. In this work, dual-functional complex microcapsules (PDADMAC/PAZO)4-(DAR/Nafion)2 containing both diazonium and aozbenzene groups were proposed as clear examples to realize a time-dependent UV response for successive encapsulation and release. Upon exposure to UV light, the DAR/Nafion layers underwent a rapid in situ cross-linking and hence to seal the capsule shells through diazonium-related photolysis. Then further gradual shell swelling was followed by realignment of azobenzene molecules in PDADMAC/PAZO layers. Fluorescent polymers were consequently studied as cargo substances. Results indicated that continuous UV light triggered rapid cargo encapsulation over minutes time scale and gradual release with continuous irradiation over hours. PMID:24083649

  2. Triggering cascades and statistical properties of aftershocks

    NASA Astrophysics Data System (ADS)

    Gu, C.; Davidsen, J.

    2011-12-01

    Applying a recently introduced general statistical procedure for identifying aftershocks based on complex network theory, we investigate the statistical properties of aftershocks for a high-resolution earthquake catalog covering Southern California. In comparison with earlier studies of aftershock sequences, we show that many features depend sensitively on how one defines aftershocks and whether one includes only first-generation of aftershocks or one also takes all indirectly triggered aftershocks into account. This includes the temporal variation in the rate of aftershocks for mainshocks of small magnitude, for example, as well as the variation in the rate of aftershocks for short to intermediate times after a mainshock. Other features are, however, robust indicating that they truly characterize aftershock sequences. These include the p-values in the Omori-Utsu law for large mainshocks, B{aa}th's law and the productivity law with an exponent smaller than the b-value in the Gutenberg-Richter law. We also find that, for large mainshocks, the dependence of the parameters in the Omori-Utsu law on the lower magnitude cut-off are in excellent agreement with a recent proposition based on B{aa}th's law and the Gutenberg-Richter law, giving rise to a generalized Omori-Utsu law. Our analysis also provides evidence that the exponent p in the Omori-Utsu law does not vary significantly with mainshock magnitude.

  3. Trigger Laws: Does Signing a Petition Give Parents a Voice?

    ERIC Educational Resources Information Center

    Bacon, David

    2011-01-01

    Parent trigger laws, according to their proponents, give parents power. Gregory McGinity, managing director of policy for the Broad Education Foundation, calls them "a way for parents' voices to be heard." Sounds good. But is the parent trigger concept a way to put parents in charge of their kids' education, or is it part of a political agenda…

  4. 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.

  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. 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....

  7. 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…

  8. 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…

  9. Studying Triggers for Interest and Engagement Using Observational Methods

    ERIC Educational Resources Information Center

    Renninger, K. Ann; Bachrach, Jessica E.

    2015-01-01

    In this article, we discuss the contribution of observational methods to understanding the processes involved in triggering interest and establishing engagement. We begin by reviewing the literatures on interest and engagement, noting their similarities, differences, and the utility to each of better understanding the triggering process. We then…

  10. Dynamic triggering: Stress modeling and a case study

    NASA Astrophysics Data System (ADS)

    Gonzalez-Huizar, Hector; Velasco, Aaron A.

    2011-02-01

    Changes in the static stress can trigger nearby earthquakes that occur within a few fault lengths from the causative event. Transient stresses caused by passage of surface waves commonly trigger events at remote distances, yet little is documented or understood about the processes and stresses necessary for remote triggering. To understand the causative stresses and environments behind remote, or dynamic, triggering, we must decipher the stresses caused by the passage of the surface waves in relation to the local stress field and fault conditions where the triggered events occur. In this study, we model the change in the stress field that the passing of Rayleigh and Love waves causes on a fault plane of arbitrary orientation relative to the direction of propagation of the waves, and we apply a Coulomb failure criterion to calculate the potential of these stress changes to trigger reverse, normal, or strike-slip failure. We compare these model results with data from dynamically triggered earthquakes in the Australian Bowen Basin, an area with low seismicity and mapped regional stress and that is at the margin of a stable continental craton. Our data analysis shows that for this region, surface waves arriving at 45° from the average strike direction are the most likely to trigger local seismicity. This agrees with our observations.

  11. 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

  12. A programmable systolic trigger processor for FERA bus data

    NASA Astrophysics Data System (ADS)

    Appelquist, G.; Hovander, B.; Selldén, B.; Bohm, C.

    1993-04-01

    A generic CAMAC based trigger processor module for fast processing of large amounts of ADC data, has been designed. This module has been realised using complex programmable gate arrays (LCAs from XILINX). The gate arrays have been connected to memories and multipliers in such a way that different gate array configurations can cover a wide range of module applications. Using this module, it is possible to construct complex trigger processors. The module uses both the fast ECL FERA bus and the CAMAC bus for inputs and outputs. The latter, however, is primarily used for setup and control but may also be used for data output. Large numbers of ADCs can be served by a hierarchical arrangement of trigger processor modules, processing ADC data with pipe-line arithmetics producing the final result at the apex of the pyramid. The trigger decision will be transmitted to the data acquisition system via a logic signal while numeric results may be extracted by the CAMAC controller. The trigger processor was originally developed for the proposed neutral particle search experiment at CERN, NUMASS. There it was designed to serve as a second level trigger processor. It was required to correct all ADC raw data for efficiency and pedestal, calculate the total calorimeter energy, obtain the optimal time of flight data and calculate the particle mass. A suitable mass-cut would then deliver the trigger decision. More complex triggers were also considered.

  13. New optical technology for low mass intelligent trigger and readout.

    SciTech Connect

    Underwood, D.; Salvachua-Ferrando, B.; Stanek, R.; Lopez, D.; Liu, J.; Michel, J.; Kimerling, L. C.

    2010-07-01

    New optical devices offer the potential for reductions in mass, power, and cost of data paths for on-board trigger and readout of tracking detectors. We give examples of optical modulators, MEMS beam steering devices, and optical coupling. We also present results on radiation hardness of materials as well as different approaches to using optics in triggering.

  14. 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…

  15. 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.

  16. Mathematical Model of the Biosensors Acting in a Trigger Mode

    PubMed Central

    Baronas, Romas; Kulys, Juozas; Ivanauskas, Feliksas

    2004-01-01

    A mathematical model of biosensors acting in a trigger mode has been developed. One type of the biosensors utilized a trigger enzymatic reaction followed by the cyclic enzymatic and electrochemical conversion of the product (CCE scheme). Other biosensors used the enzymatic trigger reaction followed by the electrochemical and enzymatic product cyclic conversion (CEC scheme). The models were based on diffusion equations containing a non-linear term related to Michaelis-Menten kinetics of the enzymatic reactions. The digital simulation was carried out using the finite difference technique. The influence of the substrate concentration, the maximal enzymatic rate as well as the membrane thickness on the biosensor response was investigated. The numerical experiments demonstrated a significant gain (up to dozens of times) in biosensor sensitivity when the biosensor response was under diffusion control. In the case of significant signal amplification, the response time with triggering was up to several times longer than that of the biosensor without triggering.

  17. The BTeV trigger and data acquisition system

    SciTech Connect

    Butler, Joel N.; /Fermilab

    2004-10-01

    The BTeV trigger inspects every beam crossing of the Fermilab Tevatron, running at a luminosity of 2 x 10{sup 32}/cm{sup 2}-s, and selects events that have ''detached vertices'' from B decays occurring downstream of the main interaction. The system uses a massively parallel system of FPGAs and microprocessors to produce a trigger decision on average every 396 ns. The trigger calculations are facilitated by the 23 Million channel pixel detector that provides the input to the trigger. Front end electronics sparsifies the remainder of event data and sends it to large, Tbyte, memory buffers that store it until the trigger decision can be made. This complex system presents special challenges in fault monitoring and power and cooling.

  18. 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

  19. 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.

  20. Earthquake Triggering by High Power Electric Pulses

    NASA Astrophysics Data System (ADS)

    Novikov, Victor; Konev, Yuri; Zeigarnik, Vladimir

    2010-05-01

    The study carried out by the Joint Institute for High Temperatures in cooperation with the Institute of Physics of the Earth and the Research Station in Bishkek of Russian Academy of Sciences in 1999-2008 showed a response of weak seismicity at field experiments with electric pulsed power systems, as well as acoustic emission of rock specimens under laboratory conditions on high-power electric current pulses applied to the rocks. It was suggested that the phenomenon discovered may be used in practice for partial release of tectonic stresses in the Earth crust for earthquake hazard mitigation. Nevertheless, the mechanism of the influence of man-made electromagnetic field on the regional seismicity is not clear yet. One of possible cause of the phenomenon may be pore fluid pressure increase in the rocks under stressed conditions due to Joule heat generation by electric current injected into the Earth crust. It is known that increase of pore fluid pressure in the fault zone over a critical pressure of about 0.05 MPa is sufficient to trigger an earthquake if the fault is near the critical state due to accumulated tectonic deformations. Detailed 3D-calculaton of electric current density in the Earth crust of the Northern Tien Shan provided by pulsed electric high-power system connected to grounded electric dipole showed that at the depth of earthquake epicenters (over 5 km) the electric current density is lower than 10-7 A/m2 that is not sufficient for increase of pressure in the fluid-saturated porous geological medium due to Joule heat generation, which may provide formation of cracks resulting in the fault propagation and release of tectonic stresses in the Earth crust. Nevertheless, under certain conditions, when electric current will be injected into the fault through the casing pipes of two deep wells with preliminary injection of conductive fluid into the fault, the current density may be high enough for significant increase of mechanic pressure in the porous two

  1. 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. PMID:19951734

  2. Nonsense codons trigger an RNA partitioning shift.

    PubMed

    Bhalla, Angela D; Gudikote, Jayanthi P; Wang, Jun; Chan, Wai-Kin; Chang, Yao-Fu; Olivas, O Renee; Wilkinson, Miles F

    2009-02-13

    T-cell receptor-beta (TCRbeta) genes naturally acquire premature termination codons (PTCs) as a result of programmed gene rearrangements. PTC-bearing TCRbeta transcripts are dramatically down-regulated to protect T-cells from the deleterious effects of the truncated proteins that would otherwise be produced. Here we provide evidence that two responses collaborate to elicit this dramatic down-regulation. One is rapid mRNA decay triggered by the nonsense-mediated decay (NMD) RNA surveillance pathway. We demonstrate that this occurs in highly purified nuclei lacking detectable levels of three different cytoplasmic markers, but containing an outer nuclear membrane marker, suggesting that decay occurs either in the nucleoplasm or at the outer nuclear membrane. The second response is a dramatic partitioning shift in the nuclear fraction-to-cytoplasmic fraction mRNA ratio that results in few TCRbeta transcripts escaping to the cytoplasmic fraction of cells. Analysis of TCRbeta mRNA kinetics after either transcriptional repression or induction suggested that this nonsense codon-induced partitioning shift (NIPS) response is not the result of cytoplasmic NMD but instead reflects retention of PTC(+) TCRbeta mRNA in the nuclear fraction of cells. We identified TCRbeta sequences crucial for NIPS but found that NIPS is not exclusively a property of TCRbeta transcripts, and we identified non-TCRbeta sequences that elicit NIPS. RNA interference experiments indicated that NIPS depends on the NMD factors UPF1 and eIF4AIII but not the NMD factor UPF3B. We propose that NIPS collaborates with NMD to retain and degrade a subset of PTC(+) transcripts at the outer nuclear membrane and/or within the nucleoplasm. PMID:19091751

  3. The high-level trigger of ALICE

    NASA Astrophysics Data System (ADS)

    Tilsner, H.; Alt, T.; Aurbakken, K.; Grastveit, G.; Helstrup, H.; Lindenstruth, V.; Loizides, C.; Nystrand, J.; Roehrich, D.; Skaali, B.; Steinbeck, T.; Ullaland, K.; Vestbo, A.; Vik, T.

    One of the main tracking detectors of the forthcoming ALICE Experiment at the LHC is a cylindrical Time Projection Chamber (TPC) with an expected data volume of about 75 MByte per event. This data volume, in combination with the presumed maximum bandwidth of 1.2 GByte/s to the mass storage system, would limit the maximum event rate to 20 Hz. In order to achieve higher event rates, online data processing has to be applied. This implies either the detection and read-out of only those events which contain interesting physical signatures or an efficient compression of the data by modeling techniques. In order to cope with the anticipated data rate, massive parallel computing power is required. It will be provided in form of a clustered farm of SMP-nodes, based on off-the-shelf PCs, which are connected with a high bandwidth low overhead network. This High-Level Trigger (HLT) will be able to process a data rate of 25 GByte/s online. The front-end electronics of the individual sub-detectors is connected to the HLT via an optical link and a custom PCI card which is mounted in the clustered PCs. The PCI card is equipped with an FPGA necessary for the implementation of the PCI-bus protocol. Therefore, this FPGA can also be used to assist the host processor with first-level processing. The first-level processing done on the FPGA includes conventional cluster-finding for low multiplicity events and local track finding based on the Hough Transformation of the raw data for high multiplicity events. PACS: 07.05.-t Computers in experimental physics - 07.05.Hd Data acquisition: hardware and software - 29.85.+c Computer data analysis

  4. 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.

  5. 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.

  6. Triggered Snap-Through of Bistable Shells

    NASA Astrophysics Data System (ADS)

    Cai, Yijie; Huang, Shicheng; Trase, Ian; Hu, Nan; Chen, Zi

    Elastic bistable shells are common structures in nature and engineering, such as the lobes of the Venus flytrap or the surface of a toy jumping poppers. Despite their ubiquity, the parameters that control the bistability of such structures are not well understood. In this study, we explore how the geometrical features of radially symmetric elastic shells affect the shape and potential energy of a shell's stable states, and how to tune certain parameters in order to generate a snap-through transition from a convex semi-stable state to concave stable state. We fabricated a series of elastic shells with varying geometric parameters out of silicone rubber and measured the resulting potential energy in the semi-stable state. Finite element simulations were also conducted in order to determine the deformation and stress in the shells during snap-through. It was found that the energy of the semi-stable state is controlled by only two geometric parameters and a dimensionless ratio. We also noted two distinct transitions during snap-through, one between monostability and semi-bistability (the state a popper toy is in before it snaps-through and jumps), and a second transition between semi-bistability and true bistability. This work shows that it is possible to use a set of simple parameters to tailor the energy landscape of an elastic shell in order to generate complex trigger motions for their potential use in smart applications. Z.C. acknowledge support from Society in Science-Branco Weiss Fellowship, administered by ETH Zurich.

  7. 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.

  8. 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

  9. Construct development: The Suicide Trigger Scale (STS-2), a measure of a hypothesized suicide trigger state

    PubMed Central

    2010-01-01

    Background This study aims to develop the construct of a 'suicide trigger state' by exploring data gathered with a novel psychometric self-report instrument, the STS-2. Methods The STS-2, was administered to 141 adult psychiatric patients with suicidal ideation. Multiple statistical methods were used to explore construct validity and structure. Results Cronbach's alpha (0.949) demonstrated excellent internal consistency. Factor analyses yielded two-component solutions with good agreement. The first component described near-psychotic somatization and ruminative flooding, while the second described frantic hopelessness. ROC analysis determined an optimal cut score for a history of suicide attempt, with significance of p < 0.03. Logistic regression analysis found items sensitive to history of suicide attempt described ruminative flooding, doom, hopelessness, entrapment and dread. Conclusions The STS-2 appears to measure a distinct and novel clinical entity, which we speculatively term the 'suicide trigger state.' High scores on the STS-2 associate with reported history of past suicide attempt. PMID:21144063

  10. 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.

  11. 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

  12. 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. PMID:26504306

  13. Electrophysiological characteristics according to activity level of myofascial trigger points

    PubMed Central

    Yu, Seong Hun; Kim, Hyun Jin

    2015-01-01

    [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. PMID:26504306

  14. A programmable systolic trigger processor for FERA-bus data

    NASA Astrophysics Data System (ADS)

    Appelquist, G.; Hovander, B.; Sellden, B.; Bohm, C.

    1992-09-01

    A generic CAMAC based trigger processor module for fast processing of large amounts of Analog to Digital Converter (ADC) data was designed. This module was realized using complex programmable gate arrays. The gate arrays were connected to memories and multipliers in such a way that different gate array configurations can cover a wide range of module applications. Using this module, it is possible to construct complex trigger processors. The module uses both the fast ECL FERA bus and the CAMAC bus for inputs and outputs. The latter is used for set up and control but may also be used for data output. Large numbers of ADC's can be served by a hierarchical arrangement of trigger processor modules which process ADC data with pipeline arithmetics and produce the final result at the apex of the pyramid. The trigger decision is transmitted to the data acquisition system via a logic signal while numeric results may be extracted by the CAMAC controller. The trigger processor was developed for the proposed neutral particle search. It was designed to serve as a second level trigger processor. It was required to correct all ADC raw data for efficiency and pedestal, calculate the total calorimeter energy, obtain the optimal time of flight data, and calculate the particle mass. A suitable mass cut would then deliver the trigger decision.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. On the proposed triggering of Jovian radio emissions

    NASA Astrophysics Data System (ADS)

    Desch, M. D.; Kaiser, M. L.

    1985-09-01

    Calvert (1985) has proposed that solar type III radio bursts can trigger the onset of certain Jovian hectometer wavelength emissions. The authors show, using the data obtained by the Voyager Planetary Radio Astronomy experiment, that this triggering hypothesis is not supported statistically. Furthermore, the authors question the causality of this proposed triggering 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.

  1. 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.

  2. Quasi-static versus dynamic triggering of fault slip

    NASA Astrophysics Data System (ADS)

    Wu, W.

    2013-12-01

    The quasi-static triggering of fault slip has long been recognized as a mechanism of earthquakes. The dynamic triggering of fault slip is associated with earthquake aftershocks and man-made geological hazards, such as rock collapse in underground excavations and induced seismicity in geothermal productions. The objective of this study is to experimentally investigate the differences between quasi-static and dynamic triggering of fault slip. A direct-shear configuration (Fig. 1) is developed to simulate fault slip, which consists of an incident norite plate (1000 × 120 × 30 mm) and a transverse norite plate (500 × 80 × 30 mm). A quartz sand layer is sandwiched between the incident and transverse plates to simulate a granular fault zone. A servo-controlled quasi-static loading system induces the quasi-static triggering of fault slip, and a dynamic loading system containing two parallel compressed springs instantaneously launches a striker norite plate (100 × 120 × 30 mm) to induce an incident P-wave (a half-wavelength of 750 mm). The P-wave propagates in the incident plate and causes the dynamic triggering of fault slip. The dynamic triggering of fault slip is designed to be solely induced by the P-wave before wave reflection at the plate end. Both quasi-static and dynamic triggering induce non-uniform shear stress distribution along the fault zone. There is a shear stress at the trailing edge, which controls the fault slip, and a rebound stress at the leading edge, which is caused by a small moment. The fault slip is triggered when the maximum shear stress reaches a critical value at the trailing edge and is accompanied by shear stress drop. The quasi-static triggering of fault slip is unrecoverable and includes a main slip and a few short slips before and after the main slip. The dynamic triggering of fault slip can be partially recovered after the P-wave and consists of a few unrecovered slips. The duration of the dynamic triggering of fault slip is a few

  3. The Level-0 calorimetric trigger of the NA62 experiment

    NASA Astrophysics Data System (ADS)

    Ammendola, R.; Barbanera, M.; Bizzarri, M.; Bonaiuto, V.; Ceccucci, A.; Checcucci, B.; De Simone, N.; Fantechi, R.; Federici, L.; Fucci, A.; Lupi, M.; Paoluzzi, G.; Papi, A.; Piccini, M.; Ryjov, V.; Salamon, A.; Salina, G.; Sargeni, F.; Venditti, S.

    2016-02-01

    The NA62 experiment at the CERN SPS aims at measuring the branching ratio of the very rare kaon decay K+ → π+ ν bar nu (expected 10-10) with a 10% background. Since an high-intensity kaon beam is required to collect enough statistics, the Level-0 trigger plays a fundamental role in both the background rejection and in the particle identification. The calorimetric trigger collects data from various calorimeters and it is able to identify clusters of energy deposit and determine their position, fine-time and energy. This paper describes the complete hardware commisioning and the setup of the trigger for the 2015 physics data taking.

  4. 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.

  5. Can Trauma Trigger Violent Crime in Mentally Ill?

    MedlinePlus

    ... the trigger, especially in people with schizophrenia and bipolar disorder, Fazel said. People diagnosed with these conditions have ... 000 had schizophrenia, and nearly 30,000 had bipolar disorder. More than 2.7 million healthy individuals were ...

  6. Effector-triggered defence against apoplastic fungal pathogens.

    PubMed

    Stotz, Henrik U; Mitrousia, Georgia K; de Wit, Pierre J G M; Fitt, Bruce D L

    2014-08-01

    R gene-mediated host resistance against apoplastic fungal pathogens is not adequately explained by the terms pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) or effector-triggered immunity (ETI). Therefore, it is proposed that this type of resistance is termed 'effector-triggered defence' (ETD). Unlike PTI and ETI, ETD is mediated by R genes encoding cell surface-localised receptor-like proteins (RLPs) that engage the receptor-like kinase SOBIR1. In contrast to this extracellular recognition, ETI is initiated by intracellular detection of pathogen effectors. ETI is usually associated with fast, hypersensitive host cell death, whereas ETD often triggers host cell death only after an elapsed period of endophytic pathogen growth. In this opinion, we focus on ETD responses against foliar fungal pathogens of crops. PMID:24856287

  7. 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.

  8. 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.

  9. 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.

  10. Could Germ from Cat Poop Trigger Rage Disorder in People?

    MedlinePlus

    ... medlineplus/news/fullstory_157922.html Could Germ From Cat Poop Trigger Rage Disorder in People? Those with ... 2016 WEDNESDAY, March 23, 2016 (HealthDay News) -- Your cat's litter box could be a source of explosive ...

  11. Death of Loved One May Trigger Heart Rhythm Trouble

    MedlinePlus

    ... nlm.nih.gov/medlineplus/news/fullstory_158176.html Death of Loved One May Trigger Heart Rhythm Trouble ... likely to develop an irregular heartbeat following the death of their spouse or life partner, particularly if ...

  12. Smoking Triggers Big Changes in Mouth Bacteria, Study Finds

    MedlinePlus

    ... nlm.nih.gov/medlineplus/news/fullstory_158024.html Smoking Triggers Big Changes in Mouth Bacteria, Study Finds ... 29, 2016 TUESDAY, March 29, 2016 (HealthDay News) -- Smoking can dramatically change the balance of bacterial species ...

  13. Chronic Pain May Trigger Many Cases of Painkiller Addiction

    MedlinePlus

    ... Chronic Pain May Trigger Many Cases of Painkiller Addiction: Survey Drug counselors should consider whether people are ... a major driver behind the recent surge in addiction to prescription painkillers, a new survey finds. Opioid ...

  14. HERA-B higher-level triggers: architecture and software

    NASA Astrophysics Data System (ADS)

    Gellrich, Andreas; Medinnis, Mike

    1998-02-01

    HERA-B will be studying CP-violation in the B-system in a high-rate hadronic environment. To accomplish this goal, HERA-B needs a sophisticated data acquisition and trigger system. Except for the first level, all trigger levels are implemented as PC-farms, running the Unix-like operating system, Linux, thus blurring the sharp border between online and offline application software. The hardware architecture and software environments are discussed.

  15. Auroral kilometric radiation triggered by type II solar radio bursts

    NASA Technical Reports Server (NTRS)

    Calvert, W.

    1985-01-01

    The previously-reported triggering of auroral kilometric radiation (AKR) during type III solar radio bursts was attributed to the incoming radio waves rather than other aspects of the burst's causative solar flare. This conclusion has now been confirmed by ISEE-1 and ISEE-3 observations showing AKR which seems to have been triggered also by a subsequent type II solar radio burst, up to eleven hours after the flare.

  16. Upgrade and Operation of the DZero Central Track Trigger

    SciTech Connect

    Pangilinan, M.P.; Buehler, M.D.; /Virginia U.

    2007-04-01

    The D{O} experiment at the Fermilab p{bar p} Tevatron collider (Batavia, IL, USA) has undergone significant upgrades in anticipation of high luminosity running conditions. As part of the upgrade, the capabilities of the Central Track Trigger (CTT) to make trigger decisions based on hit patterns in the Central Fiber Tracker (CFT) have been much improved. We report on the implementation, commissioning and operation of the upgraded CTT system.

  17. 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.

  18. Selection of tau leptons with the CDF Run 2 trigger system

    SciTech Connect

    A. Anastassov; S. Baroiant; M. Chertok

    2003-07-01

    We have implemented triggers for hadronically decaying tau leptons within a framework of the CDF Run 2 trigger system. We describe the triggers, along with their physics motivations, and report on their initial performance.

  19. Molecular triggers of egg activation at fertilization in mammals.

    PubMed

    Sanders, Jessica R; Swann, Karl

    2016-08-01

    In mammals, the sperm activates the development of the egg by triggering a series of oscillations in the cytosolic-free Ca(2+) concentration (Ca(2+) i). The sperm triggers these cytosolic Ca(2+i) oscillations after sperm-egg membrane fusion, as well as after intracytoplasmic sperm injection (ICSI). These Ca(2+) i oscillations are triggered by a protein located inside the sperm. The identity of the sperm protein has been debated over many years, but all the repeatable data now suggest that it is phospholipase Czeta (PLCζ). The main downstream target of Ca(2+) i oscillations is calmodulin-dependent protein kinase II (CAMKII (CAMK2A)), which phosphorylates EMI2 and WEE1B to inactivate the M-phase promoting factor protein kinase activity (MPF) and this ultimately triggers meiotic resumption. A later decline in the activity of mitogen-activated protein kinase (MAPK) then leads to the completion of activation which is marked by the formation of pronuclei and entry into interphase of the first cell cycle. The early cytosolic Ca(2+) increases also trigger exocytosis via a mechanism that does not involve CAMKII. We discuss some recent developments in our understanding of these triggers for egg activation within the framework of cytosolic Ca(2+) signaling. PMID:27165049

  20. Alcohol and migraine: trigger factor, consumption, mechanisms. A review.

    PubMed

    Panconesi, Alessandro

    2008-02-01

    This study investigates the importance of alcohol as a migraine trigger factor, the prevalence of alcohol consumers and the mechanism of headache provocation. A MEDLINE search from 1988 to October 2007 was performed for "headache and alcohol", "headache and wine", "migraine and alcohol" and "migraine and wine". In retrospective studies, about one-third of the migraine patients reported alcohol as a migraine trigger, at least occasionally, but only 10% of the migraine patients reported alcohol as a migraine trigger frequently. Regional differences were reported, perhaps depending in part on alcohol habits. No differences were found between migraine and tension headache and different genders. However, prospective studies limit considerably the importance of alcohol as a trigger. Recent studies show that migraine patients consume less alcohol than controls. Red wine was reported to be the principal trigger of migraine, but other studies show that white wine or other drinks are more involved. Then, the discussion based on the different composition of the various alcoholic beverages, in order to discover the content of alcoholic drinks responsible for migraine attack, reflects this uncertainty. Biogenic amines, sulphites, flavonoid phenols, 5-hydroxytryptamine mechanisms and vasodilating effects are discussed. The fact that few headache patients cannot tolerate some alcoholic drinks does not justify the consideration that alcohol is a major trigger and the suggestion of abstinence. In fact, low doses of alcohol can have a beneficial effect on patients such as migraineurs, who were reported to have an increased risk of cardiovascular disease. PMID:18231712